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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 343 records · Page 19Linked to original sources

Antegrade colonic enemas.

Thirteen children aged 6-14 (mean 8) years in whom an antegrade colonic enema procedure was performed were reviewed retrospectively. All presented with refractory constipation or faecal soiling over a 3-year period. Nine of the children had previously undergone pull-through procedures for Hirschsprung's disease or high anorectal malformations. Two were suffering from spina bifida and two from idiopathic functional constipation. The operation was performed through a right iliac fossa incision. A catheterizable conduit was created. The appendix was brought out to the wound edge and made continent by intussuscepting the appendix base into the caecum. When the appendix was absent or unusable, a caecal tube was formed. Five patients suffered minor morbidity, six required a further operative procedure and two eventually required a sigmoid colostomy. However, the eventual outcome of a continent stoma was attained in 11 of the 13 children, all of whom would have been considered for sigmoid colostomy before introduction of the antegrade colonic enema procedure.

Adolescent↗

Inhibition of human plasma and serum butyrylcholinesterase (EC 3.1.1.8) by alpha-chaconine and alpha-solanine.

The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.

Butyrylcholinesterase↗

Hepatic influence on pulmonary neutrophil sequestration following intestinal ischemia-reperfusion.

Intestinal ischemia-reperfusion (I/R) causes a myriad of systemic physiologic derangements including pulmonary neutrophil (PMN) sequestration, increased microvascular permeability, and adult respiratory distress syndrome. It has been suggested that the observed lung injury is mediated by transhepatic passage of portal venous blood from ischemic intestine resulting in hepatic Kupffer cell activation and cytokine secretion. The purpose of this investigation was to test the hypothesis that PMN sequestration and microvascular permeability reflect Kupffer cell activity and/or portal venous blood flow. Experiments were designed to independently test the contribution of (1) Kupffer cell activity and (2) portal venous blood flow. In the first set of experiments, Kupffer cells were eliminated by treatment with gadolinium chloride 10 mg/kg iv (KC-ablated, n = 11). Control rats were treated with saline (KC-intact, n = 10). Intestinal ischemia was induced by SMA occlusion for 2 hr followed by 2 hr of reperfusion. In additional studies, the liver was excluded from the circulation by creation of a complete portosystemic shunt (portal vein to right femoral vein; shunt, n = 23). Control rats were treated by insertion of a loop of tubing within the intact portal vein (sham, n = 23). Intestinal ischemia was induced by SMA occlusion for 15 min followed by reperfusion for 1-3 hr. In both models, lung PMN accumulation and pulmonary microvascular permeability were assessed by myeloperoxidase (MPO) activity and 125I-albumin lung/blood ratio (AL/BR), respectively. Kupffer cell elimination had no effect on PMN accumulation (MPO: KC-intact 29 +/- 8 vs KC-ablated 26 +/- 5 delta A/min/g; P = NS) or microvascular permeability (AL/BR: KC-intact 0.22 +/- 0.01 vs KC-ablated 0.23 +/- 0.03; P = NS). Hepatic exclusion also had no effect on either PMN accumulation or permeability after reperfusion for 1 hr (MPO: sham 38 +/- 12 vs shunt 42 +/- 14 delta A/min/ g; AL/BR: sham 0.24 +/- 0.02 vs shunt 0.23 +/- 0.03; P = NS), 2 hr (MPO: sham 27 +/- 5 vs shunt 29 +/- 7 delta A/min/g; AL/ BR: sham 0.29 +/- 0.02 vs shunt 0.26 +/- 0.05; P = NS), or 3 hr (MPO: sham 24 +/- 12 vs shunt 32 +/- 7 delta A/min/g; AL/ BR: sham 0.33 +/- 0.03 vs shunt 0.33 +/- 0.01; P = NS). In this animal model, pulmonary PMN sequestration and microvascular permeability following intestinal I/R are independent of hepatic portal blood flow and Kupffer cell activity.

Animals↗

Ethylene receptor expression is regulated during fruit ripening, flower senescence and abscission.

Using the Arabidopsis ethylene receptor ETR1 as a probe, we have isolated a tomato homologue (tETR) from a ripening cDNA library. The predicted amino acid sequence is 70% identical to ETR1 and homologous to a variety of bacterial two component response regulators over the histidine kinase domain. Sequencing of four separate cDNAs indicates that tETR lacks the carboxyl terminal response domain and is identical to that encoded by the tomato Never ripe gene. Ribonuclease protection showed tETR mRNA was undetectable in unripe fruit or pre-senescent flowers, increased in abundance during the early stages of ripening, flower senescence, and in abscission zones, and was greatly reduced in fruit of ripening mutants deficient in ethylene synthesis or response. These results suggest that changes in ethylene sensitivity are mediated by modulation of receptor levels during development.

Amino Acid Sequence↗

Peanut bud necrosis tospovirus S RNA: complete nucleotide sequence, genome organization and homology to other tospoviruses.

The complete nucleotide sequence of the S RNA of peanut bud necrosis virus (PBNV) has been determined. The RNA is 3 057 nucleotides in length, contains inverted repeats and two open reading frames (ORFs) with an ambisense coding strategy that are separated by an A+U-rich intergenic region. One ORF (1 320 nucleotides in the viral sense strand) encodes a Mr 49.5 kDa protein, identified as the nonstructural (NSs) protein based on similarity to published tospovirus sequences. The second ORF (831 nucleotides in virus complementary strand) encodes a Mr 30.6 kDa protein. This protein was identified as the nucleocapsid (N) protein based on sequence similarities. Amino acid sequence comparison of N and NSs proteins revealed identities of 22-34% with the reported tospovirus isolates of serogroups I, II, and III, whereas it had 82-86% identity with viruses in serogroup IV, watermelon silver mottle virus (WSMV) and tomato isolate of peanut bud necrosis (PBNV-To). Two subgenomic RNA species detected in PBNV infected tissue corresponded to the predicted sizes (1.65 and 1.4 kb) of the NSs and N mRNAs. The data presented show conclusively that PBNV should be included in serogroup IV, along with WSMV and PBNV-To.

Amino Acid Sequence↗

Thermosensitive transfer of antimicrobial resistances and citrate utilization and cotransfer of hydrogen sulfide production from an Escherichia coli isolate.

A hydrogen-sulfide producing, citrate-positive strain of Escherichia coli isolated from urinary tract infection was found to be resistant to chloramphenicol (Cm), tetracycline (Tc), streptomycin (Sm), trimethoprim (Tmp), sulfamethoxazole (Smx), and cotrimoxazole (Tmp/Smx). The strain contained 7 plasmids of molecular sizes 120, 35, 5.0, 3.2, 3.0, 2.6, and 2.4 megadaltons (Md), as detected by agarose gel electrophoresis of plasmid DNA. Thermosensitive transfer of Cm, Tc, and citrate utilization occurred conjugally to E. coli K-12 recipient strains at a frequency of approximately 10(-6) per donor cell after an 18 hour incubation. The transconjugants were also resistant to Sm and Smx and produced hydrogen-sulfide. Two plasmids of about 120 Md, pNH222, and 35 Md, pNH223, were detected in these transconjugants. Transformation or 1-hour conjugal transfer experiments at 26 degrees C with selection for Cm or Tc yielded only the 120 Md species. Plasmid pNH222 showed one way incompatibility with F plasmids, a characteristic shown previously to be typical of Inc HI1 plasmids. Transformation experiments with selection for Sm yielded transformants with one plasmid species, (pNH223), 35 Md in size, which carried the gene(s) for H2S production but not for raffinose fermentation. The fact that characteristics such as citrate utilization and hydrogen sulfide production, used in the identification of enteric bacteria, can be transmitted to E. coli by plasmids is of important taxonomic significance.

Anti-Bacterial Agents↗

Standardisation of a self-report questionnaire for use in evaluating cognitive, affective and behavioural side-effects of anti-epileptic drug treatments.

The development and standardisation of an inventory for measuring anti-epileptic drug effects on cognition and affect is described. The Side Effect and Life Satisfaction inventory (SEALS) was derived from symptoms and side-effects reported by a patient population. It was administered to 45 patients on two occasions and test-retest reliability was demonstrated. It was administered to 923 patients with epilepsy. An underlying factor structure was produced by principal components analysis, consisting of five sub-scales which were stable when data from males and females were analysed separately or together. Validity was evaluated by comparing inventory scores of patients undergoing a number of treatment trials to show that the inventory was sensitive to treatment differences when other variables were controlled. Patients taking two or more anti-epileptic drugs had poorer SEALS scores than those taking a single drug. Patients taking vigabatrin and one other AED had poorer scores than those taking lamotrigine (LTG) and one other AED. A comparison of changes from baseline to week 4 of a double blind comparison of carbamazepine (CBZ) and LTG showed significantly greater improvement in SEALS scores for patients taking LTG, and significantly poorer scores in those patients taking CBZ who dropped out of the study, than in those who continued. It is concluded that SEALS is a valid and reliable tool for use in anti-epileptic drug trials.

Adolescent↗

Endoscopic treatment of vesico-ureteric reflux in neurogenic bladder--8 years' experience.

During an 8-year period, 51 children with neurogenic bladder had endoscopic injection of Teflon (STING) for the management of 69 refluxing ureters. There were 21 boys and 30 girls (age range, 10 month to 16 years). Vesico-ureteral reflux (VUR) had been present for a mean of 4.1 years, and severity distribution was as follows: grade I, 1 ureter; grade II, 5 ureters, grade III, 9 ureters; grade IV, 39 ureters; and grade V, 15 ureters. The follow-up period ranged from 3 months to 8 years (mean, 4 years). Reflux ceased in 57 ureters (82%); in four ureters the VUR recurred (9 months to 6 years later). Bilateral vesico-ureteric junction (VUJ) obstruction occurred in one patient, which required surgical correction 3 years after STING. These data suggest that for difficult cases of VUR in neurogenic bladders, STING is a safe and effective option and should be the initial treatment of choice. However, because of the possibility of late recurrence of VUR or obstruction at the VUJ, long-term follow-up is required.

Adolescent↗

Defining the critical limit of oxygen extraction in the human small intestine.

Although animal models have been used to characterize the relation between oxygen consumption and blood flow, reliable data have not been generated in the human small intestine. We perfused segments of human small intestine by using an ex vivo perfusion circuit that allowed precise manipulation of blood flow and perfusion pressure. Our goal was to define the critical level of intestinal blood flow necessary to maintain the metabolic needs of the tissue. Human small intestine (n = 5) tissue obtained at transplantation harvest was transported on ice to the laboratory. A 40-cm mid-jejunal segment was selected for perfusion, and appropriate inflow and outflow vessels were identified and cannulated. Perfusion with an autologous blood solution was initiated through an extracorporeal membrane oxygenation circuit. After a 30-minute equilibration period, arterial and venous blood gases were measured at varying flow rates while maintaining a constant hematocrit level. Arterial and venous oxygen content, arteriovenous oxygen difference (A-VO2 diff), and oxygen consumption (VO2) were then calculated. Our results demonstrated that at blood flows > 30 ml/min/100 g, VO2 is independent of blood flow (1.6 +/- 0.06 ml/min/100 g), and oxygen extraction is inversely related to flow. Below this blood flow rate of 30 ml/min/100 g, oxygen extraction does not increase further (6.3 +/- 0.3 vol%), and VO2 becomes flow dependent. This ex vivo preparation defines for the first time a threshold value of blood flow for small intestine below which oxygen consumption decreases (30 ml/min/100 g). Previous animal studies have correlated such a decrease in oxygen consumption with functional and histologic evidence of tissue injury. This "critical" flow rate in human intestine is similar to that found previously in canine and feline intestine, but lower than that of rodent species.

Animals↗

Regulation of second messengers by the inositol polyphosphate 5-phosphatases.

The inositol polyphosphate 5-phosphatases are an enlarging family of enzymes that terminate the signals generated by the phosphoinositide kinases and phospholipase C. Given the diverse signalling functions of both the polyphosphoinositides and Ins(1,4,5)P3, it is predicted that the 5-phosphatases will play a critical role in regulating many cellular events, in particular membrane trafficking and cell growth.

Amino Acid Sequence↗

The effect of introducing guidelines for cervical spine radiographs in the accident and emergency department.

OBJECTIVE: To assess the effect of guidelines for x ray requests on requests for cervical spine x rays. SETTING: Accident and emergency (A&E) department of tertiary referral centre. METHODS: Guidelines for all x ray requests were introduced in the (A&E) department of the Royal Infirmary of Edinburgh in February 1992. The effect of the guidelines on requests for cervical spine x rays was assessed by retrospective review of all such x rays taken over two 30 d periods, before and after the introduction of the guidelines. Junior staff had been in post for 3 months during both periods assessed. Films were reviewed for quality by a consultant radiologist. RESULTS: Guidelines reduced the number of inappropriate requests significantly; however, 26% of requests were still unnecessary. The standard of radiography improved but 49% of x rays remained inadequate, usually because the C7/T1 level was not demonstrated on the lateral view. The A&E doctors correctly interpretated the radiographs in 95% of examinations. CONCLUSIONS: Guidelines reduce inappropriate x ray requests. Further improvements can be expected with continued education.

Cervical Vertebrae↗

Balancing act.

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Activities of Daily Living↗

[Physical 3-dimensional testing of the lumbar spine using the IsoStation B-200].

Low-back pain is not only one of the major medical problems, but the most common. Up to 80% of the population is expected to experience back pain at least once in their lifetime. The functional disability caused by LBP has a major influence on quality of life, as well as its economic aspects. Psychological and social factors are highly involved with LBP. Therefore any advance in objective assessment of LBP is of major importance. We present a relatively new system used for the past 2 years by our departments, the IsoStation B-200 (Isotechnologies Co., NC). This system enables simultaneous 3-D measurements of range of motion, speed of movement and torques in the lumbar back in a highly accurate and reproducible manner. The results are used to classify the status of LBP in terms of severity and disability. They enable us to assess quality of performance and to detect the "symptom magnification syndrome" (SMS), patients with non-physiologic complaints and behavior. We describe in detail the measurement protocol and the exact definitions and criteria used in the process of patient classification. Finally we present the results of our first 238 patients tested. A highly significant difference in almost all measured and calculated parameters was found between the patients with physiologic behavior and those with SMS or nonphysiological behavior. Findings related to all classifications are presented.

Biomechanical Phenomena↗

[Women in the medical profession in Israel].

This paper describes the current status of women physicians in Israel at various stages in their professional careers: in medical school, in the medical specialties and in academia. In the past, as in most western countries, medicine in Israel was regarded as a man's profession. The last decade has seen major demographic changes: the proportion of women entering medical school is now similar to that of men, and as a result of immigration from the former Soviet Union, the percentage of women physicians is approaching the level in eastern European countries. Recent findings show an increase in women in all specialty areas. However, they are concentrated in the lower status strata and in primary care, occupying the base of the academic pyramid. It appears that when objective criteria are employed, such as for admission to medical school and licensing examinations, women and men have similar levels of achievement. However, when subjective criteria are used, such as in admission to residency training, gender-based differences in distribution in the medical specialties are apparent. We suggest implementing objective standards for acceptance for residency training which should help equalize the status of women in the Israeli medical establishment.

Emigration and Immigration↗

Human CD8 transgene regulation of HLA recognition by murine T cells.

A series of human CD8 transgenic (hCD8 Tg) mice with differential expression in the thymus and periphery were produced to investigate CD8 coreceptor regulation of repertoire selection and T cell responses. Expression of hCD8 markedly enhanced responses to both HLA class I molecules and hybrid A2/Kb molecules providing functional evidence for a second interaction site, outside of the alpha 3 domain, which is essential for optimal coreceptor function. Peripheral T cell expression of hCD8 was sufficient to augment responsiveness to HLA class I, as hCD8 Tg mice which lacked thymic expression responded as well as mice expressing hCD8 in the thymus and periphery. Both murine CD8+ and CD4+ T cells expressing hCD8 transgenes exhibited markedly enhanced responses to foreign HLA class I, revealing the ability of T cell receptor repertoires selected on either murine class I or class II to recognize human class I major histocompatibility complex (MHC). In contrast to recognition of foreign class I, thymic expression of hCD8 transgenes was absolutely required to enhance recognition of antigenic peptide restricted by self-HLA class I. Thus, our studies revealed disparate requirements for CD8 coreceptor expression in the thymus for selection of a T cell repertoire responsive to foreign MHC and to antigenic peptides bound to self-MHC, providing a novel demonstration of positive selection that is dependent on human CD8.

Amino Acid Sequence↗

Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification.

OBJECTIVE: To quantify changes in size and severity of myocardial perfusion abnormalities by positron emission tomography (PET) in patients with coronary artery disease after 5 years of risk factor modification. DESIGN: Randomized controlled trial. SETTING: Outpatient community setting. INTERVENTION: Randomization of patients to risk factor modification consisting of very low-fat vegetarian diet, mild to moderate exercise, stress management, and group support (experimental group, n = 20) or to usual care by their own physicians, consisting principally of antianginal therapy (control group, n = 15). MAIN OUTCOME MEASURES: Quantitative coronary arteriography and PET at baseline and 5 years after randomization. Automated, objective measures of size and severity of perfusion abnormalities on rest-dipyridamole PET images and of stenosis severity on arteriograms were made by computer algorithms. RESULTS: Size and severity of perfusion abnormalities on dipyridamole PET images decreased (improved) after risk factor modification in the experimental group compared with an increase (worsening) of size and severity in controls. The percentage of left ventricle perfusion abnormalities outside 2.5 SDs of those of normal persons (based on 20 disease-free individuals) on the dipyridamole PET image of normalized counts worsened in controls (mean +/- SE, + 10.3% +/- 5.6%) and improved in the experimental group (mean +/- SE, -5.1% +/- 4.8%) (P = .02); the percentage of left ventricle with activity less than 60% of the maximum activity on the dipyridamole PET image of normalized counts worsened in controls (+13.5% +/- 3.8%) and improved in the experimental group (-4.2% +/- 3.8%) (P = .002); and the myocardial quadrant on the PET image with the lowest average activity expressed as a percentage of maximum activity worsened in controls (-8.8% +/- 2.3%) and improved in the experimental group (+4.9% +/- 3.3%) (P = .001). The size and severity of perfusion abnormalities on resting PET images were also significantly improved in the experimental group as compared with controls. The relative magnitude of changes in size and severity of PET perfusion abnormalities was comparable to or greater than the magnitude of changes in percent diameter stenosis, absolute stenosis lumen area, or stenosis flow reserve documented by quantitative coronary arteriography. CONCLUSIONS: Modest regression of coronary artery stenoses after risk factor modification is associated with decreased size and severity of perfusion abnormalities on rest-dipyridamole PET images. Progression or regression of coronary artery disease can be followed noninvasively by dipyridamole PET reflecting the integrated flow capacity of the entire coronary arterial circulation.

Adult↗