Inhibitory effect of nifedipine on cholecystokinin-induced gallbladder contraction in man

A prospective study was performed on seven male and eight female patients with normal hepatobiliary findings to investigate the effect of 20 mg nifedipine on cholecystokinin-induced gallbladder contraction. Each patient received 1 IDU (Ivy dog unit) cholecystokinin per kg body weight intravenously on two consecutive days, with additional administration of 20 mg nifedipine sublingually on the second day. Gallbladder volumes were assessed by ultrasonography over a period of 25 minutes. Cholecystokinin induced a maximal reduction in the mean initial volume of 56.8 +/- 3.6%. After nifedipine, this volume change was significantly reduced to 30.9 +/- 5.1% (p less than 0.001). Thus our data suggest for the first time that the calcium-channel-blocking agent nifedipine can have an effect on human gallbladder kinetics.     

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.     

Transthoracic esophagectomy and lobectomy performed in a patient with synchronous lung cancer and combined esophageal cancer and esophageal leiomyosarcoma.

We report a pitfall deriving from the assumption of metastatic disease based upon seemingly identical histology in a pulmonary lesion and in the esophagus. In a 60-year-old patient, cT1 esophageal squamous cell carcinoma was found. One of the two pulmonary nodules was histologically diagnosed as metastasis. When esophageal perforation occurred during palliative therapy, esophagectomy became necessary together with the right lower lobectomy for the removal of the remaining pulmonary lesion. Definitive histology showed pT1N0 cancer of the esophagus, primary esophageal sarcoma and pT4N0 bronchogenic carcinoma. The other pulmonary lesion was re-evaluated and defined as intralobar M1 of bronchogenic carcinoma.     

Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Amyloid fibril formation by human stefin B: influence of pH and TFE on fibril growth and morphology.

As shown before, human stefin B (cystatin B) populates two partly unfolded species, a native-like state at pH 4.8 and a structured molten globule state at pH 3.3 (high ionic strength), from each of which amyloid fibrils grow. Here, we show that the fibrils obtained at pH 3.3 differ from those at pH 4.8 and that those obtained at pH 3.3 (protofibrils) do not transform readily to mature fibrils. In addition we show that amorphous aggregates are also a source of fibrils. The kinetics of amyloid fibril formation at different trifluoroethanol (TFE) concentrations were measured. TFE accelerates fibril growth at predenaturational concentrations of the alcohol. At concentrations higher than 10%, the fibrillar yield decreases proportionately as the population of an all alpha-helical, denatured form of the protein increases. At an optimum TFE concentration, the lag and the growth phases are observed, similarly to some other amyloidogenic proteins. Morphology of the protein species at the beginning and the end of the reactions was observed using atomic force microscopy and transmission electron microscopy. Final fibril morphologies differ depending on solvent conditions.     

Alterations of lens metabolism with experimentally induced cataract in rats

Rat lenses with experimentally induced cataract (either by naphthalene or by streptozotocin) were analyzed biochemically. Both noxae had some effects in common. Water-soluble protein and aldose reductase activity decreased, and glucose-6-phosphate dehydrogenase, phosphofructokinase and glutathione reductase activity increased. A specific effect of streptozotocin was the rise in glucose, fructose and sorbitol. A specific effect of naphthalene was increased amounts of water-insoluble protein.     

In vitro effects of fungi isolated from equine hooves on primary human keratinocytes.

The effects of two dermatophytes (Microsporum gypseum and Trichophyton mentagrophytes) and four moulds (Scopulariopsis brevicaulis, Alternaria alternata, Geotrichum candidum and Penicillium spp.) on living keratinocyte cultures were examined in vitro using primary human keratinocytes. Rates of apoptosis of infected cells were determined using a colorimetric TUNEL system which detects the characteristic nuclear DNA fragmentation of apoptotic cells. The cytotoxicity of the individual fungi was tested by quantitatively measuring cytosolic enzyme lactate dehydrogenase, released upon cell lysis, in culture supernatants. Additionally, the cell structures within the infected keratinocytes in cultures were examined by scanning electron microscopy. All of the fungi exhibited high cytotoxicity, whereas the development of only the two dermatophytes and the mould Scopulariopsis brevicaulis resulted in distinctly increased apoptosis. Electron microscopy showed that all fungi studied caused similar alterations in the cell structure, with Microsporum gypseum being the most harmful. Increasing loss of cell adhesion as a consequence of a decreasing number of reticulating cell appendices and a reduced cell plasticity were the most evident alterations.