Massive splenomegaly complicating left percutaneous renal surgery.
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Aged↗
Biomedical subjects
M Watson
Publications and source records attributed to M Watson.
Staphylococcus lugdunensis endocarditis.
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Bacterial Typing Techniques↗
ATP-dependent regulation of a G protein-coupled K+ channel (GIRK1/GIRK4) expressed in oocytes.
Recent studies suggest that activation of the atrial muscarinic K+ current by acetylcholine (ACh) involves an ATP-dependent process that is then inhibited by a cytosolic protein to result in the rapid desensitization. To obtain further evidence in support of such a dually regulated process, we studied the properties of GIRK1 and GIRK4, which, when coexpressed in oocytes, form a heteromultimer that closely resembles the muscarinic K+ channel. ACh activated an inwardly rectifying K+ current that desensitized slowly. In cell-attached patches with ACh in the pipette, the mean open times (tau zero) of GIRK1/GIRK4 were 1.2 +/- 0.1 (28%) and 6.7 +/- 0.8 ms (72%) and did not change significantly with time. However, in inside-out patches, the tau zero of GIRK1/GIRK4 activated with guanosine 5'-O-(3-thiotriphosphate) was 1.3 +/- 0.1 ms (100%), and the channel activity (NP0) was almost fivefold lower. These changes in channel kinetics did not occur in the presence of sodium orthovanadate (3 mM), an inhibitor of phosphatase. Addition of 1 mM ATP, but not adenylimidodiphosphate, to inside-out patches resulted in increases in NP zero (4.8-fold) and the open-time duration of GIRK1/GIRK4, such that tau zero were 1.2 +/- 0.2 (32%) and 6.2 +/- 0.6 ms (68%). Single channel conductances were unchanged (34 +/- 1 pS). Cytosolic extract from atria, but not oocytes, could reverse these effects of ATP. These results provide further evidence that the antagonistic modulation of G protein-gated K+ channels by ATP and the atrial cytosolic protein produces the early rapid desensitization in atrial cells. In oocytes the ATP-dependent step is dominant and thus provides a major component of the total GIRK1/GIRK4 current activated by ACh.
Acetylcholine↗
Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.
PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS: The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION: The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.
Adenocarcinoma↗
Cardiovascular risk factor screening and intervention in African American adults.
The Cardiac Health and Rehabilitation program of St. Thomas Hospital in Nashville, Tennessee, has developed a project to assess the effectiveness of a community-based cardiovascular risk assessment and intervention program directed at African American adults. The specific aim of this program is to assess the feasibility of implementing a community-based cardiovascular disease risk factor reduction program directed at African American adults. Its ultimate goal is to be able to teach African American adults cost-efficient, simple methods of exercise, nutrition, and weight management; smoking cessation; and blood pressure control. The program is expected to raise the African American community's awareness of the importance of modifiable cardiovascular disease risk factors and their effect on cardiac morbidity and mortality. The program is also expected to be able to evaluate the success of cardiovascular disease risk factor intervention and patient satisfaction with the program.
Adolescent↗
Neonatal intensive care unit. Caring for mothers too.
The provision of adequate care for the mother of an infant hospitalised within the Neonatal Intensive Care Unit (NICU) is often more complex than is immediately obvious. The needs of the mother while her infant is in the NICU are many and varied, as each individual responds differently to the demands and stresses of her infant's hospitalisation. Only by adopting a synchronised approach to the care of the mother and infant can an effective system of care be created.
Adult↗
Association of prostate cancer with vitamin D receptor gene polymorphism.
The incidence of prostate cancer in the United States is second only to skin cancers, and the disease kills almost the same number of men as breast cancer does women. Relatively few risk factors are known for prostate cancer, although several lines of evidence suggest that vitamin D may be an important determinant of prostate cancer risk. A series of common polymorphisms in the vitamin D receptor gene were recently reported to be associated with bone density and risk of osteoporosis (Morrison et al., Nature (Lond.), 367: 284-287, 1994). These genetic variants have been correlated with both circulating levels of active vitamin D hormone and in vitro measures of gene expression (Morrison et al., Nature (Lond.), 367: 284-287, 1994). We tested the hypothesis that vitamin D receptor gene polymorphisms are associated with prostate cancer risk using a case-control study of 108 men undergoing radical prostatectomy and 170 male urology clinic controls with no history of cancer. Among the white control group, 22% were homozygous for the presence of a TaqI RFLP at codon 352 (genotype tt), but only 8% of cases had this genotype (P < 0.01). A similar trend was seen among the small number of blacks in this study (13% for controls, 8% for cases), although the difference was not statistically significant. Race-adjusted combined analysis suggests that men who are homozygous for the t allele (shown to correlate with higher serum levels of the active form of vitamin D) have one-third the risk of developing prostate cancer requiring prostatectomy compared to men who are heterozygotes or homozygous for the T allele (odds ratioMH = 0.34; 95% confidence interval, 0.16-0.76; P < 0.01). These results support recent ecological, population, and in vitro studies suggesting that vitamin D is an important determinant of prostate cancer risk and, if confirmed, suggest strategies for chemoprevention of this common cancer.
Black or African American↗
Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for esophagogastric adenocarcinoma: response, toxicity, quality of life, and survival.
BACKGROUND: The results of chemotherapy for patients with esophagogastric carcinoma have generally been modest but regimens developed more recently have produced higher response rates, and rekindled interest in neoadjuvant chemotherapy. One such regimen is epirubicin, cisplatin, and 5-fluorouracil (ECF). This study evaluates its efficacy, toxicity, impact on quality of life (QL), and impact on survival in a large consecutive series of patients with metastatic and locally advanced disease (LAD). METHODS: Patients with histologically confirmed esophagogastric carcinoma were treated with ECF (epirubicin 50 mg/m2 and cisplatin 60 mg/m2 every 3 weeks with continuous infusion of 5-fluorouracil (5-FU) 200 mg/m2/d). Responses were evaluated with computed tomography (CT) scan and endoscopy. QL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS: A total of 235 patients were treated, 173 with metastatic disease and 62 with LAD. The mean number of cycles delivered was 6 (range: 1-11) and patients were followed-up for a median of 8 months. Response was observed in 135 of 220 (61%) evaluable patients, with a complete response (C(R)), 11% of the patients and a partial response in 50% of the patients. Patients with moderately differentiated adenocarcinomas and LAD responded most favorably. Symptomatic improvement was achieved in the majority of cases (63-78% depending on the symptom). Toxicity was generally only mild to moderate, with severe non hematologic toxicity in less than 12% of the patients and only 6 (2.5%) treatment related deaths. QL assessment showed no significant negative impact on emotional functioning and good symptomatic control. Surgery following response to ECF was performed in 29 of the LAD patients, and in 19 cases (66%) a potentially curative resection was possible, with histologic CR in 32% of the patients. CONCLUSIONS: ECF is a highly active regimen with acceptable toxicity in patients with esophagogastric adenocarcinoma. In a proportion of patients with LAD, chemotherapy enabled potentially curative surgery to be performed. The results justify further investigation of this regimen in a neoadjuvant setting.
Adenocarcinoma↗
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↗
Genetic testing in breast/ovarian cancer (BRCA1) families.
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Attitude to Health↗
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↗
Health promotion. Heart attack.
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Community Health Planning↗