Release of gastrin from the skeletal muscles and from the antral mucosa in cats induced by sulfonuric drugs

The present observations indicate that sulfonuric drugs release gastrin both from peripheral nerves in striated muscles and from endocrine-like cells in the gastrointestinal tract. Gastrin appears in perfusates of extirpated cat legs after administration of tolbutamide or glibenclamide (5–50 μg/kg or 5–500 μg/kg perfused tissue respectively) to the perfusion medium. Furthermore gastrin is released into the portal vein of cats after i.v. administration of glibenclamide (5–50 μg/kg). The finding that sulfonuric drugs not only release insulin from β-cells in the pancreas, but also gastrin from gastrin producing cells in the stomach as well as from nerve fibers in the skeletal muscles, indicate that sulfonuric drugs have more wide spread effects than previously assumed. Possible consequences of the drug induced release of peptides from peripheral nerves as well as of the release of gastrin from the gastrointestinal tract are discussed.     

Senile Macular Degeneration – The Effects and Management: The Pathological Processes

ABSTRACT This paper, the second in the series on the effects and management of senile macular degeneration (SMD), presents an overview of the pathological processes in the evolution of SMD. The normal macula is first defined and the ageing and degenerative changes which can occur are then described. The histological changes are related to the clinical observations of pigmentary disturbance in the development of either geographic atrophy or disciform macular degeneration. The importance of the appearance of drusen as an indicator of the stage of degeneration is detailed.     

Effect of nutritional hyperparathyroidism on experimental periodontitis in the dog

abstract – The purpose of the present investigation was to induce osteopenia of the alveolar process by feeding dogs a calcium-deficient, phosphorus-rich diet, and to determine whether dogs suffering from nutritional secondary hyperparathyroidism (NSH) developed: (1) increased tooth mobility, (2) gingivitis and (3) periodontitis with marginal alveolar bone resorption in plaque-free areas and in areas where plaque and calculus were allowed to accumulate. The experiments were performed on six, 12-month-old Beagle dogs. During an experimental period of 18 months, four dogs (test group) were fed a low calcium, high phosphorus diet of a soft consistency. The controls were fed an adequate but soft diet. The teeth of the right jaws were regularly subjected to thorough cleaning. NSH and osteopenia of the alveolar bone were induced in the test dogs. Osteopenia, however, did not result in an increased tooth mobility or gingivitis in the absence of plaque. In areas where dental deposits were allowed to accumulate, pathologic pockets gradually developed in both test and control animals, but the degree of attachment loss was the same in both groups.     

Fine Needle Aspiration Compared with Scintigraphy for Detection of Liver Neoplasia

ABSTRACT The diagnostic accuracy of fine needle aspiration and scintigraphy was compared prospectively in a series of cases of suspected liver neoplasm. The results of both techniques showed a close correlation to final diagnosis. Biopsy, easily and rapidly performed with simple equipments, is a cost-saving procedure with as good a sensitivity as scintigraphy. Furthermore, the possible finding of specific cytological pictures of primary liver carcinoma or tumours of the amino precursor uptake decarboxylating cell series lend further weight to the biopsy technique.     

RETINAL DEVELOPMENT IN HUMANS: THE ROLES OF DIFFERENTIAL GROWTH RATES, CELL MIGRATION AND NATURALLY OCCURRING CELL DEATH

The distribution of ganglion cells throughout the retinal ganglion cell layer is non-uniform in adult mammals. This paper reviews some of our data describing the development of retinal ganglion cell topography in the human fetus. Results indicate that early in the fetal period the distribution of ce/fe in the ganglion cell layer is almost uniform, but by the end of gestation there is a gradient in cell density of about 10:1 (centrahperipheral). Peripheral retina grows more rapidly than the central retina prior to about 23 weeks gestation, but this differential growth rate apparently has little effect on the development of a centre-peripheral density gradient. The gradient appears between about 18 and 30 weeks gestation, and during this period there appears to be a greater rate of cell death in the ganglion cell layer of the peripheral retina. Cell density at the developing fovea is less than the perifoveal cell density at all ages, suggesting that ganglion cells migrate from fovea/ into perifoveal regions throughout the fetal period.     

First Clinical Experience With Celt ACD®: A Femoral Arterial Puncture Closure Device

Introduction

This prospective nonrandomized study compared the safety and efficacy of a novel arterial closure device (ACD) in common femoral artery procedures to that of the FDA submitted historical manual pressure control group, who underwent either a diagnostic angiogram (DA) or a percutaneous coronary intervention (PCI) procedure.

Methods and Results

A total of 55 patients were enrolled in this study of the novel ACD. Of the 55 patients, 39 were enrolled in the DA group and 16 were enrolled in the PCI group. Six patients were excluded. A device was deployed in 49 patients. Time to hemostasis (TTH), time to ambulation (TTA), device function, and device‐related vascular complications were measured. In the device group, the TTH for the combined DA and PCI patients was 32 seconds (0.54 ± 0.93 minutes), significantly lower when compared with 16.0 ± 12.2 minutes (P < 0.0001) for the control group. Overall major vascular complication rate did not differ significantly, device group (1/49) and the historical control group (1/217). TTA in the combined PCI and DA device group was 226.4 ± 231.9 at the German site (site ambulation policy). In the Irish site, the average TTA in the PCI group was 187 minutes (n = 8) and 85 minutes (n = 14) in the DA group.

Conclusion

The Celt ACD® device is safe, effective, and significantly decreases the TTH compared to manual pressure and has a low vascular complications rate. The device may be effective in early ambulation and discharge of patients postcoronary intervention procedures.

     

Antigen topography is critical for interaction of IgG2 anti-red-cell antibodies with Fcγ receptors

IgG antibodies to the Rh D polypeptide on red cells are normally IgG1 or IgG3, whereas antibodies produced in response to carbohydrate antigens such as the A and B blood groups are predominantly IgG2. The consequences of this isotype restriction for the immune destruction of red cells were investigated. Human IgG2 anti-D and IgG2 anti-A were isolated by affinity purification from an unusual anti-D serum (DEL) and anti-A sera, respectively. These antibodies were compared with IgG1 and IgG3 monoclonal anti-D in in vitro functional assays of the interaction between IgG-coated red cells (EA-IgG) and cells bearing IgG Fc receptors (FcγR). Dimeric IgG2 anti-D bound efficiently to cell lines transfected with FcγRIIa-H131, an allotypic form of FcγRIIa which readily interacts with IgG2, IgG1 and IgG3. Unexpectedly, however, -D-phenotype red cells coated with IgG2 anti-D did not form rosettes with these cells, whereas EA-IgG2 anti-A and EA-IgG1 and EA-IgG3 anti-D effectively formed rosettes with these transfectants at the same sensitization level (100 000 molecules IgG/red cell). In antibody-dependent cell-mediated cytotoxicity (ADCC) assays, lysis of EA-IgG2 anti-A was mediated via FcγRIIa, whereas lysis of EA-IgG1 and EA-IgG3 anti-D was mediated via FcγRI or FcγRIII; EA-IgG2 anti-D was inactive in all functional assays. These experiments suggest that both IgG subclass and antigen structure affect functional IgG–FcγR interactions. The topography of the Rh D antigen, an integral membrane protein, ensures that anti-D is bound near the lipid bilayer surrounded by the glycocalyx. This may sterically hinder access of FcγRIIa-H131 to the FcγR recognition site on the relatively inflexible IgG2 anti-D, but not to that of IgG1 or IgG3 anti-D. In contrast, IgG2 bound to the A antigen on glycoproteins is not so constrained. The topography of the D and A antigens may thus determine whether functional interactions of red-cell-bound IgG2 anti-D and IgG2 anti-A with cells bearing Fcγ receptors can occur.     

Electrical Restitution and Conduction Intervals of Ventricular Premature Beats in Man: Influence of Heart Rate

Monophasic action potentials (MAP) were obtained from the outflow tract of the right ventricle during apical pacing in 20 patients with coronary artery disease. The electrical restitution was studied by interpolation of extrasystoles with various coupling intervals to the preceding steady-state beat at basic paced cycle lengths (CL) of 700, 600, and 500 msec. At higher frequencies the ventricular effective refractory periods (V-ERP) and duration of MAPs became shorter and the electrical restitution curves were displaced downwards (P less than 0.001). With increasing diastolic intervals preceding the extrasystole up to a maximum of 100 msec, the duration of premature MAPs increased at all frequencies. An obvious hump of the electrical restitution curve was observed at coupling intervals of 100 msec due to a later transient decrease (P less than 0.01) in duration of MAPs at the basic CL of 500 msec. No significant hump was observed at lower heart rates. Thus, a different time course of the electrical restitution was observed at various CLs. The intraventricular conduction intervals were shorter at the shorter basic CLs when compared to the 700 msec cycles (P less than 0.05). The conduction intervals were also modified by the coupling interval between the interpolated stimulus and the preceding steady-state action potential (AP). The premature beats elicited 30 msec or earlier after refractoriness were conducted more slowly at all basic cycle lengths (P less than 0.005), and those between 60 and 150 msec after the V-ERP more rapidly (P less than 0.01) than the steady-state beats. These observations have implications for the protocols used for introducing two or more frequencies during programmed stimulation in man. Furthermore, the conduction pattern in vivo cannot be interpreted from single cell studies.