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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 109 records · Page 6Linked to original sources

Early white matter changes on brain magnetic resonance imaging in a newborn affected by merosin-deficient congenital muscular dystrophy.

In 1996 we reported sequential magnetic resonance imaging study in an infant with merosin-deficient congenital muscular dystrophy with normal brain magnetic resonance imaging at 3 weeks and white matter changes by 6 months. We now report an infant with merosin-deficient congenital muscular dystrophy with a mild degree of white matter changes already present on brain magnetic resonance imaging at 5 days of age. The difference may be due to a difference in the T2 sequences used. The images in this present case were obtained with a fast spin echo sequence (echo time: 210 ms). The increased T2 weighted may be responsible for a better detection of the white matter changes at an early stage, when they can be missed on conventional, less weighting T2 sequences. These results suggest that, by using appropriate sequences, mild white matter changes may be detectable on brain magnetic resonance imaging in the first days of life in infants with merosin-deficient congenital muscular dystrophy.

Age of Onset↗

Molecular epidemiology of tuberculosis among eight hospitals in New York City, 1996-1997.

OBJECTIVE: To determine the molecular epidemiology of tuberculosis isolated from patients cared for at eight hospitals scattered throughout New York City. MATERIALS AND METHODS: Cases of tuberculosis occurring in 1996 and 1997 at collaborating hospitals were identified, and demographic data were extracted from patient charts. All available isolates were analyzed by IS6110 for genetic relatedness. The molecular fingerprints were compared both to each other and to the larger repository of strains from New York City developed and maintained at the Public Health Research Institute. RESULTS: One hundred and eighty cases were fully characterized. Compared with New York City cases, study patients were more likely to be Asian and less likely to be non-Hispanic blacks. Overall, 97 (54%) of the cases were clustered with respect to other study strains or with respect to the other New York City isolates. Clustered strains were significantly more likely to be from non-Hispanic blacks or patients born in the United States. The largest cluster (n = 17) was the "W" strain previously associated with an outbreak of multidrug-resistant tuberculosis in New York City. In the current study, the majority of W strain isolates were fully drug-susceptible. CONCLUSIONS: High rates of genetically related tuberculosis continue to occur among patients in New York City, in spite of improved control of nosocomial outbreaks and dramatic decreases in the overall case rates. The use of molecular techniques to suggest patterns of transmission has become essential in developing and assessing routine tuberculosis control strategies.

Adult↗

Long-term assessment and serial evaluation of cardiorespiratory exercise performance and cardiac function in patients with atrial switch operation for complete transposition.

BACKGROUND: At present, a considerable number of patients survive who underwent an atrial switch operation for correction of complete transposition. Our study aimed to assess their long-term exercise performance and the serial evolution of cardiac function. METHODS: We studied 22 patients 5 to 17 years after an atrial switch operation, and followed them serially for 3.5 +/- 2 years after the first evaluation. Cardiorespiratory exercise function was assessed by analysis of gas exhange and by determination of the ventilatory anaerobic threshold. Echocardiography was performed on all evaluations. RESULTS: All patients were in Class I of the classification of the New York Heart Association at all assessments. Ventilatory anaerobic threshold, however, was significantly lower than normal. It averaged 77.9% +/- 13.7 of the normal mean value at the initial evaluation, and remained stable when re-evaluated later (76.2 +/- 13.7%). At the initial study, the increase in oxygen uptake during graded exercise was below the 95% confidence limit in 6 of the patients, and was below this level in 10 patients at re-assessment. The subnormal values for oxygen uptake during submaximal exercise were associated with moderate to severe haemodynamic dysfunction. At echocardiography, 15 of 17 patients studied twice had mild to moderate right ventricular dilation and tricuspidregurgiation, which remained virtually the same at reasssesment. A stable sinus rhythm was initially present in 17 patients, and persisted in 15 patients during follow-up. CONCLUSION: At medium term follow-up, cardiorespiratory exercise performance remains stable in patients after atrial switch repair. Serial exercise testing appears useful, because in individual patients in the present study, a decreasing exercise tolerance correlated with development of haemodynamic sequels.

Adolescent↗

Inhibition of nicotine-induced seizures in rats by combining vaccination against nicotine with chronic nicotine infusion.

The ability of a nicotine vaccine to protect against nicotine-induced seizures was studied in rats. Groups of 10 rats were vaccinated with 3 doses of either a nicotine conjugate vaccine over 6 weeks to elicit high titers of nicotine-specific antibodies or with a control vaccine. Rats were then pretreated with a 1-week subcutaneous infusion of either nicotine 1 mg/kg/day or saline and then received a single 2 mg/kg ip dose of nicotine to provoke seizures. Vaccination reduced the incidence of seizures. The combination of vaccination and pretreatment with nicotine infusion was more effective than either treatment alone. These data suggest that vaccination is protective against this toxic effect of nicotine and that combining vaccination and chronic nicotine administration may provide a novel strategy for blocking some effects of nicotine.

Animals↗

The impact of a 10-year audit cycle on blood usage in a district general hospital.

As clinical governance moves from concept to practice, it is emerging as a realistic strategy to promote and improve quality within the National Health Service, as well as satisfying the demand for external accountability. In the context of blood transfusion, the area of responsibility encompasses product liability, as well as efficient use of blood as a resource and transfusion as an appropriate clinical response. Clinical governance may be a modern catch phrase, but the principles it enshrines have long been established within blood transfusion, and in other aspects of haematology. Here, an audit cycle comprising four audits over a 10-year period to monitor the use of cross-matched blood in a large district general hospital is described. Initially, blood use was considered by hospital site, and by the surgical procedure for which it was requested. Later, the scope of the audit was expanded to consider usage by individual consultant. A standard of efficient use of cross-matched blood was taken to be a cross-match to transfusion ratio of < 1.5. The information was reviewed by the hospital transfusion committee, who have a key role in co-ordinating and assessing the practice of transfusion within a hospital. In this hospital, audit has been one of the main tools for improving practice, in particular by enabling the implementation and continuous revision of a maximum blood order schedule. Further, as the process of audit has developed, problem areas have been highlighted, and strategies to improve usage have been brought in with encouraging results. The audit is now being expanded again to include a greater focus on usage of cross-matched blood in the nonsurgical setting.

Blood Loss, Surgical↗

Tiagabine: efficacy and safety in adjunctive treatment of partial seizures.

PURPOSE: To assess the efficacy and safety of tiagabine (TGB), a new antiepileptic drug (AED), as add-on therapy in patients with refractory partial seizures. METHODS: This response-dependent study used an open-label screening phase (in which patients were titrated to their optimal TGB dose, < or =64 mg/day) followed by a double-blind, placebo-controlled, crossover phase. Initial eligibility criteria included (a) seizures inadequately controlled by existing AEDs, and (b) six or more partial seizures during an 8-week baseline period. Patients showing benefit from TGB (> or =25% reduction in total seizure rate relative to baseline) were eligible for randomization into the double-blind phase, which comprised two 7-week assessment periods separated by a 3-week crossover period. RESULTS: Forty-four (50%) of the 88 enrolled patients entered the double-blind phase of the study during which there were significant reductions compared with placebo in all partial (p < 0.01), complex partial (p < 0.001), and secondarily generalized tonic-clonic seizure rates (p < 0.05). Thirty-three percent of patients experienced a reduction of > or =50% in the all partial seizure rate. Eight (22%) patients receiving TGB during the double-blind phase reported adverse events, of which dizziness and incoordination were the most frequent. Three patients withdrew from treatment during the double-blind phase because of adverse events; two during treatment with TGB and one during treatment with placebo. TGB did not affect plasma concentrations of other coadministered AEDs. CONCLUSIONS: TGB was significantly better than placebo in terms of seizure rate reduction and was generally well-tolerated in patients with difficult to control seizures.

Adolescent↗

ATP synthase activity in ovine ceroid lipofuscinosis [OCL6].

We measured ATP synthase activities in mitochondria isolated from livers of lambs with ceroid lipofuscinosis (OCL6) and compared them with those from similar isolations from obligate heterozygous and control lambs. Addition of excess Ca2+ to the incubation mixture resulted in an up-regulation of activity in mitochondria from control lambs but down-regulation in those from OCL6 affected lambs. The mean change in activity with Ca2+ for heterozygous animals was midway between those from control and affected groups being significantly different from control but not from affected. The change in ATP synthase activity to added Ca2+ was also measured in isolated mitochondria from affected and control lambs from 3 days to 25 months of age. As above, there was down-regulation to the addition of Ca2+ in affected lambs. There was a fall in percentage change to Ca2+ with age in both affected and control lambs. This was not significantly different in affected lambs indicating it was not associated with the stage of disease. The above in vitro results, if extrapolated to neurons in vivo, imply a potential dysfunction of mitochondria in OCL6 lambs that could lead to calcium mediated neurotoxicity and neuron death due to production of free radicals as implicit in the energy-linked excitotoxic hypothesis.

Animals↗

A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.

The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy, comparing the effects of gabapentin with lamotrigine on efficacy, behaviour and mood. An open-label, randomized, parallel group, multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted: 39 patients were randomized to gabapentin and 44 to lamotrigine. The study population had a range of learning disabilities and severe partial epilepsy. The percentage of patients achieving a greater than or equal to 50% reduction in seizure frequency on gabapentin was 50%, (mean reduction in seizures was 51%). Compared to 48.6% of lamotrigine patients, no statistically significant treatment differences could be identified. The safety profile of both drugs was consistent with that seen in previous clinical trials. Carer-rated visual analogue scales detected significant improvements (P< 0.05) for the gabapentin-treated patients in seizure severity, attention, general health and sleeping pattern, while for lamotrigine seizure severity improved significantly. For learning disabled patients with resistant epilepsy, gabapentin and lamotrigine provide safe and effective treatment, with positive benefits on behaviour.

Acetates↗

Continuing professional development: medico-legal aspects of epilepsy.

Generally protection against possible litigation and good clinical practice go hand in hand. Situations in which the law has special relevance for people with epilepsy, those who work with them, and their clinicians are reviewed with special reference to the topics of driving, employment, duties of social carers, the clinician's everyday role, the responsibilities of researchers and epilepsy and the criminal law. What constitutes professional negligence is discussed, with special reference to the United Kingdom. Clinicians are advised to think clearly, write clearly, communicate clearly and have a good relationship with their patients.

Automobile Driving↗

Personal view: Randomized controlled trials in epilepsy specialist nursing: the seduction of content by form.

Research into the effectiveness of epilepsy specialist nursing needs to take into account a number of factors, which have not been adequately addressed in previous studies. Nursing outcome measures are different to medical ones and it is inappropriate to confuse these. Specialist nurses affect the whole culture of a service, and their impact on service quality may go beyond that of their individual patient contacts. Thus randomized studies within a service that already has specialist nurses may not give valid results. Some service users will benefit more from direct contact with a specialist nurse than others, and people who give informed consent to take part in randomized controlled trials might not be representative of those who would benefit most from specialist nurse access. The stampede for level one evidence risks failing to address the issues properly by overvaluing research process (form) against its appropriateness (content), yet there remain great opportunities for good quality research in this area.

Epilepsy↗

The amoeba-to-flagellate transformation test is not reliable for the diagnosis of the genus Naegleria. Description of three new Naegleria spp.

Trophozoites of several isolates from one location in Australia have failed consistently to transform into flagellates, although they display all other characteristics of the genus Naegleria. When changing the standard transformation test, flagellates were produced. In phylogenetic trees derived from partial small subunit ribosomal DNA (SSUrDNA) sequences, one of these strains branches close to a cluster comprising N. clarki, N. australiensis, N. italica and N. jadini. It is proposed that these Australian isolates represent a new species, named N. fultoni (strain NG885). Failing to form flagellates since their isolation, even when different transformation procedures are used, are two Naegleria strains from Chile and Indonesia. In SSUrDNA-based phylogenetic trees the Chilean strain clusters with N. pussardi and the Indonesian strain clusters with N. galeacystis, but the degree of sequence difference from these described species (3.5% and 2.2%, respectively) is sufficient to propose that both of the strains represent new species, named N. chilensis (strain NG946) and N. indonesiensis (strain NG945), respectively. The close relationships between each of the new species and the Naegleria species with which they cluster in SSUrDNA-based trees were confirmed by ribosomal internal transcribed spacer region (ITS) sequence comparisons. In France, several non-flagellating N. fowleri strains were isolated from one location. ITS rDNA sequence comparisons indicated that they correspond to a 'type' of N. fowleri found in both Europe and the USA. A redefinition of the genus Naegleria is proposed as a consequence of these and previous findings.

Amebiasis↗

Role of LIM domains in mediating signaling protein interactions.

LIM domains are double zinc-finger motifs that mediate protein interactions between transcription factors, cytoskeletal and signaling proteins. This review outlines the protein interactions mediated by LIM domains with signaling proteins including tyrosine and serine/threonine kinases and phosphatases.

Actins↗

Insulin lispro and regular insulin in pregnancy.

We assessed the safety of insulin lispro in gestational, type 1 and type 2 diabetes mellitus, analysing 635 pregnancies over a period of 7 years. We also evaluated patient satisfaction, sending an internationally-accepted anonymous diabetes treatment satisfaction questionnaire to 22 patients (three type 1, 19 gestational diabetes) who received regular and lispro insulin in successive pregnancies. The success rate of pregnancies in women with gestational diabetes managed with diet alone (n=325) was 99.3%. All 213 pregnancies in women with gestational diabetes requiring insulin were successful. There was no difference in maternal or fetal outcomes whether patients used regular insulin (n=138) or insulin lispro (n=75), but pre-delivery HbA1c was lower with insulin lispro (p<0.05). Pregnancy loss in patients with pre-gestational diabetes (89 pregnancies in type 1 and eight in type 2 diabetes) was 18.6% for insulin and 3.7% for insulin lispro (p=0.10). The incidences of congenital anomalies with regular insulin were 7.9% and 15.8% in gestational and pre-gestational diabetes, respectively; the figures for insulin lispro were 6.6% (p=0.79) and 3.8% ( p=0.16), respectively. Nineteen of the 22 surveyed patients completed the questionnaire. Satisfaction was higher with insulin lispro (26.3+/-2.3 vs. 18+/-8.9, p=0.0005). We found no increase in adverse outcome using lispro insulin in diabetic pregnancies, in either gestational or pre-gestational diabetes. Patient satisfaction favoured insulin lispro. Several patients with type 1 diabetes who used regular insulin during pregnancy, chose lispro after delivery, but all who used lispro in pregnancy preferred to continue.

Adolescent↗