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Biomedical subjects

D Heath

Publications and source records attributed to D Heath.

At least 109 records · Page 6Linked to original sources

The thickness of the alveolar capillary wall in guinea-pigs at high and low altitude.

The thickness of the alveolar-capillary wall was measured in the lungs of seven guinea-pigs born and living at La Raya, in the Peruvian Andes, at an altitude of 4200 m and in seven sea-level representatives of the same species. This was achieved by carrying out morphometric studies on electron micrographs to obtain the so-called arithmetic and harmonic mean thicknesses. The arithmetic mean thickness was always the larger, this being due to the greater emphasis which the technique employed places on the copious amounts of connective tissue in the interstitial space of the alveolar capillary wall in this species. These thicker portions of the alveolar wall are not concerned with gaseous diffusion. The harmonic mean thickness probably gives a more physiologically realistic estimate of the magnitude of the diffusion barrier to oxygen. This proved to be smaller in the animals from high altitude and may facilitate diffusion of oxygen from alveolar spaces to blood, thus making less steep the "oxygen cascade" from inspired air to mitochondria.

Altitude↗

The carotid bodies in a case of ventricular septal defect.

A woman of 62 years with Turner's syndrome died in congestive cardiac failure secondary to a large ventricular septal defect with biventricular hypertrophy. During her last few months the lifelong left-to-right shunt underwent reversal exposing her carotid bodies to hypoxaemia. The carotid bodies were not enlarged, thus demonstrating that hyperplasia of glomic tissue is not brought about by increased myocardial mass per se. They were, however, abnormally cellular with more dark cells ( a variant of chief cells), many of which were abnormally large and showed ultrastructural features of metabolic activity. These changes may represent the earliest histological response of the carotid body to hypoxaemia and later, the dark cells may mature into the more familiar and common light variant. It seems likely that this dark cell activity precedes, probably by a long period, the sustentacular cell hyperplasia and proliferation of nerve axons which we have reported elsewhere as the chronic reaction of the carotid bodies to hypoxaemia.

Cardiomegaly↗

Use of bovine follicular fluid to increase ovulation rate or prevent ovulation in sheep.

Romney ewes were injected intramuscularly once or twice daily for 3 days with 0, 0.1, 0.5, 1 or 5 ml of bovine follicular fluid (bFF) treated with dextran-coated charcoal, starting immediately after injection of cloprostenol to initiate luteolysis on Day 10 of the oestrous cycle. There was a dose-related suppression of plasma concentrations of FSH, but not LH, during the treatment period. On stopping the bFF treatment, plasma FSH concentrations 'rebounded' to levels up to 3-fold higher than pretreatment values. The mean time to the onset of oestrus was also increased in a dose-related manner by up to 11 days. The mean ovulation rates of ewes receiving 1.0 ml bFF twice daily (1.9 +/- 0.2 ovulations/ewe, mean +/- s.e.m. for N = 34) or 5.0 ml once daily (2.0 +/- 0.2 ovulations/ewe, N = 25) were significantly higher than that of control ewes (1.4 +/- 0.1 ovulations/ewe, N = 35). Comparison of the ovaries of ewes treated with bFF for 24 or 48 h with the ovaries of control ewes revealed no differences in the number or size distribution of antral follicles. However, the large follicles (greater than or equal to 5 mm diam.) of bFF-treated ewes had lower concentrations of oestradiol-17 beta in follicular fluid, contained fewer granulosa cells and the granulosa cells had a reduced capacity to aromatize testosterone to oestradiol-17 beta and produce cyclic AMP when challenged with FSH or LH. No significant effects of bFF treatment were observed in small (1-2.5 mm diam.) or medium (3-4.5 mm diam.) sized follicles. Ewes receiving 5 ml bFF once daily for 27 days, from the onset of luteolysis, were rendered infertile during this treatment period. Oestrus was not observed and ovulation did not occur. Median concentrations of plasma FSH fell to 20% of pretreatment values within 2 days. Thereafter they gradually rose over the next 8 days to reach 60% of pretreatment values where they remained for the rest of the 27-day treatment period. Median concentrations of plasma LH increased during the treatment period to levels up to 6-fold higher than pretreatment values. When bFF treatment was stopped, plasma concentrations of FSH and LH quickly returned to control levels, and oestrus was observed within 2 weeks. The ewes were mated at this first oestrus and each subsequently delivered a single lamb.

Animals↗

Histological changes associated with ageing of the human carotid body.

A qualitative and quantitative histological study was made of the carotid bodies obtained at necropsy from 47 subjects ranging in age from 14 to 100 years. With increasing age there is a loss of more than a third of the amount of glomic tissue with a diminution in the size of the lobules. In young people the basic histological pattern of clusters, composed of cores of chief cells with surrounding rims of sustentacular cells, has commonly superimposed on it prominence of the dark variant of chief cells. In middle-aged subjects there is proliferation of sustentacular cells which appear to merge imperceptibly into fibrosis of the lobules and becomes associated with diffuse or focal infiltrates of lymphocytes.

Adolescent↗

Comparative pathology of the enlarged carotid body.

A histological study was made of the carotid bodies of man and various animal species from low and high altitudes. The animals studied were the alpaca, llama, cattle, guinea-pig, rabbit, dog, rat and man. As well as a qualitative microscopic study, a differential cell count was carried out to determine the percentage of the light and dark variants of chief cells and of sustentacular cells present. The investigation showed that the carotid bodies enlarge in cattle, guinea-pigs and rabbits living in the hypobaric hypoxia of high altitude to which they have to acclimatize. The carotid bodies are not enlarged in llamas and alpacas which show Darwinian adaptation to high altitude. There is no single histopathological appearance to be found with enlargement of the carotid body; on the contrary, there appears to be a characteristic histological reaction for different species. Thus, man shows hyperplasia of sustentacular cells, cattle show focal dark cell proliferation and rabbits, guinea-pigs, and dogs show striking hyperplasia and vacuolation of chief cells. In the rat, the enlargement of the carotid body is not characterized by the differential proliferation of any specific element and, as a result, it does not appear to be a good model for the human organ. In man and rat, carotid body enlargement occurs in response to systemic hypertension as well as to chronic hypoxaemia and the histological response to the 2 stimuli is the same, depending on the species. The normal rabbit carotid body is more reminiscent of that of man but, in this species, the reaction of glomic tissue differs from that of human glomic tissue.

Altitude↗

Gonadotrophin-stimulated cyclic AMP production by granulosa cells from Booroola x Romney ewes with and without a fecundity gene.

The influence of follicular size and health on FSH and LH stimulation of cAMP production by granulosa cells in vitro was studied in cells from Booroola X Romney ewes, with (F+) and without (++) a fecundity gene. The granulosa cells were obtained 0-48 h after the initiation of luteolysis on Day 10 of the oestrous cycle by cloprostenol. The highest mean amounts of cAMP produced by granulosa cells challenged with FSH or LH were not significantly different between the genotypes. However, they were achieved using granulosa cells from follicles greater than 3-4 mm in diameter in F+ ewes but from follicles greater than 4 mm in diameter in ++ ewes. Follicles may thus attain ovulatory maturity at a smaller diameter in F+ ewes than in ++ ewes. Granulosa cells from most atretic follicles gave a poor cAMP response to FSH or LH, compared to cells from non-atretic follicles. Granulosa cell responsiveness to FSH was independent of the time the cells were recovered after cloprostenol treatment in F+ ewes, but not in ++ ewes. Cellular responsiveness to LH was independent of time for sheep of both genotypes. There was a significant positive relationship for sheep of both genotypes between the level of aromatase activity in granulosa cells and cellular responsiveness to FSH and LH.

Animals↗

Nerve axons in carotid body hyperplasia. A quantitative study.

The nerve density, expressed as total length of nerve fibers per square millimeter of tissue section, was measured in both carotid bodies from five subjects free from cardiopulmonary disease and from eight subjects with carotid body hyperplasia. Six of the cases with enlargement of the carotid body had been exposed to chronic hypoxemia in life (due to panacinar pulmonary emphysema in five instances and the pickwickian syndrome in one case), and the other two cases had had systemic hypertension. The cases of carotid body hyperplasia showed an increased nerve density associated with the characteristic proliferation of elongated cells. These findings confirm that the proliferating cells in carotid body hyperplasia are both sustentacular and Schwann's cells, not fibroblasts, and suggest that these cells develop to support an increased number of nerve axons. The mechanisms by which two such different stimuli as chronic hypoxemia and raised intravascular pressure bring about an increased nerve density are obscure.

Aged↗

Invasive pulmonary haemangiomatosis.

Invasive pulmonary haemangiomatosis is a recently described disease in which exceedingly thin-walled vessels of capillary or venous dimensions infiltrate the lung parenchyma and pulmonary blood vessels. The angiomatous vessels, of obscure origin, infiltrate the media and intima of muscular pulmonary arteries, pulmonary veins and venules. The occlusion of the veins and venules by the thin-walled vessels, and the reactive intimal fibrosis they provoke, leads to pulmonary capillary dilatation, collections of intra-alveolar siderophages, fibrosis of alveolar walls and osseous nodules. This secondary pulmonary veno-occlusive disease in turn leads to hypertensive pulmonary vascular disease. Hence invasive pulmonary haemangiomatosis represents a fourth cause of 'unexplained pulmonary hypertension', the other three being unexplained plexogenic pulmonary arteriopathy, recurrent pulmonary thromboembolism, and pulmonary veno-occlusive disease. Two previously reported cases of invasive pulmonary haemangiomatosis presented with recurrent haemoptysis and the gradual development of chronic respiratory insufficiency associated with diffuse infiltrates in the chest radiograph. In one of these cases a haemothorax had developed. Such clinical features may be of importance in coming to the correct diagnosis.

Angiomatosis↗

Dark cell proliferation in carotid body hyperplasia.

The histopathology of the enlarged carotid bodies, in both qualitative and quantitative terms, is described in two cases. One was in a woman of 80 years with systemic hypertension and the other in a man of 72 years with pan-acinar emphysema complicated by chronic hypoxaemia. In both instances there was generalized hyperplasia of sustentacular cells, perhaps with involvement of Schwann cells and fibrocytes, with superimposed focal proliferation of dark or 'pyknotic' variants of chief cells. The functional significance of both froms of tissue response in the carotid bodies is speculated upon.

Aged↗

The pulmonary arteries of the yak.

A quantitative histological study was carried out on the pulmonary arteries of a female yak (Bos grunniens), a member of the genus Bos which comprises the various types of cattle. A characteristic feature of cattle is a muscular pulmonary vasculature which responds sensitively to alveolar hypoxia by constriction. The yak studied had thin-walled pulmonary arteries and showed no evidence of right ventricular hypertrophy. It is suggested that this may be a feature of adaptation (as contrasted to acclimatisation) to a life in the hypobaric hypoxia of high altitude.

Adaptation, Physiological↗

Glomic cells and blood vessels in the hyperplastic carotid bodies of spontaneously hypertensive rats.

Carotid bodies from 21 normotensive Wistar albino rats were compared with those from 20 spontaneously hypertensive rats of the Okamoto strain. From serial histological sections the volume of the carotid bodies was estimated by Simpson's rule. Differential and absolute cell counts were also performed on the chief and elongated cells which surround them. The glomic vasculature was examined by light and electron microscopy. Although the carotid bodies of Okamoto rats were nearly three times as large as those of Wistar rats of comparable body weight, there was no difference in the proportion of the two types of cell. The organisation of glomic cells was also similar in the two strains. The main carotid body artery consists of a muscular tube with a valve-like cushion at its orifice. In the Okamoto rats branches of this artery were occluded by intimal proliferations of myofibroblasts embedded within a copious, loose matrix of acid mucopolysaccharide ground substance. These proliferations appeared to originate from intimal pads situated at the origins of many glomic arteries and arterioles. These findings are in sharp contrast to those in the hyperplastic human carotid body.

Animals↗

Seasonal differences in ovarian activity in cows.

The plasma concentrations of LH and prolactin and various parameters of ovarian function were examined in cows on known days of the oestrous cycle during May and June (autumn and winter) and during October (spring). Luteinizing hormone peak frequency and plasma prolactin concentrations were significantly higher in October than during the May-June period (LH, P less than 0.05; prolactin, P less than 0.01). The mean diameters of large healthy follicles (greater than or equal to 8 mm diameter) and the dominant oestrogen-secreting follicles were significantly larger (P less than 0.01 for both follicle types) and each follicle contained more granulosa cells (both P less than 0.01) in May-June than in October. The LH responsiveness of theca interna with respect to androstenedione production and the levels of aromatase activity in granulosa cells did not differ with time of year. The corpora lutea were heavier (P less than 0.05) and secreted more progesterone (P less than 0.01) in May-June than in October. It is concluded that seasonal differences in ovarian activity exist in cows and that these differences are probably the consequence of seasonal differences in gonadotrophin secretion.

Androstenedione↗

Consensual accommodation.

Consensual accommodation, like other consensual responses, may be a useful diagnostic indicator. The consensual interocular lag (direct accommodative response minus consensual accommodative response) was measured under a variety of accommodative conditions in four normal subjects, one of whom later underwent cryosurgery for a retinal tear. There was no consensual interocular lag when subjects were orthophoric , but when slightly exophoric at near distances a small lag does occur. A subject with large exophorias at near showed a more complex accommodative pattern. The consensual interocular lag proved to be the most sensitive measure of accommodative loss and subsequent recovery after retinal cryosurgery.

Accommodation, Ocular↗

Homology between the female paraurethral (Skene's) glands and the prostate. Immunohistochemical demonstration.

Homology between female paraurethral glands and the prostate has often been suggested. A means was developed that would lend histochemical support to this hypothesis. Female urethra from autopsy and surgical material was serially sectioned and studied in 19 patients ranging in age from newborn to 86 years. Paraurethral glands were identified in 18 of these. The tissue was stained with antibodies to prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAcPh) using the peroxidase-antiperoxidase method. Of those cases in which paraurethral glands were seen, 83% were positive for PSA and 67% for PSAcPh. Intensity of staining was semi-quantitatively evaluated. In addition, intraluminal secretions and urethral columnar epithelium showed positive enzyme and antigen staining. There was no discernible variation of glandular development or pattern of staining with patient age. This study demonstrates the homologous nature of the female paraurethral glands and the prostate and supports speculations about functional similarity.

Adolescent↗

Electron microscopy of carotid body hyperplasia.

Hyperplastic carotid bodies from an 80-year-old woman with sustained systemic hypertension were examined ultrastructurally and compared with those from six normal subjects. Hyperplasia involved both elongated sustentacular and Schwann's cells, both of which were more numerous than normal. They formed concentric whorls around a diminished core of chief cells. The Schwann's cells adopted a peripheral position in each cell cluster, whereas the sustentacular cells were located closer to the central core. The characteristics of both types of cell were similar so that they could not be distinguished from each other in every instance. They were associated with numerous nerve axons with which they usually displayed a simple mesaxonal relationship. The myelin sheaths formed by Schwann's cells were well developed but those encountered in sustentacular cells were usually rudimentary. A few fibroblasts were also present, but generally the process of hyperplasia was not one of fibrosis; neither did it involve pericytes.

Aged↗

The vasculature of the carotid body.

A histological and electron microscopical study was carried out on the vasculature of the carotid bodies in seven subjects coming to necropsy. None of these had suffered from chronic hypoxaemia or systemic hypertension during life and none had hypertrophy of the right or left ventricle. The vasculature of the carotid bodies showed three distinct components. There was a proximal portion, comprising elastic interlobular arteries, which had a wall in which elastic tissue predominated and in which many nerve fibrils could be demonstrated. This is considered to be baroreceptor in nature. There was an intermediate portion comprising muscular intralobular arterioles which are believed to be capable of controlling the level of blood supply to the parenchyma of the carotid bodies. Finally there are glomic capillaries surrounded by elongated pericytes and sustentacular cells. One or other of these elongated cells is thought to be responsible for the carotid body hyperplasia which is associated with systemic hypertension and states of chronic hypoxaemia.

Adult↗