Inhibition of Nifedipine Metabolism in Dogs by Erythromycin: Difference between the Gut Wall and the Liver

The purpose of this study was to evaluate possible interaction of nifedipine with erythromycin or rokitamycin in the intestinal mucosa. Male beagle dogs were orally administered nifedipine (10 mg), with or without oral pre-medication with erythromycin (300 mg), and 300 mg erythromycin or rokitamycin twice a day for 3 days. The experiments were of randomized cross-over design with a two-week wash-out period between dosing regimens. Erythromycin pre-medication for 3 days resulted in a significant increase in the area under the serum nifedipine concentration-time curve (AUC), whereas the curve for one nifedipine metabolite (M-2) decreased significantly. When the effects of erythromycin on the metabolism of nifedipine were studied using dog liver microsomes it was found that erythromycin significantly inhibited formation of M-2 but not of the metabolite M-1. These results indicate that formation of M-2 from M-1 in the liver might be reduced by erythromycin premedication. To avoid possible metabolism in the gut, the dogs were then administered 8 mg nifedipine into the peritoneal cavity, with or without multiple dose pre-treatment with erythromycin for 3 days. After intraperitoneal administration of nifedipine, the maximum concentration (C_max) of nifedipine increased significantly. After pre-administration of erythromycin the relative bioavailability of nifedipine after oral administration was increased compared with injection into the peritoneal cavity. In-vitro study using rat intestinal microsomes and the in-vivo rat intestinal loop technique also showed that pre-administration of erythromycin inhibits nifedipine metabolism in the small intestine.     

Enhancement of J–ST-Segment Elevation by the Glucose and Insulin Test in Brugada Syndrome

NOGAMI, A., et al. : Enhancement of J–ST-Segment Elevation by the Glucose and Insulin Test in Brugada Syndrome. The effects of glucose and insulin on J–ST-segment elevation were evaluated in seven men   (mean age 45 ± 10 years)   with Brugada syndrome. Six patients had been reanimated from VF and one patient had experienced syncope. The effects of intravenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined. Pilsicainide significantly enhanced J-ST elevation in all patients and induced VF in 1 patient. A significant accentuation of the abnormal J-ST configuration was observed in all patients at a mean of   51 ± 40   minutes after glucose and insulin infusion. Changes in blood glucose and serum potassium concentration were   111 ± 158 mg/dL   and   −0.30 ± 0.48 mEq/L   , respectively. These changes were not directly related to the ECG changes. Glucose infusion without insulin caused a subtle increase in J-ST elevation. In conclusion, the administration of glucose and insulin safely unmasked or accentuation the J–ST-segment elevation in Brugada syndrome. Blood glucose and insulin concentrations may be factors modulating the circadian or day-to-day ECG variations in this syndrome. (PACE 2003; 26[Pt. II]:332–337)     

Prospective follow-up study of hepatitis C virus infection in patients undergoing maintenance haemodialysis: Comparison among haemodialysis units

A prospective follow-up study on hepatitis C virus (HCV) infection was conducted in seven haemodialysis units from April 1990 to March 1995. A total of 634 patients were undergoing maintenance haemodialysis in the seven units. Of those, 302 patients participated in the follow-up study; 179 were initially HCV antibody negative and 123 were initially positive. Nine of the 179 initially negative patients became positive for HCV antibody during the follow-up period. In accordance with the appearance of HCV antibody, indicating new infection of HCV, all nine of these patients were diagnosed with HCV viraemia. As no other routes were apparent, HCV infection in all nine patients was likely due to nosocomial transmission. Prevalence of HCV antibody at the start of follow up was significantly higher ( P < 0.001) in haemodialysis units A-C (37.9%) than in haemodialysis units D-G (17.0%). Incidence of new HCV infection was significantly higher ( P = 0.005) in the former units (2.2% per year) than in the latter (0.2% per year). Ten of the 123 patients who were initially positive for the HCV antibody exhibited a loss of reactivity during the follow-up period; of these 10 patients, nine were negative for HCV-RNA from the start of the study. In conclusion, the incidence of new HCV infection seen in patients undergoing haemodialysis suggests that their risk of acquiring HCV infection is directly related to the prevalence of HCV antibody positive patients being treated in the units.     

A case of Turner syndrome with schizophrenia: Genetic relationship between Turner syndrome and psychosis

Abstract An 82-year-old woman with Turner syndrome and schizophrenia, and her 46-year-old daughter with schizophrenia are described. 45X/46XX chromosomal mosaicism was identified in the peripheral leukocytes of the mother, who showed several Turner dysmorphisms and cavum septi pellucidum in the brain. She had a normal reproductive life-span. The daughter resembled the mother in terms of schizophrenic symptoms, but she did not show any signs of Turner dysmorphism or chromosomal abnormality. The phenotype-karyotype relationship of Turner syndrome and the genetic relationship with psychosis are discussed.     

Pyruvate dehydrogenase complex deficiency with multiple minor anomalies

Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency caused by a mutation in exon 11 of the pyruvate dehydrogenase (PDH) Elα gene is described. Her facial features were as follows: frontal bossing, upslanting palpebral fissures, a short upturned nose, a long philtrum and low set ears. These anomalies are characteristic not only of a malformation syndrome or chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency requires early treatment, metabolic disorders should be kept in mind in a patient with dysmorphic features. Further, she had multiple minor anomalies including bilateral inguinal herniae, an umbilical hernia and small hands and feet, which have not been described in previous reports.     

Inhibitory Effect of Laser Irradiation on Dermal Syngeneic Tumor Growth in Mice

Mice (C57BL/6) with established intradermal tumors (melanomaB-16 or glioma 203G1) and inbred Swiss mice (SWM/Ms) with establishedintradermal tumors (3-methylcholanthrene-induced sarcoma) weretreated by either surgical excision or laser irradiation. Laserirradiation is effective in preventing the growth of dermalmelanoma, and laser therapy may be more efficacious than surgicaltherapy for induction of a reaction against melanoma in mice. The results also suggest that determination of a suitable laserwavelength may be required to obtain a good therapeutic effecton each tumor.     

Performance monitoring during sleep inertia after a 1‐h daytime nap

Performance monitoring is an essential function involved in the correction of errors. Deterioration of this function may result in serious accidents. This function is reflected in two event‐related potential (ERP) components that occur after erroneous responses, specifically the error‐related negativity/error negativity (ERN/Ne) and error positivity (Pe). The ERN/Ne is thought to be associated with error detection, while the Pe is thought to reflect motivational significance or recognition of errors. Using these ERP components, some studies have shown that sleepiness resulting from extended wakefulness may cause a decline in error‐monitoring function. However, the effects of sleep inertia have not yet been explored. In this study, we examined the effects of sleep inertia immediately after a 1‐h daytime nap on error‐monitoring function as expressed through the ERN/Ne and Pe. Nine healthy young adults participated in two different experimental conditions (nap and rest). Participants performed the arrow‐orientation task before and immediately after a 1‐h nap or rest period. Immediately after the nap, participants reported an increased effort to perform the task and tended to estimate their performance as better, despite no objective difference in actual performance between the two conditions. ERN/Ne amplitude showed no difference between the conditions; however, the amplitude of the Pe was reduced following the nap. These results suggest that individuals can detect their own error responses, but the motivational significance ascribed to these errors might be diminished during the sleep inertia experienced after a 1‐h nap. This decline might lead to overestimation of their performance.     

DETECTION OF EARLY LESIONS OF "UNGUAL" MALIGNANT MELANOMA

Background. The nail area is commonly affected by malignant melanoma. The prognosis of malignant melanoma of the nail is poor, becuase at the time of diagnosis most lesions are in the advanced stage. Correct diagnosis of early lesions could improve the prognosis. Methods. For 3 years, all patients with nail pigmentation at the dermatology clinic were screened for five specific criteria for the diagnosis of early lesions of malignant melanoma. Histologic examination was performed on 10 of 29 lesions. Results. Five of the 29 lesions were advanced malignant melanoma, easily diagnosed clinically. Two of the remaining 24 lesions fulfilled most of our clinical criteria of early malignant melanoma of the nail apparatus; that is, they appeared as melanonychia striata during adulthood, were wide in breadth measuring 9 and 11 mm, and showed variegated shades of brown. Periungual pigmented macule (Hutchinson's sign) was observed in one of the two cases. Total resection of the lesions was performed, followed by skin grafting. Conclusions. Histologically, an increased number of atypical melanocytes, mainly arranged as solitary units, were observed only in the epithelia of the nail matrix and of the nail-bed, confirming that these lesions were “ungual” malignant melanoma in situ. Such an early lesion of malignant melanoma of the nail apparatus can be completely cured with conservative excision, and the phalanx of the affected digit can be preserved.