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Gastroesophageal reflux in infants. Clinically significant gastroesophageal reflux occurs in one in 500 infants. Symptoms resolve in 60 to 80 percent of infants by 18 months of age. Thickened formula and position changes are often recommended. Medication and surgical intervention may be needed in refractory cases.

Genetic diagnosis of Lynch syndrome II in an extended colorectal cancer-prone family. Knowledge of colon cancer genetics, with particular attention to precision in hereditary cancer syndrome diagnosis, can often enable highly targeted surveillance and management strategies for patients at high genetic risk. Unfortunately, the patient's family history of cancer is often given minimal attention, and knowledge of hereditary cancer syndromes is frequently limited. Indeed, many physicians still consider familial adenomatous polyposis (FAP) as the only genetic risk factor for colorectal cancer. This concern with FAP was noted in a colorectal cancer-prone kindred which for decades had been thought to manifest that syndrome. However, after meticulous genetic, medical, and pathologic studies, the cardinal phenotypic characteristics of Lynch syndrome II were observed. The potential for cancer control in current and future generations of families like this one clearly mandates the need for computerized registries which could transmit current information about hereditary colon cancer syndrome diagnosis, surveillance, and management.

Renal angioplasty for renovascular disease: a reappraisal. The exact role of percutaneous transluminal angioplasty (PTA) for the treatment of renal artery stenoses (RAS) remains unclear. Therefore we analysed the outcome of unselected renal artery PTA in 30 subjects with angiographically proven unilateral RAS (Group I) compared with that of 19 who had RAS but were treated medically (Group II) and 21 who had essential hypertension but who underwent angiography (Group III). Good blood pressure control was achieved in all three groups but those who underwent PTA had a small but significant fall in their requirement for antihypertensive medications (p less than 0.05). However, no patient was "cured" of hypertension and blood pressure was able to be controlled in both Group II and Group III subjects without an increase in their number of antihypertensives. Serum creatinine did not improve significantly during follow-up in those who underwent PTA and was not different from that of Group II subjects at follow-up. Although unselected renal artery PTA for RAS may make blood pressure control easier it does not delay or prevent further deterioration in renal function and should not be used for this purpose.

Caseating hepatic granulomas in Hodgkin's lymphoma. A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver.

Immunization and protection against malaria during murine pregnancy. Normal and immune mice were evaluated for their ability to resist infection to the rodent malaria parasite, Plasmodium yoelii, during pregnancy. Parasitemia levels were slightly higher and time-to-death shorter in the nonimmunized pregnant group infected with virulent parasites relative to virgin controls. Subinoculation experiments revealed that numerous virulent organisms were present in the placentas of unprotected gravida but were absent from the fetal livers of their conceptuses. It was also found that mice preimmunized with irradiated P. yoelii survived a usually lethal challenge infection during mid-gestation and delivered healthy newborns. Associated with this protection against transplacental spread of parasites was the additional key finding that placental macrophages were as effective as peritoneal exudate cells in phagocytosing parasite derived material in vitro. This murine malaria-pregnancy model should provide new insights on the various factors (virulence, immunogenicity) of microbial infections affecting the fetal-maternal relationship, as well as on the expression of immune effector mechanisms and immunoregulation, during the reproductive process.

Glomerular binding and contractile response to angiotensin II in rats with chronic experimental cirrhosis of the liver. 1. The effects of angiotensin II on glomerular filtration rate and renal plasma flow were studied in surgically instrumented conscious control and cirrhotic rats. In addition, angiotensin II binding and the contractile response to angiotensin II were studied in glomeruli isolated from cirrhotic and control rats. 2. Cirrhotic rats had a higher glomerular filtration rate and a higher renal plasma flow than control animals. A non-pressor dose of angiotensin II induced small but significant decreases in glomerular filtration rate and renal plasma flow in both control and cirrhotic rats, the effect on renal plasma flow being the most pronounced. 3. Plasma renin and aldosterone concentrations were similar in control and cirrhotic rats. 4. The cross-sectional area of glomeruli from cirrhotic rats was 42% greater than that of glomeruli from control animals. Angiotensin II (10(-9) mol/l) decreased the cross-sectional area of glomeruli from control animals by 6.4 +/- 0.9% and of glomeruli from cirrhotic rats by 6.6 +/- 0.8% (P = not significant for comparison between control and cirrhotic animals). 5. There were no differences between control and cirrhotic rats in the affinity of angiotensin II for its glomerular receptors. However, the angiotensin II receptor density was higher in cirrhotic than in control rats, thereby producing an increased total angiotensin II binding in cirrhotic rats. 6. Since no functional differences between control and cirrhotic animals were present in the response to angiotensin II, even though angiotensin II binding was increased, a post-receptor blockade of the angiotensin II signal could be present in cirrhotic rats.

Angina, ischemia, and effort tolerance with vasodilating beta-blockers. beta-Blockers are known to suppress exercise-induced ischemia but give rise to such problems as fatigue or dyspnea on effort and also bradycardia. In a series of double-blind, placebo-controlled studies of celiprolol (a cardioselective beta 1-blocker with beta 2-agonist and vasodilatory properties) in patients with hypertension and angina and in normal volunteers, it was found that celiprolol did not produce bradycardia when given in combination with verapamil. Celiprolol did reduce exercise-induced ischemia, but there was no reduction in cardiac output at rest or on exercise compared with placebo. Compared with atenolol, celiprolol produced less dyspnea and fatigue at submaximal levels of exercise. It is concluded that celiprolol possesses certain differences, compared with conventional beta-blockers, that may be of direct clinical benefit.

Central nervous system bioaminergic responses to mechanical trauma. An experimental study. Changes in biogenic amines in the brain and spinal cord following penetrating injury were studied in male Wistar rats using high-performance liquid chromatography with electrochemical detection. Rapid increase in hemispheric concentration of these substances was noted beginning shortly after trauma. This trend continued until they were about three to four times control levels by about 24 to 48 hours postinjury. In the spinal cord, however, there was an initial sharp reduction in regional concentrations 2 hours postinjury followed by a slow rise thereafter. By 48 hours postinjury, levels of norepinephrine, dopamine, and serotonin of the cords of injured animals were still less than those of nontraumatized controls. This variation in the central nervous system bioaminergic response with the level of injury raises questions as to its precise role in neurological damage following mechanical insult.

Repair of supravalvar aortic stenosis: cardiovascular morphometric and hemodynamic results. Supravalvar aortic stenosis is associated with normal systolic pressure in the aorta and its branches with the singular exception of the coronary arteries, which are hypertensive. This uncommon lesion has been treated by patch aortoplasty of several types. We examined hemodynamics and morphometrics in 13 patients who underwent operation for supravalvar aortic stenosis from 1979 through 1988. They ranged in age from 2 to 43 years (mean age, 14.5 +/- 3.8 years [+/- standard error of the mean]). There were no operative deaths. Preoperative and postoperative (1 to 5 years) catheterization or echocardiography or a combination of these was done in all but 3 patients (1 died late suddenly without a postmortem examination; 1 was lost to follow-up; and 1 has not yet been restudied). Pressure gradients across the stenosis in patients treated with a single-sinus patch (n = 4) were 65 +/- 18 mm Hg preoperatively and 5 +/- 3 mm Hg postoperatively (p less than 0.05) and in patients with a bisinus patch (n = 6), 83 +/- 15 mm Hg preoperatively and 6 +/- 2 mm Hg postoperatively (p less than 0.05); the two groups were not significantly different. Measurements of the diameters of the coronary arteries, aortic annulus, and descending aorta were made, and calculation of the ratio of the coronary artery and annulus diameters to the descending aortic diameters both preoperatively and postoperatively was possible in 5 patients. The left coronary artery was larger than normal before and after operation. Preoperatively there was a disproportionate increase in left coronary artery and annulus size during systole. Left ventricular wall thickness decreased significantly postoperatively (p less than 0.05). Repair of supravalvar aortic stenosis (localized and diffuse) by both single sinus and bisinus patch repair is safe and hemodynamic results are good.

Linear scleroderma associated with ptosis and motility disorders. A case is reported in which an 11-year-old girl developed progressive ptosis and a subsequent motility disorder of the right eye. The diagnosis linear scleroderma en coup de sabre was established. Atrophy of the upper levator palpebral and superior rectus muscle could be shown on CT scan.

Sudden death from acute cocaine intoxication in Virginia in 1988. A review of medical examiners' autopsy records revealed that in 1988, 33 residents of Virginia died of acute cocaine intoxication. The subjects were 19 to 45 years old; most were men, used cocaine intravenously, and used other toxic substances with the lethal dose of cocaine.

Psychological and behavioral implications of abnormal mammograms. OBJECTIVE: To evaluate women's psychological responses to abnormal mammograms and the effect on mammography adherence. To identify psychological responses and other factors that predict mammography adherence in women with normal or abnormal mammograms. DESIGN: Survey study with prospective analysis of factors associated with mammography adherence. SETTING: Health Maintenance Organization of Pennsylvania and New Jersey (HMO PA/NJ). PATIENTS: Study patients, members of HMO PA/NJ who were 50 years of age or older, and who had had mammography done 3 months earlier, included women with normal mammograms (n = 121), women with low-suspicion mammograms (n = 119), and women with high-suspicion mammograms (n = 68), but not women with breast cancer. MEASUREMENTS: Psychological responses 3 months after mammography and adherence to subsequent annual mammography were assessed. MAIN RESULTS: Women with high-suspicion mammograms had substantial mammography-related anxiety (47%) and worries about breast cancer (41%). Such worries affected the moods (26%) and daily functioning (17%) of these women, despite diagnostic evaluation excluding malignancy. For each variable, a consistent trend (P greater than 0.05) was seen with degree of mammogram abnormality. Sixty-eight percent of women with normal results, 78% of women with low-suspicion results, and 74% of women with high-suspicion results obtained their subsequent annual mammograms (P greater than 0.05). The number of previous mammograms (odds ratio, 3.2; 95% CI, 1.6 to 6.2) and the effect of the previous results on concerns about breast cancer (odds ratio, 0.5; CI, 0.2 to 1.0) were independent predictors of adherence in logistic regression analyses (P less than 0.05). CONCLUSIONS: A substantial proportion of women with suspicious mammograms have psychological difficulties, even after learning that they do not have cancer. Such sequelae do not appear to interfere with subsequent adherence.

Influence of age and endocrine factors on the volume of benign prostatic hyperplasia. To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH.

Effects of recombinant human interleukin-3 on human hematopoietic progenitor and precursor cells in vivo. DNA-synthesis rates and concentrations of bone marrow (BM) and peripheral blood (PB) progenitor cells were studied in 22 patients treated with recombinant human interleukin-3 (rhIL3) as part of a clinical phase I/II study. Recombinant hIL3 at doses of 60 to 500 micrograms/m2 was administered by subcutaneous bolus injection for 15 days to 13 patients with solid tumors and preserved hematopoietic function and to nine patients with bone marrow failure, including five with myelodysplastic syndromes. Following treatment with rhIL3, the percentage of actively cycling BM erythroid (BFU-E) and multilineage (CFU-GEMM) progenitors in patients with preserved hematopoietic function increased from 16% to 36% (P less than .05) and from 10% to 40% (P less than .01), respectively. The DNA-synthesis rates of early and late granulocyte macrophage progenitor cells increased from 11% to 26% (CFU-GM day 14; P less than .02) and from 13% to 30% (CFU-GM day 7; P less than .05). There was an increase in BM cellularity from 37% to 58%, and of the myeloid to erythroid ratio from 1.4 to 3.2, while the concentration of marrow progenitors on a per cell basis was unchanged or slightly decreased. The frequencies of blast cells in the BM were unchanged. Mean levels of PB CFU-GM day 14 and CFU-GEMM were 100% and 72% above baseline values after 7 days of rhIL3 but only 25% and 28% above initial levels at the end of treatment. Peripheral blood BFU-E were reduced in the majority of patients with normal marrow after both 7 and 15 days of rhIL3. No augmentation of circulating BFU-E and CFU-GEMM was seen in 5 patients with MDS who had few or no PB BFU-E or CFU-GEMM initially. Total leukocyte, neutrophil, and eosinophil counts increased significantly (P less than .01) in 21 of 22 patients with a peak response after a median of 13 days of rhIL3. While a small increase in reticulocytes was not accompanied by an elevation of the hemoglobin or hematocrit, platelet counts increased by 50% in patients with preserved marrow function. Thus, rhIL3 induces a multilineage response in vivo, apparently by stimulating proliferation of multipotential and lineage-restricted progenitors. It remains to be determined whether this is due to direct or indirect effects on the progenitor cells.

Percutaneous rotational contact biliary lithotripsy: initial clinical results with the Kensey Nash lithotrite. The percutaneous rotary lithotrite introduces a new concept to fragmentation and percutaneous removal of gallstones. A fluid vortex is generated, pulling calculi into a high-speed blade that fragments stones to predominantly under 500 microns. The results of treating the first 10 patients with this instrument reveal that large stone burdens as well as small stones (2-3 mm) of any composition can be removed if the gallbladder is of sufficient size to accommodate the six-pronged basket. Rotation times of 7-39 minutes were required. Nine of 10 procedures were completed; access was lost in one case. One major complication occurred. At repeat oral cholecystography, the gallbladder was visualized after 3-6 weeks in eight of the nine patients. Ursodeoxycholic acid was administered from 3 to 12 months to five patients with either residual stones or aggregates. The hospital stay ranged from 48 to 72 hours. All patients (except the patient who underwent surgery) resumed light activity in 3-4 days and strenuous activity and full diet within 3 weeks.

Glossopharyngeal schwannoma: review of five cases and the literature. Glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8%-10% of intracranial tumors. There have been 23 reported cases in the literature. This report of five cases is the largest series of these tumors. The presentation, radiological workup, operation, and long-term postoperative results will be presented, along with a review of the literature.

The internal oblique-iliac crest free flap in composite defects of the oral cavity involving bone, skin, and mucosa. The reconstruction of oromandibular defects following ablative surgery is a challenging undertaking. When the defect involves skin as well as mucosa, the challenge becomes even greater. The internal oblique iliac crest osteomyocutaneous free flap is particularly useful for reconstruction of through-and-through composite defects due to the inclusion of two separate soft-tissue flaps on the same vascular pedicle. We report our experience with this flap in the reconstruction of 10 patients with such defects. The utility, and the limitations of this form of reconstruction are discussed in detail.

Ruptured mature cystic teratoma of the ovary with recurrence in the liver and colon 17 years later. A case report. A mature cystic teratoma of the ovary occurred in a 51-year-old woman and recurred as a large intrahepatic tumor mass as well as a small mass in the transverse colon 17 years after rupture, intraperitoneal spillage of tumor contents and subtotal surgical removal of the ovarian lesion and peritoneal implants. The patient was treated with a partial hepatectomy and a segmental transverse colectomy. The recurrent lesions, which contained histologically fully mature teratomatous elements only, were excised; the result was a complete cure. To our knowledge this is the first documented report on such a complication of mature cystic teratoma of the ovary.

Use of N2O/O2/enflurane anesthesia for dental treatment of the handicapped. To develop an anesthesia maintenance method that could be expected to maintain a reasonably stable state during dental treatment of the handicapped, three methods (N2O/O2 [0% enflurane (E), n = 12], N2O/O2/0.6% E [n = 8], N2O/O2/1.5% E [n = 7]) were evaluated in terms of changes in plasma levels of cortisol, epinephrine (EP), and norepinephrine (NE). During a treatment period of 60 minutes, cortisol levels increased in the 0% E group (from 9.5 +/- 1.8 micrograms/dL to 19.4 +/- 2.4 micrograms/dL, P less than .01), did not change in 0.6% E group, and decreased in 1.5% E group (from 9.3 +/- 1.7 micrograms/dL to 5.8 +/- 1.0 micrograms/dL, P less than .01). Epinephrine and NE levels increased in the 0% E group, but were suppressed in the 0.6% E and 1.5% E groups. It is suggested that N2O/O2 inhalation anesthesia supplemented with low-dose enflurane produces a stable state during dental treatment with respect to cortisol, EP, and NE responses.

A case of unilateral posterior ischemic optic neuropathy after radical neck dissection. We present a case of unilateral posterior ischemic optic neuropathy after bilateral radical neck dissection. Etiologic factors are discussed.

Comparison of two ascitic fluid culture methods in cirrhotic patients with spontaneous bacterial peritonitis. The conventional method of ascitic fluid culture detects bacteria in only 50% of cirrhotic patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis (SBP). We have prospectively compared two ascites culture methods in cirrhotic patients with spontaneous bacterial peritonitis: 1) conventional (on chocolate agar, blood agar, Mac Conkay agar, and thioglycolate broth), and 2) modified [inoculation of 10 ml of ascites in a tryptic soy broth (TSB) blood culture bottle at the patient's bedside]. In a 21-month period, 70 episodes of SBP were diagnosed according to our criteria in 60 cirrhotic patients. Both culture methods were performed simultaneously. The conventional grew bacteria in 40 episodes (57%), whereas the modified grew bacteria in 54 episodes (77%), a significantly higher sensitivity (p = 0.0001). In 16 cases (23%), ascitic culture was negative by both methods. The mortality rate was higher among patients with culture-positive SBP than those with culture-negative SBP (46% vs 37%), but did not reach statistical significance. We conclude that ascitic fluid inoculated into a TSB blood culture bottle at the patient's bedside should be used routinely for ascites culture in cirrhotic patients.

Extrahepatic portal vein aneurysm associated with a tortuous portal vein. Portal vein aneurysm is rare and its etiology is controversial. A case of extrahepatic portal vein aneurysm associated with an unusually tortuous portal vein is described. Real-time ultrasonography showed anechoic masslike lesions at the porta hepatis communicating with the superior mesenteric vein and intrahepatic portal branches. This suggested the presence of two saccular portal vein aneurysms, 27 x 21 mm and 21 x 13 mm in size. Magnetic resonance imaging and portal venography confirmed the portal vein aneurysms and an unusually tortuous portal vein curving caudally between them. The liver was histologically normal and there was no evidence of portal hypertension. It is speculated that these portal vein aneurysms may have been congenital and that the associated tortuous portal vein might have been secondary to hemodynamic changes in the portal venous system.

Anisocoria in unilateral ophthalmic disease. Pupillary diameters in the affected and unaffected eyes of 327 patients with uniocular red eye were assessed during fixation of a distant target. The mean pupillary diameters were similar in the unaffected eyes in each of eight diagnostic groups, but were significantly different (F = 3.84, p less than 0.001) in the diseased eyes. With corneal abrasions (p less than 0.001), marginal keratitis (p less than 0.05), and acute anterior uveitis (p less than 0.001) the mean pupillary diameter for the affected eye was significantly smaller than that of the unaffected eye. The observed differences of pupillary diameter probably reflect the role of neuronal and autocoid mechanisms in the unilateral control of pupillary size.

Entrapment of a folded-over introducer sheath in the iliofemoral artery: an unusual complication of PTCA guiding catheter exchange An arterial introducer sheath became folded over in the iliac artery during PTCA. This probably resulted from withdrawal of a doubled over Judkins left coronary guiding catheter through the introducer sheath. Nonsurgical, atraumatic removal was accomplished after the acute bend of the introducer sheath had been withdrawn to the site of arterial entrance.

Mapping genes in diabetes. Genetic epidemiological perspective. Research on mapping diabetes-susceptibility genes is dependent on several factors, including the existence of a single major gene for susceptibility, genetic homogeneity, and the existence of appropriate clinical material. The power to detect susceptibility genes is dependent on the risks in relatives and the distance of genetic markers from the susceptibility genes. For insulin-dependent diabetes mellitus (IDDM), the best-fitting risk models are those with a single major locus with residual polygenic factors. The major locus effect is likely represented by genes in the HLA complex, because specific genotypes have been found to affect IDDM risk significantly. Thus, mapping the remaining polygenic IDDM susceptibility factors--each of small effect--is a difficult and long task. For non-insulin-dependent diabetes mellitus (NIDDM), the likely risk models result in few genes with moderate effect. Models of NIDDM have significant residual polygenic variation remaining, reflecting the importance of multiple loci with small effect, environmental effects, or genetic heterogeneity; however, the prospects for mapping genes that provide at least moderate susceptibility for NIDDM now appear promising.

Neglected factors in chronic pain treatment outcome studies--referral patterns, failure to enter treatment, and attrition. An increasing number of chronic pain treatment outcome studies have appeared in the literature. In general, these studies support the efficacy of multidisciplinary pain programs, as well as specific treatment modalities such as biofeedback and relaxation. Reviews of this literature have tended to be cautiously optimistic. Some concerns, however, have been raised about the methodological adequacy of these studies, particularly in terms of the lack of control groups, the brief duration of follow-up periods, and the vague criteria used for establishing the success of the therapeutic interventions. Other factors that mitigate conclusions regarding the generalizability of the favorable results reported need to be considered. In this paper 3 rarely discussed topics that are implicit within most treatment outcome studies and that need to be given greater attention are examined. These topics include: (1) referral patterns to pain clinics (who are referred to pain clinics, when, and how representative is the referred sample?); (2) failure to enter treatment (e.g., exclusion criteria, lack of available financial support to cover the cost of treatment, patient's refusal to accept recommendations), and consequently, the representativeness of the treated sample; and (3) patient's attrition. In this paper we discuss each of these factors as they underscore important qualifications that have to be made in evaluating treatment outcome studies.

Liver transplantation for hepatoblastoma. The American experience. The current role of liver transplantation in treating malignant tumors of the liver is uncertain, except for select histologic types. Pooled data on the results of liver transplantation in 12 children with hepatoblastoma is presented here. One half of the children are alive 24 to 70 (44 +/- 19) months after transplantation with no evidence of recurrence. Three patients (25%) died of tumor recurrence and three (25%) died of other causes. Unifocal and intrahepatic tumors were associated with better prognosis compared to the multifocal tumors and tumors with extrahepatic spread (p = 0.04 and 0.13). Microscopically vascular invasion and the predominance of embryonal and/or anaplastic epithelium were associated with a poor prognosis compared to the tumors with no vascular invasion and with predominantly fetal epithelium (p = 0.08 and 0.1). It is concluded that continued efforts to treat unresectable hepatoblastomas by liver transplantation is justified and the role of adjuvant chemotherapy in improving the results needs to be better defined.

A case of myelinoclastic diffuse sclerosis in an adult. We report a case of rapidly progressive cerebral demyelinating disease in a previously healthy 40-year-old woman. This case satisfies the diagnostic criteria for myelinoclastic diffuse sclerosis (MDS), but is unusual in the age of onset. This is the 1st case of MDS in an adult with full documentation of clinical, biochemical, radiographic, and pathologic features.

Effect of coronary hyperemia on Emax and oxygen consumption in blood-perfused rabbit hearts. Energetic consequences of Gregg's phenomenon. To assess the relation between increases in contractile function and oxygen consumption (VO2) during increased coronary flow (Gregg's phenomenon), we measured the end-systolic pressure-volume relation and the relation between VO2 and left ventricular systolic pressure-volume area (PVA, a measure of total mechanical energy output) in blood-perfused, isovolumically contracting rabbit hearts during control and intracoronary adenosine infusion. During adenosine infusion at a constant perfusion pressure (93 +/- 11 mm Hg), coronary flow increased by 99 +/- 76% (p less than 0.01), and the slope of the end-systolic pressure-volume relation, Emax (ventricular contractility index), increased by 18 +/- 15% (p less than 0.01). When compared at the same left ventricular volume, PVA increased by 20 +/- 14% (p less than 0.01) and VO2 by 19 +/- 15% (p less than 0.01) with adenosine. The VO2-PVA relation was linear under each condition (both median r = 0.98). With increased coronary flow, the VO2-intercept of the VO2-PVA relation (unloaded VO2) increased by 22 +/- 18% (p less than 0.01) without a change in the slope; that is, a parallel upward shift was observed, indicating that the contractile efficiency (energy conversion efficiency of the contractile machinery) remained constant. These increases in Emax and unloaded VO2 were not eliminated by beta-adrenergic blockade with propranolol. We conclude that increased coronary flow with adenosine at a constant perfusion pressure augments both Emax and the nonmechanical energetic cost for excitation-contraction coupling and basal metabolism via nonadrenergic mechanisms, without changing contractile efficiency.

Transesophageal echocardiography in the awake elderly patient: its role in the clinical decision-making process. To assess the impact on the management and safety of transesophageal echocardiography (TEE) in the elderly population, the results and limitations of this technique were retrospectively analyzed in 88 patients. TEE was indicated whenever the transthoracic approach was not diagnostic or was inconsistent with the clinical setting. The most frequent clinical indications were to investigate the source of emboli, assess valvular regurgitation, and identify valvular vegetations. In 72 patients (82%) TEE significantly influenced management decisions. In selected patients TEE avoided the use of more invasive diagnostic procedures. Adverse effects included occasional premature atrial or ventricular beats (11 patients), sinus bradycardia (six patients), and protracted nausea (one patient). We conclude that in elderly patients with cardiovascular diseases, TEE plays a significant role in the decision-making process without adding a significant risk.

Neuro-ophthalmic manifestations of human immunodeficiency virus infection. Both the afferent visual pathways and ocular motor system may be affected by human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Coexisting infections and neoplastic processes in the eye and brain create a diagnostic challenge for the clinician. This article discusses neuroophthalmic manifestations associated with HIV and AIDS, with emphasis on clinical presentation, diagnosis, and treatment.

Effects of atenolol alone, nifedipine alone and their combination on ambulant myocardial ischemia. The effects of atenolol (100 mg/day) and nifedipine (20 mg 3 times daily) and their combination on ambulant myocardial ischemia were investigated using a randomized, double-blind, placebo-controlled, crossover trial. Eighteen men with symptomatic coronary artery disease, exercise-induced ischemia and minimal symptoms, underwent 4 blinded treatment periods of 2 weeks' duration (2 placebo, 1 atenolol, 1 nifedipine). Those that did not have ischemia eliminated by monotherapy received combination therapy with both drugs. Forty-eight-hour ambulatory electrocardiographic monitoring was used to quantitate ischemic parameters at the end of each period. Both nifedipine and atenolol as monotherapy reduced the number of ischemic episodes and the average duration of each episode compared with placebo (p less than 0.05). Compared with placebo, nifedipine reduced the total duration of ischemia (p less than 0.05) but the effect of atenolol on ischemia duration was of borderline significance (p = 0.066). There were no differences in reduction of ischemic parameters when atenolol was compared with nifedipine (difference not significant). In the 9 patients who continued to have ischemia with monotherapy, combination therapy eliminated it in 2 and reduced the duration by greater than 50% in the remaining patients compared with placebo. In conclusion, monotherapy with nifedipine or atenolol is similarly effective in eliminating or reducing ambulant ischemia. Combination therapy can provide additional benefit in those with continued ischemia.

Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder. Twelve children with IQ scores of 50 to 74 (educable mental retardation) who met rigorous diagnostic criteria for attention deficit hyperactivity disorder participated in a double-blind crossover study of the efficacy of two doses of methylphenidate compared with placebo. Dependent measures included behavioral ratings, classroom work output, laboratory measures of attention and learning, and direct observations of social behavior. Improvement with medication on the Conners Hyperactivity Index was observed in 75% of subjects. Significant increases in work output, on-task behavior, and attentional skills were associated with methylphenidate. However, gains in measures of attention were not associated with improvement in learning, as measured by a paired associate learning task. Additionally, no significant increases in appropriate social interactions during free play were associated with methylphenidate. The results suggest that mentally retarded children with attention deficit hyperactivity disorder respond to methylphenidate at similar rates and in similar domains to that of the nonretarded population.

New biological properties of pyrroloquinoline quinone and its related compounds: inhibition of chemiluminescence, lipid peroxidation and rat paw edema. Pyrroloquinoline quinone (PQQ) inhibited the chemiluminescence (CL) from mouse peritoneal cells initiated by zymosan, carrageenin and N-formyl-methionyl-leucyl-phenylalanine and CL generated by the xanthine-xanthine oxidase reaction and the lipid peroxidation in the rat brain homogenate. The inhibitory activity of PQQ was more potent than that of idebenone, alpha-tocopherol and ascorbic acid in all the three assay systems. In the xanthine-xanthine oxidase reaction, PQQ had no effect on the formation of uric acid at the concentration of CL inhibition. These results suggest that PQQ might have a radical scavenger-like activity. Structure-activity relationship of PQQ and its six related compounds showed that the 7- and 9-carboxyl groups of PQQ as well as the orthoquinone structure are responsible for the radical scavenger-like activity. In addition, the -NH group in the pyrrole ring of PQQ seemed to be essential for the antilipid peroxidative activity in the rat brain homogenate. When administered i.p., PQQ inhibited the development of 0.1% carrageenin-induced paw edema in rats. These results suggest that PQQ might have therapeutic effects on various diseases, of which development or exacerbation has been known to be associated with radical oxygens.

Treatment of vaginal candidiasis: orally or vaginally? Vaginal candidiasis continues to be the most common cause of vaginal discharge. A large variety of topical drugs and a selection of orally active antifungals are currently available. The choice between the use of oral drugs or intravaginal agents will depend on the therapeutic results obtained with the different agents, side effects, pregnancy status, and patient preference. The results obtained in the Maria Hospital, Tilburg, The Netherlands, and a review of foreign data suggest the following: (1) For acute infection oral and topical agents produce equivalent results. (2) For chronic infections oral medication is preferred. (3) Oral therapy should not be given to pregnant patients or to patients not using reliable contraceptive measures. (4) Half the patients prefer oral medication; only 5% prefer intravaginal therapy, and the others had no clear preference.

Diarrhea. Diarrhea is one manifestation of GI disturbance. Symptoms may be acute if caused by such things as infections, drug reactions, alterations in diet, heavy metal poisoning, or fecal impaction. Chronic diarrhea is a symptom of GI diseases such as irritable bowel syndrome, lactase deficiency, cancer of the colon, inflammatory bowel disease, and malabsorption diseases. Chronic diarrhea may also be associated with GI surgery, radiation therapy, laxative abuse, alcohol abuse, and chemotherapeutic agents. When interventions are required to deal with diarrhea, they may include such things as alteration in tube feeding products and methods of administration, fluid replacement by oral rehydration procedures, a rapid return to feeding, and education aimed at the health information clients need to prevent or control the symptom of diarrhea.

Impact of active immunisation against enteritis necroticans in Papua New Guinea. Enteritis necroticans, known locally as pigbel, has been a major cause of illness and death among children in the highlands of Papua New Guinea. After a successful trial of active immunisation against the beta toxin of the causative organism, Clostridium perfringens type C, immunisation of children was begun in 1980. The effects of the immunisation programme on pigbel admissions in 3 of the 5 major highland hospitals were assessed. In each of the centres studied the proportion of admissions due to enteritis necroticans dropped significantly after immunisation was introduced (p less than 0.001) and hospital admissions for pigbel in 1984-86, when immunisation was well established, were less than one fifth of previous figures.

Technetium-99m-methylene diphosphonate (MDP) uptake in a sympathetic effusion: an index of malignancy and a review of the literature. We report a patient with a sympathetic pleural effusion secondary to T-cell lymphoma that accumulated the bone imaging agent, Technetium-99m-methylene diphosphonate (99mTc-MDP). This case is significant in that malignant cells were not present on three cytologic examinations of the pleural fluid or multiple pleural biopsies. We also present a review of the published literature on pleural effusions that accumulate bone tracers. We conclude that pleural effusions that accumulate 99mTc-MDP should be considered malignant or secondary to a malignancy and further work-up is essential even if the cytologic exam of the pleural fluid is unremarkable.

Immunohistochemical characterization of microvascular endothelial cells in primary B cell lymphoma of the gastrointestinal tract. Microvascular endothelial cells (EnC) in primary B cell lymphoma of the gastrointestinal tract were immunohistochemically studied. Based on the morphological structure, the microvasculatures were divided into high endothelial cell vessels (HEV) and flat endothelial cell vessels (FEV). There were distinct phenotypic differences between HEV and FEV in lymphoma tissues. HEV were characterized as OKM1- OKM5-, accompanied by the cluster of non-neoplastic T lymphocytes, and FEV were OKM1- OKM5+ not accompanied by T lymphocyte infiltration. Factor VIII-related antigen was clearly identified in both EnC, and major histocompatibility complex (MHC) class II antigens and interleukin 1 were absent or only faintly visible on EnC in lymphoma tissues, whereas they were expressed on EnC in non-lymphoma tissues. These findings suggest that microvascular EnC in primary B cell lymphoma of the gastrointestinal tract lack a property as antigen-presenting cells, and that HEV are involved in the migration of non-neoplastic T lymphocytes.

Vitamin E and cancer prevention. Some animal experiments and human studies suggest that vitamin E may protect against cancer. Serum alpha-tocopherol concentration was studied for its prediction of cancer in a cohort of 36,265 adults in Finland. During a mean follow-up of 8 y, cancer was diagnosed in 766 persons. The levels of serum alpha-tocopherol were determined from stored serum samples (at -20 degrees C) taken from these cancer patients and from 1419 matched control subjects. Individuals with a low level of alpha-tocopherol had about a 1.5-fold risk of cancer compared with those with a higher level. The strength of the association between serum alpha-tocopherol level and cancer risk varied for different cancer sites and was strongest for some gastrointestinal cancers and for the combined group of cancers unrelated to smoking. The association was strongest among nonsmoking men and among women with low levels of serum selenium. The findings agree with the hypothesis that dietary vitamin E in some circumstances protects against cancer.

Retrograde recanalization of an occluded posterior tibial artery by using a posterior tibial cutdown: two case reports. Recanalization of two occluded posterior tibial arteries was successfully achieved by utilizing a retrograde approach via a posterior tibial artery cutdown at the level of the ankle. Both cases were previously unsuccessfully attempted by using an antegrade approach. Thus, the choice of access vessel (arterial entry site) becomes a crucial determinant of angioplasty success.

Vena caval flow: assessment with cine MR velocity mapping. The authors used cine magnetic resonance (MR) velocity mapping to study flow in the superior vena cava (SVC) and inferior vena cava (IVC) of 13 healthy control subjects and 13 patients with right-sided cardiac disease. In the control subjects, peaks of flow in systole and diastole were observed, and mean SVC flow was 35% of the cardiac output. Respiratory gating was used in six control subjects to acquire images at end inspiration and end expiration, and although the systolic peak was reduced at end expiration, total flow was unchanged. A reduced systolic peak and retrograde flow in the IVC were observed in patients with tricuspid regurgitation. A reduced diastolic peak was seen in patients with pulmonary hypertension, pericardial constriction, and right ventricular dysplasia, reflecting reduced diastolic compliance of the right ventricle. In the patient with obstruction of the SVC, absence of flow was confirmed, and retrograde flow was seen in the azygos vein. The authors believe that cine MR velocity mapping is a reliable method of studying vena caval flow noninvasively and that it has important potential applications for the investigation of disorders of the right side of the heart.

Permanent external striated sphincter stents in patients with spinal injuries. Nine patients with complete quadriplegia underwent external striated sphincter stenting with the Wallstent in place of an external striated sphincterotomy. Although suprapubic catheters were placed to provide an outlet should problems develop with the stent, they were successfully removed within 6 weeks in all but 1 patient. Complete bladder emptying with reduced voiding pressures was achieved, together with a significant reduction in the duration of hyper-reflexic contractions. Epithelialisation of the stent was almost complete within 3 months and intermittent catheterisation or endoscopy (and resection) is possible through the stent. Although this is a preliminary report of this new technique, it is hoped that sphincter stenting will provide a rapid, safe and effective method of treating high pressure hyper-reflexia and detrusor sphincter dyssynergia in quadriplegic patients.

The management of malignant bone tumors in children and adolescents. A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma, fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978 to 1988. Ninety-eight percent of the patients received chemotherapy and 63% had a surgical resection. Sixty-five percent of all patients were alive at 30 months and were considered disease free. The functional results after surgery were evaluated according to the Musculoskeletal Tumor Society score. In all diaphyseal resections and resections of the upper extremity and pelvis, the results were excellent or good in 60% of the cases. In resections of the proximal femur, distal femur, or proximal tibia and reconstruction with nonexpansible prostheses, the results were excellent or good in 75%. On the other hand, when arthrodeses of the lower extremity were used, only 14% of cases had a good result. This correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth.

Ruptured abdominal aortic aneurysm: the Harborview experience. During the last decade (1980 to 1989) 186 patients with ruptured abdominal aortic aneurysm were admitted to a single urban hospital. Ninety-six percent of these patients had a prehospital systolic blood pressure less than 90 mm Hg. Management included paramedic field resuscitation and transport, an emergency department diagnostic protocol completed in an average of 12 minutes, rapid transport to a dedicated emergency operating room, aneurysmorrhaphy by general surgery chief residents under the supervision of specialist vascular surgeons, and skilled postoperative intensive care unit care. Nevertheless, 130 (70%) patients died in the first 30 postoperative days--3% in the emergency department, 13% in the operating room, 51% in the intensive care unit, and 3% on the ward or at home. Certain features--age greater than 80 years, female gender, persistent preoperative hypotension despite aggressive crystalloid and blood replacement, admission hematocrit less than 25, transfusion requirements exceeding 15 units--were associated with a greater than 90% likelihood of death. No patient with preoperative cardiac arrest survived more than 24 hours. From this experience we conclude that, although "optimal" prehospital, emergency department, operating room, and postoperative care can improve the outcome of patients with ruptured abdominal aortic aneurysms in shock, most such patients will die. Certain clinical features predict such excessive mortality rates after ruptured abdominal aortic aneurysms that withholding operation may be reasonable. Screening of patients at high risk for abdominal aortic aneurysm, followed by elective aneurysmorrhaphy, is clearly indicated.

Adult hepatic fibropolycystic disease presenting as obstructive jaundice. Obstructive jaundice caused by compression of the common hepatic duct by a simple hepatic cyst in a 31 year old Europid man is reported. The jaundice and duct compression resolved after percutaneous aspiration of the cyst under ultrasound direction and the patient has been well for 12 months.

Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension BACKGROUND. To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS. Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS. Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS. In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction.

Expandable venous stents for treatment of the Budd-Chiari syndrome. The goals of treatment of the Budd-Chiari syndrome are relief of portal hypertension, relief of inferior vena cava syndrome, if present, and preservation of hepatic function. This study presents a patient with clinical resolution of the Budd-Chiari syndrome after placement of expandable metallic stents in the inferior vena cava and hepatic veins. A 26-year-old man with severe ascites and lower extremity edema but with relatively preserved hepatic function had a small gradient across a suprahepatic caval web, large gradients across an intrahepatic caval stenosis and the left hepatic vein, and an occluded right hepatic vein. Under angiographic control, web and caval stenosis were balloon-dilated, and modified Gianturco expandable metallic stents were placed in the intrahepatic vena cava. The left hepatic vein was dilated twice and a stent was placed. All gradients were completely eliminated. There were no complications and after 1 year, the stents have fully expanded without migration, edema and ascites have resolved, hepatic function has normalized, and the patient has returned to work. This new technique provides a simple, safe, effective, relatively inexpensive, and potentially long-lasting treatment for selected patients with the Budd-Chiari syndrome.

Renovascular beta adrenergic hypersensitivity and hyperinsulinemia in rats with dietary-induced obesity. To determine whether obesity alters responsiveness to vasoactive drugs, we compared the cardiovascular effects of angiotensin, phenylephrine and isoproterenol in unanesthetized age-matched control and obese Oscai rats. Obesity was induced by programming pups to overeat immediately after birth and then feeding them a high-fat diet thereafter. Elevations in tail-cuff systolic and mean pressures from 7 through 11 months of age and in plasma insulin at 8 months of age indicated that obese rats had developed borderline hypertension and hyperinsulinemia. Cardiovascular responsiveness was then tested by recording blood pressure, heart rate and renal blood flow from chronically implanted arterial catheters and flow probes while graded doses of the three test drugs were infused intravenously. Heart rate and renal blood flow decreased during pressor responses to angiotensin and phenylephrine and were oppositely increased during depressor responses to isoproterenol. Magnitude of all cardiovascular receptors was dose-dependent. Obese rats had weaker reflex bradycardic responses to angiotensin and phenylephrine than control rats. More importantly, they also had larger renal vasoconstrictor responses to 2 ng/100 g of angiotensin or vasodilator responses to 15 ng/100 of isoproterenol. Whether or not the changes in cardiovascular responsiveness were related to hyperinsulinemia was undetermined. Our results suggest that, in addition to being overweight, slightly hypertensive and hyperinsulinemic, obese Oscai rats have impaired baroreflexes and a renal vascular bed more responsive to beta adrenergic vasodilation.

Anorectal dysfunction in patients with urologic disturbance due to multiple sclerosis. Anorectal function was evaluated in 11 patients with voiding dysfunction due to multiple sclerosis. In six patients with constipation, three also had symptoms of obstructed defecation and one patient was incontinent due to stercoral diarrhea. One patient was only fecal incontinent and one patient had obstructed defecation as the only symptom. Three patients had no anorectal symptoms. Anal manometry in the women compared with a control group revealed significant lower anal resting and squeeze pressures, although no significant difference of rectal sensation to distention with air was found. Pudendal nerve terminal latencies were obtained in seven patients and were all normal. In four patients latency could not be demonstrated due to poor contraction of the sphincter on stimulation of the pudendal nerve. Two of these patients were incontinent and two had both constipation and obstructed defecation. It is concluded that patients with voiding symptoms due to multiple sclerosis often reveal anorectal symptoms or motility disorders. Although anal sphincter function is reduced, fecal incontinence is not prevalent in this group. The reason for this lies probably in the fact that many of the patients are constipated, thus securing fecal continence.

Repetitive conservative surgery for recurrence of endometriosis. We evaluated the recovery of fertility and the relief of pain symptoms in a long-term follow-up of 42 women undergoing repetitive conservative surgery for recurrent endometriosis. The mean age of the patients was 31.1 +/- 4.3 years. At the time of their second operation the disease was stage IV in 14 women, stage III in 25, and stage I in three. After reoperation, the patients were followed for a mean period of 41.8 +/- 30.3 months. Pain symptoms returned in eight women, dysmenorrhea and deep dyspareunia in eight, and pelvic pain in seven. Eight of the 28 women (28.6%) who attempted to conceive achieved a total of 13 pregnancies. The corrected pregnancy rate was 35%, and the cumulative rate at 27 months was 30.7%. A third operation was necessary in six women after a mean period of 35 months. Conservative surgery is an effective therapeutic option for infertile patients with recurrent endometriosis.

Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Intestinal perforation due to cytomegalovirus (CMV) infection in patients with AIDS is the most common life-threatening condition requiring emergency celiotomy in these patients. The authors describe a patient with AIDS with intestinal perforation due to CMV infection, and review 14 additional cases reported in the English-language surgical literature. The diagnostic triad of pneumoperitoneum on x-ray, evidence or history of CMV infection, and AIDS occurred in 70 percent of patients. The most common site of intestinal perforation was the colon (53 percent), followed in frequency by the distal ileum (40 percent) and appendix (7 percent); perforation usually occurred between the distal ileum and splenic flexure of the colon. Colonoscopy, rather than sigmoidoscopy, is recommended as a screening examination in patients with AIDS suspected of having colonic ulceration due to CMV infection. Multiple biopsies of ulcerated tissue should be obtained. Gross and microscopic analyses of involved intestinal tissue reveal the characteristic findings of ulceration and CMV infection. Despite aggressive therapy, the operative mortality rate in patients with AIDS with intestinal perforation due to CMV infection was 54 percent and the overall mortality rate was 87 percent. Postoperative complications occurred in most patients and consisted mainly of systemic sepsis and pneumonia caused by Pneumocystis carinii infection. An increased awareness of this syndrome by physicians frequently called on to manage patients with AIDS is recommended.

Circadian variations in myocardial ischemia. Implications for management. Extended ambulatory electrocardiographic monitoring in the patient's customary environment provides clear evidence of circadian patterns in myocardial ischemic episodes. In patients with effort angina, the highest activity occurs between 6 AM and noon. This coincides with peaks in diurnal variation of frequency of acute myocardial infarction, stroke, and sudden death. A number of potential underlying common triggering mechanisms, including catecholamine secretion, sympathetic nervous system activity, blood pressure, heart rate, cortisol secretion, and aggregability of platelets, exhibit similar surges. As a result of these coinciding morning peaks, myocardial oxygen demand is increased and oxygen supply reduced after a person arises in the morning. Attention to this vulnerable period is merited in the timing and choice of medication, both to prevent or reduce ischemia and to modify potential disease-triggering mechanisms.

Lower extremity arterial disease in elderly subjects with systolic hypertension. The ratio of ankle-to-arm systolic blood pressure (ankle/arm index or AAI) appears to be a non-invasive indicator of flow-significant atherosclerosis and may be a useful measure of burden of disease in a high risk population. The prevalence of lower extremity arterial disease (LEAD) was assessed by this method in the Systolic Hypertension in the Elderly Program (SHEP). Subjects were aged 60 and older with systolic blood pressure greater than 160 mmHg upon entry to the study. An AAI of 0.90 or less was considered indicative of flow-significant LEAD. The prevalence of LEAD by this method was 26.7% (50/187), while the prevalence of intermittent claudication (IC) was only 6.4% (12/187). Of those with IC, 66.7% (8/12) had confirmed LEAD. The prevalence of LEAD as measured by AAI increased with age in women and was associated with a history of current smoking and lower levels of high density lipoproteins. In this study population with systolic hypertension, LEAD, as measured by the AAI, is more prevalent than previously described in elderly populations and is associated with other risk factors for atherosclerosis.

pH-adjustment and discomfort caused by the intradermal injection of lignocaine [published erratum appears in Anaesthesia 1991 Mar;46(3):242] One hundred adult day-case patients who required intravenous access had cannulae inserted using local anaesthesia with 1% lignocaine, 1% lignocaine with adrenaline or the corresponding pH-adjusted solutions. The local anaesthetic solutions were modified by the addition of 1 ml 8.4% sodium bicarbonate to 10 ml lignocaine. Pain scores at different stages of cannulation were noted and showed a significant reduction after use of pH-adjusted solutions (p less than 0.02 for the plain lignocaine, and less than 0.001 for the lignocaine with adrenaline). Modification of the pH of lignocaine solutions by the addition of sodium bicarbonate is a simple method significantly to reduce the discomfort caused by the infiltration of the local anaesthetic.

Recombinant Epstein-Barr virus with small RNA (EBER) genes deleted transforms lymphocytes and replicates in vitro. Strains of Epstein-Barr virus (EBV) with deletions of the small RNA (EBER) genes were made by homologous recombination using the EBV P3HR-1 strain, which has undergone deletion of the essential transforming gene that encodes the EBV nuclear antigen, EBNA-2, and a DNA fragment that was wild type at the EBNA-2 locus but from which the EBER genes had been deleted. Even though the EBER and EBNA-2 genes are separated by 40 kilobases, selection for transforming P3HR-1 recombinants that required a restored EBNA-2 gene resulted in 20% cotransfer of the EBER deletion. EBER-deleted recombinants transformed primary B lymphocytes into lymphoblastoid cell lines (LCLs), which were indistinguishable form LCLs transformed by wild-type EBV in their proliferation, in latency-associated EBV gene expression, and in their permissiveness for EBV replication cycle gene expression. EBER-deleted virus from infected LCL clones could infect and growth-transform primary B lymphocytes. These procedures should be applicable to the construction of other EBV recombinants within 40 kilobases of the EBNA-2 gene. The EBER-deleted EBV recombinants should be useful in further evaluating the role of EBERs in EBV infection.

Percutaneous cholangioscopic or transpapillary insertion of self-expanding biliary metal stents. Fifty-two self-expanding metal stents were implanted in 39 patients with malignant (35 patients) or benign (4 patients) biliary stenoses. The stents were inserted and properly released by means of a 7 or 9 French gauge delivery catheter via the percutaneous (20 patients) or transpapillary (19 patients) route. In all cases the endoprostheses expanded to a diameter of 7 to 10 mm and achieved complete biliary tract drainage. Jaundice disappeared in 36 of the 39 patients. No early complication was observed. After a median follow-up of 121 days (range, 30 to 422 days), 19 of 36 patients are still alive and 17 died of non-procedure-related causes. Biliary re-obstruction occurred in five patients due to tumor overgrowth above or below the prosthesis (four patients) or bile encrustation (one patient). In patients with malignant stenoses, the probability of stent patency is 78% after 200 days. We conclude that large-bore metal stents are safe, effective, and provide better long-term patency than conventional endoprostheses.

Pathogenesis and therapy of peptic ulcer disease. The epithelial cells of the stomach and duodenum are normally protected from the damaging effects of acid and pepsin by a balancing mechanism of mucosal resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching has emphasized the importance of acid (and pepsin) as the cause of this imbalance; however, it is clear that acid and pepsin are not the only important factors in the pathogenesis of peptic ulcer. More recent investigative efforts have been directed at what constitutes mucosal resistance and how it can be disrupted to produce, in the presence of gastric acid, a peptic ulcer. Depletion of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as prominent theories. As evidence exists both to support and refute these theories in humans, any definitive conclusions cannot be made at this time. The acute management of peptic ulcer disease is directed at relieving pain, accelerating ulcer healing, and preventing complications. Peptic ulcers can be healed with antisecretory agents (i.e., H2-receptor antagonists, omeprazole), antacids, prostaglandins, and sucralfate. Because they are effective, safe, and convenient, the H2-receptor antagonists are the most widely used agents for the management of peptic ulcer disease. Because the H2-receptor antagonist agents are equally effective in their indicated uses and are equally safe based on scientifically valid data, selection should be based primarily on cost. Omeprazole is the newest antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for 24 h. The agent offers little advantage over H2-receptor antagonists for the majority of patients with peptic ulcer.

Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: relationship to laterality and nature of paroxysmal discharges. We compared the pulsatile secretion of luteinizing hormone (LH) between 13 men with clinically and electrographically documented temporal lobe seizures and 8 age-matched controls. Serum for LH measurement was drawn every 15 minutes during 8 hours of EEG telemetry in both groups. The 2 groups did not differ significantly in average mean baseline LH secretion, total LH secretion, or average pulse amplitude. The group with seizures, however, showed a significantly greater (p less than 0.05) variability of baseline LH secretion and pulse frequency. Among the men with unilateral paroxysmal EEG findings, pulse frequency was significantly greater (p = 0.05) with right epileptiform discharges or left slowing (6.4 +/- 0.4) than with left epileptiform discharges or right slowing (3.0 +/- 1.3). The relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities can be attributed to medication alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion.

Gastrointestinal function and structure in HIV-positive patients. We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.

Bacteremia with otitis media. To investigate the occurrence and outcome of bacteremia associated with otitis media, charts were reviewed from patients who were 3 to 36 months of age, had temperatures greater than or equal to 39 degrees C, and were diagnosed with isolated clinical otitis media. A total of 2982 patients were identified. Blood cultures were obtained from 1666 (56%). Of the 1666 patients, who had blood drawn for cultures, 50 (3.0%) had bacteremia. These included 39 with Streptococcus pneumoniae, 4 with Haemophilus influenzae, 2 with Neisseria meningitidis, 3 with Salmonella species, and 2 with Staphylococcus aureus. The incidence of bacteremia increased at higher temperatures, being 1.9% at temperatures less than or equal to 40 degrees C and 5.0% at temperatures greater than 40 degrees C. Younger children were more likely to have bacteremia; 3.7% less than or equal to 12 months of age, 2.4% 13 to 24 months of age, and 1.9% 25 to 36 months of age had blood culture results that were positive (not significant). Reevaluation of the 50 bacteremic patients showed that 9 patients had continued fever, 3 patients had persistent bacteremia, pneumonia developed in 1 patient, and meningitis developed in 1 patient. It was concluded that (1) 3% of young febrile children with otitis media have bacteremia at the time of evaluation, a rate comparable to that previously reported in children with no focus of infection; (2) the incidence of bacteremia increases at higher temperatures; and (3) most febrile children with otitis media do well. The clinician must therefore weigh the potential benefit of drawing a blood culture to identify children at risk for complications against the inherent cost, inconvenience, and discomfort.

Carcinoma of the breast: measurement and the management of treatment. I. The value of the data. This is the first of a series of papers in which we shall explore some insights into the biological changes which accompany the treatment of human tumours which may be obtained through estimation of volume changes in relation to treatment. We have adopted a working hypothesis that regression slopes reflect the composition of individual tumours and, indirectly, their intrinsic growth rate rather than the effectiveness of treatment. The breast has proved to be a suitable site for measurement and our interpretation of the results has led to the development of a new style of management for carcinoma of the breast: measurement based sequential therapy (MBST). In this paper the method of measurement and detailed statistical evaluation of the quality of the data from 262 patients (263 tumours) is presented. Exponential regression lines have been fitted to describe volume changes in relation to treatment by radiation, chemotherapy and hormones. A simple classification of steepness of slopes is introduced.

Ultrastructural study of Norrie's disease. We studied the clinicopathologic and ultrastructural features of a full-term infant with Norrie's disease. The infant had bilateral retrolental fibrous vascular masses and retinal detachment with no other apparent physical abnormalities and no family history of ocular defects. A vitrectomy and a membrane peeling were attempted, and specimens of the retina, the retrolental membrane, and a vascularized epiretinal peripheral mass were examined by light and electron microscopy. The retrolental membrane was composed of layered collagenous tissue and contained structures resembling blood vessels. Inner and outer neuroblastic layers were identified in the retinal tissue, but no vessels were present. In the epiretinal mass, portions of retina and cortical vitreous were seen along with primitive vascular structures. The histologic appearance of these specimens suggests that the major pathologic event of Norrie's disease occurs in the retina in the third to fourth gestational month. We believe the subsequent ocular abnormalities found in this patient were secondary to this early retinal malformation and did not represent a progressive ocular disorder.

General principles of therapy of pyogenic meningitis. In bacterial meningitis, several pharmacodynamic factors determine therapeutic success-when defined as sterilization of the CSF: (1) Local host defense deficits in the CNS require the use of bactericidal antibiotics to sterilize the CSF. (2) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity. Protein binding, low pH, and slow bacterial growth rates are among the factors that may explain the high antibiotic concentrations necessary in vivo. (3) High CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth, even during relatively long dosing intervals. (4) Penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier and thus, very high serum levels are necessary to achieve the CSF concentrations required for optimal bactericidal activity. Beyond these principles, recent data suggests that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active products from the lysed bacteria. Since rapid CSF sterilization remains a key therapeutic goal, the harmful consequences of bacterial lysis present a major challenge in the therapy of bacterial meningitis. Currently, dexamethasone represents that only clinically beneficial approach to reduce the harmful effects of bacterial lysis, and novel approaches are required to improve the outcome of this serious infection.

High-resolution ultrafast chest CT in the clinical management of febrile bone marrow transplant patients with normal or nonspecific chest roentgenograms Plain chest roentgenograms may be normal or show nonspecific abnormalities during the frequent febrile episodes that occur in patients after bone marrow transplantation. In this group, ultrafast 10-mm and 3-mm high-resolution CT scans were prospectively performed in 33 patients to determine if useful information was provided that either changed the patient's clinical management or added confidence to the clinical diagnosis. The 36 symptomatic episodes that occurred in 33 patients included fever in 20 episodes and fever combined with cough, dyspnea, chest pain, or rales in 16. Fourteen chest roentgenograms were interpreted as normal, and 22 were interpreted as demonstrating nonspecific changes; however, none of the roentgenograms was considered helpful in that they did not provide sufficient information for further management. In 2 of 14 episodes in patients with normal chest roentgenograms and in 9 of 22 episodes in patients with nonspecific chest roentgenograms, CT scanning resulted in a change in clinical management that included performing bronchoscopy, increasing or changing antibiotic coverage, starting white blood cell transfusions, requesting surgical biopsy, or a combination of these. In 1 of 14 episodes in patients with normal chest roentgenograms and in 8 of 22 episodes in patients with nonspecific roentgenograms, CT added confidence to the diagnosis. In the remaining 16 episodes, CT scans provided no additional information. We conclude that in many instances, noncontrast ultrafast chest CT scans can provide information that may either change a patient's clinical management or more clearly establish the extent of pulmonary disease.

Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals. Stagnara wake-up tests, blood flow measures, somatosensory evoked potentials (SEPs), and neurogenic-motor evoked potentials (NMEPs) were elicited from 20 hogs before and after spinal cord overdistraction at L3-L4. Overdistraction was maintained from 5 to 30 minutes after loss of NMEPs. Results suggest that the longer the duration of overdistraction the greater the likelihood of paraplegia. Blood flow measures indicated that reduced perfusion was greatest at the distraction site but extended proximally and distally. Finally, NMEPs were more sensitive to onset of overdistraction and a more valid indicator of paraplegia than SEPs. NMEPs should provide the surgeon with more time for initiation of intervention techniques than SEPs. Because NMEPs and SEPs provide information regarding different spinal cord tracts, the authors continue to use both methods for monitoring the functional integrity of the human spinal cord during corrective spine surgery.

Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection Indium-111-labeled leukocyte images of 92 cemented total-hip arthroplasties were correlated with final diagnoses. Prostheses were divided into four zones: head (including acetabulum), trochanter, shaft, and tip. The presence (or absence) and intensity of activity in each zone was noted, and compared to the corresponding contralateral zone. Though present in all 23 infected arthroplasties, periprosthetic activity was also present in 77% of uninfected arthroplasties, and was greater than the contralateral zone 51% of the time. When analyzed by zone, head zone activity was the best criterion for infection (87% sensitivity, 94% specificity, 92% accuracy). Fifty of the arthroplasties were studied with combined labeled leukocyte/sulfur colloid imaging. Using incongruence of images as the criterion for infection, the sensitivity, specificity, and accuracy of the study were 100%, 97%, and 98%, respectively. While variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection, the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure.

Histology of the lens in the Weill-Marchesani syndrome. The Weill-Marchesani syndrome is a rare systemic connective tissue disease characterised by small stature, brachydactyly, ectopia lentis, and spherophakia. Three siblings with typical manifestations of this syndrome were reported. The ophthalmological findings in all these cases were spherophakia, severe myopia, a shallow anterior chamber, and narrow angle glaucoma. Two cases underwent laser iridotomy and drug treatment. In the third case the lens was removed from the eye because of injury, and this lens was examined by light and electron microscopy.

Esophageal motility, heartburn, and gastroesophageal reflux: variations in clinical presentation of esophageal dysphagia. Dysphagia is a potentially important symptom, often leading to the finding of an anatomical or motility disorder of the esophagus. Dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders. To explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders, we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory. A clear statistical association of symptomatic dysphagia and heartburn was established; however, no pattern diagnostic of a specific motility disorder was discernible. A sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility. A significant portion of dyspeptic patients exhibited both normal motility and acid exposure. The differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients.

Historical review of pancreaticoduodenectomy. The performance of pancreaticoduodenectomy by Whipple in 1935 demonstrated that the operation was feasible technically and compatible with reasonable function after recovery. From the mid- to late 1940s until the last 10 years, the procedure was condemned by many because of its associated mortality and morbidity. For reasons that are not clear, the risk of pancreaticoduodenectomy in the last 10 years has fallen to less than 10% and in several centers, less than 5%. Postoperative complications have been reduced and blood transfusions are unnecessary in an increasing number of patients. Furthermore, a normal productive life without the need for medication and with no digestive disorder is expected. Seventy-one percent of patients are able to return to their preoperative occupation.

Progressive coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension: report of two cases. Two cases of neurological deterioration and coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension and invasion of the 3rd ventricle are presented. Emergency ventricular shunting led to prompt neurological improvement, which, supplemented by radiation therapy, allowed long-term amelioration of symptoms. Three possible explanations for this complication are offered: 1) traction of the attached 3rd ventricle into the decompression site, causing increased obstructive hydrocephalus, 2) vasopressin release by surgical manipulation of the pituitary stalk and circumventricular organs causing cerebral edema, and 3) edema in the residual tumor secondary to surgical manipulation causing further hydrocephalus. Subsequent patients with similar clinical and imaging criteria will have a planned perioperative ventricular shunting procedure performed.

Magnetic resonance imaging of cardiac rhabdomyosarcoma. Quantifying the response to chemotherapy. This report illustrates the use of cardiac magnetic resonance imaging (MRI) to quantify the initial extent of a cardiac rhabdomyosarcoma and, more importantly, its response to chemotherapy. Image slices spanning the heart and adjacent structures were analyzed using Simpson's rule applied to the image slices to estimate the tumor volume initially, then after 5 weeks, and again after 4 months of chemotherapy. A substantial, progressive reduction in tumor volume during chemotherapy was shown. After chemotherapy was discontinued, an increase in tumor volume was shown. It is suggested that, in addition to being useful in patient care, the technique may be useful in clinical investigations by providing an objective, quantitative measure of tumor response to therapy.

Contracturing granulomatous myositis: a separate entity. Granulomatous muscle disease is most commonly seen in sarcoidosis, but may be seen in association with a wide variety of other disorders or in isolation. Patients with granulomatous myositis usually present with slowly progressive muscle pain and weakness affecting mainly proximal muscles. There are, however, a few reports of granulomatous muscle disease presenting with flexion contractures of the limbs. Two further patients with granulomatous muscle disease and flexion contractures of the limbs, but with no evidence of systemic granulomatous disease, is presented. It is suggested that such patients represent a separate clinical entity that is distinct from idiopathic granulomatous myositis presenting with muscle pain and weakness. The association of contracturing granulomatous myositis with a long-standing vasculitis in one patient suggests that the two conditions may be related.

Central nervous system involvement in patients with facial palsy due to borrelial infection. Patients with a peripheral facial palsy due to an underlying Ixodes-borne borreliosis often have cerebrospinal fluid findings indicating meningeal involvement. The aim of the present study was to identify signs of CNS involvement by means of brain-stem evoked response audiometry (BSER) in patients with a facial palsy due to borreliosis, as well as in patients with a facial palsy of unknown aetiology. Bell's palsy. Abnormalities in BSER were found to be significantly more common along the borrelial patients. Furthermore, a reversal of these abnormalities following treatment with benzyl-penicillin was found in the majority of patients with borreliosis. The results of the present study emphasize the importance of diagnosing and treating an underlying borreliosis in patients with a peripheral facial palsy.

Infantile spasms. Infantile spasms are a seizure disorder in young infants with diverse etiologies, suggesting that they arise from any disturbance of central nervous system function during susceptible periods of development. The prognosis for normal intellectual and neurologic development parallels that of the underlying etiology. Early and appropriate treatment with ACTH may lead to seizure control in a majority of patients. The treating physician must anticipate the side effects of this modality.

Clinical and electrophysiologic determinants, treatment and survival of patients with sustained malignant ventricular tachyarrhythmias occurring late after myocardial infarction To assess the clinical and electrophysiologic determinants, treatment and survival of patients with sustained malignant ventricular tachyarrhythmias late after myocardial infarction, a total of 108 patients (mean age 61 +/- 10 years) were studied. Thirty-two patients (Group I) had sustained ventricular tachyarrhythmias 8 to 60 days (mean 13 +/- 9) after acute myocardial infarction. The remaining 76 patients (Group II), who served as a control group, had no sustained ventricular tachyarrhythmias less than or equal to 60 days after infarction. The most significant independent determinants of sustained ventricular tachyarrhythmias late after infarction were the presence of late potentials (chi square = 16.07, p = 0.0001), defined as an abnormal signal-averaged QRS complex in association with an abnormal root-mean-square voltage in the terminal 40 ms of the QRS complex, and an abnormal ejection fraction of less than 40% (chi square = 10.09, p = 0.001). Sustained ventricular tachycardia was induced in 27 (96%) of 28 Group I patients. Among the 32 patients in Group I, antitachycardia therapy included antiarrhythmic drug therapy as the sole preventive measure in 14 (44%); map-guided surgery or coronary artery bypass surgery, or both, in 14 (44%) and the automatic cardioverter-defibrillator in 4 (12%). The arrhythmias were rendered noninducible in 83% of patients after map-guided surgery and in 41% after drug therapy. During a follow-up period of 20 +/- 14 months, five Group I patients (15%) had an arrhythmic event and four (9.3%) had a cardiac-related death. All five patients who had an arrhythmic event were receiving antiarrhythmic drug therapy.

Acute angiographic and clinical outcome of high speed percutaneous rotational atherectomy (Rotablator). Percutaneous rotational atherectomy (Rotablator), a high speed (greater than 100,000 RPM) rotational burr, was used successfully in 38 of 43 patients (88%) (mean age: 65 +/- 7 years) with 82 lesions (71 stenoses and 11 occlusions). The clinical indications were claudication (84%), nonhealing ulcer (7%), and renovascular hypertension (7%). Rotablation was successful in 78 of 82 lesions (95%): 68 of 71 (96%) stenoses (12 of 12 iliac, 11 of 11 femoral, 7 of 8 popliteal, 36 of 37 tibial, and 2 of 3 renal arteries; 60% of lesions were diffuse, i.e., greater than or equal to 4 cm in length), and 10 of 11 (91%) occlusions (5 of 6 femoral, 1 of 1 popliteal, 3 of 3 tibioperoneal, 1 of 1 brachial artery). The Rotablator significantly (p less than 0.001) reduced the arterial obstruction (stenoses: 85 +/- 11% to 12 +/- 12%); occlusions: 100% to 25 +/- 10%). The effective final burr size for arteries varied at 3.5-4.5 mm for renal, 3.0-3.5 mm for femoral, and 2.0-3.0 mm for brachial and tibial. Complications included gross hemoglobinuria without sequelae in 27 patients (63%), groin hematoma in 10 (23%), arterial spasm in 10 (23%), and arterial bypass in 2 (5%). The Rotablator was successfully used, without concomitant conventional balloon angioplasty, to open arterial lesions with excellent angiographic results in both diffuse and segmental peripheral vascular disease. There was gratifying patient clinical improvement.

Entrapment neuropathy of the median nerve at the level of the ligament of Struthers. The presence of a supracondylar process and Struthers' ligament is a rare congenital anomaly that may cause compression of either the median nerve, the brachial artery, or both. The authors present a case in which the supracondylar process and Struthers' ligament compressed both the median nerve and the brachial artery. This case is unusual, in that the symptoms of compression of the brachial artery increased--namely, the pulse intensity decreased and the pain increased with elbow flexion.

Third ventricle cavernous angioma: report of two cases. Cavernous angioma arising in the third ventricle is an extremely rare disease. We have reviewed five cases previously reported, as well as our own two cases, and discuss the clinical characteristics of and surgical approach to cavernous angioma at this site. The bifrontal craniotomy and interhemispheric translamina terminalis approach minimize the damage to the brain and allow for an approach to the third ventricle in a wide operative field with minimal compression of the brain itself. We have found this approach to be suitable for surgery on angiomas of the anterior half of the third ventricle.

Increased Ca2+ signaling after alpha-adrenoceptor activation in vascular hypertrophy. In an effort to explain the increased sensitivity to agonists of hypertrophic vascular muscle, intracellular Ca2+ concentration ([Ca2+]i)-signaling mechanisms were studied in normal and hypertrophic rat aortas from normotensive and coarctation-hypertensive rats. Based on both fura 2 fluorescence and aequorin luminescence measurements, qualitatively different patterns of Ca2+ mobilization occur in normal and hypertrophic rat aortic muscle. Normal rat aortic muscle contracts to phenylephrine with little or no increase in [Ca2+]i, whereas the angiotensin II-induced contraction is accompanied by a marked [Ca2+]i transient. In contrast, hypertrophic rat aortic muscle shows a dramatic increase in Ca2+ signaling after phenylephrine stimulation. Moreover, both the amplitude of the angiotensin-induced [Ca2+]i transient and the contractile sensitivity to this agonist are decreased in the hypertrophic muscle. Our results strongly suggest that the amplitude of the [Ca2+]i transient after agonist stimulation determines the contractile sensitivity and that there is an altered coupling of the alpha-adrenoceptor in the hypertrophic vascular muscle.

Atrial fibrillation in the elderly: management update. Non-valvular atrial fibrillation is associated with a markedly increased risk of embolic stroke in elderly persons. Evidence is accumulating that anticoagulation with warfarin or aspirin may be effective in reducing this risk.

Recurrent transient ischemic attacks and stroke in association with an internal carotid artery web Fibromuscular dysplasia is a nonatherosclerotic vascular disease that most commonly affects cervical carotid arteries at the C1-C2 level when cephalic arteries are involved. Several histopathologic and angiographic subtypes of fibromuscular dysplasia exist; most have a benign natural history. We describe the third reported case of a pathologically proven, symptomatic proximal internal carotid artery web and suggest that patients with this lesion are at a higher risk for stroke.

Fatal fungal pericarditis after cardiac surgery and immunosuppression. The cases of two patients with fulminant pericarditis after cardiac surgery are reported. Both fungal infections developed after rethoracotomy for open-chest cardiac resuscitation and high-dose glucocorticoid treatment. Although the time course of both infections from the inoculation of fungi during rethoracotomy and immunosuppression with glucocorticoids to the lethal outcome was strikingly similar, histopathologic studies disclosed the disparate character of the two fungal pathogens responsible: the yeast Candida albicans and the angiotropic mold Aspergillus fumigatus.

Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence. The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease.

Hilar malignancy: treatment with an expandable metallic transhepatic biliary stent. An expandable metallic transhepatic biliary endoprosthesis was used to treat 20 patients with hilar malignancy and isolated right and left intrahepatic ducts. In 12 patients, only one intrahepatic ductal system was drained; in eight patients, both systems were drained. In five patients, both systems were drained through a single transhepatic track by arrangement of two stents in a T configuration. The initial technical success rate in placing the stents and achieving internal drainage was 100%. Complications necessitating further intervention occurred in two of the 20 patients. Short-term clinical follow-up was available for 19 of the 20 patients. Two months after stent insertion, two patients complained of persistent jaundice, two patients died without jaundice, and 15 patients were free of symptoms of biliary obstruction. A variety of geometric configurations are possible with this endoprosthesis. The relative merits of these stent arrangements are discussed, and a new technique for placing the stents in a T configuration is described.

Adult phosphorylase b kinase deficiency. Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both.

Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state. The present study investigates the nature of humoral component(s) generated in tumor-bearing hosts to induce immune dysfunction of T cells. Cell-free ascitic fluid and culture supernatant (SN) were obtained from the ascites and cultures allowing MH134 hepatoma cells to grow. These ascites and SN samples were tested for their abilities to influence the generation of CTL responses to TNP and alloantigens. The generation of the anti-TNP CTL responses that require self H-2-restricted CD4+ Th cells was markedly suppressed by addition of the ascites or SN under conditions in which these samples did not inhibit anti-allo CTL responses capable of using alternate pathways of allo-restricted CD4+ and CD8+ Th. The activation of CD8+ CTL precursors and CTL activity were also resistant to the ascites or SN. The ascites- or SN-induced suppressive effect to which CD4+ Th were most susceptible was found to be mediated by transforming growth factor-beta (TGF-beta) activity, because: 1) the TGF-beta activity was detected in the MH134 ascites and culture SN; 2) the suppression of CD4+ Th function required for anti-TNP CTL responses was almost completely prevented by addition of anti-TGF-beta antibody to cultures and; 3) rTGF-beta also induced similar patterns of immunosuppression to those observed by ascites or SN. These results indicate that TGF-beta produced by tumor cells induces deleterious effects on T cell, especially on the CD4+ Th subset, and provide an explanation for the molecular mechanism underlying the previously observed CD4+ Th-selective suppression in the tumor-bearing state.

Fibrin glue inhibits intra-abdominal adhesion formation. To determine the effect of fibrin glue on intra-abdominal adhesion formation, 45 rats were randomized to three groups. Each animal received two adhesion models. Group 1 received no further treatment. Groups 2 and 3 had the adhesion models covered with fibrinogen from fresh frozen plasma (1.77 g/L) and cryoprecipitate (23.6 g/L), respectively. In group 1, 13 of 15 rats had high-grade adhesions in both models. In group 2, high-grade adhesions were noted in nine of 15 rats in model 1 and in 12 of 15 rats in model 2. In group 3, however, high-grade adhesions were seen in only three of 15 rats in model 1, with 11 rats having no adhesions, and in only two of 15 rats in model 2. Histologic analysis suggested accelerated healing in group 3. We conclude that (1) fibrin glue inhibits intra-abdominal adhesion formation in rats, (2) the inhibitory action is dependent on the fibrinogen concentration of the fibrin glue, and (3) adhesions are reduced by fibrin glue regardless of whether the peritoneal defect is closed.

Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine. We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year-old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect.

Chronic pain. Understanding of the etiology of chronic pain is growing rapidly as researchers seek to integrate physiologic and psychosocial mechanisms. When nurses assess clients with chronic pain, they should make their assessments using both verbal and nonverbal methods and realize that no one instrument is comprehensive enough to be used alone. The key to successful treatment of these difficult clients lies in the use of a comprehensive approach that takes the client seriously and integrates both physiologic and psychosocial approaches.

Brain imaging abnormalities in mental disorders of late life. Psychiatric inpatients with dementia (N = 61) or depression (N = 67) in late life were 2.6 times more likely to manifest magnetic resonance imaging abnormalities of the brain than were elderly controls (N = 44). Controlling for the effects of age and gender, demented patients were distinguishable from controls by an increased prevalence of cortical atrophy and infarction, while depressed patients exhibited an increased prevalence of cortical infarctions and leukoencephalopathy. Patients with dementia were distinguishable from those with major depression by an increased prevalence of cortical atrophy. These results indicate that major depression in late life, like dementia, is associated with a remarkable increase in overt pathologic changes in the brain.

Use of autologous blood in total hip replacement. A comprehensive program. We evaluated the effectiveness of a comprehensive program for the use of autologous blood in reduction of the need for transfusion of homologous blood in total hip replacement in a prospective study of a consecutive series of patients. Transfusion of homologous blood was minimized through transfusion of preoperatively deposited autologous blood, intraoperative and postoperative salvage of washed red blood cells, and use of the clinical condition of the patient as the sole criterion for transfusion of non-autologous blood, regardless of the hematocrit. The cases of 143 patients who had had 154 primary total hip replacements were studied. One hundred and forty-three procedures were done on patients who had not been prevented from donating blood for medical reasons, and 93 per cent of these 143 procedures were performed with the availability of one to five units of preoperatively deposited autologous blood. The patients predeposited an average of 2.6 units of blood for each procedure. Ninety-two per cent of the procedures for which autologous blood had been predeposited were performed without transfusion of homologous blood. In the entire group of patients, almost 90 per cent of the transfused blood was autologous blood. Intraoperative salvage of red blood cells was successful in 148 procedures, and salvage was continued in the recovery room for all of these patients. An average of 408 milliliters of red blood cells was saved and reinfused, and this was 28 per cent of the average total loss of blood (1435 milliliters) for this series of procedures.

Vasopressin-related bullous disease of the legs. We report a 33-year-old man who developed cutaneous necrosis of the lower extremities with extensive bulla formation after i.v. administration of vasopressin for the treatment of bleeding esophageal varices. Due to its potent nonselective vasoconstrictive action, vasopressin not only may induce cardiac and gastrointestinal ischemia, but cutaneous ischemia as well. As in our patient, this may lead to extensive necrotic skin lesions at sites distant from the infusion.

Treatment of squamous cell carcinoma of the anal canal. Progress in the prognosis of patients with squamous cell carcinoma of the anal canal has followed the use of multimodality therapy. From 1977 to 1985, 42 patients with squamous cell carcinoma of the anal canal were treated with mitomycin C (15 mg/m2) and 5-fluorouracil (750 mg/m2) on day 1, 5-FU (750 mg/m2/d) alone on days 2 to 5, and radiation therapy (3000 cGy) on days 7 to 28. They were evaluated 4 to 6 weeks after completion of the chemotherapy/radiation therapy protocol and received local excision, abdominoperineal resection, or both. Patient follow-up times ranged from 7 to 161 months, with a mean follow-up time of 71 months. Pathologic examination showed no residual carcinoma in 19 (45%) patients. The authors could not predict, based on clinical evaluation, which patients would have a complete response. Of the patients with a complete clinical response, 44% had tumor in the pathology specimen. Wide local excision was the most common initial operation (23 of 42 patients; 55%), with five of these patients subsequently requiring abdominoperineal resection. Anal continence was retained in 18 of 42 (43%) patients. Eleven patients experienced recurrent disease: six local recurrences, one distant, and four both local and distant. The 5-year overall survival rate was 82% and the 5-year disease-specific survival rate was 87%. There were no treatment related deaths. Preoperative tumor size was the only factor significantly related to survival. Contrary to other reports, tumor in the pathology specimen did not adversely affect long-term survival. Hence, patients should be treated after chemotherapy/radiation therapy with surgical therapy sufficient to control local disease.

Evoked potentials in assessment and follow-up of patients with Wilson's disease. Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.

Conservative therapy for adnexal torsion. A case report. Adnexal torsion has traditionally been treated with oophorectomy because of the fear that untwisting the ovarian pedicle may result in a thrombotic embolus. Such a patient had bilateral adnexal torsion secondary to dermoid cysts. Since standard therapy, oophorectomy, was performed, the patient was surgically castrated. A review of the literature revealed no reported cases of a thrombotic embolus arising from the untwisting of twisted adnexa and supported conservation of the adnexa rather than routine extirpation, except when necrotic.

Detection and evaluation of intrapulmonary vascular shunt with "contrast Doppler" transesophageal echocardiography. Contrast echocardiography is useful for detecting intrapulmonary right-to-left shunt lesions. In a patient with suspected pulmonary arteriovenous fistula, contrast transesophageal echocardiography was used to demonstrate the presence of a right-to-left shunt. By use of a combination of two-dimensional echocardiography, contrast injection, and pulsed Doppler echocardiography, each pulmonary vein was successfully interrogated for evidence of contrast shunting. This case demonstrates that contrast transesophageal echocardiography is useful for the detection of intrapulmonary fistulas and that it has the potential for localization of the shunt lesion.

Long-term results of Ionescu-Shiley valve in the tricuspid position. A retrospective analysis of the long-term results of using the Ionescu-Shiley pericardial bioprosthesis in the tricuspid position was carried out on 73 patients (8 men, 65 women). Of these procedures, ten were tricuspid valve replacement alone and the remainder were in combination with other valve procedures. The mean follow-up was 9.6 years (range, 4 to 18 years). The mean age of the patients was 53 years (range, 27 to 78 years). Seventy-one of the patients suffered tricuspid valve dysfunction from rheumatic heart disease. There were 13 postoperative deaths (within 30 days), giving a mortality rate of 17.8%. The actuarial survival at 10 years was 71% +/- 4.2%. Of the survivors, 49 (79.6%) were in functional class I or II. Primary tissue valve failure in the tricuspid position occurred in 1 patient 12 years after implantation and required reoperation. In another patient bioprosthetic tricuspid valve endocarditis developed. There was no incidence of thromboembolic complications. We conclude that the Ionescu-Shiley pericardial bioprosthesis was a satisfactory prosthesis in the tricuspid position in patients with acquired valvar dysfunction.

The value of push-type jejunal endoscopy in familial adenomatosis coli/Gardner's syndrome. Push-type jejunal endoscopy using a long forward-viewing duodenofiberscope was performed in 10 patients with familial adenomatosis coli/Gardner's syndrome. Jejunal polypoid lesions were detected in nine of the 10 patients (90%). The lesions appeared sessile, whitish, and measured 3 mm or less in diameter. Histologic findings of the biopsy specimens from these polypoid lesions revealed tubular adenoma in all nine patients. In addition, this method led to the detection of duodenal adenomas in one patient, in whom duodenofiberscopy with the side-viewing instrument revealed no polypoid lesions in the bulb and second portion of the duodenum. In view of these results, we recommend that push-type jejunal endoscopy, as well as side-viewing duodenofiberscopy, should be added to the usual preoperative examinations done in patients with this disease.

Effect of atenolol and diltiazem on heart period variability in normal persons. Several time and frequency domain measures of heart period variability are reduced 1 to 2 weeks after myocardial infarction, and a reduced standard deviation of normal RR intervals over a 24 h period (SDNN) is associated with increased mortality. The predictive accuracy of heart period variability may be reduced by drugs used to treat patients after myocardial infarction. Accordingly, a randomized, three period, placebo-controlled, crossover (Latin square) design was used to determine the effect of atenolol and diltiazem on time and frequency measures of heart period variability calculated from 24 h continuous electrocardiographic recordings during treatment with atenolol, diltiazem and placebo in 18 normal volunteers. During atenolol treatment, the 24 h average normal RR (NN) interval increased 24% (p less than 0.001). The three measures of tonic vagal activity were significantly increased (p less than 0.001) during atenolol treatment: percent of successive normal RR intervals greater than 50 ms = 69%, root mean square successive difference of normal RR intervals = 61% and high frequency power in the heart period power spectrum = 84%. Low frequency power also increased 45% (p less than 0.01), indicating that this variable also is an indicator of tonic vagal activity over 24 h. Diltiazem had no significant effect on the 24 h average NN interval or on any measure of heart period variability. The decreased mortality rate after myocardial infarction associated with beta-adrenergic blocker but not calcium channel blocker therapy may be attributed in part to an increase in vagal tone caused by beta-blockers.