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Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 127 records · Page 7Linked to original sources
PubMed2000

Expression and function of striatal nAChRs differ in the flinders sensitive (FSL) and resistant (FRL) rat lines.

Rats of Flinders Sensitive (FSL) and Flinders Resistant lines (FRL) differ in their susceptibility to physiological and associated behavioral responses elicited by nicotine. In the present study, we measured dopamine (DA) content in striatal dialysates to investigate the sensitivity of FSL and FRL rats to nicotine delivered locally through a microdialysis probe placed in the striatum. We also measured the expression density of striatal high-affinity nicotinic acetylcholine receptors (nAChRs), and that of mRNAs encoding for alpha3, alpha4, alpha7 and beta2 nAChR subunits in both lines. The DA content of dialysates was measured before and after a 1-min perfusion of nicotine (6, 10 or 20 nmoles/min) and the resulting DA increase was taken as a measure of the alkaloid's intrinsic activity for nAChRs involved in the release of DA. The nicotine-induced increase of striatal DA release was greater in FSL than in FRL rats for all concentrations of nicotine, suggesting that the intrinsic activity of nicotine was greater in the FSL than in the FRL rats. This was further supported by our finding that the density of high-affinity nAChRs in the striatum of FSL rats was 44% greater than in the FRL rats, whereas affinity (K(D)) was virtually the same in the two lines of rats. Also the expression of mRNAs encoding for alpha(4), alpha(7), and beta(2) subunits in the striatum was greater in FSL than in FRL rats (attomol/microg total RNA, alpha(4):98+/-10 vs. 77+/-7; alpha(7):279+/-16 vs. 184+/-16; beta(2):310+/-19 vs. 201+/-12). We hypothesize that the difference in nicotine-induced DA release in the striatum of FSL and FRL rats depends on the difference in nAChR subunit expression in the striatum between the two lines. The Flinders rats could be used as a model for nicotine self-administration studies to evaluate the susceptibilities of FSL and FRL rats to nicotine dependence.

Animals↗
PubMed2000

Recurrent anomalies of 6q25 in chondromyxoid fibroma.

Chondromyxoid fibroma is a rare benign bone tumor most commonly arising in the metaphysis of long bones in young adults. Histopathologically, chondromyxoid fibroma may be difficult to distinguish from other cartilaginous neoplasms. Recently, a pericentric inversion of chromosome 6 [inv(6)(p25q13)] has been proposed as a specific genetic marker for chondromyxoid fibroma. In this study, cytogenetic and spectral karyotypic analyses of 2 chondromyxoid fibroma cases showed clonal abnormalities of chromosome 6 but at a breakpoint on the long arm (q25) distal to that described in the pericentric inversion. These findings suggest that several distinct breakpoints on chromosome 6 are nonrandomly involved in chondromyxoid fibroma.

Adult↗
PubMed2000

Cytogenetic findings in a case of epithelioid sarcoma and a review of the literature.

Cytogenetic studies of epithelioid sarcoma, a rare malignant soft tissue neoplasm of adolescents and young adults, are few. A characteristic anomaly has not yet been identified for this sarcoma. In this study, cytogenetic studies of a primary epithelioid sarcoma of a 15-year-old male revealed the following abnormalities: t(6;8)(p25;q11.2) and add(7)(p15).

Adolescent↗
PubMed2000

Treatment of HIV-associated invasive anal cancer with combined chemoradiation.

There is an increased frequency of invasive anal cancer in HIV-seropositive men. Early treatment strategies in this patient group employed reduced dosages of chemotherapy or radiotherapy alone to reduce toxicity. Since 1989 we have used combined modality treatment consisting of chemotherapy 5-fluorouracil (5-FU) and mitomycin C, and concomitant radical radiotherapy to the pelvis (38-51 Gy in 20-30 fractions), with most patients receiving a perineal boost (10-18 Gy). 12 homosexual HIV-positive men have been treated. The median CD4 count at diagnosis of anal cancer was 209 cells/microl (range: 29-380 cells/microl), 5 had prior AIDS defining diagnoses. No patients had metastatic disease. Complete remissions were obtained in 9/11 evaluable patients and in 1 further patient following surgery. 2 patients relapsed both within 6 months of diagnosis. At a median follow-up of 4.8 years (range: 0.4-10 years), 4 patients have died (2 from anal cancer, 1 from treatment-related consequences and 1 from opportunistic infection in remission). Actuarial 2-year survival is 60% (95% confidence interval (CI): 29-91%). Grade 3 haematological toxicity was recorded in 3 patients, grade 4 and 5 gastrointestinal toxicity in 1 patient each and grade 3 skin toxicity in 1 patient. Radical chemoradiation may be given safely at conventional doses in HIV-positive patients, with a high complete response rate.

Adult↗
PubMed2000

Weekly alternating combination chemotherapy for good prognosis AIDS-related lymphoma.

Early studies reported that the major adverse prognostic factors in AIDS-related non-Hodgkin's lymphoma (ARL) are low CD4 cell count, prior AIDS defining diagnosis and poor performance status. Since 1989 we have adopted a prognosis-stratified approach for ARL. In this study, we identified a group of good prognosis patients. These patients with one or no adverse prognostic factors were treated with alternating weekly chemotherapy using the bleomycin, etoposide, vincristine, methotrexate, prednisolone/cyclophosphamide, doxorubicin (BEMOP/CA) schedule (Bower M, Block C, Gulliford T, et al. Cancer Chemother Pharmacol 1995, 38, 106-109). Modifications to the regimen with the aim of reducing toxicity were a briefer duration (12 weeks) and the addition of prophylaxis against pneumocystis and mycobacteria. Intrathecal methotrexate was administrated fortnightly to patients with Burkitt's histology, meningeal involvement or base of skull disease. 30 patients were treated, including 5 with prior AIDS, 3 with ECOG status 3 and 1 with CD4 <100/microl. The mean age was 40 (range 22-60 years), the median CD4 cell count at ARL diagnosis was 262/microl (range 44-588/microl). The International non-Hodgkin's lymphoma (NHL) prognostic factors project classifications were low risk 8 (maximum 5.4 years) (27%), low-intermediate risk 6 (20%), high-intermediate risk 11 (37%) and high risk 5 (17%). The median follow-up was 2.1 years. 3 patients withdrew from treatment within 2 weeks due to toxicity, 2 patients died within 2 weeks of starting chemotherapy. The major toxicity was myelosuppression with 14 patients developing grade 4 neutropenia. The 2-year overall survival rate is 46% (95% confidence interval (CI)=27-65%), and lymphoma-specific survival at 2 years is 59% (95% CI: 40-78%). For selected patients with good prognosis ARL 12 weeks BEMOP/CA therapy produces good overall survival at 2 years.

Adult↗
PubMed2000

Childhood nutrition and poverty.

One in three children in Britain lives in poverty (households whose income was less than 50% average earnings). Low income is associated with poor nutrition at all stages of life, from lower rates of breast-feeding to higher intakes of saturated fatty acids and lower intakes of antioxidant nutrients. Moreover, there is increasing evidence that poor nutrition in childhood is associated with both short-term and long-term adverse consequences such as poorer immune status, higher caries rates and poorer cognitive function and learning ability. These problems arise primarily because parents do not have enough money to spend on food, not because money is being spent unwisely. Policy options to improve the dietary health of poor children include: giving more money to the parents by increasing Income Support (social security) payments, providing food stamps or vouchers, and using food budget standards to inform the levels of income needed to purchase an adequate diet; feeding children directly at school (not only at lunchtime but also at breakfast or homework clubs), by providing free fruit at school, and by increasing entitlement to free food amongst children living in households with low incomes; improving access to a healthy and affordable diet by first identifying 'food deserts' and then considering with retailers and local planners how best to provide food in an economical and sustainable way. The value of using food budget standards is illustrated with data relating expenditure on food to growth in children from 'at-risk' families (on low income, overcrowded, headed by a lone parent or with four or more children under 16 years of age) living in a poor area in London. Lower levels of expenditure are strongly associated with poorer growth and health, independent of factors such as birth weight, mother's height, or risk score. The present paper provides evidence that supports the need to review Government legislation in light of nutrition-related inequalities in the health of children.

Budgets↗
PubMed2000

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy.

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

Anti-HIV Agents↗
PubMed2000

T-cell expansions in patients with multiple myeloma have a phenotype of cytotoxic T cells.

The presence of T-cell clones in peripheral blood has been previously shown to be associated with a survival advantage in patients with multiple myeloma and suggests that the expanded T-cell populations may be involved in an anti-tumour response. We studied the T-cell receptor (TCR) repertoire of 38 patients with myeloma to identify and characterize the expanded T-cell populations by flow cytometry. T-cell expansions were found in 79% of the patients. The expansions occurred randomly among the 21 variable regions of the TCR beta chain (Vbeta) studied, representing 62% of the V-beta repertoire, and were stable during an 18-month follow-up. The phenotype of the expanded V-beta populations was predominantly CD8+, CD57+, CD28- and perforin+, which differed significantly from the other non-expanded Vbeta populations. The expression of the apoptosis markers Fas (CD95) and bcl-2 were similar between the expanded and non-expanded Vbeta populations. In conclusion, expanded T-cell populations were frequent in patients with myeloma, they remained unchanged during follow-up and had phenotypic characteristics of cytotoxic T cells. These data add further support to the concept that the T-cell expansions may have an immunoregulatory role in myeloma.

Aged↗
PubMed2000

Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.

Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.

Adult↗
PubMed2000

Survey of dietetic provision for patients with diabetes.

AIMS: To survey dietitians involved in diabetes care regarding the provisions for patients with diabetes. METHODS: A national survey of 512 dietitians known to be engaged in provision of diabetes care was conducted in 1997 and 391 (76%) responded. RESULTS: Nationally the median provision of dietetic care for diabetes reported was 10.7 h per 100,000 general population per week, but the provision was uneven ranging from 2.0 to 27.6 h per 100,000. Eighty-five per cent of dietitians worked in areas where the provision was less than 22 h per 100,000 general population per week (the current recommended minimum standard). Dietetic provision was greater in secondary care (median 9.1 h per 100,000 general population per week) than in general practice, residential homes and other locations (median 4.4 h per 100,000 general population per week). Provision was greater in those areas in which a designated dietitian had responsibility for co-ordinating the dietetic service for diabetes than in areas where the co-ordinator was not a dietitian or where there was no co-ordinator. Over 90% of dietitians reported following British Diabetic Association (BDA) recommendations regarding advice on carbohydrate, sugar, fat and fibre consumption, but only one-third routinely advised on salt restriction. Of the 17% of dietitians who continue to use carbohydrate exchanges, all combine this method with other approaches. Of the recommendations made by the Clinical Standards Group, only 69% of dietitians reported seeing more than half of newly diagnosed adult patients within four weeks, and less than 50% reported offering half or more of their patients an annual review. Amongst the literature in current use, 98% of dietitians use BDA literature for teaching patients and 90% use BDA publications in their own education. Seventy-six per cent of dietitians believed that there was a role for commercial slimming organizations in weight management of people with diabetes. CONCLUSIONS: Given the proven value of dietetic input in diabetes management, there would be advantages to correcting the regional inequalities in dietetic provision for diabetes care in the UK.

Adult↗
PubMed2000

Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial--an early report.

Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored. The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels. Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment. This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.

Adenoma↗
PubMed2000

HIV associated culture proved tuberculosis has increased in north central London from 1990 to 1996.

OBJECTIVES: To examine rates of culture proved tuberculosis in HIV infected patients in three specialist centres in north central London. METHODS: Cases of tuberculosis in patients with previously documented HIV infection from 1990 to 1996 were identified retrospectively from microbiological/clinical records at Chelsea and Westminster, St Mary's, and University College London Hospitals. RESULTS: Between 1990 and 1996 202 cases of culture proved tuberculosis were identified at the three centres. Of these, 132/202 (65.3%) occurred in homosexual/bisexual men, 41/202 (20.3%) were in patients with heterosexual contact in sub-Saharan Africa, and 29/202 (14.4%) were in "others." Overall 148/202 (73.3%) had pulmonary tuberculosis. The total number of HIV infected individuals seen at the three centres increased from 4298 in 1990 to 5048 in 1996. Rates of tuberculosis in the three centres increased from 0.46% in 1990 to 0.83% in 1996. Part of this increase was due to an increase in tuberculosis among Africans from 1993 to 1996. CONCLUSIONS: Rates of HIV associated tuberculosis increased in these three centres in north central London between 1990 and 1996. In part this was due to an increase in the number of African patients with HIV infection attending the three centres. In addition, there was circumstantial evidence of recent transmission among homosexual men with HIV infection. Prospective "real time" surveillance of tuberculosis in HIV infected patients is needed in order to detect case clustering and to improve tuberculosis control.

Africa↗
PubMed2000

The use of D-dimers in the diagnosis of occult pulmonary emboli in HIV pulmonary disease--two case reports.

Pulmonary thromboembolism is not considered a common cause of morbidity in HIV disease. Although anti-phospholipid antibodies are often seen in HIV disease, they are not associated with an increased thrombotic risk. Computed tomographic (CT) pulmonary angiography has been described as the imaging modality of first choice, as abnormal baseline chest X-rays may reduce the diagnostic utility of ventilation perfusion (VIQ) scanning. In HIV-negative individuals D-dimer testing has been shown to be a good screening tool in suspected pulmonary embolism. We present 2 cases where the diagnosis of pulmonary embolus was established using tests for the clotting degradation products D-dimers.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Blood-brain phenylalanine relationships in persons with phenylketonuria.

OBJECTIVES: Clinicians caring for persons with phenylketonuria (PKU) have been perplexed by the occasional normal individual with the classical biochemical profile consistent with the diagnosis of PKU. Usually untreated subjects with the biochemical profile of blood phenylalanine (Phe) levels >1200 micromol/L are severely mentally retarded and may have neurological findings. Preliminary reports have recently appeared suggesting that low brain Phe levels, in comparison with elevated blood Phe levels, account for the occurrence of these occasional unaffected individuals with the biochemical profile consistent with PKU. METHOD: Magnetic resonance imaging/magnetic resonance spectroscopy was used to measure brain Phe content compared with simultaneously obtained blood Phe levels determined on the amino acid analyzer. This comparison was obtained in 5 normal non-PKU persons, 4 carriers of the gene causing PKU, and in 29 individuals with the proven form of the disorder. RESULTS: Blood-brain measurements in 5 normal persons ranged from.051 to.081 mmol/L, with a mean of.058 mmol/L. Their simultaneously measured brain levels of Phe ranged from.002 to.15 mmol/L, with a mean of.09 mmol/L. Similar measurements were obtained in 4 carriers of the gene causing PKU. Their blood levels varied between.068 and.109 mmol/L, with a mean of.091 mmol/L and simultaneously obtained brain levels of Phe varied between.06 and.21 mmol/L, with a mean of.11 mmol/L. Twenty subjects with a mean IQ of 104 exhibited a mean blood level of 1.428 mmol/L and a simultaneous mean brain level of.23 mmol/L, whereas 9 persons with a mean IQ of 98.7 exhibited a mean blood Phe level of 1.424 and a mean brain Phe level of.64 mmol/L. The correlation between blood and brain levels was not significant. CONCLUSION: In usual cases, intellectually normal persons who have never been treated but who have a biochemical profile consistent with classical PKU exhibit lower brain levels of Phe. Such individuals are exceptional and may not need the vigorous restriction of their blood Phe levels that is required by the majority of persons with PKU.

Adolescent↗
PubMed2000

Behavior of resting Aedes aegypti (Culicidae: Diptera) and its relation to ultra-low volume adulticide efficacy in Panama City, Panama.

The resting behavior of Aedes aegypti (L.) adults was investigated in 14 districts of Panama City, Panama, in relation to ground ultra-low volume (ULV) applications of malathion. Adults primarily rested inside the premises (75.1%) at a distance > 6 m from the street (86.4%). Both sexes rested mainly in bedrooms, living rooms, and bathrooms. The small ULV aerosol droplets (2-4 microns) penetrated all indoor resting sites of Ae. aegypti, but in low amounts. Because of the low amount of insecticide reaching the primary resting sites within the premises, limited control of the Ae. aegypti was obtained. This limited the potential effectiveness of ground vehicle ULV applied insecticide as a dengue epidemic control method.

Aedes↗
PubMed2000

Central nervous system infections in the pediatric population.

Central nervous system infections and sequelae in the pediatric population may present differently depending on the patient's stage of development. Infections contracted from conception through the neonatal period may affect central nervous system formation, whereas infections acquired later tend to cause parenchymal destruction. This article discusses congenital, focal parenchymal, extra-axial, and diffuse parenchymal infections and their effect on the developing brain.

Brain Damage, Chronic↗