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Biomedical subjects

D Kelly

Publications and source records attributed to D Kelly.

At least 37 records · Page 2Linked to original sources

Digestive development of the early-weaned pig. 1. Effect of continuous nutrient supply on the development of the digestive tract and on changes in digestive enzyme activity during the first week post-weaning.

Gastric intubation was adopted to examine the effect of continuous nutrient supply on digestive development of the pig during the immediate post-weaning period. The 14 d-weaned animals were slaughtered at 3, 5 and 7 d post-weaning (3W, 5W and 7W respectively) and the suckled animals were slaughtered at 14 and 22 d of age (14SR and 22SR respectively). The weight of the pancreas (g/kg bodyweight) was significantly greater (P less than 0.05) in the 5W and 7W groups, as was the weight of large intestine (g/kg) in all weaned groups (P less than 0.01) compared with sow-reared pigs. The stomach weight (g/kg) tended to be greater in the weaned groups. Weaning, in conjunction with a continuous nutrient supply, did not significantly alter the time-related changes in the weight of the small intestine (SI) or the SI mucosa, although both variables tended to be lowest in the 3W group. However, there was a 20% reduction in the protein content of the mucosa within the first 3 d post-weaning (P less than 0.01) which persisted during the 7 d experimental period. Lactase, (beta-galactosidase; EC 3.2.1.23) activity (mumol/g protein and mol/d) of the 7W group was reduced to approximately 40% of the 22SR value. Hence, continuous nutrient supply may have delayed, but did not prevent, the loss of lactase activity at weaning. The activity of sucrase (sucrose-alpha-glucosidase; EC 3.2.1.48) was significantly higher in 22SR compared with 14SR animals. Sucrase activity in weaned pigs was intermediate to the values for sow-reared pigs whereas maltase (alpha-glucosidase; EC 3.2.1.20) and glucoamylase (glucan 1,4-alpha-glucosidase; EC 3.2.1.3) were significantly increased in relation to their sow-reared counterparts. Continuous nutrient supply did not prevent the reduction in villous height and the crypt hypertrophy associated with weaning. The results of the present study suggest that there may be some degree of interaction between nutrient intake and gut development during the immediate post-weaning period but that there is also a component of the adaptive response which is independent of nutrient intake. They confirm the rapid substrate induction of the brush-border glucoamylases and indicate the importance of considering total as well as specific enzyme activity for satisfactory interpretation of changes in digestive function.

Animal Nutritional Physiological Phenomena

Digestive development of the early-weaned pig. 2. Effect of level of food intake on digestive enzyme activity during the immediate post-weaning period.

Gastric intubation was adopted as a means of comparing the effect of two feeding levels, continuous nutrient supply (C) and restricted nutrient supply (R), on the digestive development of pigs weaned at 14 d of age, during the first 5 d post-weaning. The absolute weights of the stomach and the pancreas were significantly greater (P less than 0.001) in C compared with R pigs. The effect was not significant for pancreas weight when expressed per kg body-weight but was significant (P less than 0.05) for stomach weight. The weights of the small intestine (SI), SI mucosa and total mucosal protein were significantly higher (P less than 0.001) in C pigs but protein content per g mucosa was similar in the C and R groups. There was no significant effect of treatment on the activity of lactase (beta-glucosidase; EC 3.2.1.23) or sucrase (sucrose-alpha-glucosidase; EC 3.2.1.48) irrespective of the basis of comparison used. The specific activity (mumol/min per g protein) of maltase (alpha-glucosidase; EC 3.2.1.20) and of glucoamylase (glucan-1,4-alpha-glucosidase; EC 3.2.1.3) were similar in C and R groups but activities of maltase (mumol/g mucosa) (P less than 0.05), and maltase and glucoamylase (mol/d) (P less than 0.01) were significantly higher in C pigs. Villous height and crypt depth were significantly greater in C pigs (P less than 0.001 and P less than 0.05 respectively). Enteroglucagon was significantly (P less than 0.05) higher in C compared with R pigs. Xylose absorption and the digestibility of energy were not affected by treatment. Digestibility of dry matter, organic matter, crude protein (nitrogen x 6.25) and carbohydrate were significantly higher (P less than 0.001, P less than 0.01, P less than 0.05 and P less than 0.001 respectively) in R pigs compared with C pigs but the differences were small, ranging from 1.3 to 2.5%. These results demonstrate that (1) nutrient intake in the weaned pig affects the anatomy, morphology and function of the gut, (2) there is considerable 'spare capacity' for digestion of cereal-based diets even in pigs weaned at 14 d of age, (3) measurements in vitro of digestive function are of limited value unless supported by information in vivo on absorption/digestibility.

Animal Nutritional Physiological Phenomena

The viability of microorganisms in preservation solutions.

In 1988 the University of Wisconsin solution was introduced into clinical transplantation. This solution is unique in that it contains no glucose but rather raffinose, lactobionate, and hydroxyethyl starch. In addition, it contains two antibiotics, penicillin and bactrim. Prior studies have shown that other preservation solutions allow the transmission of bacterial contamination from organ donor to recipient. However, there are no data on whether UW solution, with its unique composition and extended preservation times, allows bacterial transmission. We undertook the present study to establish if bacteria remain viable in UW solution at extended preservation times. Cultures of both aerobic (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa) and anaerobic (Bacteroides fragilis) bacteria were suspended at 10(5), 10(4), 10(2), and 10(1) org./ml (calibrated from a .5 Macfarland turbidity standard) in both Eurocollins and UW preservation solutions. Samples were then stored in an ice bath to stimulate organ preservation. The organisms were removed and plated on blood and chocolate agar at 0, 6, 12, 18, 24, and 36 hr postsuspension. The samples were then incubated at 37 degrees C and read for growth at 24-48 hr after plating. Our results showed growth of all organisms except S epi in both preservation solutions, at all dilutions and preservation times. S epi grew in the Eurocollins solution at all dilutions and preservation times but did not grow in the UW solution. When the experiment was repeated omitting penicillin from the UW solution, S epi grew at all dilutions and preservation times. These results demonstrate that in spite of the inclusion of two different antibiotics, the majority of the common bacterial contaminants of the organ donor remain viable in UW solution with extended preservation times. It may be possible therefore to omit these antibiotics from the UW solution and obtain similar results. It is also important to note that routine culturing remains an expensive but necessary part of organ procurement and preservation.

Adenosine

Trauma in cirrhosis: an indicator of the pattern of alcohol abuse in different societies.

While some morbidities associated with the excessive use of alcohol are related to the total amount of alcohol consumed--cirrhosis being an example--other pathologies, such as trauma and those of psycho-social origin, are mainly related to the frequency of acute alcoholic intoxication rather than to the total amount consumed. The balance between these two types of alcohol-associated morbidities can provide an indication of the relative frequency of intoxication, and thus of the pattern of alcohol abuse in a population. Since trauma is highly associated with acute alcoholic intoxication, the prevalence of bone fractures was determined in cirrhotics in nine countries. The prevalence of rib and vertebral fractures on routine chest x-rays showed a 17-fold variation in the different countries, from 2% and 6% in Spain and Italy to 30% and 34% in Canada and the USA, suggesting marked differences in the pattern of alcohol abuse to intoxication. Conversely, the prevalence of cirrhosis is twice as high in Spain and Italy than in Canada and the USA. A strong positive correlation between per capita consumption and cirrhosis mortality (r = 0.86; p less than 0.01) exists among the nine countries studied, while the correlation between per capita alcohol consumption and the prevalence of trauma is not statistically significant (r = 0.40). Supporting a strong association between trauma and alcoholic intoxication, the prevalence of trauma was found to be highly correlated: r = 0.88, p less than 0.002, with the degree of concern for the psycho-social consequences of alcohol abuse in the different countries. Data indicate that trauma can be used as an objective indicator to assess the pattern of alcohol abuse in a population.

Alcohol Drinking

Hemolytic and sphingomyelinase activities of Clostridium perfringens alpha-toxin are dependent on a domain homologous to that of an enzyme from the human arachidonic acid pathway.

The N-terminal domain of Clostridium perfringens alpha-toxin, homologous with the nontoxic phospholipase C of Bacillus cereus, was expressed in Escherichia coli and shown to retain all of the phosphatidylcholine hydrolyzing activity of the alpha-toxin, but not the sphingomyelinase, hemolytic, or lethal activities. The C-terminal domain of alpha-toxin showed sequence and predicted structural homologies with the N-terminal region of arachidonate 5-lipoxygenase, an enzyme from the human arachidonic acid pathway which plays a role in inflammatory and cardiovascular diseases in humans.

Amino Acid Sequence

Effect of lactation on the decline of brush border lactase activity in neonatal pigs.

It has been shown that during the early phase of lactation porcine milk contains high concentrations of hormones and growth factors. The aim of the present investigation was to examine the hypothesis that the temporal coordination of intestinal maturation in piglets can be extrinsically regulated through changes in the composition of milk during the suckling period. Gut morphology and the ontogeny of brush border lactase activity were investigated in piglets reared on two suckling regimens designed to expose the animals to compositionally distinct milk. The first group of animals were cross-fostered onto postcolostrum sows and thereafter suckled normally for up to eight weeks. These normally suckled (N) animals consequently received both early and late lactation products. The second group of piglets were cross-fostered each week, for up to eight weeks, onto newly farrowed sows which were postcolostrum. As a result of this repeated cross-fostering (CF) these animals received only early lactation products. Animals were sacrificed at one, three, five, seven, and eight weeks postpartum. Biochemically active lactase decreased significantly (p less than 0.001) in both groups over eight weeks, but the rate of loss of activity was greater in the CF animals than in the N pigs by approximately 50% at week 3 and 25% at week 8. Quantitative histochemical analysis of lactase activity corroborated the biochemical data. At three weeks maximal enzyme activity was observed approximately 400 microns from the villus/crypt junction. Histochemically detected lactase decreased throughout the suckling period, but the intensity of reaction product was consistently weaker over the entire villus surface in the CF animals. Immunocytochemically detectable lactase was identified at the same sites as the histochemical reaction products. In addition, immunofluorescence microscopy showed the presence of histochemically undetectable enzyme on the basolateral and brush border membranes of both villus and crypt cells. Villus/crypt ratios were significantly lower (p<0.001) in the CF animals than in the N pigs between weeks 3 and 5. The results of this study suggest that lactation products can accelerate the loss of brush border lactase activity. The observed decline in biochemically and histochemically detected lactase was considered to be a consequence of reduced enterocyte lifespan, decreased synthesis of enzyme protein, or altered post-translational modification of enzyme protein, or a combination of there.

Animals

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