Biomedical subjects
R Scott
Publications and source records attributed to R Scott.
Confirmation of cervical neoplasia using a hand-held, lighted magnification device.
OBJECTIVES: The objective of this study was to estimate the sensitivity and specificity of visual inspection with acetic acid and magnification (VIAM) using the AviScope device to confirm high-grade cervical intraepithelial neoplasia or carcinoma. METHODS: VIAM was performed on 142 women aged 18-50 years referred to three colposcopy clinics because of abnormal cervical cytology. Each woman then had a colposcopic examination with cervical biopsy when indicated. RESULTS: The AviScope device identified 24 of the 40 women who had CIN 2, 3, or carcinoma, yielding a sensitivity of 60.0% (95% CI 43.4, 74.7). The AviScope correctly identified 60 of 87 women negative for dysplasia or cancer, yielding a specificity of 69.0% (95% CI 58.0, 78.2) compared with colposcopy and cervical histology. CONCLUSION: VIAM using the AviScope device was moderately sensitive and specific for the confirmation of high-grade cervical lesions in women referred with abnormal cervical cytology.
Administration of recombinant human FSH (solution in cartridge) with a pen device in women undergoing ovarian stimulation.
This study evaluated the first multiple-use pen device for the self-administration of recombinant FSH. The pen device is used for the subcutaneous injection of a pre-mixed ready-to-use solution of follitropin beta from a multiple-dose cartridge, and has flexible dosing capabilities. In the ease-of-use questionnaire, 90% of subjects rated the overall experience of self-injecting follitropin beta using the pen device as 'very good' (on day 6). The comprehension questionnaire revealed that prior to the first injection and during the second injection, the follitropin beta cartridge was properly loaded into the pen device by 96.7 and 100% of the subjects respectively. The questionnaire also showed that the correct dose was selected and self-administered by 98.3 and 100% of the subjects respectively. Biochemical and ongoing pregnancy rates per attempt were 56.7 and 45.0% respectively. The pen device is safe, effective, and easy to use for self-administering recombinant FSH during ovarian stimulation.
A case of a uniocular pterygium related to an unusual occupation.
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Integrin alpha(v)beta6-associated ERK2 mediates MMP-9 secretion in colon cancer cells.
There is general consensus that matrix metalloproteinases are involved in tumour progression. We show herein that inhibition of integrin alpha(v)beta6 expression in colon cancer cells suppresses MMP-9 secretion. This integrin-mediated event is dependent upon direct binding between the beta6 integrin subunit and extracellular signal-regulated kinase 2. Targetting either beta6 or its interaction with extracellular signal-regulated kinase in order to inhibit matrix metalloproteinase activity may offer a useful therapeutic approach in preventing growth and spread of colon cancer.
Answering the unanswered questions: ongoing trials of statins and antihypertensives in type 2 diabetes.
Dyslipidaemia and hypertension contribute to an excess risk of coronary heart disease (CHD) in patients with type 2 diabetes. A number of landmark primary and secondary prevention trials have demonstrated that lipid-lowering therapy with HMG-CoA reductase inhibitors (statins), and antihypertensive therapy with angiotensin-converting enzyme inhibitors and calcium channel blockers (CCBs), reduce CHD risk in the non-diabetic population. However, many questions remain unanswered about the use of these therapies in patients with type 2 diabetes. To address the most important of these questions, several major trials are under way that will provide more data on the benefits of lipid-lowering and antihypertensive therapy in type 2 diabetes. These include studies of atorvastatin, an established member of the statin class, with over 22 million patient-years' experience and an excellent safety profile. Similarly, the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) will determine the efficacy of the CCB, amlodipine, in patients with concomitant type 2 diabetes and hypertension.
Phenylketonuria in adulthood: a collaborative study.
During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.
Unexpected visual improvement with a pinhole in central retinal artery occlusion and cilioretinal artery sparing fovea.
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Electrophysiological confirmation of the zona incerta as a target for surgical treatment of disabling involuntary arm movements in multiple sclerosis: use of local field potentials.
Lesioning or chronic deep brain stimulation (DBS) of the nucleus ventralis intermedius results in abolition of tremor in the contralateral limbs in Parkinson's disease (PD) and also in essential tremor. Recently, chronic DBS of the subthalamic nucleus has also proved to be very effective in reducing contralateral limb tremor in PD. These targets have been less effective in controlling the complex limb tremor often seen in multiple sclerosis (MS). Consequently, other targets have been sought in cases of MS with tremor. We describe a patient with MS with disabling proximal and distal involuntary arm movements in whom we were able to obtain sustained control of contralateral arm tremor and achieve functional improvement of the affected arm by chronic DBS of the region of the zona incerta. We also highlight the important role played by local field potentials recorded from the brain, with simultaneous recording of corresponding EMGs, in target localisation.
Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts.
Although both c-Ret and GFRalpha1 are required for responsiveness to GDNF, GFRalpha1 is widely expressed in the absence of c-Ret, suggesting alternative roles for "ectopic" sites of GFRalpha1 expression. We show that GFRalpha1 is released by neuronal cells, Schwann cells, and injured sciatic nerve. c-Ret stimulation in trans by soluble or immobilized GFRalpha1 potentiates downstream signaling, neurite outgrowth, and neuronal survival, and elicits dramatic localized expansions of axons and growth cones. Soluble GFRalpha1 mediates robust recruitment of c-Ret to lipid rafts via a novel mechanism requiring the c-Ret tyrosine kinase. Activated c-Ret associates with different adaptor proteins inside and outside lipid rafts. These results provide an explanation for the tissue distribution of GFRalpha1, supporting the physiological importance of c-Ret activation in trans as a novel mechanism to potentiate and diversify the biological responses to GDNF.
Bactericidal effect of chlorine on Mycobacterium paratuberculosis in drinking water.
AIMS: One possible route of transmission of Mycobacterium paratuberculosis from cattle to humans is via contaminated water supplies. The aim of this work was to determine whether this organism can survive standard water treatment processes. METHODS AND RESULTS: Two strains of M. paratuberculosis (bovine strain, NCTC 8578 and human strain Linda, ATCC 43015) were subjected to various chlorine concentrations (0.5, 1.0 and 2.0 microg ml(-1)) for 15 and 30 min. Chlorine test solutions were made up in two types of water, sterile water that had been deionized and subjected to reverse osmosis (DRO) and DRO water containing MgCl(2), CaCl(2), NaHCO(3) and bovine serum albumin (0.3% w/v), the latter to mimic conditions the organism would experience in commercial water treatment operations. CONCLUSION: The data showed that when initial inoculum levels were high (10(6) cfu ml(-1)) neither M. paratuberculosis strain was completely killed at the free chlorine concentrations and contact times applied. Log10 reductions in the range 1.32-2.82 were observed. The greatest log(10) reduction in cell numbers (2.82 and 2.35 for the bovine and human strains, respectively) was observed at the highest chlorine concentration (2 microg ml(-1)) and longest contact time (30 min). SIGNIFICANCE AND IMPACT OF THE STUDY: This work highlights the need for further research into the survival of M. paratuberculosis during water treatment.
Aggressive versus moderate lipid-lowering therapy in postmenopausal women with hypercholesterolemia: Rationale and design of the Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES) trial.
BACKGROUND: Electron beam tomography (EBT) is a noninvasive technique that allows the study of the entire coronary artery tree during a brief imaging session without the injection of any contrast media. Atherosclerosis is identified vicariously through the visualization of coronary calcific deposits. Quantitative assessments of calcium burden, such as calcium volume scores, have been shown to be a useful means to assess treatment-related changes in the extent of atherosclerotic plaques. Historically, the elderly female population has received less medical recognition regarding the risk and severity of coronary heart disease (CHD). METHODS: In the BELLES (Beyond Endorsed Lipid Lowering with EBT Scanning) trial, the presence of asymptomatic CHD in 600 postmenopausal women will be assessed by EBT. In this 1-year, multicenter, randomized, double-blind, parallel-group study, aggressive lipid-lowering treatment will be compared with moderate lipid-lowering treatment in postmenopausal women with hypercholesterolemia. The hypothesis we will test is that aggressive lipid-lowering therapy with 80 mg/d atorvastatin can produce greater reductions in atherosclerotic plaque burden as assessed by volumetric calcium scores than a moderate treatment with 40 mg/d pravastatin. The primary outcome measure will be the percent change from baseline in total CVS determined by EBT at 12 months. CONCLUSIONS: The results of the BELLES trial will help assess the actual incidence of CHD in postmenopausal women and the relative ability of two different lipid-lowering therapies to halt its progression.
Perinatal pathology in 2001.
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Lesioning the subthalamic nucleus in the treatment of Parkinson's disease.
Ever since it was demonstrated about twenty years ago by two independent groups (Aziz et al. and Bergman et al.) that the cardinal clinical features of MPTP-induced Parkinson's disease (PD) in non-human primate models can be alleviated by lesions of the subthalamic nucleus (STN), this structure has been the focus of interest for functional neurosurgeons involved in the treatment of PD. Initially lesioning and later chronic high frequency stimulation of the STN has become the standard surgical target of akinetic PD. In this brief report we present our experience with 14 STN lesions (8 unilateral and 3 bilateral) confirmed by post-operative imaging. We found significant improvement in OFF rigidity and in ON tremor following unilateral lesions. The major complications were speech disturbance and L-Dopa resistant limb dystonia. Functional disability scores showed inconsistent reduction. There was insufficient data to comment on the significance of bilateral lesions; however, there was a similar pattern of improvement in tremor and speech disturbance. In addition, there was worsening of gait. We comment on the lower degree of improvement in motor scores in our series compared to the few others in recent literature and stress that even in these studies the UPDRS benefits did not translate directly into functional benefit for the patients.
Nurse anesthesia: the silent profession.
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Mammalian GFRalpha -4, a divergent member of the GFRalpha family of coreceptors for glial cell line-derived neurotrophic factor family ligands, is a receptor for the neurotrophic factor persephin.
Four members of the glial cell line-derived neurotrophic factor family have been identified (GDNF, neurturin, persephin, and enovin/artemin). They bind to a specific membrane-anchored GDNF family receptor as follows: GFRalpha-1 for GDNF, GFRalpha-2 for neurturin, GFRalpha-3 for enovin/artemin, and (chicken) GFRalpha-4 for persephin. Subsequent signaling occurs through activation of a common transmembrane tyrosine kinase, cRET. GFRalpha-4, the coreceptor for persephin, was previously identified in chicken only. We describe the cloning and characterization of a mammalian persephin receptor GFRalpha-4. The novel GFRalpha receptor is substantially different in sequence from all known GFRalphas, including chicken GFRalpha-4, and lacks the first cysteine-rich domain present in all previously characterized GFRalphas. At least two different GFRalpha-4 splice variants exist in rat tissues, differing at their respective COOH termini. GFRalpha-4 mRNA is expressed at low levels in different brain areas in the adult as well as in some peripheral tissues including testis and heart. Recombinant rat GFRalpha-4 variants were expressed in mammalian cells and shown to be at least partially secreted from the cells. Persephin binds specifically and with high affinity (K(D) = 6 nm) to the rat GFRalpha-4 receptor, but no cRET activation could be demonstrated. Although the newly characterized mammalian GFRalpha-4 receptor is structurally divergent from previously characterized GFRalpha family members, we suggest that it is a mammalian orthologue of the chicken persephin receptor. This discovery will allow a more detailed investigation of the biological targets of persephin action and its potential involvement in diseases of the nervous system.
Realistic priorities for AIDS control.
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A program for relapse prevention in schizophrenia: a controlled study.
BACKGROUND: This study examined whether a program for relapse prevention (PRP) is more effective than treatment as usual (TAU) in reducing relapse and rehospitalization rates among outpatients with schizophrenia. METHODS: Eighty-two outpatients with DSM-III-R schizophrenia or schizoaffective disorder were randomly assigned to receive either PRP (experimental group, n = 41) or TAU (control group, n = 41) and were followed up for an 18-month prospective controlled study. Patients in both groups were prescribed standard doses of maintenance antipsychotic medication. Treatment with PRP consisted of a combination of psychoeducation, active monitoring for prodromal symptoms with clinical intervention when such symptoms occurred, weekly group therapy for patients, and multifamily groups. The TAU consisted of biweekly individual supportive therapy and medication management. RESULTS: Outcome rates over 18 months were 17% for relapse (7 patients) and 22% for rehospitalization (9 patients) in the PRP group, compared with 34% for relapse (14 patients) and 39% for rehospitalization (16 patients) in the TAU group (P = .01 and P = .03, respectively). Addition of age, sex, baseline Global Assessment Scale score, Positive and Negative Syndrome Scale scores (3 measures), and substance abuse to the proportional hazards regression models all yielded nonsignificant effects. The PRP teams were much more likely than the TAU psychiatrists to identify prodromal episodes before patients met objective relapse criteria or needed hospitalization. CONCLUSIONS: The PRP was effective in detecting prodromal symptoms of relapse early in an episode. Crisis intervention including increased antipsychotic medication use during the prodromal phase reduced relapse and rehospitalization rates.