Relationships between gastric emptying, intragastric meal distribution and blood glucose concentrations in diabetes mellitus

The aim of this study was to evaluate the prevalence of disordered intragastric meal distribution and the relationships between gastric emptying, intragastric distribution, glycemic control and gastrointestinal symptoms in diabetes mellitus. METHODS: Eighty-six patients with diabetes mellitus had measurements of gastric emptying and intragastric distribution of a radioisotopically labeled solid/liquid meal (100 g beef and 150 ml 10% dextrose), glycemic control (plasma glucose concentrations), upper gastrointestinal symptoms (questionnaire) and autonomic nerve function (cardiovascular reflexes). Results were compared to those obtained in 20 normal volunteers. RESULTS: Solid and liquid gastric emptying were delayed in the diabetic patients and correlated weakly. Intragastric meal distribution was also often abnormal, with increased retention of both solid and liquid in the proximal stomach and increased retention of solid but not liquid in the distal stomach. In all patients with increased retention of solid in the proximal stomach, emptying from the total stomach was delayed. Gastric emptying of liquid was slower in those subjects who had a mean plasma glucose > 15 mmol/liter during the gastric emptying measurement, when compared to the remainder of the group. CONCLUSION: In patients with diabetes mellitus, there is poor relationship between solid and liquid gastric emptying and intragastric meal distribution is frequently abnormal. Interpretation of the results of gastric emptying measurements should consider meal composition and plasma glucose concentrations.     

Randomized controlled trial of open and closed haemorrhoidectomy

BACKGROUND: This study was a prospective randomized comparison of healing following open and closed haemorrhoidectomy. METHODS: Sixty-seven consecutive patients (mean(s.e.m.) age 45(1.7) years; 35 men, 32 women) with three prolapsed piles were randomized to open haemorrhoidectomy (n = 34) or closed haemorrhoidectomy (n = 33). RESULTS: Mean(s.e.m.) follow-up was 8.7(0.2) months. There were no differences in the linear analogue pain scores, analgesic requirements and length of hospitalization after open haemorrhoidectomy and closed haemorrhoidectomy. Complete wound healing took significantly longer after closed haemorrhoidectomy (mean(s.e.m.) 6.9(0.7) weeks) compared with open haemorrhoidectomy (4.9(0.4)weeks) (P < 0.05). This was related to wound dehiscence in eight patients. Complication rates, however, were similar except for prolonged serous discharge from unhealed wounds. The anal manometry findings after both procedures were equivalent. CONCLUSION: Open haemorrhoidectomy leads to faster and more reliable wound healing, although this did not result in less pain or fewer complications.     

ACTH-producing carcinoma of the pituitary with haematogenic metastases

Two laboratories equipped with CAS 200 (Becton Dickinson Image Cytometry Systems, San Jose, CA) instruments participated in this study of variability of DNA analysis of bladder tumor specimens. Formalin fixed paraffin embedded specimens were disaggregated and centrifuged onto microscope slides from ten bladder tumor specimens and two specimens of normal urothelium. Sources of variability considered were Specimen, Slide, Run, Laboratory, and Error. Slides were systematically scanned and 200 cells measured followed by the operator selecting 100 nuclei with abnormal morphology. DNA index (DI) and hyperdiploid fraction (HDF) were calculated from the DNA frequency distributions. For systematic sampling, 92% of the variability was due to Specimen indicating that differences in HDF values between specimens reflect biological differences. With selective sampling, only 67% of the variability in HDF is due to Specimen differences. Other factors, Laboratory, Error, and Laboratory x Specimen interaction each accounted for approximately 10% of the variability. Similarly variability of DI with selective sampling was also higher, and less specimen dependent than systematic sampling. It is important that sampling schemes and selection criteria be carefully documented in order to control variability. Enriched (or selective) sampling for abnormal cells has the potential to increase sensitivity but specimen classification based on these measurements must depend on determination of the frequency of such cells in the total population.     

Value of determining serum cholesterol levels in patients with coronary heart disease]

Cholesterol synthesis (HMG-CoA reductase) inhibitors have proven their value in preventing cardiovascular events, especially in patients with manifest coronary heart disease. Besides cholesterol lowering a number of effects have been described which may contribute to the beneficial influence of these agents on the process of atherosclerosis. Measurement of serum lipids is still necessary for various reasons, namely, to know the degree of elevation in serum cholesterol and specific disturbances in lipid metabolism, the extent to which serum lipids must be lowered and the compliance with cholesterol lowering therapy.     

Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice

Recent studies have suggested the use of lipoproteins as an adjuvant treatment of lethal gram-negative infections. However, other important microorganisms for the etiology of sepsis, such as Candida species, grow better in lipid-rich environments. We investigated the effect of hyperlipoproteinemia on systemic candidiasis in low-density-lipoprotein-receptor-deficient (LDLR-/-) mice, in which the loss of the receptor results in a seven- to ninefold-higher plasma LDL level than that in their wild-type littermates (C57BL/6J). LDLR-/- mice died earlier, and the outgrowth of Candida albicans in the kidneys and livers of LDLR-/- mice was significantly higher compared with that of controls. After infection, circulating cytokine concentrations were significantly higher in LDLR-/- mice. In vitro, C. albicans grew better in plasma samples of LDLR-/- mice than in control plasma samples and peritoneal macrophages of LDLR-/- mice challenged with heat-killed C. albicans produced more cytokines than did those of controls. This latter phenomenon was probably due to increased binding of yeast cells to macrophages of LDLR-/- mice. These data suggest that hyperlipoproteinemia is deleterious in systemic candidiasis.     

BIACORE analysis of histidine-tagged proteins using a chelating NTA sensor chip

While BIACORE instruments are routinely used for kinetic measurements and for the determination of binding constants, the immobilization of a ligand onto the sensor chip surface has to be individually optimized for every system. We show here that the histidine (His) tag, routinely used in protein purification and in detection is an ideal tag for immobilization, despite the intrinsically low affinity between an immobilized metal ion and the His tag. This is due to strong rebinding effects caused by the high surface density of immobilized Ni2+-nitrilotriacetic acid (NTA) on the chips used here. The immobilization of the ligand can be adjusted to a low level using the same chip, such that mass transport limitation and rebinding of the analyte to the immobilized ligand is minimal. Nine different proteins with different numbers of His tags were tested for stable binding to the Ni2+-NTA surface. Most proteins with one His tag dissociate very rapidly from the Ni2+-NTA surface, and the KD for the interaction between His tag and Ni2+-NTA was estimated to about 10(-6) m at neutral pH. In contrast, two His tags are usually found to be sufficient for stable binding. The kinetics of the chaperonin system of Escherichia coli GroEL and GroES were analyzed as a model using this system and found to be very similar to those obtained with covalently immobilized ligands. The sensor chip can be reused many times, because of the powerful regeneration methods. The ligand can be freshly immobilized after each cycle, thus eliminating potential denaturation upon regeneration as a source of error.     

Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine

Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60 degrees head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of treatment with L-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.