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.     

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.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

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.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system

Recently, in-vitro maturation (IVM) of immature human oocytes recovered from non-stimulated follicles has been applied in the treatment of infertility. However, in previous reports, very few embryos cultured in conventional medium have reached the expanded blastocyst stage following in-vitro maturation and fertilization (IVM/IVF). The objective of this study was to investigate whether the developmental competence of human embryos following IVM/IVF could be enhanced by the use of a human ampullary cell co-culture system. Immature human oocytes were aspirated from small follicles at Caesarean section and then cultured in medium containing human menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes were randomly cultured either in conventional culture medium alone or in the co-culture system. Of 48 embryos cultured in conventional medium alone, all arrested at the 2-16- cell stage on day 3 after insemination. Of 46 embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at the 2-16-cell stage. Six embryos (13%) developed to the morula stage. Fourteen embryos (30.4%) developed to expanded blastocysts and two blastocysts were hatching on day 7 after insemination. We conclude that co-culture significantly enhances the development of blastocysts in embryos resulting from IVM/IVF.      

Comparison of MICs of ceftiofur and other antimicrobial agents against bacterial pathogens of swine from the United States, Canada, and Denmark.

The MICs of ceftiofur and other antimicrobial agents, tested for comparison, for 515 bacterial isolates of pigs from the United States, Canada, and Denmark with various diseases were compared. The organisms tested included Actinobacillus pleuropneumoniae, Escherichia coli, Pasteurella multocida, Salmonella choleraesuis, Salmonella typhimurium, Streptococcus suis, Streptococcus dysgalactiae subsp. equisimilis, Streptococcus equi subsp. equi, and Streptococcus equi subsp. zooepidemicus. In addition to ceftiofur, the following antimicrobial agents or combinations were tested: enrofloxacin, ampicillin, sulfamethazine, trimethoprim-sulfadiazine (1:19), erythromycin, lincomycin, spectinomycin, lincomycin-spectinomycin (1:8), tilmicosin, and tetracycline. Tilmicosin was only tested against the U.S. isolates. Overall, ceftiofur and enrofloxacin were the most active antimicrobial agents tested against all isolates, with MICs inhibiting 90% of isolates tested (MIC90s) of < or = 2.0 and < or = 1.0 microgram/ml, respectively. Erythromycin, sulfamethazine, spectinomycin, and lincomycin demonstrated limited activity against all of the organisms tested, with MIC90s of > or = 8.0, > or = 256.0, > or = 32.0, and > or = 16.0 micrograms/ml, respectively. Trimethoprim-sulfadiazine was active against isolates of A. pleuropneumoniae, S. choleraesuis, S. typhimurium, P. multocida, S. equi, and S. suis (MIC90s, < or = 0.5 microgram/ml) but was less active against the E. coli strains tested (MIC90, > 16.0 micrograms/ml). Ampicillin was active against the P. multocida, S. suis, and S. equi isolates tested (MIC90s, 0.5, 0.06, and 0.06 micrograms/ml, respectively) and was moderately active against S. typhimurium (MIC90s, 2.0 micrograms/ml). However, this antimicrobial agent was much less active when it was tested against A. pleuropneumoniae, S. cholerae-suis, and E. coli (MIC90s, 16.0, > 32.0, and 32.0 micrograms/ml, respectively). Against the U.S. isolates of A. pleuropneumoniae and P. multocida, tilmicosin was moderately active (MIC90s, 4.0 and 8.0 micrograms/ml, respectively). However, this compound was not active against the remaining U.S. isolates (MIC90s, > 64.0 micrograms/ml). Differences in the MICs from one country to another were not detected with enrofloxacin, ceftiofur, or lincomycin for the strains tested, but variations in the MICs of the remaining antimicrobial agents were observed.