CARDIOVASCULAR EFFECTS OF NICOTINE DURING PHYSICAL ACTIVITY AND FOLLOWING MEAL CONSUMPTION

1. In two separate studies using healthy male smokers as subjects, the acute cardiovascular effects of a measured dose of nicotine (15 micrograms/kg) were examined in conjunction with light physical activity and following consumption of a meal, conditions typical of nicotine intake via smoking. 2. Increases in heart rate and systolic blood pressure attributable to nicotine were similar during rest, physical activity, and following eating, demonstrating additivity with the cardiovascular effects of activity and a caloric load. Diastolic blood pressure was less affected by nicotine. 3. These results indicate that cardiovascular activity is acutely increased following nicotine (smoking) regardless of other influences on the cardiovascular system. Such effects may help explain increased risks of acute cardiac abnormalities due to smoking.     

Proliferation kinetic examinations on an experimental renal tumour with high portion of hypoxic tumour cells (author's transl)

By autoradiographic examination by means of pulse labelling with 3H-thymidine cell cycle times were determined in solid Ehrlich carcinomas (early carcinomas) in order to obtain comparative values for irradiated tumours. The subcells of the initially labelled cells near the capillaries were found to distribute themselves in the course of 48 h over the whole tumour and to emigrate to hypoxic tumour areas.     

Morphology and histochemistry of medullary thyroid carcinomas (author's transl)

The medullary thyroid carcinoma was characterized as clinicopathological entity by Hazard, Hawk and Crile as early as 1959. As reported in literature the incidence of these tumors ranges from 3.5 to 11.9% of the thyroid carcinomas. In the study presented the morphological, histochemical and electron microscopical investigations in 8 cases of medullary thyroid carcinoma are reported. Different methods are used to demonstrate polysaccharides, proteins, especially polypeptide hormones, and amyloid. Furthermore several silver impregnation techniques for differentiation of argentaffin and argyrophilic cells were performed. The age of the 8 patients ranged from 30 to 65 years, 5 patients were females, the sex ratio of females to males runs to 1.7:1. In 4 cases metastases in regional lymph nodes were found. The tumor tissue preponderately showed a solid-travecular pattern. The tumor cells were seen in cord-like and nest-like arrangement. In places also a typical endocrine structure was present revealing an orientation of cells around capillaries here and there. A differentiation of light and dark cells was possible. Electron microscopically these light microscopical observations could be confirmed: dark cells possessed more organeles than light cells. Infiltrations of blood vessels did not occur, but infiltrations of lymph vessels were the rule. The tumors contained variable amounts of amyloid which could be seen by fluorescence and polarization microscopical methods in fine fiber-like structures or in coarse deposits. At the ultrastructural level typical secretory granules varying in electron density and having a diameter of 220-560 nm were visible. Some light tumor cells exhibited 50-120 A thick fibrils which could not be distinguished from extracellular amyloid fibrils. The histochemical findings evidenced moderately abundant proteins in the cytoplasm of tumor cells. Histochemically the amyloid corresponds to the so-called apudamyloid. A great deal of the proteins is orderly arranged in amyloid whereas this is not the case in the tumor cell cytoplasm as proved by the coupled tetrazonium reaction which was evaluated polarization microscopically. In amyloid tryptophan was absent. The medullary thyroid carcinoma has a low-grade malignancy and, in accordance to other authors, it is to be stated that this tumor is histogenetically related to the parafollicular cells (C-cells). Its distinction from other thyroid tumors is warranted basing on morphological and pathophysiological features. Structural patterns common with those of other endocrine tumors are demonstrable. The findings point to a relationship of medullary thyroid carcinoma with the APUD series or Feyrter's Helle-Zellen-System. Considering the possible simultaneous occurrence of pheochromocytomas and adenomas of the parathyroid gland it must be assumed that the medullary thyroid carcinoma is one of the dysplasias of the neural ectoderm.     

High-dose melphalan dosage adjustment: possibility of using a test-dose

Summary Previous pharmacokinetic studies of i.v. highdose melphalan (HDM) have demonstrated large interindividual variations in the pharmacokinetic parameters. We therefore studied the possibility of using a test dose of the drug to determine the level of a subsequent therapeutic dose. This study was undertaken to establish whether the pharmacokinetics of melphalan were linear and reproducible within the same patient and determine whether a linear extrapolation could be carried out from the test dose. The first eight patients were studied on two occasions separated by 2 hours (repeatability stage). Although reasonable evidence for linear pharmacokinetics was obtained from these patients, the data suggested a number of factors that might have introduced errors. Therefore, the second group of ten patients were treated on a slightly different protocol on two occasions 24 h apart (linearity stage). The ratios of the two doses ranged from 1 to 8 (repeatability stage) and from 2.6 to 10 (linearity stage). During both stages there was a good correlation between the AUC measured for the second infusion and that predicted from the first (r=0.929 and r=0.943, respectively). We conclude that a test dose can be used to determine the subsequent dose of melphalan necessary to produce a desired AUC.     

Effects of 3-isobutyl-1-methylxanthine on neonatal pancreatic islets maintained in tissue culture

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) promoted the formation of monolayers in cultured pancreatic islets isolated from neonatal rats. Immunofluorescence with specific antisera to insulin and glucagon revealed B-cells and A-cells in these monolayers. Glucose-mediated insulin release was increased by raising the glucose concentration from 5 to 10 mmoles/l. Addition of IBMX (0.1 mmoles/l) to medium containing 10 moles/l glucose produced a further increase in insulin release. Recovery of total insulin, i.e. intracellular insulin plus insulin secreted, was also increased by approximately 50% after 8 days of culture. The B-cells showed a marked biosynthetic response to an acute glucose challenge after prior culture with 10 mmoles/l glucose. Although both unstimulated (1.5 mmoles/l glucose) and stimulated rates (1.5 mmoles/l glucose) of [3H]leucine incorporation into (pro)insulin were significantly higher following culture in 10 mmoles/l glucose plus IBMX (0.1 mmoles/l) than after prior culture with 10 mmoles/l glucose alone, the percentage of (pro)insulin synthesized in relation to total protein synthesis was only increased at the low concentration of glucose. These studies demonstrate that monolayer cultures of neonatal B-cells can be readily produced by IBMX and maintained in a functional state, as defined by their secretory and biosynthetic response. It is suggested that the phosphodiesterase inhibitor exerts a sensitizing effect on the responsiveness of the B-cell to glucose. Moreover, the culture system employed in the present study may prove to be useful for further studies of various agents affecting the B-cell function.     

HLA-D typing with an association of Dw2 and absent immune responses towards herpes simplex (type i) antigen in multiple sclerosis.

We have confirmed that HLA-Dw2 is increased in MS patients to 47% (normals 20%). Lymphocyte transformation and antibody studies with herpes simplex antigen show that many of the DW2-positive MS patients have low or absent responses. The association of low responses to HSV and the presence of Dw2 is statistically significant at a p value less than 0.01.