Effects of therapeutic doses of lactulose vs. polyethylene glycol on isotopic colonic transit

Background Lactulose and polyethylene glycol are osmotic agents used to treat idiopathic chronic constipation. Aim To compare the effects of low doses of lactulose and PEG 4000 on transit time measured by scintigraphy in normal subjects. Methods For 5 days, 10 healthy subjects received either 10 g b.d. of lactulose or PEG 4000 in a randomized, double‐blind, crossover study. On the evening of day 4, they took a capsule containing Amberlite resin pellets labelled with ¹¹¹In. On day 5, after a 1000 kcal test meal labelled with 99Tcm, gastric, small bowel and colonic transits were measured. Results Gastric emptying and small bowel transit time were not different. Ascending colon emptying curve was significantly accelerated with lactulose in comparison with polyethylene glycol (P = 0.001) and, respectively, 50 ± 18% vs. 35 ± 18% of the radioactivity had left the ascending colon at the end of the study (P < 0.05). The descending colon filling curves, variations in the geometric centre and numbers of scintigraphic movements were not different. Conclusions In healthy subjects, in comparison to PEG 4000, usual therapeutic doses of lactulose significantly accelerate ascending colon emptying. This result supports a stimulating motor effect of colonic fermentation of lactulose.     

A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in glomeruli, and an increased concentration of plasma apolipoprotein (apo) E. Previous studies have shown that a genetic disorder of apo E may be associated with the genesis of this disease. METHODS: An apo E mutation was analyzed in a 57-year-old Japanese male with LPG and systemic atherosclerotic complications. Apo E phenotypes were analyzed by isoelectric focusing and immunoblotting. Apo E genotypes were determined by restriction fragment isotyping with HhaI. Polymerase chain reaction (PCR) products of apo E coding region exons 3 and 4 were cloned into pT7Blue-T-vector and were sequenced. RESULTS: A novel apo E mutation was identified in this patient and his family. There was a discrepancy between an apo E phenotype (E1/3) and genotype (E3/3). Sequence analysis showed a 54 bp deletion in exon 4 of the apo E gene, causing the 18-amino acid deletion (Gln 156-Gly 173-->0). This deletion mutation was further confirmed by the detection of a short fragment of PCR-amplified DNA using polyacrylamide gel electrophoresis. The patient was a heterozygote with apo E1, and this mutation was determined to be the structural basis for the apo E1 phenotype. One of two daughters was a heterozygous carrier of apo E1, although she did not have proteinuria or atherosclerotic diseases. CONCLUSIONS: Apo E1 (Gln 156-Gly 173-->0) is a novel mutation of apo E that may be etiologically related to LPG and to the development of atherosclerosis. The result of this family study suggests that the occurrence of LPG may involve other genetic or environmental factors.     

Double-blind,placebo-controlled comparison of zolpidem,triazolam, and temazepam in elderly patients with insomnia

Sleep disturbances and need for hypnotics are disproportionately greater in the elderly compared to younger adults. The present study provides a placebo-controlled subjective hypnotic efficacy of zolpidem, triazolam, and temazepam in elderly insomniacs. After a single-blind placebo screening week (DSM-III-R criteria), 335 elderly insomniacs (ages 60 to 85) were randomized to 28 days of double-blind treatment with zolpidem 5 mg, triazolam 0.125 mg, temazepam 15 mg, or placebo, followed by a 4-day single-blind, placebo withdrawal period. The primary efficacy parameters were self-reported sleep latency (SSL) and self-reported total sleep duration (SSD); they were measured by responses on daily Morning Questionnaires. SSL values were compared by Cox proportional hazards regression technique. SSD values were compared by ANOVA. Compared to placebo, zolpidem and temazepam produced significantly shorter SSL over the 4 treatment weeks, but triazolam did not. In the zolpidem group, SSL was significantly shorter than in the placebo group at all four treatment weeks; in the temazepam group, SSL was significantly shorter than in the placebo group at weeks 1, 3, and 4. SSD was increased above baseline levels in all groups. No tolerance to the subjective effects or rebound above baseline levels occurred in any of the treatment groups. Overall, the drugs were well tolerated. No difference was found among the placebo and treatment groups in overall adverse event incidence rates. However, compared with zolpidem and placebo, temazepam produced significantly higher incidences of drowsiness and fatigue, and triazolam produced a significantly higher incidence of nervousness than zolpidem. Drug Dev. Res. 40:230–238, 1997. © 1997 Wiley-Liss, Inc.     

Extended‐release antiepileptic drugs: A comparison of pharmacokinetic parameters relative to original immediate‐release formulations

Many antiepileptic drugs (AEDs) have short half‐lives with large fluctuations in peak‐to‐trough plasma concentrations. Consequences of these pharmacokinetic (PK) properties may include adverse events (AEs) and breakthrough seizures, potentially leading to poor adherence. To address these challenges, newer formulations of these AEDs have been developed using unique extended‐release (ER) technologies. These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence. Available ER formulations have the potential to minimize the spikes in maximum plasma concentrations (C_max) at steady‐state that often contribute to AEs during treatment with immediate‐release (IR) products. In so doing, tolerability advantages may lead to increased AED effectiveness by improving adherence and allowing higher doses if clinically indicated. Direct PK comparison studies of IR and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, oxcarbazepine, levetiracetam, and phenytoin) have found that dose‐normalized ER formulations may or may not be bioequivalent to their IR counterparts, but most ER formulations have a lower fluctuation index ([C_max–C_min]/C_avg) compared with the IR versions. This results in flatter concentration‐time plots. Not all ER preparations improve the various PK parameters to the same extent, and PK nuances may impact the effectiveness, tolerability, and adherence rates of various ER formulations.     

Primary scarring alopecia: A retrospective study of 89 patients in Taiwan

Primary scarring alopecia (PSA) is caused by irreversible damage to the hair epithelial stem cells that reside in hair follicles. There is limited published work regarding PSA amongst the Asian population. The aim of this study was to evaluate the clinical features and to characterize the subtypes of PSA in southern Taiwan. In this retrospective case series, we reviewed 89 patients with pathology‐confirmed PSA. The data was collected from National Cheng Kung University Hospital between 1988 through 2016. The clinical and histological data were reviewed, and the patients were characterized into different subtypes of PSA based on the clinical features and histological findings. We noted seven different subtypes of PSA. The most common type was dissecting cellulitis (DC) (30.3%), followed by lichen planopilaris (LPP) (23.5%), central centrifugal cicatricial alopecia (CCCA) (12.4%) and acne keloidalis nuchae (AKN) (12.4%). The other subtypes include folliculitis decalvans (FD), discoid lupus erythematosus (DLE) and pseudopelade of Brocq (PPB). Interestingly, FD, DC and AKN were more common in males, while CCCA, LPP, DLE and PPB had a female predominance. The mean age of patients with DLE, DC and AKN were younger, while patients with CCCA, LPP, PPB and FD tend to be older. The pattern of hair loss was more likely to be unifocal‐ragged border in CCCA and DLE, multifocal‐interconnected in LPP and FD, and multifocal‐separated in DC. The pathogenesis of PSA may be influenced by sex, age and genetic background. It is important to identify the hair loss pattern to differentiate the subtypes of PSA.