Biomedical subjects
Publications and source records attributed to P Gerber.
A 38-year-old man presented with a 2-month history of progressive leg pain. An x-ray film of both tibial bones showed multiple osteolysis. At the same time, nasal polyps were present. A biopsy of the tibial bone remained unclear. A carcinoma was not found. A biopsy of the nasal polyps revealed a Rosai-Dorfman-Destombes disease.
In 2004, a new insulin analogue was launched, Detemir insulin (Levemir). Detemir insulin is a long acting insulin and has a lower within-subject variability in comparison with other insulins. The recently published results of the CARDS study (atorvastatin treatment) also emphasize the need for a more aggressive attitude toward cardiovascular risk in diabetics even if LDL-cholesterol values are not particularly elevated. We will end this short review discussing the future of the inhibitor of GLP-1 degradation which in addition to a modest hypoglycaemic effect seems to be able to prevent apoptosis of insulin producing beta cells.
A common method to induce enhanced short-term endogenous porphyrin synthesis and accumulation in cell is the topical, systemic application of 5-aminolevulinic acid or one of its derivatives. This circumvents the intravenous administration of photosensitizers normally used for photodynamic therapy (PDT) of fluorescence photodetection. However, in the majority of potential medical indications, optimal conditions with respect to the porphyrin precursor or its pharmaceutical formulation have not yet been found. Due to ethical restrictions and animal right directives, the number of available test objects is limited. Hence, definition and use of nonanimal test methods are needed. Tissue and organ cultures are a promising approach in replacing cost intensive animal models in early stages of drug development. In this paper, we present a tissue culture, which can among others be used routinely to answer specific questions emerging in the field of photodynamic therapy and fluorescence photodetection. This technique uses mucosae excised from sheep paranasal sinuses or pig bladder, which is cultured under controlled conditions. It allows quasiquantitative testing of different protoporphyrin IX precursors with respect to dose-response curves and pharmacokinetics, as well as the evaluation of different incubation conditions and/or different drug formulations. Furthermore, this approach, when combined with the use of electron microscopy and fluorescence-based methods, can be used to quantitatively determine the therapeutic outcome following protoporphyrin IX-mediated PDT.
The significance of aerosols in medicine is increased when the distribution of inhaled aerosols in the different respiratory tract compartments and their interaction with lung structures are known. The aim of this study was to investigate the retention of the hydrophobic Teflon spheres used in human beings so as to analyze their regional distribution and to study their interaction with lung structures at the deposition site. Six intubated and anesthetized Syrian Golden hamsters inhaled aerosols of Teflon particles with an aerodynamic diameter of 5.5 microns by continuous negative-pressure ventilation adjusted to slow breathing. Lungs were fixed by intravascular perfusion within 21 minutes after inhalation was started, and tissue samples were taken and processed for light and electron microscopy. The stereological (fractionator) analysis revealed that particle retention was the greatest in alveoli (72.4%), less in intrapulmonary conducting airways (22.9%), and the least in extrapulmonary mainstem bronchi (0.3%) and trachea (4.4%). Particles were found submerged in the aqueous lining layer and in close vicinity to epithelial cells. In intrapulmonary conducting airways, 21.5% of Teflon particles had been phagocytized by macrophages. This study with highly hydrophobic Teflon particles clearly demonstrates that for spheres of this size, surface tension and line tension forces rather than the particles' surface free energy are decisive for the displacement of particles into the aqueous phase by surfactant. It was this displacement that enabled subsequent interaction with macrophages. Refined knowledge of particle retention may help us to better understand the biological response to inhaled particles.
Here we present the first report of heart rate, blood pressure, and locomotive activity of a female common marmoset (Callithrix jacchus) that was moving freely in its home cage during gestation, parturition, and lactation. We collected the data by using a miniaturized telemetry and data-acquisition system (Data Sciences, St. Paul, MN) that had been adapted for marmosets (1). The parameters were recorded continually from 12 days before to 15 days after parturition. Parturition lasted about 3.5 h, during which marked changes in heart rate, systolic blood pressure, and diastolic blood pressure occurred. To obtain control values, we again measured these parameters for 13 days during a "physiologically neutral" phase (4 months after parturition), when the female was neither pregnant nor lactating. Heart rate was 200% higher, systolic blood pressure was 25% higher, and diastolic blood pressure was 75% higher during parturition than during the neutral phase.
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There is a general belief that, once in the witness box, doctors are compelled to reveal confidential information about their patients if asked by counsel. Where no issue of public interest is involved, a medical witness should ask the court to rule in its inherent discretion that the information sought is confidential and privileged.
Compared with other angiotensin-converting enzyme (ACE) inhibitors, the elimination of temocapril is less dependent on renal function. To investigate the metabolic and antihypertensive effects of temocapril in diabetic hypertensives, 30 patients with diabetes mellitus type 2 and mild to moderate hypertension [diastolic blood pressure (BP) 90-115 mm Hg] and without azotemia (plasma creatinine < 180 microM) were evaluated in a prospective randomized double-blind placebo-controlled study. After a 4-week placebo run-in, they received temocapril, 20 mg daily (n = 19), or placebo (n = 11) for 6 weeks. Insulin sensitivity index (SI), determined by the Minimal Model method of Bergman, serum lipoproteins, plasma renin activity, fibrinogen, and microalbuminuria were assessed at the end of the placebo run-in phase and the double-blind treatment phases. Temocapril but not placebo administration produced a significant decrease in supine BP (152/92+/-5/3 vs. 162/98+/-5/2 mm Hg; p < 0.01) and increase in plasma renin (p < 0.05). Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment). During administration of temocapril or placebo, no significant changes in fasting plasma glucose, insulin, and serum levels of total triglycerides, cholesterol, lipoprotein cholesterol fractions, or fibrinogen were observed. Microalbuminuria decreased significantly on temocapril treatment (49+/-10 vs. 79+/-17 mg/24 h; p < 0.01) but not on placebo. These findings demonstrate that in hypertensive patients with diabetes mellitus type 2, short-term treatment with temocapril is neutral to insulin sensitivity, lipoprotein metabolism, and fibrinogen, and significantly reduces microalbuminuria.
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Functional disorders of the thyroid, in particular hypothyroidism, can be the cause of reduced fertility in women. These dysfunctions may also increase the frequency of spontaneous miscarriage and/or fetal malformations. It is important to know the physiological adaptation-mechanisms of the thyroid in this special situation in order to understand and to diagnose such malformations and miscarriages. After a review of the physiology the most frequently observed thyroid disorders of mother and fetus during pregnancy are mentioned. Diagnostic methods and therapeutic measures are described. Finally a frequently misdiagnosed disorder of the thyroid, manifesting itself within the months following a delivery is presented: the postpartal thyroiditis.
This paper describes a new method for the elucidation of the disulphide bonding pattern in a protein from an initial set of unrefined nuclear magnetic resonance solution structures. The use of both local and global proton-proton nuclear Overhauser enhancement (NOE) distance information for the identification of the disulphide bridge network in cysteine-rich polypeptides was investigated by statistical analysis of the crystal structures of a selected group of proteins. There are six different types of inter-cysteine proton-proton distances which can potentially be used for the prediction of disulphide links. The uniqueness and the extent to which disulphide bonds could be identified by these distances was evaluated. Only NOEs between C beta H/C beta H and C alpha H/C beta H were shown to have positive predictive values for the characterization of disulphide links. Contrarily, the observation of an NOE between C alpha H and NH is a strong indication for the absence of a disulphide bridge between the two residues. The global analysis of the nuclear magnetic resonance data starts with the calculation of an initial set of conformers. First, pairing weights wij were assigned to all putative cysteine pairs in the protein according to a Gaussian-type distribution function from the C beta-C beta interatomic distances. In a second step, all conceivable disulphide patterns were formed by an exhaustive combinatorial enumeration. Statistical weights were then assigned to all patterns from the weights of the participating cysteine pairs. This method was validated with protein crystal structures deposited in the Brookhaven Protein Data Bank having three or more cysteine residues. It was then used to determine the previously unknown disulphide bonding pattern of the 12 cysteine residues of flavoridin.
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Apolipoprotein E polymorphism was examined in an Italian population of Type 2 (non-insulin-dependent) diabetic patients. There were significant differences (p < 0.05) in allele frequencies between male and female patients due to an under-representation of the E4 allele in the female group. No differences in allele frequencies were noted when non-diabetic male and female control subjects were compared. Both control groups exhibited similar allele distributions to that of male diabetic patients, but were significantly different (p < 0.05) from female diabetic patients. A closer examination of the female diabetic population revealed that under-representation of the E4 allele was principally confined to patients aged 60 years or older. This subgroup showed a significantly different (p < 0.05) allele frequency profile from control subjects (both men and women) and diabetic men, whereas this was not observed in the younger diabetic women (< or = 59 years). The results are consistent with the suggestion that the E4 allele may be a particular risk factor for female diabetic patients.