Lethal hyperkinetic ventricular arrhythmias and echocardiographic findings in patients with arrhythmogenic right ventricular disease

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Lethal hyperkinetic ventricular arrhythmias and echocardiographic findings in patients with arrhythmogenic right ventricular disease     

The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones

1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca²⁺-activated K⁺ (BK_Ca) channel present in neurones isolated from the rat motor cortex.
2. Classical neuroleptic compounds including chlorpromazine and haloperidol applied to the intracellular surface of inside-out patches produced a concentration-dependent reduction in BK_Ca channel activity. Similar effects were observed when these compounds were applied to the extracellular surface of outside-out patches.
3. In contrast, the atypical neuroleptic compounds clozapine and sulpiride did not affect BK_Ca channel activity (100 nM–1 mM) in either inside-out or outside-out patches, while 10 μM pimozide produced 73% of the inhibition produced by 10 μM chlorpromazine.
4. BK_Ca channel activity was also unaffected by application of structurally related tricyclic compounds including the anti-cholinesterase tacrine and the anti-epileptic carbamazepine. The tricyclic antidepressant drug amitriptyline was found to inhibit BK_Ca channel activity but was much less effective than the classical neuroleptic compounds.
5. It is concluded that compounds belonging to the classical neuroleptic group of drugs inhibit BK_Ca channel activity in the rat motor cortex in a structurally-specific manner. This observation may be of clinical significance as it may contribute to some of the side effects associated with classical neuroleptic drug therapy.

     

Percutaneous nephrostomy - recovered renal-function in 50 obstetric and gynecologic patients undergoing percutaneous nephrostomy

Percutaneous nephrostomy (PN) will rapidly correct renal failure due to ureteral obstruction. Complications of the procedure are few and the procedure can be quickly accomplished on an outpatient basis using local anesthesia. A retrospective review of fifty patients who underwent PN led to derivation of a formula which predicts the expected degree of correction of renal function. Measurement of renal intracalyceal pressures at the time of PN was not helpful in predicting-outcome.     

Radiography in forensic dental identification--a review

It is recognised that reliable objective evidence is provided by medical and dental radiographs in forensic identification. This depends on the observation and comparison of anatomical and artificial structures recorded in both ante-mortem and post-mortem radiographs, and which can be regarded as unequivocal evidence. The introduction of new technology into the area of radiographic imaging provides both clear advantages and also some cause for concern where image enhancement can be carried out which may give rise to dispute if this technology is to be applied to forensic dental identification. To date there have been no published forensic case reports involving the use of directly acquired digital radiographs but it is anticipated that this will change. The technical advantages and known limitations need to be considered if this method of radiography is to be applied in forensic dental identification.     

Cross-cultural development of a quality of life measure for men with erection difficulties

Erection difficulties have a profound effect on a man's quality of life, however, the emotional consequences are often overlooked in quantitative research where most sex-related questionnaires focus on a man's functional ability. Consequently, we developed a cross-cultural instrument to measure quality of life specific to male erection difficulties (QOL-MED). The items in the QOL-MED originated from interviewing forty men with erection difficulties in Seattle and Boston. Twelve men in the USA and 29 men in England helped us refine the instrument. Testing the QOL-MED's psychometric properties involved two administrations over a two-week period in the USA (n=40) and the UK (n=29). For discriminant validity, we predicted quality of life would worsen with increased self-perceived severity of the condition. After controlling for years with erection difficulties in a linear regression model, we found a significant negative association between self-perceived severity and quality of life for men in the UK only (p<0.01). The expectation that the measure would produce evidence for convergent validity by being more closely correlated to well-being than functional status was not confirmed. Both the USA and UK instruments were internally consistent (Cronbach's =0.94 and 0.96, respectively), and reproducible (0.78 and 0.95, respectively). This instrument provides a promising tool for studying therapies and understanding quality of life in patients with erectile dysfunction.This research was supported from a research grant from Syntex, Inc.Mr. Wagner is now a doctoral student at the University of California at Berkeley, Berkeley, CA, USA.     

A role for a non-androgenic anovulant in the management of hirsutism

Sixty-nine patients who had Ferriman/Gallwey hirsutism scores (FG) of ≥8 were treated with Diane, an anovulant containing cyproterone acetate, 2 mg, an anti-androgenic progesterone and ethinyl oestradiol, 5.0 μg. Twenty-one of these had been previously treated with dexamethasone (DEX) and did not respond, i.e. FG >50% of pre-treatment value. Prior to Diane treatment, plasma total testosterone (T) values, 1.4±0.5 nmol/l, mean ±S.D., were similar to those in 43 normal women, 1.23±0.3 nmol/1, as were plasma androstenedione levels, 6.8±2.5 and 6.0±1.7 nmol/1 respectively. However, plasma sex hormone-binding globulin (SHBG) values were suppressed being 36.2116 nmol/I in hirsute women and 45.8115 nmol/1 in normal women, p<0.01. The T/SHBG ratio, an index of free testosterone, was elevated in hirsute women, 4.8+4.1, compared to values in normal women, 2.911.0, p<0.001. Following Diane therapy (2-24 months), 73% of patients responded clinically. There was no change in T, but SHBG was increased to 181±54 nmol/1, p<0.001 and T/SHBG was decreased markedly to 0.9±0.4, p<0.001. Androstenedione fell also to 4.8±1.7 nmol/1, p<0.001. The clinical and hormone response to Diane was similar in both DEX-resistant and previously untreated groups. We conclude that Diane is an effective agent in the treatment of hirsutism while it avoids the adverse effects of androgenic progesterone and of high dose cyproterone acetate therapy.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.