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Biomedical subjects

D Bell

Publications and source records attributed to D Bell.

At least 55 records · Page 3Linked to original sources
PubMed1999

Everting suture correction of lower lid involutional entropion.

AIMS: To assess the long term efficacy of everting sutures in the correction of lower lid involutional entropion and to quantify the effect upon lower lid retractor function. METHODS: A prospective single armed clinical trial of 62 eyelids in 57 patients undergoing everting suture correction of involutional entropion. Patients were assessed preoperatively and at 6, 12, 24, and 48 months postoperatively. The main outcome variables were lower lid position and the change in lower lid retractor function. RESULTS: When compared with the non-entropic side, the entropic lid had a greater degree of horizontal laxity and poorer lower lid retractor function. These differences however, were not significant. At the conclusion of the study and after a mean follow up period of 31 months, the entropion had recurred in 15% of the patients. There were no treatment failures in the group of five patients with recurrent entropion. The improvement in lower lid retractor function after the insertion of lower lid everting sutures did not reach statistical significance. There was no significant difference between the treatment failure group and the group with a successful outcome with regard to: the degree of horizontal lid laxity or lower lid retractor function present preoperatively; patient age or sex; an earlier history of surgery for entropion. There was neither a demonstrable learning effect nor a significant intersurgeon difference in outcome. The overall 4 year mortality rate was 30%. CONCLUSIONS: The use of everting sutures in the correction of primary or recurrent lower lid involutional entropion is a simple, successful, long lasting, and cost effective procedure.

Aged↗
PubMed1999

Accreditation by the National Committee on Quality Assurance (NCQA): a description.

The objective of this article is to describe the National Committee on Quality Assurance (NCQA). The NCQA is one of many organizations that is addressing the issues of quality assurance of health care for HMOs. It is of concern that when HMOs focus on cost they may stint on services. Also it is difficult for HMOs to compete for both quality and cost if there is not a comparable objective standard of measurement. The NCQA offers a level of accreditation that is representative of organizational structure and resources. The Health Plan Employer Data and Information Set (HEDIS) is used to compare outcomes and professional resources. The results of both the accreditation and the HEDIS measures are compiled in a national data base, The Quality Compass. There is skepticism that the NCQA is measuring the correct data for basing quality measurement decisions and also the data obtained is severely underutilized by health care purchasers (employers with less than 1,000 employees).

Accreditation↗
PubMed1998

Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells.

The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional light chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferase expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is the opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.

Animals↗
PubMed1998

Germline mutations in PTEN are an infrequent cause of genetic predisposition to breast cancer.

Heterozygous germline mutations in PTEN are responsible for most cases of Cowden Syndrome, a rare familial trait characterized by hamartomas and by predisposition to cancer of the breast and thyroid. The variable and often subtle clinical findings that characterize Cowden Syndrome are frequently unrecognized, raising the possibility that germline PTEN mutations may confer susceptibility to breast cancer in women who have not been diagnosed with this syndrome. To determine whether such mutations contribute to genetic predisposition to breast cancer within the general population, we analysed a cohort of women with early-onset breast cancer (< age 40), a subset of the population at increased risk for genetic susceptibility. Lymphoblast cell lines were analysed using either direct nucleotide sequencing (28 cases), denaturing gradient gel electrophoresis (DGGE) (34 cases) or a yeast-based truncation assay (110 cases). No definitive, truncating mutations were observed in 172 patients. Missense changes were noted in the germline of 2/60 patients analysed by direct nucleotide sequencing or DGGE, including a non-conservative amino acid substitution within the phosphatase domain, but neither showed loss of the wild-type allele in the corresponding breast tumor specimen. We conclude that germline mutations in PTEN are an uncommon cause of genetic predisposition to breast cancer within the general population.

Adult↗
PubMed1998

Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer.

BACKGROUND: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer. METHODS: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as the number of putative high-risk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). CONCLUSIONS: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.

Breast Neoplasms↗
PubMed1998

A community-based study of well-being in adults reporting childhood abuse.

OBJECTIVE: This study examined well-being and satisfaction with community services in adult survivors of childhood abuse. METHOD: A community sample of 109 individuals, 34 reporting childhood abuse (sexual, physical and/or emotional), completed a questionnaire package as part of a study of community well-being. The package included measures of demographic variables, satisfaction with community services, physical well-being, consumption of drugs (including nicotine & alcohol), loneliness, depression, and life stress. RESULTS: Less than half of those reporting abuse had confided in someone about their experience and only 14.3% had discussed it with a counsellor. The abuse versus no abuse groups did not differ in terms of general living circumstances (e.g., income, marital status, employment status, quality of housing). Despite this, the abuse group reported poorer well-being on several measures. CONCLUSIONS: There are clear limitations to the present data. Nonetheless, the results suggest that those reporting childhood abuse tend to experience poorer well-being than those who do not report abuse, even when the "objective" aspects of their circumstances are similar.

Adaptation, Psychological↗
PubMed1998

D-myo inositol 1,2,6, triphosphate (alpha-trinositol, pp56): selective antagonist at neuropeptide Y (NPY) Y-receptors or selective inhibitor of phosphatidylinositol cell signaling?

1. D-myo inositol 1,2,6 trisphosphate (alpha-trinositol, pp56), an isomer of the second messenger substance, D-myo inositol 1,4,5 trisphosphate, has an interesting pharmacological profile that includes anti-inflammatory and analgesic effects and antagonism of neuropeptide Y (NPY)-mediated cellular responses. 2. However, not all responses elicited by this neuropeptide are sensitive to antagonism by pp56. Evidence is emerging, at least in certain tissues, that other receptor populations, in addition to those for NPY, are also sensitive to inhibition by pp56. 3. A direct or allosteric interaction of pp56 at receptors for NPY is now considered unlikely and it is more probable that pp56 might interfere at some point in the phosphatidylinositol signaling pathway, possibly at the level of the plasmalemmal inositol 1,3,4,5, tetrakisphosphate receptor. 4. Full realization of the therapeutic potential of this novel compound, however, must await a thorough characterization of the cellular mechanism(s) associated with the various pharmacological effects of pp56.

Animals↗
PubMed1998

A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer.

BACKGROUND: Most patients with advanced ovarian cancer will relapse following platinum-based combination chemotherapy and be considered for second-line treatment. Gemcitabine, a nucleoside analogue, is active against a range of solid tumors. This phase II study investigated the activity of single-agent gemcitabine in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients with FIGO stage III (34%) or IV (64%) ovarian cancer who were previously treated with platinum-containing regimens were enrolled. Patients received 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a 28-day cycle. RESULTS: Patients completed an average of 3.6 cycles. Two complete and three partial responses were seen in 36 evaluable patients, for an overall response rate of 13.9% (95% CI: 4.7%-29.5%). The median survival time was 6.7 months. Toxicities were generally mild. The most common were grade 3-4 neutropenia and grade 3 leukopenia reported in 23.7% and 10.5% of patients, respectively. One patient had grade 4 pulmonary toxicity. CONCLUSION: Single-agent gemcitabine is active and well tolerated in patients with recurrent ovarian cancer.

Adult↗
PubMed1998

Rates of and risk factors for trichomoniasis among pregnant inmates in New York City.

BACKGROUND: Trichomonas vaginalis is a common pathogen that is associated with adverse pregnancy outcomes and may serve as a cofactor in human immunodeficiency virus (HIV) transmission. GOAL: To define the epidemiology of trichomoniasis in a population of newly incarcerated pregnant women in New York City. STUDY DESIGN: Prospective study of 213 pregnant prisoners attending prenatal clinic. Patients participated in an interview regarding sexual and drug-related behaviors, and underwent direct culture for T. vaginalis in addition to routine testing for syphilis, gonorrhea, and chlamydia. RESULTS: The prevalence of trichomoniasis was 46.9%. On univariate analysis, there was a significant association between trichomoniasis and older age, crack use, prostitution, known HIV infection, and positive serological test for syphilis. Multivariate analysis showed a significant association of trichomoniasis with crack use and positive serological test for syphilis. CONCLUSION: Trichomoniasis is highly prevalent in pregnant prisoners in New York City. The extent of disease observed may justify a formal program of testing and treatment and emphasizes the urgent need for harm reduction education and expanded HIV counseling and testing services in this high-risk population.

Adolescent↗
PubMed1998

Type 2 diabetes mellitus and Aboriginal Australians. Options for oral therapy in the control of glyceamia.

BACKGROUND: Type 2 diabetes mellitus is a major and increasing cause of morbidity and early mortality among the Aboriginal population of northern Australia. Due to differing social, dietary and probably metabolic factors, management needs differ from the mainstream Australian diabetic population. OBJECTIVE: This paper concentrates on the options for oral therapy in the control of glycaemia, taking into account various current guidelines and recent trials of oral antihyperglycaemic therapy, and the specific metabolic and clinical associations with type 2 diabetes mellitus in this population. DISCUSSION: In the abscence of specific contraindications, and in variance with some present guidelines, the evidence suggests that initial therapy with metformin rather than the sulphonylureas is likely to provide greater clinical benefit, and have a greater margin of safety.

Administration, Oral↗
PubMed1997

Evidence for Y1 and Y2 subtypes of neuropeptide Y receptors linked to opposing postjunctional effects observed in rat cardiac myocytes.

The aim of this study was to confirm the existence of and identify the receptor subtypes for neuropeptide Y that are present post-junctionally in myocardium. The effects of the selective agonists, [Leu31, Pro34] neuropeptide Y (neuropeptide Y Y1 receptors), neuropeptide Y-(13-36) and peptide YY-(3-36) (neuropeptide Y Y2 receptors), and neuropeptide Y and the related peptide YY, which have differential action at neuropeptide Y Y3 receptors, on amplitudes of contraction of adult rat ventricular cardiomyocytes were studied. Also, the effect of the neuropeptide Y Y1-selective antagonist, bis(31/31')[[Cys31, Trp32, Nva34] neuropeptide Y-(31-36)] on neuropeptide Y-mediated changes in myocyte contraction was investigated. Neuropeptide Y, peptide YY, neuropeptide Y-(13-36) and peptide YY-(3-36) attenuated the isoprenaline (10(-7) M)-stimulated contractile response, and the EC50 values were 9.0 x 10(-9), 4.3 x 10(-10), 3.1 x 10(-11) and 8.5 x 10(-11) M, respectively. [Leu31, Pro34] neuropeptide Y increased the contractile response of cardiomyocytes, and the EC50 values were 8.1 x 10(-9) and 1.5 x 10(-9) M, in the absence and presence of isoprenaline, respectively. Since [Leu31, Pro34] neuropeptide Y caused a positive effect on ventricular myocyte contraction and neuropeptide Y-(13-36) and peptide YY (3-36) produced the most potent negative effects, it is proposed that both neuropeptide Y Y1 and neuropeptide Y Y2 receptors, linked respectively to the positive and negative responses, are expressed in cardiomyocytes. The finding of receptors with neuropeptide Y Y2 characteristics on cardiomyocytes represents a further example of a postjunctional location for this subtype. As there was no significant discrepancy between the potencies of peptide YY and neuropeptide Y to attenuate the contractile response, it appears that neuropeptide Y Y3-like receptors are not linked principally to contractile function in rat cardiomyocytes. Bis(31/31')[[Cys31, Trp32, Nva34] neuropeptide Y-(31-36)] antagonised the neuropeptide Y-mediated stimulation of contractile activity through neuropeptide Y Y1 receptors, but the compound also inhibited the attenuation of isoprenaline-stimulated contraction, apparently by acting as a partial agonist at the neuropeptide Y Y2 receptors.

Animals↗
PubMed1997

Calcitonin gene-related peptide (CGRP) increases cell surface area and induces expression of skeletal alpha-actin ANP mRNA in hypertrophying neonatal cardiomyocytes.

We have reported previously that calcitonin gene-related peptide (CGRP) exerts hypertrophic effects, defined in the broadest sense as increased mass of protein per cell, in adult rat ventricular in vitro. The aim of the present investigation was to determine whether the peptide also increases the cell surface area of, and induces expression of ANP and skeletal alpha-actin mRNA in hypertrophying neonatal rat ventricular cardiomyocytes. Cells cultured in the presence of CGRP were invisibly hypertrophied after 48 h compared to cells cultured in serum-free MEM for the same period. CGRP, 100 pM and 1 nM, increased cell surface area significantly and to values 1.82- and 2.15-fold greater, respectively, than in the absence of peptide (659.64 +/-23.48 microns 2, n = 10). The selective antagonist at CGRP1, receptors, CGRP8-37(200nM), significantly attenuated the effects of CGRP (100 pM and 1 nM). CGRP caused a marked up-regulation of the expression of mRNA encoding skeletal alpha-actin and ANP, respectively, maximally after 12 h and at a concentration of 100 pM, to values approximately 3.6- and 2.5-fold greater than in the absence of peptide. These effects of the peptide were completely abolished in the presence of CGRP8-37(100 nM). In conclusion, CGRP increases cell surface area and induces expression of ANP and skeletal alpha-actin mRNA in hypertrophying cardiomyocytes via the CGRP1, receptor subtype.

Actins↗
PubMed1997

Transcriptional induction of cholesterol 7alpha-hydroxylase by dexamethasone in L35 hepatoma cells requires sulfhydryl reducing agents.

It is known that hepatic levels of reduced glutathione correlate with the activity of the liver-specific enzyme cholesterol-7alpha-hydroxylase. We examined the possibility that sulfhydryl reducing agents activate transcription of cholesterol 7alpha-hydroxylase. Adding dithiothreitol (DTT, 1 mM) and dexamethasone to L35 hepatoma cells increased the content of 7alpha-hydroxylase mRNA 3-fold above the levels observed with dexamethasone alone. Without dexamethasone, DTT had no affect. The addition of reduced glutathione to L35 cells demonstrated a similar potentiation of expression dependent on dexamethasone. Nuclear run-on assays showed that in the presence of both dexamethasone and DTT, the transcription of the 7alpha-hydroxylase gene was clearly increased. In contrast, by itself, dexamethasone did not cause a detectable increase in the transcription of the 7alpha-hydroxylase gene. Dexamethasone and DTT did not affect the transcription of beta-actin, suggesting a selective induction of the 7alpha-hydroxylase gene. DTT reversed repression of 7alpha-hydroxylase expression by insulin but not the repression by phorbol ester. Our data show for the first time that the sulfhydryl redox potential of the hepatocyte (i.e. level of reduced glutathione) has a marked influence on the transcription and expression of the liver-specific gene 7alpha-hydroxylase.

Animals↗
PubMed1997

Use of D-myo inositol 1,2,6 trisphosphate to inhibit contractile activity in rat ventricular cardiomyocytes induced by neuropeptide Y and other cardioactive peptides through phospholipase C.

1. D-Myo inositol 1,2,6 trisphosphate (alpha-trinositol, pp56), an isomer of the second messenger substance, inositol 1,4,5 trisphosphate, has an interesting pharmacological profile that includes antagonism of a number of neuropeptide Y (NPY)-mediated cellular processes. The ability of pp56 to inhibit selectively the myocardial contraction mediated by NPY in relation to the responses to other cardioactive peptides, including endothelin-1, calcitonin gene-related peptide (CGRP), secretin and vasoactive intestinal peptide (VIP), was assessed. In order to investigate the possible interaction of pp56 with mechanisms of inositol phosphate signalling generated in heart muscle cells by activation of the beta-isoenzyme of phospholipase C (PLC beta), noradrenaline was used as a positive control, and isoprenaline and forskolin were included as negative controls. 2. Ventricular cardiomyocytes, isolated from the hearts of adult rats, were stimulated to contract at 0.5 Hz in the presence of calcium ion (2 mM). The concentrations of agonists used were in the region of their maximally effective concentrations for myocyte contraction and the concentration of pp56 was in the range of 1-100 microM. Contractile activity was monitored by video microscopy and maximum shortening determined by image analysis. 3. In the absence of agonist, contractile amplitudes following 20 min preincubation with pp56 were not different from that observed in the absence of pp56. Pp56 (1-100 microM) inhibited significantly the positive contractile response to noradrenaline (5 microM) in the presence of propranolol (500 nM), such that the response was almost completely attenuated at the highest concentration of the inhibitor. Pp56 did not inhibit the positive contractile responses to forskolin (40 microM) or isoprenaline (100 nM). 4. NPY alone does not influence the basal level of contraction of cardiomyocytes, but can attenuate isoprenaline-stimulated contraction and can increase contractile amplitude from basal when the transient outward current is blocked with 4-aminopyridine. In the presence of isoprenaline (100 nM), the negative response to NPY (100 nM) was attenuated significantly by pp56 (1-100 microM). With 4-aminopyridine, the positive contractile response to NPY (200 nM) was decreased by pp56, although this was not statistically significant. 5. Pp56 inhibited the positive contractile responses to CGRP (1 nM) and endothelin-1 (20 nM) completely, but did not affect the responses to secretin (20 nM) or VIP (20 nM). 6. In conclusion, these data challenge the previously obtained selectivity of pp56 as an antagonist of NPY-mediated cellular processes, since responses to CGRP and endothelin-1 were at least equally sensitive. Furthermore, as pp56 discriminated clearly in its inhibition of responses to alpha-adrenoceptor by comparison with beta-adrenoceptor/adenylate cyclase stimulation, it appears that pp56 may be a useful pharmacological agent with which to distinguish between PLC beta-dependent and PLC beta-independent coupling mechanisms. On this basis, further evidence has been obtained that, in rat cardiomyocytes, the contractile responses to NPY, CGRP and endothelin-1 are attributable to the activation of PLC beta-dependent pathways, whereas the responses to secretin and VIP are mediated by PLC beta-independent pathways.

Animals↗