Comparison of the effects of pentagastrin and meal-stimulated gastrin on plasma calcitonin in normal man

We compared the effects of exogenous pentagastrin and meal-stimulated gastrin on plasma immunoreactive calcitonin (iCT) in various studies of 13 normal adult men. Bolus intravenous injection of pentagastrin (0.5 μg/kg) produced increases of iCT in 8 of 9 men. There was a linearly increasing response of iCT concentrations to increasing doses of pentagastrin (0.0625, 0.125, 0.25, and 0.5 μg/kg) and to achieved serum immunoreactive pentagastrin concentrations (r=0.72, P<0.01). To determine the effects of endogenous gastrin upon peripheral iCT concentrations, we measured serum immunoreactive gastrin (iG) and plasma iCT in four men at frequent intervals for 240 min after ingestion of low-(100 mg) and high- (400 mg) calcium meals. Serum iG increased in all subjects, with a peak at ～30 min. However, plasma iCT levels were unchanged from basal throughout the study. The increase of pentagastrin (0.3 pmol/ml) which caused a barely detectable increase of iCT was five-to tenfold greater than the mean maximal increases of gastrin after low- and high-calcium meals (0.04 and 0.06 pmol/ml, respectively). These results suggest that increases of plasma iCT concentrations after administration of pentagastrin in man reflect pharmacologic phenomena and that postprandial gastrin secretion may be insufficient to affect peripheral iCT concentrations.     

Cardiopulmonary exercise variables in diastolic versus systolic heart failure

The response to cardiopulmonary exercise (CPX) in patients with heart failure (HF) with normal left ventricular (LV) ejection fractions (EFs) is not well characterized. To determine if CPX testing could distinguish between patients with HF with normal EFs (>50%; i.e., diastolic HF) and those with decreased EFs (> or =50%; i.e., systolic HF), CPX responses were compared between 185 patients with systolic HF (79% men, mean age 62.6 +/- 10.9 years) and 43 with diastolic HF (54% men, mean age 67.4 +/- 9.8 years) enrolled in a phase II multicenter clinical trial. All patients were evaluated with echocardiography and a standardized CPX test as part of the trial. CPX variables, including oxygen uptake at peak exercise (peak VO(2)) and the slope of the ventilation/carbon dioxide production ratio (VE/VCO(2)), were determined and analyzed by core laboratory personnel. Echocardiographic measurements included the LV EF, the E/A ratio, filling time, cavity volumes, right ventricular function, and mitral regurgitation. Patients in the diastolic HF group tended to be older (p <0.08), with more women (p <0.006) and with greater body mass indexes (p <0.02), than those in the systolic HF group. There was no significant difference in the use of beta blockers or the incidence of coronary artery disease. Patients with diastolic HF had decreased E/A ratios (0.9 +/- 0.4 vs 1.4 +/- 1.1, p <0.02, diastolic HF vs systolic HF) and increased filling times (30.4 +/- 3.2 vs 26.5 +/- 4.7 ms, p <0.01, diastolic HF vs systolic HF). No significant differences in peak VO(2) (14.4 +/- 1.9 vs 15.6 +/- 3.2 ml/kg/min, p = 0.06, diastolic HF vs systolic HF) were observed. The VE/VCO(2) ratios for the 2 groups were abnormal and comparable (32 2 +/- 7.5 vs 34.0 +/- 8.3, p = 0.3, diastolic HF vs systolic HF). In conclusion, the CPX response in patients with diastolic HF and systolic HF is markedly abnormal and indistinguishable with regard to peak VO(2) and ventilation despite marked differences in the LV EF.     

Candida guilliermondii: biotechnological applications, perspectives for biological control, emerging clinical importance and recent advances in genetics

Candida guilliermondii (teleomorph Meyerozyma guilliermondii) is an ascomycetous species belonging to the Saccharomycotina CTG clade which has been studied over the last 40 years due to its biotechnological interest, biological control potential and clinical importance. Such a wide range of applications in various areas of fundamental and applied scientific research has progressively made C. guilliermondii an attractive model for exploring the potential of yeast metabolic engineering as well as for elucidating new molecular events supporting pathogenicity and antifungal resistance. All these research fields now take advantage of the establishment of a useful molecular toolbox specifically dedicated to C. guilliermondii genetics including the construction of recipient strains, the development of selectable markers and reporter genes and optimization of transformation protocols. This area of study is further supported by the availability of the complete genome sequence of the reference strain ATCC 6260 and the creation of numerous databases dedicated to gene ontology annotation (metabolic pathways, virulence, and morphogenesis). These genetic tools and genomic resources represent essential prerequisites for further successful development of C. guilliermondii research in medical mycology and in biological control by facilitating the identification of the multiple factors that contribute to its pathogenic potential. These genetic and genomic advances should also expedite future practical uses of C. guilliermondii strains of biotechnological interest by opening a window into a better understanding of the biosynthetic pathways of valuable metabolites.     

Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples.

Uric acid excretion can be measured in milligrams of urinary uric acid per decilitre of glomerular filtrate by obtaining the product of urinary uric acid and serum creatinine concentrations and dividing by the urine creatinine (all concentrations in mg/dL). In 29 normal adult men, the excretion rate in spot, midmorning samples was 0.4 +/- 0.1 (SD) mg of uric acid per decilitre of glomerular filtrate. Eight of 36 untreated gouty men excreted acid at a rate more than three standard deviations above normal. Excretion of uric acid is conveniently and physiologically assessed by this simple method.     

How does Helicobacter pylori cause duodenal ulcer disease: The bug, the host, or both?

Abstract Helicobacter pylori infection is the most common cause of duodenal ulcer disease, yet duodenal ulcer is an uncommon outcome of H. pylori infection. We reviewed the possible explanations such as differences in the host or in the strain of H. pylori. Host factors reviewed included genetic susceptibility to H. pylori infection and excess gastric acid secretion. The role of potential H. pylori virulence factors not present in all strains such as the cagA gene and the results of other molecular methods to identify disease-specific differences among isolates was also reviewed. Although cure of H. pylori infection resolves gastrin releasing peptide stimulated acid secretion there was no change in parietal cell mass. Twin studies have shown genetic differences in H. pylori susceptibility. There was no difference in the prevalence of the cagA gene between H. pylori infected asymptomatic volunteers and duodenal ulcer patients ( P = 1.0). DNA-DNA hybridization of whole genomic DNA in solution and cluster analysis of rep-PCR genomic DNA fingerprints suggest that isolates from patients with duodenal ulcer disease are different from those obtained from individuals with asymptomatic gastritis. Cluster analysis of the rep-PCR DNA fingerprints revealed two major groups of the strains; one set consisted of strains from patients with duodenal ulcer disease and the second cluster consisted largely of strains from individuals with asymptomatic gastritis. Recent molecular studies suggest that disease-specific cell lineages or strains may exist among H. pylori isolates leading to the various outcomes observed in patients with H. pylori infection.     

Synovial permeability in rheumatoid arthritis

In patients with rheumatoid arthritis, as well as in persons with other kinds of synovitis, proteins enter the knee joint more rapidly than in normal individuals (P < 0.001). The rheumatoid synovium, however, is less permeable to small molecules (tritiated water, P < 0.02; urate, P < 0.05; and glucose, P < 0.002) than is the normal joint lining. This difference is explained if rheumatoid microvascular changes enhance synovial permeability to proteins while coexisting interstitial changes diminish synovial permeability to smaller molecules.     

Deliberate self-harm in adolescents in Oxford, 1985-1995

Deliberate self-harm (DSH) has been one of the major health problems of adolescents in the U.K. for many years. Any changes in rates of DSH or the demographic characteristics of the patient population are likely to have important implications for clinical services and for future suicidal behaviour. Following a decline in rates in the late 1970s and mid 1980s, there were signs in the late 1980s that rates were beginning to increase again. We have used data collected by the Oxford Monitoring System for Attempted Suicide on the basis of patients presenting to the general hospital in Oxford to review trends in DSH in under 20-year-olds between 1985 and 1995. There was a substantial increase in the numbers of teenage DSH patients during the 11-year study period, with an increase between 1985-1986 and 1994-1995 of 27.7% in males, 28.3% in females, and 28.1% overall. There were no demographic changes within the catchment area to explain a change of this size. As rates of repetition of DSH also increased in both sexes during the study period the overall number of episodes of DSH rose even more between 1985-1986 and 1994-1995 (+56.9% in males, +46.3% in females, and +49.4% overall). As in previous studies the majority of adolescents had interpersonal problems and/or difficulties with studying or employment. Self-poisoning with paracetamol and paracetamol compounds became increasingly common such that by 1995 these were used in almost two-thirds of overdoses. The recent increase in DSH in adolescents has important implications for general hospital and adolescent psychiatric services. The greater frequency of repetition of DSH may herald increased future suicide rates. The case for restricting the amount of paracetamol available is overwhelming. Evaluative trials of specific interventions following adolescent DSH are urgently required.