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Biomedical subjects

H Brown

Publications and source records attributed to H Brown.

At least 109 records · Page 6Linked to original sources
PubMed1994

Genetically modified keratinocytes transplanted to wounds reconstitute the epidermis.

Normal and retrovirally transfected keratinocyte suspensions expressing either the beta-galactosidase gene or the human growth hormone (hGH) gene were transplanted into chamber-enclosed skin full-thickness wounds of Yorkshire pigs. Immunostaining of sequential skin biopsies obtained for 4 weeks after transplantation showed survival of the transplanted keratinocytes as well as expression of beta-galactosidase. Transfected keratinocytes were first seen in the neodermal portions of the wounds, then in the regenerating basal epidermal layer, and finally in the terminally differentiating cells of the stratum spinosum. When keratinocytes transfected with the hGH gene were transplanted into similar wounds, hGH was detected for 10 days in wound fluid. In contrast, hGH was detected in vitro for 47 days. Wounds transplanted with either transfected or normal keratinocytes restored the epithelial barrier function significantly faster than nontransplanted controls (P < 0.05). The study confirms the successful transplantation of keratinocyte suspensions, their reconstitution of the epidermis, and their acceleration of repair. Further, this apparently normal incorporation of genetically engineered transplanted keratinocytes expressing either beta-galactosidase or hGH suggests the possibility of introducing other genes expressing therapeutic proteins into wounds to favorably affect healing. Wound fluid detection of the expressed peptide provided early demonstration of successful transfer of the hGH gene.

Animals↗
PubMed1994

Validity of Euroqol--a generic health status instrument--in patients with rheumatoid arthritis. Economic and Health Outcomes Research Group.

The main aim of this pilot study was to test the 'construct' validity of Euroqol, a new generic health status instrument which consists of a questionnaire and visual analogue scale. Its ability to measure both current health status and change in health status was assessed in 55 patients with RA. The Euroqol questionnaire and visual analogue scales showed significant and clinically relevant correlations with other condition-specific instruments measuring loss of function, joint pain, joint tenderness and mood; change in these symptoms as measured by the condition-specific instruments was also predictive of change in Euroqol scores. Either component of the Euroqol instrument provide an index of current clinical status and these data provide preliminary evidence for the 'construct' validity of Euroqol in RA. Further work is needed to evaluate more fully the sensitivity of Euroqol to change over time.

Adolescent↗
PubMed1994

Simultaneous quantitation of facial movements: the maximal static response assay of facial nerve function.

An assay is described that enables the simultaneous measurement of bilateral facial movements within zones relevant to facial nerve function. The assay allows the accurate quantitation of movement of the eyebrows, radix, lower eyelids, philtrum, mentum, and oral commissures relative to these points on the resting face. Global or region-specific facial nerve dysfunction is detectable using this assay, as shown in examples of patients having single branch facial nerve palsy and bilateral facial palsy (Möbius syndrome variant). Because facial movement is tested by region, with the remainder of the face relaxed, synkinesis can be detected when present. The assay has potential to be used as an adjunct to the presently used ordinal scales of facial nerve function, by allowing actual quantitation of region-specific facial movement. This feature may prove helpful in vector planning for reanimation procedures and may allow the tracking of functional responses after such procedures, thereby providing a measurement of their efficacy.

Adult↗
PubMed1994

Measurement of the extravascular concentration of renal agents following intravenous bolus injection.

The extravascular concentration (Ce) of some renal agents, in relation to the simultaneous plasma concentration (Ci), was calculated as a function of time after intravenous injection. Four agents were studied: 51Cr-ethylenediamine tetraacetate (EDTA) (n = 11), 125I-hippuran (n = 11), 99Tcm-dimercaptosuccinic acid (DMSA) (n = 11) and 99Tcm-mercaptoacetyl triglycine MAG3 (n = 20). Plasma clearance curves were constructed from data acquired from multiple blood sampling and fitted with two exponentials. The extravascular content of tracer at any time is equal to the injected dose remaining after subtraction of the intravascular tracer content and the total amount of tracer cleared from plasma. Mean Ce/Ci at equilibrium (defined as the time, > 120 min, when Ce/Ci reaches its maximum value) was 1.087 (S.D. 0.019) for EDTA, 1.73 (0.48) for hippuran, 0.37 (0.2) for DMSA and 0.64 (0.3) for MAG3. Corresponding clearance (F) values were 68 (13), 415 (149), 15.6 (9.5) and 214 (52) ml min-1 1.73 m-2. Ce/Ci correlated with F and was also related to protein binding in plasma. Extrapolation of the regressions of Ce/Ci on F to F = 0 at several time points after injection gives a curve of Ce/Ci (at F = 0) against time which represents the rate of equilibration of the tracer throughout its distribution volume that would be seen with zero clearance, and therefore allows measurement of the in vivo protein binding of the tracer in plasma. Protein binding was zero for EDTA, 30% for hippuran, 86% for DMSA and 88% for MAG3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

'Alarming but very necessary': working with staff groups around the sexual abuse of adults with learning disabilities.

This study focused on the knowledge of front line staff, as individuals and in groups, in relation to the sexual abuse of adults with learning disabilities and was designed to inform staff training and policy initiatives and to explore gender dynamics. It showed that front line staff were alert to the possibility of sexual abuse but unclear about their roles and responsibilities making this an area of great concern to them. One third knew of people who had been abused but these had been dealt with haphazardly, leaving front line staff holding disproportionate anxiety on behalf of the service as a whole.

Adult↗
PubMed1994

Endobronchial urokinase for dissolution of massive clot following transbronchial biopsy.

Endobronchial streptokinase has been used previously to dissolve blood clots caused by massive spontaneous hemoptysis, in settings including sarcoidosis, cavitary histoplasmosis, and multiple myeloma. To our knowledge, however, the use of thrombolytic agents to dissolve clots following transbronchial biopsy has not been reported previously. We describe a patient in whom endobronchial urokinase was used for successful dissolution of clots secondary to massive bleeding after transbronchial biopsy.

Biopsy↗
PubMed1993

Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9.

Virulence of the human malaria parasite Plasmodium falciparum is believed to relate to adhesion of parasitized erythrocytes to postcapillary venular endothelium (asexual cytoadherence). Transmission of malaria to the mosquito vector involves a switch from asexual to sexual development (gametocytogenesis). Continuous in vitro culture of P. falciparum frequently results in irreversible loss of asexual cytoadherence and gametocytogenesis. Field isolates and cloned lines differing in expression of these phenotypes were karyotyped by pulse-field gel electrophoresis. This analysis showed that expression of both phenotypes mapped to a 0.3-Mb subtelomeric deletion of chromosome 9. This deletion frequently occurs during adaptation of parasite isolates to in vitro culture. Parasites with this deletion did not express the variant surface agglutination phenotype and the putative asexual cytoadherence ligand designated P. falciparum erythrocyte membrane protein 1, which has recently been shown to undergo antigenic variation. The syntenic relationship between asexual cytoadherence and gametocytogenesis suggests that expression of these phenotypes is genetically linked. One explanation for this linkage is that both developmental pathways share a common cytoadherence mechanism. This proposed biological and genetic linkage between a virulence factor (asexual cytoadherence) and transmissibility (gametocytogenesis) would help explain why a high degree of virulence has evolved and been maintained in falciparum malaria.

Agglutination↗
PubMed1993

Can simultaneous ambulatory blood pressure and activity monitoring improve the definition of blood pressure?

In this study we measured activity and sleep time, using a wrist actigraph, in a population of 319 patients referred for ambulatory blood pressure monitoring (ABPM). Mean waking and sleeping blood pressure (BP) and the diurnal BP variation derived with this technique were compared to daytime (defined variously as 7 AM to 8 PM, 7 AM to 10 PM, or 7 AM to midnight) and nighttime pressure. To study the relationship of actigraph-derived activity data to BP variability in more detail, 30 patients underwent paired monitoring 1 to 18 (mean 8) days apart. Mean waking BP was then corrected for activity to determine whether this technique could improve reproducibility. Statistically but not clinically significant differences between waking and daytime BP were seen, with larger and potentially clinically relevant differences between sleeping and nighttime BP. The midnight to 7 AM time period gave the best estimate of observed sleeping time and the nocturnal dip of BP. The average correlation between activity and BP was 0.25 for systolic and 0.34 for diastolic BP, but with wide variation in the strength of the relationship both between and within individual patients. On average, activity accounts for 20% of systolic and 26% of diastolic BP variation. Correcting the mean waking BP to a standard activity level reduced within-patient variation by 6%/9%. This made no significant difference to overall reproducibility, perhaps because variability in this sample was low before adjustment, with the standard deviation of the difference equal to 8/4 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1992

Correlation of bronchial eosinophil and mast cell activation with bronchial hyperresponsiveness in children with asthma.

Bronchial hyperresponsiveness in asthma has been associated with increased numbers of eosinophils and mast cells in the bronchial airway. It is unclear if these cells are important in the pathogenesis of hyperresponsiveness, and the role of mast cells has been discounted because they are effectively stabilized by beta-adrenergic drugs. Because the pathogenesis of asthma in children may be different from that in adults, and to find out if cellular activation is associated with bronchial reactivity, we studied 17 children with mild to moderately severe chronic asthma who had been treated with intermittent brochodilator therapy and compared their bronchial responsiveness to histamine with the levels of eosinophil cationic protein and mast cell tryptase in broncholavage fluid. The number of eosinophils in lavage fluid was correlated with histamine responsiveness (r = -0.444, p < 0.05) but not with levels of cationic protein (r = 0.33, p = NS). Bronchial responsiveness to histamine was highly correlated with mast cell tryptase (r = -0.714, p < 0.005), but there was no correlation with eosinophil cationic protein (r = -0.355, p = NS). We conclude that in children with chronic asthma mast cells as well as eosinophils contribute to bronchial hyperresponsiveness. Activated mast cells may play a primary role, possibly by tryptase-induced upregulation of bronchial smooth muscle tone.

Adolescent↗
PubMed1992

Paracentral rheumatoid corneal ulceration. Clinical features and cyclosporine therapy.

Six patients with rheumatoid arthritis (eight eyes) presented with small paracentral perforating corneal ulcers in otherwise quiet eyes. Initial management in five patients (seven eyes) consisted of systemic immunosuppression and therapeutic tissue adhesive with a bandage contact lens or tectonic keratoplasty. Ulceration recurred in all of these eyes, and recurrent ulcers treated with repeat tectonic keratoplasty or therapeutic tissue adhesive and a bandage contact lens all developed recurrent ulceration. The introduction of topical cyclosporine therapy in five eyes with recurrent corneal ulceration was associated with arrest of keratolysis and rapid re-epithelialization of the ulcer in all cases. One corneal ulcer was successfully treated initially with topical cyclosporine, tissue adhesive, and a bandage contact lens. In patients with rheumatoid arthritis and small paracentral corneal ulcerations or perforations, application of tissue adhesive and a bandage contact lens and introduction of topical cyclosporine may be the preferred initial treatment.

Aged↗
PubMed1991

The effect of in vivo glutathione depletion with buthionine sulfoximine on rat embryo development.

Glutathione is an abundant endogenous nucleophile whose depletion may have adverse effects on a number of cellular processes, including protein and DNA synthesis, amino acid transport, and detoxification of reactive electrophiles. Previous studies have indicated that a certain basal level of glutathione is essential for normal development in vitro in the whole rat embryo culture system. The objective of this study was to determine the effect of glutathione depletion with buthionine sulfoximine on the development of rat embryos in vivo. Timed pregnant Sprague-Dawley rats were treated by gavage on days 10 and 11 of gestation with saline (control) or with L-buthionine-(S,R)-sulfoximine (4 or 8 mmol/kg). Pregnancy outcome was assessed on day 12 or day 20 of gestation. The glutathione content of embryos and of maternal organs was measured on day 12. Glutathione concentrations were significantly decreased in the embryos and in maternal muscle and ovary but not in maternal liver and kidney. Glutathione depletion, when assessed on day 12 of gestation, was found to result in an increase in the numbers of dead and malformed embryos. Treatment with the higher dose of buthionine sulfoximine resulted in the death of 13.2% of the total implanted embryos; of the surviving embryos, 21.7% were malformed. There was also a significant decrease on day 12 after treatment with the higher dose of buthionine sulfoximine in the embryonic total morphological score, a measure of the developmental stage of the embryos (control, 57.7 +/- 1.0; 8 mmol/kg buthionine sulfoximine, 52.8 +/- 1.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man.

1. The effects of the subcutaneous administration of a long-acting somatostatin analogue (octreotide) or of placebo on the splanchnic blood flow response to a mixed solid meal has been examined in eight normal subjects by using a transcutaneous Doppler ultrasound technique. Each subject was studied on two occasions more than 1 week apart. 2. On the control day, feeding had a pronounced effect on both superior mesenteric artery and portal venous blood flows, causing a peak rise of 82% in superior mesenteric artery blood flow at 15 min and of 75% in portal venous blood flow at 30 min post-prandially (P less than 0.001). Blood flows remained elevated 2 h after the meal. Pulse and blood pressure showed no significant changes from baseline. 3. Octreotide reduced fasting superior mesenteric artery blood flow by 59% (P less than 0.05) and portal venous blood flow by 49% (P less than 0.01) and blunted the normal post-prandial rise. Pulse and blood pressure did not change in response to either the injection or the ingestion of the meal. 4. Octreotide suppressed the release of insulin, glucagon and pancreatic polypeptide in response to feeding and resulted in post-prandial hyperglycaemia. 5. The mechanism of action of octreotide on splanchnic blood flow is uncertain. It may be mediated via a direct vascular effect or it may act via suppression of vasoactive intestinal hormones.

Adult↗