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Biomedical subjects

K M Kerr

Publications and source records attributed to K M Kerr.

At least 91 records · Page 5Linked to original sources

Actual growth rate and tumour cell proliferation in human pulmonary neoplasms.

Measurement of the Doubling Times [DT] for 27 human pulmonary neoplasms have been made. Squamous and large cell tumours had a wide range of values for DT whereas for small cell undifferentiated carcinoma, and possibly large cell undifferentiated carcinomata without stratification, the range was narrower. Mean DT for different primary bronchogenic carcinoma groups were: Squamous cell 146 days, Adenocarcinoma 72 days, Small cell 66 days, and Large Cell 111 days. The number of adenocarcinomata is very small in number and our value of 72 days is probably not representative of this group of tumours. Relationship between DT and tumour differentiation was difficult to identify in our series. Of these 27 a unique series of 17 have parallel data on DT and Potential Doubling Time (DTpot) and the Cell Loss Factor [0] calculated. Great discrepancy between DT and DTpot existed in each case and cell loss was high, ranging from 54% to 99%. All primary bronchogenic carcinomata had cell loss of greater than 70%; in almost two thirds of these cases the value was 90% or more. All undifferentiated tumours and a majority of poorly differentiated tumours had cell loss of 90% or more. As cell loss increased, tumour thymidine labelling index (TLI) increased and the tumours tended to be less well differentiated. The relationship, if any, between cell loss and DT was unclear.

Adenocarcinoma↗

Subacute toxicity of methylene-bis-(2,6-diisopropylaniline) in the rat and hamster.

Methylene-bis-2,6-diisopropylaniline (MDPA), a chemical having potential application as a polyurethane chain extender or an epoxy curing agent, was administered daily by gavage to male Fischer 344 rats and male Syrian golden FVG hamsters. Rats were administered MDPA at 10.5, 21.0, 42.0, 63.0, or 87.5 mg/kg in corn oil for 5, 10, or 28 d. Hamsters received 87.5 or 875 mg MDPA/kg daily for the same periods. Histopathologic evaluation of rat tissue showed diffuse vacuolar change and periacinar vacuolar degeneration of the livers, with congestion, hemosiderosis, and hematopoiesis in the spleen. Hepatic periacinar vacuolar degeneration decreased in incidence and severity from d 5 to d 28, and livers of rats sacrificed 28 d after cessation of MDPA treatment (d 56) were normal. Hepatic vacuolar change was characterized by lipid inclusions. Electron microscopic evaluation found no structural abnormalities in hepatocytes with a moderate level of lipid vacuolization, while degeneration was seen in cells with extensive vacuolization. Stage III, stage IV, and maximal respiratory rates of mitochondria isolated from livers of test animals were higher than age-matched controls after 28 d treatment. At the high dose (875 mg/kg), MDPA produced liver lesions consisting of periacinar vacuolar change, vacuolar degeneration, hepatocytic swelling, and necrosis in hamsters. The high dose also produced acute toxic tubular nephrosis and a high mortality rate. At a dose (87.5 mg/kg) equuimolar to the high dose in the rat, however, the only lesion observed in the hamster was periacinar vacuolar change. In summary, the degenerative hepatic lesion produced in liver decreased in incidence with continued administration, and higher doses were required to produce this lesion in the hamster than in the rat.

Aniline Compounds↗

Histological and ultrastructural evaluation of cardiac lesions in idiopathic cardiomyopathy in dogs.

Described are pathological studies of eight dogs which died in congestive heart failure, with a clinical diagnosis of congestive cardiomyopathy. Examination revealed marked dilatation and enlargement of all four chambers of the heart. The ventricular walls were thin with small atrophic papillary muscles. Histological studies on the myocardium revealed scattered areas of myocardial necrosis, especially around the papillary muscles of the left ventricle and random scattered areas of fibrosis. Electron microscopic studies revealed fewer and disoriented myofibrils, myocytolysis, increased numbers of mitochondria with swelling and inclusions, increased glycogen granules and increased numbers of lysosomes, lipofuscin granules and lipid droplets. Mild Z-band abnormalities were found throughout the myofibers.

Animals↗

Microbial transformations of pergolide to pergolide sulfoxide and pergolide sulfone.

Fifty-eight microorganisms were investigated for their ability to effect the biotransformation of the ergoline alkaloid pergolide. A majority of these organisms formed pergolide sulfoxide, and a Helminthosporium species was investigated in greater detail since it yielded significant amounts of pergolide sulfoxide. A preparative-scale transformation afforded material which was identified as the sulfoxide based on melting point, spectral, and chromatographic comparison with authentic material as well as its conversion to pergolide by reduction with triphenylphosphine. An analytical high-performance liquid chromatographic determination of the enzymatic versus spontaneous air-oxidation of pergolide in growing cultures and controls showed negligible air-oxidation and an approximately 40% enzymatic conversion of pergolide to the sulfoxide. Several organisms, including Aspergillus alliaceus formed a second metabolite, pergolide sulfone, which was identified on the basis of co-chromatographic data.

Aspergillus↗

In vitro thymidine labelling of human pulmonary neoplasms.

The in vitro thymidine labelling indices (TLI) of 58 human lung tumours were assessed using autoradiography. The labelling technique involved incubation of 1 mm3 tumour fragments with 3H-thymidine (5 muCi ml-1) under conditions of hyperbaric oxygenation at a pressure of 3 atmospheres. Only a rim of labelling was achieved along the edges of fragments and the depth of this rim varied from tumour to tumour. A technique for counting TLIs was therefore devised to take this into account. In general, those tumours showing low TLI values of less than 5.0% showed a greater depth of labelling. The common malignant tumours of the bronchus showed a wide range of values (2.2-30.4%) though the adenocarcinomata had a lower average value than the other groups. With the squamous carcinomata a relationship with differentiation was shown. The mean value for small cell carcinomata (16.9%)--a highly aggressive tumour--was no higher than for the other groups. The low grade malignant tumours showed TLIs of less than 3.0% and these values correlate with their less aggressive clinical behaviour. Labelling of stromal cells and inflammatory cells varied greatly from tumour to tumour; however, no correlation was found with the TLIs of tumour cells.

Cell Division↗

Morphologic variations and aging in the atrioventricular conduction system of large breed dogs.

The microscopic anatomy of the atrioventricular node, bundle of His, both bundle branches and surrounding fibrous cardiac skeleton was studied in 40 large breed dogs of various ages. In the AV conduction system of all dogs over five years of age there was an increase of fibrous connective tissue, an infiltration of adipose tissue, loss of conduction fibers and focal fibrosis extending from the central fibrous body. Fibrosis was seen in the summit of the interventricular septum posterior to the AV node in dogs of all ages. Chondroid metaplasia was consistently observed in the central fibrous body and the root of the aorta in large breed dogs, including ten Doberman Pinschers of all ages. This metaplasia varied from a few chondroblasts and chondrocytes to mature chondrocytes with mineralization. Bone formation was seen in eight dogs. These changes appeared in close approximation to the cardiac conduction system above the bundle of His. No degenerative changes were seen in the AV bundle. Approximately one-half of the large breed dogs five years of age and older had thickened medial and intima proliferation in the small coronary arterioles supplying the AV node. The results of this study suggest that the presence of cartilage and bone in the central fibrous body is a normal occurrence in large breed dogs at all ages.

Aging↗

Pharmacokinetics and dosage of oxytetracycline in dogs.

The pharmacokinetics of oxytetracycline, which was given as a single intravenous dose (5 mg/kg), was studied in normal beagle dogs. Renal function was evaluated by the single injection technique and based on clearance of the radioiodine compounds 125I-iothalamate and 131I-iodohippurate. Values of GFR (4.42+/-0.77 ml/kg/min) and ERPF (12.91+/-1.49 ml/kg/min) showed normal renal function. The disposition curve describing decline of oxytetracycline activity in serum was described mathematically by a triexponential expression. Body clearance was 4.23+/-1.29 ml/kg/min. A dosage regimen (intravenous route of drug administration), based on overall elimincation rate constant (0.1155 h-1) and apparent specific volume of distribution (2 litre/kg), and consisting of a priming dose (10 mg/kg) followed by maintenance doses (7.5 mg/kg) at 12 h intervals was proposed. This dosage regimen was predicted to rapidly achieve and maintain steady state serum concentrations within the range 1.25 to 5.0 microgram/ml, which is therapeutic level for the majority of susceptible microorganisms.

Animals↗