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Biomedical subjects

M Watson

Publications and source records attributed to M Watson.

At least 109 records · Page 6Linked to original sources

Gastric antral vascular ectasia (watermelon stomach) in patients with systemic sclerosis.

This report describes 5 patients with systemic sclerosis (SSc) who developed severe, recurrent upper gastrointestinal (GI) bleeding due to gastric antral vascular ectasia (GAVE). The clinical records, the endoscopic findings, and the histologic appearance of biopsy specimens and surgically resected gastric tissue from the patients were reviewed. All 5 patients developed severe and recurrent episodes of upper GI bleeding leading to severe anemia requiring multiple transfusions. The cutaneous involvement was diffuse in 3 patients and limited in 2. All but 1 had cutaneous telangiectasias. The diagnosis of GAVE was established by endoscopy within 3 years of the diagnosis of SSc in all cases. One patient required heater probe cautery, 2 required laser coagulation, and 2 underwent surgical resection of the gastric antrum for control of the GI bleeding. The possibility of GAVE should be considered in SSc patients who have recurrent upper GI bleeding. It is suggested that the antral vascular lesions in these patients may represent a component of the spectrum of vascular alterations of SSc.

Adult↗

A modular questionnaire for the assessment of longterm quality of life in leukaemia patients: the MRC/EORTC QLQ-LEU.

We describe the psychometric analysis of a supplementary quality of life measure (MRC/EORTC QLQ-LEU) for evaluating long term sequelae of leukaemia treatments. The questionnaire under development was administered to 388 patients entered into the EORTC-GIMEMA AML 8A and the MRC AML10 clinical trials who were in complete remission for at least one year after completion of treatment on these trials. Results indicated a measure which is useful in evaluating the long-term effects of treatment in relation to chronic graft-vs-host disease and infection susceptibility. The performance of this measure in terms of its sensitivity and specificity between treatment arms was established by comparisons between the three treatment modalities in the above-mentioned trials and is the subject of further investigation. The new Leukaemia Module can be recommended for use alongside generic QOL instruments as a measure of long-term quality of life in leukaemia trials.

Acute Disease↗

Inpatient cost of primary total joint arthroplasty.

The financial and medical records of 98 patients undergoing either primary total hip or total knee arthroplasty were analyzed to determine the inpatient cost of their surgery. Eleven patients were excluded, leaving a total of 87 patients available for analysis who underwent 50 primary total hip and 37 primary total knee arthroplasties. Ten separate cost centers such as implant, anesthesia/operating room, nursing/hospital room, physical therapy, and laboratory were included in the evaluation. Correlations between total cost and demographic parameters such as patient sex, age, and length of stay were determined. Seventy-six percent of the inpatient cost of all total joint procedures consisted of implant, anesthesia/operating room, and nursing/hospital room costs. Reductions in the cost of these components represent a potential for cost containment. The strongest correlate for total cost was hospital length of stay (P < .0005). Unfortunately, there is evidence that length of stay has reached a plateau and cannot be reduced further without affecting the quality of care and the incidence of complications.

Adult↗

Familial breast cancer: a controlled study of risk perception, psychological morbidity and health beliefs in women attending for genetic counselling.

The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attending the Royal Marsden and Mayday University Hospital genetic counselling services and 62 matched GP attenders (controls). Levels of general psychological morbidity were found to be similar between cases and controls; however, cases reported significantly higher breast cancer-specific distress despite clinic attendance [mean (s.d.) total Impact of Event Scale score, 14.1 (14.3) cases; 2.4 (6.7) controls, P < 0.001]. Although cases perceived themselves to be more susceptible to breast cancer, many women failed correctly to recall risk figures provided by the clinic; 66% could not accurately recall their own lifetime chance. Clinics appeared to have a positive impact on preventive behaviours and cases tended to engage more regularly in breast self-examination (monthly, 66% of cases vs 47% of controls), although few differences were found between groups in terms of health beliefs. We conclude that counselees and GP controls showed considerable similarities on many of the outcome measures, and risk of breast cancer was not predictive of greater psychological morbidity; although cases were more vulnerable to cancer-specific distress. Despite genetic counselling, many cases continued to perceive their risk of breast cancer inaccurately.

Adult↗

Targeted delivery of an antisense oligonucleotide in the retina: uptake, distribution, stability, and effect.

In this article, we describe the preliminary results of the development of an animal model that will enable us to study the effect of photoreceptor-derived debris accumulation on the normal function of the retina in vivo. An antisense oligonucleotide (Cat 5), saline, and two control oligonucleotides were injected into the vitreous of 7-week-old RCS-rdy+ rats. The uptake, distribution, and persistence of the antisense oligonucleotide in the retina was demonstrated by fluorescent confocal microscopy, and the stability of the oligonucleotide was shown by GeneScan analysis using a fluorescein-labeled derivative of Cat 5 (Cat 5F). The accumulation of photoreceptor-derived debris was monitored by the number of undigested phagosomes in the RPE layer by light microscopy. Following intravitreal injection of Cat 5F, penetration of the oligonucleotide was observed in the ganglion cell layer in 2 hours and in the photoreceptor and pigment epithelial layers 3 days later. However, at 7, 28, and 56 days postinjection, only the RPE layer had significant amounts of Cat 5F present. Using GeneScan analysis, it was demonstrated that the fluorescein-labeled oligonucleotide present in the RPE layer was not degraded and it retained its original 19-mer length. There was no statistically significant difference in the number of phagosomes found in the RPE layer of control uninjected, saline-injected, and two sense and two antisense oligonucleotides-injected animals at 7 and 28 days postinjection. In contrast, the number of phagosomes was significantly higher (p < 0.001) in the RPE layer of Cat 5 antisense oligonucleotide-injected animals at 7 and 28 days postinjection. This difference, however, disappeared by 56 days postinjection. The inner nuclear layers of the retina of control and experimental animals were not affected by the injections.

Adolescent↗

Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness.

To investigate genetic factors in asthma and atopy, we sought allelic associations for 12 markers near candidate loci for serum total, immunoglobulin E (IgE), and bronchial hyperresponsiveness (BHR) to inhaled histamine in 131 families comprising 685 individuals, selected randomly without regard to atopy or asthma. Nonparametric linkage and association analyses were performed with the Nonparametric Analysis of Lineage and Association (NOPAR) program, and parametric analyses were performed with the Complex Inheritance with Diathesis and Severity (COMDS) program on an ordered polychotomy of ranked scores. On chromosome 11q, allele 168 at the D11S527 locus was significantly associated with BHR (p<0.0003) but not with log IgE. At the D11S534 locus, allele 235 was significantly associated with log IgE (p = 0.007) but not with BHR. Both D11S527 and D11S534 were too distant from the gene encoding the high-affinity IgE receptor FcepsilonRIbeta to account for the association. At the interleukin-9 (IL-9) locus, the 118 allele showed significant association with serum total IgE (p<0.003) but not with histamine BHR. Parametric tests are more conservative, perhaps because they demand consistency with mendelian inheritance and tight linkage. These findings provide support for the view that both chromosomes 5 and 11 may contain genes relevant to asthma and atopy, a possible candidate being the interleukin-4 (IL-4) gene cluster. Because these associations are extremes in a large number of tests, they require confirmation in other samples.

Adolescent↗

Bipolar salvage shoulder arthroplasty. Follow-up in 14 patients.

A bipolar spacer was inserted for severe arthritic destruction of the shoulder in 14 patients, and followed up for a mean of 5.9 years. In one patient the operation failed because of infection. Two others required revision for loss of low-friction properties which caused loosening of the humeral component. At the end of the follow-up all the patients showed improvement. The Hospital for Special Surgery pain score had increased from 5.3 to 18.9 and the movement score from 7.5 to 20.1.

Aged↗

Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer.

Exposure to carcinogens present in the diet, cigarette smoke, or the environment may be associated with increased risk of colorectal cancer. Aromatic amines (aryl- and heterocyclic) are a class of carcinogens that are important in these exposures. These compounds can be N- or O-acetylated by the NAT1 or NAT2 enzymes, resulting in activation or in some cases detoxification. Recent studies have shown that both NAT2 and NAT1 genes exhibit variation in human populations and that rapid acetylation by the NAT2 enzyme may be a risk factor for colorectal cancer. In this study we have analyzed for genetic polymorphism in both NAT1 and NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from Staffordshire, England. We find significantly increased risk (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = 0.009) associated with the NAT1*10 allele of NAT1, an allele that contains a variant polyadenylation signal. Individuals with higher stage tumors (Duke's C) were more likely to inherit this variant allele (odds ratio, 2.5; 95% confidence interval, 1.3-4.7; P = 0.005). In contrast, rapid acetylation genotypes of NAT2 were not a significant risk factor in this English population. However, we found that the risk associated with the NAT1 variant allele (NAT1*10) was most apparent among NAT2 rapid acetylators (odds ratio, 2.8; 95% confidence interval, 1.4-5.7; P = 0.003), suggesting a possible gene-gene interaction between NAT1 and NAT2 (test for interaction; P = 0.12). This is the first study to test for cancer risk associated with the NAT1 gene, and these positive findings suggest that NAT1 alleles may be important genetic determinents of colorectal cancer risk.

Adenocarcinoma↗

Identification of abuse in emergency departments: effectiveness of a two-question screening tool.

OBJECTIVE: A national health objective for the year 2000 is that at least 90% of hospital emergency departments have protocols for routine identification, treatment, and referral for victims of spouse abuse. An effective assessment tool is needed to implement such protocols. METHODS: To test the effectiveness of a two-question, nurse-administered, screening tool to detect physical abuse, 416 black, Hispanic, and white women coming to public and private emergency departments with vaginal bleeding were asked two questions. Additionally, a 14-item Danger Assessment Scale to determine risk factors of homicide was administered to all women. RESULTS: In response to the two-question abuse assessment screen, 38% of the 416 women reported a history of physical or sexual abuse. For 61% of the women, the last episode of abuse occurred within the last 12 months. White women reported significantly more abuse than other ethnic groups (chi 2 = 18.71; df = 2; p = 0.00009). Teenagers reported more risk factors of homicide. DISCUSSION: Abuse to women who seek care in emergency departments is common and easily detected with a straightforward two-question screen. Universal assessment and accompanying information on safety and community resources is essential to interrupt abuse, prevent further trauma and potential homicide, and promote the health and safety of women.

Adolescent↗

Bartonella henselae is a causative agent of cat scratch disease in Australia.

We report the first isolation of Bartonella henselae from the blood and fleas of a cat of a patient with cat scratch disease (CSD) in Australia. A 49-year-old man presented with a history that 3 weeks after he had removed fleas from his cat he had developed fever, lethargy and anorexia for 3 days. This was followed by the appearance of axillary lymphadenopathy. There was no history of a bite or scratch and no primary lesion on the skin. Two fine needle aspirates of the axillary lymph node showed granulomatous lymphadenitis with no organisms seen by Warthin-Starry silver staining or electron microscopy. No organism was cultured from the patient's lymph node aspirates or blood cultures processed by lysis centrifugation. However, the polymerase chain reaction (PCR) using p24E and p12B primers gave a 280 bp band indistinguishable from Bartonella henselae when using DNA extracted from the lymph node aspirates and the patient's blood leucocytes. DNA sequencing of the PCR product from the patient's blood showed that the DNA was from Bartonella henselae. The patient's serum had a titre of 1024 in an indirect immunofluorescence antibody test for Bartonella henselae. Bartonella henselae was subsequently cultured from fleas and blood taken from the patient's cat. This case provides evidence that Bartonella henselae is a causative agent of CSD in Australia and supports a possible role for fleas in transmission of the disease.

Animals↗

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↗

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↗

Promoting an awareness of retractions: the Louisiana State University Medical Center in Shreveport experience.

The current mission statement of the Medical Library Association states that it is "dedicated to improving health through professional excellence and leadership of its members in the ... provision of information services and educational programs ..." With this goal in mind, retractions offer medical librarians a professional challenge to become involved in the scientific process. Through results of a survey conducted among the consortium of South Central Academic Medical Libraries (SCAMeL), this paper reveals opinions on the importance of retraction awareness and who is responsible for disseminating this knowledge. The paper also reports what the Louisiana State University Medical Center at Shreveport Library and other SCAMeL member libraries are doing to promote awareness.

Academic Medical Centers↗

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↗

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↗