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Biomedical subjects

S McConnell

Publications and source records attributed to S McConnell.

At least 19 recordsLinked to original sources

Exercise for osteoarthritis of the hip or knee.

BACKGROUND: Biomechanical factors, such as reduced muscle strength and joint mal-alignment, have an important role in the initiation and progression of osteoarthritis (OA) of the hip or knee. Currently, there is no known cure for OA, however, disease-related factors, such as impaired muscle function and reduced fitness, are potentially amenable to therapeutic exercise. OBJECTIVES: To determine whether land-based therapeutic exercise is beneficial for people with OA of the hip or knee in terms of reduced joint pain, improved physical function and/or the patient's global assessment of therapeutic effectiveness. SEARCH STRATEGY: Five databases (the Cochrane Controlled Trials Register, the Cochrane Musculoskeletal Group Trials Register, MEDLINE, CINAHL, PEDro) were searched up until November 2002. SELECTION CRITERIA: All randomized controlled trials comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in the water) with a non-exercise group. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed methodological quality. All analyses were conducted on continuous outcomes. MAIN RESULTS: Only 2 studies totaling about 100 participants, could potentially provide data on people with OA of the hip. However, for OA of the knee, 17 included studies provided data on 2562 participants. For pain, combining the results revealed a beneficial treatment effect (standardised mean difference) of.39 (95% confidence interval (CI).30 -.47) while for self-reported physical function a beneficial treatment effect of.31 (95% CI.23 -.39). Group format programs appeared to be as effective as treatments provided on a one-to-one basis. The results were sensitive to various aspects of study design methodology. REVIEWER'S CONCLUSIONS: Land-based therapeutic exercise was shown to reduce pain and improve physical function for people with OA of the knee. There were insufficient data to provide useful guidelines on optimal exercise type or dosage. Supervised exercise classes appeared to be as beneficial as treatments provided on a one-to-one basis.

Exercise Therapy↗

Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls.

Several proton magnetic resonance spectroscopy (1H MRS) studies in schizophrenia have found reduced N-acetyl aspartate (NAA) concentrations in pre-frontal and temporal regions of the brain. Reductions in NAA may reflect abnormalities of neuronal structure (e.g. reduced neuronal density or viability) or abnormalities of neuronal function. Diffusion tensor imaging (DTI) measures diffusion anisotropy, an indicator of the structural integrity of a neuronal tract. Both techniques were used to examine the anatomical basis of pre-frontal dysfunction in schizophrenia. Ten patients with DSM-IV schizophrenia were compared with 10 healthy controls. 1H MRS and DTI were performed on a clinical MR system and analysed with a region of interest approach. NAA concentrations and diffusion anisotropy were measured in the same pre-frontal white matter region. Diffusion anisotropy was also measured in a control region (occipital white matter). 1H MRS revealed non-significant but consistently reduced NAA concentrations (by 10-15%) in the pre-frontal white matter in schizophrenic subjects. Diffusion anisotropy measures revealed no such differences between schizophrenics and controls. It is concluded that the abnormalities of 'connectivity' reported in brain-imaging studies of schizophrenia may not be attributable to structural abnormalities of white matter and that reduced NAA in the pre-frontal white matter may reflect abnormal function of structurally intact neurons.

Adult↗

Results of autologous stem cell transplant in multiple myeloma patients with renal failure.

Data are presented on 81 multiple myeloma (MM) patients with renal failure (creatinine > 176.8 micromol/l) at the time of autologous stem cell transplantation (auto-SCT), including 38 patients on dialysis. The median age was 53 years (range: 29-69) and 26% had received more than 12 months of prior chemotherapy. CD34+ cells were mobilized with granulocyte colony-stimulating factor (G-CSF) alone (n = 51) or chemotherapy plus G-CSF (n = 27), yielding medians of 10 and 16 x 106 CD34+ cells/kg respectively (P = 0.003). Sixty patients (27 on dialysis) received melphalan 200 mg/m2 (MEL-200). Because of excessive toxicity, the subsequent 21 patients (11 on dialysis) received MEL 140 mg/m2 (MEL-140). Thirty-one patients (38%) completed tandem auto-SCT, including 11 on dialysis. Treatment-related mortality (TRM) was 6% and 13% after the first and second auto-SCT. Median times to absolute neutrophil count (ANC) > 0.5 x 109/l and to platelets > 50 x 109/l were 11 and 41 d respectively. Non-haematological toxicities included mucositis, pneumonitis, dysrhythmias and encephalopathy. At a median follow up of 31 months, 30 patients have died. Complete remission (CR) was achieved in 21 patients (26%) after first SCT and 31 patients (38%) after tandem SCT. Two patients discontinued dialysis after SCT. Median durations of complete remission (CR) and overall survival (OS) have not been reached; probabilities of event-free survival (EFS) and OS at 3 years were 48% and 55% respectively. Dialysis dependence and MEL dose did not affect EFS or OS. Sensitive disease prior to SCT, normal albumin level and younger age were independent prognostic factors for better OS. In conclusion, renal failure had no impact on the quality of stem cell collections and did not affect engraftment. MEL-140 had an acceptable toxicity and appeared equally effective as MEL-200. In the setting of renal failure, the role of auto-SCT early in the disease course and benefits of tandem SCT require further evaluation.

Adult↗

Paracheck-Pf: a new, inexpensive and reliable rapid test for P. falciparum malaria.

We compared the performance of Paracheck-Pf, a new and cheap rapid malaria test, with ICT-Pf/PvR and microscopy in two malaria surveys in Thai villages on the Thai-Burmese border. The specificity, sensitivity, predictive positive and negative values of the Paracheck-PfR and ICT-PfR tests were calculated taking microscopy results as the gold standard. The 294 ICT-Pf/Pv tests resulted in two invalid (no control line) and 11 doubtful results. Both the ICT-Pf/PvR and Paracheck-PfR tests reliably detected P. falciparum infections. However, Paracheck-PfR failed to detect three P. falciparum cases and likewise, ICT-Pf/PvR failed to detect the same three cases and an additional four cases. These seven cases were detected by microscopy and had a parasitaemia under 150 parasites/microl. At a cost of c. US $1.00, the Paracheck-PfR test, based on the detection of the P. falciparum specific HRP-2 protein, is a reliable, easy to use and affordable tool for the diagnosis of P. falciparum malaria.

Animals↗

Changes in the incidence of gastroenteritis and the implementation of public water treatment.

There are few data available on the incidence of endemic waterborne disease in the developed world. This study aims to determine if there was a measurable decline in gastroenteritis related faecal specimens following the introduction of water treatment. The rate of faecal specimens for gastroenteritis was obtained for 17 communities one year before and after the introduction of water treatment in two states of Australia between 1992 and 1996. Of these 17 systems, 10 had filtration added to existing disinfection, while seven had both disinfection and filtration or disinfection alone added to no existing treatment. The rate of faecal sampling varied from a reduction of 55% to an increase of 198%. Large changes in water quality parameters occurred following treatment but there was no significant correlation between these changes and changes in the rate of faecal specimens. In this study there was no consistent change in gastrointestinal related faecal specimens despite marked changes in water quality. This suggests that the reduction in endemic gastrointestinal disease as a result of the introduction of water treatment was small as a percentage of all gastroenteritis. However, water treatment remains essential to protecting public health.

Australia↗

Comparison of renal function following anesthesia with low-flow sevoflurane and isoflurane.

STUDY OBJECTIVE: To evaluate postoperative renal function after patients were administered sevoflurane under conditions designed to generate high concentrations of compound A. STUDY DESIGN AND SETTING: A multicenter (11 sites), multinational, open-label, randomized, comparative study of perioperative renal function in patients who have received low-flow (< or = 1 L/min) sevoflurane or isoflurane. PATIENTS: 254 ASA physical status I, II and III patients requiring endotracheal intubation for elective surgery lasting more than 2 hours. INTERVENTIONS: After induction, low-flow anesthesia was initiated at a flow rate < or = 1 L/min. Blood and urine samples were studied to assess postoperative renal function. MEASUREMENTS AND MAIN RESULTS: Measurements of serum BUN and creatinine, and urine glucose, protein, pH, and specific gravity were used to assess renal function preoperatively and up to 3 days postoperatively. Serum inorganic fluoride ion concentration was measured at preinduction, emergence, and 2, 24 and 72 hours postoperatively. Compound A concentrations were measured at two sites for those patients receiving sevoflurane. Adverse experience data were analyzed. One hundred eighty-eight patients were considered evaluable (98 sevoflurane and 90 isoflurane). Peak serum fluoride concentrations were significantly higher after sevoflurane (40 +/- 16 microM) than after isoflurane (3 +/- 2 microM). Serum creatinine and BUN decreased in both groups postoperatively; glucosuria and proteinuria occurred in 15% to 25% of patients. There were no clinically significant differences in BUN, creatinine, glucosuria, and proteinuria between the low-flow sevoflurane and low-flow isoflurane patients. CONCLUSIONS: There were no statistically significant differences in the renal effects of sevoflurane or isoflurane in surgical patients undergoing low-flow anesthesia for up to 8 hours. Low-flow sevoflurane anesthesia under clinical conditions expected to produce high levels of compound A appears as safe as low-flow isoflurane anesthesia.

Anesthetics, Combined↗

Histopathologic and ultrastructural alterations of white liver disease in sheep experimentally depleted of cobalt.

Many cobalt-deficient sheep develop liver lesions known as ovine "white liver" disease, but the etiology of these changes is controversial. It has been suggested that cofactors are required for development of liver damage in cobalt-deficient sheep. In this study, one group of lambs (n = 5) was fed a diet low in cobalt (4.5 micrograms/kg) while a group of control lambs (n = 4) received the same diet after it had been supplemented with cobalt (1000 micrograms/kg). All cobalt-depleted lambs had reduced growth rate, anorexia, lacrimation, and alopecia, and they eventually became emaciated (mean body weight at end of study: 83% of initial body weight). Plasma concentrations of bilirubin and serum activity of glutamate-oxaloacetate transferase were elevated in these animals, while plasma concentrations of vitamin B12 were reduced (less than 220 pmol/L from day 42). Fatty degeneration of the liver associated with reduced concentrations of vitamin B12 (14.5 pmol/g) was seen in these animals at necropsy at 196 days. Microscopic liver lesions included accumulation of lipid droplets and lipofuscin particles in hepatocytes, dissociation and necrosis of hepatocytes, and sparse infiltration by neutrophils, macrophages, and lymphocytes. Ultrastructural hepatocytic alterations included swelling, condensation and proliferation of mitochondria, hypertrophy of smooth endoplasmic reticulum, vesiculation and loss of arrays of rough endoplasmic reticulum, and accumulation of lipid droplets and lipofuscin granules in cytoplasm of hepatocytes. No liver lesions were seen in control lambs. The results of this study indicate that cofactors are not a prerequisite to development of hepatic damage in cobalt-deficient sheep. Reduced activities of the vitamin B12-dependent enzymes, methylmalonyl CoA mutase and methionine synthase, and lipid peroxidation are of likely pathogenetic importance in the development of the lesions.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.

Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2. To obtain numbers suitable for therapy (>10(11)), TIL were expanded using a large-scale system of cell culture and harvesting. While the largest number of biopsies was obtained from melanoma patients, TIL were successfully grown from 160 of 255 tumor biopsies representing all 4 histologies. Under the culture conditions employed, several characteristics of TIL expansion were observed. The cell surface phenotype of TIL which grew out from the tumor biopsies was generally a mix of CD3+/CD4+ or CD3+/CD8+ lymphocytes. Only TIL from melanoma biopsies were found to be consistently cytolytic and, in many cases, lysed autologous tumor cells preferentially. Interestingly, TIL derived from extra-nodal sites of metastatic melanoma biopsies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to have these cytolytic characteristics than TIL derived from tumor-involved lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed for the large-scale growth and harvesting of TIL. In addition, it summarizes the laboratory effort supporting previously published clinical reports on TIL from our group.

Breast Neoplasms↗

Melanoma tumor-infiltrating lymphocytes derived from four distinct anatomic sites obtained from a single patient: comparison of functional reactivity and melanoma antigen recognition.

Tumor-infiltrating lymphocytes (TILs) were grown from four distinct anatomic sites from a patient with metastatic melanoma. The metastatic sites included a tumor-involved lymph node, a subcutaneous lesion obtained from the chest wall, a portion of bowel, and adrenal gland. TILs grown from each anatomic site over the course of 20 days in the presence of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates. Between days 30 and 45, the TILs were a mixture of CD3+ CD4+ and CD3+ CD8+ lymphocytes expressing the alpha beta form of the T-cell receptor. TILs derived from each anatomic site specifically lysed autologous tumor obtained from all four anatomic sites. In fine specificity analysis, the TILs exhibited human leukocyte antigen (HLA-A2)-restricted lysis of fresh tumor targets and cultured melanoma cell lines. Each TIL recognized a product of the MART-1 gene, and specifically, the monomer peptide MART-1(27-35). Thus lymphocytes reactive with the MART-1 melanoma antigen appeared to be widely distributed in diverse metastases in this patient. This information, along with previous data on the reactivity of multiple patients to this antigen, attests to its dominance in the immune reactivity of humans to melanoma.

Adrenal Gland Neoplasms↗

Vaccination of newborn pigs in the presence of low levels of pseudorabies colostral antibodies.

To test the hypothesis that newborn pigs with pseudorabies virus (PRV) colostral antibodies might be actively immunized with a PRV glycoprotein gIII-deleted vaccine (Omnimark-PRV), 23 piglets were obtained from four sows that had been immunized 4 weeks and 2 weeks before farrowing with this vaccine. Thirteen piglets were immunized with Omnimark-PRV when they were less than 3 days old and ten piglets served as non-vaccinated controls. Piglets were weaned at 28 days of age and challenged with virulent PRV (Shope) when they were 49 days old, at which time the vaccinated and control pigs were seronegative for PRV virus neutralizing (VN) and gIII antibodies, and all control pigs and ten vaccinees were seronegative for PRV antibodies by the latex agglutination test (LAT). Two vaccinees were LAT(+) and one was LAT(+/-). Central nervous system signs and/or respiratory disease signs were observed in six of ten control pigs with the death of one control, while two of 13 vaccinees showed only very mild and transient clinical disease signs and there were no fatalities. Non-vaccinees lost weight until postchallenge day (PCD) 6 and did not regain prechallenge weight until PCD 8. All vaccinees gained weight after challenge and at PCD 11 had mean weight gains nearly twice that of the controls. On PCD 11, the geometric mean titre for VN antibodies of non-vaccinees was 9.3, while that of vaccinees was 49.0, indicating that the vaccinated group had been immunologically primed.

Animals↗

Policy issues surrounding special care units.

What is specialized care for Alzheimer's patients? Is it really specialized, or could that word simply be a marketing ploy? Home care agencies that care for patients with Alzheimer's disease will face these questions with their patients and undergo the same questions that the nursing home industry faces.

Aged↗

Development of active immunity in newborn pigs with colostral antibodies by vaccination with gIII-deleted PRV.

Maternal antibodies interfere with active immunization of swine by gI-deleted pseudorabies virus [(PRV); Aujeszky's disease virus] vaccines. To test the hypothesis that modified-live (MLV) vaccines retaining the PRV gI and with deletions in the PRV glycoprotein gIII and thymidine kinase (TK) genes might be efficacious in circumventing colostral antibody interference, the OMNI-MARK-PRV (gI+ gIII- TK-) vaccine was administered intramuscularly to 13 newborn pigs with colostral antibodies, while 10 pigs from the same litters served as nonvaccinated controls. At 49 days of age, when PRV virus neutralization (VN) antibodies were negative and all nonvaccinated pigs as well as 10 vaccinates were latex agglutination test (LAT)-negative, the pigs were challenged intranasally with the virulent PRV(SHOPE) strain. In support of the hypothesis, it was found that several central nervous system and respiratory disease signs developed in 6 of 10 nonvaccinates, with one fatality, while 2 of 13 vaccinates showed only very mild and transient disease signs. Nonvaccinates lost weight until post challenge day (PCD) 6, did not regain prechallenge weight until PCD 8, and at PCD 11 had gained only 4.9 pounds/pig. Vaccinates gained weight after challenge and at PCD 11 showed a 9.4 pounds/pig weight gain. On PCD 11, the geometric mean titer (GMT) for VN antibodies of the nonvaccinates was 9.3, while the GMT of the vaccinates for VN antibodies was 49.0, showing that vaccinated pigs had been immunologically primed.

Animals↗

Coronary angioplasty with gradual versus rapid balloon inflation: initial results and complications.

Although a variety of coronary angioplasty balloon inflation protocols are employed, prior studies have not evaluated the relation of rate of inflation to the type and extent of arterial damage produced by angioplasty. We randomized 103 patients to either a gradual (gradual, incremental increase to peak inflation pressure) or rapid inflation protocol (rapid increase to peak inflation pressure). Fifty-one patients with 72 lesions underwent gradual and 52 patients with 73 lesions received rapid inflation protocols. There were no significant group differences with regard to age, sex, artery dilated, number of diseased vessels, presence of unstable angina and lesion morphological characteristics except for more lesions located on a bend in the gradual inflation group (p < 0.02). Although there was a tendency towards a higher success rate in patients with gradual inflation, the complete success rates were high in both groups (100% vs. 93%, p < 0.08). The dissection rate was higher in patients with rapid inflation (43/73 [59%] vs. 26/72 [36%], p < 0.01). The collective complication rate was higher in patients with rapid inflation (19% vs. 6%, p < 0.03). No deaths occurred in either group. Thus a gradual compared to rapid coronary angioplasty balloon inflation protocol reduces the frequency of dissection despite similar inflation pressure and balloon/vessel diameter ratio. Gradual inflations may reduce the frequency of procedure-related complications.

Angioplasty, Balloon, Coronary↗