Hyperhomocysteinemia: detection, risk assessment, and treatment

OBJECTIVE: The aim of this study was to evaluate both the importance of the screening strategy and the familial aggregation characteristics of families with hypercholesterolemic children. PATIENTS AND METHODS: Ninety-one families (369 subjects) with one hypercholesterolemic child were studied. In addition to clinical and general biochemical evaluation, lipids including apo A-I and B-100 were examined. LDL was quantified under ultracentrifugation. RESULTS: Among the 91 children studied, 10 (10.99%) suffered heterozygous hypercholesterolemia, while 81 (89.01%) suffered polygenic hypercholesterolemia. Following a diet, polygenic children exhibited normal lipid parameters. In heterozygous children a decrease of 19% for total cholesterol, 19.9% for LDL-cholesterol and 16.3% for apo B were observed. When starting the study, 77.5% of the family members thought that they had normal serum lipid values. At the end of the study it was confirmed that only 28% were really normolipemic, indicating that 49.4% of the individual did not know that they were suffering dyslipemia. The study also showed that fathers exhibited the highest incidence of hypercholesterolemia (80.2%) followed by brothers (65.6%) and mothers (61.5%). Therefore, 69.4% of the individuals studied exhibited dyslipemia. CONCLUSIONS: The screening strategy allows one to diagnose a high percentage (almost 50%) of individuals suffering hypercholesterolemia in families with a child previously diagnosed of this pathology. Moreover, in these families there is a high degree of familiar aggregation of dyslipemia.     

Chances of cure are not compromised with sphincter-saving procedures for cancer of the lower third of the rectum

BACKGROUND: The goal of this study was to compare patterns of recurrence and long-term outcome after sphincter-saving procedures (SSPs) and abdominoperineal resection (APR) in patients with tumors located in the lower third of the rectum. METHODS: We reviewed the charts of 1001 patients operated on for primary rectal adenocarcinoma between 1980 and 1991. All patients with tumors located between 5 and 7 cm from the anal verge and treated with curative intent were included. RESULTS: Of the 261 patients who met our criteria, 162 had undergone SSP and 99 had undergone APR. The local recurrence rates for SSP and APR were 8% and 11%, respectively (p = 0.41), and the distant metastases rates were 23% and 28%, respectively (p = 0.35). Recurrence and distant metastases rates for SSP and APR, respectively, did not differ by TNM classification: state I, 10% versus 9% (p = 0.9); stage II, 25% versus 43% (p = 0.13); and stage III, 56% versus 57% (p = 0.92). Five-year disease-free survival rates for SSP and APR patients were 70.5% and 62.3%, respectively (p = 0.2). CONCLUSIONS: Tumors in the lower third of the rectum can be treated with sphincter-saving procedures without compromising the chance of cure.     

The role of urodynamics in the evaluation of voiding dysfunction in men after cerebrovascular accident

PURPOSE: The etiology of voiding dysfunction was determined in men after a cerebrovascular accident who were at risk for obstructive uropathy to evaluate whether the cause of voiding dysfunction could be predicted by the type (obstructive or irritative) or onset of symptoms. MATERIALS AND METHODS: We evaluated 38 men with complaints of voiding dysfunction following a cerebrovascular accident. All patients were of the age when bladder outlet obstruction secondary to benign prostatic hyperplasia would otherwise be prevalent. After a comprehensive history and physical examination, all patients underwent multichannel urodynamic studies at a medium fill rate (20 to 50 ml. per minute). Findings were classified by the Abrams-Griffiths nomogram as obstruction, no obstruction or equivocal. RESULTS: Mean patient age was 70 years (range 54 to 87). Patients were grouped according to the presenting voiding complaints (purely irritative in 42%, purely obstructive in 34% or mixed in 24%). In 34 patients (89%) the onset of symptoms paralleled the occurrence of the cerebrovascular accident. Detrusor hyperreflexia was noted in 82% of the patients. There was no statistically significant difference in the occurrence of detrusor hyperreflexia among the 3 symptom groups (Fisher's exact test). Pressure-flow analysis clearly showed obstruction in 24 patients (63%), no obstruction in 9 (24%) and equivocal results in 5 (13%) according to the nomogram. There was no statistically significant difference in the incidence of obstruction among the 3 symptom groups (Fisher's exact test). CONCLUSIONS: Presenting symptoms did not predict the urodynamic findings of bladder outlet obstruction or detrusor hyperreflexia. The significant incidence of onset of symptoms after stroke suggests that the cerebrovascular accident induced voiding dysfunction in the face of preexisting bladder outlet obstruction may exacerbate the symptoms of the latter condition or vice versa.     

Drinking patterns as predictors of alcohol withdrawal reactions in DBA/2J mice

Individually housed DBA/2J mice were fed a liquid diet in which ethanol supplied 33% of the calories. The level of physical dependence that developed was estimated by scoring convulsions, elicited by handling the mice, after discontinuing the alcohol diet. The severity of the withdrawal reaction increased progressively with duration (5-12 days) of alcohol administration. A 2-day period on the diet produced no withdrawal reaction. Pretreatment of the mice with alcohol in their drinking water slightly increased the subsequent intake of the liquid diet. "Effective" alcohol intake was defined as uninterrupted alcohol consumption above 10 g/kg/day. Withdrawal scores correlated better with effective intake than with total intake under a variety of conditions. We interpret this to mean that brief interruptions in drinking (1 day) may allow the accrued physical dependence to disappear. On the basis of their effective alcohol intake, mice could be assigned to nondependent, moderately dependent or severely dependent groups for further study of the nature of physical dependence.     

Pantoprazole does not interact with the pharmacokinetics of carbamazepine

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.