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.     

Enantioselective Pharmacokinetics of Homochlorcyclizine: Disposition of (+)- and (–)-Homochlorcyclizine after Intravenous and Oral Administration of Racemic Homochlorcyclizine to Rats

Abstract— Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg^?1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg^?1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (–)-isomer. The AUC_0-x values of the (+)- and (–)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (–)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.     

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.     

Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunode?ciency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.     

Oral Sustained-release Cisplatin Preparation for Rats and Mice

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II); cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin–ethylcellulose–stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg^?1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg^?1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 ± 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 ± 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL^?1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10–16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL^?1 in mice serum in which the total cisplatin concentration was 0.30 mg mL^?1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.     

Intestinal Brush-border Membrane Transport of Monocarboxylic Acids Mediated by Proton-coupled Transport and Anion Antiport Mechanisms

Intestinal brush-border membrane transport of monocarboxylic acids was investigated by using rabbit intestinal brush-border membrane vesicles (BBMVs) and isolated intestinal tissues mounted on Ussing-type chambers. [³H]Mevalonic acid uptake by BBMVs showed an overshoot phenomenon in the presence of an inwardly directed proton gradient, but not in the presence of an inwardly directed sodium gradient or an outwardly directed HCO₃^? or chloride gradient. Initial uptake of mevalonic acid was saturable in the presence of a proton gradient. Uptake of [³H]mevalonic acid was inhibited by various monocarboxylic acids, including acetic acid, benzoic acid, lactic acid, nicotinic acid, pravastatin, salicylic acid and valproic acid, but not by dicarboxylic acid or amino acids. Acetic acid, which is transported by both anion antiport and proton-coupled transport systems, induced serosal bicarbonate-dependent alkalinization in the mucosal-side bathing solution of rabbit jejunal tissues, when examined in Ussing-type chambers. Pravastatin, which is a structural analogue of mevalonic acid and is absorbed via proton-coupled transport like mevalonic acid, did not. The result demonstrates that acetic acid is transported by the bicarbonate-dependent anion antiport system, whereas pravastatin is not. So, it is suggested that monocarboxylic acids are transported by at least two independent transporters, namely, a proton-coupled transporter for most monocarboxylic acids, including mevalonic acid, pravastatin and acetic acid, and an anion antiporter for acetic acid, but not for mevalonic acid or pravastatin. Activation of anion antiporter can induce HCO₃^? secretion in intact intestine.