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Biomedical subjects

M McCarthy

Publications and source records attributed to M McCarthy.

At least 145 records · Page 8Linked to original sources
PubMed1999

Hemodialysis prognostic nutrition index as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. Council on Renal Nutrition National Research Question Collaborative Study Group.

OBJECTIVE: Prospectively examine the use of a hemodialysis prognostic nutrition index (HD-PNI) as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. DESIGN: Prospective randomized collaborative study group. SETTING: There were 211 chronic hemodialysis centers; 202 from 43 United States, 9 from Canada. PATIENTS: There were 1527 hemodialysis patients undergoing treatment a minimum of 3 months and at least 18 years of age. Sample mirrored United States Renal Data System data for age, sex, race, and etiology of renal failure. INTERVENTIONS: None; routinely collected demographic, biochemical, and clinical data for 8-month baseline and 3-month predictive phases. METHODS: HD-PNI calculated from baseline data as linear mathematical equation using level of serum albumin, level of serum creatinine, and number of days and times hospitalized; HD-PNI risk defined as >/=0.8. Adequacy of dialysis calculated as urea reduction ratio (URR) from baseline data; adequacy risk defined as URR of </=65%. MAIN OUTCOME MEASURES: Number of times and days hospitalized, mortality. RESULTS: For this research, 1167 patients completed the study (76%) with 360 (24%) dropped due to death, incomplete data, transfer, or change in modality. Patients completing study with HD-PNI risk (n = 208, 18%) compared with patients who had no HD-PNI risk (n = 959, 82%) were hospitalized more often (57.2% v 28.5%, P <. 01), hospitalized with infection more often (14.6% v 4.6%, P <.01), and had greater mortality (7.7% v 2.5%, P <.01). Stratification of HD-PNI risk by URR of >/=65% did not significantly improve prediction. CONCLUSIONS: Use of HD-PNI is an effective screening tool to identify hemodialysis patients at risk for morbidity and mortality. No correlation was found between URR and HD-PNI.

Adult↗
PubMed1999

Effects of neonatal capsaicin administration on the numbers and volumes of neurons in left and right T10 dorsal root ganglia in the rat.

The long-term effects of neonatal capsaicin were studied in left and right dorsal root ganglia (T10) from control and capsaicin-treated groups of Wistar rats. At 12 hours post partum, 5 females per group were injected subcutaneously with capsaicin or vehicle solution and killed at 6 months of age. Tissues were perfusion-fixed, embedded in resin and serially sectioned. A Nissl stain was used to distinguish between A and B neurons and systematic random sampling schemes were employed to obtain stereological estimates of numbers of neurons and mean volumes of their perikarya. Numbers were calculated from ganglion volumes (estimated via the Cavalieri principle) and neuron packing densities (estimated using physical disectors). Mean perikaryal volumes were calculated from packing densities and volume densities (estimated by point counting). Data were analysed to isolate main and interaction effects of neuron subtype, laterality and treatment. There was no evidence of lateral asymmetry or interaction effects. Control ganglia contained 3320 (coefficient of variation, CV, 8%) neurons. Most (73%) were B cells with a mean volume of 13,100 microm(3) (CV 17%) of which the nucleus accounted for 1,800 microm(3) (CV 18%). About 22% were A cells with a mean volume of 79,800 microm(3) (CV 24%) and a nucleus of 6,100 microm(3) (CV 26%). After capsaicin, over half the original population of cells was destroyed and B cell loss was significantly greater than that of A cells (about 80% of all cells lost were B cells). The mean size of A cells was greater after capsaicin due to selective loss of smaller cells and a greater volume of cytoplasm. B cell perikaryal volume was not affected but nuclear volume declined. The findings show that capsaicin destruction of peripheral sensory neurons is bilaterally symmetrical. In general, smaller neurons are selectively destroyed but this operates differently in A and B cells. It is size-dependent in A cells but size-independent (possibly random) in B cells.

Animals↗
PubMed1999

Developing surveillance for HIV transmission and risk behaviours among high-risk groups in a central London health district.

BACKGROUND: Our aim was to describe surveillance data on HIV transmission and risk behaviours in Camden and Islington, an inner London health district (population 360 000). This information is required to assess the effectiveness of HIV-AIDS prevention. METHODS: We focused on two groups in the local population most severely affected by the HIV epidemic: homosexual and bisexual men, and injecting drug users. Data were drawn from routine and survey data, national and local sources, and a special local survey. RESULTS: There were estimated to be 9250 homosexual men, with an estimated prevalence of 7.7 per cent (confidence interval (CI) 5.9-11.0) diagnosed with HIV infection resident within the health district, and 9900 injecting drug users, with an estimated prevalence of 0.8 per cent (CI 0.6-1.1), diagnosed with HIV infection. New HIV infections diagnosed amongst homosexual men having a named test in HIV testing services averaged 281 and was unchanged between 1992 and 1996. However, unlinked anonymous seroprevalence surveys showed a decline in HIV prevalence for both homosexual men attending a genito-urinary medicine clinic and for injecting drug users attending services. Local surveys indicated that, in the preceeding year, one in three homosexual men had had unprotected anal intercourse with a man, and 13 per cent of intravenous drug users had shared equipment. There appeared to be no change in these levels over the years studied. CONCLUSION: Population-based information on HIV is available at local level in England. It can be used for surveillance of HIV transmission and behaviour in high-risk groups, especially homosexual and bisexual men and intravenous drug users. Resources for HIV prevention are provided to all NHS districts, and surveillance is a cost-effective measure of the outcome of HIV prevention.

Adolescent↗
PubMed1999

The "Let's Get Alarmed!" initiative: a smoke alarm giveaway programme.

OBJECTIVES: To reduce fires and fire related injuries by increasing the prevalence of functioning smoke alarms in high risk households. SETTING: The programme was delivered in an inner London area with above average material deprivation and below average smoke alarm ownership. The target population included low income and rental households and households with elderly persons or young children. METHODS: Forty wards, averaging 4000 households each, were randomised to intervention or control status. Free smoke alarms and fire safety information were distributed in intervention wards by community groups and workers as part of routine activities and by paid workers who visited target neighbourhoods. Recipients provided data on household age distribution and housing tenure. Programme costs were documented from a societal perspective. Data are being collected on smoke alarm ownership and function, and on fires and related injuries and their costs. RESULTS: Community and paid workers distributed 20,050 smoke alarms, potentially sufficient to increase smoke alarm ownership by 50% in intervention wards. Compared with the total study population, recipients included greater proportions of low income and rental households and households including children under 5 years or adults aged 65 and older. Total programme costs were 145,087 Pounds. CONCLUSIONS: It is possible to implement a large scale smoke alarm giveaway programme targeted to high risk households in a densely populated, multicultural, materially deprived community. The programme's effects on the prevalence of installed and functioning alarms and the incidence of fires and fire related injuries, and its cost effectiveness, are being evaluated as a randomized controlled trial.

Adolescent↗
PubMed1999

Chronic systemic administration of tumor necrosis factor alpha and HIV gp120: effects on adult rodent brain and blood-brain barrier.

Since tumor necrosis factor alpha (TNF-alpha) and HIV gpl20 glycoprotein are both neurotoxic, the possibility that systemic sources of these two agents mediate AIDS-associated blood-brain barrier (BBB) breakdown and brain damage was tested in two murine models: (1) intramuscular implantation of a TNF-alpha-transfected tumor in nu/nu mice and (2) daily subcutaneous injections of HIV gpl20 in BALB/c mice. The BBB remained intact; brain damage was not found, and apoptotic cell numbers did not increase. These results show that normal adult brain and BBB is unaffected by exposure to TNF-alpha or HIV gpl20 and suggest that severity of brain disease is not directly affected by systemic levels of these compounds.

Animals↗
PubMed1999

Genetic abnormalities in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a very common endocrinopathy and is the major cause of anovulatory infertility. It is also associated with an increased risk of non insulin dependent diabetes (NIDDM) in later life. Despite the importance of PCOS to women's health, little is known about its aetiology. Because of the well-known familial clustering of cases of PCOS, recent studies in our department have focused on clinical and molecular genetic studies in an attempt to identify key genes which may be involved in its aetiology. We have found evidence that a polymorphism in the regulatory region of CYP11a (encoding P450 cholesterol side chain cleavage, also an important enzyme in the steroidogenic pathway) is associated with and linked to PCOS. In examination of the insulin gene (INS), we have shown, in three separate populations, that class III alleles in the INS-VNTR (the minisatellite in the regulatory region of the insulin gene) are associated with PCOS. Variation in this element has also been implicated in the aetiology of NIDDM. We propose that PCOS is an oligogenic disorder in which a small number of key genes interact with environmental factors (notably dietary), the balance of which factors determine, the typically heterogeneous, clinical and biochemical phenotype.

Cholesterol Side-Chain Cleavage Enzyme↗
PubMed1998

Genetics of polycystic ovary syndrome.

We have found evidence for the involvement of two major genes in the aetiology of PCOS. The results of both linkage and association studies suggest that CYP11a (coding for P450 cholesterol side chain cleavage) and the insulin VNTR regulatory polymorphism are important genes in the aetiology of PCOS and may explain, in part, the heterogeneity of the syndrome. Differences in expression of CYP11a could account for variation in androgen production in women who have polycystic ovaries and those subjects who are homozygous for III alleles at the insulin gene VNTR locus are more likely to be hyperinsulinaemic. It is likely that other genes are involved in the aetiology of PCOS. Recent results lend weight to the idea that PCOS represents a complex trait in which several genes--but perhaps a relatively small number of key genes--contribute, in conjunction with nutritional factors, to the observed clinical and biochemical heterogeneity.

Androgens↗
PubMed1998

Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells. Evaluation of the role of the nitric oxide signaling pathway and potential defects in hypertension.

In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures. Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression. Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression. Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production. Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression. To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK. These inhibitors abolished the effect of insulin on MKP-1 expression. Only PD98059 inhibited insulin-mediated iNOS protein induction. Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity. Treatment with sodium nitroprusside and 8-bromo-cGMP restored MKP-1 mRNA expression to levels comparable with controls. We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression.

Androstadienes↗
PubMed1998

Telencephalic progenitors maintain anteroposterior identities cell autonomously.

Grafting experiments have demonstrated that determination of anteroposterior (AP) identity is an early step in neural patterning that precedes dorsoventral (DV) specification [1,2]. These studies used pieces of tissue, however, rather than individual cells to address this question. It thus remains unclear whether the maintenance of AP identity is a cell-autonomous property or a result of signaling between cells within the grafted tissue. Previously, we and others [3-5] have used transplants of dissociated brain cells to show that individual telencephalic precursor cells can adopt host-specific DV identities when they integrate within novel regions of the telencephalon. We have now undertaken a set of transplantations during the same mid-neurogenic period used in the previous studies to assess the ability of telencephalic progenitors to integrate and differentiate into more posterior regions of the neuraxis. We observed that telencephalic progenitors were capable of integrating and migrating within different AP levels of the central nervous system (CNS). Despite this, we found that telencephalic progenitors that integrated within the diencephalon and the mesencephalon continued to express a telencephalic marker until adulthood. We speculate that during neurogenesis individual progenitors are determined in terms of their AP but not their DV identity. Hence, AP identity is maintained cell autonomously within individual progenitors.

Animals↗
PubMed1998

Neutralization of tumor necrosis factor activity shortly after the onset of dendritic cell hematopoiesis reveals a novel mechanism for the selective expansion of the CD14-dependent dendritic cell pathway.

The CD14-dependent and -independent dendritic cell (DC) pathways are instituted simultaneously when CD34(+) progenitor cells are treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor (TNF) +/- stem cell factor (SCF) (GTS). If TNF activity is neutralized within 48 hours of cytokine exposure, DC development is halted and myelogranulocytic hematopoiesis takes place. In this study, we show that disruption of TNF activity at a later time point produced a distinct alteration within the DC system. Instead of downregulating DC development, treatment of GTS cultures with antibodies to TNF (anti-TNF) on day 3 provoked the selective expansion of the CD14-dependent (monocyte) DC pathway from progenitor cell populations lacking CD14 and CD1a. After an initial decrease in proliferation, anti-TNF produced a rebound in cell growth that yielded intermediate myeloid progenitors exhibiting CD14-dependent DC differentiation potential and CD14(+)CD1a+ DC precursors. Cultures enriched in CD14-dependent DCs were more potent stimulators of a mixed leukocyte reaction, compared with control GTS cultures containing both types of DCs. The intermediate progenitors expanded in the presence of anti-TNF were CD115(+)CD33(+)DR+, long-lived, and displayed clonogenic potential in methylcellulose. When exposed to the appropriate cytokine combinations, these cells yielded granulocytes, monocytes, and CD14-dependent DCs. Antigen-presenting function was acquired only when DC maturation was induced from these myelodendritic progenitors with GM-CSF + interleukin-4 or GTS. These studies show a novel mechanism by which TNF regulates the DC system, as well as providing a strategy for the amplification of the CD14-dependent DC pathway from immature progenitors. Although TNF is required to ensure the institution of DC hematopoiesis from CD34(+) progenitor cells, its activity on a later progenitor appears to limit the development of CD14-dependent DCs.

Antibodies, Monoclonal↗