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A Michalowski

Publications and source records attributed to A Michalowski.

8 recordsLinked to original sources
PubMed1990

Cisplatin-induced reductions in renal functional reserve uncovered by unilateral nephrectomy: an experimental study in the pig.

Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to approximately 90, approximately 120 and approximately 150 mg/m2) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [99 mTc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically, and GFR and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with greater than or equal to 2 mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S1 portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GFR and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was less than 50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically "silent" until exposure to an additional nephrotoxic insult.

Animals↗
PubMed1990

The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma.

The regional distribution of blood flow to the LBDS1 fibrosarcoma, transplanted into the subcutaneous site in rats, was investigated using the readily diffusible compound 14C-iodo-antipyrine (14C-IAP). Quantitative autoradiography was used to establish absolute values of specific blood flow F for 100 X 100 X 20 microns adjacent tissue volumes of the unperturbed tumour. Mean blood flow to whole tumours was found to decrease with increase in tumour size. This relationship was abolished if blood flow was only measured in sections cut from the periphery of the tumours. Detailed analysis of a sub-group of tumours showed that blood flow to individual tumours was heterogeneous. The range of blood flow was large, indicating that mean blood flow to a whole tumour is a poor reflection of the blood perfusion pattern of that tumour. Necrotic tumour regions were usually very poorly perfused. With the exception of the smallest tumours studied, blood flow was lower in the centre of tumours than in the periphery. Necrosis also tended to develop centrally. However, the peripheral to central gradient of blood flow was apparent even when densely cellular, viable tumour regions and necrotic regions were analysed separately. The decrease in blood flow with tumour size was also apparent in densely cellular, viable tumour regions when analysed separately. Qualitative comparison of tumour histology and regional blood flow showed that there were areas of very low blood flow associated with viable tumour regions. Less common were areas of rather high blood flow associated with necrotic tumour regions. A complicated relationship exists between tumour histology and blood flow. The quantitative autoradiography technique is suitable for investigating the most poorly perfused and the most well perfused viable fractions of animal tumours which may limit the efficacy of different types of therapy.

Animals↗
PubMed1990

On radiation damage to normal tissues and its treatment. I. Growth factors.

The first part of the review outlines the classical interpretation of radiation damage to normal organs based on dose-response relationships for clonogenic cell survival and tissue kinetics. Proliferative organization of critical cell lineages (three-compartmental or H-type and one-compartmental or F-type) is considered as an additional determinant in the development of overt radiation injury. This leads to testable predictions concerned with divergent outcomes of stimulation of cell proliferation after radiation exposure using polypeptide growth factors. The prediction of favourable effects of such stimulation in H-type lineages is borne out by recent experiments on treatment with cytokines of radiation-induced haemopoietic insufficiency. The second prediction of deleterious effects of proliferative stimulation in recently, heavily irradiated F-type cell lineages remains to be verified or refuted.

Animals↗
PubMed1990

Histamine, histamine formation capacity and gastrin in cysteamine-induced peptic ulcer.

We attempted to induce chronic peptic ulcer in the rat by injection of consecutive doses of cysteamine. We investigated the incidence of peptic ulceration and measured gastric mucosal histamine, histamine formation capacity (HFC), plasma gastrin and tissue (oesophagus, duodenum, liver and lung) histamine in rats 1, 7, 14, 21, and 28 days after injection of cysteamine-HCl (300 mg/kg s.c. and 100 mg/kg 8 h later). Saline injections were used in control rats. After 24 h all rats given cysteamine had duodenal ulcers and the ulcer incidences after 7 and 14 days were 60 and 40%, respectively. After Day 21 no ulcers were found. Microscopy revealed ulcer healing seen as epithelialized scars from Day 14 onwards. A rising incidence of gastric metaplasia of the duodenal mucosa was noted from Day 7 after cysteamine treatment, which may have pathophysiological significance. Gastric mucosal histamine was higher and plasma gastrin was lower after 24 h compared with controls and values obtained later in the study. Rats with duodenal ulceration had significantly higher gastric mucosal histamine than those without lesions and control rats. A direct relationship was found between plasma gastrin and HFC in rats given cysteamine. A small but significant increase in histamine content of the liver was also observed after 24 h. No significant changes were found in other tissue specimens. Thus, a rise in gastric histamine is associated with duodenal ulcers in this model.

Animals↗
PubMed1988

Effect of gastric irradiation on gastric secretion and histamine in mice.

Gastric irradiation selectively inhibits acid secretion. Histamine may have a role in the inhibitory process. Seven days after gastric irradiation with 9 Gy X-rays, mice underwent a stomach perfusion and secretion test. Under pentagastrin stimulation (62.5 micrograms/kg), acid and histamine secretion was significantly lower than that of the unirradiated controls, while pepsin and potassium outputs were unchanged. Histamine concentration in the oxyntic region of the stomach assayed after the perfusion test was significantly lower than that of controls. It is postulated that the fall in the endogenous histamine store may contribute to the reduction in acid production.

Animals↗