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Biomedical subjects

M Watson

Publications and source records attributed to M Watson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Exclusion from proximal 11q of a common gene with megaphenic effect on atopy.

We have typed three markers on proximal 11q in 131 random families with three or more children studied for atopy. A summary map that includes the FCER1B candidate was constructed. Using a 2-locus disease model, we performed combined segregation and linkage analysis of three models, none of which suggested linkage. Nine marker loci on other chromosomes were also negative. In the regions swept by these 12 markers we cannot rule out a rare gene, perhaps of large effect, nor a common gene of small effect. However, a common gene of large effect is excluded. These results and alternative strategies are discussed in the perspective of inconsistent evidence for a major atopy gene.

Alleles↗
PubMed1995

Impact of protracted venous infusion fluorouracil with or without interferon alfa-2b on tumor response, survival, and quality of life in advanced colorectal cancer.

PURPOSE: The aim of this study was to investigate the effects of adding interferon alfa-2b (IFN) to protracted venous infusion fluorouracil (PVI 5-FU) from the start of treatment in patients with advanced colorectal cancer. PATIENTS AND METHODS: Patients who attended our unit with histologically confirmed advanced colorectal cancer were randomized to receive either PVI 5-FU 300 mg/m2/d via Hickman line, and IFN 5 MU subcutaneously three times weekly, or PVI 5-FU alone. Treatment was given for a maximum of two 10-week blocks, with a 2-week gap for reassessment of all parameters. Quality of life (QL) was measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) pretreatment and every 6 weeks thereafter. RESULTS: A total of 160 patients were randomized, with 155 eligible for assessment. Radiologic response was observed in 43 patients (28%): 17 of 77 (22%) in the 5-FU-plus-IFN arm (all partial responses [PRs]) and 26 of 78 (33%) in the 5-FU-alone group (complete responses [CRs] and 22 PRs) (difference not significant). Symptomatic improvement occurred in the majority of patients, and equally in both arms: 61% to 80% depending on the symptom. There was no significant difference between the two groups in failure-free survival (median, 161 v 193 days) or overall survival (median, 328 v 357 days). However, patients who received IFN did experience significantly more toxicity in the form of leukopenia (P = .001), neutropenia (P = .04), mucositis (P = .008), and alopecia (P = .0002). There were no toxic deaths and few notable differences in QL between the two arms. CONCLUSION: This study confirms that PVI 5-FU is effective in treating the symptoms associated with metastatic colorectal carcinoma, with only mild to moderate toxicity and maintenance of QL. IFN 5 MU three times weekly does not enhance these palliative benefits.

Adolescent↗
PubMed1995

Inhibin forms in human plasma.

In order to identify the molecular weight forms of bioactive and immunoactive inhibin in human plasma, plasma/serum was sequentially fractionated by immunoaffinity chromatography (using immobilised inhibin alpha subunit antiserum), reversed phase HPLC and preparative SDS-PAGE. The electroeluted gel fractions were assayed for inhibin in vitro bioactivity and immunoactivity, the latter by RIA. Initial experiments examined human follicular fluid as an inhibin-rich source. Bioactive and immunoactive fractions of 30, 35, 53, 65 and approximately 120 kDa were identified in addition to bio-inactive, immunoactive fractions of 26 kDa and 32 kDa. These molecular weights correspond to those of known inhibin forms and are attributed to differing degrees of glycosylation of the inhibin alpha subunit and variable processing of the alpha and beta inhibin subunits. Fractionation of male plasma pools revealed the presence of higher molecular weight immunoactive forms (55-120 kDa) as well as 28-31 kDa forms although the molecular weight distribution of activity between pools varied. To assess if the molecular weight pattern was modified by storage and/or subsequent fractionation, protease inhibitors were added initially to plasma and fractionated as above. The molecular weight distribution of immunoactivity was largely unaffected by the treatment, indicating that minimal processing had occurred. Postmenopausal serum itself showed low to undetectable activity. The addition of recombinant human 31 kDa inhibin to postmenopausal serum resulted in a molecular weight profile of inhibin immunoactivity consistent with the presence of 31 kDa inhibin. Fractionation of a serum pool from women undergoing gonadotrophin stimulation, in which inhibin levels were elevated, showed a range of bioactive and immunoactive inhibin forms over the 30-120 kDa range.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Affinity↗
PubMed1995

Differential in vivo induction of immediate early genes by oxotremorine in the central nervous system of long- and short-sleep mice.

Long-sleep (LS) and short-sleep (SS) mice show differential sensitivity to both acute and chronic ethanol administration. Previous data also showed differential behavioral responses to muscarinic acetylcholine receptor agonist or antagonist treatment. We now report significantly greater inductions of c-fos, c-jun, jun-B, and Egr-1, but not jun-D, mRNA in the central nervous system (CNS) of LS versus SS mice after the intraperitoneal administration of oxotremorine. These genomic responses were dose dependent and completely inhibited (in both strains) by scopolamine, a specific muscarinic receptor antagonist. In situ hybridization studies verified the greater immediate early gene (IEG) inductions in LS mice, as initially observed by Northern analysis, and specifically showed that c-fos mRNA induction occurred predominantly in the thalamus, olfactory bulb, cerebellum, and cerebral cortex. Oxotremorine-induced c-jun mRNA was increased in cerebellum, CA1 hippocampal field, and cerebral cortex of both strains. Induced jun-B and Egr-1 transcripts were determined to have very similar CNS distribution patterns. Both mRNA species were induced in the cerebral cortex, caudate nucleus and putamen, hippocampal structures, and olfactory bulb. To further determine whether these differential IEG inductions reflect regional differences in receptor numbers, we determined the distributions and levels of each of the five muscarinic receptor subtypes in both strains by in situ hybridization. These data show that differences in receptor numbers alone may not account for the differential IEG inductions observed between the strains. Differential coupling constraints among CNS muscarinic receptors in LS versus SS mouse CNS may also play a significant role in producing differential IEG inductions.

Animals↗
PubMed1993

Anticipatory nausea and vomiting: broadening the scope of psychological treatments.

Anticipatory nausea and vomiting, as a side-effect of cancer chemotherapy, is a well-recognised phenomenon known to affect a substantial minority of patients. Although explicable using a conditioning model, it may have a complex aetiology with affective and cognitive elements as well as specific pharmacological factors playing a role in its onset and maintenance. It is amenable to treatment using psychological techniques but to treat successfully it is important to understand the aetiology and formulate treatment plans according to those factors that make a significant contribution to the cause. It is suggested here that a behavioural model provides an over-simplistic conceptualization and that cognitive factors play a central role in onset. As such, treatment plans need to be broader in scope by focusing on a range of strategies to enhance coping and particularly cognitive coping techniques. More recently there has also been some indication that psychological factors may contribute to symptoms of nausea and vomiting occurring during or after chemotherapeutic infusion. Should this effect be replicated, the scope for psychological treatments within the care of patients receiving chemotherapy would be widened.

Antineoplastic Agents↗
PubMed1993

Identification of a polymorphism in the human neurotensin receptor gene.

A complementary DNA (cDNA) clone encoding the neurotensin receptor was isolated from a human substantia nigra cDNA library. The deduced amino acid sequence of this clone was almost identical to that of a cDNA for this receptor cloned from a previously described HT29 human colonic adenocarcinoma cell line. We found three base changes between the previously reported HT29 cDNA clone and the current cDNA clone. We investigated these changes by using polymerase chain reactions to amplify these areas from various human samples. One of the differences, which resulted in an amino acid change at AA194 (a leucine in the HT29 sequence was a phenylalanine in the current sequence), was found in some, but not in all, human samples. This finding represents genetic variability in human neurotensin receptors, the first such report for a peptide receptor. Both of these receptors, however, when expressed separately in transfected cell lines, had similar affinities for neurotensin and some related peptides.

Amino Acid Sequence↗
PubMed1993

HIV/AIDS health promotion: a way forward.

Health promotion on HIV/Aids should be integral to the work of health visitors and school nurses, writes Michael Watson. But this work must be fully evaluated to ensure effectiveness. Here he describes the evaluation of HIV/Aids health promotion and looks in particular at approaches and methods suitable for individual professionals and districts.

Community Health Nursing↗
PubMed1992

Adjuvant psychological therapy for patients with cancer: a prospective randomised trial.

OBJECTIVE: To determine the effect of adjuvant psychological therapy on the quality of life of patients with cancer. DESIGN: Prospective randomised controlled trial comparing the quality of life of patients receiving psychological therapy with that of patients receiving no therapy, measured before therapy, at eight weeks, and at four months of follow up. SETTING: CRC Psychological Medicine Group of Royal Marsden Hospital. PATIENTS: 174 patients aged 18-74 attending hospital with a confirmed diagnosis of malignant disease, a life expectancy of at least 12 months, or scores on various measures of psychological morbidity above previously defined cut off points. INTERVENTION: Adjuvant psychological therapy, a brief, problem focused, cognitive-behavioural treatment programme specifically designed for the needs of individual cancer patients. MAIN OUTCOME MEASURES: Hospital anxiety and depression scale, mental adjustment to cancer scale, Rotterdam symptom checklist, psychosocial adjustment to illness scale. RESULTS: 156 (90%) patients completed the eight week trial; follow up data at four months were obtained for 137 patients (79%). At eight weeks, patients receiving therapy had significantly higher scores than control patients on fighting spirit and significantly lower scores on helplessness, anxious preoccupation, and fatalism; anxiety; psychological symptoms; and on orientation towards health care. These differences indicated improvement in each case. At four months, patients receiving therapy had significantly lower scores than controls on anxiety; psychological symptoms; and psychological distress. Clinically, the proportion of severely anxious patients dropped from 46% at baseline to 20% at eight weeks and 20% at four months in the therapy group and from 48% to 41% and to 43% respectively among controls. The proportion of patients with depression was 40% at baseline, 13% at eight weeks, and 18% at four months in the therapy group and 30%, 29%, and 23% respectively in controls. CONCLUSIONS: Adjuvant psychological therapy produces significant improvement in various measures of psychological distress among cancer patients. The effect of therapy observed at eight weeks persists in some but not all measures at four month follow up.

Adolescent↗
PubMed1992

Anticipatory nausea and emesis, and psychological morbidity: assessment of prevalence among out-patients on mild to moderate chemotherapy regimens.

The prevalence of nausea and emesis among a series of out-patients (n = 95) receiving mainly mild-to moderately-emetic cytotoxics, was assessed, along with levels of psychological morbidity. Particular focus was given to the rates of psychologically-based (anticipatory) nausea and emesis. Results indicated that 23% of patients experienced anticipatory nausea and the majority reported that this occurred before at least half of the previous treatment cycles. Both emetic challenge of chemotherapy regimen and younger age were linked to this anticipatory effect. The data clearly indicated that nausea and emesis, both post-treatment and in anticipation of treatment, carried a psychological cost with anxiety being highest in those experiencing anticipatory nausea and/or emesis. The role of anxiety in the aetiology of psychologically-based nausea and emesis was not evaluated and it is considered that a prospective study is needed to clarify the exact contribution of psychological factors in the incidence of both post-treatment and anticipatory side-effects.

Adult↗
PubMed1992

Portal and systemic hemodynamics and humoral factors in cirrhosis with and without ascites.

The pathogenesis of salt and water retention in cirrhosis remains unclear. Systemic and portal hemodynamic parameters, including cardiac output, portal pressure gradient and systemic vascular resistance, were measured in six patients with untreated ascites and in six patients with hepatic cirrhosis with no history of ascites. Renal blood flow, urinary volume, and humoral factors, including plasma renin, aldosterone, angiotensin II, and urine kallikrein, were measured. Significant differences were seen between the two groups in urine volume, urine sodium and fractional sodium excretion, plasma angiotensin II, and the ratio between plasma renin activity and urinary kallikrein excretion (PRA:UKallV). A strong correlation existed between urinary sodium excretion and the PRA:UKallV ratio. No significant differences were detected between the groups in portal, renal, and systemic hemodynamics. The present results suggest that humoral changes occur early in ascites. Altered relationships between intrarenal hormone systems, such as the renin-angiotensin and kallikrein-kinin systems, may be important in salt and water retention.

Ascites↗