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8793565
Transmembrane signaling through CD80 (B7-1) induces growth arrest and cell spreading of human B lymphocytes accompanied by protein tyrosine phosphorylation.
We addressed the issue of the role for CD80 (B7-1) expressed on human B cells in transmembrane signaling. Cross-linking of CD80 on B lymphoma Raji cells induced tyrosine phosphorylation in 160-, 120-, 55-, 46- and 44-kDa proteins, which was inhibited by genistein. CD80-mediated signaling resulted in the inhibition of DNA replication of B cells and induced the changes in morphology like macrophages or fibroblasts. This cell spreading was inhibited by the pre-treatment of the cells with genistein. These results suggest that the CD80 antigen is involved in transmembrane outside-in signaling in B cells and its biological effects appear to be mediated by tyrosine kinases.
8793566
Secretory component, the receptor for polymeric immunoglobulin, has nothing to do with beta-galactosyltransferase in human milk.
ponent (SC) in external secretions is a soluble form of the polymeric immunoglobulin-receptor that is expressed on the cell membrane of mucosal epithelial cells. beta-(1-4)galactosyl transferase (beta-GT) is an enzyme that transfers galactose to non-reducing N-acetylglucosamine residues on various glycoproteins and is present in a soluble form in secretions as well as in a membrane-bound form. beta-GT is considered to have affinity for glycoproteins, including IgA in secretion. It has been claimed that these two proteins are related to or identical with each other. In the present study, we defined that the SC and the beta-GT are each independent molecules by the following facts; (1) both molecules are separable either by antibody-affinity chromatography, conventional ion-exchange or molecular exclusion chromatography, (2) conventionally purified SC from human milk contained neither enzymatic activity or antigenic determinants of the beta-GT, (3) binant beta-GT does not show reactivity with antibodies to SC, and (4) the SC showed no reactivity with antibody to beta-GT.
8793567
Effect of calcitonin gene-related peptide and vasoactive intestinal peptide on murine CD4 and CD8 T cell proliferation.
The effects of alpha calcitonin gene-related peptide (alpha CGRP) and vasoactive intestinal peptide (VIP) on the proliferation of CD4 and CD8 T-murine lymphocytes were investigated. When stimulated by bination of phorbol 12-myristate-13-acetate (PMA) and calcium ionophore (A23187), both neuropeptides in a range of 10(-7)-10(-10) M had an inhibitory effect on the proliferative response of unfractionated splenocytes as well as of purified CD4 and CD8 T lymphocytes. The inhibitory effect of these two neuropeptides pletely or partially blocked by the antagonists of CGRP and VIP receptors. CGRP8-37 and (p-Cl-D-Phe6, Leu17VIP, respectively. The inhibitory effects of each neuropeptide on purified T cells were observed within 4 h after PMA/A23187 activation and their inhibitory actions were correlated with a decrease of IL-2 production. In addition, the two neuropeptides in a range of 10(-7)-10(-10) M induced a rapid and dose-dependent increase in intracellular cAMP in CD4 and CD8 T cells. This suggests the involvement of this second messenger in the inhibitory effects of these two neuropeptides. Taken together these results show that CD4 and CD8 spleen cells represent at least two of the cellular targets for CGRP and VIP inhibition of proliferation mediated by the same type of mechanism.
8793570
ACE inhibitors and unilateral renal artery stenosis--what price?
The effects of ACE inhibitors on the stenosed kidney in patients with unilateral arterial stenosis are not well characterised. While there are conflicting reports, some experimental and clinical evidence suggest that the stenosed kidney may undergo atrophy: secondary to effective blood pressure lowering and decreased perfusion pressure distally, or due to other mechanism/s. Such a loss of renal function may go unrecognised. In view of the widespread use of ACE inhibitors, the fate of the stenosed kidney needs to be more accurately known.
8793571
Evaluation of patients with minimally obstructive coronary artery disease and angina.
Atherosclerotic coronary artery disease is a progressive process adversely affecting the integrity of the coronary vasculature. In past years, most studies have focused on the morphological changes leading promised coronary blood flow in atherosclerosis. However, in recent years it has e apparent that abnormal coronary vasomotor regulation may precede or pany gross morphological changes in coronary atherosclerotic disease. In fact, the pathophysiology of angina pectoris in many patients with risk factors for atherosclerosis and minimally obstructive disease may involve abnormal coronary vasomotor tone regulation. The aim of the present article is to describe a clinical approach to patients with angina pectoris and minimally obstructive coronary artery disease based on current knowledge of coronary vasomotor regulation.
8793572
Outpatient cardiac catheterisation.
Cardiac catheterisation is increasingly performed in an outpatient setting. The majority of series of outpatient cardiac catheterisation are in laboratories with immediate access to cardiovascular surgery. However, some units may be sited more distantly, although still generally close to a hospital. Compared to an inpatient procedure, outpatient cardiac catheterisation increases bed availability and there are considerable financial rewards with suggested savings of 11-54% of inpatient costs. Most patients are satisfied with an outpatient procedure and, although a quarter may have unanswered questions afterwards, this level may not differ from that found with inpatients. No study has been large enough to detect differences in the plication rate which occur infrequently in whichever setting, and there is considerable variation between studies in the incidence of plications after outpatient procedures. In the only study which randomised all eligible patients to an inpatient (189 patients) or outpatient (192 patients) procedure, seven outpatients (3.6%) suffered bleeding or developed haematomas at the site of percutaneous femoral artery puncture towards the end of the mobilisation period and one patient was syncopal. These events were thought to be a direct result of the procedure being carried out in the outpatient setting. The proportion of patients considered eligible for outpatient cardiac catheterisation varies widely between different series from 20% to more than 80%. Whereas some of this variation may result from the implementation of different exclusion criteria for patients with potentially severe disease, the differences are so large that it is likely that different populations were studied. Unplanned admission rates varied from less than 1% to nearly 19%. With the currently available data no absolute guidelines can be derived to exclude all patients at risk plications, but the American College of Cardiology/American Heart Association (ACC/AHA) task force recently published guidelines which identified low risk patients suitable for outpatient procedures. These guidelines have been used to select patients for investigation in two mobile units in the USA, and only 0.9% required urgent transfer for clinical instability, and 0.6% developed plications. However, most patients did not need referral to a tertiary centre for additional procedures and there may be less scope for selecting patients within the ACC/AHA guidelines in the pared with the USA.
8793573
Spontaneous closure of interatrial septal openings in infants: an echocardiographic study.
Four-hundred-and-fifteen neonates were evaluated by echocardiographic means in order to detect interatrial septal openings and were followed for a maximum time of 18 months. In 68.67% of them, interatrial septal openings were present at the first week of life. The defects were larger than 3 mm in 50.18% of these infants. At the end of the 18th month, openings persisted in 3 cases. The statistical analyses showed significant difference about the percent of closing between the groups with initial opening sizes lesser and bigger than 3 mm. Also, there was a positive correlation between the initial size and the spontaneous closure time. Spontaneous closure incidences were not different in boys and girls. In a small group of infants (4.64%), interatrial openings close forming septal aneurysms. In 12.3% of the newborns without an opening, septal aneurysms were detected during the initial evaluation.
8793574
Intracoronary cyclic-GMP and cyclic-AMP during percutaneous transluminal coronary angioplasty.
We investigated intracoronary cyclic-guanosine monophosphate (c-GMP) levels during percutaneous transluminal coronary angioplasty (PTCA) since experimental studies have shown the endothelial origin of c-GMP production. Intracoronary c-GMP and cyclic adenosine monophosphate (c-AMP) were measured during coronary angioplasty in 24 patients with chronic coronary artery disease. Four coronary blood samples were taken through a catheter from the coronary artery the first sample before coronary angiography and the other three from distal to coronary obstruction, as follows: before the balloon inflation, at the maximum inflation and 5 min after restoration of coronary flow. c-GMP increased from 7.9 +/- 1.0 pmol/ml and 7.5 +/- 0.9 pmol/ml before angiography and balloon inflation to 11.1 +/- 1.3 pmol/ml at the maximum inflation (P < 0.01), with a trend to decrease 5 min after the end of the intervention (9.5 +/- 1.0 pmol/ml, P: NS). Intracoronary c-AMP levels remained almost unchanged. Five venous samples were taken to measure c-AMP before coronary angiography, before PTCA, and 5 min, 2 h and 24 h after PTCA. c-AMP values 2 and 24 h after PTCA (17.8 +/- 1.7 pmol/ml and 17.5 +/- 1.7 pmol/ml, respectively) were lower than the highest value (22.1 +/- 2.1 pmol/ml) found 5 min after PTCA, (P < 0.001). c-GMP increases distal to coronary obstructive lesion during PTCA at the time of balloon inflation, while c-AMP remains unchanged. c-AMP rises in venous circulation only. PTCA stimulates the mechanism of c-GMP release, while systemic c-AMP increase seems to be related to the stress occurring during catheterisation and PTCA.
8793575
Use of dopamine in prevention of contrast induced acute renal failure--a randomised study.
We report the use of dopamine in renal doses (5 micrograms/kg/min) to prevent contrast induced nephropathy (CIN). Forty patients with diabetes mellitus who were undergoing coronary angiography were randomly divided into two groups. Gr I (20 patients) was infused with dopamine starting 30 min before cardiac catheterization and continued for 6 h thereafter. Gr II (20 patients) did not receive dopamine. Baseline blood chemistry was performed before catheterization and then repeated 24 h after the procedure. The mean age and sex distribution were similar in both the groups. Urograffin (76%; 120-150 ml) was used in all the cases. The mean serum creatinine and blood urea nitrogen (BUN) levels in Gr I patients before catheterization were 1.5 +/- 0.32 mg % and 16.3 +/- 8.05 mg %, respectively. The corresponding values for Gr II were 1.52 +/- 0.68 mg % and 19.6 +/- 13.4 mg %, respectively. After angiography, Gr I patients did not show significant changes in renal parameters (serum creatinine, 1.37 +/- 0.25 mg % and BUN, 14.7 +/- 5.5 mg %) while Gr II patients showed a significant rise (serum creatinine, 1.96 +/- 1.2 mg % and BUN, 23.25 +/- 12.7 mg %; P = 0.01 and P = 0.05, respectively). Ten patients in Gr II (50%) developed a 25% rise in serum creatinine levels within 24 h of injection of the contrast. None of the patients developed renal failure severe enough to warrant dialysis. Hence alterations of renal function mon after cardiac catheterization. Dopamine in renal doses appears to be an effective means to prevent deterioration in renal function induced by contrast.
8793576
The prognostic value of serum troponin T in unstable angina.
Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator.
8793577
Mechanism of the positive inotropic action of cocaine in the guinea pig atrium.
We studied the mechanism of the positive inotropic action of cocaine in isolated guinea pig atria superfused with Tyrode's solution at 31 degrees C while attached to a force transducer to measure peak tension developed, maximum velocity of development of tension, and time to peak tension. Cocaine 2.9 microM enhanced peak tension developed and velocity of development of tension, and prolonged time to peak tension. The increase in peak tension developed produced by cocaine was not affected by propranolol. On the other hand, the cocaine-induced increase in velocity of development of tension was reduced, but not abolished. In the presence of propranolol and bined, the cocaine-induced prolongation of time to peak tension was abolished and the increases of both peak tension developed and velocity of development of tension were significantly smaller than those observed in the absence of the two adrenergic blockers. For all practical purposes, pletely abolished the increase in peak tension developed induced by cocaine. It is concluded that the positive inotropic effect of cocaine in the guinea pig atrial muscle is predominantly the result of adrenergic-dependent, both alpha- and beta- receptor mediated, as well as adrenergic-independent increases in calcium influx through the L-type calcium channels in the sarcolemma.
8793578
Jugular venous pressure and pulse wave form in the diagnosis of right ventricular infarction.
Jugular venous pressure (measured clinically) and pulse wave form (recorded at 100 mm/s) were analysed in 44 cases of first acute myocardial infarction and 10 age-matched controls. Patients were divided into different groups according to site of infarction decided by detailed 2-D echocardiography. Raised jugular venous pressure had high specificity (96.8%) but low sensitivity (39%) in diagnosing right ventricular infarction. Positive Kussmaul's sign had equal specificity but lower sensitivity (26.1%). Rapid 'y' descent had high specificity (100%) but low sensitivity (17.3%) in diagnosing right ventricular infarction. Jugular venous pressure and pulse wave form are significantly affected by the magnitude of damage to interventricular septum and left ventricular free wall.
8793580
Genetic basis of left ventricular remodeling after myocardial infarction.
The purpose of the present study was to assess whether the insertion (I)/deletion (D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) were associated with left ventricular dilatation after myocardial infarction. In 103 patients with myocardial infarction, the left ventricular (LV) end-diastolic volume index (EDVI) and the end-systolic volume index (ESVI) were assessed by echocardiography at two time points, namely at 7 +/- 4 days and at 3.9 +/- 1.3 months (mean +/- S.D.) after the infarction. The increases in the LVEDVI and LVESVI on the second echocardiogram were significantly higher in subjects with the DD and ID genotypes than in patients with the II genotype (P < 0.05 and P < 0.005, respectively). Multiple regression analysis revealed that the LVESVI at the first echocardiographic examination and the ACE I/D genotype were significant predictors of the LVEDVI and LVESVI at the second echocardiographic examination. However, the AGT M235T genotype was eliminated. In conclusion, the DD and ID genotypes of the ACE gene were significantly associated with the progression of the LVEDVI and LVESVI after myocardial infarction. The presence of the deletion allele of the ACE gene may be a risk factor of congestive heart failure after a myocardial infarction.
8793579
Contribution of cardiopulmonary indices in the assessment of patients with silent and symptomatic ischemia during exercise testing.
Cardiopulmonary and radionuclear indices were used to evaluate pare cardiac function during exercise testing in patients with symptomatic and silent ischemia. The prised 58 patients aged 35-74 years, divided into three groups: Group I-20 patients (controls) with neither ST depression nor chest pain; Group II-22 patients with ST depression > 1 mm and no chest pain; Group III-16 patients with both ST depression and chest pain. All patients in Groups II and III demonstrated significant coronary artery disease. No antianginal medication was taken at least 24 h before testing. All patients underwent a cardiopulmonary exercise test and a multigated acquisition radionuclear study. The following variables were measured: oxygen consumption (VO2), CO2 output (VCO2), minute ventilation (VE), O2-pulse, ventilatory anaerobic threshold (VAT), left ventricular ejection fraction (LVEF) at rest (r) and at maximal effort (ex). Probability values were significant for all variables (P < 0.01-0.0001) except left ventricular ejection fraction-rest (P not significant between the three groups). No significant differences in extent of coronary artery disease were noted between Groups II and III. These findings suggest that during exercise testing patients with silent ischemia have better overall cardiac function than patients with symptomatic ischemia. Their value for both cardiopulmonary and radionuclear indices are closer to those of the control group than to the symptomatic group, regardless of the severity of the coronary artery disease Summary of results: (mean +/- 1 S.D.) Group VO2-max O2-Pulse max VAT (%) VAT (ml/min) LVEF-rest delta LVEF (ex-r) I 25.2 +/- 6.3 15.7 +/- 3.4 51.2 +/- 6.6 1075 +/- 289 54.7 +/- 7 5.4 +/- 4.85 II 22.4 +/- 2.8 14.5 +/- 2 47.0 +/- 5.3 854 +/- 136 52 +/- 10 1.2 +/- 6.7 III 16.0 +/- 2.5 11.4 +/- 2 41.6 +/- 7.7 683 +/- 105 51 +/- 8.5 -5.87 +/- 6.3
8793581
Electrical injury to the heart may cause long-term damage to conducting tissue: a hypothesis and review of the literature.
Electrical injury, particularly alternating current, may lead to disease of conducting tissue, myocardial damage or may cause sudden cardiac death. Subtle abnormalities, particularly of sinus node function, may pose diagnostic difficulties and may not present for many years. The long-term follow-up of patients, perhaps as part of a registry, will help to define the clinical spectrum of cardiac presentations of electrical injury.
8793582
Efficiency of heating during radiofrequency catheter ablation of accessory atrioventricular pathways.
Adequate heating with myocardial thermal injury is necessary for successful ablation. This study was designed to examine the relationship between power, temperature, and efficiency of heating during radiofrequency catheter ablation of accessory pathways in 76 patients. During each application of radiofrequency energy, temperature was continually monitored by use of an ablation catheter with a thermistor embedded in the tip of the distal electrode. The efficiency of heating varied by location, with the greatest efficiency of heating for posteroseptal energy applications (2.7 +/- 2.3 degrees C/W), which were significantly greater than for left-sided (2.1 +/- 1.9 degrees C/W, P < 0.01) or right-sided (1.0 +/- 1.1 degrees C/W, P < 0.01) applications. For patients with left free wall and posteroseptal pathways, the temperature, radiofrequency power, time to peak temperature and efficiency of heating were similar between the successful and unsuccessful pulses. However, the mean temperature (53.5 +/- 4.5 vs. 45.1 +/- 5.1 degrees C, P < 0.01) and radiofrequency power (49.6 +/- 5.2 vs. 40.3 +/- 10.2 watt, P < 0.05) differed significantly between the successful and unsuccessful ablation pulses in patients with right free wall pathways. To achieve greater efficiency of heating and higher temperature, it is reasonable to use higher power outputs (40-50 W) in radiofrequency ablation of right free wall pathways, whereas less power outputs (30-40 W) are likely to produce adequate heating of posteroseptal and left free wall pathways, and minimize the risk of impedance rise and coagulum formation.
8793583
Correlation between late potentials duration and QTc dispersion: Is there a causal relationship?
QTc interval dispersion (QTcd) analysis (difference between maximum and minimum QTc calculated from at least five of the standard 12 ECG leads) and signal-averaged electrocardiograms were performed on 23 patients referred to our coronary care unit because of acute myocardial infarction. Late potentials were considered positive if all three of the following criteria were satisfied: (1) total QRS duration (QRSd) > 114 ms; (2) duration of QRS under 40 muV (LAS 40) > 38 ms; (3) root mean square voltage of the last 40 ms of QRS (RMS 40) < 25 muV. Patients were divided into two groups according to the presence (group A, 9 patients) or absence of late potentials (group B, 14 patients). Group A patients showed a significantly higher QTcd (0.0652 +/- 0.0177 s vs. 0.0448 +/- 0.0201 s; P = 0.021) and a significantly longer mean QTcm (0.43117 +/- 0.01817 s vs. 0.40472 +/- 0.03013 s; P = 0.028) than group B patients. Among the three different parameters used to define the presence of late potentials, QTcd was significantly related to LAS 40 (r = 0.418, P = 0.047) and mean QT cm to QRSd (r = 0.497; P = 0.016). We also found a significant correlation between QTcd and mean QTcm (r = 0.426; P = 0.043). In conclusion, our data suggest that (1) the presence of late potentials is associated with a greater dishomogeneity of ventricular recovery time; (2) the longer the duration of late potentials, expressed by LAS 40, the greater the QTcd, suggesting that the dispersion of repolarization could be attributed to slowly conducting areas from which late potentials arise; (3) mean QTcm is not useful to identify these areas because it is more affected by total rather than by terminal QRS duration; (4) regional discrepancies of ventricular recovery time are connected with general repolarization duration.
8793584
Heart rate variability in hypertensive subjects.
Hypertension is often associated with findings of sympathetic hyperactivity. Evidence shows that adrenergic receptor stimulation can induce left ventricular hypertrophy. Using an autoregressive algorithm in a power spectrum analysis of heart-rate variability in 14 subjects with mild hypertension (mean age 41 +/- 9.0 years) and 9 age-matched normotensives pared autonomic nervous system function at baseline (rest) and during sympathetic stress (passive head-up tilt). The prised four spectral frequency-domains: total power (0.0033-0.40 Hz), high-frequency power (0.16-0.40 Hz), low-frequency power (0.04-0.15 Hz) and very-low-frequency power (0.0033-0.04). The high-frequency ponent predominantly reflects vagal activity, the ponent sympathetic nervous system activity. The ratio between low-and high-frequency power expresses the sympathovagal balance. Results were expressed as natural logarithms of power and normalized units. In addition, pared spectral densities obtained, with the left ventricular mass index evaluated by M-mode echocardiography. Hypertensive subjects had greater low-frequency and low-high frequency ratio values (P < 0.001) than normotensive controls. They also had a low capacity for increase after tilt. Multiple regression analysis showed that the left-ventricular mass index was independently associated with the body mass index (P < 0.0027), very-low frequency (P < 0.043), and low frequency (P < 0.0138) expressed as the natural logarithm, low-high frequency ratio (P < 0.0172) and systolic blood pressure (P < 0.0353). Our findings confirm enhanced sympathetic activity in hypertensive subjects. They also indicate a close association between the left-ventricular mass index and spectral indices of sympathetic activation.
8793585
Thallium-201 myocardial perfusion imaging in patients before and after successful percutaneous transluminal coronary angioplasty.
We studied the value of exercise thallium-201 (Tl-201) scintigraphy for evaluation of myocardial perfusion improvement and the detection of restenosis in patients after successful percutaneous transluminal coronary angioplasty (PTCA). Fifty-three patients (43 male and 10 female) ages 38-71 years (mean 55.3) were analysed. Exercise Tl-201 scintigraphy was performed before PTCA, and 6-10 days and then 3-6 months after the procedure. In all patients repeated coronary angiography was done 3-6 months after PTCA. Before PTCA myocardial perfusion defects were observed in all patients. Immediately after PTCA, an improvement in myocardial perfusion was noted in 36 patients (61%). Total normalisation of the scintigraphic picture was observed in only 12 patients. Coronary angiography after 3-6 months showed patency of dilated vessels in 11 out of those 12 patients (91.3%). In scintigraphy, performed 3-6 months after PTCA, a normal scan was present in 20 patients and recurrence of stenosis was found in only 2 of those 20. Stenosis was found in 22 (60%) of 33 patients with perfusion defects. For the purpose of describing the character of the myocardial perfusion changes, statistical analysis of a number of segments was performed. The predictive value of Tl-201 scintigraphy for detection of restenosis was established. The positive value for the procedure performed 6-10 days after PTCA was 56%, and the negative value of prediction of restenosis was 91%. Three to 6 months after PTCA, a high negative value of scintigraphy was observed (-90%) and a low positive predictive value was still present (63%).
8793586
Multiplane transoesophageal echocardiography is the only definitive ultrasound approach in adult supravalvular aortic stenosis.
This report describes a rare case of isolated supravalvular aortic stenosis (SVAS) in a 28 year-old female patient. A congenital heart defect, diagnosed at birth, was until 1994 suspected to be a valvular aortic stenosis (VAS). Cardiac catheterization led to the diagnosis of supravalvular aortic stenosis, which could easily be confirmed by multiplane but not by monoplane transoesophageal echocardiography (TEE). Precordial examinations had not revealed the vitium, probably because the SVAS is a rare malformation of the ascending aorta, but with multiplane TEE the aortic narrowing could be imaged clearly and pressure parable to those found with invasive measurements were established. The advantage of this non-invasive method for diagnosis and preoperative preparation are discussed in detail.
8793587
Torsades de pointes induced by transesophageal atrial stimulation after administration of almokalant.
This case-report describes a patient who developed a torsades de pointes tachycardia after infusion of almokalant, a selective class III antiarrhythmic agent. The patient was studied with transesophageal atrial stimulation because of Wolff-Parkinson-White syndrome. After a base-line procedure during which an orthodromic tachycardia was induced and pace-terminated, almokalant was given intravenously. The corrected QT interval was markedly prolonged despite similar plasma pared to the rest of the studied patients. During the continued pacing protocol several episodes of non-sustained ventricular tachycardia was observed after pacing induced pauses. A sustained orthodromic tachycardia with left bundle branch morphology was induced, and another almokalant infusion was given. At a plasma concentration of approximately 252 nmol/l the corrected QT interval was further prolonged to 680 ms and the patient developed a torsades de pointes tachycardia after a pacing induced pause. The tachycardia degenerated into ventricular fibrillation that required immediate defibrillation. One week later the patient underwent ablation of the accessory pathway. The QT interval was in the absence of preexcitation normal, and programmed electrical stimulation did not reveal any ventricular arrhythmias. Further studies will have to be performed to clarify whether an early and marked QT interval prolongation, such as observed in this patient, will be useful in identifying patients prone for proarrhythmias in relation to therapy with selective class III drugs.
8793588
Lp(a) levels in Greek patients with heterozygous familial hypercholesterolemia.
We undertook the present study to evaluate the lipid profile in 82 (51 male, 31 female) Greek individuals with heterozygous familial hypercholesterolemia (FH), aged 13-61 years from 22 families. FH heterozygotes had significantly elevated serum Lp(a) levels parison with 82 normal controls. Serum Lp(a) levels were also increased in FH pared to their controls. Additionally, serum Lp(a) concentration was elevated in the FH pared to their unaffected first degree relatives.
8793590
The role of cytokines in cardiac surgery.
Cytokines are a large and rapidly expanding group of polypeptides produced by many different cell types. Increasing interest has been focused on the role of cytokines as mediators of metabolic, immunological and endocrine responses to surgery. The cytokine response in patients undergoing cardiac surgery during cardiopulmonary bypass (CPB) is fairly well-defined and dominated by the proinflammatory cytokines IL-6, TNF alpha and IL-8 and the antiinflammatory cytokine IL-10. Little is known about the cytokine response in patients who develop plications but CPB with mechanical trauma and blood contact to artificial membranes is definitely an unphysiological state and may contribute to an uncontrollable response similar to that of patients with multiorgan failure and septic shock.
8793589
An unusual case of cardiac tamponade following electrical cardioversion.
The clinical presentation of cardiac tamponade may uncover underlying pericardial disease. We describe a patient who was being treated for lone atrial fibrillation. In this case, direct current cardioversion for recurrence of atrial fibrillation plicated by a life-threatening hemopericardium. A history of asbestos exposure was subsequently related to the subclinical pericarditis.
8793591
Preventing the inflammatory response to open-heart surgery: the role of aprotinin and other protease inhibitors.
This review discusses the role of protease inhibition in reducing or preventing certain of the deleterious effects of major surgery. The ability of agents such as aprotinin to inhibit bleeding and reduce the need for donor blood transfusions is now well established. What is less well recognized is that aprotinin is not simply an antifibrinolytic but is a polyvalent enzyme inhibitor of many of the enzymes which are involved in inflammatory and hemostatic processes. Inappropriate activation of these pathways is considered to be important in the genesis of the inflammatory response to open-heart surgery. The first part of the article reviews aspects of the inflammatory and hemostatic systems which have mon basis and which utilize proteolytic actions for their control. In the later part of the review, the effect of a period of cardiopulmonary bypass on organ and tissues is discussed together with the effects of protease inhibition to prevent any abnormal or inappropriate response to the stimulus. Consideration of these aspects will hopefully allow a more rational and scientific approach to the uses, possible benefits and perceived or real safety issues following administration of these agents.
8793592
Evidence for morphine downregulating immunocytes during cardiopulmonary bypass in a porcine model.
Cardiopulmonary bypass is associated with both cellular immunosuppression and an inflammatory response. Previous studies have demonstrated that morphine, a naturally occurring substance, can downregulate granulocyte, monocyte and endothelial activity. It can even prevent the activation caused by exposing these cells to plasma obtained from patients undergoing cardiopulmonary bypass. The present study demonstrates that preadministering a high dose of morphine (3.3 mg/kg) to pigs prior to cardiopulmonary bypass also diminishes the activation levels of these cells. In animals not given morphine, monocyte activation levels were pared to 14% exposed to the opiate. Granulocytes also exhibited the same statistically significant (P < 0.05) drop in cellular activation. Activation is determined puter-assisted microscopic image analysis whereby cellular shape is indicative of the cells activity. Additionally, in animals pretreated with morphine, a twofold increase in the number of cells was obtained, indicating that the endothelium also was downregulated.
8793593
Hyperstimulation of leukocytes by plasma from cardiopulmonary bypass patients is diminished by alpha-MSH pretreatment.
Cardiopulmonary bypass (CPB) results in a diffuse inflammatory response characterized in part by hyperstimulation of leukocytes. We have previously shown that this hyperstimulation appears to be due, in part, to an increase in the release of biological response modifiers (BRMs) such as cytokines. In the present study, we evaluated the ability of a naturally occurring immunocyte inhibitory substance, alpha-melanocyte-stimulating hormone (alpha-MSH), to prevent the hyperstimulation caused by CPB. Monocytes and granulocytes were pretreated with alpha-MSH (10(-6) M) before exposing the cells to plasma obtained from patients who had undergone CPB, as CPB plasma would stimulate native monocytes and granulocytes in a manner similar to that observed in CPB patients. Pretreatment of these cells with alpha-MSH significantly diminished the hyperstimulation induced by CPB plasma in a concentration-dependent manner. In contrast, when the cells were first or simultaneously exposed to CPB plasma and then to alpha-MSH, alpha-MSH had no effect. Furthermore, use of the specific neutral endopeptidase inhibitor, phosphoramidon, significantly increased the efficacy of alpha-MSH in inhibiting CPB-induced immunocyte activation. The data demonstrate that pretreatment of monocyte/macrophages and granulocytes with alpha-MSH effectively inhibits the immune hyperstimulation induced by CPB-plasma exposure. In addition, the data strongly suggest that preexposure to other naturally occurring immune inhibitory substances may diminish the hyperstimulation associated with CPB. The study also further confirms that this hyperstimulation may, in part, be due to BRMs released from immunocytes.
8793594
Aprotinin diminishes inflammatory processes.
Many of the recent reports concerning cytokine levels in cardiopulmonary bypass have documented changes in the levels of these trauma indicators. In the present report, we also document their levels but in the presence of Aprotinin. Aprotinin is a protease inhibitor used not only to diminish bleeding, but also to diminish elements of the diffuse inflammatory response associated with this type of surgery. We report in plasma obtained from 20 patients that initially interleukin-8 (IL-8) levels (53.4 +/- 7 pg/ml) plasma to 185.5 +/- 30 pg/ml) increased 20 min from the start of surgery. This is followed by IL-6 (5.3 +/- 1.1 to 200 +/- 50 pg/ml) peaking 15 h post surgery. These levels return to normal by day 3 postop. IL-1 beta and tumour necrosis factor (TNF) levels remained at baseline for the observation period. Associated with these changes in cytokine levels is the activity state of immunocytes (granulocytes and monocytes) noted by conformational changes obtained puter-assisted microscopy. The cells exhibited an ameboid conformation and became mobile (67%), peaking at 120 min after surgery began and returned to a more rounded conformation with only 6% exhibiting the ameboid conformation by day three. In in-vitro experiments, where immunocytes not exposed to cardiopulmonary bypass were exposed to plasma obtained from patients having undergone this surgery, their activity level rose to 65%. In the same experiment, when Aprotinin was added to the cell-plasma mixture, the level of activation dramatically dropped to 25%. Thus, aprotinin was found at high doses to lower cytokine and cellular activation associated with the acute inflammatory responses of cardiopulmonary bypass, suggesting that this may be initiated by hyperstimulated immunocytes.
8793595
Surgical anticipatory stress manifests itself in immunocyte desensitization: evidence for autoimmunoregulatory involvement.
The immunocyte behavior (conformational changes and otion in response to signal molecule challenge) in patients about to undergo elective cardiac surgery was studied to elucidate the effect of psychological anticipatory stress on the immune system. Granulocytes and monocytes from 10 patients and 35 non-surgical controls were examined. Computer-assisted microscopic image analysis, capable of measuring cellular conformational and velocity changes, was used to measure the responsiveness of these immunocytes to peptidergic and cytokine stimulation. Immunocyte desensitization would appear to account for the reduction in their abilities to respond to chemotaxic challenge associated with the pre-cardiac surgery state. Their abilities to respond to D-Ala2-Met-enkephalinamide (DAMA) were observed only at much higher concentrations than previously reported (10-11 M vs. 10-9 M prior to surgery). This finding, together with the observed decrease in adrenocorticotropin pared to non-surgical controls, suggests that neutral endopeptidase activity was elevated just prior to surgery. Indeed, neutral endopeptidase activity is statistically elevated in the pre-cardiac surgery state. Furthermore, glucocorticoid levels remained constant, within normal resting limits, in both groups. Thus, surgical anticipatory stress may manifest itself, in part, as a desensitization of various immunocytes. Thus, a psychological anticipatory stress response may be a precipitant of the desensitization. Although this desensitization seemed not to involve the entire hypothalamic-pituitary-adrenal axis, the data suggest that psychological anticipatory stress may initially involve and influence autoimmunoregulation.
8793596
Protease activated receptors modulate aortic vascular tone.
The effect of agonists of the known protease activated receptors (PAR), the thrombin and the PAR-2 receptors, on vasoactive mediator release and vascular tone were studied using rings of rat aorta. Stimulation of aortic rings with the thrombin receptor agonist, Trap-14, or the PAR-2 agonist, SLIGRL, resulted in a rapid release of nitric oxide. Trap-14 and SLIGRL-induced nitric oxide release was reduced by pre-treatment with BQ-788, an ETB endothelin receptor-specific antagonist. Consistent with a role for endothelin-1 receptor activation in Trap-14 and SLIGRL-induced nitric oxide release, endothelin-1 levels were increased significantly following 5 min treatment of aortic rings with Trap-14 or SLIGRL. Cumulative addition of Trap-14 to aortic rings denuded of endothelium resulted in dose-dependent contraction with an EC50 value of 23 +/- 5 microM, whereas SLIGRL addition failed to induce aortic contraction. These data suggest that the known protease activated receptors are functionally coupled to nitric oxide release. In addition, the thrombin receptor appears to modulate both vasodilator and contractile responses, whereas the PAR-2 receptor is linked only to vasodilation.
8793597
Heparin-coated bypass circuits in cardiopulmonary bypass: improved biocompatibility or not.
Heparin bonding to bypass circuits has been found to reduce plications. Here, this process is reviewed with special attention to markers of inflammation and clinical e. Indicators of inflammation (i.e. cytokine levels, elastase ponents) are decreased when using heparin bonded pared to conventional bypass circuits. The decrease in the levels of these response modifiers appears minimal. Clinical es, other than plications, have not been studied to any great extent with this technology. These lower levels of the various biological response modifiers are not correlated with lower levels plications or shorter hospital stays. We conclude based on this data that it is not clear if this decrease translates into a clinical benefit in routine operative cases that require cardiopulmonary bypass.
8793598
Pharmacokinetics and drug interactions--relevant factors for the choice of a drug.
Pharmacokinetics serve as a useful tool in drug development by identifying the drug's disposition and elimination characteristics, the absorption characteristics of the biopharmaceutical formulation, and the therapeutic dose regimen in various patient populations. Where two or more drugs of a class have a similar efficacy, the choice of the drug may depend upon the reproducibility of the pharmacokinetics and the minimal risk of drug interaction. Pantoprazole, a selective proton pump inhibitor, appears to meet the above criteria. As opposed to other members of the class, pantoprazole exhibits linear, predictable pharmacokinetics and lack of drug interactions.
8793601
Lack of pharmacokinetic interaction as an equivalence problem.
The demonstration that itant administration of drug B does not affect the pharmacokinetics of drug A can be adequately handled as an equivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range. This will usually correspond to the bioequivalence range accepted for parison of different formulations of drug A. Equivalence, i.e. lack of pharmacokinetic interaction, is concluded if the 90%-confidence interval for the ratio (difference) of the expected medians for test and reference is entirely within the equivalence range. This decision procedure ensures that the consumer risk of incorrectly concluding "lack of interaction" is limited to 5%. Moreover, the producer risk of incorrectly concluding "interaction" can be controlled by appropriate sample sizes.
8793599
Pharmacokinetics of pantoprazole in man.
The proton pump inhibitor pantoprazole is a substituted benzimidazole sulphoxide for the treatment of acid-related gastrointestinal diseases such as reflux esophagitis, duodenal and gastric ulcers. Pantoprazole, administered as a 40 mg enteric coated tablet, is quantitatively absorbed. Its absolute bioavailability is 77% and does not change upon multiple dosing. Following a single oral dose of 40 mg, Cmax is approximately 2.5 mg/l, with a tmax of 2-3 h. The AUC(0,inf.) is approximately 5 mgxh/l. Pantoprazole shows linear pharmacokinetics after both i.v. and oral administration. Pantoprazole is extensively metabolized in the liver, has a total serum clearance of 0.1 l/h/kg, a serum elimination half-life of about 1.1 h, and an apparent volume of distribution of 0.15 l/kg. 98% of pantoprazole is bound to serum proteins. Elimination half-life, clearance and volume of distribution are independent of the dose. The main serum metabolite is formed by demethylation at the 4-position of the pyridine ring, followed by conjugation with sulphate. Almost 80% of an oral or intravenous dose is excreted as metabolites in urine; the remainder is found in feces and originates from biliary secretion. The pharmacokinetics of pantoprazole are unaltered in patients with renal failure. In patients with severe liver cirrhosis, the decreased rate of metabolism results in a half-life of 7-9 h. The clearance of pantoprazole is only slightly affected by age, its half-life being approximately 1.25 h in the elderly. itant intake of food had no influence on the bioavailability of pantoprazole. Pantoprazole showed lack of cytochrome P450 interaction with itantly administered drugs in any of the studies conducted to date. Lack of interaction was also demonstrated with a coadministered antacid. The absence of inductive effects on metabolism after chronic administration was first shown by using antipyrine as a probe for mixed functional oxidative cytochrome P450 enzymes. Absence of CYP1A2 induction was confirmed using the specific probe caffeine. As sensitive probes for CYP3A enzyme induction, urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol were also unchanged.
8793600
Dose linearity of the pharmacokinetics of the new H+/K(+)-ATPase inhibitor pantoprazole after single intravenous administration.
Pantoprazole is a specific inhibitor of the H+/K(+)-ATPase of the gastric parietal cell. The dose-dependency of a range of pantoprazole pharmacokinetic characteristics was studied. Twelve healthy male subjects were given 10, 20, 40 and 80 mg pantoprazole intravenously according to a randomized, single blind, 4-period change-over scheme. The area under the concentration vs time curve (AUC) and the maximum serum concentration (Cmax) showed a linear increase in line with the dose. Apparent volume of distribution (Vd area), clearance (Cl) and terminal half-life (t1/2) were independent of the dose. The dose-independent elimination of pantoprazole was attributed to the lack of interaction of the drug with cytochrome P450. In clinical practice, a good predictable response, as well as a low potential for interaction with other drugs might be expected.
8793602
Lack of pantoprazole drug interactions in man: an updated review.
This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Various mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In contrast to omeprazole, pantoprazole has a low potential to interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, substrates for all relevant cytochrome P450 families involved in the metabolism of drugs in man were investigated. Pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, caffeine, carbamazepine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, a hormonal contraceptive (combination of levonorgestrel and ethinylestradiol), metoprolol, nifedipine, phenprocoumon, phenytoin, theophylline and warfarin in man. Pantoprazole also neither induced the metabolism of antipyrine or caffeine, nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole.
8793603
Lack of influence of pantoprazole on the disposition kinetics of theophylline in man.
The potential influence of pantoprazole (BY1023/SK&F96022), a newly developed selective inhibitor of the gastric H+,K(+)-ATPase, on therapeutic serum theophylline concentrations was investigated in a crossover study in 8 healthy male volunteers (age 25-30 [median 27] years, body weight 63-80 [median 68] kg). Steady-state serum theophylline concentrations were obtained by a two-step intravenous infusion scheme of approximately 350 mg theophylline each over 0.5 h and subsequently over approximately 10 h, respectively. In the test period, 30 mg pantoprazole were injected over 2 min on 5 consecutive days and theophylline was infused on day 4. In the reference period, placebo was administered i.v. on 2 consecutive days and theophylline on day 1. Serum pantoprazole concentrations were measured up to 12 h, serum theophylline concentrations up to 36 h. Pantoprazole was well tolerated with and without theophylline. There were no clinically relevant changes in blood pressure, heart rate, ECG and routine clinical laboratory parameters. Primary characteristic for confirmative assessment of no interaction was the area under the concentration/time curve (AUC). Lack of interaction in the sense of equivalence was concluded both for theophylline (with and without pantoprazole) and pantoprazole (with and without theophylline), as the 90%-confidence intervals of the AUC-ratio test/reference were within the equivalence range of 0.8 to 1.25. Further explorative analysis of theophylline disposition kinetics revealed this inclusion also for clearance and volume of distribution, but not for the half-life. In the case of pantoprazole, the corresponding 90%-confidence intervals for any of the secondary characteristics clearance, volume of distribution and half-life were within the above mentioned range. In conclusion, repeated once-daily i.v. injections of 30 mg pantoprazole have no clinically relevant influence on steady-state theophylline serum concentrations, nor does theophylline at therapeutic serum concentrations influence the pantoprazole disposition kinetics. Hence, in clinical practice theophylline and pantoprazole can be administered itantly without dose adjustment.
8793604
Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction.
Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, monly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers were given a) a single 30 mg i.v. doses of pantoprazole, b) a single 5 mg/kg oral dose of antipyrine, or c) coadministered pantoprazole and antipyrine according to a randomized three-period change-over design. In the chronic study, another 12 volunteers received 40 mg once-daily oral doses of pantoprazole on day 3 and on days 5-12, and a single oral 5 mg/kg dose of antipyrine on days 1, 12 and 14. Antipyrine plasma concentrations were measured without pantoprazole (day 1), on the last day of chronic dosing with pantoprazole (day 12) and 48 hours after the last dose of pantoprazole (day 14) to differentiate between inhibition and induction, respectively. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or laboratory parameters were observed during treatment. The point estimates of the respective AUC-and Cmax-ratios for antipyrine with and without pantoprazole were 0.99 and 0.98 in the acute study, and 1.01 and 0.93 on day 12, and 1.04 and 0.99 on day 14 of the chronic study. The corresponding 90%-confidence intervals were all within the equivalence range of 0.8-1.25 so that lack of interaction either by inhibition or induction can be concluded.
8793605
Lack of interaction between pantoprazole and digoxin at therapeutic doses in man.
Substituted benzimidazole inhibitors of the gastric H+/K+ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs. On the other hand, changes in intragastric pH might alter the absorption of other drugs. The primary aim of the present study was to determine whether pantoprazole modifies the steady-state serum concentrations of orally administered digoxin. Secondary aims were the influence of digoxin on the pharmacokinetics of pantoprazole as well as safety and tolerability. Eighteen healthy volunteers received a single oral dose of pantoprazole (40 mg) and serum concentrations were determined. Three to 10 days later, subjects received in a single-blind, randomized, crossover fashion oral beta-acetyldigoxin (0.2 mg) twice daily and itant oral pantoprazole (40 mg) or placebo once daily for 5 days. Serum concentrations of pantoprazole and digoxin were determined on day 5. Primary characteristics for confirmative assessment of no interaction were AUC and Cmax of digoxin. Lack of interaction in the sense of equivalence was concluded for both digoxin (with and without pantoprazole) and pantoprazole (with and without digoxin) as the 90%-confidence intervals of the respective AUC- and Cmax-ratios were within the equivalence range of 0.8-1.25. Pantoprazole did not influence the characteristic ECG modifications (T-wave) caused by digoxin. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or clinical laboratory parameters were observed during treatment. In conclusion, pantoprazole and digoxin may be administered itantly without the need for dose adjustment.
8793606
No influence of pantoprazole on the pharmacokinetics of phenytoin.
Twenty-three healthy, male pleted this doubleblind, randomized, placebo controlled, 2-period crossover study to assess the influence of multiple doses of pantoprazole on single-dose phenytoin pharmacokinetics. During each treatment period, the volunteers received either one 40 mg pantoprazole tablet or placebo for 7 days. In addition, a single-dose of 300 mg (3 x 100 mg capsules) phenytoin sodium was administered on day 4 of each treatment period. A 14-day wash-out period was allowed between phenytoin administrations. The results indicate that pantoprazole neither affects the rate nor the extent of absorption, nor the elimination of phenytoin.
8793607
Lack of pharmacokinetic interaction between pantoprazole and diclofenac.
The new H+/K+ ATPase inhibitor pantoprazole is extensively metabolized by the liver. As substituted benzimidazoles may potentially interact with the cytochrome P450 system, the influence of pantoprazole on the pharmacokinetics of the NSAID diclofenac was investigated. Diclofenac is widely used in the treatment of rheumatic diseases and is mainly metabolized in the liver by CYP2C9. Twenty-four healthy volunteers (13 male/11 pleted a randomized crossover study. As test they received orally 40 mg pantoprazole and itantly 100 mg diclofenac. As respective references 100 mg diclofenac or 40 mg pantoprazole were given alone. Diclofenac and pantoprazole serum concentrations were measured. Lack of pharmacokinetic interaction was handled as an equivalence problem. The 90% confidence intervals (CI) of the ratios of the primary characteristic AUC and the secondary characteristic Cmax of diclofenac were entirely within the equivalence range of 0.8-1.25. Hence, no influence of pantoprazole on the pharmacokinetics of diclofenac was concluded, either petition with the CYP2C9 or by the reduction of gastric acid secretion. Vice versa, diclofenac did not affect the pharmacokinetics of pantoprazole. All treatments were safe and well tolerated. No dose adjustment is required during itant treatment with diclofenac and pantoprazole.
8793608
Pantoprazole does not interact with nifedipine in man under steady-state conditions.
The new H+/K(+)-ATPase inhibitor pantoprazole is extensively metabolized by the liver. As substituted benzimidazoles can interact with the cytochrome P450 system, the influence of pantoprazole on the steady-state pharmacokinetics of the calcium antagonist nifedipine was investigated. Nifedipine is widely used in the treatment of cardiovascular diseases and is mainly metabolized in the liver by CYP3A4. Additionally possible influence of gastric pH on the absorption of nifedipine is discussed. Twenty-four healthy volunteers (13 m/11 pleted a randomized crossover study. As test they received orally 40 mg pantoprazole s.i.d. for 10 days and itantly 20 mg nifedipine sustained release (SR) b.i.d. from day 6 to 10. During the reference period 20 mg nifedipine SR were dosed b.i.d. for 5 days. Nifedipine and pantoprazole serum concentrations were measured over one dosing interval on the last day of each period. Lack of pharmacokinetic interaction was handled as an equivalence problem. The 90%-confidence intervals (CI) of the ratios of the primary characteristics AUC and Cmax of nifedipine were entirely within the equivalence range of 0.8-1.25. Hence no influence of pantoprazole on the pharmacokinetics of nifedipine was concluded, either petition with the CYP3A4 or by the reduction of gastric acid secretion. As secondary criterion nifedipine had no relevant influence on the pantoprazole pharmacokinetic characteristics. All treatments were safe and well tolerated. No dose adjustment is required during itant treatment with nifedipine and pantoprazole.
8793609
Beta-adrenoceptor blocking agents for the treatment of heart failure.
Congestive heart failure is associated with high morbidity and mortality. Modification of neurohormonal activation by use of angiotensin converting enzyme inhibitors has been shown to decrease symptoms and prolong survival. More recent evidence has suggested that beta-adrenoceptor blocking agent therapy may be also beneficial in patients with congestive heart failure, possibly by down-regulating the activation of the adrenergic system. A large number of randomized trials of beta-adrenoceptor blocking agents in heart failure have been performed. These studies demonstrated improvement in symptoms of congestive heart failure, functional classification, and reduction in the number of patients requiring cardiac transplantation. beta-adrenoceptor blocking agents have not been shown to decrease mortality, however, the current trials have been too small to be conclusive in this regard.
8793610
Correlations between subjective compliance, objective compliance, and factors determining compliance in geriatric hypertensive patients treated with triamterene and hydrochlorothiazide.
There are correlations between objective and pliances on the one hand and factors pliance (3 times drug intake per day, no support by the family to get over the disease and no nicotine abuse). In agreement with the literature, mainly subjective criteria (due to disease, therapy, doctor, and environment) pliance strongly. To realize their personal psychological task to help the patients even better it is of importance for the doctors to analyze the variability of these parameters. Measures to pliance, such as better psychological guidance for the patient taking these factors and the patient's personality into consideration, can be helpful to improve the relatively pliance reported in the literature to be as little as 20-50%.
8793611
Lack of pantoprazole drug interactions in man: an updated review.
This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Various mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In contrast to omeprazole, pantoprazole has a low potential to interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, substrates for all relevant cytochrome P450 families involved in the metabolism of drugs in man were investigated. Pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, caffeine, carbamazepine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, a hormonal contraceptive (combination of levonorgestrel and ethinylestradiol), metoprolol, nifedipine, phenprocoumon, phenytoin, theophylline and warfarin in man. Pantoprazole also neither induced the metabolism of antipyrine or caffeine, nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole.
8793612
Comparison of captopril-thiazide and enalapril-thiazide combinations in the management of mild to moderate black hypertensive patients: how important is diuretic dose and duration of action of the ACE-inhibitor?
A double-blind, randomized, parallel-group study was performed pare the efficacy and tolerability of captopril-thiazide and binations. After a 3-week placebo run-in period, 47 Black patients with mild to moderate essential hypertension (mean 24-hour diastolic blood pressure (BP) > 90 mmHg and < 115 mmHg) were randomized to receive 1 of bination tablets: captopril 50 mg plus hydrochlorothiazide 25 mg (CAP, n = 24) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (COR, n = 23) once daily. After 12 weeks of active treatment the mean 24-hour ambulatory BP was reduced from 152 +/- 11/99 +/- 6 to 133 +/- 13/86 +/- 7 mmHg (p < 0.005) in the CAP group and 157 +/- 15/100 +/- 6 to 141 +/- 18/90 +/- 12 in the COR group (p < 0.005). Target BP (24-hour diastolic BP < 90 mmHg) was achieved in 75% (18/24) of patients on CAP and 48% (11/23) on COR (p = n.s.). 24-hour BP load fell significantly with both CAP (from 69% to 34%, p < 0.001) and COR (from 67% to 37%, p < 0.001). Left ventricular mass index decreased by 7% with CAP and 11% with COR. Cardiac index and fractional shortening remained essentially unchanged in both groups. Both treatments were well tolerated and overall incidence of side effects was very low. It is concluded that both CAP and COR are effective, safe first-line antihypertensive choices in Black patients with mild to moderate hypertension with the former showing a trend towards greater efficacy than the latter.
8793613
Biochemical and clinical assessment of histamine blockade.
The effects of antihistamines on biochemical stress indicators and on psychomotor and physiological functions were studied in 60 healthy patients receiving in a randomized, double-blind study either 25 mg promethazine, 150 mg ranitidine, both drugs or placebo (n = 15 in each group). Different aspects of the premedications were evaluated by determining various hormone, neurotransmitter and neurotransmitter metabolite levels in blood and cerebrospinal fluid, and subjectively using questionnaires concerning the quality of the preoperative night's sleep and visual analogue scales, and objectively by measuring changes in blood pressure and heart rate, impairment of vigilance with the Maddox wing apparatus and the critical flicker fusion threshold test. The relationships between the subjective assessments and the biochemical stress indicators were also investigated. There were no differences between the study groups in the quality of the preoperative night's sleep, estimated fear, apprehension or dizziness, or in the various physiological stress indicators. Only few statistically significant correlations were found between the subjective and biochemical assessments. It is concluded that histamine receptor antagonists used in clinical doses do not interfere with the biochemical, clinical preoperative, and physiological responses.
8793614
Nuclear transplantation from stably transfected cultured cells of Xenopus.
By nuclear transplantation we have generated embryos from enucleated Xenopus eggs and nuclei of stably transfected Xenopus cell lines. We have devised a novel method of transplantation in which cell permeabilization is controlled by a temperature effect on streptolysin O-treated cells. This method is easier and quicker to operate than the conventional cell rupture technique. Single nuclei from cell lines transfected with the lacZ reporter gene were transplanted to Xenopus eggs in which the egg nuclei were destroyed by UV irradiation. We show that the lacZ transgene is transmitted from donor cells to nuclear transplant embryos. Expression of the lacZ transgene has been controlled by the elongation factor 1-alpha promoter (Krieg et al., Dev. Biol. 133: 93-100, 1989). In the nuclear transplant embryos, beta-galactosidase transcripts are expressed at the expected time of development, that is after the mid-blastula transition. In addition, we show that early embryo-specific genes, not expressed in cultured cells, are normally activated in nuclear transplant embryos. Therefore, expression of these genes can be used to monitor the effects of transfected test genes. Although most of the nuclear transplant embryos do not develop beyond the gastrula stage, explants of equatorial tissue from these embryos can undergo differentiation characterized by the expression of muscle and notochord markers. The use of nuclear transplantation, as described here, provides a means of avoiding the mosaic expression of DNA or mRNA injected into Xenopus eggs.
8793615
The LIM homeodomain protein Lim-1 is widely expressed in neural, neural crest and mesoderm derivatives in vertebrate development.
Polyclonal antibodies to Xlim-1 homeodomain protein of Xenopus laevis were used to study the developmental expression pattern of this protein in Xenopus, rat and mouse. Western blotting of embryo extracts injected with different Xlim-1 constructs confirmed the specificity of the antibody. Beginning at the gastrula stage, Xlim-1 protein was detected in three cell lineages: (i) notochord, (ii) pronephros and (iii) certain regions of the central nervous system, in agreement with earlier studies of the expression of Xlim-1 RNA (Taira et al., Development 120: 1525-1536, 1994a). In addition, several new locations of Xlim-1 expression were found, including the olfactory organ, retina, otic vesicle, dorsal root ganglia and adrenal gland. Similar expression patterns were seen for the Lim-1 protein in frog and rodent tissues. These observations implicate the Xlim-1 gene in the specification of multiple cell lineages, particularly within the nervous system, and emphasize the conserved nature of the role of this gene in different vertebrate animals.
8793616
Expression of Hoxb-1 during gastrulation and segmentation stages of carp (Cyprinus carpio).
This report describes the cDNA sequence and embryonic RNA expression pattern of carp Hoxb-1. Carp Hoxb-1 is a labial-like, homeobox-containing gene of the 3' end of the Hox gene cluster. The expression pattern in carp pared to that of homologs in other vertebrates. As holds for other Hox genes, carp Hoxb-1 is expressed with highest intensity at a sharp anterior boundary, and expression fades out towards posterior. At later stages, gaps were found in the domain. The gene is expressed from late gastrulation onwards, first mainly in the hypoblast but later in all germ layers. Its most prominent expression area is rhombomere 4 (r4) of the hindbrain. Transcripts were also found in the neural tube, mesoderm (lateral, head and presomite), epidermis and neural crest. At 30 hours post fertilization, Hoxb-1 was still expressed in r4, in the anterior trunk neural tube and in the branchial arches posterior to r4. Hox genes are thought to be involved in the specification of positional values along the embryonic anterior-posterior axis, and Hoxb-1 expression in r4 is supposed to be important for specifying the unique identity of this hindbrain segment. The conserved expression in r4 suggests that this is also true for carp Hoxb-1.
8793617
Xenopus oocyte maturation: cytoplasm alkalization is involved in germinal vesicle migration.
In Xenopus laevis oocytes a transient increase in intracellular pH has been reported to occur during progesterone-induced maturation. Using a cytological approach, we have systematically analyzed germinal vesicle breakdown and meiotic spindle formation in various experimental conditions either preventing or promoting pHi changes. Injection of a neutral buffer (MOPS pH 6.9) induced a cytosolic acidification of 0.3 pH unit and inhibited by 30% the formation of the maturation white spot after progesterone exposure; in oocytes displaying a white spot, only half showed a spindle, often located far from the plasma membrane. Similar results were observed with a Na-free medium which prevents oocyte alkalization. Injection of an alkaline buffer (Tris pH 9) was able to induce migration of the germinal vesicle in 25% of the oocytes in the absence of progesterone, but failed to induce GVBD. Taken together, these results suggest that the increase in pHi observed during maturation may be involved in the migration of the germinal vesicle towards the plasma membrane. We also incubated oocytes in the presence of procaine, a weak base often used to artificially alkalize the oocyte cytoplasm. The changes induced by exposure to procaine were different from those resulting from alkaline buffer injection. Indeed procaine promoted GVBD, as well as spindle formation and chromosome condensation. However these events appeared without migration of the germinal vesicle, suggesting that the expected alkalization did not occur.
8793619
Apoptosis is involved in the disappearance of the diastemal dental primordia in mouse embryo.
Three transient dental primordia (D1, D2 and D3) exist in the upper diastema in mouse embryos and their regression is associated with the presence of cell death. In order to specify the type of cell death and its temporo-spatial distribution, staining with hematoxylin, supravital staining with Nile Blue, TUNEL method, electron microscopic analysis puter assisted 3-D reconstructions were performed. These data demonstrated that apoptosis is involved in the disappearance of the diastemal dental rudiments. Apoptosis occurred first with prevalence in the buccal part of the epithelium of the diastemal dental primordia and extended later to the whole epithelium of the dental rudiments and the dental lamina interconnecting them with the incisor and molar epithelia. Cell death occurred only sporadically in the adjacent mesenchyme. The prospective upper diastema in mouse embryos may provide a model for studies of developmental determination of toothless areas in the jaw as well as a tool for analyses of regulatory mechanisms of programmed cell death in morphogenesis.
8793618
Delayed expression of the insulin-like growth factor I (IGF-I) gene in the XY sex-reversed female mouse ovary.
When the Y chromosome of Mus musculus domesticus (YDOM) mouse strain from Tirano (Italy) or Mus musculus poschiavinus (YPOS) from Poschiavo (Switzerland), is placed onto the C57BL/6J (B6) inbred background, the YDOM chromosome fails to induce normal testicular differentiation and instead allows development of ovaries and ovotestes in embryonic life. During postnatal development some hermaphroditic males e fertile whereas the XY females lack normal estrus cyclicity, produce low levels of gonadal steroids and cannot carry pregnancy to term. Here we studied the transcription of the IGF-I gene known to be involved in steroidogenesis. RNA was isolated from the XX and the XY ovaries at 1 to 40 d.p.p. and subjected to RT-PCR analysis. Immunocytochemical staining for IGF-I was performed to identify the cell type of IGF-I peptide localization, and protein expression was examined by Western blot analysis. The present results indicate that the IGF-I transcript was expressed at 1 d.p.p. in the XX ovary throughout the studied stages whereas in the XY ovary mRNA IGF-I was not detected until 15 d.p.p. IGF-I protein was identified in theca cells in the whole XX control ovary, while in the XY ovary, strong staining for IGF-I was found in the theca cells of the cortex. Faint staining was also seen around the medullary sterile cords. Western blot analysis showed normal onset in the XX and the XY ovary, but a different staining pattern for IGF-I in the XY ovary at 11 and 26 pared to the XX control ovary. We propose that delayed expression of IGF-I in the XY mouse ovary may be responsible for low steroid production and fertility problems in the XY sex-reversed adult female mouse.
8793620
An identical effect mediated by thyroid deficiency or oncogene v-erbA in the chick embryo.
We have shown earlier that the association of v-myc and v-erbA (MAHEVA construct) is responsible for the appearance of a specific phenotype in chick embryos inoculated at E3. This prises rapidly growing heart rhabdomyomas (induced by v-myc alone) and within these tumors secondarily appearing cartilage nodules (Bachnou et al., Oncogene 6: 1041-1047, 1991). Here we report that v-erbA can be replaced by thyroid deficiency. When decapitated embryos were inoculated with virus MC29 (v-myc alone) or when v-myc inoculated embryos were treated with thiourea, 100% of the embryos reaching E17 to E19 displayed tumoral hearts bearing cartilage nodules. We thus report in vivo evidence that v-erbA acts by antagonizing the effects of thyroid hormones. Remarkably, thyroid deficiency rendered embryos more sensitive to the effect of v-myc, since 100% developed heart rhabdomyomas and cartilage nodules, versus about 70% affected when either v-myc or MAHEVA were inoculated. Thyroid deficiency did not alter the species-specific character of transdifferentiation, since only chick but not quail embryos developed cartilage nodules after thyroidectomy or MAHEVA infection.
8793621
Analysis of parent-specific gene expression in early mouse embryos and embryonic stem cells using high-resolution two-dimensional electrophoresis of proteins.
Genomic imprinting is an important genetic mechanism in mammals whereby certain genes are epigenetically modified and their expression altered according to their parental origin. The most important consequence of this is the requirement for both a maternal and a paternal genome for normal development to proceed to term. Although there are many instances of specific phenotypes (in the mouse) and diseases (in humans) resulting from imbalances in the parental chromosomes, it is only in the past few years that some of the imprinted genes responsible have been identified. It is however unclear what proportion of the genome is imprinted, particularly in the early embryo. To address the question to what extent parent-specific gene expression occurs in the early embryo and with a possible view to identifying new imprinted genes, the protein profiles of parthenogenetic and normal blastocysts pared using the technique of high-resolution two-dimensional electrophoresis. The protein profiles of parthenogenetic, androgenetic and normal embryonic stem cells were pared. Hence parent-specific gene expression was examined in embryonic and extraembryonic lineages of the early embryo. Approximately 1000 polypeptides were examined in each of the analyses, however no parent-specific differences were observed for any of these polypeptides. From this result, it is concluded that expression of genes encoding these polypeptides is identical from the parental chromosomes. These findings have important implications for estimates of the number of imprinted genes in the genome and for the interpretation of phenotypes of parthenogenetic and androgenetic embryos.
8793622
Thyroid hormone regulation of germ cell-specific EF-1 alpha expression during metamorphosis of Xenopus laevis.
In situ hybridization was used to follow the distribution of the mRNAs encoding the somatic form of elongation factor 1 alpha (EF-1 alpha S) and the germinal counterparts of this factor, thesaurin a and EF-1 alpha O, throughout metamorphosis in the gonads of Xenopus laevis tadpoles. EF-1 alpha S mRNA is detected before metamorphosis in both the somatic and germ cells of the gonads. In contrast, thesaurin a and EF-1 alpha O mRNAs are first detected in spermatogonia and oogonia at stages 60-62, corresponding to the climax of metamorphosis and to the peak of circulating thyroid hormone. To determine whether thyroid hormone, the instigator of metamorphosis, is involved in regulating the expression of the germinal gene EF-1 alpha O, Xenopus XTC cells were transfected with an EF-1 alpha O promoter sequence inserted in front of the luciferase reporter gene. Addition of T3 to the cell culture medium induced a dose-dependent increase in transcription from the EF-1 alpha O promoter. This effect was enhanced when the construct was cotransfected with an expression vector for a Xenopus thyroid hormone receptor. Our data show that germ cells switch from a somatic to a germ-cell specific mode of expression during metamorphosis. Furthermore, this switch appears to be induced by thyroid hormone.
8793623
Parthenogenetic activation of mouse oocytes using calcium ionophores and protein kinase C stimulators.
Fertilization involves the production of inositol trisphosphate and diacylglycerol with a subsequent increase in intracellular calcium concentration ([Ca2+]i) and the activation of a calcium-dependent protein kinase, the so-called protein kinase C (PKC). Methods of parthenogenetic activation have focused on this calcium wave which seems to be large enough to generate all the responses associated with fertilization and even finally inducing the activation of PKC activity. The specific stimulation of PKC by phorbol esters in turn elicits [Ca2+]i oscillations although no reports exist claiming that the mere activation of this protein is capable of sustaining embryonic development. In this paper we describe the effect of different calcium ionophores and phorbol esters as parthenogenetic agents on mouse pared with ethanol as the standard procedure. Phorbol esters (OAG) fail to activate a significant number of oocytes, with very few reaching blastocyst stage. However, when a calcium ionophore (A23187) is added, the percentage of embryos reaching the blastocyst stage increases to such an extent that it is the best chemical method assayed to date. We conclude that incubation with bined inhibits feed-back processes between the above reactions and so induces a more physiologic parthenogenetic activation.
8793624
A WHO Collaborative Study of Maternal Anthropometry and Pregnancy Outcomes.
To evaluate to what degree anthropometric measurements are useful and efficient in predicting maternal and fetal es in different country settings and to develop appropriate reference curves for maternal weight gain.
8793625
Resistance to chloroquine therapy in pregnant women with malaria parasitemia.
The objective of the study was to determine the efficacy of chloroquine in pregnant women with Plasmodium falciparum parasitemia at therapeutic doses of 25 mg/kg body weight divided over 3 days.
8793626
Treatment of cervical pregnancy with methotrexate.
To review our experience with early ultrasonographic diagnosis and plete medical treatment of cervical pregnancy.
8793627
Appendectomy in the surgical staging of ovarian carcinoma.
Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma.
8793628
Office hysteroscopic tubal occlusion with siloxane intratubal devices (the Ovabloc method).
To study the results of the Ovabloc method for female sterilization used in an outpatient setting.
8793629
Management of perineal endometriosis.
To demonstrate the appropriate diagnosis and management of perineal endometriosis.
8793633
ACOG technical bulletin. Sterilization. Number 222--April 1996 (replaces no. 113, February 1988). American College of Obstetricians and Gynecologists.
Sterilization provides a safe and effective contraceptive method. Both female and male sterilization have few long-term sequelae. Several new methods of transcervical sterilization are under development, but laparoscopy and minilaparotomy are likely to remain the most popular methods of female sterilization.
8793635
A discourse on human hair fibers and reflections on the conservation of drug molecules.
A gross discourse on human hair fibers and their formation is presented stressing the various interdisciplinary aspects, such as the morphological, biological, structural and biochemical data considered to be important in the field of hair analysis. An attempt is made to explain the incorporation of drug molecules during hair fiber formation by using the classical concepts of drug absorption based on lipoid theory and the pH-partition hypothesis as well as a modern biological approach on the permeability of cell membranes. In addition to the physiochemical considerations of the transport properties of a particular drug molecule such as a) the lipophilicity, which determines permeability through the membrane, b) the pKa value, c) the plasma protein binding and d) the molecular size and shape of the drug molecule, drug absorption is thought to be limited by the surface area and the residence time in the hair bulb. The thermodynamic approach according to the Kedem-Katchalsky equations seems even more satisfying. When the principles of biological transport across cell membranes are applied to the cell populations present in the hair root, a hypothesis of extracellular and intracellular drug localizations results. It is speculated that the cell plex (CMC) and the melanin granules present the main sources of incorporated drug molecules within the keratinized hair fibers.
8793636
Concentrations of delta 9-tetrahydrocannabinol, cocaine and 6-monoacetylmorphine in hair of drug abusers.
Hair samples taken from 850 individuals with presumed drug abuse were tested simultaneously for delta 9-tetrahydrocannabinol (THC), cocaine, heroin, the primary heroin metabolite 6-monoacetylmorphine (6-MAM) and morphine. The drugs were extracted with methanol under sonication. Compared to other extraction procedures this solvent extraction technique provides high extraction yields and less experimental effort. The analyses were carried out using gas chromatography-mass spectrometry (GCMS) in selected ion monitoring (SIM) mode. This procedure allows the simultaneous detection of amphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxylamphetamine (MDE). THC was found in 104 (12.2%), cocaine in 230 (27%) and 6-MAM in 141 (16.6%) samples. In addition to 6-MAM, morphine was detected in 87 (10.2%) and heroin in 38 samples (4.5%). The concentrations found were in a range 0.009-16.7 ng/mg for THC, 0.037-129.68 ng/mg for cocaine, 0.028-79.82 ng/mg for 6-MAM, 0.045-53.14 ng/mg for heroin and 0.011-7.800 ng/mg for morphine. The statistical distribution of the drug pared with the self-reported consumption behaviour of the users may possibly lead to a better understanding of the relationship between drug dosage and corresponding concentrations in hair.
8793637
Population genetics of STR loci in Caucasians.
STR loci are ing increasingly important in forensic casework. In order to be used fairly and efficiently, the population genetics of these loci must be investigated and the implications for forensic inference assessed. A key population genetics parameter is the "coancestry coefficient", or FST, which is the correlation between two genes sampled from distinct individuals within a subpopulation. We present analyses of STR data, at geographic scales which range from national to regional, from the UK and other European sources. We implement a likelihood-based method of estimating FST, which has important advantages over alternative methods: it allows a range of plausible values to be assessed, rather than presenting a single point estimate, and it allows a subpopulation to pared with a larger population from which a database has been drawn, which is the parison in forensic work. Our results suggest that values of FST appropriate to forensic applications in Europe are too large to be ignored. With appropriate allowance, however, it is possible to make use of STR evidence in a way which is efficient yet avoids overstatement of evidential strength.
8793638
Semiparametric approach to match probability calculations using single locus probes.
A semiparametric approach to match probability calculations using single locus probes has been developed pared graphically with other standard methods by a one-sample simulation. The density functions obtained using this method are closer to the real distributions than those obtained by conventional approaches. Our method does not need to establish an arbitrary match threshold, which has been a source of problems in practical applications of standard methods. Moreover, it can be adjusted to any particular conditions by setting the experimental error and correlation of each laboratory. To assess the practical performance of this method we carried out parison experiment using a sample of 229 individuals analysed in duplicate.
8793641
Population study of the STRs HUMTH01 (including a new variant) and HUMVWA31A in Catalonia (northeast Spain).
Allele and genotype frequencies for 2 short tandem repeat loci were determined in a population sample from Catalonia (Spain) using the polymerase chain reaction. After denaturing PAG electrophoresis, mon and one variant (13.3) alleles were identified for HUMTH01 in a sample of 234 unrelated individuals, and seven alleles were found for HUMVWA31A in 162 individuals. No deviation from Hardy-Weinberg equilibrium was found. The observed heterozygosities are 76.92 and 79.62 respectively. The discrimination power determined for the individual loci is 0.928 and 0.937 respectively.
8793639
Failed PCR amplifications of MBP-STR alleles due to polymorphism in the primer annealing region.
The PCR-based STR system MBP-B (myelin basic protein locus B) has been reported to exhibit a high rate of mutations. Using a newly designed pair of primers we present evidence that this is due to failed amplifications caused by a polymorphism in the annealing region of the reverse primer originally designed. With the new reverse primer described here no exclusions were found (out of 59 mother/child pairs analysed) while one was detected with the old set of primers. The results obtained with both pairs of primers in a random population sample (n = 112) from North Portugal pared. In this sample 13 individuals typed as homozygotes with the pair of primers originally described, were found to be heterozygous when the amplifications were performed with the new reverse primer. By sequence analysis, a substitution in the reverse primer binding sequence originally described was determined. This substitution is located upstream from the repetition site and consists of G-->A transition. This variation reaches polymorphic frequency and is responsible for the relatively frequent null alleles due to failed amplifications when the previously designed primers are used.
8793640
The STR systems HumVWA and HumACTBP2 in a Hungarian population.
Allele frequencies of the Short tandem repeat systems HumVWA and HumACTBP2 were determined from 105 unrelated individuals from the area of Szeged, Hungary. A total of 8 alleles was detected for VWA, and 23 alleles were found for ACTBP2. In both systems no deviations from Hardy-Weinberg equilibrium were observed. parison of the Hungarian and German frequency profiles revealed significant differences at both STR loci.
8793642
Allele detection and population study in Japanese using two STR loci (CYP19 and HUMTH01).
Allele fragments at two polymorphic short tandem repeat (STR) loci, CYP19 and HUMTH01, were simultaneously amplified in a sample of 200 unrelated Japanese individuals living in the Kanto area, including Tokyo. After electrophoresis in PAG, the new alleles 7, 10, 11, 12, and 13 were detected at the CYP19 locus in Japanese. HUMTH01 allele frequencies in Japanese differed greatly from those reported for Caucasians and Asians living in the US. The polymorphism information content (PIC) in Japanese was calculated as 0.46 for CYP19 and 0.66 for HUMTH01. The power of discrimination (PD) was 0.7 for CYP19 and 0.86 for HUMTH01, and bined PD was calculated as 0.96. No significant deviations from Hardy-Weinberg equilibrium could be observed for these systems.
8793643
The detection of picoplankton 16S rDNA in cases of drowning.
Picoplankton belonging to the Synechococcus genus in cyanobacteria (approximately 1 micron in size) are found ubiquitously in Lake Biwa, Japan. However, they could not be morphologically discriminated from other bacteria by microscopy. In this study we attempted to use picoplankton for the diagnosis of drowning by PCR analysis of the 16S ribosomal DNA (rDNA). We designed plementary to the variable regions of 16S rDNA of the picoplankton we had sequenced. parison was made of the PCR products from the three picoplanktons, five other cyanobacteria, Melosira (diatom), Staurdstrum (green alga), bacteria from Lake Baikal, and humans. The picogram order of template DNA from picoplankton was specifically amplified by the primers. When the template of picoplankton was mixed with human lung tissue, at least 10 ng of template DNA was needed to obtain a PCR product. The isolation of the picoplankton from human lung tissue increased the sensitivity of PCR more than a hundred-fold. The specific PCR products of the picoplankton were obtained from formalin-fixed drowning tissue. Molecular biological diagnosis of drowning was successful using picoplankton 16S rDNA.
8793645
Teaching medical students by role playing: a model for integrating psychosocial issues with disease management.
Medical students on third-year rotations seem to be focused more on the particulars of disease management than on patient management. They often pay too little attention to the psychological and social needs of the patient and to the importance of working in a multidisciplinary team. The authors postulated that a model for teaching breast cancer management that included role playing, self-study, and active student involvement would facilitate the integration of psychosocial and affective issues into scientific content and would demonstrate the importance of the team approach in managing patients with breast cancer.
8793646
Communication, accrual to clinical trials, and the physician-patient relationship: implications for training programs.
Previous studies have demonstrated that less than 20% of fully eligible patients participate in cancer clinical trials. One of the major factors determining whether patients will be successfully accrued to trials is the quality of munication occurring between the physician and patient (and family members if present). The accrual process is embedded within the longer-term relationship between the physician and the patient. It is argued that the interaction occurring during the consent process is part of an "alliance building" that the physician and patient use to confront the uncertainty inherent in both the disease itself and the e of therapy.
8793647
Oral cancer education in dental schools: survey of Texas dental students.
Senior dental students at the three Texas dental schools were surveyed about their attitudes and perceptions of their knowledge and skills in areas related to prevention, detection, and diagnosis of oral cancer, and the management of oral sequelae of cancer therapy methods. A 16-item survey was distributed to a total of 251 fourth-year dental students. A total of pleted surveys were returned, for a response rate of 79%.
8793648
Tumor board formats: "fascinating case" versus "working conference".
To test the hypothesis that a "working conference" (WC; tumor board format in which any case requiring multispecialty input is presented for discussion) was preferable to a "fascinating case" (FC; only "interesting" or "unusual" cases presented) format, tumor board format at the Portland Veterans Affairs Medical Center was changed from FC to WC.
8793649
Cancer-risk-related health behaviors and attitudes of older workers. Working Well Research Group.
The National Cancer Institute's Working Well Trial was a randomized controlled trial of a prehensive, worksite-based cancer control intervention.
8793650
Attitudes about skin cancer prevention: a qualitative study.
Skin cancer represents a significant threat to the health and well-being of Americans. By engaging in both primary and secondary preventive behaviors, individuals can reduce their risks of developing skin cancer.
8793651
Children's return to school after treatment for cancer: study days for teachers.
As greater numbers of children return to school after treatment for cancer, their teachers need information and assurance in order to facilitate the reintegration process.
8793652
Use of effective feedback to facilitate adult learning.
Effective feedback plays a critical role in helping adult learners achieve their educational goals and reach their maximum potential. It should be an integral part of every adult education program. Both formal and informal feedback should be provided by teachers, based on the underpinnings of effective feedback techniques. The feedback source, message, and recipient exert influences on the process and must be considered in this context. For maximum impact, the source of feedback must be considered credible and trustworthy by the recipient. The message should provide clear information about performance standards and the performance of the student, in order to elucidate any differences. Positive information should be shared before negative information, and the feedback should be specific, objective, consistent, and timely. The environment in which feedback is provided must be supportive, and should encourage an open dialog between the teacher and the student. Both parties should discuss various items in a spirit of collaboration, and clearly define the goals that need to be achieved. A plan for follow-up and ongoing reinforcement must be developed and implemented. In addition to oral and written feedback, other modes of providing feedback, such puters, audiotapes, and videotapes, should be considered, and used as appropriate. Skills of faculty members in providing effective feedback may be enhanced through faculty-development programs, such as workshops and self-study modules.
8793653
Clinical and histological features of poor prognosis in cutaneous metastatic melanomas.
Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor e. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell-stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n = 59) and lesions from patients with a longer survival (n = 285). Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1 +/- 14.1 years versus 58.8 +/- 15.3 years), had developed earlier after the primary tumor (mean time of 21.7 +/- 19.9 months versus 43.3 +/- 27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p < 0.001) and PRECOLL (82.8% versus 57.6; p < 0.01) were more frequent in metastases of poor e. The same was true for SCSIMPLE (50% versus 25.6%; p < 0.01) and PREFAT (68.1% versus 46.8%; p < 0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen. In conclusion, melanoma deposits metastatic to the skin with particular poor e differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.
8793654
p75 nerve growth factor receptor staining helps identify desmoplastic and neurotropic melanoma.
Melanoma is a malignant tumor with a varied histologic appearance. posed of spindle cells may include desmoplastic and neurotropic melanoma. The histologic diagnosis of desmoplastic and neurotropic melanoma can be difficult. Although S100 protein stains a majority of these melanomas, the staining may be weak or focal. HMB-45, a more specific marker of melanoma, is frequently negative in desmoplastic and neurotropic melanoma. In order to aid the identification of desmoplastic and neurotropic melanoma, we stained 13 spindle cell melanomas (5 neurotropic melanomas, 5 desmoplastic melanomas, 3 spindle cell melanomas without either desmoplasia or neurotropism) with p75 NGF-R pared the staining results with S100 and HMB-45. p75 NGF-R is the low affinity nerve growth factor receptor reported to be present on the surface of neural-crest-derived cells. Conventional melanoma as well as neurotized nevi, neurofibroma, spindle squamous carcinoma, atypical fibroxanthoma, dermatofibroma and scars were also stained with p75 NGF-R. p75 NGF-R stained all of the desmoplastic and neurotropic melanomas tested. In each of these cases, negative HMB-45 staining of the spindle cells was seen. In many cases the number and intensity of the spindle cells staining with p75 NGF-R was greater than with S100. Neurofibroma, neurotized nevi and focal cells in round cell melanoma also were stained with p75 NGF-R. All the squamous cell carcinomas, atypical fibroxanthomas, dermatofibromas and scars were negative for p75 NGF-R. Based on our results, p75 NGF-R may be useful as an additional confirmatory antibody in a melanoma panel, especially in differentiating desmoplastic and neurotropic melanomas from non-neural-crest-derived spindle cell lesions. We feel it also can be helpful in better identifying margins of excision of these melanomas. p75 NGF-R, like S100 protein, will not differentiate desmoplastic and neurotropic melanomas from other neural-crest-derived lesions.
8793655
Involvement of the adherens junction-actin filament system in acantholytic dyskeratosis of Hailey-Hailey disease. A histological, ultrastructural, and histochemical study of lesional and non-lesional skin.
Hailey-Hailey disease is a blistering genodermatosis that shows acantholytic dyskeratosis throughout the epidermis. The aim of our study was to investigate the involvement of adherens structures and cytofilaments in this particular type of acantholysis. Both lesional and non-lesional skin from 18 patients was studied histologically and ultrastructurally. Additionally, the samples were stained for desmosomes, adherens junctions, keratin filaments, actin filaments, and actin-associated proteins, and finally investigated with an electron and a confocal laser scanning microscope (CLSM), respectively. Acantholytic dyskeratosis was not only confined to lesions, but was also focally detectable in clinically unaffected skin. Despite disruption and internalization of the desmosomes, keratinocytes remained linked together by well-preserved adherens junctions. Staining for actin filaments with fluorochrome-labeled phalloidin showed a remarkable formation of actin stress fibers in these keratinocytes. Thus, plete acantholysis, as demonstrable in both lesional and non-lesional skin of Hailey-Hailey patients, may be due to a cohesive function of the adherens junction-actin system succeeding the dissolution of desmosomes. Most remarkably, none of the adnexal epithelia expressed the intrinsic defect of cell adhesion. This finding offers an explanation for the successful treatment of Hailey-Hailey disease by dermabrasion, which plete removal of the involved epidermis results in reepithelialization from skin appendages.
8793656
Vla and alpha 6 beta 4 integrin expression in neuroendocrine carcinomas of the skin (their xenografts on nude mice and a corresponding primary culture).
Immunohistological expression of VLA1-5 and alpha 6 beta 4 integrins have been studied in 21 cases of primary neuroendocrine carcinomas of the skin (NECS), three xenografts on nude mice and one NECS cell culture. The phenotypic properties of NECS cells were largely maintained in NECS grafted on athymic nude-mice and in the corresponding cell line. Our results indicate that alpha 1 beta 1 and to a lesser extent alpha 3 beta 1, alpha 5 beta 1 are the main integrins expressed in NECS. In addition, VLA2, 4 and alpha 6 beta 4 are heterogeneously expressed in the same group of tumors and very sparsely present. These data suggest that like neuroblastoma and primitive peripheral neuroectodermal tumor (pPNET) the absence or the heterogeneous distribution of such integrins is correlated with the aggressive behaviour of NECS although long-term follow-up was not available for our cases. On the other hand, the alpha 1 expression could be regarded as a novel marker for differential diagnosis between NECS (alpha 1+) and pPNET (alpha 1-). The alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1 heterodimers in the 21 NECS studied showed an uniform pericellular staining of both the peripheral cells and central cells of the tumor islands. The predominant expression of alpha 1 beta 1 is consistent with the hypothesis of a primitive epithelial totipotential origin in NECS.
8793657
p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours.
p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from petent individuals. Skin lesions examined included 52 viral warts, 50 dysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).
8793658
Intermediate- and low-molecular-weight keratin detection with the monoclonal antibody MNF116. An immunohistochemical study on 232 paraffin-embedded cutaneous lesions.
Immunohistochemical detection of certain low to intermediate molecular weight keratins often is impaired in routinely processed specimens due to masking of these antigens by formalin fixation. Despite standard enzymatic digestion, AE1:AE3 and CAM 5.2, two of the most currently utilized antikeratin antibody preparations, either stain weakly or fail to stain basal keratinocytes and posed of basaloid keratinocytes in paraffin sections of formalin-fixed tissue. We present here our experience with the monoclonal antibody MNF116 which detects keratins 5, 6, 8, 17, and 19 (DAKO, Carpinteria, CA). We have studied 232 routinely-processed skin lesions with MNF116 pared the staining with that of AE1:AE3 mixture or CAM 5.2. In normal skin, the staining achieved with MNF116 was particularly strong on the basal cells of the epidermis and adnexae. MNF116 was positive in all 154 epithelial tumors and negative in all but one (a a) of 78 mesenchymal and melanocytic tumors. AE1:AE3 mixture was positive in all but four poorly-differentiated squamous cell carcinomas and it was only weakly positive in most basal cell carcinomas. CAM 5.2 was positive in tumors of the sweat apparatus, Merkel cell carcinomas, metastatic carcinomas, and 5/15 basal cell carcinomas. We consider that, in routinely processed specimens, MNF116 is very useful and convenient for detection of cytokeratin expression in cutaneous lesions, and therefore helpful in the evaluation of tumors with small cells and other poorly differentiated neoplasms of the skin.
8793659
Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery.
The eruption of lymphocyte recovery occurs after marrow ablative antineoplastic chemotherapy, with the earliest reappearance of lymphocytes in the peripheral circulation. The typical histopathologic findings are not specific, consisting of a perivascular lymphocytic infiltrate in the upper dermis with mild overlying epidermal changes. Since the initial report, 21 additional biopsy specimens from eruptions of lymphocyte recovery were obtained at our institution. Of these specimens, 18 displayed the expected findings while 3 specimens contained a relatively heavy lymphocytic infiltrate with nuclear pleomorphism and hyperchromasia. The majority of lymphocytes from the heavily inflamed tissues expressed CD3 and CD4; rare CD8+ cells were observed. The cells with large irregular nuclear contours displayed an "activated" phenotype, consisting of CD30, HLA-DR, and CD25, accounting for roughly 50% of the total infiltrate. The three patients from whom these specimens were obtained had received human binant cytokines in pharmacologic doses (2 granulocyte-macrophage colony stimulating factor, 1 interleukin-3). Three patients in this series also received human binant cytokines, but developed eruptions with the typical scant infiltrate of small lymphocytes. These findings extend the histologic spectrum of the eruption of lymphocyte recovery and suggest that the administration of human binant cytokines prior to marrow recovery may alter the appearance and phenotype of lymphocytes migrating into the skin.
8793660
Perivascular mast cells in urticaria pigmentosa.
We have quantified perivascular mast cells in cases of urticaria pigmentosa, urticaria, and dermal hypersensitivity reactions. To facilitate reproducibility, the mast cells were counted for a precisely defined vessel unit. These vessel units were divided arbitrarily into those < or = 55 microns and > 55 microns in largest diameters. Urticaria pigmentosa showed an average of 6.4 +/- 1.9 and 22.8 +/- 13.2 mast cells for vessel unit < or = 55 microns and > 55 microns, respectively. Urticaria yielded a lower number of mast cells: 1.5 +/- 0.2 and 2.9 +/- 0.9 for the same respective vessel units. Dermal hypersensitivity reactions revealed an average of 1.6 +/- 0.4 and 2.2 +/- 0.7 mast cells, and the normal skin showed 1.5 +/- 0.3 and 2.4 +/- 0.6 mast cells for each of the vessel units of < or = 55 microns and > 55 microns. The perivascular mast cell distributions of urticaria pigmentosa are statistically different from those of urticaria and dermal hypersensitivity reactions with p < 0.0001. No statistical difference was noted between urticaria, dermal hypersensitivity reactions, and normal skin. The percentages of vessel units < or = 55 microns with > or = 5 mast cells and vessel units > 55 microns with > or = 10 mast cells were determined for each case. The average percentage of vessel units for the former and latter in urticaria pigmentosa was 82.6% and 58.9%, respectively. Urticaria yielded 0% and 0.2%, respectively. None of vessel units in the dermal hypersensitivity reactions or normal skin contained more than 5 mast cells in vessel units < or = 55 microns and more than 10 mast cells in vessel units > 55 microns. Cases of urticaria pigmentosa can be distinguished from other cutaneous eruptions containing mast cells using a simple counting technique on Giemsa stained sections.
8793661
Skin lesions revealing neonatal acute leukemias with monocytic differentiation. A report of 3 cases.
Acute myelo-monoblastic (AMML) and acute monoblastic (AML) leukemias have a bad prognosis, especially in children when occurring in the first months of life. We report 3 cases of such leukaemias in which skin lesions preceded and revealed the leukemia. For the 3 infants, cutaneous lesions appeared about one month before the other signs of leukaemia (2 AML and 1 AMML). Skin biopsies from all 3 infants revealed a heavy dermic infiltration by large cells with round or irregular vesicular nuclei and abundant pale cytoplasm. These atypical cells did not express any lymphoid markers but reacted strongly with monocytic-macrophagic antibodies (CD68, CD13 and CD14). Two infants were treated by mitoxanthrone and cytarabine plete remission. The third one was not treated because of a very poor general status. Skin involvement is frequent in these nonlymphoid leukaemias (30% to 50% of cases). In only 7% of cases, leukemic skin lesions precede and reveal the other signs of leukemia by weeks or months. Then, it is very important to repeat the blood cell counts and to biopsy the skin lesions in order to make a diagnosis of leukemia as early as possible.
8793662
Mucinous differentiation in adnexal sweat gland tumors.
We report an eccrine acrospiroma, on the cheek of a 29-year-old female, in which the presence of abundant mucinous (goblet cell) metaplasia closely mimicked a primary mucoepidermoid carcinoma. To determine the frequency of mucinous differentiation in benign adnexal sweat gland tumors, we evaluated sixty-five cases in hematoxylin and eosin stained sections for the presence of goblet cells and sixty of these for mucicarmine positivity. Goblet cell metaplasia was seen in 3 of 12 acrospiromas, 1 of 8 mixed tumors, and in 1 of 9 cases of syringocystadenoma papilliferum. All goblet cells were positive for mucicarmine, except in one case of acrospiroma, where goblet cells were not detected on the section stained with mucicarmine. In addition, intracellular mucin, inclusive of goblet cells, was seen in 5 of 12 acrospiromas, 1 of 11 poromas, 5 of 8 mixed tumors, 3 of 13 spiradenomas, 1 of 5 cylindromas, 3 of 9 cases of syringocystadenoma papilliferum and 1 of 3 nipple adenomas. The majority of the tumors had both extracellular mucicarmine positivity (40 of 60) and luminal mucicarmine positivity (39 of 60). We conclude that mucinous differentiation in sweat gland tumors, as defined by the presence of goblet cells and/or intracellular mucicarmine positivity, mon and does not indicate aggressive behavior. Mucinous differentiation in benign sweat gland tumors should not be confused with more aggressive mucoepidermoid carcinomas of salivary gland origin or adenosquamous carcinoma.
8793663
Neutrophilic spongiosis in pemphigus herpetiformis.
Pemphigus herpetiformis is a rare pemphigus variant with light microscopic features that have historically been described as either "acantholytic dermatitis herpetiformis" or as "eosinophilic spongiosis in pemphigus". The clinical features of this form of pemphigus are reminiscent of dermatitis herpetiformis; however, the direct immunofluorescence finding of epidermal inter-cellular IgG deposition is that of the pemphigus group. We report two patients with clinical presentations suggestive of dermatitis herpetiformis in whom the histopathologic features were those of a neutrophilic intraepidermal blistering disorder. Biopsies showed marked epidermal spongiosis with midepidermal acantholytic vesicles containing predominantly neutrophils and a few eosinophils. Direct immunofluorescence was positive for epidermal intercellular IgG; IgA deposition was not present. Neutrophilic spongiosis, in the absence of a prominent eosinophilic infiltrate, should be recognized as an early finding in some cases of pemphigus, and immunofluorescence studies are justified when this histologic feature is encountered in a skin biopsy.
8793664
Pityriasis rubra pilaris with acantholysis.
Two patients developed a papulosquamous eruption in a widespread distribution which progressed with islands of sparing of uninvolved skin characteristic clinically of adult-onset pityriasis rubra pilaris (PRP). Biopsies from both patients showed multiple areas of nonfollicular and follicular suprabasilar and intra-epidermal acantholysis with minimal dyskeratosis. They also showed the usual histologic features of PRP with a thickened orthokeratosis and parakeratosis, a retained and sometimes thickened granular cell layer, and psoriasiform epidermal hyperplasia with a perivascular lymphohistiocytic infiltrate in the superficial dermis. Two previous patients with PRP have been reported with nonfollicular, focal acantholytic dyskeratosis and both were interpreted as most likely representing an incidental finding. We believe the acantholysis in these two cases is related to the disease process, and in our second patient, was helpful in establishing the diagnosis.
8793665
Histiocytic sarcoma that mimics benign histiocytosis.
A 28-year-old man presented with a histiocytic a of a very mon origin, as it had developed for several years like a benign cutaneous histiocytosis resembling generalized eruptive histiocytoma before ing acute, with nodal and massive pulmonary involvement. Despite various chemotherapies, the patient died within 8 months. Skin biopsies showed histiocytic proliferation in the dermis and node biopsies showed histiocytic proliferation with a sinusoidal pattern. Immunohistochemical analysis, performed on paraffin-embedded sections, demonstrated strong labeling of tumoral cells for CD68 and moderate labeling for CD3 and CD4. CD30 labeling was negative. S-100 protein was positive on a Langerhans' cell reactive subpopulation. Electron microscopy confirmed the histiocytic nature of malignant cells and showed cytoplasmic inclusions such as regularly laminated bodies, dense bodies and pleomorphic inclusions. No Birbeck granules were seen. A gene rearrangement study of T-cell receptor gamma and immunoglobulin heavy chain genes showed a germline configuration. Histiocytic a is an extremely rare true histiocytic malignancy, the existence of which has been recently debated since it has often been mistaken in the past for large cell lymphomas. Such a deceptive onset as benign cutaneous histiocytosis has not been described in the literature to our knowledge.
8793666
Unusual features of primary dermatofibrosarcoma protuberans and its myxoid recurrence.
A case of a Protuberans (DFSP) with unusual clinical and histological features is presented. The lesion recurred one year after surgical removal and showed myxoid degeneration of the entire lesion. Only a few cases with myxoid degeneration of the entire lesion are described in the literature. We found CD 34 stain, bination with a panel of antibodies including fXIIIa, S100 and actin, useful in the diagnosis of this type of tumor in order to differentiate it from other neural, fibrous or muscular neoplasms.
8793667
An objective measurement of the anchoring strength of anagen hair in an adult with the loose anagen hair syndrome.
A 21-year-old male presented with the life-long symptom of slowly growing, easily extractable hair lacking sheath remnants. The distribution and density of all his hair regions appeared normal and there was no alopecia. A hair-pull test was painless and resulted in all hairs being removed, all in keeping with a diagnosis of loose anagen hair syndrome (LAHS). The trichogram was normal. Electronically measured epilation revealed values which were significantly lower than controls. His hair follicles were remarkable for this syndrome in that they looked perfectly normal with light microscopy; however, the segment of the follicle with the keratogenous zone was significantly shorter than normal. It is postulated that a subtle intercellular defect must reside in the line of shear proximal to the level of cuticular differentiation to account for the weak anchoring of the root in the follicle. A consequence of a genetic error probably causes both the weak anchoring and the slow hair growth.
8793669
Replacement of the ascending aorta with composite valve grafts: long term results.
Long term survival after replacement of the aortic root is improving. The mon cause of late death is progression of disease in the remaining aorta (dissection or atherosclerosis). The purpose of this study was to review our clinical experience posite graft replacement of the aortic root with special reference to long term results.
8793670
Functional results after aortic valve repair in aortic root ectasia.
Aortic insufficiency due to dilation of the aortic root is mon finding. bined replacement of the aortic valve and the ascending aorta is regarded as standard treatment, total replacement of the proximal aorta with a tube graft and resuspension of the valve is a new alternative.
8793671
Aortic dissection in puerperium: a case report.
An acute type A aortic plicated by massive aortic regurgitation, was diagnosed in the case of a 32-year-old woman, thirty-three days post partum. Emergency operation (Cabrol II) was performed with an uneventful postoperative course. We draw attention to this high risk event, which is particularly apt to involve women within a short time after an otherwise uneventful pregnancy.
8793672
Systolic and diastolic mitral regurgitation in a patient with annulo-aortic ectasia demonstrated by color Doppler flow imaging.
A rare case of annulo-aortic ectasia is reported in a 65-year-old man who had aortic and mitral regurgitation during systole and diastole. He was hospitalized for further examination of the heart due to cardiomegaly and heart murmurs. Aortography revealed severe aortic regurgitation. On color Doppler flow imaging, we could detect red aortic regurgitant signals in the left ventricular cavity during diastole, and mosaic and blue mitral regurgitant signals in the left atrial cavity during systole and diastole associated with a relatively long R-R interval, respectively. The unique observation of diastolic mitral regurgitation is discussed.

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