Primary malignant melanoma of the bladder

Primary malignant melanomma of bladder is extremely rare: 18 cases are reported to date. An 82 year-old man underwent trans-urethral resection of bladder for a bleeding tumor of the posterior wall. Histological diagnosis was melanoma of the bladder. There was no history of previous or regressed cutaneous malignant melanoma. Margins of the bladder lesion contained atypical melanocytes similar to those commonly seen in the periphery of primary mucous membrane lesions. Clinical studies and radiological examinations were negative for other primary site of melanoma. The patient had a bladder recurrence that was consistent with primary tumor and died of widespread disease 9 months after diagnosis.     

Stability of subtilisins and related proteinases (subtilases)

The stability towards thermal and chemical (guanidine hydrochloride, GnHCl) denaturation of six inhibited subtilases (mesentericopeptidase, subtilisins BPN′, Carlsberg and DY, proteinase K and thermitase) has been investigated by kinetic and equilibrium studies. The unfolding processes were monitored by circular dichroic and fluorescence spectroscopy. Experiments in the absence and presence of extraneous calcium in the concentration range 2×10^?3-10^?1 M were performed. The presence of calcium in the weak calcium binding site changes the denaturation drastically. The heat- (or GnHCl-) induced unfolding curves obtained using CD spectroscopy show two independent transitions which seem not to have been resolved before. The presence of Ca²⁺ in the second (third in the case of thermitase) binding site increases the T_m, values by 11-21 °C and the δG_D(H₂O) values obtained from denaturation experiments in GnHCl by 6.7-7.2 kcal/mol when an extraneous Ca²⁺ concentration of 2 × 10^?2 M was used. One interpretation is that the initial step of denaturation in the presence of added calcium is the formation of a partially unfolded intermediate form, retaining a highly ordered structure with 60-85% of the a-helix structure of the native enzyme. This intermediate then unfolds at a temperature considerably higher than that of the same proteinases in the absence of added Ca²⁺. The free energy of stabilization of the intermediates is increased by 1.8-2.8 times in comparison with that for the unfolding reactions of the subtilases with empty Ca2/Ca3 binding sites. A second interpretation is that the two steps in the unfolding curves correspond to enzyme without and with calcium in the weak binding site. Fluorescence experiments confirm the mechanism involving the formation of intermediate states. The results are discussed in relation to the X-ray models of the six subtilases.     

Stability of the Defibrillation Probability Curve with the Development of Ventricular Dysfunction in the Canine Rapid Paced Model

Most patients with implantable defibrillators have diminished cardiac function. Progressive heart failure might impair defibrillation efficacy, leading to interpreted device, failure. This study sought to determine the effect of ventricular dysfunction on defibrillation energy using a biphasic endocardial system. Eleven dogs were ventricularly paced at 225 pulses/min for 2 weeks to induce ventricular dysfunction, and five control dogs remained unpaced. Dose response defibrillation probability curves were generated for each animal at baseline, after 2 weeks (at which time the pacemakers were turned off in the paced group), and then 1 week later. The defibrillation thresholds, ED₂₀, ED₅₀, and ED₈₀ (the 20%, 50%, and 80% effective defibrillation energies, respectively) were determined for each dog at each study. In the paced dogs, the mean ejection fraction fell from 55% to 25% after pacing (P < 0.0001), and rose to 46% after its discontinuation (P = 0.0002). The defibrillation threshold, ED20, ED₅₀, and ED80 remained unchanged in both the control and paced groups for all three studies, even after adjustment for dog weight or left ventricular mass. Rapid pacing produced no change in left ventricular mass. It induced ventricular cavity dilatation and wall thinning, which had opposing effects on defibrillation energy requirements, resulting in no net change of the ED₅₀ in heart failure. In conclusion, the defibrillation efficacy of a biphasic transvenous system is not changed by the development of heart failure using the rapid paced canine model.     

Atrioventricular Node Ablation for Optimization of Pacemaker Treatment in Hypertrophic Obstructive Cardiomyopathy

Dual chamber pacing is a new indication for the treatment of drug resistant hypertrophic obstructive cardiontyopathy (HOCM) in patients with normal atrioventricular (AV) conduction. In sinus rhythm, the efficacy of the treatment is mainly related to the ability to bypass the normal AV conduction system in order to obtain a complete and permanent right ventricular (RV) capture. This is achieved by programming short AV delays. On the other hand, patients with HOCM frequently have co-existing left ventricular diastolic dysfunction, and the atrial contribution to left ventricular filling is critical. The lack of improvement, rarely encountered, is probably due to incomplete RV capture andlor to the deleterious effect of short AV delay. Instrumental AV node prolongation may he indicated in this situation. This procedure should be undertaken when previous drug-induced AV prolongation has failed. In theory, AV node modulation (i.e., creating a I ± AV block) seems ideal. However, this technique remains difficult, with disappointing chronic results. Most authors hence perform "conventional" AV node ablation. Particular attention is taken in order to perform a proximal node ablation, resulting in a complete AV block with narrow QRS escape rhythm. The reported incidence of AV node prolongation ranges from 7.5%-37.5%. The efficacy of the procedure on symptoms is explained by improved left ventricular filling and/or a further reduction in the systolic gradient evoked by complete RV capture. Another indication for AV node ablation in HOCM is the occurrence of atrial fibrillation, in order to restore adequate and permanent RV capture .     

Multicenter Pilot Study of a Serpentine Balloon-Expandable Stent (beStentTM): Acute Angiographic and Clinical Results

The beStent is a new stainless steel, balloon-expandable mesh stent which has a unique serpentine design. Rotation of the unique low stress junctions upon expansion leads to orthogonal locking of the wires, maximizing radial strength and assuring zero shortening. The stent has delineating gold markers which assure precise positioning. We aim to present the initial acute results in a pilot registry for stent evaluation. Two hundred eighty-four stents were used in a total of 217 patients (age 57.9 ± 3.10 years; 178 males; 39 females) in seven centers, for variable indications. Stents of 15-, 25-, and 35-mm length were used. The arteries treated were the left anterior descending (n = 112, 42%), circumflex (n = 54, 20.2%), right coronary (n = 95, 35.5%), left main (n = 1, 0.4%), and vein graft (n = 5, 1.9%). Lesion types were: A in 42 patients (16.5%); B1 in 53 patients (20.7%); B2 in 81 patients (31.8%); and C in 79 patients (31%). One hundred fifty-nine patients required one stent, 40 patients required two stents, and 18 patients required three or more stents. Anticoagulation protocol included procedural heparin with aspirin with/without ticlopidine. Smooth angiographie results were obtained in all cases with no plaque herniation. Acute angiographic success was obtained in 97% of the patients, and acute clinical success in 95% of the patients. Complications within 30 days were: 3 deaths (1.4%) (2 noncardiac); 2 (0.9%) myocardial infarctions; and 2 (0.9%) stent thromboses. Therefore, the beStent is useful in treatment of complex lesions of variable length and complexity, providing excellent acute results with a low complication rate, in spite of unfavorable basic clinical and angiographie characteristics.     

Developmental Toxicology Studies of Vancomycin Hydrochloride Administered Intravenously to Rats and Rabbits

Pregnant CD rats were given vancomycin intravenously in dosesof 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6–15;pregnant New Zealand white rabbits were given 0, 40, 80, or120 mg/kg intravenously on GD 6–18. Cesarean sectionswere performed on rats and rabbits on GD 20 and 28, respectively.In rats, maternal toxicity was indicated in the 120- and 200-mg/kgtreatment groups by cortical tubular nephrosis. Maternal bodyweight gain and food consumption and fetal viability, weight,and morphology were not adversely affected by vancomycin. Maternaland developmental no observed adverse effect levels (NOAELs)in the rat were 40 and 200 mg/kg, respectively. In rabbits,maternal toxicity was indicated by cortical tubular nephrosisin the 80- and 120-mg/kg treatment groups; a single death anddepression of body weight gain and food consumption occurredin the 120-mg/kg treatment group. Developmental toxicity wasindicated by depression of fetal weight in the 120-mg/kg treatmentgroup; fetal viability and morphology were not adversely affectedby vancomycin. Maternal and developmental NOAELs in the rabbitwere 40 and 80 mg/kg, respectively. Based on these data, vancomycindid not exhibit selective toxicity toward the developing rator rabbit conceptus.     

Clinical Experience with Expanded Polytetrafluoroethylene Gore-Tex® Surgical Membrane for Pericardial Closure: A Study of 110 Cases

Complete closure of the pericardium after cardiac operations has the advantage of avoiding injury of the heart and great vessels during reoperation. Between 1985 and 1987, the pericardium was closed with Gore-Tex Surgical Membrane (SM) in a selected series of 110 patients 1 month to 76 years of age. Fifty-three patients had congenital heart lesions and 57 patients had acquired heart disease. Overall hospital mortality was 3/110 cases. In no instance was there a relationship between occurrence of death and pericardial closure with SM. There was one episode of cardiac tamponade on the seventh postoperative day. One patient developed fever and leukocytosis due to a mediastinal hematoma. During a mean follow-up of 15 months, four patients had to be reoperated upon three, four, eight weeks, and eight months after primary operation. The anterior wall of the heart had no adhesion with the SM and the other parts of pericardium could be dissected easily. Scanning electron microscopic examination of the explanted SM patches showed neither cellular ingrowth nor immunocompetent cellular elements. The Gore-Tex Surgical Membrane has the advantages of easy availability and lack of reaction between its surface and the epicardium and pericardium. We believe its routine use should be encouraged in patients with high probability of reoperation after repair of complex cardiac anomalies, implantation of bioprostheses, coronary revascularization for one- or two-vessel disease, and repair of degenerative disease of the ascending aorta.     

Effects of stress and shock anticipation on prepulse inhibition of the startle reflex

The effects of shock anticipation and attention to external stimuli on prepulse inhibition (PPI) were compared. In the threat-of-shock experiment, acoustic startle stimuli were presented with and without prepulses when aversive shocks were or were not anticipated. In the control experiment, startle and prepulse stimuli were delivered during periods with attended or ignored external stimuli. In the threat-of-shock experiment, startle was potentiated (fear-potentiated startle) and PPI was increased by shock anticipation. A gradual reduction in the overall PPI throughout the experiment was also found. In the control experiment, only PPI was increased in the attend condition. The PPI level remained constant throughout the experiment. The increase in PPI in the threat and attend conditions may have resulted from an increase in the general level of alertness that facilitated the processing of the prepulse. The gradual decrease in PPI in the threat experiment was hypothesized to result from a progressive deficit in sensory functioning due to the stressful nature of repeated shock anticipation.     

Evening administration of melatonin and bright light: Interactions on the EEG during sleep and wakefulness

Both the pineal hormone melatonin and light exposure are considered to play a major role in the circadian regulation of sleep. In a placebo- controlled balanced cross-over design, we investigated the acute effects of exogenous melatonin (5 mg p.o. at 20.40 hours) with or without a 3-h bright light exposure (5000 lux from 21.00 hours–24.00 hours) on subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in healthy young men. The acute effects of melatonin, bright light and their interaction were measured on the first day (treatment day), possible circadian phase shifts were assessed on the post-treatment day. On the treatment day, the evening rise in subjective sleepiness was accelerated after melatonin and protracted during bright light exposure. These effects were also reflected in specific changes of EEG power density in the theta/alpha range during wakefulness. Melatonin shortened and bright light increased sleep latency. REMS latency was reduced after melatonin administration but bright light had no effect. Slow-wave sleep and slow-wave activity during the first non-rapid eye movement (NREMS) episode were suppressed after melatonin administration and rebounded in the second NREMS episode, independent of whether light was co-administered or not. Self rated sleep quality was better after melatonin administration whereas the awakening process was rated as more difficult after bright light. On the post-treatment day after evening bright light, the rise in sleepiness and the onset of sleep were delayed, independent of whether melatonin was co-administered or not. Thus, although acute bright light and melatonin administration affected subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in a additive manner, the phase shifting effect of a single evening bright light exposure could not be blocked by exogenous melatonin     

On the VIP-ergic innervation of the uterotubal junction

Chronic ACTH treatment (3 IU/kg daily for 8 days) caused an increase in wet weight of the interscapular brown adipose tissue (ISBAT) in the rat without affecting the enzyme activities of the cardiac or skeletal muscles or of ISBAT. On the other hand, chronic β-blockade (alprenolol 10 mg/kg daily for 8 days) induced elevated activities in the oxidative enzymes of the ISBAT but not of the muscle tissues measured. Combined ACTH and alprenolol treatment also increased significantly the citrate synthase and malate dehydrogenase activities and protein concentration, but decreased the weight of ISBAT to normal. The results suggest that, although a direct antagonism between the β-blockers and ACTH has not been demonstrated, β-blockers can abolish the ACTH-induced weight gain of the ISBAT.