The real millennium bug.
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Biomedical subjects
Publications and source records attributed to J McConnell.
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Lupus specific autoantigens are exposed on apoptotic cells. The increased number of apoptotic lymphocytes reported in systemic lupus erythematosus (SLE) may be attributable to abnormalities of lymphocyte Fas expression or serum soluble Fas. In the present study we analysed the count of circulating apoptotic lymphocytes in SLE patients (n=50), by flow cytometry using Annexin V, compared to rheumatoid arthritis patients (RA, n=20), inflammatory bowel disease patients (IBD, n=20) and normal controls (n=20). Lymphocyte Fas expression and serum soluble Fas were measured and related to numbers of apoptotic lymphocytes. The percentage of apoptotic lymphocytes, determined by Annexin V binding, was significantly increased in peripheral blood of SLE patients (median=4.2%) compared with normal healthy donors (median=1.1%) and IBD patients (median=2. 0%) but not RA (median=3.9%). SLE lymphocyte Fas expression was not significantly different from RA or IBD patients. Serum soluble Fas in SLE patients correlated positively with apoptotic lymphocytes and antibodies to double stranded DNA. This study suggests that increased apoptotic lymphocytes and increased lymphocyte Fas expression may not be specific to SLE. Serum soluble Fas may have a role in the regulation of lymphocyte apoptosis in SLE.
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A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45(-), and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.
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BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effect of patellar taping on the onset of activity of the vastus medialis obliquus muscle (VMO) and the vastus lateralis muscle (VL). SUBJECTS AND METHODS: Fourteen female subjects with patellar pain walked up and down stairs in two conditions: (1) with the patellofemoral joint of the painful lower extremity taped so that the pain was reduced by at least 50% on a pain provocation test and (2) without patellar taping. RESULTS: When the patellofemoral joint was not taped, there was no difference in the onset of activity between the VMO and the VL during the step-up and step-down tasks. During the step-up task, the onset of VMO activity occurred earlier with taping but there was no change in the onset of VL activity with taping. During the step-down task, the onset of VMO activity occurred earlier and the onset of VL activity was delayed with taping. When the patellofemoral joint was taped, the VMO was activated earlier than the VL during the step-up and step-down tasks. CONCLUSION AND DISCUSSION: Taping of the patellofemoral joint in the manner used in this study changed the timing of VMO and VL activity in subjects with patellofemoral pain during step-up and step-down tasks. The earlier activation of the VMO may alter the movement of the patella, and further research is needed to determine whether this occurs and whether it is beneficial.
Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations.
Inborn errors of the pyruvate dehydrogenase complex (PDC) are associated with lactic acidosis, neuroanatomic defects, developmental delay, and early death. PDC deficiency is a clinically heterogeneous disorder, with most mutations located in the coding region of the X-linked alpha subunit of the first catalytic component, pyruvate dehydrogenase (E1). Treatment of E1 deficiency hs included cofactor replacement, activation of PDC with dichloroacetate, and ketogenic diets. In this report, we describe the outcome of ketogenic diet treatment in seven boys with E1 deficiency. These patients were divided into two groups based on their mutations (R349H, three patients; and R234G, four patients, two sibling pairs). All seven patients received ketogenic diets with varying degrees of carbohydrate restriction. Clinical outcome was compared within each group and between siblings as related to the intensity and duration of dietary intervention. Subjects who either had the diet initiated earlier in life or who were placed on greater carbohydrate restriction had increased longevity and improved mental development. Based on the improved outcomes of patients with identical mutations, it appears that a nearly carbohydrate-free diet initiated shortly after birth may be useful in the treatment of E1 deficiency.
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Patellofemoral pain is often a challenge for the physiotherapist, because of its complex aetiology. Physiotherapists with their understanding of soft tissue structure and muscle function are well positioned to effectively manage most patellofemoral problems by improving the extensibility and mobility of tight structures and improving the timing of the elongated muscles. This will involve recognising the biomechanical factors contributing to the symptoms, adequately explaining to the patient the cause of the symptoms and teaching the patient how to manage the symptoms. Specific training of certain muscles with accurate feedback to change the timing of these muscles during functional and sporting activities will be required if this problem is not to recur.
The aim of the paper is to establish firmly the phenomenon of an irrelevant picture effect and to demonstrate that the phenomenon can be used to investigate the characteristics of the visuo-spatial sketchpad. Experiment 1 introduces the use of dynamic visual noise as an interfering technique. This technique is shown to cause interference with a word list learned under visual mnemonic mediation instructions but to cause no interference when the word list is learned under verbal mediation instructions. Experiment 2 serves both to replicate this selective interference effect and to illustrate how the dynamic visual noise technique can be used to characterize further the nature of interference in the visuo-spatial sketchpad. Experiment 3 confirms the robustness of the dynamic visual noise technique. Additionally, this experiment demonstrates a double dissociation between two types of interference, dynamic visual noise and irrelevant speech, and two types of mediation, rote and visual mnemonic.
The prevalence of BPH is high in elderly men with more than 60% of patients over the age of 60 experiencing some form of prostatism. Balancing the superior benefit of TUR/P are the small but significant risks and complications of surgery and the high cost of the procedure. The WHO guidelines recommend finasteride or alpha-blockers as treatment options for men with bothersome symptoms. Finasteride therapy reduces the volume of the hyperplastic prostate gland by more than 20%, improves the urinary flow rate and the symptoms associated with bladder outlet obstruction. Although statistically significant, results obtained with finasteride are just slightly better than placebo and TUR/P still offers the greatest improvement of symptoms. Finasteride is well tolerated and adverse events are rare. However, it decreases serum PSA (prostate specific antigen) by 50%, suggesting careful monitoring and exclusion of prostate cancer before initiation and during therapy. Current research is focusing on developing new 5-alpha-reductase inhibitors (type I and II) using polyunsaturated fatty acids and nonsteroidal inhibitors. Given the multifactorial nature of BPH, further clinical trials combining 5-alpha-reductors inhibitors and 5-alpha-receptor blockers are still needed.
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We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.