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Biomedical subjects

R A Brown

Publications and source records attributed to R A Brown.

At least 37 records · Page 2Linked to original sources

Percutaneous endoscopic gastrostomy in children--a 5-year experience.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) has been performed on children since 1979. The indications for a PEG are wide ranging and while there are well-established benefits, it remains a procedure with recognised complications. GOALS AND OBJECTIVES: The goal of this study was to review our experience with this procedure at a South African paediatric tertiary referral hospital over a 5-year period. The objectives were to review PEGs with regard to patient characteristics, indications, anaesthesia time required and complications. METHODS: The study was a retrospective case record review. RESULTS: A total of 70 PEGs were performed. Patients had a mean age of 4 years and 3 months, and a mean weight of 12.2 kg at the time of performing the procedure. The mean anaesthetic time required for performing a PEG was 27 minutes. Fifty-four PEGs (77%) were performed for inability to swallow, 15 (21%) to improve caloric intake, and 1 (1%) for continuous enteral feeding. There were no deaths, 5 patients had major complications (6%), and 12 patients (17%) needed antireflux surgery subsequent to the placement of a PEG. DISCUSSION: There is an increasing demand for PEGs at our institution. The indications for a PEG in this series are similar to those reported in other series, although we may be underutilising PEGs to improve caloric intake. Our complication rates compare favourably with those reported in other series. We have, however, identified post-PEG gastrooesophageal reflux disease as a complication we would like to reduce, and suggest a practical approach to do so.

Adolescent↗

Engineering and cell attachment properties of human fibronectin-fibrinogen scaffolds for use in tissue engineered blood vessels.

Tissue engineered constructs reported to date have been prepared primarily from poly(glycolic) acid or collagen scaffolds onto which cells are grown and matured. In this paper we report experimental data to demonstrate the use of a natural, human protein, as a tubular scaffold for vascular grafting. Using a manual and a scalable dip-coating technique we prepared fibronectin-based tubes up to 12 cm in length and up to 3 mm in diameter. The tubes were flexible and their mechanical properties, measured in terms of tensile strength and burst pressure as a function of humidity, demonstrated their suitability as scaffolds for use in vascular grafting, e.g. coronary artery by pass grafting. In vitro tests involved the attachment of endothelial cells pumped under laminar flow conditions through the tube lumen and the adherence of smooth muscle cells on the outer surface of the tubes. These tests, carried out in multiwells, showed that the scaffolds had excellent cell attachment and guidance characteristics.

Journal Article↗

Contraction-mediated pinocytosis of RGD-peptide by dermal fibroblasts: inhibition of matrix attachment blocks contraction and disrupts microfilament organisation.

Force generation in collagen and matrix contraction are basic functions of fibroblasts and important elements of tissue repair. Cell-matrix attachment is critical to this contraction, involving RGD-binding integrins. We have investigated how this process operates, in terms of force generation (in the Culture Force Monitor) and cytoskeletal structure, using a synthetic RGD-decapeptide. The RGD-peptide blocked force generation over the first 6 h, followed by near complete recovery by 20 h. However, dose response was complex indicating multiple processes were operating. Analysis of cytoskeletal structure after treatment with RGD-peptide indicated major disruption with condensed aggregates of actin and microtubular fragmentation. Fluorescent labeling and tracking of the RGD-peptide demonstrated intracellular uptake into discrete cytoplasmic aggregates. Critically, these RGD-peptide pools co-localised with the condensed actin microfilament aggregates. It is concluded that RGD-peptide uptake was by a form of contraction-mediated pinocytosis, resulting from mechanical tension applied to the untethered RGD-peptide-integrin, as contractile microfilament were assembled. These findings emphasize the importance of sound mechanical attachment of ligand-occupied integrins (e.g., to extracellular matrix) for normal cytoskeletal function. Conversely, this aspect of unrestrained cytoskeletal contraction may have important pathogenic and therapeutic applications.

Actin Cytoskeleton↗

Y-V advancement antropyloroplasty for corrosive antral strictures.

Accidental corrosive ingestion by children can result in damage to the oesophagus and stomach. With progressive scarring and fibrosis luminal obstruction occurs. Gastric fibrosis typically results from acid ingestion and occurs in the antrum because of pooling of the corrosive agents at that site. The antral stricture presents with symptoms of progressive outlet obstruction that may take up to 3 years to become clinically apparent. Surgery is necessary to bypass this obstruction. We describe three patients in whom we have successfully utilised a Y-V advancement antro-pyloroplasty as corrective surgery for corrosive antral strictures. The procedures required little dissection and two could be done early in the evolution of the stricture. Antro-duodenal patency was maintained on follow-up.

Burns, Chemical↗

Optical measurement of three-dimensional collagen gel constructs by elastic scattering spectroscopy.

Analysis of the formation and organization of new connective tissue formed in tissue-engineered constructs is a major requirement for tissue bioreactor technology. We have analyzed early-stage responses in collagen lattices, using elastic scattering spectroscopy to assess its potential to monitor tissue structural changes in structures up to 3 mm thick, under normal culture conditions. The method is based on an optical system in which an optical fiber delivers white light onto the tissue and the back-scattered light is collected for spectroscopy by another optical fiber. Results show correlation between changes in the spectral signatures with changes in the collagen gel contraction or internal organization in all three models of collagen construct analyzed. Therefore elastic scattering spectroscopy is a promising tool to monitor tissue-engineered constructs or early repair in collagenous tissues.

Collagen↗

Is there a need for postoperative surveillance after day case groin surgery in children?

There is increasing awareness of the value of day case paediatric surgery in fulfilling the needs of the community. Is this cost effective, are there hidden complications and is there a need for routine follow-up? Seven hundred and thirty-one children attending the Red Cross War Memorial Children's Hospital day surgery unit over a 32-month period, and undergoing 912 procedures confined to the inguinoscrotal region, were enrolled in the study. Surgical procedures performed included inguinal herniotomy, orchidopexy and circumcision. Of the 731 children, 159 consecutive children had their inguinal and perineal skin flora analysed preoperatively and in 59 of these children three skin swabs were taken from the groin area: before routine skin preparation for surgery, after the skin preparation and on completion of the operation. Staphylococcus epidermidis predominated as the normal skin flora (70%), followed by Escherichia coli (19%) and Proteus mirabilis (10%), while S. aureus was only found in 2.5% of cases. The efficacy of cleaning with 4% chlorhexidine and 2% povidone-iodine in 70% alcohol is shown by virtual complete eradication of the organisms isolated from the preoperative skin cultures. In only 2 cases (3.4%) were organisms (S. aureus and S. epidermidis respectively) isolated following skin preparation. Cultures taken at the end of operative procedures grew predominantly S. epidermidis (5 cases, 8.5%). Children were discharged from the day unit once they had taken fluids and had passed urine. The wounds were also checked for any evidence of bleeding. Follow-up was done 2 weeks later by means of a visit to the day unit where the same surgeon assessed wound healing according to the Southampton Wound Assessment Scale. Ninety-four per cent of the wounds had healed by primary intention; 4.5% had minor complications and 1.5% had septic complications. Our trial confirms that wound sepsis is an infrequent but significant complication of day case groin surgery. Routine follow-up by surgical day units of minor surgical cases is not warranted and will incur unnecessary cost. Only 1.5% of postoperative cases will require further medical attention and septic lesions in the lymphatic drainage area should be regarded as risk factors.

Ambulatory Surgical Procedures↗

Class II phosphoinositide 3-kinase is activated by insulin but not by contraction in skeletal muscle.

While the role of the class IA phosphoinositide 3-kinase (PI 3-kinase) in insulin signaling is well established, little is known about the role of the class II PI 3-kinases. We show that insulin stimulation of intact rat soleus and epitrochlearis muscles causes a 3- to 4-fold increase in the activity of the wortmannin-resistant alpha isoform of the class II PI 3-kinase (PI3K-C2alpha). This activation is rapid and parallels the insulin-induced activation of the class IA PI 3-kinase associated with IRS-1 in these muscles. However, while contraction activated p38 Map kinase, it did not stimulate the activity of the class II PI 3-kinase. Therefore, activation of class II PI 3-kinase is unlikely to provide a mechanism that explains the fact that exercise-induced activation of glucose uptake is not blocked by wortmannin. However, the results suggest that activation of class II PI 3-kinase is likely to play a role in insulin signaling pathways in skeletal muscle.

Androstadienes↗

Tumor necrosis factor receptor fragment attenuates interferon-gamma-induced non-REM sleep in rabbits.

Although the somnogenic actions of interferon-alpha (IFNalpha) and IFNbeta have been reported, the sleep effects of IFNgamma remained unknown. Thus, we investigated the effects of intracerebroventricular injection of human IFNgamma on sleep in rabbits. IFNgamma dose-dependently increased nonrapid eye movement sleep (NREMS), electroencephalographic slow wave activity and brain temperature (Tbr). These effects were markedly attenuated after the heat treatment of IFNgamma. IFNgamma suppressed rapid eye movement sleep if given during the light period, but not if given at dark onset. Although a tumor necrosis factor receptor fragment did not affect any sleep parameters when given at dark onset, it significantly attenuated IFNgamma-induced NREMS and Tbr. These data suggest that IFNgamma may be involved in the sleep responses during infection. Further, IFNgamma may have a synergistic interaction with intrinsic TNFalpha in the brain.

Amino Acid Sequence↗

Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide.

Arsenic trioxide has been shown to be effective in treating acute promyelocytic leukemia (APL), with minimal overall toxicity reported to date. A phase I/II study was initiated in June 1998 using arsenic trioxide for relapsed APL to determine the maximum tolerated or minimal effective dose and to determine the efficacy of treatment at that dose. Ten patients received 1 to 4 monthly cycles of treatment with 0.1 mg/kg per day intravenous arsenic trioxide. Six of 7 patients evaluable for response achieved cytogenetic or molecular complete remission. However, 3 patients died suddenly during the first cycle of treatment. Autopsies obtained on 2 of these failed to identify a cause of sudden death, despite evidence of pulmonary hemorrhage in one. A third patient, for whom an autopsy was not performed, became asystolic and died while on continuous cardiac telemetry. These observations suggest that arsenic trioxide may be significantly or even fatally toxic at doses currently used and that caution is warranted in its use.

Adult↗

Wet extrusion of fibronectin-fibrinogen cables for application in tissue engineering.

A method for the wet extrusion of human plasma-derived fibronectin-fibrinogen cables is described. Solutions of fibronectin and fibrinogen with and without sodium alginate and carboxymethylcellulose (CMC) are tested. The rheological properties of the protein solutions changed from Newtonian to shear thinning non-Newtonian in the presence of small quantities of these additives, the apparent viscosity increased, and the extrusion properties of the protein solutions improved. Cables were prepared using a capillary with a diameter of 1 mm and overall length of 18 mm. Cable diameter was reduced to about 0.5 mm by drawing using a series of rollers. Cables prepared with sodium alginate were found to have suitable properties, and those made with CMC were sticky and difficult to handle. Solutions containing no sodium alginate required a minimum total protein concentration of about 70 mg/mL for extrusion. Extruded cables were prepared with solutions containing 140 mg/mL total protein with 12.9 mg/mL alginate (high protein), and 46 mg/mL total protein with 47.6 mg/mL of sodium alginate (high alginate). The mechanical strength of the extruded cables was within the range suitable for application in tissue engineering. Extrusion of the protein solutions into cables was achieved in a coagulation bath. Cables with a mechanical strength of approximately 30 N/mm(2), suitable for wound repair and nerve regeneration applications, were prepared with a coagulation bath containing 0.25 M HCl, 2% CaCl(2) at a pH of <0.9. These cables also had a large average elongation at break of 52%, and showed an increase in cable length after breakage (permanent set) of 20%, demonstrating the potential for drawing the cables down to a fine diameter.

Alginates↗

A content analysis of smoking craving.

The purpose of this study was to conduct a content analysis of smoking craving in order to investigate more precisely the subjective nature of the construct with the goal of informing assessment. Thirty-two smokers interested in cessation treatment provided free response written descriptions of the level of craving they normally experience. These responses were analyzed for subjective content along five theoretical domains: physiological, affective, cognitive, behavioral, and synonyms (of craving). Although there were no differences in the relative proportion of broad content terms smokers used to describe their craving (e.g., cognitive versus affective), this analysis revealed considerable diversity in the specific terms smokers used. Some smokers described their craving in purely physiological terms whereas others used primarily cognitive terms, and still others used affective terms. To assume that smoking craving is qualitatively similar across persons, then, may mask important variations that define the individual experience of craving.

Cognitive Dissonance↗

DBP formation kinetics in a simulated distribution system.

Little is known about how the growth of halogenated disinfection by-products (DBPs) in drinking water is affected by time spent in a distribution system. Experiments were performed to compare the rate of trihalomethane and haloacetic acid production in a simulated pipe environment to that observed for the same water held in glass bottles. Results showed that although the rate of chlorine consumption in the pipe was much greater than in the bottle, there was no decrease in the amount of haloacetic acids produced and that trihalomethane levels actually increased by an average of 15%. Separate tests confirmed that this increase was due to a reservoir of organic precursor material associated with deposits on the pipe wall. This work suggests that the rate of DBP production in a distribution system will not necessarily be reduced by increased chlorine consumption due to non-DBP producing reactions with deposits on the pipe wall.

Bromides↗

Exercise attitudes and behaviors among persons in treatment for alcohol use disorders.

The present study investigated self-reported exercise behaviors and exercise-related attitudes in a sample (N = 105) of adults in treatment for alcohol use disorders (AUD) (abuse or dependence). Slightly less than half (47%) of participants reported engaging in regular physical exercise (3 times per week or more). Level of alcohol dependence was not significantly associated with level of physical exercise activity. Level of nicotine dependence was significantly and negatively associated with physical activity level. Nicotine dependence and level of depressive symptoms were both significantly negatively associated with self-efficacy for physical exercise (SPE). Exercise self-efficacy mediated the relationship between nicotine dependence and physical activity level. Tension and stress reduction were among the most strongly endorsed of the perceived benefits of physical activity. Other perceived benefits included more positive outlook and increased self-esteem. Financial costs associated with exercise, lack of motivation, and time constraints were among the most common perceived barriers to exercise in this sample. Together, these preliminary data indicate that exercise-based interventions are may be well-received by those early in recovery from AUDs.

Adolescent↗

Cognitive-behavioral treatment for depression in smoking cessation.

Cigarette smokers with past major depressive disorder (MDD) received 8 group sessions of standard, cognitive-behavioral smoking cessation treatment (ST; n = 93) or standard, cognitive-behavioral smokiig cessation treatment plus cognitive-behavioral treatment for depression (CBT-D; n = 86). Although abstinence rates were high in both conditions (ST, 24.7%; CBT-D, 32.5%, at 1 year) for these nonpharmacological treatments, no main effect of treatment was found. However, secondary analyses revealed significant interactions between treatment condition and both recurrent depression history and heavy smoking ( > or =25 cigarettes a day) at baseline. Smokers with recurrent MDD and heavy smokers who received CBT-D were significantly more likely to be abstinent than those receiving ST (odds ratios = 2.3 and 2.6, respectively). Results suggest that CBT-D provides specific benefits for some, but not all, smokers with a history of MDD.

Adult↗

Self-assessment in clinical health psychology: a model for ethical expansion of practice.

Society expects autonomous professions to ensure the competency of it practitioners, and professions should facilitate the continuing education and training of its members. Given the shift from psychology as a mental health profession to that of a health profession, the authors propose a self-assessment model for the individual practitioner to gauge his or her readiness to provide professional service in expanded areas of practice. This model could also be useful to the American Psychological Association, state psychological associations, and other purveyors of continuing education programs in systematically developing postgraduate experiences. A template for self-assessment that reflects well-accepted core domains of knowledge and skills is presented.

Education, Continuing↗

Treatment of steroid-resistant acute graft-versus-host disease with anti-thymocyte globulin.

Acute graft-versus-host disease (aGVHD) is a major cause of mortality after allogeneic stem cell transplantation. Although initial treatment with corticosteroids is effective in the majority of patients, 30--60% develop steroid resistance. Anti-thymocyte globulin (ATG) is commonly used as first-line therapy for steroid resistant (SR) aGVHD. However, data on its efficacy are limited. At two institutions we reviewed the results of treatment with ATG of 58 patients with SR aGVHD. Initial manifestations of aGVHD were treated with 2 mg/kg/day of methylprednisolone (MP). Equine ATG was administered as first-line therapy for SR aGVHD, a median of 9 days (range, 3 to 39) after initiation of MP. At the time of initiation of ATG, IBMTR severity indices B, C and D were observed in 6%, 40% and 54% of patients, respectively. Improvement was observed in 30% of patients treated with ATG. Skin disease was more likely to improve with ATG (79%), while progression of gut and liver aGVHD was observed in 40% and 66% of patients, respectively. Despite initial improvement, 52 patients (90%) died a median of 40 days after ATG therapy from progressive aGVHD and/or infection (74%), ARDS (15%), or relapse (11%). Only six patients (10%), three of whom had aGVHD limited to the skin at the time ATG was administered, are long-term survivors. We conclude that initial improvement of SR aGVHD occurs with ATG in a minority of patients, and very few patients become long-term survivors. Furthermore, this treatment is associated with a high rate of major complications.

Actuarial Analysis↗

Growth factor regulation of the novel class II phosphoinositide 3-kinases.

It is well established that the class-I phosphoinositide (PI) 3-kinases play a crucial role in growth factor signalling pathways. However, evidence has recently emerged that the alpha isoform of the class-II PI 3-kinase (PI 3K-C2alpha) is activated by growth factors, although the consequences of this are poorly understood. Here we demonstrate that the activation of PI 3K-C2alpha is not associated with a change in subcellular localization. Furthermore, we provide the first evidence that PI 3K-C2beta is activated by insulin, albeit with slower kinetics than activation of PI 3K-C2alpha. These findings suggest that both these class-II PI 3-kinase isoforms are likely to participate in insulin-signalling pathways in the cell.

Animals↗