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Biomedical subjects

D Kelly

Publications and source records attributed to D Kelly.

At least 163 records · Page 9Linked to original sources

Risks of premature death and cancer predicted by body weight in early adult life.

In a study of 30 months duration, involving 600 male and 600 female Wistar rats fed on 12 different diets/dietary regimes, none of which involved deliberate exposure to any known genotoxic carcinogen, highly significant between-group differences were observed in survival and incidence of various neoplastic and non-neoplastic diseases. A full report of the findings is being prepared. Here we report that, irrespective of diet or dietary regime, there were highly significant correlations of body weight at 29 weeks of age with premature death (P less than 0.0001 in both males and females), with development of benign or malignant neoplasm of any site (P less than 0.0001 in males and P less than 0.01 in females) and with development of malignant neoplasm at any site (P less than 0.0001 for sexes combined). Numerous kinds of neoplasm contributed to these overall correlations. The most significant were pituitary tumour (P less than 0.0001), mammary gland tumour (P less than 0.0001), squamous or anaplastic carcinoma of the jaw (P less than 0.001), and subcutaneous mesodermal tumours (P less than 0.05). The 20% of rats that were heaviest at 29 weeks were more than twice as likely to die prematurely than the lightest 20% (2.56 times--males, and 2.11 times--females), and almost twice as likely to develop a malignant tumour (1.87 times for the sexes combined). These findings have important implications for the design and interpretation of carcinogenicity tests in rodents and of laboratory and human studies of relationships between diet, ageing-related degenerative diseases, and cancer.

Animals↗

The effects of sulindac and diclofenac in essential hypertension controlled by treatment with a beta blocker and/or diuretic.

A placebo-controlled, double blind crossover study of the non-steroidal anti-inflammatory drugs (NSAIDs) sulindac and diclofenac was conducted in 16 patients with essential hypertension that was controlled by treatment with a beta blocker, a diuretic or co-administration of both. In 4 cases, another antihypertensive agent (prazosin or verapamil) was also co-administered. In every patient, plasma creatinine concentration was less than 0.14 mmol/l (normal range 0.07-0.12 mmol/l). Sulindac and diclofenac were each given for 7 weeks. Diclofenac caused a decrease of borderline significance in plasma aldosterone concentration. Neither NSAID altered the mean values for systolic or diastolic blood pressure, body weight, plasma electrolyte concentrations, urate clearance, creatinine clearance or plasma renin activity. However, rises in plasma creatinine concentration and falls in creatinine clearance occurred during NSAID therapy in three individual subjects. No significant differences were observed in this study between the effects on renal function or blood pressure of sulindac and diclofenac, both of which appear not to interfere with the antihypertensive actions of beta blockers and diuretics.

Adrenergic beta-Antagonists↗

A retrospective study on hypothyroid patients.

A retrospective study of 58 hypothyroid patients attending the Endocrine Clinic, University Hospital of the West Indies, Jamaica, between July and August 1989, was undertaken. The age range at initial presentation varied from one month to eighty-four years. The majority of cases (51 or 87.9%) were between 21 and 70 years. There were 50 females (86.2%) and 8 males (13.8%). The underlying causes were idiopathic hypothyroidism (35 or 60.3%), posthyroidectomy (13 or 22.4%), post I131 therapy (6 or 10.4%), panhypopituitarism (3 or 5.2%), hypophysectomy (1 or 1.7%). Biochemical parameters used in diagnosis were serum thyroxine (T4) and thyroid-stimulating hormone (TSH). Forty-six patients (79.2%) had elevated TSH, indicative of a high correlation of elevated TSH with hypothyroidism. Duration of symptomatology prior to diagnosis was one year in 27 patients (46.5%), 2-10 years in 23 (39.6%) and 10 years in 4 cases (6.9%). The major presenting signs and symptoms were lethargy (20 or 34.5%), anaemia (mixed normochromic, microcytic (16 or 27.6%), slow relaxation of tendon reflexes (16 or 27.6%), coarsening of skin (15 or 25.9%), weight gain 10 or 17.2%), hoarseness (9 or 15.5%) and psychiatric symptoms (7 or 12%). The known association of primary hypothyroidism with other autoimmune disorders was not borne out in this study. The time-lapse in diagnosis from symptomatology emphasized the need for clinicians to be more alert to the subtle and varied presentation of hypothyroidism.

Adolescent↗

The skeletal framework of human kidney and renal cell carcinoma. A scanning electron microscopic study.

The three dimensional architecture of the connective tissue framework of normal human kidney and three renal cell carcinomas was studied. A sodium hydroxide maceration technique was used to remove the cellular elements thus exposing the underlying connective tissue structures. The collagen fibrillar network was visualized using the scanning electron microscope. In normal kidney the fibres were fine, and smooth, and corresponded to the shapes of the original parenchymal constituents. The fibres of the kidney tumours were coarse in nature and irregularly distributed. The technique provides a rapid method for studying connective tissue fibres in normal and diseased tissue. The three dimensional architecture thus exposed enhances our knowledge of tumour stroma.

Carcinoma, Renal Cell↗

Regulation and expression of transforming growth factor type-beta during early mammalian development.

We have examined the effect of differentiation on the expression of different members of the transforming growth factor type-beta (TGF-beta) family using embryonal carcinoma (EC) cells and early mammalian embryos. We determined that TGF-beta activity increases approximately 25-100% when the mouse EC cell line, F9, is induced to differentiate with retinoic acid (RA). Interestingly, the increased TGF-beta activity reflects the induction of TGF-beta 2 secretion following differentiation of both F9 EC cells and the human EC cell line, NT2/D1. Using the technique of reverse transcription-polymerase chain reaction (RT-PCR), we have verified that differentiation induces the expression of TGF-beta 2 as well as a distant member of the TGF-beta family, Vgr-1. Transcripts for TGF-beta 2 and Vgr-1 were readily detected in the differentiated cells of F9 and PC-13 but not in their undifferentiated counterparts. Moreover, TGF-beta 2 mRNA was readily detected in NT2/D1 cells following differentiation. In addition, transcripts for TGF-beta 2 were detected by RT-PCR in mouse morulae, preimplantation blastocysts and cultured blastocysts. Based on the data presented, it appears that the expression of both TGF-beta 2 and Vgr-1 is closely associated with the induction of differentiation during early development.

Animals↗

Expression of transforming growth factor-beta 3 by embryonal carcinoma cells, parietal endoderm-like cells and early mouse embryos.

Utilizing the technique of reverse transcription-polymerase chain reaction (RT-PCR), we have examined the expression of transforming growth factor-beta 3 (TGF-beta 3) by embryonal carcinoma (EC) cells, EC-derived differentiated cells and early mammalian embryos. Using a TGF-beta bioassay, we determined that PYS-2 cells express considerable TGF-beta activity that cannot be completely neutralized by antibodies specific for TGF-beta 1 and TGF-beta 2. We also have determined that PYS-2 cells, as well as F9 EC cells and their differentiated cells, express transcripts for TGF-beta 3. In addition, we have determined that blastocysts, cultured for three days in serum-containing medium, express TGF-beta 3 transcripts. Thus, our data suggest that expression of TGF-beta 3 is initiated during early stages of mammalian development.

Animals↗

A case-control study of congenital heart block: association with maternal antibodies to Ro(SS-A) and La(SS-B).

A case control study of congenital complete heart block (CHB) was undertaken to determine the degree of association of this condition with maternal connective tissue disease and with maternal autoantibodies, in particular those to Ro(SS-A). Mothers of cases (n = 18) and controls (n = 72) completed a self-administered questionnaire and donated 10 ml of blood. The odds of giving birth to a child with CHB were increased by a factor of 22 for women with antibodies to Ro(SS-A) and/or La(SS-B) compared with women who did not have these antibodies. Thus the association between CHB and both anti-Ro(SS-A) and anti-La(SS-B) antibodies has been demonstrated in an Australian population and indicates that anti-La(SS-B), as well as anti-Ro(SS-A) antibodies may be a risk factor for the development of CHB.

Adolescent↗

The cycling of combination antirheumatic drug therapy in rheumatoid arthritis.

In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications. Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein. This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment. Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months. Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects.

Activities of Daily Living↗

Tenoxicam compared with diclofenac in patients with ankylosing spondylitis.

A randomized study was performed on 24 patients with ankylosing spondylitis to compare the efficacy and tolerability of 20 mg tenoxicam daily with 50 mg diclofenac twice daily. There were 6 withdrawals from the group taking tenoxicam and 4 from the diclofenac group. Depression in 1 patient taking tenoxicam was the only significant adverse event. Both drugs were otherwise well tolerated. Tenoxicam and diclofenac were rated as good or excellent by 27% and 55% of patients, respectively. Global assessment, pain and duration of morning stiffness were improved with both drugs but this improvement was not statistically significant and there was no statistically significant difference between the two groups. This study confirms that tenoxicam is effective and well tolerated but larger numbers would be required to detect a small difference between groups.

Adult↗

Effect of creep feeding on structural and functional changes of the gut of early weaned pigs.

Dose-dependent hypersensitivity responses mounted against antigenic constituents of creep feeds have been previously implicated in intestinal damage, digestive disorders and impaired performance of early weaned pigs. In the present study biochemical and histological investigations of the small intestine were undertaken to determine the putative relationship between creep feed level and hypersensitivity response in pigs weaned at 14 days. Creep feed was administered by gastric intubation and weaned pigs received the same diet by gastric intubation for five days. Mucosal structure and function at weaning were not affected by creep feeding regimen. Villus height decreased and crypt depth increased in weaned compared to suckled pigs, but morphology was unaffected by prior exposure to creep. Xylose absorption was not influenced by either creep feed level or weaning. Intraepithelial lymphocyte numbers increased during weaning but were not affected by the creep feeding regimen. Mucosal carbohydrase activity in weaned pigs was not significantly affected by preweaning treatment. The results do not support the hypothesis that post weaning changes in structure and function of the gut are related to creep feed level or to immune responses to dietary antigens.

Animal Feed↗

Effect of creep feeding on the incidence, duration and severity of post-weaning diarrhoea in pigs.

The effect of creep feeding on the response of pigs weaned at two or three weeks old to infection with an enteropathogenic strain of Escherichia coli (O149; K91[B], K88 a, c [L]) was studied in two separate experiments. Gastric intubation was adopted to regulate the intake of creep feed during the sucking period. Animals were given the enteropathogenic strain either before weaning or at weaning and the course and outcome of the infection followed bacteriologically and clinically. The response of the animals to the infection varied considerably in accord with recent reports of multiple phenotypes (to K88 +ve organisms) among pigs but consumption of creep feed before weaning did not significantly affect the prevalence, duration or severity of the diarrhoea induced experimentally by the organism. Hence reputed immunological responses mounted against dietary antigens did not predispose to or protect against this infection.

Animal Feed↗

The value of routine admission chest radiographs in adult asthmatics.

One hundred twenty-five consecutive admissions in 102 patients hospitalized for acute bronchospasm were studied to determine the need for routine admission chest radiography in asthmatics. Patients were categorized as complicated or uncomplicated asthmatics based on data recorded in the emergency department. Thirteen admission chest radiographs in 44 complicated asthmatics had an impact on management, whereas none of the 81 radiographs in the uncomplicated group affected patient care (P less than .001). Our study suggests that routine admission chest radiographs in uncomplicated asthmatics may be unnecessary.

Acute Disease↗

Evaluation of infant feeding in acute gastroenteritis.

Sixty-eight bottle-fed babies under 9 months of age with mild acute gastroenteritis were observed to evaluate current feeding regimens following acute gastroenteritis in infancy. All babies were fed for 24 h with a glucose-electrolyte mixture (GEM) and then randomly assigned to either a gradual reintroduction to their normal milk, i.e., slow regrade; immediate return to full-strength formula; or a rapid regrade to a hypoallergenic whey hydrolysate formula. All groups were well matched for age, sex, ethnic origin, nutritional state, and degree of hydration. There was no significance difference in stool frequency or reducing substances, vomiting, and duration of hospital stay between the three groups. Many infants (6/24) refused to take the whey hydrolysate formula, presumably because of unpalatability. Weight gain was more rapid when full-strength milk was given. Clinical relapse developed in 12 (17%) of patients. An enteric pathogen was detected in eight of this group and cow's milk protein intolerance in three (one from each feeding group). No infant had clinically significant lactose intolerance, in marked contrast to previous experience at Queen Elizabeth Hospital. In this group of previously healthy, well-nourished babies with mild acute gastroenteritis, there was no advantage in regrading slowly to milk or a hypoallergenic formula. An immediate return to normal formula 24 h after GEM feeding was well tolerated and simpler for parents.

Acute Disease↗

Inhibitory effects of transforming growth factor-beta on laminin production and growth exhibited by endoderm-like cells derived from embryonal carcinoma cells.

Previous studies have shown that two mouse embryonal carcinoma (EC) cell lines do not express cell surface receptors for transforming growth factor type-beta (TGF-beta) until they are induced to differentiate. To understand the effects of TGF-beta in this model system, we have examined the effects of TGF-beta on parietal endoderm-like cells derived from EC cells. We have determined that TGF-beta exerts three effects on these cells. TGF-beta inhibits proliferation of the parietal endoderm-like cells, and this occurs even in the presence of growth factors that stimulate their proliferation. TGF-beta also alters the morphology of the parietal endoderm-like cells by increasing their spreading. Moreover, the morphological effect of TGF-beta is observed in the presence of dibutyryl cyclic AMP (dbcAMP), which reduces the spreading of these cells. Lastly, TGF-beta, but not other growth factors, decreases the production of laminin by the parietal endoderm-like cells. This was unexpected since TGF-beta has been shown to increase the production of extracellular matrices in other systems. Thus, our findings indicate that parietal endoderm-like cells provide a useful system for broadening the study of TGF-beta. Furthermore, our findings provide additional support for the possibility that TGF-beta plays important roles during the early stages of mammalian development.

Animals↗

Antenatal screening for hepatitis B is medically and economically effective in the prevention of vertical transmission: three years experience in a London hospital.

We describe our experience over a three-year period in the detection of antenatal patients with hepatitis B virus (HBV) carriage, and the successful prevention of vertical transmission in the infants of HBsAg-positive women. Nine of the 26 infants born to HBsAg-positive mothers were considered to be at high risk of infection. Eight of these nine remained HBsAg-negative after passive or passive/active immunization. The majority of infants tested had anti-HBs antibody titres above 10 i.u./l from the first month. In comparison with the cost of caring for patients with chronic hepatitis B infection and decompensated cirrhosis, non-selective testing of pregnant women for HBsAg is found to be cost effective.

Carrier State↗

Human perioral directional sensitivity.

The capacity of 41 neurologically healthy young adults to distinguish opposing directions of brush motion across the skin innervated by the mental nerve was determined. The velocity and orientation and the length and width of skin traversed by the moving tactile stimuli were carefully controlled. Directional sensitivity, d', was found to vary curvilinearly with velocity over the range 0.5 to 32 cm/s. Because the data from most subjects were well described by a generalized gamma function, it was possible to characterize this velocity dependency quantitatively. Specifically, indices derived from these functions were found to describe the subject's peak (i.e., maximal) sensitivity, the velocity which resulted in peak sensitivity (i.e., the optimal velocity), and the degree to which stimulus velocity influenced the ability to recognize direction of motion (i.e., the velocity-tuning of d'). Peak sensitivity, optimal velocity, and the degree of global velocity-tuning were found to differ between males and females. Confidence limits (the lower and upper 2.5% points) for the normative data were determined to enable detection and characterization of deficits in orofacial tactile motion sensitivity in individuals with damaged mandibular nerves.

Adult↗

Primary amyloidosis of lower urinary tract.

Primary amyloidosis of the lower urinary tract is a rare condition with an excellent prognosis in most cases. Three patients with this condition are described. In the cases of localized amyloidosis of the urethra and urinary bladder, the clinical presentation mimicked cancer of the respective sites. This was also true in the case of primary systemic amyloidosis involving the bladder. If significant associated systemic or local disease can be excluded, management is symptomatic and expectant.

Aged↗