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Biomedical subjects

D J Brown

Publications and source records attributed to D J Brown.

At least 19 recordsLinked to original sources

A study of the alpha-1 adrenoceptor blocker prazosin in the prophylactic management of autonomic dysreflexia in high spinal cord injury patients.

The ability of the alpha-1 adrenoceptor antagonist, prazosin, to reduce the severity and duration of episodes of autonomic dysreflexia was studied in cervical and high thoracic spinal cord injury patients with documented episodes of autonomic dysreflexia. Sixteen patients participated in a double blind parallel group study comparing prazosin 3 mg b.d. with placebo given for 2 weeks. Both groups were matched for age, sex and baseline severity of autonomic dysreflexia episodes. Prazosin was well tolerated and did not produce a significant lowering of resting blood pressure. Compared to baseline measurements, patients allocated to prazosin therapy were found to have fewer severe episodes of autonomic dysreflexia and during these episodes to have significant reductions in average rise in systolic and diastolic blood pressure, symptom duration and requirement for acute antihypertensive medication. The severity of headache during individual autonomic dysreflexia episodes was also diminished with prazosin therapy. No symptom parameter was significantly altered by placebo therapy. It is concluded that prazosin is superior to placebo in the prophylactic management of autonomic dysreflexia and that these findings are consistent with suggestions that alpha-1 adrenoceptors play an important role in the pathogenesis of this syndrome.

Adolescent

Salmonella enterica: infection, cross infection and persistence within the environment of a broiler parent stock unit in Denmark.

A total of three hundred and ninety nine isolates of Salmonella enterica were recovered from 3106 cloacal swab cultures, chicken carcasses and environmental samples taken from a broiler breeding farm over six successive generations. S. enterica serovars Berta (S. Berta), 4,12:b:-, Taksony, Binza and Typhimurium were identified. One hundred and seventy one strains of S. Berta were analysed by plasmid profiling to determine the epidemiological relationships between isolates from each generation and from each house section of the production unit. All isolates contained plasmids; plasmids of eleven different molecular weights were identified. Eighteen different plasmid profiles were identified throughout the observation period. An increase in the diversity of plasmid profiles in each successive generation, the restriction of particular plasmids to particular houses and their persistence within that house were taken to indicate that contamination within the unit was due to persistence and cross-infection rather than to a reintroduction of serovar Berta into new generations of stock.

Animals

Biochemical and molecular characterization of Salmonella enterica serovar berta, and comparison of methods for typing.

Strains of Salmonella enterica serovar berta (S. berta) from Denmark and seven other countries have been characterized with the aim of developing a rational typing strategy in connection with outbreak investigations. Biotyping divided the strains into H2S-positive (90%) and H2S-negative (10%) biovars. Six percent of the strains were resistant to one or more antimicrobial agents. Eighty-eight percent of the strains carried plasmids and 52 different plasmid profiles were recognized. Six of the common plasmid sizes in these profiles were shown by restriction enzyme analyses to contain more than one plasmid species. More than 90% of the strains had the same ribotype with the restriction enzymes Sma I and EcoR I and the same whole cell protein profile. Outer membrane protein profiles and isoenzyme profiles were identical in all S. berta analysed. Plasmid profiling in combination with restriction enzyme analysis of plasmids seemed to be the most rational typing strategy for S. berta. The results indicated that S. berta strains regardless of geographical source or host are possibly clonal in nature.

Animals

Suicide following acute traumatic spinal cord injury.

The rate of suicide following spinal cord injury has not been extensively studied but appears to be greater than in the general population. Six patients who died by suicide, from a total of 342 patients who were treated for acute spinal cord injury over a 5 year period are described. Clinical features shared by this group of patients included being male; having schizoid, depressive or narcissistic personality traits; alcohol or drug abuse; family or significant others favouring death as a preferred option; and the development of significant depression.

Acute Disease

Electrical stimulation of the lumbrical muscles in an incomplete quadriplegic patient: case report.

The increasing number of incomplete cervical spinal cord injuries means that more attention needs to be focused on the rehabilitation of the incomplete quadriplegic hand. A case study, describing the application of electrical stimulation for strengthening the paretic lumbrical muscles, is presented. A 2 week strengthening program resulted in a 33% increase in the force produced by the lumbrical muscles. No loss of strength had occurred 4 weeks after cessation of the treatment. The magnitude and speed of this result should be of interest to those clinicians who seek to maximise patient independence in minimal time.

Adult

Cardiovascular and vasoactive hormone responses to bladder distension in spinal and normal man.

Many patients with high spinal cord injury experience exaggerated blood pressure rises in response to bladder distension. To examine the humoral mechanisms associated with these responses, ECG heart rate, blood pressure and vasoactive hormone levels were measured at baseline and during bladder distension following slow bladder filling in 23 subjects: 9 high spinal lesion patients, 7 low spinal lesion patients and 7 normal control subjects. Systolic blood pressure rose significantly during bladder distension in the high spinal lesion group by an average of 56 mm Hg (48%) and diastolic blood pressure rose by 22 mm Hg (47%), while heart rate fell by a mean of 7.4 beats per minute (15%). By contrast, neither systolic or diastolic blood pressure nor heart rate changed significantly during bladder distension in the low spinal lesion or normal control group. There were no significant changes in plasma levels of noradrenaline, renin, aldosterone, vasopressin, arginine, or atrial natriuretic peptide during bladder distension to account for the blood pressure rise in the high spinal lesion group. These findings suggest that humoral mechanisms are unlikely to play a major role in the mediation of pressor responses to bladder distension in high spinal lesion patients.

Blood Pressure

Risk factors for cardiovascular disease in chronic spinal cord injury patients.

To establish whether the reported increased cardiovascular (CV) morbidity in spinal cord injury (SCI) patients is due to increased levels of established CV risk factors, we assessed overall CV risk in 102 consecutive patients aged 25-64 by calculation of a 'risk factor score' (RFS) derived from the MRFIT study (age, diastolic blood pressure (DBP), total cholesterol (TC) level, cigarettes/day, sex), obtaining a percentile position amongst an age and sex matched peer group from the 1983 Australian Risk Factor Prevalence Study. Chronic SCI patients had a very low overall percentile position of risk of 26.03 + 15.06 (mean +/- S.D.) and those patients with SCI for greater than 10 years had only a slightly higher risk position of 33.16 +/- 29.66. The low relative risk in SCI patients was due mainly to significantly lower DBP levels (67 +/- 13 mm hg), as TC levels (5.38 +/- 1.60 mmol/L) and cigarette consumption (31% smokers, mode 11-20/day) were similar to the control population (83 +/- 12 mmHg, 5.68 +/- 1.2 mmol/L, 28% smokers, mode 11-20/day, respectively). As other known risk factors such as lipoprotein cholesterol fractions were not included in the RFS index, these were measured in 327 consecutive SCI patients. HDL cholesterol levels, which are negatively correlated with CV risk, were significantly lower in SCI patients (1.12 +/- 0.30 mmol/L) compared to controls (1.35 +/- 0.35 mmol/L) and those patients more than 10 years post SCI had still lower levels (1.02 +/- 0.40). These data suggest that the reported increased incidence of CV disease in SCI patients is unexplained by increases in BP, TC or smoking. However, low HDL levels may contribute to CV risk and the role of other risk factors such as increased vascular reactivity remain to be established.

Adult

Nutritional evaluation of the trypsin (EC 3.4.21.4) inhibitor from cowpea (Vigna unguiculata Walp.).

The effect of feeding rats purified cowpea (Vigna unguiculata Walp.) trypsin (EC 3.4.21.4) inhibitor in a semi-synthetic high-quality diet based on lactalbumin (10 g inhibitor/kg) for 10 d was a moderate reduction in the weight gain of rats in comparison with controls, despite an identical food intake in the two groups. The reduction in the growth rate was about 20% on a live weight basis. However, the corresponding value calculated from the weight of dry carcasses was less, only about 7%, probably because the water content of the body of the two groups of rats was different. Although most of the cowpea trypsin inhibitor (CpTI) was rapidly broken down in the digestive tract, its inclusion in the diet led to a slight, though significant, increase in the nitrogen content of faeces but not of urine. Accordingly, the net protein utilization of rats fed on inhibitor-containing diets was also slightly depressed while their energy expenditure was elevated. In agreement with results obtained for the protease inhibitors of soya bean, the slight anti-nutritional effects of CpTI were probably due mainly to the stimulation of the growth and metabolism of the pancreas. Thus, the nutritional penalty for increased insect-resistance after the transfer of the cowpea trypsin inhibitor gene into food plants is slight in the short-term.

Animals

Pressor dose responses and baroreflex sensitivity in quadriplegic spinal cord injury patients.

OBJECTIVE: To assess the relative contribution of impaired baroreceptor reflexes and enhanced cardiovascular reactivity to the exaggerated blood pressure rises which occur in quadriplegic spinal cord injury patients with automatic hyperreflexia. DESIGN: Pressor dose responsiveness was evaluated by determining the steady-state dose of phenylephrine, alpha-methylnoradrenaline and angiotensin II required to achieve a blood pressure rise of 20 mmHg and the steady-state dose of isoprenaline required to increase heart rate by 20 beats/min in eight quadriplegic spinal cord injury patients and eight control subjects. RESULTS: The dose of phenylephrine alpha-methylnoradrenaline and angiotensin II to achieve a rise in blood pressure of 20 mmHg was significantly reduced in the spinal cord injury group, whilst the dose of isoprenaline required to raise heart rate by 20 beats/min did not differ significantly from the control group. Baroreceptor sensitivity, assessed by straight line regression of change in heart period with change in blood pressure during steady-state infusions of phenylephrine, did not differ statistically between the two groups, but the results could not exclude some evidence of impairment in the spinal cord injury patients. Baroreceptor sensitivity was much less variable in spinal cord injury patients than in controls. CONCLUSIONS: These findings suggest that quadriplegic patients with spinal cord injury have exaggerated pressor responses with significantly less variability in baroreflex sensitivity. The former probably contributes to the autonomic hyperreflexia seen in these patients. The latter provides some support to the suggestion that centrally mediated psychogenic responses contribute to the variability in baroreceptor sensitivity seen in normal subjects.

Adult

Plasmid profiles as an epidemiological marker in Salmonella enterica serovar berta infections. Comparison of isolates obtained from humans and poultry.

Plasmid profiles of 674 Salmonella berta strains isolated in the period 1985-1989 from 674 cases of human infections were recorded. Five hundred and eighty-nine of the strains examined (87.4%) contained plasmids and the mean number of plasmids was 1.8 per strain. Sixteen different plasmid sizes were recognized, 13 of which had also been reported from S. berta of poultry origin. The plasmids formed 90 different profiles. Forty-five of these profiles, comprising 90.7% of isolates, had previously been recorded among poultry strains. Only 12 human isolates (1.8%) carried plasmids which were not demonstrated among isolates obtained from broilers. The prevalences of the 20 most commonly demonstrated profiles were not significantly different among isolates obtained from humans and broilers. The average difference between the prevalences of individual plasmid profiles was 2.1, with a standard deviation of 4.2. Based on the results, indications are that broilers represent the main reservoir for human S. berta infections in Denmark.

Animals

Psychiatric consultation in a spinal injuries unit.

The function of a consultation liaison service to a spinal injuries unit is described. Within this context, a study was conducted in which sociodemographic and clinical data were collected over a 4 year period for consecutive admissions to the unit. Data are presented for 227 patients admitted during this period. Forty-seven patients were found to have discrete psychiatric disorders (DSM III) which required treatment during the course of their inpatient care. For forty-two of these patients the psychiatric disorder first developed following spinal cord injury.

Activities of Daily Living

N.m.r. determination of the solution conformation and dynamics of the A.G mismatch in the d(CGCAAATTGGCG)2 dodecamer.

A.G base-paired mismatches that occur during replication are among the most difficult to detect by repair enzymes. Such purine.purine mispairs can exist in two conformations, one of which is stabilized by protons [Gao & Patel (1988) J. Am. Chem. Soc. 110, 5178-5182]. We have undertaken a 1H-n.m.r. and 31P-n.m.r. study of the mismatched dodecamer d(CGCAAATTGGCG)2 as a function of both temperature and pH to determine the conformational features of the A.G mismatch. At pH greater than 7 the mispaired bases are each in the anti conformation and are stacked in the B-like helix. As the pH is decreased, a second conformation becomes populated (apparent pKa approx. 5.9) with concomitant changes in the chemical shifts of protons of the mispaired bases and their nearest neighbours. Data from two-dimensional nuclear-Overhauser-enhancement spectroscopy show unequivocally that, at low pH, the dominant conformation is one in which the mismatched G residues are in the syn conformation and are hydrogen-bonded to the A residues that remain in the anti conformation. Residues not adjacent to the A.G sites are almost unaffected by the transition or the mispairing, suggesting considerable local flexibility of the unconstrained duplexes. Despite the bulging of the mispaired bases, the conformation of the A(anti).G(anti) duplex is very similar to the native dodecamer, whereas the AH+(anti).G(syn) duplex shows a greater variation in the backbone conformation at the mismatched site. According to the chemical shifts, the duplex retains twofold symmetry in solution. The equilibrium between the syn and anti conformations of G9/G21 is strongly dependent on pH, but only weakly dependent on temperature (delta H approx. 16 kJ.mol-1). The first-order rate constant for the transition is approx. 9 s-1 at 283 K and approx. 60 s-1 at 298 K, with an activation enthalpy of approx. 100 kJ.mol-1. The stabilization of the A(anti).G(syn) conformation by protons is consistent with models invoking N1 protonation of adenine. Using the derived glycosidic torsion angles we have used restrained molecular dynamics to build models of the neutral and protonated d(CGCAAATTGGCG)2 oligomers. The results confirm that the A(anti).G(anti) and AH+(anti).G(syn) conformations are favoured at high pH and low pH respectively, in accord with n.m.r. and single-crystal X-ray data.

Base Sequence