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EUS-guided paracentesis for the diagnosis of malignant ascites. BACKGROUND EUS and EUS-guided fine-needle aspiration (EUS-FNA) have well-defined roles in the diagnosis and staging of GI and pancreaticobiliary malignancy. Malignant ascites usually represents peritoneal carcinomatosis, increases disease stage, and portends a poor prognosis. There are limited data regarding the yield of EUS-guided paracentesis (EUS-P) for the diagnosis of malignant ascites. OBJECTIVE To determine the usefulness of EUS-P for the diagnosis of malignant ascites. DESIGN Prospective case series. SETTING Tertiary referral academic center. PATIENTS Those presenting for EUS examination for suspected or proven malignancy over a 16-month period were evaluated prospectively for the presence of ascites. INTERVENTIONS EUS-P was performed via a transgastric or transduodenal approach if ascites was detected. MAIN OUTCOME MEASUREMENTS Sensitivity, specificity, positive predictive value, and negative predictive value of EUS-P for diagnosing malignant ascites. RESULTS Six hundred twenty-nine patients were studied. Twenty-five patients with ascites who met inclusion criteria comprised the study cohort. The mean volume of ascites aspirated was 6.8 mL (range, 1-20 mL). Sixty-four percent (16 of 25) of EUS-P samples revealed malignant cytology. Of the group with negative ascitic cytology, 67% (6 of 9) had a proven malignancy. There was one false-negative cytology result. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-P for diagnosing malignant ascites was 94%, 100%, 100%, and 89%, respectively. The complication rate was 4%; 1 patient developed bacterial peritonitis after EUS-P. LIMITATIONS The study did not address cost savings in patient care based on the diagnosis of malignant ascites. CONCLUSIONS EUS-P is highly sensitive and specific for diagnosing malignant ascites. The finding of malignant ascites significantly alters patient management, so an active search for ascites and use of EUS-P should be incorporated into the diagnosis and staging of upper GI and pancreaticobiliary malignancy.

Success and complications of endoscopic removal of giant duodenal and ampullary polyps: a comparative series. BACKGROUND Increasing reports suggest that endoscopic removal of benign ampullary and duodenal polyps is safe and frequently definitive; however, most reported polyps have been small in size (<3 cm). We have developed experience with endoscopic removal of increasingly large and complex polyps. PATIENTS Fifty-one cases of endoscopic removal were attempted and grouped according to size: group A (n = 22) polyps 1 to 3 cm and group B (n = 29) polyps 3 cm or larger, including 7 cases larger than 5 cm. When the ampulla was involved, biductal sphincterotomy and prophylactic pancreatic duct stent placement was performed first, followed by saline solution-assisted piecemeal polypectomy, argon plasma coagulation, selective endoclip placement, and recovery of all polyp fragments. INTERVENTIONS Endoscopic removal of duodenal and ampullary adenomas. RESULTS The outcomes of small and large adenoma removal include mean number of endoscopic retrograde cholangiopancreatographies required for complete removal (2.09 vs 2.56, P = .392), number of complications (4.5% vs 13.9%, P = .375), discovery of unsuspected cancer (0% vs 10.3%, P = .242), and final definitive resolution (100% vs 86.2%, P = .124). Complete removal was achieved in 92.2% of all patients. LIMITATIONS This was a single center retrospective study. CONCLUSIONS Large (>/=3 cm) ampullary and duodenal polyps comprised 56.9% of our endoscopically treated cases and present special challenges to definitive endoscopic removal. Successful removal of even very large sessile lesions is possible with minimal increase in risk.

Repeat colonoscopy has a low yield even in symptomatic patients. BACKGROUND In many regions, the demand for colonoscopy exceeds its availability. Patients undergoing repeat examinations comprise a significant proportion of those on waiting lists. OBJECTIVE To assess the yield of repeat colonoscopy in varied clinical settings. DESIGN Cohort study. SETTING Endoscopic database of an Australian tertiary referral hospital. PATIENTS Adults who had >/=2 colonoscopies between 1992 and 2004. Patients were excluded if the repeat procedure was for completion or for high-risk surveillance. MAIN OUTCOME MEASUREMENTS Yield for neoplasia by indication, interval to repeat examination, and appropriateness for surveillance (determined by National Australian guidelines). RESULTS A total of 4974 colonoscopies in 2075 patients were studied. The mean age was 63.1 years (range, 19.2-92.4 years). The mean number of examinations was 2.4 (range, 2-8), with a mean interval between examinations of 2.9 years. Colorectal cancer (CRC) was significantly more prevalent at initial colonoscopy compared with subsequent colonoscopies (7.9% vs 0.6%; prevalence ratio 14.2, 95% confidence interval [CI] 8.5-23.7, P < .001), as were advanced adenomas (15.3% vs 4.8%; prevalence ratio 3.2, 95% CI 2.6-3.9, P < .001). No CRCs were detected in symptomatic patients undergoing polyp surveillance examinations performed before the recommended interval. LIMITATIONS Retrospective design. CONCLUSIONS Yield of repeat colonoscopy is significantly lower than for initial colonoscopy, irrespective of indication. In symptomatic patients within a polyp surveillance program, the yield is negligible when a colonoscopy is performed before the recommended surveillance interval. The need for a repeat colonoscopy should be carefully considered, and patients who have never had a colonoscopy must take priority on waiting lists over those awaiting repeat examinations.

A novel method for estimating the safe margin and the adequate direction of endoscopic biliary sphincterotomy in choledocholithiasis with complications (with videos). BACKGROUND It is difficult to estimate the safe upper margin and the proper direction of endoscopic biliary sphincterotomy (EBS) in cases of choledocholithiasis complicated by periampullary diverticulum (PAD) or previous EBS. OBJECTIVE This study evaluated the clinical usefulness of an inflated-balloon-pulling (IBP) technique for assessing the safe margin and the proper direction of EBS in affected patients. DESIGN Prospective feasibility study. SETTING Academic tertiary center. PATIENTS From March 2003 to November 2003, the IBP technique was applied to patients with choledocholithiasis in whom EBS was difficult because of concomitant PAD or previous EBS. INTERVENTIONS AND MAIN OUTCOME MEASUREMENTS After the endoscopically visible papillary roof of the ampulla of Vater was fully dissected, an inflated 11.5- or 15-mm retrieval balloon was inserted in the bile duct and was pulled toward the duodenal lumen, creating an artificial bulge. This bulge was considered an endoscopic landmark to indicate the residual intramural portion and the direction of the bile duct. RESULTS A total of 19 patients (12 men, 7 women), with a mean age of 61.5 years, were consecutively enrolled. Of these patients, 7 had PAD, 7 had recurrent choledocholithiasis, and 5 had both conditions. The mean length of the IBP-induced residual intramural bile duct was 6.6 mm (range, 3-15 mm). The previous EBS was not oriented toward the bile duct in 4 of 12 patients with recurrent choledocholithiasis (33.3%). After EBS extended completely, choledocholithiases were successfully removed in all patients (1 by mechanical lithotripsy). Of the 19 patients, 2 had complications (11%; 1 mild hemorrhage, 1 mild pancreatitis), which were managed medically. There was no case of perforation. CONCLUSIONS The IBP technique is a feasible and a reliable method for safe and effective EBS in patients with choledocholithiasis in whom EBS is difficult because of PAD or/and previous EBS. The clinical significance of the direction of previous EBS needs to be defined.

Laparoscopic-assisted double-balloon enteroscopy for small-bowel polyp surveillance and treatment in patients with Peutz-Jeghers syndrome. BACKGROUND Surveillance and treatment of small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS) can be challenging and may require intraoperative enteroscopy. While initial reports that used double-balloon enteroscopy (DBE) for the resection of small-bowel polyps in patients with PJS appear promising, complete enteroscopy when using this technique may require multiple procedures or may not be possible at all. OBJECTIVE To develop a single-procedure approach to the surveillance and the treatment of small-bowel polyps in patients with PJS. DESIGN Retrospective review. SETTING Single, North American tertiary-care center. PATIENTS Individuals with PJS and small-bowel polyps identified by other modalities. INTERVENTIONS DBE was combined with laparoscopy as a single-procedure surveillance and therapeutic strategy for small-bowel PJS polyps. MAIN OUTCOME MEASUREMENTS Completion of enteroscopy, number of polyps resected, procedure duration, complications. RESULTS Three patients with a history of PJS and known small-bowel polyps underwent laparoscopic-assisted DBE (LADBE). Complete enteroscopy was performed, and all polyps larger than 0.5 cm were resected endoscopically. No cases of cancer or dysplasia were noted; procedure times lasted from 1 to 4 hours. Postoperative complications included ileus in 2 patients. LIMITATIONS Small sample size, single-center experience. CONCLUSIONS LADBE holds promise as a new technique that can be used as both a surveillance and a therapeutic tool for small-bowel polyps in patients with PJS.

Epithelioid angiosarcoma of the small bowel. BACKGROUND Angiosarcoma is a rare soft-tissue neoplasm that occurs most often in the skin and the subcutaneous tissues but very rarely in the GI tract. DESIGN We report a case of multifocal epithelioid angiosarcoma involving skin and bowel and review the 18 previously reported cases of epithelioid intestinal angiosarcoma. MAIN OUTCOME MEASUREMENTS Our patient presented with weakness from anemia. Two small blue-black nodules were present on the skin. Fecal occult blood tests were positive, but gastroscopy and colonoscopy showed normal results. Enteroscopy revealed small ulcerated nodules in the distal duodenum and the proximal jejunum. Biopsy specimens of skin and duodenal nodules showed epithelioid angiosarcoma. RESULTS The intestinal nodules were treated with argon plasma coagulation, but the patient died 6 weeks after diagnosis. CONCLUSIONS The survival rate of intestinal angiosarcoma is poor, and most cases progress rapidly, with a 2-month median survival after diagnosis. Because of the infiltrative and the multifocal nature of this malignancy, complete surgical excision is often not possible. Further studies are needed to establish the role of adjuvant radiation or chemotherapy in the treatment of angiosarcoma.

Current surgical therapy for Ebstein anomaly in neonates. OBJECTIVE Neonates with profound heart failure resulting from Ebstein anomaly have historically had poor outcomes. We report our institutional experience with the surgical management of Ebstein anomaly in severely symptomatic neonates. METHODS A retrospective review of all patients (n = 16) undergoing neonatal intervention for Ebstein anomaly between 1992 and 2005 has been carried out. The indications for operation were overt heart failure, cyanosis, and acidosis associated with tricuspid regurgitation, depressed right ventricular function, and severe cardiomegaly. The magnitude of cardiac enlargement was assessed by cardiothoracic ratio and Great Ormond Street ratio (area of right atrium + atrialized right ventricle/area of functional left atrium + left ventricle). The operative strategy was first to assess for the possibility of tricuspid valve repair with or without right ventricular outflow tract reconstruction. If this was not feasible, then right ventricular exclusion was performed by oversewing the tricuspid valve with a pericardial patch. A reduction atrioplasty was done and, depending on the extent of the atrialized portion of the right ventricle, plication was performed. A modified Blalock-Taussig shunt provided pulmonary blood flow. This univentricular approach (Starnes procedure) evolved to include a fenestration in the tricuspid valve patch to allow for right ventricular decompression. Analysis included overall and group-specific survival as well as the testing of perioperative clinical, morphologic, and surgical variables for correlation with mortality and morbidity. RESULTS Mean age and weight at operation were 8 +/-10 days and 3.1 +/- 0.4 kg. Tricuspid valve repair was undertaken in 3 patients with 1 requiring conversion to right ventricular exclusion 3 months after the initial operation. In those with right ventricular exclusion, the tricuspid valve patch was fenestrated in 10 and nonfenestrated in 3. One patient had heart transplant as the initial procedure. There were 5 hospital deaths (31%) and no late deaths among the survivors. Survival in the cohort with a fenestrated tricuspid valve patch was 80% (8/10) versus 33% (1/3) for the nonfenestrated group. This difference did not reach statistical significance, although the trend seems clinically important. There was no difference in the cardiothoracic ratio (0.82 fenestrated vs 0.84 nonfenestrated: P = .802) or the Great Ormond Street ratio (1.2 fenestrated vs 1.02 nonfenestrated: P = .477) between the two groups. Among the 9 survivors of right ventricular exclusion, 3 have had completion of their Fontan, and all 9 have undergone a bidirectional Glenn procedure. All operations including homograft placement in the right ventricular outflow tract, whether during repair or during right ventricular exclusion, ended in death. CONCLUSION Right ventricular exclusion with a fenestrated tricuspid valve patch combined with right atrioplasty and right ventriculoplasty and a Blalock-Taussig shunt (Starnes procedure) has provided effective palliation for neonates presenting with critical Ebstein anomaly and a tricuspid valve that cannot be repaired.

High-dose atorvastatin is associated with impaired myocardial angiogenesis in response to vascular endothelial growth factor in hypercholesterolemic swine. OBJECTIVES The disappointing results of myocardial angiogenic therapy have been attributed, in part, to endothelial dysfunction present in patients with coronary disease. Statins have established proendothelial properties but seem to have dose-dependent effects on angiogenesis. We investigated the functional and molecular effects of high-dose atorvastatin on vascular endothelial growth factor-induced myocardial angiogenesis in hypercholesterolemic swine. METHODS Yucatan miniswine (20-30 kg) were fed either a normal (ND group, n = 8) or high-cholesterol diet, with (HC-ATOR group, n = 8) or without (HC group, n = 8) atorvastatin (3 mg x kg(-1) x d(-1)), for 13 weeks. Chronic ischemia was induced by ameroid constrictor placement around the circumflex artery, followed 3 weeks later by perivascular vascular endothelial growth factor administration (2 microg over 4 weeks) with a sustained release osmotic pump. Microvessel relaxation responses, myocardial perfusion, and myocardial expression of angiogenic mediators were assessed 4 weeks later. RESULTS Hypercholesterolemic swine demonstrated impaired microvessel relaxation to vascular endothelial growth factor (P < .01 vs ND group) and adenosine diphosphate (P < .001 vs ND group), which was normalized in the HC-ATOR group. After perivascular vascular endothelial growth factor administration, collateral-dependent myocardial perfusion was significantly increased in the ND group but decreased in both the HC and HC-ATOR groups (both P < .01 vs the ND group). The animals in the HC-ATOR group demonstrated increased myocardial expression of the antiangiogenic protein endostatin and increased Akt phosphorylation without significant changes in Akt and endothelial nitric oxide synthase expression. CONCLUSIONS Atorvastatin treatment reverses hypercholesterolemia-induced endothelial dysfunction without appreciable improvements in collateral-dependent myocardial perfusion in response to vascular endothelial growth factor treatment. Increased myocardial endostatin expression and chronic Akt activation, associated with atorvastatin therapy, might account for the lack of improvement in the angiogenic response to vascular endothelial growth factor therapy.

Keeping the heart empty and beating improves preservation of hypertrophied hearts for valve surgery. OBJECTIVE This study was designed to determine whether keeping the heart empty and beating improved myocardial fluid homeostasis and energy metabolism of hypertrophied pig hearts in comparison with cardioplegic arrest. METHODS Twenty piglets underwent a 8-weeks (corrected) ascending aortic banding to induce left ventricular hypertrophy. Isolated hypertrophied hearts were divided into 4 groups (n = 5 in each group). Two groups underwent normothermic normokalemic simultaneous perfusion. The other 2 groups were subjected to normothermic hyperkalemic simultaneous perfusion and used as controls. Intramyocardial hydrostatic pressure was monitored with a microtip pressure transducer. Volumes of intracellular and extracellular compartments and myocardial energy metabolism were monitored by using phosphorus 31 magnetic resonance spectroscopy. RESULTS Normothermic normokalemic simultaneous perfusion (NNSP) maintained intramyocardial hydrostatic pressure at a significantly lower level (13.0 +/- 0.6 mm Hg) compared with normothermic hyperkalemic simultaneous perfusion (NHSP) (23.3 +/- 1.2 mm Hg) during a 90-minute preservation. NNSP maintained the normal volume of the intracellular compartment throughout the preservation period, whereas NHSP caused significant enlargement (to 123% +/- 6% of its normal volume) of the intracellular compartment. Expansion of the extracellular compartment during preservation was significantly less in the NNSP group (124% +/- 6%) than in the NHSP group (152% +/- 7%). NNSP maintained normal levels of phosphocreatine and adenosine triphosphate until coronary perfusion flow was reduced to 50% of the initial control level. No decrease in energy metabolites was observed in the NHSP group even when coronary perfusion flow was reduced to 10% of the initial control level. CONCLUSIONS Keeping the heart empty and beating improves myocardial fluid homeostasis for hypertrophied hearts relative to cardioplegic arrest. Its ability to maintain energy metabolism depends on the degree of coronary stenosis. This technique may be a promising protective strategy for hypertrophied hearts.

Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure. OBJECTIVES Cellular cardiomyoplasty using skeletal myoblasts or angiopoietic progenitor cells offers a promising approach for the treatment of ischemic heart failure. Although several studies have shown encouraging results in acute myocardial infarction, the efficacy of cell therapy using skeletal myoblasts and angiopoietic progenitor cells in chronic ischemic heart disease remains undetermined. METHODS Ischemic heart failure was induced by left anterior descending coronary artery ligation in nude rats: (1) Culture medium, (2) homologous skeletal myoblasts (SM), (3) human AC-133+ cells (SC), and (4) both skeletal myoblasts and AC-133+ cells (Comb) were injected in the infarct (SM) and peri-infarct area (SC) 4 weeks after infarction. Assessment of myocardial function included echocardiography 4 weeks after cell delivery. Histology was based on quantification of myocardial fibrosis, apoptosis, and capillary density. RESULTS Left ventricular dilatation was attenuated and ejection fraction improved significantly after cell transplantation (SM: 59.4% +/- 8.8%, SC: 60.3% +/- 6.6%, Comb: 68.2% +/- 5.6% vs control: 41.5% +/- 7.4%, P = .0013). Quantification of scar tissue showed a significant reduction of infarct area in cell-treated animals (SM: 22.3% +/- 9.1%, SC: 19.8% +/- 7.6%, Comb: 13.2% +/- 5.8% vs controls: 36.5% +/- 8.2%, P = .008). Improvement of myocardial function was associated with reduced apoptotic index (SM: 3.2% +/- 0.9%, SC: 3.1% +/- 0.6%, Comb: 1.8% +/- 0.8% vs controls: 10.3% +/- 1.6%, P = .0002) and increased vascular density (SM: 5.2 +/- 1.2, SC: 8.3 +/- 1.8, Comb: 12.3 +/- 2.3, controls: 1.9 +/- 0.3, all capillary vessels/high-power field, P = .007) in animals after cellular cardiomyoplasty. CONCLUSIONS Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells results in ventricular function improvement, reduction of scar size and myocardial apoptosis, and increased neoangiogenesis in chronic ischemia. Clinical studies are warranted to prove this new therapeutic concept.

Recurrent mitral regurgitation after repair: should the mitral valve be re-repaired? OBJECTIVE We sought to evaluate the clinical and echocardiographic outcomes of reoperation for failed mitral valve repair. METHODS One hundred forty-five patients with recurrent mitral regurgitation after primary mitral valve repair of degenerative leaflet prolapse underwent mitral valve reoperations between January 1, 1970, and January 1, 2005. The mean age was 66 years, and 102 (70%) were men. RESULTS The mean duration from initial repair to reoperation was 4.1 years (standard deviation = +/- 5.1 years). Indications for reoperation were regurgitation alone (n = 109 [75%]), hemolysis (n = 27 [19%]), obstruction from systolic anterior motion (n = 3 [2%]), endocarditis (n = 3 [2%]) and stenosis-other (n = 3 [2%]). New pathology was found in 80 (55%) patients, and failure of the initial repair was found in 61 (42%) patients. The mitral valve was re-repaired in 64 (44%) patients and replaced in 81 (56%) patients. Early operative mortality was similar after re-repair and replacement (1.6% vs 4.9%, P = .38). Independent predictors of improved survival on multivariate analysis were mitral re-repair (hazard ratio = 0.44, P = .03), younger age (hazard ratio = 1.06, P = .001), and an operative indication of mitral regurgitation alone (hazard ratio = 0.31, P = .005). Seven patients had a third mitral operation (all replacements), 6 after re-repair and 1 after replacement. At last follow-up echocardiogram (n = 96), ejection fraction was greater (P < .001) and left ventricular end-systolic dimension was smaller (P = .009) in patients undergoing re-repair compared with values in those undergoing valve replacement. CONCLUSION Recurrent mitral regurgitation after prior repair is frequently caused by new valve pathology. Mitral re-repair is performed in almost half of patients and is associated with superior survival, improved ejection fraction, and greater regression in ventricular dimension compared with valve replacement.

Carotid artery cannulation in aortic surgery. OBJECTIVE Carotid artery cannulation was initially established at our clinic for surgery of acute aortic dissection, and it became the standard approach for procedures in which circulatory arrest is necessary. The aim of the study was to evaluate this method's efficiency regarding postoperative outcomes after the first 100 procedures. METHODS Between July 2002 and October 2005, 100 patients underwent aortic surgery using carotid artery cannulation by a side graft for arterial return with a mean flow rate of 4.6 +/- 0.5 L/min. There were 27 patients with acute and 2 with chronic type A aortic dissection. Sixteen patients had had prior cardiac surgery. During circulatory arrest, the arterial line was used for unilateral cerebral perfusion in moderate hypothermia (mean rectal temperature 28 degrees C +/- 1.6 degrees C) with a mean flow rate of 0.85 +/- 0.2 L/min. RESULTS Carotid artery cannulation offered adequate arterial return in all patients. In no case was a switch to another cannulation site necessary for arterial return. Furthermore, no complications related to the cannulation site were observed. One patient with acute dissection and 1 with chronic aneurysm died during the early postoperative course. Thus, 30-day mortality was 2.0% for the whole group and 3.7% for the dissection group. Two patients with severe calcification of the aortic valve had strokes. There were no strokes in the dissection group, although there were preoperative signs of cerebral malperfusion in 4 patients. CONCLUSIONS Carotid artery cannulation is a fast, safe, and efficient method of arterial cannulation even in very obese patients. In addition, it simplifies the procedure of unilateral cerebral perfusion through the arterial line during circulatory arrest, making it completely unnecessary to interrupt cerebral perfusion.

Acute type A aortic dissection complicated by stroke: can immediate repair be performed safely? OBJECTIVE Emergency surgical intervention for acute type A aortic dissection complicated by stroke remains controversial. The urgency of immediate repair in this setting is tempered by the concern that cerebral reperfusion may worsen neurologic outcome. The purpose of this study was to report and analyze our results with acute type A aortic dissection complicated by stroke. METHODS Between September 1999 and March 2005, 151 consecutive patients presented with acute type A aortic dissection. Of this group, 16 (10.6%) patients had sustained a preoperative stroke. Mean age was 56 years (range 43-73 years), with 6 (38%) women. Right hemispheric, left hemispheric, and bilateral strokes occurred in 81%, 13%, and 6%, respectively. Computed tomographic scan or transesophageal echocardiography diagnosed aortic dissection; clinical examination, computed tomographic scan, or transcranial Doppler ultrasound diagnosed stroke. Aortic repair was performed with cardiopulmonary bypass, profound hypothermic circulatory arrest, and retrograde cerebral perfusion. One patient with complete neurologic devastation (coma) was not operated on. RESULTS Overall hospital mortality was 18.8% (3/16). Mortality in 2 patients who did not undergo surgery (1 patient who was neurologically devastated, and 1 patient whose aorta ruptured while awaiting surgery) was 100% (2/2). Operative mortality was 7% (1/14). Among patients undergoing surgery, neurologic status completely recovered in 2 (14%) patients, improved in 6 (43%) patients, remained the same in 6 (43%) patients, and worsened in none. Median time from onset of stroke to surgery was 9 hours (range 1-240 hours). Eighty percent of patients who underwent surgical repair within 10 hours had improvement in neurologic status, where as none operated on beyond 10 hours improved (P < .02). CONCLUSIONS In our experience, surgical repair of acute type A aortic dissection can be performed in the setting of preoperative stroke with acceptable mortality. Moreover, no worsening of neurologic condition was observed after surgical repair. Immediate surgical repair is warranted even if acute type A aortic dissection is complicated by stroke.

Degeneration of the pulmonary autograft: an explant study. OBJECTIVE We sought to determine the histologic features of pulmonary autografts explanted after the Ross operation. METHODS Histologic sections of 30 explanted autografts and 8 normal heart valves were compared and semiquantitatively scored by a blinded cardiovascular pathologist. RESULTS Pulmonary autografts (n = 30) were explanted on average 6.1 +/- 0.6 years (median, 6.6 years; range, 0.1-11.7 years) after the Ross operation (n = 28) or removed at autopsy (n = 2). Twelve (43%) of the patients undergoing reoperation had no or negligible autograft insufficiency on early transthoracic echocardiography, 12 (43%) had grade 1 autograft insufficiency, and 4 (14%) had grade 1-2 autograft insufficiency. Valve regurgitation with root dilatation was the most common indication for reoperation after root replacement (n = 26 [93%]) and regurgitation after subcoronary implanted autografts (n = 2 [7%]). Microscopy of the autograft explants revealed normal laminar architecture and cellularity. Wall specimens were characterized by reduced and fragmented elastin and increased collagen levels (fibrosis). Medial elastin changes were associated with the presence of hypertrophic smooth muscle cells. Fibrosis was most severe in the adventitia. Intimal thickening was a common finding. Valve explants showed significant thickening caused by fibrocellular tissue on the ventricular surface and marked thickening of the free margin. An autopsy explant with normal function before death showed similar features. CONCLUSIONS Pulmonary autograft explants showed severe aneurysmal degeneration of the wall, which was characterized by intimal thickening, medial elastin fragmentation, and adventitial fibrosis. Valve leaflets were thickened. The presence of these features in a nonfailing explant suggests these changes represent a common mode of remodeling.

Freedom from atrial arrhythmias after classic maze III surgery: a 10-year experience. OBJECTIVES We studied the persistence of favorable outcome, the occurrence of new atrial arrhythmias, and sinus node dysfunction in patients who underwent the maze III procedure. METHODS Preoperative, in-hospital, and follow-up data of 203 patients who underwent the maze III procedure between June 1993 and June 2003 were collected. A total of 139 patients underwent the maze procedure for lone atrial fibrillation, and 64 patients underwent the maze procedure and concomitant cardiac surgery. RESULTS There was no 30-day postoperative mortality. During a mean follow-up of 4.0 +/- 2.6 years, 12 patients (6%) died (2 cardiac related). At the end of follow-up, freedom from supraventricular arrhythmias was 80% for the lone atrial fibrillation group and 64% for the concomitant atrial fibrillation group. Freedom from stroke during follow-up was 100% in the lone atrial fibrillation group and 97% in the concomitant group. Multivariate analysis revealed that rhythm at 1-year follow-up (P < .001; odds ratio 9.56, 95% confidence limits 3.92-23.31) and preoperative left atrium dimension (P = .028; odds ratio 1.06 for every millimeter, 95% confidence limits 1.01-1.12) were predictors of success at the end of follow-up. CONCLUSIONS This study shows that the favorable results of the maze III procedure in terms of freedom from supraventricular arrhythmias persist in most patients for at least 4 years.

Sexual dimorphism in degenerative disorders of the spine. Sexual dimorphism is evident during formation, growth, and development of the spine. Pregnancy alters spine physiology and is a risk factor for back pain. The processes of aging and spinal degeneration adversely affect men and women slightly differently. Although degenerative changes are observed at similar rates in both sexes, women seem to be more susceptible to degenerative changes leading to instability and malalignment, structural deterioration, such a stenosis or disc degeneration. Surgical satisfaction is greater in men, which has been attributed to poorer preoperative function secondary to more advanced disease at time of surgery and lower patient expectations for clinical improvement, both observed in women.

Sexual dimorphism of the foot and ankle. Lower extremity musculoskeletal injuries are extremely common. Sports-related sex differences, in addition to osteoporosis issues, have raised the level of social awareness that women's health care issues may be different than those of their male counterparts. Traditional research investigation for the foot and ankle is focused on shoe style differences and the effect that these shoes have had on foot pain and injury (eg, bunion, lesser toe malalignment). In addition to the extrinsic factor of footwear, intrinsic factors, such as foot structure, ligamentous laxity, muscle strength, and proprioception, predispose individuals to injury. This article reviews the literature to examine the intrinsic and extrinsic differences between men and women in relationship to the foot and ankle and explores, where available, the influence that these factors have on injury.

Female athlete triad and stress fractures. Stress fractures are a common occurrence in athletes, and the incidence of stress fractures in female Division 1 collegiate athletes is double that of men. Hormonal influences on bone and bone morphology may influence the risk for fracture. A high level of suspicion and special imaging procedures allow for accurate diagnosis of these fractures. In stress fractures that are associated with the female athlete triad, addressing the three aspects of the triad--eating disorders, amenorrhea, and osteoporosis--are critical for successful treatment. Preparticipation screening for the presence of signs of the female athlete triad by monitoring weight, energy level, menstrual cycles, and bone mineral density may help to prevent the occurrence of stress fractures in this population.

Dimorphism and patellofemoral disorders. Sex is defined as the classification of living things according to their chromosomal compliment. Gender is defined as a person's self-representation as a male or female or how social institutions respond to that person on the basis of his or her gender presentation. One frequently divides the topic or dimorphism into the biologic response inherent in their sex and the environmental response that might be better termed "gender differences." Clinicians have anecdotally agreed for years that patellofemoral disorders are more common in women. Given the difficulty in classifying patellofemoral disorders, literature support for this assumption is meager. For the purposes of this article we divide patellofemoral disorders into three categories: patellofemoral pain, patellofemoral instability, and patellofemoral arthritis. possible sex difference in these disorders are reviewed.

Retinal pigment epithelium. Retinal pigment epithelium (RPE) arises from neuroectoderm and plays a key role in support of photoreceptor functions. Several degenerative eye diseases, such as macular degeneration or retinitis pigmentosa, are associated with impaired RPE function that may lead to photoreceptor loss and blindness. RPE derived from human embryonic stem (hES) cells can be an important source of this tissue for transplantation to cure such degenerative diseases. This chapter describes differentiation of hES cells to RPE, its subsequent isolation, maintenance in culture, and characterization.

Setup and characterization of a human head and neck squamous cell carcinoma xenograft model in nude rats. OBJECTIVE To develop and characterize a new head and neck cancer animal model. STUDY DESIGN A human head and neck squamous cell carcinoma (HNSCC) xenograft model in nude rats was established via subcutaneous inoculation of a human-origin HNSCC cell line, SCC-4. The tumor was evaluated for growth characteristics, pathologic features by hematoxylin-eosin (HE) staining, and immunohistochemistry of epidermal growth factor receptor (EGFR). 2-[18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging characteristics were studied too. RESULTS A new HNSCC animal model was successfully established. Tumor sizes reached about 1 cm3 on day 15 after tumor cell inoculation. HE staining pathology has confirmed that this tumor is a typical SCC. EGFR immunohistochemistry demonstrated this tumor model to be strongly EGFR positive. 18F-FDG PET study has shown that 18F-FDG accumulated in tumors. CONCLUSIONS This study has demonstrated that this tumor model is an appropriate HNSCC tumor model for animal studies on HNSCC.

Head and neck space infections. OBJECTIVE The purpose of this study was to evaluate the incidence, causes, management, and complications of the different head and neck space infections in a Melanesian population. STUDY DESIGN AND SETTING We conducted a retrospective study in a tertiary referral and teaching hospital. RESULTS Of the total 103 patients with deep neck space infections (DNSI), odontogenic causes and suppurative lymphadenitis were responsible in 62 (60%) patients. A wide range of DNSI was encountered in our series. Ludwig's angina was the most commonly encountered infection seen in 38 (37%) patients, whereas prevertebral abscess was only seen in 1 (1%) patient. A combination of surgical drainage and medical treatment was the main mode of treatment. Nine (8.7%) patients with DNSI with upper airway obstruction underwent tracheostomy; 9 (8.7%) patients with DNSI succumbed to their infection. CONCLUSION DNSI needs early detection and aggressive management in order to evade dreaded complications.

One-phase management of severe obstructive sleep apnea: tongue base reduction with hyoepiglottoplasty plus uvulopalatopharyngoplasty. OBJECTIVES To describe the results of a 1 phase surgical procedure for the treatment of severe obstructive sleep apnea (OSA) attributable to tongue base obstruction. STUDY DESIGN AND SETTING A retrospective nonrandomized study at S Orsola Malpighi University Hospital of Bologna, Italy. METHODS Ten male patients affected by severe OSA (mean apnea/hypopnea index [AHI] of 54.7), underwent uvulopalatopharyngoplasty (UPPP) associated with tongue base reduction and hyoepiglottoplasty (TBRHE). The indications to this surgical procedure were based on the presence of hyolingual abnormalities and absence of craniofacial deficiencies determined by preoperative assessment. RESULTS Mean AHI decreased from 54.7+/-11.5 to 9.4+/-5.4 whereas the mean low SaO2 value went from 77%+/-6.2 to 90.7%+/-3 and the time of sleep with SaO2<90% improved from 53%+/-17.2 to 7.3%+/-8. The overall success rate was 100%. CONCLUSIONS AND SIGNIFICANCE TBRHE is an effective and safe treatment in patients with severe OSA attributable to tongue base obstruction and in absence of craniofacial deficiencies.

Obstructive sleep apnea in patients undergoing supracricoid horizontal or frontolateral vertical partial laryngectomy. OBJECTIVE To assess obstructive sleep apnea (OSA) in patients undergoing supracricoid horizontal partial laryngectomy (SCPL) or frontolateral vertical partial laryngectomy (VPL) for the treatment of laryngeal carcinoma and correlate it with age, body mass index, physical examination, and upper airway evaluation. STUDY DESIGN AND SETTING A prospective study was carried out involving 22 patients between 50 and 80 years of age divided into 2 equal groups. The patients underwent SCPL and VPL, and were evaluated by anamnesis, otolaryngologic examinations, nasopharyngolaryngoscopy, and polysomnography. RESULTS A significant direct correlation was observed between the apnea/hypopnea index (AHI) and age of the patients. An inversely proportional relation was found between glottic opening and AHI. The presence of OSA was 81% in SCPL and 91% in VPL. CONCLUSION We observed a high incidence of OSA in patients undergoing SCPL and VPL.

Closure of nasal septal perforation via endonasal approach. OBJECTIVE We report our experience in nasal septum perforation surgery using the endonasal approach. The role of rhinomanometry and nasal endoscopy in the management of septal perforation repair is also discussed. STUDY DESIGN AND SETTING We reviewed a sample of 30 patients with septal perforation. Patients underwent preoperative and postoperative nasal endoscopy and rhinomanometry. They were all treated using the Cottle technique with the backward extraction-reposition of nasal septum and inverted sliding flap suture technique. RESULTS Closure rate for small-sized and middle-sized perforations was 94% and 75%, respectively. It was 86.6% if calculated for all patients. Preoperative nasal resistances was normal in patients with isolated septum perforation, and high in patients with associated septum deformity or hypertrophic turbinates. CONCLUSION The Cottle technique is a viable procedure for the closure of small- and middle-sized perforations. Endoscopy and rhinomanometry help provide a correct and complete understanding of this nasal alteration.

Application of mitomycin-C for head and neck keloids. Keloids of the head and neck are a relatively common entity in darker-skinned races, occurring in 5%-15% of skin wounds. Keloids are fibrotic lesions that are a result of an abnormal wound-healing process that lacks control of the mechanisms that regulate tissue repair and regeneration. The proliferation of normal tissue-healing processes results in scarring that enlarges well beyond the original wound margins. Many treatment modalities for keloids have been tried with variable amounts of success. Surgical excision, compressive therapy, silicon dressings, corticosteroid injections, radiation, cryotherapy, interferon therapy, and laser therapy have all been used alone or in combination. Despite this wide range of available treatments, recurrence rates typically remain in the 50%-70% range. In this study, we present our results in a series of 10 patients who were treated with surgical excision of head and neck keloids and the application of topical mitomycin-C. Mitomycin-C is a chemotherapeutic agent that inhibits DNA synthesis and fibroblast proliferation. It has been used in ophthalmologic procedures and airway surgery to decrease scar formation. In these 10 patients, we combined surgical excision of keloids with the application of topical mitomycin-C. The patients were then followed postoperatively for recurrence (range, 7-14 months). We have found topical application of mitomycin-C to be an effective therapy for prevention of keloid recurrence in the head and neck, with a success rate of 90% as reported in this series.

Effort thrombosis (Paget-Schroetter syndrome) in active young adults: current concepts in diagnosis and treatment. Effort thrombosis or Paget-Schroetter syndrome most often affects young, active adults who are engaged in sports activities or whose professions require repetitive arm movements causing trauma to the axillary-subclavian vein and precipitating deep vein thrombosis. The presence of unilateral edema in the upper extremity is often thought to be attributable to trauma from an exercise regimen rather than acute deep vein thrombosis or compression of the subclavian vein by extrinsic anatomic structures. Because this syndrome occurs in young, active adults it has the potential for considerable long-term morbidity if it remains undetected or inadequately treated. Inadequate or inappropriate treatment may cause a loss of productivity over a lifetime and significantly affect the quality of life. Although more prevalent in male athletes, it is now increasingly affecting young women as they become more seriously involved in athletic endeavors. The purpose of this article is to increase the awareness of the prevalence, clinical significance, and importance of early detection of effort thrombosis of the axillary-subclavian vein, also known as Paget Schroetter syndrome, to educate health care providers regarding the limitations of some diagnostic tools, and to introduce new methods of treatment that offer better long-term results. The prevalence, differential diagnosis, diagnostic modalities, and medical and surgical interventions that have been successfully used to treat Paget-Schroetter syndrome are discussed, and evidence is provided to support the selections. The results of patients who were identified and treated within the last 2 years at the University of Southern California Center for Vascular Care are reviewed.

Effect of intoxication among blunt trauma patients selected for head computed tomography scanning. STUDY OBJECTIVE We examine the prevalence and types of intracranial injuries sustained by intoxicated blunt trauma patients. METHODS The study was conducted as a secondary analysis of National Emergency X-Radiography Utilization Study II head injury database. Treating physicians prospectively assessed presenting signs and symptoms on all blunt trauma patients who underwent head computed tomography (CT). Intoxication status was determined by the examining physician and was based on a history of intoxication, positive toxicologic screen result, or physical evidence suggesting intoxication. Intracranial injury diagnoses were based on final CT interpretations provided by attending radiologists. RESULTS Intracranial injury was detected in 1,193 of the 13,728 enrolled patients (8.7%), and intoxication was evident in 3,356 (24.4%) patients. Physicians were unable to assess intoxication status in 620 individuals. Intracranial injury was present in 231 intoxicated patients (231/3,356; 6.9%; 95% confidence interval [CI] 6.0 to 7.8), 789 of 9,752 nonintoxicated patients (8.1%; 95% CI 7.6% to 8.6%), and 173 of the 620 patients who could not be assessed for intoxication (prevalence 27.9%; 95% CI 24.4% to 31.6%). Intracranial injury was identified in only 5 of 299 intoxicated patients (1.7%) who had normal neurological examination results and no evidence of trauma to the calvarium. CONCLUSION The prevalence of intracranial injury among intoxicated blunt trauma patients who are selected for head CT is lower than among nonintoxicated patients selected for imaging, which likely represents heightened concern in the presence of intoxication, even without other findings suggestive of intracranial injury. This conclusion is supported by the fact that few intoxicated patients with normal neurologic findings and no evidence of trauma to the calvarium had positive findings on CT imaging.

Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Hemodynamic responses that control blood pressure and the distribution of blood flow to different organs are essential for survival. Shear forces generated by blood flow regulate hemodynamic responses, but the molecular and genetic basis for such regulation is not known. The transcription factor KLF2 is activated by fluid shear stress in cultured endothelial cells, where it regulates a large number of vasoactive endothelial genes. Here, we show that Klf2 expression during development mirrors the rise of fluid shear forces, and that endothelial loss of Klf2 results in lethal embryonic heart failure due to a high-cardiac-output state. Klf2 deficiency does not result in anemia or structural vascular defects, and it can be rescued by administration of phenylephrine, a catecholamine that raises vessel tone. These findings identify Klf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function.

Recombinant expression of Taenia solium TS14 antigen and its utilization for immunodiagnosis of neurocysticercosis. In order to evaluate the potential use of TS14 antigen in an enzyme-linked immunosorbent assay (ELISA) for immunodiagnosis of neurocysticercosis (NC), its open reading frame (ORF) was amplified by RT-PCR from mRNA isolated from Taenia solium cysticerci. The ORF was subcloned into the expression vector pET-28a, and was used to transform Escherichia coli BL21 (DE3) cells to produce TS14 antigen. The His-tagged expressed protein was purified on a nickel affinity column. Using the HISTS14 as antigen, ELISA was positive for 100% of cerebrospinal fluid (CSF) and 97% of serum samples from NC patients. No positive results were observed with sera and CSF samples from control groups. Cross-reactivity with sera from patients with schistosomiasis and Chagas' disease was not observed. Serum samples from patients with taeniasis were evaluated and 2 of 13 cases showed reactivity in this assay. Our data indicate the usefulness of HISTS14 in ELISA for an accurate and rapid assay for diagnosis of NC and seroepidemiological studies.

The human lateral pterygoid muscle. One of the jaw muscles particularly implicated in temporomandibular disorders (TMD), a common form of non-dental chronic orofacial pain, is the human lateral pterygoid muscle. The precise role of this muscle in TMD is unclear as is the nature of the interaction between pain and motor function particularly involving this muscle. This research group has adopted a two-stage approach to studying the effects of pain on motor function. The first is to study normal orofacial motor function through recordings of jaw movement and electromyographic (EMG) activity from a number of jaw muscles (including recordings from the lateral pterygoid muscle; verification of electrode location achieved through computer tomography imaging) during a number of standardised jaw movements. These studies have defined the detailed functional properties of, in particular, the lateral pterygoid muscle, whose physiology and function is not well understood. In summary, the data are consistent with the hypothesis previously proposed that the lateral pterygoid should be regarded as a system of fibres that acts as one muscle, with varying amounts of evenly graded activity throughout its entire range, and with the distribution of activity within the muscle being determined by the biomechanical demands of the task. Our second approach has been to study the effects of experimental masseter muscle pain on the detailed functional properties (e.g., root-mean-square EMG activity) of the jaw muscles, especially the lateral pterygoid muscle. Preliminary data from these pain studies point towards significant effects of human experimental muscle pain on jaw muscle activity and jaw movement.

Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse. The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.

Negative association of obesity and its related chronic inflammation with serum glycated albumin but not glycated hemoglobin levels. BACKGROUND Measurements of glycated albumin (GA) as well as glycated hemoglobin (HbA1c) have been applied in order to monitor chronic glycemic control in diabetic patients. Both glycated proteins are known influenced by various factors other than glycemia. It has recently been reported that GA level is low in obese, non-diabetic children and is negatively associated with body mass index (BMI) in adult diabetic patients. However, the reasons for the connection between obesity and GA remain unknown. The aim of this study was to examine whether BMI and the obesity-related inflammatory marker plasma high-sensitivity C-reactive protein (hs-CRP) are independently associated with GA and HbA1c. METHODS Two hundred and twelve non-diabetic subjects (158 with normal glucose tolerance and 54 with impaired glucose tolerance) were enrolled in this study. The effects of fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2-h glucose, age, BMI and hs-CRP on HbA1c as well as those on GA were analyzed. RESULTS FPG significantly correlated with HbA1c, and also significantly but weakly correlated with GA. BMI showed a significantly positive correlation with HbA1c, whereas it negatively correlated with GA. Plasma hs-CRP showed a weak positive correlation with HbA1c, whereas it was negatively associated with GA. By stepwise multivariate regression analyses, BMI and hs-CRP were negatively associated with GA but not with HbA1c. CONCLUSIONS These results demonstrated that BMI as well as hs-CRP were independent negative risks of GA but not of HbA1c in non-diabetic subjects. Obesity and its related chronic inflammation are involved in lower serum GA levels, but not HbA1c levels, in relation to glycemia.

Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats. This study aimed to dissect the mechanisms involved in malaise induced by the anti-cancer drug cisplatin by attempting to uncouple its effects on locomotor activity, arguably at least partly indicative of fatigue, from those effects indicative of emesis (pica, gastric stasis, reduced food intake) using pharmacological agents in the rat. Over 2 days cisplatin (6 mg/kg i.p.) reduced food intake, stimulated kaolin consumption, increased the wet weight of gastric contents and reduced locomotor activity. In animals treated with cisplatin: the 5-HT3 receptor antagonist ondansetron (1 mg/kg s.c. bd.) had no effect on either activity or weight of gastric contents but did increase food intake on day 1 (P<0.05) and the total over both days (27.6+/-1.8 vs. 19.9+/-2.3g, P<0.05), reducing kaolin consumption on day 2 (P<0.01) but not the total over both days; the NK1 receptor antagonist GR205171 (1 mg/kg s.c. bd.) was without effect on activity, but reduced the wet weight of gastric contents (P<0.05), increased food intake on day 2 (P<0.01) and total consumption over both days (28.1+/-1.7 g vs. 19.9+/-2.3 g; P<0.05) and reduced kaolin consumption on day 2 (P<0.05) but not over both days; dexamethasone (2 mg/kg s.c. bd.) blocked the cisplatin-induced reduction in activity on days 1 and 2 (P<0.01), reduced the wet weight of gastric contents by 43% (P<0.01), reduced kaolin consumption on both days (P<0.01) and arguably decreased the reduction in food intake caused by cisplatin. This study has revealed novel insights into the different spectra of activities of 5-HT3 and NK1 receptor antagonists and dexamethasone, which have implications for therapeutic strategies to alleviate the emetic, anorectic, dyspeptic and activity-reducing effects of anti-cancer chemotherapy.

Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis in mice. TS-022, {4-[(1R, 2S, 3R, 5R)-5-Chloro-2-((S)-3-cyclohexyl-3-hydroxyprop-1-y butylthio} acetic acid monohydrate, inhibits ADP-induced platelet aggregation, an effect significantly antagonized, as in the case of prostaglandin D(2) by the prostanoid DP(1) receptor antagonist (BW A868C). TS-022 is a prostanoid DP(1) receptor agonist, originally developed as a novel anti-pruritic drug for patients with atopic dermatitis. We examined the effects of TS-022 on experimental pruritus, cutaneous barrier disruption, and atopic dermatitis and in in vitro immune function tests. Topically applied TS-022 significantly suppressed scratching in skin-lesioned NC/Nga mice from a concentration of 2.5 nM, and this scratch-suppressive activity was significantly antagonized by BW A868C. Tacrolimus (FK-506) and dexamethasone, used as reference drugs for atopic dermatitis, also exhibited suppressive effects against scratching, but only at concentrations of 125 and 25,000 microM. TS-022 applied topically, once a day for 2 days, significantly accelerated repair of the cutaneous barrier disruption caused by mechanical scratching, from concentrations of 2.5 nM. This acceleration of repair of the disrupted cutaneous barrier by this drug was also significantly antagonized by BW A868C. FK-506 and dexamethasone showed no beneficial effects on the repair of the disrupted cutaneous barrier. Repeated topical application of 2.5 microM of TS-022 and 12.5 microM of FK-506 once a day for 6 weeks significantly improved the skin inflammation scores in the NC/Nga mice. In regard to the effects of TS-022 in vitro, the inhibitory activity of TS-022 against concanavalin A-induced cytokine production by splenocytes was marginal as compared with that of FK-506 or dexamethasone. These results suggest that the beneficial therapeutic effects of TS-022 in NC/Nga mice with atopic dermatitis are mediated by its suppressive effect on scratching and its effect of accelerating repair of the disrupted cutaneous barrier, both effects being attributable to its prostanoid DP(1) receptor agonistic activity.

Early excitability changes in a novel acute model of transient focal ischemia and reperfusion in the in vitro isolated guinea pig brain. The study of the early events that characterize cerebral ischemia is limited in available experimental models. The study of neurophysiological network changes that occur in brain tissue during the early minutes that follow focal ischemia induction is restricted in the in vivo condition. Very simplified systems, such as in vitro brain slices and in isolated neurons, have been utilized for this type of studies. We describe here a new model of transient focal ischemia and reperfusion developed in the isolated guinea pig brain, maintained in vitro by arterial perfusion with a complex saline solution without blood cells. In this preparation, that combines the advantage of an in vitro preparation with the functional preservation of both vascular and neuronal compartments, the arteries of the Willis circle are directly accessible by visual control. To induce transitory focal ischemia, one medial cerebral artery (MCA) was transiently tied for 30 min, while brain activity was recorded with multiple electrodes positioned in brain areas within and outside MCA territory. Anoxic depression in ischemic areas propagated to the surrounding tissue and was associated with the abolition of evoked responses due to both functional impairment of afferent olfactory input and tissue depression. Recovery of evoked responses was obtained after MCA reperfusion. The spatial distribution of hypoxic depressions was characterized and was correlated with the extension of brain damage, defined by immunohistochemical analysis with antibodies against microtubule-associated protein (MAP-2). We propose that the present model can be utilized to analyze brain activity changes that occur in early stages of focal brain ischemia and reperfusion.

Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDA. Metabolic profiling has increasingly been used as a probe in disease diagnosis and pharmacological analysis. Herein, plasma fatty acid metabolic profiling including non-esterified fatty acid (NEFA) and esterified fatty acid (EFA) was investigated using gas chromatography/mass spectrometry (GC/MS) followed by multivariate statistical analysis. Partial least squares-linear discrimination analysis (PLS-LDA) model was established and validated to pattern discrimination between type 2 diabetic mellitus (DM-2) patients and health controls, and to extract novel biomarker information. Furthermore, the PLS-LDA model visually represented the alterations of NEFA metabolic profiles of diabetic patients with abdominal obesity in the treated process with rosiglitazone. The GC/MS-PLS-LDA analysis allowed comprehensive detection of plasma fatty acid, enabling fatty acid metabolic characterization of DM-2 patients, which included biomarkers different from health controls and dynamic change of NEFA profiles of patients after treated with medicine. This method might be a complement or an alternative to pathogenesis and pharmacodynamics research.

Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation. Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

Surgically treated acetabular fractures via a single posterior approach with a follow-up of 2-10 years. The results of operative treatment of acetabular fractures as well as its role in the occurrence of post-traumatic osteoarthritis (OA) are presented. From 1990 to 2000, 50 patients (32 male and 18 female), aging from 18 to 71 years (mean: 37.8 years) underwent an open reduction and internal fixation of their displaced acetabular fracture. They were reviewed at a mean of 5.8 years (2-10 years). A typical Kocher-Langebeck approach was selected in all the patients and in 14 cases a trochanteric osteotomy was added to enhance exposure. The fractures were classified according to the Letournel-Judet classification. The aim of the operation was the anatomic reduction and stable fixation of the fracture with less than 2mm residual displacement, which was achieved in 39 of 50 cases. Post-operative protocol included low-molecular-weight heparin (LWMH) as antithrombotic prophylaxis and 75 mg of indomethacin against heterotopic ossification (HO). At the final follow-up, the patients were evaluated clinically according to D'Aubigne-Postel scoring system and radiologically based on the criteria described by Matta. The clinical results were excellent in 20 patients, good in 18, fair in 5 and poor in 7. The radiological results were excellent in 20 patients, good in 16, fair in 5 and poor in 9. Early post-operative complications included 2 peroneal nerve palsies and 3 wound infections and late complications included 1 patient with avascular necrosis of the femoral head (ANFH), 5 patients with grade III and IV heterotopic ossification according to Brooker classification and 12 patients with post-traumatic osteoarthritis of the hip joint. Although the rates of early and late complications were relatively common, the functional outcome was satisfactory in most of the cases and comparable with other larger series. We concluded that operative treatment of most of the displaced acetabular fractures--except of isolated anterior column or/and anterior wall - could be attempted via a single posterior approach, leading to good to excellent results in the majority of the cases.

Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects. The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matching placebo and to fosinopril 20mg or matching placebo. Using high resolution ultrasound, flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) was assessed at baseline and after 4 years of treatment in a total of 276 subjects. At baseline, mean+/-standard error FMD was 4.73+/-0.49% and NID was 10.86+/-0.67%. Pravastatin significantly reduced total cholesterol and LDL cholesterol (p<0.01) and randomization to pravastatin was associated with a non-significant improvement of 18.9% in FMD (+0.80+/-0.95, p=0.09), without a significant change in NID. Interestingly, pravastatin significantly increased FMD by 34.9% in men (+1.23, p=0.04), but only 1.1% in women (+0.06, p=0.95). Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion, systolic and diastolic blood pressure (all p<0.01). In conclusion, after 4 years of follow-up, pravastatin treatment tended to increase FMD and this effect was predominantly present in men. Fosinopril treatment did not modify FMD during long-term follow-up.

Stimulation of the peroxisome proliferator-activated receptor gamma (PPAR gamma) and the expression of selected blood monocyte cytokine genes in diabetic macroangiopathy. Monocytes and macrophages play a key role in the progression of atheromatous changes. The peroxisome proliferator-activated receptor gamma (PPAR gamma) can limit macroangiopathy through the control of cytokine transcription. The objectives of this study were to examine the influence of PPAR gamma and its agonist (rosiglitazone) on the TNFalpha, IL-6, IL-8 and IL-10 gene expression in monocytes of patients with diabetic macroangiopathy and to analyse obtained results in context of selected atherogenic factors ant direct indicators of endothelial lesion. TNFalpha, IL-6, IL-8, IL-10 and PPAR gamma gene expression was assessed in peripheral blood monocytes in 45 patients with type 2 diabetes before and following 22 weeks of rosiglitazone therapy (real-time PCR [Applied Biosystems]). As indicators of endothelial lesion, concentration of thrombomodulin (immunoassay [Diagnostica Stago]) and amount of circulating blood endothelial cells (immunofluorescence method with MoAb CLB-HEC19) were determined. Following rosiglitazone therapy, a statistically significant downward tendency of TNFalpha (p=0.026) and IL-8 (p=0.008) gene expression was noted. Before and following rosiglitazone treatment, PPAR gamma, IL-6 and IL-10 gene expression was undetectable in studied monocytes in vivo. In conclusion, TNFalpha and IL-8 play an important role in monocyte atherogenic activity. Rosiglitazone reduces monocyte proinflammatory readiness by influencing the expression of selected atherogenic cytokines (PPAR gamma-independent pathway).

Psychopathological and nutritional correlates of plasma homovanillic acid in adolescents with anorexia nervosa. Dopaminergic abnormalities have been described in anorexia nervosa but studies about plasma level of homovanillic acid (pHVA) have yielded conflicting results probably due to the small number and the heterogeneity of patients. Plasma HVA, nutritional and hormonal parameters and several scales - the Eating Attitudes Test (EAT), the Beck Depression Inventory (BDI), the Leyton Obsessional Inventory-child version (LOI-C) and the State and Trait Anxiety Inventory (STAI) - were assessed in 44 adolescent anorexia nervosa patients (mean age 14.7 years, SD 1.7) consecutively admitted to an Eating Disorder Unit. They were evaluated at admission, at discharge and, in 34 cases, after 9 months of follow-up. pHVA was also assessed in 16 control adolescents. Patients had significantly higher pHVA than controls (p = .002). About 31% of patients had a very high level of pHVA, a significantly higher (p = .006) mean score in the BDI and a non significantly higher mean score in the EAT. After weight recovery some laboratory parameters improved as well as the EAT (p = .019), the BDI (p = 001) and the Interference score of the LOI-C (p = .004). Moreover, pHVA decreased significantly (p=.036). At follow-up, patients with normal weight had lower (p = .037) pHVA than patients with low weight. The conclusion would be that there is a dopaminergic dysfunction in anorexic patients, specially in a subgroup with high depressive and anorexic symptomatology. With weight recovery and psychopathological improvement, pHVA tends to normalization.

Molecular deletion patterns in Duchenne and Becker muscular dystrophy patients from KwaZulu Natal. There exists much phenotypic heterogeneity in Duchenne muscular dystrophy and its allelic variant, Becker muscular dystrophy. The molecular findings on 53 patients with Duchenne and 15 patients with Becker type muscular dystrophy in KwaZulu Natal, South Africa are reported. Multiplex PCR was performed using primers targeting 18 hot-spot exons throughout the dystrophin gene. Analysis of the multiplex PCR data revealed that 39/68 (57.0%) patients included in the study showed a deletion (33 DMD and 6 BMD patients). Twenty-five patients were Black, 4 were White and 10 were Indian. Using the Chamberlain and Beggs multiplex PCR assays, the region of the genome most frequently affected by a deletion includes exons 47-51. The distal region of the dystrophin gene was most frequently affected by the deletion in both Black and Indian patients. There were too few White patients for conclusions to be drawn concerning the most frequently affected part of the gene. Although the numbers are insufficient to determine whether ethnic differences are present, the Chamberlain and Beggs multiplex PCR assays detect deletions with the same frequency in South African DMD/BMD patients as that reported in the literature.

beta1 antagonist and beta2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFalpha in rat with type II diabetes. UNLABELLED The effect of beta antagonists in the diabetic vascular lesion is controversial. We investigated the effect of celiprolol hydrochloride, a beta1 antagonist and mild beta2 agonist, on the lesions and function in type II male Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats. OLETF rats were fed regular chow with or without atenolol (25 mg/kg/day) or celiprolol (100 mg/kg/day) treatment (group DM, no treatment; group DM-a, atenolol treatment; group DM-c, celiprolol treatment), and treatment was continued for 31 days. Separately, normoglycemic control rats, LETO, were prepared as group C. On day 3, endothelial cells of the right internal carotid artery were removed by balloon injury, and the rats were evaluated 4 weeks after balloon injury. The plasma glucose and lipid levels were unchanged throughout the treatment period. Intimal thickening was observed in the right carotid artery in the DM and DM-a groups; however, little thickening was observed in those of DM-c rats. Acetylcholine-induced NO-dependent relaxation in arteries was improved in DM-c rats compared with DM and DM-a rats (maximum relaxation DM 30.8+/-4.5, DM-a 37.4+/-3.9, DM-c 48.8+/-4.6%, *P<0.05 vs. DM for DM-c rats). Tone-related basal NO release and acetylcholine-induced NO-dependent relaxation in the arteries and plasma NO(x) (sum of NO(2)(-) and NO(3)(-)) were greater in DM-c and C groups than in DM and DM-a groups. The serum TNFalpha levels did not increase in DM-c rats compared with those of the DM or DM-a groups, and were comparable with those of group C. CONCLUSION In conclusion, Celiprolol improves endothelial function in the arteries of OLETF rats, and further restore it 4 weeks after endothelial denudation in the arteries of OLETF rats. NO and O(2)(-) may have a role in the important underlying mechanisms by reducing the TNFalpha levels.

A novel mutation in the SCN5A gene is associated with Brugada syndrome. Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit (Na(v)1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in tsA201 cells, and the sodium currents (I(Na)) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Na(v)1.5/W1191X) co-transfected with the beta(1)-subunit in tsA201 cells resulted in a loss of function of Na(v)1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Na(v)1.5 activation and fast inactivation kinetics, the Na(v)1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in I(Na). No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.

Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells. Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of various cardiovascular diseases including atherosclerosis, as well as cancers. Gypenoside (Gyp) XLIX, a dammarane-type glycoside, is one of the prominent components in GP. We have recently reported Gyp XLIX to be a potent peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gyp XLIX (0-300 microM) concentration dependently inhibited TF promoter activity after induction by the inflammatory stimulus lipopolysaccharide (LPS) in human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC. Furthermore, Gyp XLIX inhibited LPS-induced TF mRNA and protein overexpression in THP-1 monocyte cells. Its inhibition of LPS-induced TF hyperactivity was further confirmed by chromogenic enzyme activity assay. The activities of Gyp XLIX reported in this study were similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, the Gyp XLIX-induced inhibitory effect on TF luciferase activity was completely abolished in the presence of the PPAR-alpha selective antagonist MK-886. The present findings suggest that Gyp XLIX inhibits LPS-induced TF overexpression and enhancement of its activity in human THP-1 monocytic cells via PPAR-alpha-dependent pathways. The data provide new insights into the basis of the use of the traditional Chinese herbal medicine G. pentaphyllum for the treatment of cardiovascular and inflammatory diseases, as well as cancers.

A role for the 'magnocellular advantage' in visual impairments in neurodevelopmental and psychiatric disorders. Evidence exists implicating abnormal visual information processing and visually driven attention in a number of neurodevelopmental and psychiatric disorders, suggesting that research into such disorders may benefit from a better understanding of more recent advances in visual system processing. A new integrated model of visual processing based on primate single cell and human electrophysiology may provide a framework, to understand how the visual system is involved, by implicating the magnocellular pathway's role in driving attentional mechanisms in higher-order cortical regions, what we term the 'magnocellular advantage'. Evidence is also presented demonstrating visual processing occurs considerably faster than previously assumed, and emphasising the importance of top-down feedback signals into primary visual cortex, as well as considering the possibility of lateral connections from dorsal to ventral visual areas. Such organisation is argued to be important for future research highlighting visual aspects of impairment in disorders as diverse as schizophrenia and autism.

Psychopathology in great apes: concepts, treatment options and possible homologies to human psychiatric disorders. Many captive great apes show gross behavioral abnormalities such as stereotypies, self-mutilation, inappropriate aggression, fear or withdrawal, which impede attempts to integrate these animals in existing or new social groups. These abnormal behaviors resemble symptoms associated with psychiatric disorders in humans such as depression, anxiety disorders, eating disorders, and post-traumatic stress disorder. Due to the outstanding importance of social interaction and the prolonged period of infantile and juvenile dependence, early separation of infants from their mothers and other adverse rearing conditions, solitary housing, and sensory deprivation are among the major albeit non-specific sources of psychopathology in apes. In contrast to the wealth of research in monkeys, psychopathology in apes has been under-studied, and only a few studies have examined how to alleviate abnormal behavior in captive apes. Recent studies have shown that the enrichment of living conditions and behavioral treatment (conditioning) may ameliorate some pathological features, and careful familiarization with novel physical and social environments can help re-socialize behaviorally disturbed animals, but usually not to the extent of successful mating and raising offspring. The possibility of psychopharmacological treatment of the most severe disturbed animal patients has only been reluctantly considered, but a few case reports have revealed encouraging results. This article proposes the need to expand research into ape psychopathology, which would require an essentially interdisciplinary approach of primatology and psychiatry, ultimately to the benefit of both.

Retinal vein occlusion and vascular mortality: pooled data analysis of 2 population-based cohorts. PURPOSE To assess the association of retinal vein occlusion (RVO) with cardiovascular and cerebrovascular mortality. DESIGN Pooled data from 2 population-based cohort studies. PARTICIPANTS At baseline, the Beaver Dam Eye Study (BDES) examined 4926 persons aged 43 to 86 years (from 1988-1990) and the Blue Mountains Eye Study (BMES) examined 3654 persons aged 49 to 97 years (from 1992 to 1994). METHODS Retinal vein occlusion was assessed from retinal photographs. Vascular deaths were determined using either death certificates (BDES) or the Australian National Death Index (BMES). Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURE Vascular (cardiovascular and cerebrovascular) mortality was determined. RESULTS Of 8384 baseline participants, 96 (1.14%) had RVO at baseline (BDES, n = 38; BMES, n = 58). Over 12 years, 1312 (15.7%) died of cardiovascular-related conditions and 341 (4.1%) died of cerebrovascular-related conditions. Age-standardized vascular mortality rates were 26.0% and 5.3%, respectively, in persons with RVO and 17.1% and 4.5%, respectively, in those without RVO. After adjusting for age, gender, body mass index, hypertension, diabetes, smoking, glaucoma, and study site, RVO was not associated with cardiovascular-related mortality (HR, 1.2; 95% CI, 0.8-1.8) or cerebrovascular-related mortality (HR, 0.9; 95% CI, 0.4-2.1) among participants of all ages. However, in persons aged less than 70 years, baseline RVO was associated with higher cardiovascular mortality (combined BDES and BMES: HR, 2.5; 95% CI, 1.2-5.2; BDES: HR, 2.5; 95% CI, 0.9-6.9; BMES: HR, 2.1; 95% CI, 0.7-6.8). CONCLUSIONS Retinal vein occlusion in persons aged 43 to 69 years may signal a doubling of the risk of cardiovascular mortality.

Natural history of the visual impairment of relapsing neuromyelitis optica. PURPOSE To describe the clinical features and natural history of the visual impairment of relapsing neuromyelitis optica. DESIGN Prospective observational case series. PARTICIPANTS Thirty patients of Afro-Caribbean origin with neuromyelitis optica and 47 patients with multiple sclerosis. METHODS A complete ophthalmologic examination was performed with each ocular attack and during a remission period at least 6 months after the last attack. MAIN OUTCOME MEASURES Incidence of unilateral and bilateral optic neuritis and incidence of unilateral and bilateral severe visual loss, defined as visual acuity (VA) < or = 20/200. RESULTS Twenty-eight patients (93%) with neuromyelitis optica were female and 2 (7%) were male. The mean age of onset was 30+/-10.5 years. Mean disease duration was 9.5+/-5.4 years. Neuromyelitis optica first manifested by an episode of optic neuritis in 23 cases (76.6%), bilateral in 4. The average number of ocular attacks per patient was 2.7+/-1.6. Twenty-one patients (70%) showed impairment in both eyes. Median times from onset to unilateral optic neuritis, bilateral optic neuritis, mono-ocular severe visual loss, and binocular severe visual loss were 0+/-0.08, 1+/-1.6, 2+/-0.8, and 13+/-3 years, respectively. Fifteen patients (50%) experienced severe visual loss in both eyes and 6 (20%) in one eye. Severe visual loss occurred in as few as 2 attacks. CONCLUSION This study is the largest series of relapsing neuromyelitis optica in a population of African descent. Neuromyelitis optica's visual impairment is very severe; it contrasts drastically with that typically observed in multiple sclerosis. We confirmed that the prognosis for optic neuritis in patients with neuromyelitis optica is worse than the prognosis in patients with multiple sclerosis.

Visual field and intraocular pressure asymmetry in the low-pressure glaucoma treatment study. OBJECTIVE To explore the relationship between asymmetric baseline intraocular pressure (IOP) and asymmetric visual field (VF) loss in the Low-Pressure Glaucoma Treatment Study. DESIGN Randomized, multicenter, controlled clinical trial. PARTICIPANTS Low-pressure glaucoma (LPG) patients 30 years or older were identified. Exclusion criteria included an untreated pressure > 21 mmHg, advanced VF loss, and contraindications to study medications. INTERVENTIONS A baseline VF was created using the average of 2 reliable Humphrey full-threshold examinations. A baseline diurnal IOP curve was performed without IOP-lowering medication. MAIN OUTCOME MEASURES Mean diurnal, peak, trough, IOP range (peak - trough), and standard deviation (SD) of IOP measurements, and mean deviation (MD) and corrected pattern SD (CPSD) of VF examinations. RESULTS One hundred ninety patients were enrolled (mean age, 64.9+/-10.7 years). Mean deviation and CPSD were not correlated with mean, peak, trough, or peak minus trough (P - T) IOP (Ps = 0.2-0.9). Among patients with unilateral VF loss (n = 53 [27.9%]), there were no differences (Ps = 0.3-0.9) in any IOP parameter between the normal VF eye and fellow glaucomatous eyes. Among patients with bilateral VF loss (n = 137 [72.1%]), mean, peak, trough, and P - T IOPs were similar in eyes with a better VF MD compared with eyes with a worse VF MD (Ps = 0.2-0.7). Cross-classified contingency tables demonstrated no relationship (Ps = 0.1-0.3) between IOP and VF MD or CPSD using chi-square analysis. CONCLUSIONS Intraocular pressure asymmetry is unrelated to VF asymmetry in the Low-Pressure Glaucoma Treatment Study, suggesting an unclear pathogenic relationship between IOP and glaucomatous damage in eyes with LPG.

Rapid assessment of avoidable blindness in Nakuru district, Kenya. OBJECTIVES To estimate the prevalence of avoidable blindness in > or =50-year-olds in Nakuru district, Kenya, and to evaluate the Rapid Assessment for Avoidable Blindness (RAAB), a new methodology to measure the magnitude and causes of blindness. DESIGN Cross-sectional population-based survey. PARTICIPANTS Seventy-six clusters of 50 people 50 years or older were selected by probability proportionate to size sampling of clusters. Households within clusters were selected through compact segment sampling. Three thousand seven hundred eighty-four eligible subjects were selected, of whom 3503 (92.6%) were examined. METHODS Participants underwent a comprehensive ophthalmic examination in their homes by an ophthalmologist, including measurement of visual acuity (VA) with a tumbling-E chart and the diagnosis of the principal cause of visual impairment. Those who had undergone cataract surgery were questioned about the details of the operation and their satisfaction with surgery. Those who were visually impaired from cataract were asked why they had not gone for surgery. MAIN OUTCOME MEASURES Visual acuity and principal cause of VA<6/18. RESULTS The prevalence of bilateral blindness (presenting VA < 3/60) was 2.0% (95% confidence interval [CI], 1.5%-2.4%), and prevalence of bilateral visual impairment (VA of <6/18-> or =6/60) was 5.8% (95% CI, 4.8%-6.8%) in the sample. Definite avoidable causes of blindness (i.e., cataract, refractive error, trachoma, and corneal scarring) were responsible for 69.6% of bilateral blindness and 74.9% of bilateral visual impairment. Cataract was the major cause of blindness (42.0%) and visual impairment (36.0%). The cataract surgical coverage was high, with 78% of those with bilateral cataract who needed surgery having had surgery at VA<3/60. The quality of surgery was of concern because 22% of the 222 eyes that had undergone cataract surgery had VA<6/60 with best correction. The main barriers to surgery were lack of awareness and cost. The RAAB methodology was easy to use, and each team could visit one cluster per day. CONCLUSIONS The prevalence of blindness in > or =50-year-olds in Nakuru district was low, in part due to the high cataract surgical coverage. The RAAB is easy to use and inexpensive and provides information about the magnitude and causes of avoidable blindness that can be used for planning and monitoring eye care services.

Retinal endovascular lysis in ischemic central retinal vein occlusion: one-year results of a pilot study. PURPOSE Retinal endovascular lysis is a new therapeutic option for patients with central retinal vein occlusion (CRVO). In this procedure, a fibrinolytic agent is injected directly into a cannulated retinal vein after pars plana vitrectomy. DESIGN Prospective interventional case series. PARTICIPANTS Thirteen strictly defined patients with ischemic CRVO. METHODS Patients with a decimal visual acuity (VA) of 0.2 or worse were scheduled for surgery within the first 5 months after onset of CRVO. A full ocular examination, determination of VA (Early Treatment Diabetic Retinopathy Study charts), and fluorescein angiography were done preoperatively and 6, 12, 26, and 52 weeks postoperatively. MAIN OUTCOME MEASURE Visual acuity 1 year after retinal endovascular lysis. Secondary study end points were (1) correlation of VA and successful recombinant tissue plasminogen activator injection into a retinal vein, (2) complication rate, and (3) number of additional surgical procedures within the first year after retinal endovascular lysis. RESULTS All patients had an ischemic CRVO and completed the 1-year follow-up visit. Preoperative decimal VA was 0.063 +0.025/-0.018 (VA range, light perception [LP]-0.2); 6-week postoperative VA, 0.049 +0.024/-0.016 (LP-0.4); 3-month postoperative VA, 0.043 +0.019/-0.014 (LP-0.3); 6-month postoperative VA, 0.035 +0.022/-0.013 (blindness-0.4); and 12-month postoperative VA, 0.04 +0.026/-0.016 (blindness-0.4). Visual acuity changed 1 year after retinal endovascular lysis by -1.923+/-1.619 lines (+6 to -16 lines; P = 0.258). We considered the retinal endovascular lysis procedure to have been technically successful in 10 eyes. Visual changes did not depend on successful lysis. Six eyes developed neovascular glaucoma, of which 2 globes ended up with painful phthisis and had to be removed. Retinal detachment was found in 3 eyes and cataract in 4. Together, the 13 eyes needed 22 additional surgical procedures. Preoperative and postoperative angiographic examinations showed no significant changes. CONCLUSION Ischemic CRVO patients did not profit from retinal endovascular lysis in this pilot study. Visual results and the risk of developing iris neovascularization and neovascular glaucoma took the natural course. Although these results may be due to the overall bad prognosis of these particular ischemic eyes, the number of postoperative complications is unacceptably high.

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia. The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

The effect of dental overbite on eustachian tube dysfunction in Iranian children. OBJECTIVE To investigate the association between deep dental overbite and eustachian tube dysfunction. METHODS It was designed as a case-control study. Among hospitalized patients in otolaryngology department at Taleghani Hospital in Tehran, Iran, from January to December 2005, 132 patients between the ages of 2 and 6 years were recruited. Dental overbite, overjet, and occlusal relationships were measured by one observer. Eustachian tube dysfunction was defined as having ventilation tubes with an abnormal tympanometry. In addition, demographic information, medical and social histories were prospectively recorded. Univariate and multivariate logistic regression model were used. RESULTS In a multivariate model, children with deep bites were 10.6 times more likely to have eustachian tube dysfunction than those without deep bites (P<0.05). Other independent risk factors for eustachian tube dysfunction identified in this model were family history of otitis media, daycare exposure, and non-breast-feeding. CONCLUSIONS Children with deep dental overbites are at a significantly increased risk for developing eustachian tube dysfunction.

Relationship between electrocardiographic and biochemical variables in coronary artery disease. BACKGROUND ECG (electrocardiogram) markers reflecting abnormal heart rate variability and abnormal repolarization as well as several biochemical markers reflecting inflammation, endothelial dysfunction, and procoagulation states were reported to show an association with increased cardiovascular mortality. ECG and biochemical markers could operate independently or they could interrelate in pathogenetic pathways of coronary disease. In this study, we aimed to explore the relationship between ECG and biochemical markers in a longitudinal study of coronary patients. METHODS A total of 499 observations from 52 patients with up to 12 repeated measurements were collected providing data on series of ECG (heart rate variability and repolarization) parameters and biochemical parameters. Generalized estimating equation models adjusting for repeated measurements were used for the analyses. RESULTS There was a significant association between ECG parameters reflecting abnormal repolarization (prolonged QT interval, lower T wave amplitude) and elevated levels of C-reactive protein and fibrinogen. Abnormal heart rate variability, increased sympathetic tone (low-frequency power) was associated with increased concentrations of soluble E-selectin, a marker of endothelial cell activation. There was no association between ECG markers and parameters reflecting increased procoagulation states. CONCLUSION These results indicate that there is an association between ECG parameters and blood markers reflecting endothelial function and inflammation in coronary artery disease patients. The pathophysiologic mechanisms of these associations remain to be elucidated.

A novel, noninvasive diagnostic probe for hydroa vacciniforme and related disorders: detection of latency-associated Epstein-Barr virus transcripts in the crusts. OBJECTIVE To establish a new diagnostic method for Epstein-Barr virus (EBV)-associated cutaneous disorders. DESIGN Skin biopsy is usually required to confirm the latent EBV infections in cutaneous lesions of EBV-associated NK/T-cell lymphoproliferative disorders, including hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). We have devised a novel, noninvasive method to detect EBV-encoded small RNA (EBER), BamHI A rightward transcripts (BARTs) in the skin crusts and scales of such patients. PATIENTS Six patients with EBV-associated cutaneous lesions were enrolled in the present study, including three patients with HV, one with HV-like eruptions and chronic active EBV infection, and two with EBV-associated cutaneous lymphoma. MAIN OUTCOME MEASURES RNA was extracted from the crusts obtained from the cutaneous lesions by forceps, converted to cDNA, and processed for polymerase chain reaction (PCR) amplification with a specific set of primers. The PCR products were assayed by a DNA sequencer. RESULTS Intact RNAs were successfully extracted from the crusts as well as control materials. EBER1 and BARTs RNAs were detected in all 7 crusts, and in 6 of 7 crusts of EBV-associated cutaneous diseases, respectively. One of 23 crusts from non EBV-associated diseases was positive for EBER1 RNA. The sensitivity and specificity of our assay for latent EBV infection were 100% and 95.8% for EBER1 RNA, and 85.7% and 100% for BARTs mRNA, respectively. The correct DNA sequence for EBER1 and BARTs was confirmed in the PCR products by a direct sequencing method. CONCLUSIONS Our procedure may be of use as a biomarker for EBV-associated cutaneous lesions, including HV, HMB, and NK/T-cell lymphomas.

Insulin secretion and insulin resistance in newly diagnosed, drug naive prediabetes and type 2 diabetes patients with/without metabolic syndrome. The relationships between insulin secretion and resistance in subjects with newly diagnosed prediabetes (preDM) and type 2 DM according to the presence of metabolic syndrome (MS) were controversial. We performed OGTT on 322 drug naive subjects with a history of hyperglycemia of < or =3 months, and divided into three groups, NGT, preDM (IFG and/or IGT), and T2DM. We also diagnosed these subjects with respect to MS according to ATP III criteria modified by Asia-Pacific guidelines and compared IGI and HOMA-IR. When compare groups stratified by the presence of MS, preDM and T2DM groups with MS showed significantly higher mean HOMA-IR and IGI than those without. When compare groups with respect to glucose tolerance, NGT, preDM, and T2DM subgroups in MS group showed significant higher HOMA-IR and lower IGI according to glucose tolerance. However, NGT, preDM, and T2DM subgroups in non-MS group showed a significant decrease in IGI but no significant difference in HOMA-IR as glucose tolerance worsened. In conclusion, deterioration in IGI and aggravation of HOMA-IR are both important in the primary pathogenesis of diabetes in those with MS. However, IGI deterioration may be the only important factor in the primary pathogenesis of T2DM in the absence of MS.

The effects of the diabetes related soft tissue hand lesions and the reduced hand strength on functional disability of hand in type 2 diabetic patients. OBJECTIVES The aim of the present study is to examine the effects of diabetes related soft tissue hand lesions such as Dupuytren's disease, trigger finger and limited joint mobility (LJM) and the reduced hand strength on the functional disability of the hand in type 2 diabetic patients. METHODS Forty-four type 2 diabetic patients and 60 age and sex matched controls were included in the study. Subjects were examined for the presence of Dupuytren's disease, trigger finger and LJM. Grip strength was tested first with Jamar dynamometer followed by pinch strength measurements using by a manual pinchmeter. Electrophysiological studies were performed in both groups. Duruz Hand Index (DHI) was used to assess the functional hand disability. RESULTS The mean DHI score of the diabetics was significantly higher than controls (p<0.0001). Dupuytren's disease, trigger finger or LJM was not correlated with DHI in diabetic patients (p>0.05). The grip and pinch strengths were significantly lower in diabetic patients than the non-diabetic controls (p<0.05) and the grip and pinch strengths were negatively correlated with DHI in type 2 diabetic patients (p<0.001). CONCLUSION Dupuytren's disease, trigger finger and LJM did not cause to functional disability of hand but low hand strength was found to cause functional disability of hand in our type 2 diabetic patients.

Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience. BACKGROUND Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). METHODS The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n=242) compared to observation (n=240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. RESULTS Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p=0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p=0.04) and worse QoL (SOB item, p=0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p=0.08) in patients with lower nadir during-treatment Hb and to longer OS (p=0.06) and RFS (p=0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p=0.003) and worse QoL (fatigue item, p=0.07). CONCLUSIONS Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels.

Malignant cutaneous tumors of the scalp: a study of demographic characteristics and histologic distributions of 398 Taiwanese patients. BACKGROUND The scalp is a unique anatomic region, in which pilosebaceous follicles are concentrated. OBJECTIVE We sought to investigate demographic characteristics and histologic distributions of malignant scalp tumors. METHODS Primary and metastatic scalp malignancies diagnosed histopathologically between 1983 and 2003 were reviewed. Age at diagnosis, sex, and histologic types were analyzed. RESULTS A total of 398 Taiwanese patients (200 males, 198 females) were selected. Age at diagnosis ranged from 3 to 103 years. Most malignant scalp tumors (69.8%) occurred in those 50 years or older. Basal (41.2%) and squamous (16.6%) cell carcinomas were the most common histologic types. Surprisingly, metastatic tumors (12.8%) came in third, in which lung cancers were the most frequent primary tumor in both male and female patients. LIMITATIONS In our series, the case number of metastatic scalp malignancies was underestimated because not all patients with metastatic scalp tumors received a scalp skin biopsy. CONCLUSION Because a wide spectrum of primary and metastatic malignancies can occur on the scalp, scalp inspection should be included in general screening for either skin or internal cancers.

Calciphylaxis: natural history, risk factor analysis, and outcome. BACKGROUND Calciphylaxis is characterized by ischemic cutaneous ulceration, high mortality, and ineffective treatment. METHODS We conducted a retrospective study of 64 patients with calciphylaxis (including 49 dialysis patients age- and sex-matched to 98 dialysis controls). RESULTS The estimated 1-year survival rate of calciphylaxis was 45.8%. Risk factors for calciphylaxis included obesity, liver disease, systemic corticosteroid use, calcium-phosphate product more than 70 mg(2)/dL(2), and serum aluminum greater than 25 ng/mL. Survival rates were similar for 16 patients who received parathyroidectomy and 47 who did not. An estimated 1-year survival rate of 61.6% was observed for 17 patients receiving surgical debridement compared with 27.4% for the 46 who did not (P = .008). LIMITATIONS The study was limited by its retrospective design and there was no control group for the 15 nondialysis cases. CONCLUSIONS Calciphylaxis is multifactorial and usually fatal. Prevention of calciphylaxis may include correction of risk factors identified in this study. Surgical debridement was associated with improved survival, but parathyroidectomy was not.

Allergic contact dermatitis from pimecrolimus in a patient with tacrolimus allergy. A 15-year-old male with previously documented allergic contact dermatitis from tacrolimus was allergic to pimecrolimus. This was demonstrated by double-blinded, right-versus-left provocative use testing with pimecrolimus cream 1% versus inactive vehicle applied twice daily to normal skin. The active cream but not its vehicle caused preauricular dermatitis starting after 1 week and caused isolated papules on the extensor wrist starting after 2 weeks. Patch testing on the patient's back was weakly positive (1+) with pimecrolimus cream 1% and negative with the vehicle. Higher concentrations of pimecrolimus were not available for testing. Patch tests on 30 control patients with pimecrolimus cream 1% were negative.

Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. BACKGROUND The epidemiology of dermatofibrosarcoma protuberans (DFSP) has not been studied in detail. OBJECTIVE We sought to describe patterns of DFSP incidence and survival in the United States. METHODS Data were obtained from 9 population-based cancer registries of the Surveillance, Epidemiology, and End Results Program for 1973 to 2002. RESULTS DFSP overall annual incidence was 4.2 per million. Incidence increased by 43% (3.1-4.4 per million per year) during the study period, but this increase was restricted to whites. Annual incidence among blacks (6.5 per million) was almost double the incidence among whites (3.9 per million; P < .005, 95% confidence interval of difference 2.02-3.22). Women had higher rates of incidence than men (4.4 vs 4.2 per million per year; P = .052, 95% confidence interval of difference -0.002 to 0.60), except among the elderly. Relative 5-year survival was 99.2% (95% confidence interval 98.3-100%). LIMITATIONS The Surveillance, Epidemiology, and End Results Program lacks independent verification of diagnoses and case detail. CONCLUSIONS The racial differences in the incidence of DFSP are significant, and the cause is unknown. Previous literature had suggested that men were more frequently affected, which was not true in our data. The tumor rarely results in death. Epidemiologic investigation using population-based data is important to better understand this disorder.

Methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis presenting in the skin. A 91-year-old woman who had been taking methotrexate for approximately 5 years for rheumatoid arthritis developed papules and nodules on her face that enlarged during 6 months. A series of biopsy specimens demonstrated a lymphoplasmacytic infiltrate with increasingly atypical histopathologic features that resembled diffuse large B-cell lymphoma. Epstein-Barr virus was not identified. Withdrawal of methotrexate resulted in complete resolution of all lesions within 8 weeks. This case illustrates the rare occurrence of methotrexate-associated lymphoproliferative disorder with primary presentation in the skin and documents clinical and histopathologic progression from early changes to fully developed lesions.

Verrucous carcinoma of the scalp. Verrucous carcinoma is a distinctive form of low-grade squamous cell carcinoma. It typically involves the oral cavity, larynx, esophagus, and skin. Cutaneous lesions typically arise in the genitocrural area and plantar surface of the foot, with rare case reports of verrucous carcinoma arising elsewhere on the body. Human papillomaviruses, predominately types 6 and 11, have been associated with some case reports. We present a case of verrucous carcinoma arising on the scalp with negative human papillomavirus testing in a relatively young patient.

Glutamate-glutamine cycling in Alzheimer's disease. In addition to its definitive pathological characteristics, neuritic plaques and neurofibrillary tangles, Alzheimer's disease (AD) brain exhibits regionally variable neuronal loss and synaptic dysfunction that are likely to underlie the symptomatic memory loss and language abnormalities. A number of mechanisms that could give rise to this localized damage have been proposed, amongst which excitotoxicity figures prominently. This is the process, well attested in experimental systems, whereby brain cells are excited to death by the pathophysiological action of the brain's most-abundant excitatory transmitter, glutamate. Glutamate transmission is mediated by a range of ionotropic and metabotropic receptors which, when activated, can lead to depolarization and increased intracellular Ca2+ ion concentration in the cells on which they are located. The action of glutamate is terminated by its removal from these receptor sites by transport into nearby cells, most commonly perisynaptic astrocytes. There it is converted to physiologically inert glutamine and shuttled back to excitatory nerve terminals. Malfunctions in components of the glutamate-glutamine cycle could result in a self-perpetuating neuronal death cascade mediated by glutamate. The approval by the FDA of an ionotropic glutamate receptor antagonist to treat late-stage AD has led to renewed interest in the contribution of altered glutamatergic neurotransmission to disease pathogenesis. This review encompasses those aspects of glutamate-glutamine cycling that are altered in AD.

[Pneumococcal septic arthritis revealing a multiple myeloma]. INTRODUCTION The most common presenting features of multiple myeloma are bone pain, anemia, renal failure or hypercalcemia. Bacterial infection as the initial presentation of this desease is rare. CLINICAL CASE We report the case of a 62-year-old man with pneumococcal septic arthritis of the knee revealing a multiple myeloma. DISCUSSION Pneumococcal infection should lead to a suspicion of underlying illness and especially the multiple myeloma.

Effect of Ilex extracts and isolated compounds on peroxidase secretion of rat submandibulary glands. Free radicals are involved in diverse disorders such as tumoral, central nervous system alterations, immunological and inflammatory pathologies. Peroxidase is an oral enzyme involved in the defense of the oral cavity. Ilex species such as Ilex paraguariensis St. Hil. and the commercial product made with it "Yerba Mate" are used traditionally as antirheumatics and for the treatment of gastrointestinal diseases among others and also as a beverage with nutritional and stimulant properties. The presence of polyphenolic derivatives and flavonoids in the aqueous extract has been determined by HPLC analysis. In this study, the activity of aqueous extracts of I. paraguariensis and "Yerba Mate" on peroxidase secretion in female rat submandibular glands was investigated. The contribution to this pharmacological activity by some major hydrocynnamic acid derivatives present in the crude extracts, such as chlorogenic acid and caffeic acid and the most abundant methylxanthine, caffeine, was also evaluated. Spectrophotometrical determination of peroxidase activity showed that both extracts produced a significant increase in both secreted peroxidase and total peroxidase activity, though "Yerba Mate" showed a higher activity (EC(50) "Yerba Mate": 148+/-10 microg/ml; EC(50)I. paraguariensis: 841+/-20 microg/ml). The HPLC/DAD analysis of the crude extracts was performed and chlorogenic acid, caffeic acid and caffeine were identified and quantified. The results (expressed as W/W percentage of dried material) were as follows: I. paraguariensis: chlorogenic acid: 2.80+/-0.30, caffeic acid: 0.023+/-0.004, caffeine: 1.06+/-0.06; "Yerba Mate": chlorogenic acid: 1.98+/-0.37; caffeic acid: 0.020+/-0.003, caffeine: 0.70+/-0.06. Caffeine and chlorogenic acid were proved to play an important role in the induction of peroxidase secretion induced by the extracts.

Caries susceptibility of human fluorosed enamel and dentine. OBJECTIVE Objective of our laboratory study was to determine the impact of dental fluorosis severity on the formation of caries in the human enamel and dentine. MATERIALS AND METHODS Thirty-three human molars were grouped according to modified Thylstrup-Fejerskov index (TFI) into normal (N, TFI 0), mild fluorosis (ML, TFI 1-3) and moderate fluorosis (MD, TFI 4-6). Three mesio-distal sections were made in corono-apical axis of the tooth, giving enamel and dentine samples. They were embedded in an epoxy resin, and polished. Half of the polished surface was covered with an acid resistant varnish and immersed in standard acidified buffer solution (pH 4.5) for 48 h to create artificial caries lesions. They were treated with 5% NaOCl for 45 min and sectioned longitudinally along the center into two halves. Cut surfaces were polished and observed under a confocal laser scanning microscope for depth of demineralization. Morphology of the demineralized zones was observed under a field emission scanning electron microscope (FE-SEM). Data were analyzed using one-way ANOVA and Sheffe test (p=0.05). RESULTS Statistically significant difference in depth of demineralization was found between N and MD groups (p=0.046) in the enamel, and between N and ML (p=0.002), N and MD (p<0.001), ML and MD (p=0.029) in dentine. FE-SEM observation of the normal enamel showed direct dissolution with large fissures. Spongy appearance of intertubular dentine gradually disappeared from N to MD. CONCLUSIONS Moderately fluorosed enamel showed a significant caries resistance. In contrast, mild and moderately fluorosed dentine was significantly caries susceptible in vitro.

Anaphylactic shock: the advantages of intra aortic balloon counter pulsation for the treatment of heart failure. The authors report a patient with a history of angina pectoris who developed anaphylactic shock that was complicated by a heart failure due to focal heart ischaemia. Early coronary angiography confirmed the diagnosis of localised coronary hypoperfusion. Intra aortic balloon counter pulsation succeeded in the restoration of coronary blood flow and haemodynamic stability. The authors discuss the opportunity of such treatment when a focal coronary hypoperfusion is diagnosed.

Treatment of wide scar contracture of antecubital fossa with bipedicle flap from scar tissue. Many surgical techniques exist for reconstruction of burn scar contracture of the antecubital fossa, such as Z plasty, VY plasty, lateral arm flap, and medial arm flap. Another option is direct release of the scar contracture and skin graft of the defect area, which requires prolonged splinting and risk of graft failure. Additionally, in the areas with exposed tendons or vessels, we cannot use grafts. Recurrence of contracture remains another drawback of this treatment, in this article we present a new, simple alternative method for treatment of these cases. In this clinical trial we introduce a new technique of bipedicle flap from scar tissue for coverage of the antecubital fossa with skin grafting of the proximal and distal parts of this bipedicle flap. From July 2002 to July 2005 we used this flap in 12 patients and efficacy and versatility of this flap was studied. Seven patients were female and 5 were male with mean age of 23.7 years. The mean time between burn and our reconstructive operation was 3.2 years. The mean surface area of antecubital burn scar tissue was 77.5%. Mean extension lag before operation was 66.5 degrees , mean extension lag during operation was 4.5 degrees and after operation was 5.4 degrees . Minor complication was observed in two cases with necrosis of the flap margin. Mean follow-up period was 17 months and the appearance of operated site in antecubital fossa was acceptable in all patients. The advantage of this bipedicle flap is its simple surgical technique. The risk of flap necrosis is negligible and it is a reliable flap. Splinting time is short and the risk of recurrence of contracture with this technique is minimal.

Can ageing-related degenerative diseases be ameliorated through administration of vitamin C at pharmacological levels? Man, with other primates, lost the ability to synthesize vitamin C through an inactivating mutation of the gene encoding gulonolactone oxidase (GULO) millions of years ago. Though the consequences of this prehistoric loss must have been favorable (and thus selected for) at the population level, the inability to produce vitamin C may have serious health implications for modern humans, especially for those conditions in which antioxidants (like vitamin C) have been implicated as potential therapeutic agents. Two general types of recent findings regarding vitamin C have made re-evaluation of this important nutrient imperative. First, vitamin C is now known to be involved in several novel physiological phenomena including stem cell differentiation and respiratory development, which likely require pharmacological levels of vitamin C. Secondly, the growing recognition that many ageing-related diseases, including heart disease, neural degeneration and cancer, may have a contributing oxidative damage factor that might be reduced by dietary antioxidants such as vitamin C. In this paper, we hypothesize that high serum-level vitamin C provides important, broad-ranging therapeutic benefits in treating ageing-related degenerative diseases. This hypothesis can be readily tested using traditional and newly-developed genetically-engineered animal models.

Deriving phenotypes for molecular genetic studies of substance use disorders: a family study approach. Although, family, twin, and adoption studies indicate that genes play a significant etiologic role in the development of substance use disorders (SUDs), the specific genes involved have been difficult to detect due, in part, to uncertainties about how best to define SUDs, the possibility of genetic heterogeneity and the variable phenotypic expression of SUD genotypes. The goal of the present work was to determine if phenotypes external to the diagnosis of SUD such as psychopathology and cognitive functioning would show evidence of utility as phenotypes for genetic studies of SUD. We did this by applying factor analysis to multiple measures collected from our family-study program and then determining if these factors were heritable and were co-familial with SUDs. We used data from families recruited into six contemporaneous studies of four psychiatric conditions in children and adults. We found evidence for two SUD related phenotypes. One was an index of Psychopathology and Psychosocial Impairment; the other was an index of school failure and cognitive dysfunction. Both factors showed evidence of heritability, longitudinal stability and familial association with Parental SUD but these findings were stronger for the index of school failure and cognitive dysfunction. Results provide some support for the idea that candidate SUD phenotypes such as psychopathology and cognitive functioning, which are external to the diagnostic criteria for SUDs, may be useful for genetic studies of SUD.

Expression of Syk is associated with nasal polyp in patients with allergic rhinitis. OBJECTIVE Numerous signalings are involved in allergic inflammation. The non-receptor protein tyrosine kinase, Syk, is widely expressed in immune-potentiated cells and plays critical roles in initiating signal transduction in response to the activation of cytokine, chemokine and other types of receptors. It has been hypothesized that Syk expression in allergic nasal mucosa and polyps with allergy is different from non-allergic mucosa, and that changes in Syk expression contribute to the activation of allergic reactions. METHODS We examined whether the expression of Syk is found in allergic nasal mucosa and polyps. We investigated the expression of Syk in 46 nasal mucosa and polyps (14 samples from patients with allergic rhinitis and 32 samples with non-allergic chronic sinusitis) using an immunohistochemical technique. RESULTS Allergic polyps had more Syk positive cells than non-allergic polyps. Syk positive cells were determined to mainly be eosinophils. There was no difference in Syk expression in the lamina propria and nasal gland between allergic mucosa and non-allergic mucosa. CONCLUSION Eosinophils in allergic polyps receive an intracellular signal, although the signal is not able to determine the function in the present state. Syk appears to be a promising target molecule for anti-allergic inflammation in allergic rhinitis.

Endoscopic transnasal transethmosphenoidal approach for pituitary tumors: assessment of technique and postoperative findings of nasal and paranasal cavities. OBJECTIVE Transnasal endoscopic surgery is the most common approach to removal of pituitary tumors. This study evaluated the transnasal transethmosphenoidal approach (TTES) in terms of its operative manipulability and the postoperative status of the paranasal cavities. METHODS A total of 132 patients with pituitary tumors underwent surgery by one of the following three approaches: (1) bilateral TTES, in which the surgical procedures were performed via the bilateral paranasal cavities, (2) unilateral TTES, in which the procedures were performed via one side only, and (3) unilateral TTES and resection of the posterior portion in the nasal septum approach (RPS), which is a modification of approach (2) and enables performance of the procedures from both sides. RESULTS The degree of freedom for the surgical procedures with each of the approaches decreased in the following order: bilateral TTES, unilateral TTES and RPS, and unilateral TTES. The postoperative CT images and endoscopic findings were good with each of the surgical approaches, but the incidences of olfactory disturbance and nasal dryness were significantly higher with the bilateral TTES compared with the unilateral TTES and RPS and the unilateral TTES. CONCLUSION The unilateral TTES and RPS was for us most suitable approach of the three methods. In the case of advanced tumors, the bilateral TTES should be selected because it permits superior operative manipulability. Finally, the unilateral TTES is most appropriate for removal of tumors that are deviated to one side and localized within the sella.

Detection of herpes simplex virus type 1 in addition to Epstein-Bar virus in tonsils using a new multiplex polymerase chain reaction assay. HSV-1, HSV-2, CMV, EBV, which are the members of the herpes virus family colonize and establish latent infection in human. Although EBV is a well known virus most involved in recurrent bouts of acute tonsillitis, the role and possibility of HSV-1, HSV-2, and CMV for establishing infection in tonsils are not clear. The purpose of this study is to verify whether the tonsils might harbor the HSV-1, HSV-2, and CMV, in addition to EBV, in chronically hyperplastic nasopharyngeal lymphoid tissue. To accomplish the purpose, we developed a new Multiplex Polymerase Chain Reaction (M-PCR) assay using a single consensus forward primer and virus specific reverse primers for DNA polymerase gene of HSV-1, and 2, EBV, and CMV, and investigated its efficiency for detecting HSV1, HSV2, CMV, and EBV. The sample of 52 patients underwent tonsillectomy or adenectomy because of chronic lymphoid hyperplasia without any evidence of acute infections and were investigated for presence of HSV-1, HSV-2, CMV, and EBV. Of the 54 samples, 11 (20.4%) of them were positive for EBV, 4 of them (7.4%) were positive for HSV-1, and none of the samples were positive for HSV-2 and CMV. To the best of our knowledge, this is the first report that tonsils may be the reservoir for HSV-1 in addition to EBV, and HSV-1 may have a role in recurrent tonsillitis and systemic diseases. The MC-PCR assay presented in this study can provide a rapid, sensitive, and economical method for detection of HSV-1, HSV-2, EBV, and CMV in a single PCR tube.

Clinical findings, diagnostic approach, and outcome of Brucella melitensis epididymo-orchitis. We have studied 912 patients with brucellosis. Of these, 631 (69.2%) were male and 48 had epididymo-orchitis, giving an incidence of epididymo-orchitis of 7.6%. The duration of symptoms before diagnosis was 52.5 +/- 70 days. All the patients had fever, swelling, and scrotal pain, but only 2 (4.2%) reported urinary symptoms. Seven patients (14.5%) had leukocyte figures above 11 x 10(9)/L, and urine analysis was normal in 69% of the patients. Blood cultures were positive in 65.8% of cases. A total of 33 patients (68.8%) received a combination of doxycycline plus streptomycin and 13 (27.1%) doxycycline plus rifampin. The overall percentage of failure or relapse was 8.8%: 7.1% in the doxycycline plus streptomycin group and 20% in the doxycycline plus rifampin group. None of the patients required surgery. Pending clinical trials to confirm the results, conservative management with a combination of doxycycline for 2 months and streptomycin for 14 to 21 days appears to be adequate and could avoid unnecessary orchiectomy.

Ileal perforation and reactive hemophagocytic syndrome in a patient with disseminated histoplasmosis: the role of the real-time polymerase chain reaction in the diagnosis and successful treatment with amphotericin B lipid complex. The following case illustrates an ileal perforation and reactive hemophagocytic syndrome (RHS) resulting from disseminated histoplasmosis in a patient with Human Immunodeficiency Virus (HIV) from Puerto Rico. Although the diagnosis was established by histopathologic findings and a positive bone marrow culture, Histoplasma capsulatum-specific real-time Polymerase Chain Reaction (PCR) allowed to confirm the diagnosis from formalin-fixed, paraffin-embedded tissue. Interestingly, the Histoplasma antigens in both serum and urine samples were falsely negative. Amphotericin B lipid complex (Abelcet), followed by oral itraconazole, led to a successful response and resolution of symptoms. A short review of the clinical signs and symptoms, diagnostic tests, and therapeutic options for disseminated histoplasmosis is done, with emphasis on the role of Histoplasma-specific real-time PCR as a molecular diagnostic tool and the efficacy of treatment with one of the lipid formulations of amphotericin B.

Ghost cell odontogenic carcinoma. Ghost cell odontogenic carcinoma (GCOC) is the malignant counterpart of calcifying cystic odontogenic tumour and dentinogenic ghost cell tumour. This is the case of a middle-aged male who presented with a slow-growing maxillary tumour. He was asymptomatic until pain symptoms developed prior to initial presentation. The excised tumour was diagnosed as a ghost cell odontogenic carcinoma. More case reports are needed for further understanding of this rare malignant odontogenic tumour.

Expression of vascular endothelial growth factor (VEGF) in normal oral mucosa, oral dysplasia and oral squamous cell carcinoma. Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine implicated in tumour vasculogenesis. A significant increase in vascularity occurs during the transition from normal oral mucosa (NOM), through dysplasia, to squamous cell carcinoma (SCC). This study investigated the presence of VEGF in NOM, oral dysplasia and SCC. The correlation between VEGF expression and the grade of dysplasia or differentiation of SCC was also examined. Specimens consisting of NOM, oral dysplastic lesions and oral SCC were stained using standard immunohistochemistry methods to determine VEGF expression. Statistical analysis indicated an up-regulation of VEGF during the transition from NOM, through dysplasia to SCC. There was also a significant difference in expression according to differentiation of SCC, but not grade of dysplasia. As VEGF is a potent mediator of vascular development, these results suggest that VEGF may play an important role in the maintenance of a blood supply for developing pre-cancerous and invasive oral lesions.

Familial aggregation of depression, but no familial aggregation of individual depressive symptoms. BACKGROUND Familial aggregation of major depression might indicate a genetic liability for the disorder. The complete disorder or, alternatively, only some individual symptoms might be inherited. Under the latter condition, an increased frequency of inherited symptoms might consecutively increase the likelihood to reach the threshold for depression in relatives and, thus, might cause the familial aggregation of depression. Up to now, no study investigated the possibility of a relationship between individual depressive symptoms and the familial aggregation of depression. METHODS The familial aggregation of early-onset depression (age-at-onset < 60 years, EOD) but less so of late-onset depression (LOD) has been shown in this sample. To assess the hypothesis of an inheritance of individual depressive symptoms as a possible cause of the familial aggregation of depression, frequencies of symptoms were compared in relatives of depressed patients and of controls using forward logistic regression analyses. RESULTS Some individual depressive symptoms showed clustering in relatives of patients with depression, but the pattern of inheritance was inconsistent, i.e. the clustering of symptoms was different between non-depressed and depressed relatives of patients with EOD and LOD, respectively. No intra-familial clustering of specific depressive symptoms within families of depressed subjects could be observed. CONCLUSIONS Due to the inconsistencies in the clustering of individual symptoms in non-depressed and depressed relatives and the lack of intra-familial clustering, the familial aggregation of depression is unlikely to be caused by the aggregation of individual depressive symptoms. An inheritance of the vulnerability for complete depressive disorders influenced by environmental factors is more likely.

Antipyretic effect of Mao-to, a Japanese herbal medicine, for treatment of type A influenza infection in children. Mao-to is a Japanese traditional herbal medicine which has been used since ancient times for the treatment of influenza-like illness. This study was conducted to evaluate the effect of oral Mao-to administration in children with type A influenza, in comparison to Oseltamivir. We performed a controlled trial of 60 children, from 5 months through 13 years of age, with fever and influenza-like symptom of up to 48 h duration. Diagnosis of influenza type A was performed by virus isolation or detection of a viral gene by RT-PCR. Patients assigned into the following 3 groups: oral Mao-to powder (TJ-27) 0.06 g/kg body wt./dose three times daily (n=17), Oseltamivir 2 mg/kg body wt./dose twice daily (n=18) or both oral Mao-to plus Oseltamivir (n=14). The median duration of fever after treatment was significantly shorter in the Mao-to and Mao-to plus Oseltamivir groups, compared with the Oseltamivir only group (15 h [95%CI 13.2-22.1] p<0.01; 18 h[15.2-27.7] p<0.05; 24 h[23.5-43.0], respectively). Oral Mao-to administration was effective in the control of fever due to type A influenza infection in children.

Risk of second malignancies in long-term survivors of childhood cancer. INTRODUCTION Childhood cancer survivors are known to be at increased risk for second malignancies. PATIENTS AND METHODS The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children's Hospital AMC in Amsterdam. The median follow-up time was 16.8 years. RESULTS Sixty two malignancies were observed against 5.4 expected, yielding a standardised incidence ratio (SIR) of 11.2 (95% confidence interval: 8.53-14.4; absolute excess risk: 3.2 per 1000 person-years). New observations were the strongly increased risks of meningiomas (SIR=40) and basal cell carcinomas (SIR=9). Patients whose treatment involved radiotherapy had a 2-fold increased second cancer risk compared to patients with chemotherapy alone. DISCUSSION The relative risk of second malignancies does not decrease till at least 30 years of follow-up. With aging of the survivor cohort this results in a strong increase of the AER, due to the rising background risk of cancer with age.

The Dutch neuromuscular database CRAMP (Computer Registry of All Myopathies and Polyneuropathies): development and preliminary data. Each of the various neuromuscular diseases is rare. Consequently, solid epidemiological data are not available and it is often difficult to find sufficient patients for studies. For this reason, the Dutch neuromuscular database, CRAMP (Computer Registry of All Myopathies and Polyneuropathies), was developed in 2004 by the Dutch Neuromuscular Research Support Centre, to store information on patient characteristics and diagnoses (based on Rowland and McLeod's classification) in a uniform and easily retrievable manner. Care was taken to preserve data confidentiality. It is envisaged that CRAMP will prove particularly useful for studies in which multicentre collaboration is needed to recruit a sufficiently large number of patients. More than 10,000 patients with neuromuscular diseases (4,837 female, 5,476 male) have been registered since 2004, half of whom (n=5059) have peripheral nerve disorders.

Cancer stem cells and "stemness" genes in neuro-oncology. The main properties of stem cells include long-term self-renewal and the capacity to give rise to one or more types of differentiated progeny. Recently, much evidence was provided that leukemia and tumor maintenance and growth are sustained by a small proportion of cells exhibiting stem cell properties. In neural tumors, stem cells have been detected in glioblastoma, medulloblastoma and ependymoma. These observations imply that normal stem cells could be the origin of cancer stem cells; alternatively, a more differentiated progeny may revert to a "stem-like" status, and give rise to cancer stem cells. In adult brain residual stem cells are located in the hippocampus, the subventricular zone and possibly the cerebellum. However, evidence for the ability of more differentiated progeny (astroglia, oligodendroglia) to convert into "stem cells" in vitro has also been provided, thus greatly expanding the potential target of oncogenic mutations. In the framework of the cancer stem cell hypothesis, genes originally identified as important for normal neural stem cells may be essential to support cancer stem cells as well. Stem cell genes act in several ways: they stimulate stem cell self-replication, inhibit differentiation, control excessive replication that might lead to "exhaustion" of the stem cell pool. Mutations in man and mouse, in spontaneous or experimental brain tumors, often target stem cell genes or genes lying in their functional pathway, the main examples being the Sonic hedgehog and the Wnt pathways. Interestingly, several stem cell genes are often overexpressed in brain tumors, even if they are not mutated. This suggests that these genes may be important for the generation of cancer stem cells from more differentiated precursors, or for cancer stem cell maintenance. Cancer stem cells partially differentiate in vivo, and in vitro they also give rise to seemingly normal differentiated progeny, like normal stem cells: thus, their main defect, leading to cancer, may lie in the unbalance between self-replication and terminal differentiation of this minority cell population. Knowledge of extrinsic diffusible factors affecting the activity of stem cell genes may help identifying tools for inducing cancer stem cell differentiation, which might be of use in therapy.

Bronchoscopic gluing for post-lung-transplant bronchopleural fistula. A 44-year-old female patient diagnosed as pulmonary lymphangioleiomyomatosis with respiratory failure underwent bilateral sequential lung transplantation using an entire left lung and a post-lower-lobectomy right lung due to pneumonia. Persistent air leakage during cough was noted and bronchoscopy 12 days after transplantation demonstrated post-lobectomy bronchial stump dehiscence with a large bronchopleural fistula. We applied twice tissue glue instillation on the dehiscent bronchial stump through flexible bronchoscopy. The air leak improved and the patient was discharged 3 months after transplantation uneventfully. Two months after discharge, bronchoscopy showed complete healing of the dehiscent bronchial stump. Now, she lives independently without oxygen support.

Endocannabinoids and the control of energy balance. Two receptors have been cloned to date for the psychotropic compound Delta(9)-tetrahydrocannabinol, and termed cannabinoid CB(1) and CB(2) receptors. Their endogenous ligands, the endocannabinoids, have also been identified. CB(1) receptors and endocannabinoids are present in brain structures controlling energy intake and in peripheral cells (hepatocytes, adipocytes, pancreatic islet cells) regulating energy homeostasis. CB(2) receptors are more abundant in lymphocytes and macrophages, and participate in immune and inflammatory reactions. Metabolic hormones and peptides regulate the levels of the endocannabinoids and, hence, the activity of cannabinoid receptors in several tissues in a seemingly coordinated way. The endocannabinoids, particularly after stress and brief food deprivation, act in turn as local modulators of the expression and action of neurotransmitters, hormones and adipokines involved in metabolic control. Endocannabinoid overactivity seems to accompany metabolic and eating disorders and to contribute to the development of abdominal obesity, dyslipidemia and hyperglycemia. Accordingly, clinical trials have shown that CB(1) receptor antagonists are efficacious at reducing not only food intake, but also abdominal adiposity and its metabolic sequelae.

Substantia nigra echomorphology in the healthy very old: Correlation with motor slowing. Transcranial sonography reveals an increase in echogenicity in the substantia nigra of patients with idiopathic Parkinson's disease. Marked hyperechogenicity has also been described in 9% of the healthy population and is associated with subtle clinical or functional neuroimaging findings suggestive of changes in nigrostriatal function. It has therefore been hypothesised that a hyperechogenic substantia nigra represents an early stage of nigral degeneration or a predisposition for Parkinson's disease. In the present study, we correlated sonographic findings with motor and cognitive deficits in a group of healthy, very elderly subjects. Marked and moderately increased substantia nigra echogenicity was present in 25% and 21% of our healthy, very elderly subjects, respectively, and correlated strongly with the presence of extrapyramidal symptoms in the absence of cognitive deficits. The high incidence of substantia nigra hyperechogenicity measured in our very elderly subjects compared with previous TCS studies suggests that the prevalence of this feature increases with age and is consistent with the higher prevalence of Parkinson's disease in advanced age, as well as the increased frequency of extrapyramidal symptoms. Our results indicate that this simple technique can be used to identify and quantify brain changes associated with subtle motor dysfunction in the very elderly.

An analysis of peripheral giant cell granuloma associated with dental implant treatment. This report discusses the management of a 21-year-old male who developed a peripheral giant cell granuloma (PGCG) associated with dental implant therapy, and reviews 4 previously reported cases of PGCGs developing in association with dental implant treatment. The patient described in this report was treated with multiple dental implants to manage severe oligodontia. Six years after implant placement, with the patient lost to follow-up, he presented to his dentist complaining of increasing swelling in the right mandibular vestibule. The patient was noted to have a large exophytic, ovoid-shaped, firm, smooth-surfaced, maroon-colored lesion. The lesion was found to be a PGCG associated with a dental implant. The lesion was treated successfully by explantation of the dental implant, complete excision of the lesion, and curettage of the underlying bony defect. No evidence of recurrence was seen over 12 months of follow-up.

Opioids, sleep architecture and sleep-disordered breathing. Opioid use whether acute or chronic, illicit or therapeutic is prevalent in Western societies. Opioid receptors are located in the same nuclei that are active in sleep regulation and opioid peptides are suggested to be involved in the induction and maintenance of the sleep state. mu-Opioids are the most commonly used opioids and are recognized respiratory depressants that cause abnormal awake ventilatory responses to hypercapnia and hypoxia. Abnormal sleep architecture has been reported during the process of opioids induction, maintenance and withdrawal. During induction and maintenance of opioid use there is reduction of rapid eye movement (REM) sleep and slow wave sleep. More recently, central sleep apnoea (CSA) has been reported with chronic opioid use and 30% of stable methadone maintenance treatment patients have CSA. Given these facts, it is sobering to note the paucity of human data available regarding the effects of short and long-term opioid use on sleep architecture and respiration during sleep. In this manuscript, we review the current knowledge regarding the effects of mu-opioids on sleep and respiration during sleep and suggest research pathways to advance our knowledge and to explore the possible responsible mechanisms related to these effects.

Central retinal venous occlusion in an otherwise-healthy child. Isolated retinal venous occlusion rarely occurs in otherwise-healthy children.(1-3) We report a unilateral case of central retinal vein occlusion with secondary proliferative retinopathy and neovascular glaucoma in a 6-year-old girl. Despite an extensive workup, no etiology was identified.

Asymmetrical bilateral paresis of the superior oblique muscle. BACKGROUND To review the preoperative signs of bilateral superior oblique paresis and to analyze their presence. METHODS The proposed preoperative signs of bilateral superior oblique (SO) muscle paresis were separated into "certain signs" and "suspicious signs." The signs were analyzed for accuracy using case examples and statistics. RESULTS A strong preoperative sign of bilateral SO muscle paresis was reversal of the hypertropia in the ipsilateral (and/or ipsi-supralateral) position and/or in the contralateral head tilt position. In such cases, the addition of a light contralateral weakening procedure to the operation aimed at the elimination of the hypertropia caused by the more affected SO muscle prevented development of the clinical picture of a contralateral SO muscle paresis. A suggestive preoperative sign of bilateral SO muscle weakness was marked reduction of the hypertropia in the ipsilateral (and ipsi-supralateral) position, as well as in the contralateral head tilt position. In these cases, a contralateral inferior oblique muscle weakening was deferred until after motility could be reassessed postoperatively. An additional sign of possible bilateral SO muscle weakness was the presence of a large V pattern. CONCLUSIONS When planning surgery for apparent unilateral SO muscle paresis, the surgeon should be aware of the often subtle preoperative signs of bilateral SO muscle paresis. Early diagnosis allows the surgeon to avoid the reversal of the clinical picture or to advise the patient of the possibility of a bilateral problem.

Thymic hyperplasia in a child treated with growth hormone. OBJECTIVE To report a case of thymic hyperplasia diagnosed three months after initiation of recombinant human growth hormone (GH) for the treatment of GH deficiency. DESIGN Retrospective chart review was conducted to evaluate the temporal relationship between treatment with GH and thymic enlargement in a 7-year-old girl who had a history of embryonal rhabdomyosarcoma of the nasopharynx diagnosed at the age of 3 years. RESULTS The diagnosis of GH deficiency was made based on clinical and auxological criteria, an insufficient response to clonidine-arginine stimulation testing (peak GH level of 4.8 microg/L) and low insulin-like growth factor 1 (IGF-1) level (30 ng/mL, -2.7 SD). The patient was started on GH at a dose of 0.3mg/kg/week. At the initiation of treatment with GH, the baseline growth velocity was 0.8 cm/year (-6.0 SD) and height was 112.5 cm (-1.7 SD). After three months of treatment with GH, her height increased by 4.2 cm (from -1.7 to -1.2 SD), and the IGF-1 level from -2.7 SD to -1.1 SD. A chest CT performed at that time for recurrence surveillance showed 89% increase in thymic volume relative to previous scan before treatment with growth hormone. A thoracoscopic biopsy of the thymus was performed and revealed hyperplasia with normal thymic architecture without evidence of malignancy. CONCLUSIONS The timing of the development of thymic hyperplasia, along with data from in vitro and in vivo animal studies showing that GH and IGF-1 can directly stimulate growth of the thymus, suggests that GH contributed to the development of thymic hyperplasia in this patient.

Glial cells more than support cells? Glial cells are the most abundant cells in the human brain and have long been considered as passive supporting cells for neurons. In contrast to the extensive studies on various neuronal functions in the nervous system, we still have limited knowledge about glial cells. Recently a number of pioneering studies have provided convincing evidence that glia play active roles in development and function of the central nervous system. This review discusses recent advances in our understanding of the molecular mechanisms underlying glial cell differentiation. We then highlight some of the novel findings about glial function, i.e. the role of glia in synaptogenesis and the intricate relationship between astrocytes and adult neural stem cells. Finally, we summarize the emerging studies that implicate abnormalities in the formation or maintenance of glia leading to severe brain diseases, such as Alexander disease, glioblastoma and multiple sclerosis, and potential therapeutic strategies to tackle these diseases.

Complete change of seizure and spike lateralization in temporal lobe epilepsy at two separate monitorings. OBJECTIVE To report complete change of seizure and spike lateralization over time in bilateral temporal lobe epilepsies (TLE). METHODS Repetition of video-EEG monitorings in 115 patients; 2 cases are reported in detail; 113 other severe partial epilepsies were included to estimate retrospectively the frequency of the reported phenomenon. RESULTS In 2 cases, two video-EEG monitorings, separated by several months, revealed the first time one unilateral TL (temporal lobe) seizure and spike focus and the second time a distinct seizure and spike focus located in the opposite TL. The second monitoring was planned for these two patients because of the presence of a discordant lesion or, in the absence of a lesion, of some bilateral or discordant functional (EEG, SPECT and PET) abnormalities. No patient among the other 113 cases had this video-EEG pattern. CONCLUSIONS In TLE, two video-EEG sessions may be necessary to disclose two opposite TL epileptogenic foci. SIGNIFICANCE In rare bilateral TLE cases, the expression of seizure and spike foci can alternate between hemispheres.

The blink reflex in "chronic migraine". OBJECTIVES Activation of the trigeminovascular system and sensitisation of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the blink reflex and its habituation in patients with "chronic migraine". METHODS We studied 35 patients suffering from "chronic migraine" (IHS classification criteria) outside and during a spontaneous attack, and 35 control subjects. An EMG device with a specific habituation test program was used to elicit and record blink reflex responses and to randomly repeat stimulations at different time intervals so as to induce habituation. RESULTS The R(1) and R(2) latencies, amplitudes and areas of the basal blink reflex were similar in patients studied both outside and during an attack as well as in control subjects, whereas the blink reflex habituation responses were markedly reduced in patients studied outside an attack. The percent changes in the R(2) areas from the baseline values, obtained when stimuli were delivered at time intervals of 10, 5, 4, 3, 2 and 1s, were statistically different (p<0.01-p<0.001) from those of the same patients studied during a migraine attack and of those of control subjects. There was a significant correlation between decreased habituation of the blink reflex and a higher frequency of attacks. The stimulus intensities of the blink reflex (multiples of the detection threshold intensities) were significantly lower (p<0.001) on the side affected, or more severely affected, by headache in patients studied during a migraine attack. CONCLUSIONS The decreased habituation of the blink reflex outside an attack reflects abnormal excitability in "chronic migraine", which normalizes during the attacks. The inverse correlation between the frequency of attacks and habituation responses confirms the abnormal excitability induced by the high frequency of attacks. Central sensitisation mechanisms (allodynia) may explain the lower detection thresholds observed on the side affected by headache in patients during the attacks. SIGNIFICANCE The blink reflex and its habituation may help shed light on the subtle neurophysiological changes that occur in migraine patients between and during attacks.

Recent advances in understanding migraine mechanisms, molecules and therapeutics. Migraine is a complex, disabling disorder of the brain that manifests itself as attacks of often severe, throbbing head pain with sensory sensitivity to light, sound and head movement. There is a clear familial tendency to migraine, which has been well defined in a rare autosomal dominant form of familial hemiplegic migraine (FHM). FHM mutations so far identified include those in CACNA1A (P/Q voltage-gated Ca(2+) channel), ATP1A2 (N(+)-K(+)-ATPase) and SCN1A (Na(+) channel) genes. Physiological studies in humans and studies of the experimental correlate--cortical spreading depression (CSD)--provide understanding of aura, and have explored in recent years the effect of migraine preventives in CSD. Therapeutic developments in migraine have come by targeting the trigeminovascular system, with the most-recent being the proof-of-principle study of calcitonin gene-related peptide (CGRP) receptor antagonists in acute migraine. To understand the basic pathophysiology of migraine, brain imaging studies have firmly established reproducible changes in the brainstem in regions that include areas that are involved in sensory modulation. These data lead to the view that migraine is a form of sensory dysmodulatio--a system failure of normal sensory processing.

FSH and bone--important physiology or not? For many years, osteoporosis in women was equated with estrogen deficiency. The recent articles by Zaidi and colleagues offer a new challenge to the estrogen-deficiency-osteoporosis hypothesis by showing that follicle-stimulating hormone (FSH) stimulates osteoclastic bone resorption perhaps through tumor necrosis factor-alpha (TNF-alpha). These authors, however, neglected to mention bone abnormalities and high testosterone levels that were previously shown in FSH-receptor knockout and other modified mice. It is also possible that they have overemphasized potential relationships of these new data with human bone loss. Despite these fascinating data, the paradigm of FSH causing hypogonadal bone loss is not yet ready to displace the estrogen-deficiency-osteoporosis paradigm, although that model already faces considerable challenge.

Oral pemphigoid autoantibodies preferentially target BP180 ectodomain. Mucous membrane pemphigoid (MMP) comprises a heterogenous group of autoimmune subepithelial bullous diseases very frequently having oral involvement. Very few studies have investigated the immunological status of a subset of MMP, termed oral pemphigoid (OP), presenting with exclusive oral lesions. In this study we show that 75% of 20 OP patients without scarring phenotype possessed circulating autoantibodies against the BP180 molecule, indicating a prominent role of this protein as a target antigen in OP. Of note, the frequency of reactivity against BP180 ectodomain epitopes in OP was similar to that previously reported for MMP with cicatricial phenotype, while the lack of significant recognition of BP180 intracellular domain appears to characterize OP with respect to other diseases of the pemphigoid group. Finally, the combined use of sensitive techniques allowed the detection of circulating autoantibodies in 90% of OP patients, supporting the usefulness of this approach in the diagnosis of MMP disease.