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Biomedical subjects

D S Robinson

Publications and source records attributed to D S Robinson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa.

We have tested the hypothesis that the beneficial effects of corticosteroids in asthma may result from reduction in the number of inflammatory cells infiltrating the bronchial mucosa with inhibition of cytokine gene expression. A randomized parallel group study was performed in 18 moderately severe asthmatic patients in whom an elective trial of corticosteroid treatment was indicated. Fiberoptic bronchoscopy was performed and bronchial biopsies taken from segmental carinae before and after 2 wk treatment with prednisolone (0.6 mg/kg/d) or matched placebo tablets. Immunohistology was performed on 6-microns cryostat sections using monoclonal antibodies. The number of cells expressing cytokine messenger RNA (mRNA) was assessed by in situ hybridization using S35-labeled riboprobes. When prednisolone- and placebo-treated groups were compared there was a decrease in airway methacholine responsiveness (p < 0.01) and an increase in FEV1 (p < 0.05) after prednisolone. This was accompanied by a reduction in CD3+ T lymphocytes (p < 0.05), "activated" EG2+ eosinophils (p < 0.02), and tryptase-only (mucosal-type) MCT cells (p < 0.02) but not MCTC (tryptase+chymase positive) cells in prednisolone-treated patients. In prednisolone-treated patients there was also a reduction in the number of cells expressing mRNA for interleukin-4 (IL-4, p < 0.01), and interleukin-5 (IL-5, p < 0.03) and an increase in cells expressing mRNA for interferon-gamma (IFN-gamma) (p < 0.01). These results support the view that corticosteroid treatment in asthma may act by modulation of cytokine expression with consequent inhibition of the local bronchial inflammatory infiltrate and tissue eosinophilia.

Adult↗
PubMed1996

IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity.

Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients with the disease are skin test-negative to common aeroallergens, and have total serum IgE concentrations within the normal range. Nevertheless, the recent demonstration of increased numbers of cells expressing the high-affinity IgE receptor in bronchial biopsies from atopic and nonatopic asthmatic subjects, together with epidemiologic evidence indicating that serum IgE concentrations relate closely to asthma prevalence regardless of atopic status, suggests that IgE-mediated mechanisms may participate in the pathogenesis of both atopic and nonatopic asthma. Furthermore both variants of the disease are associated with bronchial mucosal eosinophilic inflammation. Interleukin-4 (IL-4) is an essential cofactor for IgE synthesis, and there is strong evidence that IL-5 plays a major role in eosinophil accumulation in asthmatic inflammation. For these reasons we compared the expression of IL-4 and IL-5 mRNA and protein product using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification, in situ hybridization, and immunohistochemistry in bronchial biopsies from symptomatic atopic and nonatopic asthmatic subjects and atopic and nonatopic controls. The results showed that as compared with controls, biopsies from both groups of asthmatic subjects had increased numbers of IL-4 and IL-5 mRNA copies relative to beta-actin mRNA as detected by RT-PCR. Similarly, in situ hybridization and immunohistochemistry demonstrated increased numbers of cells expressing IL-4 and IL-5 mRNA and protein in asthmatic subjects, irrespective of their atopic status. We conclude that individuals with either atopic or nonatopic asthma show infiltration of the bronchial mucosa with cells expressing Th2-type cytokines, providing further evidence for similarities in the immunopathogenesis of these clinically distinct forms of asthma.

Adult↗
PubMed1996

Increased interleukin-10 messenger RNA expression in atopic allergy and asthma.

Interleukin-10 (IL-10) inhibits T-lymphocyte proliferation and production of cytokines. We have examined expression of IL-10 messenger RNA (mRNA) in atopic asthma and in allergen and tuberculin skin responses by in situ hybridization. The proportion of bronchoalveolar lavage (BAL) cells positive for IL-10 mRNA was increased in a group of 10 symptomatic asthmatics when compared with control subjects (17.5% versus 5.2% BAL cells positive; P < 0.001). In a separate group of six mild atopic asthmatics, there was an increased proportion of BAL cells positive for IL-10 mRNA 24 h after allergen inhalation challenge compared with diluent challenge BAL from the same subjects (24% versus 10%; P < 0.005). By simultaneous in situ hybridization and immunocytochemistry, IL-10 mRNA was localized to both CD3+ T cells and CD68+ alveolar macrophages in BAL, with a significantly more prominent T-cell signal in the symptomatic asthmatics compared with control subjects and after allergen challenge compared with diluent challenge of the mild asthmatic subjects. It has been suggested that IL-10 production is a late event after T-cell activation. To examine kinetics and specificity of IL-10 mRNA expression, skin biopsies were obtained from atopic, tuberculin-sensitive subjects at 1, 6, and 48 h after cutaneous injection of allergen or tuberculin. With both stimuli, there was an increase in IL-10 mRNA-positive cells at 6 h when compared with control sites injected with appropriate diluent which were biopsied 24 h after injection (P < 0.01 for allergen and P < 0.02 for tuberculin). These findings are compatible with the hypothesis that IL-10 mRNA is expressed in both macrophages and T lymphocytes in the airway in asthma and that IL-10 mRNA expression is induced from T lymphocytes in response to allergen. This response may also occur in other types of cell-mediated inflammation.

Adolescent↗
PubMed1996

Stereotactic uses beyond core biopsy: model development for minimally invasive treatment of breast cancer through interstitial laser hyperthermia.

Light of a Nd:YAG laser presented through a fiberoptic cable to a diffusing tip can be adapted to mammographic stereotactic instruments now used for core biopsy in the hyperthermic endoablation of breast cancer. This approach to cancer destruction extends breast preservation to the point of no observable surface skin change. The initial analysis characterizes the effects of laser endohyperthermia in a physical model as well as in tissue, both ex vivo and in vivo, to create a reliable technique that will lead to human trials. A fiberoptic cable with a diffusing quartz tip placed deep within soft tissue can pass light of a neodymium laser and consequent thermal energy for the destruction of surrounding soft tissues. Because breast cancer occurs with greatest frequency in the involuted breasts of women more than 50 years of age and because this tissue is predominantly fibro-fatty in nature, our work has concentrated on model development and the determination of heat distribution and destruction of fat and fibro-fatty tissue. Following the development of a physical model, time-temperature courses were found to be similar in ex vivo human breast tissue and subcutaneous porcine fat. This led to in vivo porcine studies that confirmed similar time-temperature courses. For tissues brought to a range of 60 degrees C to 80 degrees C and sustained for the better part of 20 minutes, gross and histological analyses reveal complete destruction over a 1 1/2 cm radial region around the laser tip. This approach offers great promise for the treatment of stereotactically biopsied small T1 breast carcinomas.

Animals↗
PubMed1996

Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression.

BACKGROUND: Nefazodone hydrochloride, an antidepressant that acts as a 5-HT2 antagonist and serotonin (5-HT) and norepinephrine uptake inhibitor, was evaluated in a double-blind, imipramine- and placebo-controlled study involving 128 patients with major depression. METHOD: Eligible patients were randomly assigned to receive placebo (2 to 6 capsules/day), imipramine (100 to 300 mg/day), or nefazodone (200 to 600 mg/day) for 8 weeks. The principal efficacy outcome measure assessed was the number of patients who experienced an adequate response during treatment. RESULTS: Based on global improvement (Clinical Global Impressions-Improvement), 67% of nefazodone-treated patients (p < or = .01) and 63% of imipramine-treated patients (p < or = .05) responded during 8 weeks of treatment, compared with 36% of placebo controls. Sixty-two percent of nefazodone-treated, 53% of imipramine-treated, and 26% of placebo-treated patients had 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores < or = 10 on completion of acute treatment. Nefazodone-treated patients had a lower incidence of premature treatment discontinuation and fewer dropouts for adverse events than the imipramine group. CONCLUSION: In a three arm comparison with imipramine and placebo, nefazodone had the greatest number of patients with major depression who responded to therapy. Nefazodone, a new antidepressant with novel pharmacology, is a well-tolerated, efficacious antidepressant.

Adult↗
PubMed1996

The safety profile of nefazodone.

Comprehensive review of safety data from approximately 3500 patients who received nefazodone in premarketing clinical trials demonstrates the drug to be very well tolerated, with a favorable side effect profile compared with other antidepressant drugs. Nefazodone treatment was associated with fewer side effects than were the control drugs. The incidence of side effects was generally low, and treatment discontinuations for adverse effects were less frequent with nefazodone than with imipramine and comparable with fluoxetine. No late-appearing side effects or toxicity emerged during the long-term treatment (1 year or longer) of several hundred patients. There were no drug-related fatalities and no evidence that nefazodone caused specific organ toxicity, although some cardiovascular side effects were noted (e.g., asymptomatic reduced systolic blood pressure, asymptomatic sinus bradycardia). Experience in 488 elderly patients treated with nefazodone yielded no evidence of increased susceptibility of older patients to nefazodone-associated adverse experiences, including those pertaining to the cardiovascular system. However, treatment should be initiated at a reduced dose in elderly patients because of reduced hepatic clearance of nefazodone in this age group. Final dose range may be similar in healthy younger and older patients. Although nefazodone may interact with some other medications (e.g., increases at steady state in AUC: alprazolam, twofold; triazolam, fourfold), drug-drug interactions involving patients have been clinically minor. On the basis of the inhibition of cytochrome P450 3A4 isoenzyme by nefazodone in vitro, coadministration of terfenadine or astemizole with nefazodone is contraindicated because nefazodone can increase the plasma levels of these two drugs. Extensive clinical experience provides substantial evidence that nefazodone is an extremely safe and effective treatment for depression, with important advantages over existing therapies. Therapeutic benefits include a low incidence of clinically troublesome side effects and lack of unwanted psychic activation, sexual dysfunction, weight change, and the cardiotoxicity of other antidepressants.

Adolescent↗
PubMed1996

Therapeutic dose range of nefazodone in the treatment of major depression.

The therapeutic dose range of nefazodone for treatment of major depression was examined in a series of placebo-controlled efficacy studies carried out during phase 2 and 3 premarketing clinical evaluation. Nefazodone is a new antidepressant drug with pharmacologic effects on both serotonin and norepinephrine neurotransmitters. The usual starting dose of nefazodone for depressed patients, unless they are being switched from a serotonin selective reuptake inhibitor (SSRI), is 100 mg. b.i.d. A lower starting dose is recommended for elderly patients or patients being treated with an SSRI. Following assessment of the patient's clinical response after the first week of therapy, the daily dose should be adjusted upward for most patients. In the efficacy studies, the majority of patients were being maintained on a dose of 300 to 500 mg daily at the end of the acute treatment period. The side effects of nefazodone most often related to dosage were sedation, nausea, and visual symptoms. Imipramine-treated patients, on the other hand, had a high incidence of dry mouth, constipation, and asthenia. In these studies, nefazodone was found to be effective and well tolerated by patients, the majority of whom were being maintained at a 300- to 500-mg/day dose, following an initial starting dose of 100 mg b.i.d.

Age Factors↗
PubMed1995

Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) concentrations in serum and bronchial lavage fluid in asthma. Effect of prednisolone treatment.

BACKGROUND: Eosinophil granule proteins may contribute to bronchial hyperresponsiveness in asthma. OBJECTIVE: To measure eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in serum and bronchial lavage fluid from 20 asthmatics and 16 control subjects. To assess the effect on these eosinophil proteins of corticosteroid treatment of asthma. To determine whether serum ECP and EPX measured weekly in a longitudinal study for 10 weeks reflected changes in lung function. METHODS: Eosinophil granule proteins were measured by radioimmunoassay of bronchial wash (BW), bronchoalveolar lavage (BAL) and serum. RESULTS: Eosinophils were elevated in BAL (P < 0.01), BW (P < 0.01) and blood (P < 0.01) from asthmatics compared with control subjects. Eosinophils cationic protein concentration was significantly elevated in BAL (P < 0.05) and BW from asthmatics (P < 0.01) and EPX was increased in BAL (P < 0.05) and BW (P < 0.01). These changes were also reflected in elevated serum ECP (P < 0.01) and EPX (P < 0.01) concentrations in asthmatic subjects. There was no significant difference between subjects receiving prednisolone and the placebo group, but there was a fall in ECP in BW (P < 0.05) and serum (P < 0.01) and in EPX in BW (P < 0.01) and serum (P < 0.01) within the group receiving prednisolone. In the longitudinal study there was only a significant difference between ECP values associated with highest and lowest peak expiratory flow rate (PEFR) (P < 0.05). CONCLUSIONS: These data confirm a role for eosinophil activation in the airway in asthma pathogenesis, and add some support to the hypothesis that corticosteroids may inhibit eosinophil activation in asthma.

Adult↗
PubMed1995

Pulmonary complications of HIV disease: 10 year retrospective evaluation of yields from bronchoalveolar lavage, 1983-93.

BACKGROUND: Pulmonary disease is a major contributor to morbidity and mortality in patients with HIV infection and AIDS. The aim of this study was to describe bronchoscopic findings and the spectrum of pulmonary pathogens in HIV seropositive patients undergoing investigation of respiratory disease over a 10 year period in a major UK referral centre. METHODS: Recruitment was procedure based with data being captured when bronchoscopy was clinically indicated. Data were evaluated from 580 HIV seropositive patients (559 men, age 13-65 years) over a 10 year period from June 1983 to March 1993. RESULTS: A total of 947 bronchoscopies was performed. The most frequent pulmonary pathogen isolated from bronchoalveolar lavage (BAL) fluid in 44% of all bronchoscopies was Pneumocystis carinii. Of all patients studied, 324 (55%) had at least one cytologically confirmed episode of P carinii pneumonia; this was AIDS defining in 219 (38%) of patients who underwent bronchoscopy. Between 1987 and 1993 the overall diagnostic yield from BAL fluid was 76%; 25% of all bronchoscopies yielded positive microbiological results, the most frequent isolates being Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas spp, and Haemophilus influenzae. Mycobacteria were identified in 8% of patients; M tuberculosis was the most common being identified in 3% of lavage samples and in 4% of patients. No drug-resistant M tuberculosis was found. Viral isolates (mainly cytomegalovirus) were identified in up to 31% of BAL fluid samples. Endobronchial Kaposi's sarcoma was seen in 15% of patients at bronchoscopy. CONCLUSIONS: Of the 1956 newly diagnosed HIV seropositive patients receiving clinical care at St Mary's Hospital over this period, approximately 30% underwent bronchoscopy. Diagnostic rates for P carinii pneumonia, endobronchial Kaposi's sarcoma, and bacterial and mycobacterial infection have remained largely constant since 1989. Bronchoalveolar lavage produces high diagnostic yields generally, and P carinii pneumonia remains a common cause of pulmonary disease in these patients.

Adolescent↗
PubMed1995

Free radicals in foods.

During the last decade increasing attention has been given to the role of free radicals in biological oxidations. The subject has been of increasing interest to both the food scientist and the physiologist. Free radical scavengers in the form of both indigenous and added antioxidants are necessary for the successful preservation of food; free radicals are increasingly being implicated in the onset of, among others, ischaemic heart disease and for protection against these diseases it is suggested that the dietary intake of the antioxidant vitamins should be increased especially for diets high in polyunsaturated fats. Convenience and snack foods which absorb substantial amounts of frying oils are being increasingly consumed. Since poly-unsaturated fatty acids are particularly susceptible to oxidation by free radicals during the storage, cooking and frying of foods, the potential risk of exposure to lipid degradation products is likely to have increased. In foods the non-enzymic and lipoxy-genase catalysed oxidation of polyunsaturated fatty acids, beta-carotene and vitamin A can result in the loss of essential nutrients and the development of off-flavours.

Antioxidants↗
PubMed1995

Nefazodone: aspects of efficacy.

BACKGROUND: Nefazodone hydrochloride, a 5-HT2 receptor antagonist and serotonin (5-HT) uptake inhibitor, was evaluated in four Phase 3 double-blind, imipramine- and placebo-controlled studies involving outpatients with major depression. METHOD: Patients who qualified for well-controlled efficacy trials in major depression were enrolled in a series of active- and placebo-controlled trials to establish the comparative efficacy of nefazodone and a standard tricyclic antidepressant drug. The primary efficacy measures employed were the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Improvement (CGI) scale. Safety profiles were also compared as well as survival analyses of double-blind acute and continuation treatment of patients in efficacy trials. RESULTS: Three of four Phase 3 active- and placebo-controlled studies showed nefazodone to be an effective antidepressant drug with overall efficacy generally similar to that of imipramine. The remaining study did not differentiate either active drug from placebo controls. Superiority of nefazodone and imipramine over placebo was evidenced by greater improvement on core depression symptoms in addition to the primary outcome measures (HAM-D-17 and CGI). The incidence of side effects and premature treatment discontinuations for imipramine-treated patients was higher than for nefazodone therapy. Both drugs showed evidence of continuing efficacy during long-term treatment with significantly fewer dropouts (p < .05) than for placebo controls. CONCLUSION: Nefazodone, an antidepressant that modulates serotonin receptors and enhances serotonin-mediated neurotransmission, has been shown to be an effective and well-tolerated new antidepressant drug with greater patient acceptability and safety than imipramine.

Ambulatory Care↗
PubMed1995

Preoperative scintigraphy and operative probe scintimetry of colorectal carcinoma using technetium-99m-88BV59.

UNLABELLED: We report a pilot study of radioimmunoscintigraphy (RIS) and operative gamma probe scintimetry (OPS) using a 99mTc-labeled anti-cytokeratin human monoclonal antibody (MAb) (99mTc-88BV59) in patients with newly diagnosed, recurrent or metastatic colorectal cancer. METHODS: Twelve presurgical patients with biopsy- or contrast radiographic-proven colorectal cancer or recurrent colorectal carcinoma were studied. After chest roentgenography and abdominopelvic CT, 99mTc-88BV59 was administered intravenously, planar and SPECT external imaging was performed 3 to 6 hr after injection and planar imaging was performed 18 to 24 hr after injection. Surgery was performed immediately after late planar imaging. OPS of a standardized list of sites to document background radiation activity and of tumor sites, resection margins and tumor beds was performed. RESULTS: The patients had 23 histologically proven tumor sites. Overall sensitivity for CT, planar RIS, SPECT, surgery and OPS was 43%, 61%, 78%, 96% and 91%, respectively. SPECT was superior to CT for imaging extrahepatic abdominal and pelvic disease. OPS detected all liver and extrahepatic abdominal tumor sites and correctly predicted histological tumor-free margins and tumor beds in all cases. OPS did not identify tumor deposits that the surgeon could neither see nor feel. No patient demonstrated human anti-human immune responsiveness 1 and 3 mo after 99mTc-88BV59 infusion. CONCLUSION: Technetium-99m-88BV59 is a safe, effective radioimmunoconjugate for colorectal cancer imaging, with superior sensitivity as compared to CT.

Aged↗
PubMed1994

Optimism versus pessimism predicts the quality of women's adjustment to early stage breast cancer.

BACKGROUND: Recent studies indicate that breast cancer patients do not usually experience the devastating psychological consequences once viewed as inevitable. However, some adjust to the disease more poorly than others. This study examined the personality trait of optimism versus pessimism as a predictor of adjustment over the first year, postsurgery. METHODS: Seventy women with early stage breast cancer reported on their general optimism-pessimism at diagnosis. One day before surgery, and at 3-month, 6-month, and 12-month follow-ups, they reported their subjective well-being (mood scales and a measure of satisfaction with life). At follow-ups, they also rated their sex lives, indicated how much physical discomfort was interfering with their daily activities, and reported on thought intrusion. RESULTS: Pessimism displayed poorer adjustment at each time point by all measures except interference from pain. Even controlling for previous well-being, pessimism predicted poorer subsequent well-being, suggesting that pessimism represents a vulnerability to a negative change in adjustment. In contrast, effects of pessimism on quality of sex life and thought intrusion were not incremental over time. Additional analyses indicated that effects of the optimism-pessimism measure were captured relatively well by a single item from the scale. CONCLUSIONS: A sense of pessimism about one's life enhances a woman's risk for adverse psychological reactions to the diagnosis of, and treatment for, breast cancer. This finding suggests the potential desirability of assessing this quality informally in patients, to serve as a warning sign regarding the patient's well-being during the period surrounding and following surgery.

Adaptation, Psychological↗