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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 235 records · Page 13Linked to original sources
PubMed1996

Necrotizing fasciitis of the upper extremity.

Twelve cases of necrotizing fasciitis were identified retrospectively over a 5-year period. All were associated with a history of substance abuse by injection or with diabetes. Eleven of the 12 infections were associated with beta-hemolytic Streptococcus, a mixed anaerobic aerobic infection, or both. Three of five patients tested for human immunodeficiency virus had positive test results. A wide extensile approach was used to debride necrotic fascia. An average of 3 debridements were necessary, with a range of 1-6 debridements. Two patients under-went shoulder disarticulation because of uncontrollable infection. The rapid and destructive nature of this disease makes early recognition, aggressive debridement, and antibiotic therapy necessary to minimize morbidity.

Adult↗
PubMed1996

Extracapsular cataract extraction after vitrectomy.

OBJECTIVE: To ascertain the reliability, safety, and effectiveness of extracapsular cataract extraction (without the use of pars plana infusion) in eyes that have had vitrectomy. SETTING: The Manchester Royal Eye Hospital. METHODS: A retrospective analysis of surgical and postsurgical complications and visual acuity change in 41 patients who had one or more vitreoretinal procedures, followed by extracapsular cataract extraction and intraocular lens implantation at a subsequent date. RESULTS: No significant operative complications were encountered using an extracapsular technique without pars plana infusion. Thirty eyes (73.2%) had a significant increase in visual acuity, 10 (24.4%) did not change, and 1 worsened. CONCLUSIONS: A modified form of extracapsular extraction, with control of intraocular fluid flow but without the use of a pars plana infusion, is safe and effective in post-vitrectomy eyes.

Cataract↗
PubMed1996

Human kinesin light (beta) chain gene: DNA sequence and functional characterization of its promoter and first exon.

Kinesins are tubulin molecular motors whose function is to transport organelles within cells. Very little is known about the regulation of expression of these proteins. We have characterized the gene product of one differentially spliced mRNA of the human light chain kinesin and cloned its promoter region. A full-length kinesin cDNA was translated in vitro in a cell-free system, producing a 70-kDa protein. Using this cDNA as a probe, we isolated and sequenced the promoter, first exon, and part of the first intron of this gene from a genomic lambda EMBL3 human placental DNA library. The whole gene spans more than 90 kb. The beta kinesin promoter region confers only constitutive transcription to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene. In permanently transfected human HeLa and NB100 neuroblastoma cells, a reporter gene containing the promoter and part of the first exon of beta kinesin was 75-fold more active than the HSV-tk promoter. The first exon contains the 5'-untranslated sequence capable of forming a stable double-hairpin loop, which functions as a translational enhancer. Its deletion decreases the efficiency of in vitro translation of beta kinesin mRNA and confers increased translation to a CAT reporter gene.

Amino Acid Sequence↗
PubMed1996

Predictors of extubation success and failure in mechanically ventilated infants and children.

OBJECTIVE: To predict extubation success and failure in mechanically ventilated infants and children using bedside measures of respiratory function. DESIGN: Prospective collection of data. SETTING: A university-affiliated children's hospital with a 51-bed critical care unit. PATIENTS: All infants and children who were mechanically ventilated for at least 24 hrs, except neonates < or = 37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: Bedside measurements of cardiorespiratory function were obtained immediately before extubation. MEASUREMENTS AND MAIN RESULTS: Extubation failure was defined as reintubation within 48 hrs of extubation in the absence of upper airway obstruction. Failure rates were calculated for different ranges (selected a priori) of preextubation measures of breathing effort, ventilatory support, respiratory mechanics, central inspiratory drive, and integrated indices useful in adults. Effort of spontaneous breathing was assessed by the respiratory rate standardized to age, the presence of retractions and paradoxical breathing, inspiratory pressure, maximal negative inspiratory pressure (maximal negative inspiratory pressure), inspiratory pressure/maximal negative inspiratory pressure ratio, and tidal volume indexed to body weight of a spontaneous breath. Ventilatory support was measured by the fraction of inspired oxygen (F10(2)), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics were assessed by determination of peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the compliance, rate, oxygenation, and pressure indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. Thirty-four of the 208 patients who were studied were reintubated for an overall failure rate of 16.3% (95% confidence interval 11.3% to 21.4%). The reasons for reintubation were poor effort (n = 8), excessive effort (n = 14), altered mental status or absent airway reflexes (n = 2), cardiovascular instability (n = 3), inadequate oxygenation (n = 3), respiratory acidosis (n = 3), and undocumented (n = 1). Extubation failure increased significantly with decreasing tidal volume indexed to body weight of a spontaneous breath, increasing F10(2), increasing mean airway pressure, increasing oxygenation index, increasing fraction of total minute ventilation provided by the ventilator, increasing peak ventilatory inspiratory pressure, or decreasing mean inspiratory flow (p < .05). Dynamic compliance showed a trend of increasing failure rate with decreasing dynamic compliance but did not reach statistical significance (p = .116). Respiratory rate standardized to age, inspiratory pressure, maximal negative inspiratory pressure, inspiratory pressure/maximal negative inspiratory pressure ratio, frequency to tidal volume ratio, and compliance, rate, oxygenation, and pressure did not show any trend in failure rate with increasing or decreasing values. Threshold values that defined a low risk (< or = 10%) and a high risk (> or = 25%) of extubation failure could be determined for tidal volume indexed to body weight of a spontaneous breath, F10(2), mean airway pressure, oxygenation index, fraction of total minute ventilation provided by the ventilator, peak ventilatory inspiratory pressure, dynamic compliance, and mean inspiratory flow. Neither a low nor a high risk of failure could be defined for frequency to tidal volume ratio or the compliance, rate, oxygenation, and pressure (CROP) index. CONCLUSIONS: Bedside measurements of respiratory function can predict extubation success and failure in infants and children. Both a low risk and a high risk of failure can be determined using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in

Child↗
PubMed1996

Vancomycin-resistant Enterococcus faecium on a pediatric oncology ward: duration of stool shedding and incidence of clinical infection.

OBJECTIVE: To determine the duration of stool shedding and incidence of clinical infection among pediatric oncology patients colonized with vancomycin-resistant Enterococcus faecium (VRE) in our institution. METHODS: Stool cultures were obtained from all patients admitted from May 15 to August 2, 1994. Patients were followed for evidence of clinical VRE infection and surveillance stool results through August 15, 1995. Genetic relatedness of stool-clinical isolate pairs and serial stool samples was evaluated using pulsed field gel electrophoresis. RESULTS: Twenty-three (32%) of 73 screened patients were colonized with VRE. Eight (35%) of the colonized patients cleared VRE from stool; 10 (43%) were persistent carriers, excreting organisms for 19 to 331 days (median, 112 days); and 5 patients had an insufficient number of stools to determine length of carriage. Persistent carriers had a median of 6 hospital readmissions; 8 of 10 were positive at first or second readmission Clinical VRE infection developed in 6 of 73 patients (annual incidence, 8.2%). Clinical cases had more days of neutropenia between colonization and infection than colonized patients during a comparable follow-up (49 vs. 16 days, P = 0.04). Five of 6 stool-clinical isolate pairs were identical by pulsed field gel electrophoresis. Serial stools from 6 of 7 patients (collected 20 to 343 days apart) were identical by pulsed field gel electrophoresis. CONCLUSION: Persistent gastrointestinal colonization with VRE is common among pediatric oncology patients. Carriage of the same VRE clone for up to 1 year was demonstrated. In the majority of cases invasive and colonizing isolates were identical by DNA fingerprinting techniques, suggesting that the colonizing VRE was the source of infection. Intermittent excretion of organisms in stool makes vigilant tracking and immediate isolation of such patients crucial to control efforts. Prolonged neutropenia may increase the risk of developing clinical infection among VRE-colonized patients.

Anti-Bacterial Agents↗
PubMed1996

Topical analgesia for superficial corneal injuries.

OBJECTIVE: To assess the analgesic effects of a topical non-steroidal anti-inflammatory agent, flurbiprofen 0.03%, during healing after superficial corneal injuries. METHODS: 401 patients treated for corneal abrasion in a five month period were randomly allocated to one of four treatment groups: polyvinyl alcohol alone (control), homatropine 2%, flurbiprofen 0.03%, or homatropine 2% followed by flurbiprofen 0.03%. Treatments were given for 48 h. Ocular pain was recorded on a visual analogue scale by the patients over the first 24 h, and use of oral analgesics was also recorded. Usable responses were received from 224 patients (55.8%). RESULTS: Patients treated with flurbiprofen had significantly lower pain scores for the 24 h duration of the study than controls (P < 0.05). CONCLUSIONS: Flurbiprofen eye drops provide more effective pain relief than traditional treatments for superficial corneal injuries.

Administration, Topical↗
PubMed1996

In vivo inhibition of platelet adhesion by a cGMP-mediated mechanism in balloon catheter injured rat carotid artery.

The role of cyclic guanosine monophosphate (cGMP) versus cyclic adenosine monophosphate (cAMP) mediated mechanism in modulating platelet adhesion was investigated in balloon catheter injured rat carotid arteries. Vascular injury with balloon angioplasty significantly increased the adherence of platelets to the injured carotid arteries. Intravenous infusion of zaprinast (1 mg/kg/min), a cGMP phosphodiesterase inhibitor, or sodium nitroprusside (8 micrograms/kg/min), a stimulator of soluble guanylate cyclase, significantly attenuated the adherence of platelets to the injured carotid arteries. In comparison, infusion of milrinone, a cAMP phosphodiesterase inhibitor, or 8-bromo-cAMP failed to affect the platelet deposition in the injured carotid arteries. Nifedipine or aspirin also failed to attenuate the adherence of platelets to the injured carotid arteries. In conclusion, agents known to elevate intracellular platelet cGMP but not cAMP appear to afford the most effective protection in vivo against the adhesion of platelets to the vessel wall without intact endothelium.

Animals↗
PubMed1996

Intra-operative parathyroid hormone assay for simplified localization of parathyroid adenomas.

Lack of success in parathyroid surgery is usually due to failure to identify the abnormal parathyroid gland correctly at operation. The surgeon may be helped by rapid parathyroid hormone (PTH) assay in peripheral blood after removal of a suspected adenoma, and by frozen section histology, but these are not true localization techniques. We have adapted a non-isotopic immunoassay for rapid measurement of PTH in samples from the upper, middle and lower thyroid veins taken at operation, before exploration begins. Fifteen patients with primary hyperparathyroidism were operated on. In 10 the parathyroid adenoma was located easily, and was associated with high local venous PTH levels. In four patients the abnormal parathyroid was not immediately apparent but the assay indicated its location, which was confirmed after further exploration. In one patient there was no difference in PTH levels in the six venous samples. An ectopic adenomatous gland was successfully identified behind the thymus. The operation was successful in all patients as shown by a fall in the plasma calcium to the normal range. We conclude that intra-operative selective venous sampling and rapid PTH assay facilitates operative localization of parathyroid adenomas.

Adenoma↗
PubMed1996

Psychomotor slowing in HIV infection: a predictor of dementia, AIDS and death.

The objective of this study was to determine if sustained decline in psychomotor speed tests is associated with an increased risk of progression to dementia, acquired immunodeficiency syndrome (AIDS), or mortality in human immunodeficiency virus (HIV)-1-infected homosexual men in the Baltimore site of the Multicenter AIDS Cohort-Study (MACS). Clinical and neuropsychological data were obtained on 291 HIV+ homosexual men seen semi-annually over a nine year period (1986-1994). A proportional hazards model was used to assess the predictive value of sustained psychomotor slowing (defined as a 2.0 standard deviation (s.d.) decline in performance on either the Symbol Digit Modalities test or Trailmaking test at two consecutive evaluations). Time-dependent co-variates included in the model were sustained psychomotor slowing, number of attended visits, CD4+ lymphocyte count, hemoglobin and antiretroviral medication use. HIV+ participants with and without sustained psychomotor slowing were compared. Outcome variables were the development of dementia, AIDS and death. HIV+ subjects with sustained psychomotor slowing had an increased hazard of dementia (Risk ratio (RR) = 5.0, P = 0.008), AIDS (RR = 2.4, P = 0.02), and death (RR = 2.0, P = 0.04). A similar analysis using sustained cognitive decline in one domain from a more extensive neuropsychological test battery failed to show any predictive value. Sustained decline in psychomotor performance in HIV infection was predictive of dementia, AIDS and death. This brief neuropsychological test battery may be useful for early detection of HIV+ individuals with a poorer prognosis who may benefit from more aggressive treatment to prevent HIV dementia.

AIDS Dementia Complex↗
PubMed1996

The deep branch of the ulnar nerve in Guyon's canal: branching and innervation of the hypothenar muscles.

Thirty-seven embalmed, unpaired cadaver hands were dissected to delineate and classify the innervation of the hypothenar musculature. The deep branch of the ulnar nerve passed between the abductor digiti minimi and flexor digiti minimi and then pierced the opponens in all specimens. All branching occurred on the ulnar aspect of the deep branch of the ulnar nerve. A classification based on proximity of the different branches is prepared. Five different patterns have been noted.

Cadaver↗
PubMed1996

Molecular basis of phenylketonuria and a correlation between genotype and phenotype in a heterogeneous southeastern US population.

OBJECTIVE: To determine the molecular basis of phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) and to establish correlations between phenylalanine hydroxylase (PAH) genotypes and biochemical and clinical phenotypes in an ethnically diverse US population, PAH genotypes were determined in 35 patients with PKU or HPA and 1 carrier from the Medical Genetics Clinic of the Emory University School of Medicine. METHODOLOGY: Patients were identified through Georgia's population-based newborn screening program. PAH genotypes in these individuals were determined from dried blood spots or whole-blood samples using a combination of polymerase chain reaction-mediated amplification, denaturing gradient gel electrophoresis, and direct-sequence analysis. The phenotypic severity of patients with PKU and HPA was based on pretreatment serum phenylalanine (PHE) levels during the neonatal period and on dietary tolerance of PHE later in life. RESULTS: Sixty-eight (96%) of 71 mutant alleles were identified. Major mutations in this population included R408W (11 of 71), I65T (11 of 71), Y414C (6 of 71), L348V (4 of 71), and IVS10 (4 of 71). Five new nucleotide substitutions, E76A (1 of 71), R241L (1 of 71), Q304R (2 of 71), C334S (1 of 71), and R400R (2 of 71) were also detected. Thirty-two of the thirty-five nonrelated patients examined in this study were completely genotyped. Strong correlations were observed between the level of PAH activity predicted from the genotype, when known from previous in vitro expression studies of the mutant proteins, and pretreatment serum PHE levels (r = .841) or clinical severity (Kendall rank-order correlation coefficient, .936). CONCLUSIONS: These results demonstrate strong correlations between PAH genotype and biochemical and clinical phenotypes in this heterogeneous American sample population, extending our previous findings from relatively homogeneous European populations. These correlations further demonstrate the clinical utility of genotype analysis in the treatment of patients with PKU and HPA.

Alleles↗
PubMed1996

A randomized trial comparing 1.25 mmol/l calcium dialysate to 1.75 mmol/l calcium dialysate in CAPD patients.

BACKGROUND: Effective control of hyperparathyroidism and renal osteodystrophy in CAPD patients requires a combination of calcitriol and calcium carbonate (CaCO3), but is frequently limited by hypercalcaemia. Reducing dialysate calcium (Ca) concentration may overcome this problem, but had not been examined in a controlled trial. METHODS: 45 stable CAPD patients were randomly assigned in a prospective double-blind trial to either a study group (1.25 mmol/l Ca dialysate) or a control group (1.75 mmol/l Ca dialysate) for 12 months. Clinical, biochemical and radiological parameters of secondary hyperparathyroidism were followed. RESULTS: Twenty-three patients did not complete the study due to death (9), transplantation (7) or conversion to haemodialysis (7). Eleven patients in each group completed the study. Mean serum Ca, phosphate, ionized Ca, aluminium, alkaline phosphatase (AP), and bone mineral density (BMD) Z-scores did not differ significantly at any time within or between the two groups. Severe hypercalcaemia was more common in the control group (11 vs. 2, P = 0.027). Mean serum intact parathyroid hormone (PTH) and osteocalcin (OCN) initially rose in the study group relative to controls at 3 months (40 +/- 7 vs 12 +/- 3 pmol/l, P = 0.004, and 33 +/- 5 vs 15 +/- 2 micrograms/l, P = 0.002 respectively), but were not sustained. Median weekly dosages of calcitriol and daily dosages of CaCO3 increased significantly in the study group (O microgram to 1 microgram P = 0.014 and 1260 mg to 2520 mg P = 0.002 respectively), but not in the control group. Supplementary aluminium hydroxide (A1, (OH)3) was required for phosphate control in both study (n = 5) and control patients (n = 4). CONCLUSIONS: Lowering dialysate calcium concentration reduced the frequency of severe hypercalcaemia and allowed prescription of larger quantities of calcitriol and CaCO3. However, in this study it offered no advantage in terms of A1(OH)3 requirement, while bone mass density did and may have initially exacerbated secondary hyperparathyroidism not change.

Aluminum Hydroxide↗
PubMed1996

Acute diplopia and a solitary lung mass: a unique presentation of light-chain myeloma.

The patient described, a 51-year-old woman, had diplopia and cephalgia of two weeks' duration. On admission, the radiologic evaluation revealed a mass in the sphenoid sinus, multiple lesions in the calvarium and a solitary lung mass. Biopsy of the lung mass revealed an atypical plasmacytic infiltration. Laboratory findings confirmed the diagnosis of light-chain myeloma presenting with a pulmonary plasmacytoma and cranial nerve involvement.

Abducens Nerve↗
PubMed1996

Effect of integrated research programs on health care systems and costs.

We examined the effect of research program size on clinical costs (current dollars/work unit) and productivity (work units/ employee) in Department of Veterans Affairs (DVA) hospitals. Our data demonstrate that research programs have a small, almost negligible effect on clinical costs. The data also show that average acute medical service length-of-stay was inversely related to research program size. The indirect cost of research may have been almost entirely offset by an increased efficiency, as reflected in the shortened length of stay. This unexpected benefit of research may be due to the influence of research opportunities on the recruitment and retention of highly trained clinicians, including medical specialists. In the past, recruitment and retention was part of the justification for the DVA research program. Although this justification no longer appears to be considered politically acceptable, our data strongly support the notion that research programs can and do enhance the efficiency of medical care. Furthermore, research activities help professional staff maintain their critical thinking and analytic skills. We discuss the implications of these observations on cost containment in health care systems.

Cost Control↗
PubMed1995

Cloning and characterization of the neural isoforms of human dystonin.

Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We have identified and cloned a gene encoded at the dt locus. The product of the dt gene, dystonin, is a neural isoform of a hemidesmosomal protein bullous pemphigoid antigen 1 (bpag1). To investigate the potential role of dystonin in human neuropathies, we have cloned the neural-specific 5' exons of the human DT gene that together with the previously cloned BPAG1 sequences comprise human dystonin. The mouse and human dystonin genes demonstrate the same spectrum of alternatively spliced products, and the amino acid sequences of the neural-specific exons in the mouse and human genes are over 96% identical.

Amino Acid Sequence↗