Relationship between maternal glycaemia and birth weight in glucose-tolerant women from different ethnic groups in New Zealand.

AIM: The aim of this study was to compare the population attributable fraction(PAF) for a large baby (> or =4 kg) due to glycaemia, weight and smoking in glucose-tolerant women from different ethnic groups. METHODS: A retrospective review of screening for gestational diabetes (GDM)and associated birth weight was undertaken in New Zealand European (n= 529), Maori (n= 540) and Pacific (n= 916) women. The proportion with a large baby was compared by 1-h post 50-g glucose challenge test tertile and maternal weight tertile. RESULTS: Large babies were more common from Pacific and European than Maori women (24.3%, 18.8%, 8.9%, respectively; P<0.001). Birth weight increased significantly with increasing glucose among Pacific women (P<0.001) even after adjusting for maternal weight and other confounders. The risk of having a large baby was 2.56 (1.82-3.60)-fold greater in women in the highest maternal weight tertile (> or =84 kg), with a significantly greater PAF in Pacific women(27.2%, 12.9%, 16.4%, respectively; P<0.001). The odds ratio (OR) of having a large baby increased with even mildly elevated maternal 1-h glucose concentrations [OR for 5.6-6.2 mmol/l: 1.54 (1.11-2.14); for > or =6.3 mmol/l: 2.06 (1.50-2.82)], with no ethnic differences in PAF (11.1-11.8%, 16.7-18.7%, respectively). Smoking and being Maori were associated with smaller babies. CONCLUSIONS: Increased maternal weight and glycaemia are associated with a greater proportion of large babies among glucose-tolerant women. Growth of Pacific babies may be more sensitive to a higher maternal glucose when the mother is obese.     

Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time intervals from 0.5 to 96 hours in cornea, sclera, and conjunctiva and at six time intervals from 0.5 to 12 hours in aqueous. Two peak concentrations were noted at approximately one and eight hours, with measurable levels present at 96 hours. This study demonstrates the ability of this liposomal delivery system to prolong levels of 5-fluorouracial in normal pigmented rabbits.     

Epithelial secretion of vinblastine by human intestinal adenocarcinoma cell (HCT-8 and T84) layers expressing P-glycoprotein.

P-glycoprotein expression was demonstrated in two human intestinal adenocarcinoma cell-lines (HCT-8, ileocaecal and T84, colonic) by immunoprecipitation of a 170-180 kDa protein with monoclonal antibody JSB-1. Both HCT-8 and T84 formed functional epithelial cell layers of high transepithelial electrical resistance (greater than 700 omega.cm2) when grown on permeable matrices. These epithelial layers demonstrated vectorial secretion (net vinblastine fluxes in the basal-to-apical direction of 0.135 and 0.452 pmol h-1 cm-2 in HCT-8 and T84 cell layers, respectively, from bathing solutions containing 10 nM vinblastine). These vectorial vinblastine secretions were sensitive to inhibition by verapamil. Passive transepithelial vinblastine permeation was limited by the presence of intercellular (tight) junctions, as demonstrated by the high transepithelial electrical resistance, and verapamil increased this passive vinblastine permeation concomitant with a reduction in the electrical resistance. Cellular vinblastine loading was significantly greater from the basal side, and this was also susceptible to inhibition by basal verapamil. The demonstration of vectorial transport of vinblastine in human intestinal colonic adenocarcinoma cell layers is direct evidence in favour of the hypothesis that the function of mdr1 in epithelial from the gastrointestinal tract is to promote detoxification by a process of epithelial secretion. This study also highlights that cellular vinblastine accumulation depends not only upon P-glycoprotein function, but also upon differential apparent membrane permeabilities and the presence of intercellular (tight) junctions that may restrict drug permeation and cellular accumulation to apical or basal membrane domains.     

The role of intestinal flora on the interactions between nonparenchymal cells and hepatocytes in coculture

Kupffer cells are exposed directly to a number of factors in the portal circulation that can modify or regulate their responses to septic stimuli. The gut represents a potential source of a number of these factors including endotoxin, lymphokines, and prostaglandins. We examined Kupffer cells from germfree rats and germfree rats exposed to endotoxin or bacteria via their GI tracts to determine the importance of the intestinal flora in maintaining or modulating Kupffer cell responses. Kupffer cells from germfree animals were reduced in numbers and failed to respond to LPS in Kupffer cell: hepatocyte coculture. When germfree rats were exposed to bacterial endotoxin or bacteria via the gastrointestinal tract their Kupffer cells increased in numbers to normal and the cells responded to LPS in culture. Intestinal overgrowth with Escherichia coli for 2 days activated the Kupffer cells and significantly increased Kupffer cell sensitivity to LPS. These data suggest that the environment of the gastrointestinal tract is important for normal Kupffer cell responses and that intestinal bacterial overgrowth can modify Kupffer cell responses to septic stimuli.     

Percutaneous transhepatic dilatation in the management of bile duct strictures

Despite improvements in surgical techniques, some complex bile duct strictures continue to present difficult management problems. Strictures recurring after previous biliary-enteric bypass, those associated with established biliary cirrhosis or coexistent malignancy, and those that follow hepatic resection may pose almost insuperable technical and physiological problems. Percutaneous transhepatic balloon dilatation will not solve all problems, but can help in some instances. Six patients are presented in whom this technique has been used in attempts to overcome particular problems. The strengths and weaknesses of the method are discussed.