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Biomedical subjects

S Gore

Publications and source records attributed to S Gore.

At least 19 recordsLinked to original sources
PubMed2005

PRODOC: a resource for the comparison of tethered protein domain architectures with in-built information on remotely related domain families.

PROtein Domain Organization and Comparison (PRODOC) comprises several programs that enable convenient comparison of proteins as a sequence of domains. The in-built dataset currently consists of approximately 698 000 proteins from 192 organisms with complete genomic data, and all the SWISSPROT proteins obtained from the Pfam database. All the entries in PRODOC are represented as a sequence of functional domains, assigned using hidden Markov models, instead of as a sequence of amino acids. On average 69% of the proteins in the proteomes and 49% of the residues are covered by functional domain assignments. Software tools allow the user to query the dataset with a sequence of domains and identify proteins with the same or a jumbled or circularly permuted arrangement of domains. As it is proposed that proteins with jumbled or the same domain sequences have similar functions, this search tool is useful in assigning the overall function of a multi-domain protein. Unique features of PRODOC include the generation of alignments between multi-domain proteins on the basis of the sequence of domains and in-built information on distantly related domain families forming superfamilies. It is also possible using PRODOC to identify domain sharing and gene fusion events across organisms. An exhaustive genome-genome comparison tool in PRODOC also enables the detection of successive domain sharing and domain fusion events across two organisms. The tool permits the identification of gene clusters involved in similar biological processes in two closely related organisms. The URL for PRODOC is http://hodgkin.mbu.iisc.ernet.in/~prodoc.

Databases, Protein↗
PubMed2003

A phase II trial of three sequential doublets for the treatment of advanced müllerian malignancies.

OBJECTIVES: In an effort to improve the results of primary chemotherapy for müllerian malignancies a novel chemotherapy program was piloted that delivered three sequential chemotherapy doublets. The primary endpoints were surgically defined response rates and evaluation of toxicity. METHODS: After primary cytoreductive surgery patients were treated with three sequential doublets including three initial cycles of carboplatin and paclitaxel (doublet 1) and then two cycles of cisplatin (day 1) and gemcitabine (days 1 and 8; doublet 2), and finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet 3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5 mcg/kg/day. After therapy, all women were clinically staged and evaluated by second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for residual disease. RESULTS: A total of 49 eligible patients were enrolled with a median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2 with papillary serous carcinoma of the uterus. Eighty-four percent of patients had stage IIIc/IV tumors, with 29% having >1 cm residual disease after primary cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A total of 283 cycles of chemotherapy were delivered with acceptable toxicities. There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol hypersensitivity, 1 for gemcitabine pulmonary hypersensitivity, and 1 for serious line infection). Neutropenia, typically without fever, was relatively frequent in the first doublet. Nausea and thrombocytopenia were the predominant toxicities in doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women had restaging results consistent with a clinical complete response (CR) and underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%. CONCLUSIONS: Treatment with this sequential doublet regimen is feasible with a 38% pathologic CR rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Human AML cells in NOD/SCID mice: engraftment potential and gene expression.

Most cases of human acute myeloid leukemia (AML) engraft in irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Intravenous transfer of as few as 10(5) human AML cells resulted in engraftment. Cases with poor prognosis clinical features, including FLT3 mutations, tended to engraft efficiently. Nevertheless, AML cells obtained from patients at relapse did not engraft more efficiently than cells obtained from the same patients at initial diagnosis. One passage of human AML cells in NOD/SCID mice did not appear to select for increased virulence, as measured by serial transplantation efficiency. Finally, cDNA microarray analyses indicated that approximately 95% of genes were expressed at similar levels in human AML cells immunopurified after growth in mice, as compared to cells assessed directly from patients. Thus, the growth of human AML cells in NOD/SCID mice could yield large numbers of human AML cells for direct experimental use and could also function as a renewable, potentially unlimited source of leukemia cells, via serial transplantation.

Acute Disease↗
PubMed2002

Transferring people safely with manual handling equipment.

OBJECTIVE: To determine whether transferring equipment designed to assist a carer when moving someone who is able to take some weight through their legs is likely to affect the risk of back problems in the carer. DESIGN: Twelve pieces of equipment were tested by nurses transferring patients from commode to wheelchair and vice versa, and from wheelchair to bed and vice versa. Video recordings were taken of each transfer and freeze-frame pictures at the moment of greatest load were analysed. Compressive disc force was deduced, using a biomechanical model, from the weights of the patient and nurse and measurements of anatomical distances and angles. SETTING: The Sir Walter Puckey Gait Laboratory, in the Rehabilitation Research Unit, University of Southampton. SUBJECTS: Six female trained nurses with no recent history of hernia, back pain or pregnancy during the previous six months were recruited to use the equipment. Two female patients were chosen from those volunteering and screened for stroke, confusion and unusual footwear. The patients were able to partially weight-bear and were used to being transferred. RESULTS: The results indicate that the critical value of 3.4 kN at the L5/S1 disc (specified by the US National Institute for Occupational Safety and Health) was not exceeded when using transferring equipment. CONCLUSION: In this study, loading on the spine during transferring tasks with or without equipment was not considered harmful when good technique was employed.

Back Injuries↗
PubMed2000

Report of an international working group to standardize response criteria for myelodysplastic syndromes.

Standardized criteria for assessing response are essential to ensure comparability among clinical trials for patients with myelodysplastic syndromes (MDS). An international working group of experienced clinicians involved in the management of patients with MDS reviewed currently used response definitions and developed a uniform set of guidelines for future clinical trials in MDS. The MDS differ from many other hematologic malignancies in their chronicity and the morbidity and mortality caused by chronic cytopenias, often without disease progression to acute myeloid leukemia. Whereas response rates may be an important endpoint for phase 2 studies of new agents and may assist regulatory agencies in their evaluation and approval processes, an important goal of clinical trials in MDS should be to prolong patient survival. Therefore, these response criteria reflected 2 sets of goals in MDS: altering the natural history of the disease and alleviating disease-related complications with improved quality of life. It is anticipated that the recommendations presented will require modification as more is learned about the molecular biology and genetics of these disorders. Until then, it is hoped these guidelines will serve to improve communication among investigators and to ensure comparability among clinical trials. (Blood. 2000;96:3671-3674)

Disease Progression↗
PubMed2000

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL.

BACKGROUND: Standard therapy for lymphoma consists of a cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP) combination regimen. Liposomal daunorubicin (DaunoXome) is an alternative to doxorubicin for patients with lymphoma because of its more favorable safety profile and potentially more selective uptake in lymphoma. The objectives of this study were to determine the maximum tolerated dose (MTD) of liposomal daunorubucin with CVP (COP-X) and the tolerability of the regimen in patients with indolent lymphoma. PATIENTS AND METHODS: Patients with low-grade and intermediate-grade lymphoma having adequate cardiac, hepatic, and renal function were enrolled. Patients received C 750 mg/m2, V 1.4 mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50-100 mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1-5. MTD was the liposomal daunorubicin dose associated with 20% dose-limiting toxicity (ANC < 500/mm3 for > 5 days or febrile neutropenia). RESULTS: Twenty patients, median age 59 years, were treated. The liposomal daunorubicin MTD combined with CVP was 70-80 mg/m2, depending on patient population. No significant non-hematologic toxicity occurred. Response rate was 44% (2 complete and 5 partial responses). CONCLUSIONS: A liposomal daunorubicin dose of 80 mg/m2 in the COP-X regimen was well tolerated with little nonhematologic toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Parents' and therapists' opinion on features that make a chair useful for a young disabled child.

Children who fail to develop postural skills within a normal time scale are prescribed special seating to position them appropriately. For children to derive benefit from such seating, they must use it at home as well as in therapy sessions. A study was undertaken to explore the opinions of therapists and parents concerning the effectiveness and acceptability of a sample of special seating available on the UK market for young children. Each of the ten chairs selected to represent the range of possible styles and features was tested by 12 or 16 children in their homes (total sample of 40) for a week each, and four therapy centres for a fortnight each. Results obtained from these two populations were compared to determine whether chair features considered useful differed when used in a therapy centre or family home. Parents' rating for overall usefulness was affected by their perception of the child's comfort, as well as the child's posture, the level of support the chair offered, and other factors. Therapists' response, in contrast, seemed to be mainly influenced by the quality of posture children achieved in the chair.

Child↗
PubMed2000

Life stress, anger and anxiety, and delinquency: an empirical test of general strain theory.

General strain theory (Agnew 1992) departs from traditional strain theories by emphasizing the role of the individual's affective responses to negative life experiences in fostering deviant behavior. In this analysis, we examine the central hypotheses of general strain theory using data from a three-wave panel study of high school youths in the Boston metropolitan area (N = 939). Covariance structure models reveal that anger and hostility in response to negative life events do play a causal role in fostering more aggressive forms of delinquency, but are not significantly related to either nonaggressive delinquency or marijuana use. Furthermore, the conditional effects predicted by general strain theory, in which the impact of strain on delinquency varies by youths' personal and social resources, are inconsistent. Discussion centers on the prospect of increasing the utility of general strain theory by further imbuing it with concepts and perspectives from the sociology of mental illness.

Adolescent↗
PubMed1999

Toward improved management of NIDDM: A randomized, controlled, pilot intervention using a lowfat, vegetarian diet.

OBJECTIVE: To investigate whether glycemic and lipid control in patients with non-insulin-dependent diabetes (NIDDM) can be significantly improved using a low-fat, vegetarian (vegan) diet in the absence of recommendations regarding exercise or other lifestyle changes. METHODS: Eleven subjects with NIDDM recruited from the Georgetown University Medical Center or the local community were randomly assigned to a low-fat vegan diet (seven subjects) or a conventional low-fat diet (four subjects). Two additional subjects assigned to the control group failed to complete the study. The diets were not designed to be isocaloric. Fasting serum glucose, body weight, medication use, and blood pressure were assessed at baseline and biweekly thereafter for 12 weeks. Serum lipids, glycosylated hemoglobin, urinary albumin, and dietary macronutrients were assessed at baseline and 12 weeks. RESULTS: Although the sample was intentionally small in accordance with the pilot study design, the 28% mean reduction in fasting serum glucose of the experimental group, from 10.7 to 7.75 mmol/L (195 to 141 mg/dl), was significantly greater than the 12% decrease, from 9.86 to 8.64 mmol/L (179 to 157 mg/dl), for the control group (P < 0.05). The mean weight loss was 7.2 kg in the experimental group, compared to 3. 8 kg for the control group (P < 0.005). Of six experimental group subjects on oral hypoglycemic agents, medication use was discontinued in one and reduced in three. Insulin was reduced in both experimental group patients on insulin. No patient in the control group reduced medication use. Differences between the diet groups in the reductions of serum cholesterol and 24-h microalbuminuria did not reach statistical significance; however, high-density lipoprotein concentration fell more sharply (0.20 mmol/L) in the experimental group than in the control group (0.02 mmol/L) (P < 0.05). CONCLUSION: The use of a low-fat, vegetarian diet in patients with NIDDM was associated with significant reductions in fasting serum glucose concentration and body weight in the absence of recommendations for exercise. A larger study is needed for confirmation.

Adult↗
PubMed1999

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

Child↗
PubMed1999

Regression of columnar-lined (Barrett's) oesophagus with omeprazole 40 mg daily: results of 5 years of continuous therapy.

BACKGROUND: We have previously reported the effect of 2 years of omeprazole 40 mg daily on columnar-lined (Barrett's) oesophagus (CLO). AIMS: In the present study, follow-up has been extended to 5 years to assess the macroscopic and microscopic effects of continuing therapy. PATIENTS AND METHODS: The 23 patients have been followed for up to a further 3 years. Endoscopy with multiple biopsies was performed at the end of years 3, 4 and 5. RESULTS: Although there had been a statistically significant regression in the length of CLO after 2 years, there was no overall further measurable change after 5 years. However, one patient showed complete macroscopic and microscopic regression. The number and size of macroscopic squamous islands within the CLO continued to increase, and there was a further increase in microscopic squamous re-epithelialization of surface mucosa, gland ducts and Barrett's gland tissue. Low-grade dysplasia was found consistently in one patient in biopsies taken up to the end of year 3 but it could not be detected thereafter. CONCLUSIONS: Omeprazole 40 mg daily appears to have beneficial effects on CLO, although it rarely induces a complete regression. Whether the benefits will reduce the risk of malignant transformation is unknown.

Aged↗
PubMed1998

The co-occurrence of depression and substance abuse in late adolescence.

This article examines the role of adolescent social relationships in fostering the occurrence and co-occurrence of depression and substance abuse, using two waves of data from a community sample of adolescents (N = 900). Multinomial logistic response models were estimated to identify the extent to which risk and protective features of youths' family and peer relations were differentially linked with depressive symptoms, substance abuse, and their co-occurrence. Taking a within-person, configurational approach to adolescent adaptation, contrasts involved four subgroups of adolescents: those high on both depressed mood and substance abuse, those who experience neither problem, those evidencing high levels of depressive symptoms only, and those high on substance abuse only. Risk for depressive symptoms was differentiated by its association with conflict and lack of support in the friendship domain. Substance abuse was associated with negative peer pressure, but these youth were otherwise little different from youths with no problems. Whereas co-occurrence of depression and substance use was associated with more difficulties in both the family and peer environments, the most distinctive risk was that of low family support. Discussion centers on the developmental antecedents of co-occurring problems and family relations during adolescence.

Adolescent↗
PubMed1998

Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients.

We set out to quantify the changes in HIV-related morbidity and mortality associated with the clinical use of antiretroviral therapy via prospectively collected patient-related events (admissions, bed days, deaths, WHO stage 3 and 4 events and drug costs) on all HIV patients known to the Regional Infectious Disease Unit (RIDU) from 1 January 1987 to 31 December 1996. The introduction of zidovudine monotherapy in 1987 for those with AIDS was associated with a subsequent decline of inpatient activity for 2 years: in 1989 there was a 23% reduction in bed days but only a 6% reduction in admissions. A further dramatic decline of patient-related events in those with AIDS was noted during 1996 following the introduction of combination therapy, a 39% reduction in admissions, 44% reduction in bed days, 54% reduction in stage 4 events, 33% reduction in WHO stage 3 events and 40% reduction in the death rate. Reductions were also observed for patients without AIDS including a 42% reduction in the rate of patients developing AIDS. Similar reductions were noted when the patients were classified by immunological instead of clinical status although data for 1997 suggest an increase in patient-related activity for those with CD4 counts >200 cells/microl possibly as a result of low levels of anti-HIV therapy. The introduction of combination therapy for HIV has to date led to a minimum saving of one inpatient bed per 100 patient years which helped defray the cost of combination therapy. Although we cannot imply causality from an observational study, dramatic reductions in patient-related activity were associated with the introduction of combination therapy into clinical practice. The ultimate extent and duration of this effect cannot as yet be predicted and caution is required since similar reductions were noted with zidovudine therapy which were unfortunately time limited.

Anti-HIV Agents↗