PubMed HealthSearch

Biomedical subjects

M G Thomas

Publications and source records attributed to M G Thomas.

At least 19 recordsLinked to original sources

Tuberculosis in those with HIV infection.

AIMS: To determine the incidence, demography, clinical features, treatments and outcome for patients with tuberculosis and human immunodeficiency virus (HIV) infection in Auckland. METHODS: We reviewed the notes of all patients with HIV infection and tuberculosis seen by the Infectious Disease Unit, at Auckland Hospital since the onset of the HIV epidemic in New Zealand in 1984 until 31 December 1995. RESULTS: Eleven patients have had HIV infection and tuberculosis, 2.4% of all those with HIV infection cared for by this unit. Ten were male and eight homosexual. The median age was 30 years (range 24-57). The incidence in Pakeha was 1.2% (3 of 234), in Maori 20% (5 of 25) and in African 27% (3 of 11). Until 1990 we saw one case every two years and since then one or two cases per year. Six patients had normal chest x-rays and five had abnormal chest x-rays; of the latter, three were typical of tuberculosis and two atypical. Ten of the eleven strains of Mycobacterium tuberculosis cultured were fully sensitive but one was resistant to both rifampicin and isoniazid. Conventional treatment regimens were used. Seven patients have died of HIV infection, three continue treatment and one returned to Africa. One patient relapsed with fully sensitive tuberculosis. Three patients had major side effects to rifampicin necessitating alternative treatment. CONCLUSIONS: Tuberculosis is uncommon amongst those with HIV infection in Auckland but the incidence has risen in recent years. The risks amongst Maori and Africans are high. Multidrug resistant tuberculosis is uncommon. Those caring for patients with tuberculosis need to be mindful of HIV infection: those caring for patients with HIV infection need to be increasingly alert for tuberculosis.

AIDS-Related Opportunistic Infections

Villous adenoma of the distal appendix.

Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

Acute Disease

The steroid vitamin D3 reduces cell proliferation in human duodenal epithelium.

1. The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, controls calcium absorption in the human duodenum, an effect that is mediated by mucosal vitamin D receptor expression. Functional vitamin D receptor signalling in the human colon is suggested by the reduced colonic mucosal cell proliferation seen in response to 1,25-dihydroxyvitamin D3. Thus 1,25-dihydroxyvitamin D3 might be expected to reduce cell proliferation in the small-bowel epithelium. 2. We have used an organ-culture system combined with the metaphase arrest technique to study the effects of 1,25-dihydroxyvitamin D3 on human duodenal mucosal proliferation. To validate our technique, multiple human mucosal explants were established in organ culture and vincristine (0.6 micrograms/ml) was added at 10 h. Explants were removed sequentially from 10 to 15 h and metaphase arrest figures were demonstrated by using the Feulgen reaction. The mean number of metaphase arrest figures was plotted against time in culture to show a linear accumulation of metaphases between 11 and 15 h (correlation coefficient = 0.93, r2 = 0.87, P < 0.0001). The mean crypt cell production rate was 2.01 (0.27) cells/h per crypt. 3. Paired normal duodenal mucosal biopsies from six patients were then established in organ culture with or without 10(-10) mol/l (100 pmol/l) 1,25-dihydroxyvitamin D3. The crypt cell production rate was determined between 12 and 15 h after vincristine-induced metaphase arrest. 1,25-Dihydroxyvitamin D3 reduced the median crypt cell production rate from 2.42 (1.15-4.82) to 1.41 (0.03-2.05) cells/h per crypt (P < 0.05). Thus, vitamin D3 reduces human duodenal epithelial cell proliferation.

Aged

Regulatory roles of high-density and low-density lipoproteins in cellular proliferation and secretion of progesterone and insulin-like growth factor I by enriched cultures of bovine small and large luteal cells.

We tested the hypotheses that bovine high-density (HDL) and low-density (LDL) lipoproteins differentially influence cellular proliferation and progesterone and IGF-I production by bovine small and large luteal cells. Unit gravity sedimentation was used to produce enriched cultures of small (> 95% pure) and large (75 to 90% pure) luteal cells from corpora lutea (CL) on d 4 and 10 of the estrous cycle. Addition of LDL, HDL, or both resulted in the maintenance of higher (P < .05) numbers of 3beta-hydroxysteroid dehydrogenase (HSD)-positive small and large cells in culture and produced a marked proliferation of 3beta-HSD-negative small luteal cells compared to control medium. Low-density lipoprotein and HDL each stimulated greater (P < .01) progesterone secretion in enriched large cell cultures on both days of the cycle, and by small luteal cells on d 10, compared to the control. Together, LDL and HDL maximized this response. Lipoproteins markedly stimulated (P < .01) the secretion of IGF-I by bovine large luteal cells, and secretion was greater (P < .05) by cells from d 10 CL compared to d 4 CL. Results suggest that the actions of lipoproteins in bovine luteal cells extend beyond their widely recognized roles in steroidogenesis and include remarkable effects on cellular proliferation and IGF-I secretion. Type of lipoprotein (LDL vs HDL) did not have differential effects on any of the variables measured.

3-Hydroxysteroid Dehydrogenases

Methscopolamine bromide blocks hypothalamic-stimulated release of growth hormone in ewes.

Twenty-five nonlactating ewes were used to test the hypothesis that methscopolamine bromide (MB) blocks secretion of growth hormone (GH) by affecting hypothalamic rather than pituitary mechanisms. Ewes were randomly assigned to receive a s.c. injection of 96 mg of MB or 2 mL of saline at min = 0. Saline-treated ewes were assigned to receive a subsequent (at +60 min) i.v. injection of 10 microg of growth hormone-releasing hormone (GHRH) to test pituitary responsiveness or .3 mg of clonidine to test hypothalamic responsiveness. Methscopolamine bromide-treated ewes were assigned to receive a subsequent (at +60 min) i.v. injection of 10 microg of GHRH, .3 mg of clonidine, or 2 mL of saline. Jugular blood samples were collected at 10-min intervals from -120 min to +240 min, and serum concentrations of GH were quantified with a RIA. No difference was detected in serum concentrations of GH with respect to MB vs saline treatment (P = .20). Concentrations of GH increased in saline-pretreated ewes following injections of clonidine or GHRH (P < .01). Treatment of ewes with MB, however, limited the ability of clonidine-induced mechanisms to increase concentrations of GH, but did not affect pituitary responsiveness to GHRH (P < .01). These data support the hypothesis that MB inhibits hypothalamic and not pituitary mediated mechanisms that regulate the secretion of GH.

Adrenergic alpha-Agonists

Dietary fats varying in their fatty acid composition differentially influence follicular growth in cows fed isoenergetic diets.

The working hypothesis was that dietary fats differing in fatty acid composition would differentially influence ovarian follicular growth. Cows (n = 27) were fed isoenergetic, isonitrogenous, and isofibrous diets containing no added fat (control; CT, n = 7) or diets supplemented with fats containing primarily saturated (SAT, n = 7), polyunsaturated (PU, n = 7), or highly polyunsaturated (HPU, n = 6) fatty acids. Coincident changes in serum lipid metabolites, insulin, and GH and the concentration of IGF-I in large and medium-sized follicles also were examined. Body weights and body condition scores remained similar for all groups throughout the study. Polyunsaturated fat increased (diet x day, P = .06) the number of medium-sized follicles on d 5 through 9 of a synchronized estrous cycle within 3 wk of onset of feeding and maximized (P < .001) this to a fourfold difference at ovariectomy after 7 wk. Fats with predominantly SAT and HPU tended (P < .10) to produce these effects after 7 wk. All fat-supplemented diets increased serum concentrations of total cholesterol (P < .05), GH (P < .05), and follicular fluid IGF-I in large follicles (P < .065) compared to CT but differentially influenced serum concentrations of insulin. Polyunsaturated fat stimulated a marked increase (P < .001) in serum insulin relative to controls within 3 wk, whereas SAT and HPU increased (P < .05) serum insulin only after 6 to 7 wk. We conclude that consumption of PU fatty acids stimulates a greater rate of ovarian follicular growth in cattle compared to CT, AT, and HPU. Future research should investigate the potential role of insulin in mediating PU effects on follicular growth.

Animal Nutritional Physiological Phenomena

Meningitis complicating spinal surgery.

STUDY DESIGN: A retrospective review of all cases of bacterial meningitis after spinal surgery. OBJECTIVES: To identify the usual clinical and laboratory features, and to determine the frequency of this complication. SUMMARY OF BACKGROUND DATA: Meningitis has been recognized as a rare complication of spinal surgery, but no series of cases has been reported previously, and there are no published estimates of its frequency. METHODS: A retrospective review of the medical records of all cases of bacterial meningitis after spinal surgery in Auckland over a 3-year period was done. RESULTS: Four cases were identified after 2180 operations, an incidence of 0.18%. All four patients survived. CONCLUSIONS: This is a rare complication from which a good outcome is possible with early diagnosis and prompt management.

Adult

Hepatitis B virus variants with core gene deletions in the evolution of chronic hepatitis B infection.

BACKGROUND & AIMS: Genomic variants of the hepatitis B virus (HBV) with core gene deletions have been identified in patients with chronic active hepatitis B, but the significance of these mutations in the course of chronic HBV infection remains unknown. The aim of this study was to longitudinally analyze the changes of HBV core gene deletion variants under the enhanced immune pressure of interferon alfa treatment and hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (anti-HBe) seroconversion. METHODS: HBV precore/core gene was amplified in 358 serum samples from 67 chronic HBV carriers (all HBeAg-positive) followed up for a period of 2-11 years. The core gene deletions were analyzed by gel electrophoresis, cloning, and DNA sequencing. RESULTS: HBV mutants with core gene deletions (37-250 base pairs) were detected in patients with long-standing HBV replication and ongoing hepatic inflammation, always together with the wild-type strain. They were associated with a significantly lower level of viremia and a high rate of seroconversion to anti-HBe. Core gene deletion mutants were preferentially eliminated after seroconversion, in contrast to the accumulation of HBV strains with a precore stop codon. CONCLUSIONS: These data indicate that HBV variants with core gene deletions may inhibit HBV replication, do not persist in preference of the wild-type HBV under enhanced immune pressure, and do not confer resistance to interferon alfa treatment.

Adult

Tc-99m stannous colloid-labeled leukocyte scintigraphy in the evaluation of the painful arthroplasty.

The aim of this study was to evaluate the utility of scintigraphy using leukocytes labeled with Tc-99m stannous colloid in the assessment of painful arthroplasties. The results of three-phase bone scintigraphy and imaging with Tc-99m-labeled leukocytes in 40 patients with painful joint prostheses, requiring the exclusion of infection are reported. Results were compared with microbiologic culture and/or long-term clinical review. Bone scintigraphy had a sensitivity of 100%, a specificity of 64%, and a diagnostic accuracy of 73% in detecting prosthetic infection. Tc-99m-labeled leukocytes yielded a sensitivity of 70%, a specificity of 100%, and a diagnostic accuracy of 93%. Leukocyte scintigraphy improves the specificity of bone scintigraphy in the assessment of the painful prosthetic joint. A positive study is highly suggestive of infection and warrants appropriate treatment.

Adult

Efficient retroviral infection of mammalian cells is blocked by inhibition of poly(ADP-ribose) polymerase activity.

Integration of proviral DNA into the host cell genome is a characteristic feature of the retroviral life cycle. This process involves coordinate DNA strand break formation and rejoining reactions. The full details of the integration process are not yet fully understood. However, the endonuclease and DNA strand-joining activities of the virus-encoded integrase protein (IN) are thought to act in concert with other, as-yet-unidentified, endogenous nuclear components which are involved in the DNA repair process. The nuclear enzyme poly(ADP-ribose) polymerase (PARP), which is dependent on DNA strand breaks for its activity, is involved in the efficient repair of DNA strand breaks, and maintenance of genomic integrity, in nucleated eukaryotic cells. In the present work, we examine the possible involvement of PARP in the retroviral life cycle and demonstrate that inhibition of PARP activity, by any one of three independent mechanisms, blocks the infection of mammalian cells by recombinant retroviral vectors. This requirement for PARP activity appears to be restricted to processes involved in the integration of provirus into the host cell DNA. PARP inhibition does not affect viral entry into the host cell, reverse transcription of the viral RNA genome, postintegration synthesis of viral gene products, synthesis of the viral RNA genome, or the generation of infective virions. Therefore, efficient retroviral infection of mammalian cells is blocked by inhibition or PARP activity.

3T3 Cells

Imported malaria in Auckland in 1993.

AIM: To determine the number of people with malaria in Auckland in 1993 and determine species, sources, exposure history, use of chemoprophylaxis, outcome and geographic attack rates. METHODS: We prospectively obtained the numbers of people with laboratory diagnosed malaria from all haematology departments in Auckland and then contacted the patients and their doctors to elicit further details. RESULTS: Forty three people, 30 men and 13 women, had malaria. Twenty eight were New Zealanders, 10 migrants, three temporary visitors and two not determined. Thirty two had P vivax infection, 11 P falciparum: none had complications. The highest attack rate was in travellers to the Solomon Islands. Eighty two per cent took prophylaxis. CONCLUSIONS: Malaria is an uncommon diagnosis in Auckland. Most patients took prophylaxis. The disease is undernotified. No one died of malaria in 1993 in Auckland.

Adolescent