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Biomedical subjects

M Watson

Publications and source records attributed to M Watson.

At least 73 records · Page 4Linked to original sources

Chylothorax following oesophagogastrectomy for malignant disease.

OBJECTIVE: To define the incidence, causes, management and impact of Chylothorax after oesophagogastrectomy for malignant disease in Nottingham Thoracic Surgery unit. PATIENTS AND METHODS: Retrospective analysis of 523 patients with cancer of the oesophagus or the gastro-oesophageal junction who underwent oesophageal resection between January 1987 and November 1997 in a single unit using similar techniques and uniform routine perioperative management. RESULTS: Chylothorax occurred in 21 patients (4.0%). There were 12 males and 9 females with a mean age of 64.7 years (SD 7.5). Age, sex, tumour site, length, histological type, depth of wall penetration, nodal status and type of operative approach were not significant predisposing factors on univariate and multivariate analysis. Seventeen patients were treated conservatively (four deaths, 23.5%) and four surgically (one death, 25.0%), effective control of the chylous leak being achieved in all four cases. Eleven patients with a chylous drainage of up to 2.2 l/day, diminishing within 1 week of conservative treatment had an uneventful recovery. However, a chylous drainage of more than 2.5 l/day in the remaining ten patients was associated with increased morbidity, hospital stay, operative mortality and the need for surgical intervention. In comparison with the remaining patients (n = 502), those who developed chylothorax (n = 21) had more respiratory complications (42.8%, P = 0.008), longer mean hospital stay (23.8 days, P = 0.004), higher operative mortality (23.1%, P = 0.004) and, unexpectedly, reduced 5 year survival rate (P < 0.0001). CONCLUSIONS: There appeared to be no clear predisposing factor in the development of a chylous leak other than the routine extensive dissection. Although definitive conclusions can not be drawn, where there is early reduction of the initial amount (in this series up to 2.2 l/day) of drainage, there may be a place for successful non-surgical management; in cases of high output chylothorax, persisting after a few days of conservative treatment, however, early re-operation and ligation of the thoracic duct, seems to be advisable.

Aged↗

Memory processes and the course of anxiety and depression in cancer patients.

BACKGROUND: Intrusive memories of stressful events, many involving illness and death, are found in a minority of depressed cancer patients, and may predict the course of anxiety and depression. METHOD: Matched samples of mild to moderately depressed and non-depressed cancer patients were followed up after 6 months. Anxiety and depression at follow-up were related to measures of intrusive memories of stressful life events and autobiographical memory functioning that had been assessed at baseline. RESULTS: Levels of anxiety and depression remained fairly constant over time in the two groups, and the depressed group continued to experience high levels of intrusive memories. The presence of intrusive memories at baseline, and the extent to which these memories were consciously avoided, predicted greater anxiety at follow-up, even after controlling for initial severity of physical and psychiatric symptoms. None of the measures of memory functioning predicted levels of depression at follow-up. CONCLUSIONS: Intrusive memories appear to be a marker of more prolonged psychopathology in cancer patients and may respond to direct therapeutic intervention.

Adult↗

Children with both developmental and behavioral needs: profile of two clinic populations.

Little has been written about evaluation and intervention services for children with a combination of behavioral and developmental needs. Two multidisciplinary clinic populations were compared, a traditional Developmental Disabilities (DD) clinic and a Behavioral-Developmental Problems (BDP) Clinic that had the additional services of a child psychiatrist. The BDP clinic children had lower IQ's and more severe overall behavioral problems than children in the traditional DD clinic, but differences were not statistically significant. Children with Attention Deficit Hyperactivity Disorder (ADHD) and other psychiatric diagnoses were referred to both clinics at comparable rates. The effort to involve qualified mental health professionals in all aspects of professional training and clinical service for the DD population should be accelerated.

Adolescent↗

Irritable bowel syndrome symptom patterns: frequency, duration, and severity.

We examined symptom frequency, duration, and severity, as well as episode patterns, in 122 adult patients with irritable bowel syndrome in a 12-week study conducted in the United States, the United Kingdom, and The Netherlands. Patients used an interactive telephone data entry system daily to report symptoms. Data from 59 of the patients meeting inclusion criteria are presented, the remainder having been excluded for failing to complete at least 70 days of symptom reporting. The majority of patients experienced at least one symptom on over 50% of the reported days; however, individual symptoms were reported on less than 50% of the days, indicating that symptoms sometimes occurred sequentially rather than always simultaneously. On average, patients reported pain/discomfort on 33% of days, bloating on 28% of the days, altered stool form or stool passage on 25% and 18% of the days, respectively, and mucus on 7% of the days. The duration of symptoms was relatively short, with pain/discomfort and bloating lasting the longest, an average of five days each per episode. All symptoms but one (mucus) were moderately severe on the majority of reported days. Patients experienced an "episode" (defined as a period of days with symptoms bounded by one or more symptom-free days) on an average of 12.4 times during the study, but the duration of these episodes varied greatly among patients. These results further establish the chronic nature of irritable bowel syndrome and the burden that this condition imposes on patients.

Adult↗

Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex.

Many important cell mechanisms are carried out and regulated by multi-protein complexes, for example, transcription and RNA processing machinery, receptor complexes and cytoskeletal structures. Most of these complexes remain only partially characterized due to the difficulty of conventional protein analysis methods. The rapid expansion of DNA sequence databases now provides whole or partial gene sequences of model organisms, and recent advances in protein microcharacterization via mass spectrometry allow the possibility of linking these DNA sequences to the proteins in functional complexes. This approach has been demonstrated in organisms whose genomes have been sequenced, such as budding yeast. Here we report the first characterization of an entire mammalian multi-protein complex using these methods. The machinery that removes introns from mRNA precursors--the spliceosome--is a large multi-protein complex. Approximately half of the components excised from a two-dimensional gel separation of the spliceosome were found in protein sequence databases. Using nanoelectrospray mass spectrometry, the remainder were identified and cloned using public expressed sequence tag (EST) databases. Existing EST databases are thus already sufficiently complete to allow rapid characterization of large mammalian protein complexes via mass spectrometry.

Amino Acid Sequence↗

Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. Scottish and Newcastle Renal Artery Stenosis Collaborative Group.

BACKGROUND: Data from randomised studies are lacking on the value of interventional procedures in the management of atheromatous renal artery stenosis. This randomised prospective trial compared the effects on blood pressure (BP) and renal function of percutaneous transluminal angioplasty vs medical therapy in hypertensive patients with both unilateral and bilateral disease. METHODS: A total of 135 eligible patients were identified, of whom 55 (44%) were randomised. Eligible patients had sustained hypertension, with a minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal artery stenosis was defined by renal angiography as at least 50% stenosis in the affected vessel. All patients were observed during an initial 4-week run-in period on a fixed drug regimen and subsequent changes measured from this 4-week baseline. RESULTS: Blood pressure fell during the run-in period in all groups. In patients with bilateral renal artery stenosis randomised to angioplasty, a statistically significant (P<0.05) fall in BP was observed at latest follow-up (range 3-54 months). The mean fall in BP at latest follow-up in the angioplasty group, corrected for the medical group response, was 26/10 mm Hg. In patients with unilateral renal artery stenosis, no statistically significant or clinically important differences in outcome were observed between the two groups. No significant differences or trends in serum creatinine were observed between or within any group during follow-up. Major outcome events (death, myocardial infarction, heart failure, stroke, dialysis) were similar in the angioplasty and medical groups during follow-up. In the 40/135 patients undergoing angioplasty, serious or potentially serious complications attributable to the procedure were observed in 11 patients, bleeding at the arterial site (8 patients) being the most frequent. CONCLUSIONS: In hypertensive patients with atheromatous renal artery stenosis, percutaneous renal angioplasty results in a modest improvement in systolic BP compared with medical therapy alone. This benefit was confined to patients with bilateral disease. No patient was 'cured', renal function did not improve, and intervention was accompanied by a significant complication rate.

Adult↗

Characteristics of sexual abuse against pregnant Hispanic women by their male intimates.

There have been few research reports on sexual abuse of Hispanic women by their intimate male partners. This study examined the frequency of six types of sexual abuse of 329 pregnant Hispanic women identified during routine prenatal care in public health clinics as physically abused. Threats of abuse, physical abuse, and sexual abuse were measured with the 46-item Severity of Violence Against Women Scale. Comparisons were made between women reporting sexual abuse and those who did not. Thirty-two percent (n = 105) of the women reported sexual abuse by their male partner at least once during the prior 12 months. Sexually abused women reported significantly higher levels of threats of abuse and physical abuse than women not sexually abused. Among the sexually abused women, not living with the abuser was correlated with higher threats of abuse, physical violence, and sexual abuse scores. The results of this study support previous research proposing a continuum of violence and possible escalation of violence when an abused woman leaves her abuser. Additional longitudinal research is needed on psychosocial and behavioral characteristics of sexually abused women, particularly among ethnic minority women.

Adolescent↗

A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people.

Risk of oral cancer has been associated with exposure to tobacco smoke, alcohol and with genetic predisposition. The aromatic amines and their metabolites, a class of carcinogens present in tobacco smoke, undergo metabolism (activation or detoxification) through an N- or O-acetylation pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2. The genes that encode these enzymes, NAT1 and NAT2, have a variety of high and low activity alleles and we analyzed these genetic polymorphisms in 62 oral squamous cell carcinoma cases, and 122 healthy control subjects from Japan. NAT1 alleles tested were NAT1*3 (C1095A), NAT1*4 (functional reference allele), NAT1*10 (T1088A,C1095A), NAT1*11(9 bp deletion), NAT1*14 (G560A), NAT1*15 (C559T) and NAT1*17 (C190T). No low activity alleles (NAT1*14, NAT1*15 and NAT1*17) were observed in these Japanese subjects. We observed significantly increased risk [odds ratio 3.72; 95% confidence interval (CI) 1.56-8.90; P < 0.01] associated with the NAT1*10 allele, an allele that contains a variant polyadenylation signal. Stratifying by smoking status we found odds ratios of 5.9 (95% CI 1.13-30.6; P < 0.05) for non-smokers with the NAT1*10 allele and 3.1 (95% CI 1.09-9.07; P < 0.05) for smokers, but these risks were not significantly different from each other. Thus, we did not observe that NAT1*10 alleles confer differential risk among smokers and non-smokers. NAT2 rapid acetylation genotype was not a significant risk factor for oral cancer in this Japanese study population. This is the first study to test for oral cancer risk associated with polymorphism in the NAT1 and NAT2 genes, and these positive findings in our pilot study, while based on small numbers, suggest that the NAT1*10 allele may be a genetic determinant of oral squamous cell carcinoma among Japanese people.

Acetylation↗

Isoflurane and pentobarbital reduce the frequency of transient ischemic depolarizations during focal ischemia in rats.

UNLABELLED: Repetitive transient ischemic depolarizations (IDs) during focal cerebral ischemia are thought to contribute to ischemic damage. Isoflurane and pentobarbital reduce injury (versus the nonanesthetized state) after focal cerebral ischemia. The mechanism by which these drugs reduce injury is not known. This protective effect might be mediated by a reduction in the number of IDs. We measured the frequency of IDs during focal cerebral ischemia in animals anesthetized with isoflurane or pentobarbital and compared it with that in N2O/fentanyl anesthetized animals and in animals in which the N-methyl-D-aspartate receptor antagonist MK801 (dizocilpine) was given. Focal cerebral ischemia was induced by the occlusion of the middle cerebral artery for a period of 2 h. Cortical infarct volumes were determined after 3 h of reperfusion by image analysis of 2,3,5-triphenyl tetrazolium-stained coronal brain sections. The infarct volume was significantly greater in the N2O/fentanyl group than in the other three groups. Infarct volumes in the isoflurane, pentobarbital, and MK801 groups were similar. The frequency of IDs was significantly greater in the N2O/fentanyl group than in the other three groups, and was the least in the MK801 group. There was a direct correlation between the number of IDs and the volume of tissue injury. The data indicate that the protective effect of isoflurane and pentobarbital might, in part, be determined by their ability to reduce IDs during focal ischemia. However, the observation that the infarct volume was similar in the MK801, isoflurane, and pentobarbital groups, despite a greater frequency of IDs in the latter two groups, suggests that mechanisms other than a simple reduction in the number of IDs probably also play a role in anesthetic-mediated cerebral protection. IMPLICATIONS: Transient ischemic depolarizations during focal ischemia contribute to brain injury. Both isoflurane and pentobarbital reduced the frequency of these depolarizations. Isoflurane- and pentobarbital-mediated reduction in the frequency of depolarizations might, in part, mediate the previously documented neuroprotective effect of these drugs.

Adjuvants, Anesthesia↗

Family history of breast cancer: what do women understand and recall about their genetic risk?

The current study has two aims: (1) to look at people's recall of risk information after genetic counselling and (2) to determine the impact of receiving an audiotape of the genetic consultation on level of recall, cancer related worry, and women's uptake of risk management methods. Using a prospective randomised controlled design, subjects receiving an audiotape were compared with a standard consultation group. Participants were drawn from attenders at the genetic clinics of two London hospitals and included 115 women with a family history of breast cancer. Assessment of perceived genetic risk, mental health, cancer worry, and health behaviour was made before counselling at the clinic (baseline) and by postal follow up. Usefulness of audiotapes and satisfaction with the clinical service was assessed by study specific measures. The data indicate that cancer worry is reduced by provision of an audiotape of the genetic consultation. Recall of the genetic risk figure, however, is not affected by provision of an audiotape and neither is it related to women's overall perception of being more or less at risk of breast cancer than the average woman. Forty-one percent of women accurately recalled their personal risk of breast cancer at one month follow up; however, 25% overestimated, 11% underestimated, and 23% could not remember or did not know their breast cancer risk. Recall of the risk figure is more accurate when the clinical geneticist has given this to the woman as an odds ratio rather than in other formats. Subsequent health behaviour is unaffected by whether women have an audiotape record of their genetic consultation. Results suggest that having a precise risk figure may be less important than women taking away from the consultation an impression that something can be offered to help them manage that risk. Provision of an audiotape of the consultation is of limited usefulness. The need for psychological care to be better integrated into genetic counselling at cancer family clinics was highlighted by the study. The results are discussed in terms of future service development.

Breast Neoplasms↗

Solar UVR exposures of primary school children at three locations in Queensland.

The ultraviolet radiation (UVR) exposures of primary school children in Brisbane, Toowoomba and Mackay (latitudes 27 degrees 30', 27 degrees 33' and 21 degrees 15' south, respectively) were assessed over a period of 2 weeks at each location using UVR-sensitive polysulfone (PS) film badges attached at the shoulder. The students filled in questionnaires on their time spent outdoors for each day of the study. These data in conjunction with the ambient UVR measured by a detector/datalogger unit at each site were used to correlate the calculated exposures with those measured using the PS badges. Overall, the questionnaires indicated that the males spent more time outdoors and had higher measured UVR exposures than females. For both boys and girls at each location, there was a strong correlation between the mean measured UVR exposure and the ambient solar UVR at that location.

Child↗

Does short-term group therapy affect unexplained medical symptoms?

This paper describes an intensive time-limited group-therapy program conducted in a busy surgical clinic by two nursing staff with the support of a consultant psychiatrist. Nineteen patients with chronic idiopathic facial pain were recruited to the study and underwent weekly group therapy over 8 weeks. At the end of the study period, results showed decreases in pain, anxiety and depression scores, along with an improvement in the patients coping skills. The findings support the use of group psychological interventions undertaken by appropriately trained nursing staff in reducing symptoms associated with chronic idiopathic facial pain.

Adult↗

A prospective randomised trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer.

BACKGROUND: To compare protracted venous infusion (PVI) 5-fluorouracil (5-FU) with and without mitomycin C (MMC) in a prospectively randomised study and analyse for tumour response, survival, toxicity and quality of life (QL). PATIENTS AND METHODS: Two hundred patients with advanced colorectal cancer received PVI 5-FU 300 mg/m2/day for a maximum of 24 weeks and were randomised to PVI 5-FU alone or PVI 5-FU + MMC 10 mg/m2 (7 mg/m2 from June 1995) 6 weekly for 4 courses. RESULTS: Overall response was 54% (95% confidence interval [CI] 44.1%-63.9%) with PVI 5-FU + MMC compared to 38% (95% CI: 28.3%-47.7%) for PVI 5-FU alone (P = 0.024). The median failure free survival was 7.9 months in PVI 5-FU plus MMC and 5.4 months with PVI 5-FU alone (P = 0.033) and at one year 31.9% for the combination compared to 17.7% for PVI 5-FU alone. Median survival was 14 months with MMC and 15 months in 5-FU alone; one-year survival 51.7% vs. 57.2%. PVI 5-FU + MMC caused more overall haematological toxicity but CTC grades 3/4 was increased only for thrombocytopaenia. Two patients treated with a cumulative dose of MMC of 40 mg/m2 developed haemolytic uraemic syndrome warranting the reduction in cumulative MMC dose to 28 mg/m2. The global QL scores were better for PVI 5-FU + MMC arm at 24 weeks, but the remaining QL data showed no differences. CONCLUSIONS: PVI 5-FU + MMC results in failure-free survival and response advantage, tolerable toxicity and better QL when compared to PVI 5-FU alone but no overall survival advantage. There is no irreversible toxicity with MMC at a cumulative dose of 28 mg/m2.

Adenocarcinoma↗

A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).

Adenocarcinoma↗

Quality of life in patients with acute myelogenous leukemia in prolonged first complete remission after bone marrow transplantation (allogeneic or autologous) or chemotherapy: a cross-sectional study of the EORTC-GIMEMA AML 8A trial.

A cross-sectional study of quality of life (QOL) was performed in 98 patients in continued first complete remission (CR) for 1-7.4 years, after inclusion in the AML 8A trial which prospectively compared allogeneic bone marrow transplantation (AlloBMT), autologous BMT (ABMT) and intensive consolidation chemotherapy. Several significant differences between the three treatment groups were observed, on the basis of patient self-reports, with regard to somatic symptoms (mouth sores, cough, hair loss, headache), repeated acute medical problems, physical functioning, role functioning, leisure activities and, above all, sexual functioning. There were also significant differences for overall physical condition, and overall quality of life. For all these parameters, the ranking was uniformly AlloBMT lower than ABMT lower than chemotherapy. These differences remain significant after adjustment for time interval between CR and QOL evaluation, sex or age. These results, confirming a higher risk of permanent impairment of QOL after BMT, may have an impact on medical decisions and warrant further studies.

Adult↗