Heterogeneity of beta-cell Ca2+ responses to glucose.
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Animals↗
Biomedical subjects
P Smith
Publications and source records attributed to P Smith.
Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma.
BACKGROUND: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon alpha-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence of survival. METHODS: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT. The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n = 25) and no PDT (n = 23) were similar with respect to age, sex, tumor volume, and histology. RESULTS: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT). There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT, 21; no PDT, 17; stage IV, PDT, 0; no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar. CONCLUSIONS: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM.
Adult↗
Myoelectric evidence of peripheral muscle fatigue during exercise in severe hypoxia: some references to m. vastus lateralis myosin heavy chain composition.
Integrated electromyography (iEMG) of the m. vastus lateralis was analysed during cycle ergometry in male subjects (n = 8). Two work trials were conducted, one under normoxia (N), the other under environmental normobaric hypoxia (EH in which the oxygen fraction in inspired gas = 0.116), each trial lasting 10 min. The absolute power output (180 W) was the same for both trials and was equivalent to 77 (4)% of maximum heart rate in trial N. Maximal voluntary isometric contractions were performed after each trial to assess changes in force, muscle fibre conduction velocity (MFCV), electromechanical delay (EMD), median frequency of EMG (MF) and maximal iEMG (iEMGmax). Biopsy samples of muscle were obtained from the m. vastus medialis before testing. Myosin heavy chain (MHC) differences were determined through sodium dodecyl-polyacrylamide gel electrophoresis followed by densitometric analysis. No differences in submaximal iEMG were observed between EH and N trials during the first minute of work. At the end of both work trials iEMG was significantly elevated compared with starting values, however the iEMG recorded in EH exceeded N values by 15%. At the end of the EH trials the following were observed: a decrease in isometric force, MFCV and MF with an increase in EMD and the iEMGmax/force ratio. The iEMGmax was unchanged. No differences in any of these variables were observed after the N trial. Mean (SD) lactate concentrations following EH and N trials were 9.2 (4.4) mmol x 1(-1) and 3.5 (1.1) mmol x 1(-1), respectively. Results indicate that an increased motor unit recruitment and rate coding was needed in EH to maintain the required power output. The increased motor unit recruitment and rate coding were associated with myoelectric evidence of "peripheral" muscle fatigue. Subjects with higher compositions of type II MHC accumulated more lactate and displayed greater reductions in MF and MFCV during fatigue.
Adult↗
Morphometric variables of developing primary maxillary first molar crowns in humans.
The following morphometric variables were examined in 18 primary maxillary first molars at various stages of development, collected from archaeological excavation sites in Israel: perimeters and areas from the occlusal view; buccolingual and mesiodistal dimensions and intercusp distances; the angle between the line joining the distobuccal, mesiobuccal and lingual cusps; and the height of the mesiobuccal cusp. An image-analysing technique comprising a photographic camera, a monitor, a computer with appropriate software and a digital caliper was used. Significant correlations were demonstrated between most variables. Teeth were divided into two groups according to their stage of development: stage one included all teeth at an early stage of development in which mesiobuccal cusp height was less than 5 mm; stage two included all teeth in later stages of development where mesiobuccal cusp height was greater than 5 mm. All external variables showed an increase in size between the two stages (while, among the internal ones, only the angle between the cusps showed a very small increase). The small sample is a limitation but the results suggest the following: (1) growth of the primary maxillary molar crown occurs with 'bursts' of development ; and (2) a change in the shape of the crown occurs during its formation where the mesiobuccal cusp moves buccally and distally, and the lingual cusp moves mesially.
History, Ancient↗
Outbreak of drug-resistant tuberculosis with second-generation transmission in a high school in California.
BACKGROUND: In spring 1993, four students in a high school were diagnosed with tuberculosis resistant to isoniazid, streptomycin, and ethionamide. METHODS: To investigate potential transmission of drug-resistant tuberculosis, a retrospective cohort study with case investigation and screening by tuberculin skin tests and symptom checks was conducted in a high school of approximately 1400 students. Current and graduated high-school students were included in the investigation. DNA fingerprinting of available isolates was performed. RESULTS: Eighteen students with active tuberculosis were identified. Through epidemiologic and laboratory investigation, 13 cases were linked; 8 entered 12th grade in fall 1993; 9 of 13 had positive cultures for Mycobacterium tuberculosis with isoniazid, streptomycin, and ethionamide resistance, and all 8 available isolates had identical DNA fingerprints. No staff member had tuberculosis. One student remained infectious for 29 months, from January 1991 to June 1993, and was the source case for the outbreak. Another student was infectious for 5 months before diagnosis in May 1993 and was a treatment failure in February 1994 with development of rifampin and ethambutol resistance in addition to isoniazid, streptomycin, and ethionamide. In the fall 1993 screening, 292 of 1263 (23%) students tested had a positive tuberculin skin test. Risk of infection was highest among 12th graders and classroom contacts of the two students with prolonged infectiousness. An additional 94 of 928 (10%) students tested in spring 1994 had a positive tuberculin skin test; 22 were classroom contacts of the student with treatment failure and 21 of these had documented tuberculin skin test conversions. CONCLUSION: Extensive transmission of drug-resistant tuberculosis was documented in this high school, along with missed opportunities for prevention and control of this outbreak. Prompt identification of tuberculosis cases and timely interventions should help reduce this public health problem.
Adolescent↗
Incidence and patterns of depression following coronary artery bypass graft surgery.
A number of studies have examined the impact of coronary artery bypass graft surgery (CABG) on mood by means of cross-sectional analyses. These studies have provided a "snapshot" view of the numbers of patients showing psychological disturbance. To examine both the incidence and patterns of depression, 121 patients undergoing routine elective CABG were assessed preoperatively and postoperatively at 8 days, 8 weeks, and 12 months on the Beck Depression Inventory (BDI). The incidence findings suggested a small, transient increase in the number of patients with depression shortly after surgery. The preoperative score on the BDI was the best predictor of postoperative depression at all times of measurement. Discriminant function analysis on the patterns of depression indicated that trait anxiety maximally separated those patients who were depressed pre- and postoperatively from those only depressed shortly after the operation. The findings emphasize the value of examining patients' levels of anxiety and depression prior to surgery.
Adult↗
Evaluation and follow-up of patients with N1-3 M0 or NXM1 prostate cancer in phase III trials.
OBJECTIVES: The aim of this discussion is to review the design and conduct of phase III trials in metastatic prostate cancer, to seek ways of improving their study design, accuracy, relevance to clinical practice, acceptability to patients, and ease of participation by clinicians. We also aim to try to set uniform definitions for the evaluation of the different endpoints used in clinical trials on metastasized prostate cancer. METHODS: The work was started by correspondence between the participants in the group for the year before the consensus meeting. Two comprehensive questionnaires were circulated and the answers were distributed to all the members of the group. The statements were finalized during the consensus meeting. RESULTS: There were some differing opinions concerning the methods of evaluation of endpoints for follow-up, such as time to tumor progression and time to treatment failure. After the consensus conference, there were no major disagreements within the group. CONCLUSIONS: The aim of phase III trials is to influence clinical management. To obtain a credible result they require a sound statistical basis with appropriate power and encompassing patients from small urologic practices as well as large or academic institutions. However, deviation from routine practice may affect the accrual rate, and the trial procedure should therefore be as similar as possible to routine management. Trials inevitably involve extra work and cost. Both should be kept to a minimum to encourage participation and hasten a timely conclusion. It is mandatory to create uniform ways of designing and evaluating clinical trials in prostate cancer.
Clinical Trials, Phase III as Topic↗
Loco-regional recurrence following mastectomy for early breast carcinoma: efficacy of radiotherapy at the time of recurrence.
This study aims to define the risk factors for loco-regional relapse following mastectomy, and to assess the efficacy of radiotherapy at the time of relapse. To achieve this 272 patients with loco-regional relapse treated at a single institution with modified radical or radical mastectomy were reviewed. Tumour size, axillary node involvement and tumour grade were found to be significant risk factors for loco-regional recurrence of disease. Radiotherapy given at the time of relapse controlled disease in 61% of cases, compared with 34% of patients treated with systemic treatment only. Altogether, 146 (54%) of the 269 evaluable patients with local failure had uncontrolled disease at the same site, either at the time of death or at the date last seen. The result of this retrospective study showed that delayed radiotherapy was effective in controlling the disease in patients with developing loco-regional relapses. However, as adjuvant radiotherapy reduces the incidence of local disease recurrence it should be recommended to patients considered to be at high risk of local relapse following mastectomy; namely those with tumours bigger than 5 cm with four or more positive axillary nodes.
Adult↗
Patterns of health risk behaviors for chronic disease: a comparison between adolescent and adult American Indians living on or near reservations in Montana.
PURPOSE: To compare the chronic disease health risk behavior patterns of adolescents and adults among American Indians living on or near reservations in Montana. METHODS: We analyzed data from the 1993 Youth Risk Behavior Survey of American Indians in Grades 9-12 living on or near Montana reservations. Risk factors included tobacco use, low physical activity, attempted weight loss, and low consumption of fruits, vegetables, and green salad. Similar data were analyzed from a 1994 Behavioral Risk Factor Survey of American Indian adults living on or near reservations in Montana. RESULTS: The prevalence of most adolescent health risk behaviors was high, especially cigarette smoking (45% for males, 57% for females), smokeless tobacco use (44% for males, 30% for females), and infrequent consumption of salad or vegetables (59-76%). With the exception of daily cigarette smoking and inadequate fruit consumption among adolescents of both genders and physical inactivity among adolescent males, the prevalence of chronic disease health risk behaviors among adolescents was similar to or higher than the prevalence of the same risk behaviors among adults. CONCLUSIONS: Many health risk behaviors for chronic diseases are common by the time this group of American Indians in Montana has reached adolescence. Possible reasons may include modeling of familial behaviors, peer pressure, advertising, or age cohort effects. If these risk behavior patterns continue into adulthood, morbidity and mortality from chronic diseases are likely to remain high. Substantial efforts are needed to prevent or reduce health risk behaviors among adolescents and adults in this population.
Adolescent↗
Histopathology of breast cancer in relation to age.
Histological reports of 1869 consecutive women with invasive breast cancer have been reviewed to determine whether histological features of the tumour's were related to the patients' age. The patients, treated between 1983 and 1992, were divided into four groups, based on age. There were 148 aged < or = 39 years, 355 aged 40-49 years, 984 aged 50-69 years and 382 aged 70 years or more. The most outstanding finding was the increase in incidence of grade III infiltrating ductal carcinoma in those aged < or = 39 years (P < 0.0001). Certain tumour types, in particular lobular, were reported more frequently in the oldest age group. Additionally, there was a significant reduction of axillary lymph node metastases, vascular invasion and lymphoplasmacytic stromal reaction with increasing age, all of which were independent of tumour grade. These data suggest that there may be age-related changes in the histology of breast cancer and, in some cases, less aggressive features in the elderly. However, as the life expectancy of women over the age of 70 may be many years, treatment should be based on histological prognostic features of the primary tumour rather than age alone.
Adenocarcinoma, Mucinous↗
Mucoid breast carcinomas: histology and prognosis.
In a series of 73 patients with mucoid breast carcinomas treated at Guy's Hospital between 1973 and 1989, 24 (33%) patients had pure mucoid lesions and 49 (67%) had mixed mucoid carcinomas. The patients with pure mucoid cancers had significantly smaller tumours and, among those in whom an axillary dissection was performed, mixed mucoid cancers were more likely to be associated with axillary nodal metastases (46% vs 14%). After long-term follow-up of 64 patients, both relapse-free and overall survival were significantly better for those with pure mucoid carcinomas, for whom the 10-year actuarial overall survival was 100%. The overall proportion of the tumour that was mucoid was also positively associated with a more favourable prognosis in patients with mixed tumours. With such a good prognosis, patients with pure mucoid carcinomas may not require systemic adjuvant therapy after adequate primary treatment.
Adenocarcinoma, Mucinous↗
Mutation analysis of the WT1 gene in sporadic childhood leukaemia.
The 10 coding exons of the WT1 gene, from 39 bp upstream of the translation initiation codon to 12 bp downstream of the stop codon, were examined for point mutations in a panel of 48 sporadic childhood acute leukaemias using the single-stranded conformational polymorphism (SSCP) assay. The panel included 33 cases of acute lymphocytic leukaemia and 15 cases of acute myeloid leukaemia. This is the first study in which sporadic childhood leukaemias have been examined for WT1 point mutations across the entire coding region of the WT1 gene, however, no tumorigenic point mutations or small deletions or insertions could be identified in these patients. A previously described polymorphism in exon 7, resulting in an A to G transition in an arginine codon, was observed at a frequency of 21.5%, equivalent to that seen in the normal population. This study suggests that point mutations in the coding regions of the WT1 occur infrequently in leukaemias of childhood.
Acute Disease↗
The isolation of a 22 kDa band after SDS-PAGE of Schistosoma mansoni adult worms and its use to demonstrate that IgE responses against the antigen(s) it contains are associated with human resistance to reinfection.
In schistosomiasis endemic areas, intensities of reinfection after treatment are greater amongst young children than amongst adults, and high levels of parasite-specific IgE are associated with resistance to reinfection in an age-dependent manner. Previously we have reported that, in Western blots, a 22 kDa band was recognized by human IgE and that the incidence and intensity of S. mansoni reinfection were significantly lower amongst individuals who had IgE against this band, compared with those who did not (Dunne et al. 1992). Here we report the isolation of a 22 kDa SDS-PAGE band, its incorporation into ELISA and the demonstration that levels of human anti-22 kDa IgE had a significant negative correlation with intensities of subsequent reinfection. Rabbit anti-22 kDa band serum recognized the outer tegument, gut tegument, and the collecting ducts and flame cells of adult worms. The 22 kDa band antigen(s) was also present in "lung'- and "post-lung' schistosomula stages of S. mansoni, and in S. haematobium, S. bovis and S. japonicum adult worms. Metabolic labelling of schistosomula and worms demonstrated the in vitro synthesis and release of 22 kDa antigens.
Animals↗
Composition and antimalarial activity in vitro of the essential oil of Tetradenia riparia.
The essential oil from the leaves and stems of Tetradenia riparia was analysed by GC and GC/MS and 35 components were identified. The main constituents were alpha-terpineol (22.6%), fenchone (13.6%), beta-fenchyl alcohol (10.7%), beta-caryophyllene (7.9%), and perillyl alcohol (6.0%). Moderate antimalarial activities were recorded against two strains of Plasmodium falciparum.
Animals↗
Electrophoretic separation of myosin heavy chain isoforms in the human m. vastus lateralis: references to reproducibility and relationships with force, electromechanical delay, fibre conduction velocity, endurance and electromyography.
The aim of this investigation was to determine the relationship between muscle performance and the myosin heavy chain (MHC) composition and the reliability of electrophoretically determined MHC compositions. A total of thirty-one male subjects participated in the experiments. Maximal voluntary isometric contractions (MVC) of the knee extensors were performed at an arbitrary knee angle of 90 degrees and the following variables were recorded: maximal isometric force, muscle fibre conduction velocity (MFCV), electromechanical delay (EMD), maximal rate of force development (MRFD), median frequency of EMG (MF) and iEMG. Static isometric contractions of the knee extensors were held at an angle of 90 degrees using contractile forces of 10%, 50% and 100% MVC, respectively. These tests were conducted on separate days. Muscle biopsy samples were obtained from the left m. vastus lateralis before MVC and static endurance tests. MHC protein isoform differences were determined through sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) followed by densitometric analysis. Type I-MHC compositions of the m. vastus lateralis ranged from 20-68% with a mean of 49 +/- 18%, mean type IIa-MHC and type IIb-MHC percentages were 35 +/- 16% and 16 +/- 10%, respectively. MHC compositions of duplicate biopsy samples were not significantly different from that of original samples. The coefficients of variation calculated for duplicate biopsy samples suggested reasonable reproducibility for MHC isoform differentiation for type I-MHC and type-II MHC composition (CV = 12.6%). Differentiation between type IIa-MHC and type IIb-MHC was not always clear using the densitometric traces. Subjects with higher percentages of type II-MHC displayed significantly faster MFCV (r = 0.67, P < 0.1), isometric force development (r = 0.68, P < 0.1) and shorter periods of EMD (r = -0.72, P < 0.05). There was also a tendency toward faster MRFD in these subjects although results did not reach significance. Endurance times for isometric contractions held at 10%, 50% and 100% MVC to exhaustion were not correlated with MHC composition. No relationships between II-MHC composition and MF or iEMG were observed. It was suggested that surface electromyographic recordings obtained during isometric MVC did not reflect underlying differences in muscle fibre composition.
Adult↗
Job satisfaction of selected categories of Utah hospital managers.
In a survey of managers in Utah hospitals, 85 percent responded overall satisfaction with their jobs. Surprisingly, women in the survey reported significantly greater satisfaction with their jobs than other respondents.
Female↗
Comparison of sensitivities to two commercially available tuberculin skin test reagents in persons with recent tuberculosis.
Discrepancies have been reported between results obtained with tuberculin skin tests (TSTs) performed with use of different reagents. We compared TST results and determined the sensitivities of the two commercially available TSTs in 51 human immunodeficiency virus-negative persons with culture-confirmed active tuberculosis. Simultaneous TSTs were done with use of the Mantoux method and 5-tuberculin unit purified protein derivative (PPD) tuberculin preparations from single lots of Aplisol and Tubersol. Aplisol skin test reactions ranged from 5 mm to 26 mm (median, 16.0 mm), and Tubersol reactions ranged from 7 mm to 23 mm (median, 15.0 mm). The mean difference in paired reaction sizes for the two reagents was 0.58 mm and was not statistically different from zero (P value, 0.26). The difference in reaction sizes was < or =2 mm in 55% and > or =5 mm in 18% of patients. With a cutoff of either 5 mm or 10 mm to define a positive reaction, all results were concordant, with sensitivity of 100% and 96%, respectively. We found indistinguishable reaction size distributions and median TST results for the two commercially available PPD TST reagents, Aplisol and Tubersol, in a population with recent culture-proven tuberculosis.
Adult↗
Hospitalization of aboriginal and non-aboriginal patients for respiratory tract diseases in Western Australia, 1988-1993.
BACKGROUND: Aboriginal people have lower health standards than other Australians. Respiratory tract diseases are prominent causes of high morbidity and mortality rates in the Aboriginal population. However, very little is known about the patterns of respiratory illnesses which affect these people. METHOD: This paper compares Aboriginal and non-Aboriginal age-specific hospitalization patterns for respiratory tract diseases from 1988 to 1993 in Western Australia (WA). RESULTS: Aboriginal people were admitted for respiratory diseases 2-16 times more frequently than non-Aboriginals of the same age with considerable discrepancies in hospitalization rates particularly in infants, young children and older adults. High admission rates for acute respiratory tract infections, pneumonia and asthma occurred in Aboriginal infants. Pneumonia was a disproportionately frequent cause of admissions in Aboriginal infants, children and adults. Pneumonia is a more frequent cause of admission among non-metropolitan compared to metropolitan Aboriginals. Asthma was a frequent cause of admissions of Aboriginal children and hospitalization rates for this disease were higher in non-metropolitan than metropolitan areas. Chronic obstructive airway disease and respiratory tract carcinoma were important uses of hospitalization in older Aboriginals. CONCLUSIONS: Admission rates for respiratory conditions were consistently higher among the Aboriginal population and in non-metropolitan areas. The overwhelming importance of infections among Aboriginal admissions has significant implications for the prevention and management of respiratory diseases among Aboriginal people.
Adolescent↗