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Biomedical subjects

D Browning

Publications and source records attributed to D Browning.

At least 19 recordsLinked to original sources

Bupropion as an aid to smoking cessation: a review of real-life effectiveness.

Clinical trials rigorously demonstrate the efficacy of new products and justify their marketing. However, it is only after use in real-life settings that the clinical value (effectiveness) of a new treatment is fully known. The purpose of this review was to summarise the effectiveness data for bupropion SR as an aid to smoking cessation. Available reports of effectiveness data for bupropion SR were obtained from the literature, presentations at smoking cessation meetings and from the manufacturer. Twelve sources of effectiveness data were found and included clinical practice trials, observational studies/surveys, motivational support programme results and employer-based cessation programme results. The 6-month point prevalence smoking cessation rates ranged from 25 to 49%. There is a growing body of evidence supporting the effectiveness of bupropion SR as an aid to smoking cessation. Real-life quit rates for bupropion SR are similar to those seen in the original clinical trial programme.

Bupropion↗

Switching patients with migraine from sumatriptan to other triptans increases primary care costs.

Treatment of migraine with triptans is highly effective, although cost considerations may prompt a change in therapy. This retrospective database analysis of 3196 patients with migraine, established on sumatriptan therapy, found that 54% of the 292 experiencing a triptan switch returned to sumatriptan within 15 months, suggesting that the alternative was less acceptable. Excluding patients with unusually high use of triptans (> or = 208 tablets/year), switching therapy resulted in a significant increase of pounds sterling 53/patient in total costs, compared with patients continuing on sumatriptan (p = 0.014). Cost savings (pounds sterling 17/patient over 15 months) were observed only among the 41% of patients in whom the initial switch was successful and did not result in a further switch or return to sumatriptan. Among patients who were relatively low cost initially, switching resulted in increased costs, irrespective of the outcome. This study suggests that there is no economic justification for switching from sumatriptan to another triptan.

Adult↗

Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma.

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.

Adolescent↗

Differential gene expression between normal and tumor-derived ovarian epithelial cells.

The majority of ovarian tumors arise from the transformation of the ovarian surface epithelial cells, a single layer of cells surrounding the ovary. To identify genes that may contribute to the malignant phenotype of ovarian cancers, cDNA representational difference analysis was used to compare expressed genes in primary cultures of normal human ovarian surface epithelium (HOSE) and ovarian tumor-derived epithelial cells from the Cedars-Sinai Ovarian Cancer (CSOC) repository. A total of 255 differentially expressed genes were identified, of which 160 and 95 were specifically expressed in HOSE and CSOC cells, respectively. Using cDNA array hybridization, the expression profiles of the genes identified by cDNA-representational difference analysis were examined in an additional 5 HOSE and 10 CSOC lines. The comparison of average signal of each gene revealed 44 HOSE-specific and 16 CSOC-specific genes that exhibited at least a 2.5-fold difference in expression. A large number of genes identified in this study encode membrane-associated or secreted proteins and, hence, may be useful as targets in the development of serum-based diagnostic markers for ovarian cancer. Very few genes associated with protein synthesis or metabolism were identified in this study, reflecting the lack of observable differences in phenotypic or growth characteristics between HOSE and CSOC cells. Northern blot analysis on a subset of these genes demonstrated comparable levels of gene expression as observed in the cDNA array hybridization.

Blotting, Northern↗

Notch signaling enhances survival and alters differentiation of 32D myeloblasts.

The Notch transmembrane receptors play important roles in precursor survival and cell fate specification during hematopoiesis. To investigate the function of Notch and the signaling events activated by Notch in myeloid development, we expressed truncated forms of Notch1 or Notch2 proteins that either can or cannot activate the core binding factor 1 (CBF1) in 32D (clone 3) myeloblasts. 32D cells proliferate as blasts in the presence of the cytokines, GM-CSF or IL-3, but they initiate differentiation and undergo granulopoiesis in the presence of granulocyte CSF (G-CSF). 32D cells expressing constitutively active forms of Notch1 or Notch2 proteins that signal through the CBF1 pathway maintained significantly higher numbers of viable cells and exhibited less cell death during G-CSF induction compared with controls. They also displayed enhanced entry into granulopoiesis, and inhibited postmitotic terminal differentiation. In contrast, Notch1 constructs that either lacked sequences necessary for CBF1 binding or that failed to localize to the nucleus had little effect. Elevated numbers of viable cells during G-CSF treatment were also observed in 32D cells overexpressing the basic helix-loop-helix protein (bHLH), HES1, consistent with activation of the CBF1 pathway. Taken together, our data suggest that Notch signaling enhances 32D cell survival, promotes entry into granulopoiesis, and inhibits postmitotic differentiation through a CBF1-dependent pathway.

Animals↗

Treatment of acute severe asthma assisted by hypothermia.

A 20-year-old woman in status asthmaticus who failed to respond to conventional therapy and ventilation of the lungs with 0.5-2.0% halothane, was cooled to 30 degrees C for almost 5 days as the arterial carbon dioxide tension rose above 15 kPa. Halothane was not of immediate value, contrary to other reports. A reduction in carbon dioxide production by controlled hypothermia permitted more suitable ventilation parameters, but extensive muscle weakness caused by a steroid-induced myopathy complicated weaning from respiratory support. Prospective measurement of serum creatinine phosphokinase concentration in patients given high dose corticosteroids may herald the onset of a myopathy.

Acute Disease↗

Cytomegaloviral laryngitis and probable malignant lymphoma of the larynx in a patient with acquired immunodeficiency syndrome.

We describe a case of cytomegaloviral laryngitis and probable primary laryngeal malignant non-Hodgkin's lymphoma in a man with acquired immunodeficiency syndrome who presented to an otolaryngology clinic with odynophagia and hoarseness. While both of these disease processes have a known association with human immunodeficiency virus infection, laryngeal presentation is extremely rare. We stress the need for thorough clinical and pathologic otolaryngologic evaluation of patients with human immunodeficiency virus infection who have upper aerodigestive complaints.

Acquired Immunodeficiency Syndrome↗

Concentrations of free thyroxin and albumin in serum in severe nonthyroidal illness: assay artefacts and physiological influences.

Free thyroxin (FT4) estimates by two immunoassays were compared with the concentrations of albumin in serum of apparently euthyroid subjects who either were (n = 99) or were not (n = 327) suffering from severe nonthyroidal illness (sNTI). In neither group was FT4 significantly correlated with albumin (P greater than 0.05), according to a "labeled antibody" radioassay (Amerlex-MAB). On amalgamating both groups, correlation with albumin was positive and significant (P less than 0.001). In the group with sNTI, both FT4 and albumin concentrations were decreased (mean FT4 to 77% and mean albumin to 61% of the respective reference means). For an analog radioimmunoassay (Amerlex-M), FT4 in all groups was significantly (P less than 0.001) correlated with albumin. Correlation coefficients were greater than with Amerlex-MAB for both sNTI and euthyroid groups, as well as for the joint panel. Mean FT4 in sNTI was only 44% of the reference mean. Lower radio-tracer "analog" values in sNTI are exaggerated by additional technical artefacts resulting from tracer binding to albumin.

Adolescent↗

Radiation therapy technology: manpower survey 1987.

A chronic shortage of radiation therapy technologists exists in the United States. This report presents the data obtained in a 1987 survey of all radiation oncology facilities identified by the Patterns of Care master list. Of the 1,142 questionnaires mailed, 52% were returned. The survey identified 2,328 credentialed (ARRT) and 554 non-credentialed technologists employed in radiation therapy. Of this total of 2,882, 2,141 were identified as staff technologists. A total of 1,186 megavoltage units were identified, giving a ratio of 1.8 technologist/megavoltage unit. Two hundred sixty open funded positions and 230 unfunded positions for radiation therapy technologists were identified. The report compares the results of this 1987 Radiation Therapy Technology Manpower Survey with the results of the three previous surveys conducted in 1975, 1977, and 1981. Whereas this comparison demonstrates that progress has been made, current trends in allied health education are expected to have a negative impact on recruitment into radiation therapy technology. Program directors report that the number and quality of applicants to all allied health education programs is declining, and this trend in radiation therapy technology is substantiated by a drop in the number of students enrolled in programs, from 970 in 1986-87 to 777 in 1987-88. Our discussion addresses the areas of new program development, recruitment, retention, innovative programs, and overseas recruitment.

Allied Health Personnel↗

Testicular ischemia and infarction following herniorrhaphy or varicocelectomy: evaluation by radionuclide imaging.

The postoperative use of testicular imaging to evaluate the preservation of testicular circulation has been reported after orchiopexy, excision of a hematocele, and repair of a traumatized tunica albuginea. The authors discuss the previously unreported use of testicular imaging in patients who have undergone recent herniorrhaphy or varicocelectomy. The scan of a patient with intact testicular perfusion following herniorrhaphy is compared to the scans of two patients with absence of perfusion of a testicle five to seven days following respective herniorrhaphy and varicocelectomy surgeries.

Adult↗

Suppression of gonadotrophin secretion does not reverse premature ovarian failure.

The effect of prolonged inhibition of gonadotrophin secretion was studied in 12 women with premature ovarian failure. All the patients had plasma concentrations of follicle-stimulating hormone (FSH) greater than 20 i.u./l, and in six, primordial follicles had been seen on ovarian biopsy. Goserelin (Zoladex, ICI), a depot synthetic analogue of luteinizing hormone-releasing hormone (LHRH) was administered by three consecutive 4-weekly injections. Plasma concentrations of luteinizing hormone (LH) fell from 34 (SD 11) i.u./l to 2.4 (SD 1.9) i.u./l, and plasma concentrations of FSH fell from 106 (SD 29) i.u./l to 4.5 (SD 2.6) i.u./l 4 weeks after the first injection. Plasma concentrations of gonadotrophins returned to pretreatment values in every patient within 9 weeks of the final injection of goserelin. Regular ultrasonography during the period following the final injection failed to demonstrate the development of ovarian follicles in any patient, and plasma concentrations of oestradiol remained below 100 pmol/l. This study has failed to show that suppression of gonadotrophin secretion reverses premature ovarian failure.

Adult↗

Fetal inflammatory response in second trimester candidal chorioamnionitis.

Candidal chorioamnionitis is an uncommon and apparently rather indolent intrauterine infection in which the fetus is able to marshal some of the immunological forces at its disposal against an easily visualized antigen impinging on lung mucosal surfaces. In a retrospective histological study of one of the largest reported series of these cases, we have encountered one each of 13, 16 and 22 weeks gestation, respectively. Of these, the youngest at 13 weeks showed no inflammatory response or positive cells on immunoperoxidase staining for immunoglobulins and proliferating Candida colonies were evident in the lungs. The 16 and 22 week cases revealed a unique giant cell response in the terminal airways and increasing numbers of cells staining positively for immunoglobulins, predominantly IgM, but with an increased proportion of IgA positive cells in the older case. Preliminary studies with a pan-T-cell antiserum on paraffin-embedded lung tissue from these cases have been encouraging with few positive cells seen in sections from the 13-week or control cases but abundant cells in the lungs of the two older infected cases. Some aspects of the relationship of these uncommonly encountered cases to the ontogeny of human immunity are discussed.

Candidiasis↗