Behaviour of glibenclamide on repeated administration to diabetic patients

Summary Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating deep compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.Glossary of symbols IR- immuno-reactive - GLI glibenclamide - IRI immuno-reactive insulin - GLU glucose - AK 1 values obtained with patient AK on the first day of treatment - AK 15 values obtained with patient AK on the 15th day of treatment - b serum level - b_max maximal serum level - t time after dose - t_max time of maximal serum level - G gastro-intestinal system - B central compartment (blood) - T peripheral compartment (tissue) - E excreta - M,N coefficients of the equation of a bi-exponential decay curve - µ, v exponents of the equation of a bi-exponential decay curve - e base of natural logarithms - K_BG K_EB K_TB K_BT first order rate constants (e. g. K_BG means: into B, from G) - K_BG first order rate constants - etc. not corrected for the volume of distribution     

Chronic calf pain in athletes due to sural nerve entrapment. A report of 18 cases

We retrospectively analyzed the charts of 13 athletes (18 limbs) who had sural nerve entrapment localized in the passage of the nerve through the superficial sural aponeurosis. There were 11 men and 2 women (average age, 43 years; range, 31 to 59). All patients reported chronic calf pain that was exacerbated during physical exertion. Delay to diagnosis averaged 9 months (range, 5 to 24). Tenderness in the calf was identified along the course of the sural nerve in all cases. In 10 patients (15 limbs) electrodiagnostic testing before surgery was positive. After failure of nonoperative treatment, surgery was conducted under local anesthesia. Neurolysis was performed by incising the superficial sural aponeurosis and the fibrous band in it through which the nerve passes. The results of the operation were evaluated in terms of residual symptoms, ability to return to the former sport, and degree of patient satisfaction. A final follow-up examination was performed an average of 14 months (range, 6 to 30) after the operation. The final result was excellent in 9 limbs (2 bilateral), good in 8 limbs (2 bilateral), and fair in 1 case. The differential diagnosis of sural nerve entrapment in athletes is discussed. Increase in sural muscle mass or development of local fibrous scar tissue compromised the sural nerve in its course through the unyielding and inextensible superficial sural aponeurosis.     

Elective laparoscopic colectomy for sigmoid diverticulitis. Prospective study of 56 cases

OBJECTIVE: The aim of this prospective study was to assess the feasibility and postoperative advantages of the laparoscopic-assisted elective colectomy for diverticular disease. PATIENTS AND METHODS: From january 1989 to december 1997, among the 114 patients electively operated on for diverticulitis, 56 patients were treated by laparoscopic approach. Evaluated parameters included: gender, age, weight, size, ASA score, operating time, duration of hospital stay, of analgesic treatment, and of postoperative ileus, morbidity and mortality rate. RESULTS: The study group consisted of 35 women and 21 men. Mean age was 59 years (34-81 years); 29 patients were ASA 1 and 27 ASA 2. Overall postoperative mortality rate was 0% and morbidity rate 16% (n = 9). There were no complications directly related to laparoscopic technique. The conversion rate was 14% (n = 8). Mean operating time was 300 min (200-600 min). Mean duration of postoperative ileus was 2.4 days. Mean duration of hospital stay was 9.4 days. CONCLUSION: This study demonstrates the feasibility of elective laparoscopic-assisted colonic resection for diverticular disease in more than 80% of cases with a postoperative morbidity and mortality rate comparable to those of conventional surgery.     

Vascular cerebral thrombosis during pregnancy and post-partum

Pregnancy and puerperium are associated with a number of cerebrovascular conditions that may result in stroke. Those include cerebral venous thrombosis and cerebral arteries occlusions. Comparing stroke rates during pregnancy with those of non-pregnant women showed only a marginal excess risk during pregnancy and puerperium. Strokes due to cerebral venous thrombosis represent 10-20 per 100 000 deliveries in western countries. The cause of intracranial venous thrombosis is usually unknown. However, better understanding of abnormalities in coagulation leading to intravascular clotting in the early puerperium is resulting in better understanding of this disease. Nevertheless, an etiological work up should be performed, particularly when the thrombosis occurs during pregnancy. Its clinical manifestations often include focal neurological signs, seizures and headache. Alterations in consciousness occur as intracranial pressure increases. Arterial occlusions account for about 60% to 80% of cerebral ischemic lesions. A probable cause of ischemic stroke is diagnosed on the basis of clinical, biological and radiological data. Eclampsia is the main cause of nonhemorrhagic stroke. A search for rare causes of stroke linked to pregnancy such as post-partum cardiomyopathy, paradoxical embolism, choriocarcinoma, cardiac and hematological disorders may be appropriate.     

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension

Dihydropyridine calcium‐channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67‐year‐old hypertensive female treated with a four‐drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high‐performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.     

Frontoparietal connectivity in substance-naïve youth with and without a family history of alcoholism

Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions (ps < .05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry (ps > .34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders.     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?