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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 397 records · Page 22Linked to original sources
PubMed1994

Hallucinations and ifosfamide-induced neurotoxicity.

BACKGROUND: Hallucinations as a symptom of central neurotoxicity are a known but poorly described side effect of ifosfamide. Most cases of ifosfamide-induced hallucinations have been reported with other mental status changes. METHODS: The authors interviewed six persons with ifosfamide-induced hallucinations in the presence of a clear sensorium. All patients were receiving high-dose ifosfamide as part of their bone marrow transplant procedure. RESULTS: Hallucinations occurred only when the patient's eyes were closed and, in all but one case, were reported as disturbing or frightening. Underreporting of these hallucinations by patients is likely. CONCLUSIONS: Hallucinations may be the sole or first manifestation of neurotoxicity. The incidence may be dose and infusion-time related. The clinician should be alerted for possible ifosfamide-induced hallucinations, which may occur without other signs of neurotoxicity. "Eyes-closed" hallucinatory experiences appear to be an unusual feature of this presentation. Patients anxious about this experience respond well to support and education about this occurrence. Optimal pharmacologic management of disturbed patients is unclear. If agitation becomes marked, high-potency neuroleptics (i.e., haloperidol) may be effective.

Adult↗
PubMed1994

Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning.

Neural-cell adhesion molecules (N-CAMs) are members of the immunoglobulin superfamily mediating homo- and heterophilic cell-cell interactions. N-CAM exists in various isoforms which are generated by alternative splicing. During embryonic development, N-CAMs are expressed in derivatives of all three germ layers, whereas in the adult animal they are predominantly present in neural tissue. Processes like neurulation, axonal outgrowth, histogenesis of the retina and development of the olfactory system are correlated with the regulated expression of N-CAMs. We show here that N-CAM-deficient mice generated by gene targeting appear healthy and fertile, but adult mutants show a 10% reduction in overall brain weight and a 36% decline in size of the olfactory bulb. N-CAM deficiency coincides with almost total loss of protein-bound alpha-(2,8)-linked polysialic acid, a carbohydrate structure thought to be correlated with neural development and plasticity. The animals showed deficits in spatial learning when tested in the Morris water maze, whereas activity and motor abilities appeared normal.

Animals↗
PubMed1994

Collision of transitional cell carcinoma and renal cell carcinoma. An immunohistochemical study and review of the literature.

A case characterized by a rare synchronous occurrence of transitional cell carcinoma (TCC) of the renal pelvis and renal cell carcinoma (RCC) in the same kidney is presented. A retrospective analysis of 23 similar cases reported in the English literature over the last 71 years demonstrated a male-to-female ratio of 2:1, an average age of 64.5 years, and a left-to-right-side ratio of 3.2:1. The three most common findings at initial examination were hematuria (90%), flank pain (19%), and flank mass (14%). Moreover, 24% of patients had tumor metastases even at initial examination. Thirty-four percent of patients had bladder neoplasms, and 24% of them had a history of cigarette smoking. There is no tendency toward higher grade of malignancy or specific histologic pattern for TCC and RCC when they occur together in the same kidney. Immunohistochemical studies were used to examine TCC and RCC, with special attention paid to the site of their collision, which displayed multifocal lymphatic permeation. Both TCC and RCC were positive for epithelial membrane antigen (EMA) and cytokeratins identified by monoclonal antibodies CAM-5.2, AE1/AE3, and MAK-6. TCC was focally positive for keratin, detectable by antibody 34 beta E12, but RCC was not. The tumor tissue infiltrating the lymphatics, which seemed to be RCC, demonstrated positive staining for EMA and keratins CAM-5.2, AE1/AE3, and MAK-6 and negative staining for keratin 34 beta E12. Interestingly, the tumor in lymphatics displayed strong staining for carcinoembryonic antigen (CEA) but both TCC and RCC in the vicinity were negative. These findings suggest that keratin 34 beta E12 may play a role in the differential diagnosis between TCC and RCC and that tumor-invading lymphatics may change phenotype, including the neoexpression of CEA.

Aged↗
PubMed1994

Effect of recombinant human insulin-like growth factor I and early total parenteral nutrition on immune depression following severe head injury.

OBJECTIVE: To determine the effects of insulin-like growth factor I (IGF-I) and aggressive nutrition on CD4/CD8 ratios following head injury. DESIGN: Randomized controlled trial. SETTING: An urban level 1 trauma center. PARTICIPANTS: Head-injured patients with a Glasgow Coma Scale score of 4 to 10 within 6 hours of hospital admission requiring no major extracranial surgery with the exception of isolated lower-extremity fracture fixation. Fourteen patients were recruited and 11 completed the study. INTERVENTIONS: Patients were randomized to a continuous infusion of saline or 0.01 mg/kg per hour of recombinant human (rh) IGF-I. Both groups received parenteral nutrition and rapidly advanced to a total protein intake of 2 g/kg per day and a maximum nonprotein calorie intake of 40 kcal/kg per day. The nonprotein prescription was 1.25 times the metabolic energy expenditure determined by metabolic cart not to exceed a nonprotein calorie intake of 40/kcal. MAIN OUTCOME MEASURES: The CD4/CD8 ratios and serum IGF-I levels on days 1, 7, and 14. RESULTS: Administration of early aggressive nutrition eliminated the depressed CD4/CD8 ratio usually seen after head injury; administration of IGF-I increased the CD4/CD8 ratio while IGF-I levels were elevated. CONCLUSIONS: Infusion of rhIGF-I and aggressive early intravenous nutrition affects the immunologic response of patients with severe head injury.

Adult↗
PubMed1994

Cu/Zn superoxide dismutase activity in familial and sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that is inherited as an autosomal dominant trait in approximately 10% of cases. Recently we and others identified several single-base mutations in the Cu/Zn superoxide dismutase (SOD1) gene in patients with familial ALS (FALS). Using single-strand conformational polymorphism, we studied the C to G mutation in exon 2 of the SOD1 gene (resulting in a leucine to valine substitution in position 38) in affected and unaffected members of a large Belgian family with FALS. We measured the SOD1 activity in red blood cell lysates in 14 members of this family, including the only surviving clinically affected patient. SOD1 activity of the family members carrying the mutation was less than half that of members without the mutation. In addition, in 11 patients with sporadic ALS and 11 age- and sex-matched controls, red blood cell SOD1 activity was normal. These studies indicate that SOD1 activity is reduced in these FALS patients but not in sporadic ALS patients. Moreover, this SOD1 enzyme abnormality is detectable years before onset of clinical ALS in carriers of this FALS mutation.

Adult↗
PubMed1994

Effects of practice of serial tests of attention in healthy subjects.

The effects of practice on the serial performance of auditory and visual attention tasks were investigated in 10 healthy volunteers tested at 2 to 4 weekly intervals over eight test sessions using a battery of psychometric tests. Subjects as a group showed an ability to significantly (p = .05) improve their performances over time on all tests except for the Simple Reaction Time and Symbol Digit Modalities Test, the latter demonstrating a trend towards improvement (p = .07). Improvement when it occurred was almost uniformly linear and on tests such as the Pegboard and Stroop, was still discernable at the eighth session. On tests such as Paced Visual Serial Addition Task, floor effects were noted after five sessions and no further improvement was possible. In general, younger subjects tended to make fewer errors, perform quicker and improve for longer periods than their older counterparts. The results indicate that on tests of attention, healthy subjects have the ability to significantly improve performance with practice and this may extend over as many as eight discrete test sessions. The implications for neuropsychological research are discussed.

Adult↗
PubMed1994

Waist and neck enlargement after quadriplegia.

Changes in waist and neck size in quadriplegic patients after paralysis, noted clinically, were assessed systematically. Twenty quadriplegic men, aged 60 +/- 13 years (mean +/- 1 SD) and 20 neurologically intact men, aged 63 +/- 17 years, selected by absence of weight gain, were questioned about changes in their waist and shirt collar sizes since the onset of paralysis (20 +/- 13 years) or during the previous 20 years for control subjects. Waist size expanded 7.0 +/- 0.3 inches for quadriplegic and 1.7 +/- 1.7 inches for control subjects (p < 0.001). Changes in neck size of 0.7 +/- 1.1 inches for quadriplegic and 0 +/- 0.7 inches for control subjects were found (p < 0.02). We conclude that quadriplegia is often followed by increased waist and neck size. These changes may relate to the impaired breathing mechanisms in quadriplegia.

Abdominal Muscles↗
PubMed1994

Specific inhibition of a human papillomavirus E2 trans-activator by intracellular delivery of its repressor.

Papillomaviruses are the causative agents of benign and malignant epithelial tumors of the skin and mucosa. They encode a DNA-binding protein, E2, that regulates viral transcription and replication, making it an important therapeutic target. By deleting the amino-terminal trans-activation domain of human papillomavirus type 16 (HPV-16) E2 while retaining its carboxy-terminal DNA binding and dimerization domain, an E2 repressor (E2R) that efficiently inhibits transcriptional activation by full-length HPV E2 was generated. To deliver this repressor protein into animal cells, we have utilized the human immunodeficiency virus type 1 (HIV-1) Tat protein which itself is taken up efficiently into intact cells. Chimeras of E2R and the cellular uptake domain of Tat specifically inhibited E2-dependent reporter gene expression in COS-7 cells. Treatment of cervical intraepithelial neoplasia cells having episomally replicating HPV-31 DNA with this Tat-E2R protein led to a dose-dependent loss of HPV DNA copies and inhibition of cell growth. Tat-mediated delivery can be a valuable tool for assessing protein function and may allow the development of novel therapeutic proteins having intracellular targets.

Amino Acid Sequence↗
PubMed1994

Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia.

OBJECTIVE: The aim was to examine the relationship between changes in myocyte function to changes in protein and mRNA content of components of the beta adrenergic system with tachycardia induced cardiomyopathy. METHODS: Contractile function and beta adrenergic responsiveness were measured in isolated myocytes from control pigs (n = 6) and in pigs subjected to three weeks of pacing induced supraventricular tachycardia (n = 6). beta Receptor density and affinity, the relative content of the stimulatory (Gs) and inhibitory (Gi) subunits of the G protein complex, and adenylate cyclase activity were determined from sarcolemmal preparations. In order to determine whether these changes were accompanied by alterations in steady state mRNA levels for specific components of the beta adrenergic system, mRNA content for the beta 1 adrenergic receptor and the G alpha s and G alpha i2 subunits of the G protein complex was measured. RESULTS: Chronic supraventricular tachycardia caused a 36% increase in left ventricular end diastolic dimension and a 61% decrease in left ventricular fractional shortening compared to controls. The velocity of isolated myocyte shortening was 50% lower in myocytes from hearts with tachycardia cardiomyopathy than in control myocytes. In the presence of 50 nM isoprenaline or 2 microM forskolin, the velocity of myocyte shortening was 65% lower in the myopathic myocytes than in the controls. With the development of tachycardic cardiomyopathy, beta adrenergic receptor density fell by 25% with no change in affinity, Gs decreased by 35%, and Gi increased by over 50% compared to controls. Basal adenylate cyclase activity and isoprenaline and forskolin stimulated adenylate cyclase activity fell by over 50% with supraventricular tachycardia compared to controls. The relative content of G alpha i2 mRNA increased threefold with the development of tachycardic cardiomyopathy with no change in the relative abundance of mRNA for the beta 1 receptor or G alpha s when compared with controls. CONCLUSIONS: The changes in myocyte beta adrenergic responsiveness with the development of tachycardic cardiomyopathy are due to alterations in cellular mechanisms (decreased beta receptor and Gs density, increased Gi) and in molecular mechanisms (increased Gi mRNA content).

Adenylyl Cyclases↗
PubMed1994

Molecular analysis of the topoisomerase II alpha gene and its expression in human ovarian cancer.

BACKGROUND: DNA topoisomerase II enzymes are key targets for the group of anti-tumour agents known as topoisomerase inhibitors. In general, cell lines which express high levels of topoisomerase II are sensitive to the cytotoxic effects of the topoisomerase poisons. The levels of topoisomerase II expression in tumour biopsies may therefore predict response to treatment with enzyme inhibitors. In the current study we have analysed ovarian tumours for expression of topoisomerase II alpha and genetic change at the topoisomerase II alpha locus on chromosome 17. MATERIALS AND METHODS: We have used methodology which allows the sequential extraction of protein and genomic DNA from the same biopsy sample to study the topoisomerase II alpha locus and the expression in ovarian cancer. Topoisomerase II alpha expression was quantified by Western blot analysis in 54 tumours. RESULTS: Topoisomerase II alpha expression was detected in 65% of ovarian tumours with a 16 fold range in level. In adenocarcinomas, the topoisomerase II alpha gene can become amplified due to its proximity to ERBB2 on chromosome 17q. Of 86 ovarian tumours studied only 1 had amplification of ERBB2 and none had amplification of topoisomerase II alpha a sequences. CONCLUSIONS: Topoisomerase II alpha expression was detected in ovarian carcinomas by Western blot analysis. A sixteen-fold range in expression was detected with significantly higher levels of topoisomerase II alpha expression in advanced stage IV and grade III tumours. Molecular analysis of the topoisomerase II alpha locus failed to reveal any gross genetic alterations which could account for the variation in levels of expression.

Adenocarcinoma↗
PubMed1994

Accidents and incidents involving patients in a mental health service.

Healthcare givers, and their managers, have a duty to monitor the frequency and types of accidents and untoward incidents which occur to patients in their care. The purpose of this study was to systematically examine accidents and incidents (AIs) involving patients in a mental health service unit. Data were collected on all inpatient and day patient AIs over a 6-month period (January to June 1991). The data were then analysed to identify: (a) the nature of AIs occurring in the unit; (b) the frequencies of the AIs, and (c) the times at which AIs occurred. In the wards for elderly patients, an increase of AIs was noted from 05.00 hours; after this time the frequency of AIs remained fairly constant until 20.00 hours when a decrease occurred. In the other wards, a rise in AIs could be seen from 07.00 hours and a fall occurred after 01.00 hours. However, within the time period of 07.00-01.00 hours, further patterns were noted in the data for all AIs in the wards for non-elderly patients, as well as for incidents involving aggression and self-harm. Possible reasons for these findings are suggested, and recommendations made for the examination of some nursing practices within the unit.

Accidental Falls↗
PubMed1994

Techniques and results in bilateral sequential single lung transplantation. The National Heart & Lung Replacement Service.

Lung transplantation continues to evolve as a therapeutic option for patients with end-stage lung disease. Bilateral sequential single lung transplantation (BSSLTx) is a recent addition to the lung transplant surgeon's armamentarium that incorporates the benefits of single lung transplantation in patients who require double lung replacement while avoiding the morbidity inherent in the en bloc double lung transplant procedure. Between November 1992 and October 1993, 17 recipients underwent 18 bilateral BSSLTx procedures for a variety of indications. In 53% of patients, the procedure was completed without the requirement for cardiopulmonary bypass. Telescoping of the bronchial anastomosis has proved satisfactory. Induction cytolytic therapy has not been utilized. Patients received methyl prednisolone from day 1 and as maintenance prednisolone therapy. Actuarial 1-year survival is 87%; 12 of the 15 survivors are in Functional Class I. BSSLTx is an evolving transplant option for patients who require double lung replacement. Definitive clinical diffusion of the procedure will depend upon intermediate and long-term outcomes for specific recipient pathologies.

Adult↗
PubMed1994

The development of gender differentiation in young children.

A sample of 128 boys and girls in four age groups (three, five, seven, nine years) undertook tasks designed to assess their ability to categorize by gender, gender constancy, evaluations of gender groups, and gender discrimination in the allocation of prizes in a task performance setting. Results indicated that all children could categorize accurately by gender although nine-year-olds tended to adopt more complex criteria. Gender constancy increased with age, although not monotonically--seven-year-olds displayed less constancy than five-year-olds. Gender differentiation in attitudes was very marked from five years upwards, and even earlier in girls (both groups viewed their own gender more favourably). This greater own gender favouritism among girls was even clearer in the discrimination task: girls awarded girls' groups more desirable toys even when they had ostensibly performed less well than the boys' group. The boys attended more to performance information. Girls also made more negative comments about boys than vice versa.

Child↗