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Biomedical subjects

S W Moore

Publications and source records attributed to S W Moore.

At least 19 recordsLinked to original sources

Anti-acetylcholinesterase antibodies display cholinesterase-like activity.

A monoclonal antibody (mAb) raised against human acetylcholinesterase (AChE) was found to have catalytic activity. A similar phenomenon was observed in a polyclonal antibody raised against the same antigen. The antibodies were demonstrated to be pure, and no contamination with either AChE or butyrylcholinesterase was found. Both antibodies hydrolyzed acetylthiocholine, an AChE substrate, and the mAb followed Michaelis-Menten kinetics. Six other mAb and one other polyclonal antibody showed no evidence of catalytic activity. This development of cholinesterase-like behavior by certain anti-AChE antibodies may have arisen by stable complexation of the enzyme with a substrate or inhibitor during antigen presentation. This phenomenon may have implications for the diagnostic measurement of AChE activity as well as in assessing the immunological reasons for the markedly raised AChE level in developmental conditions such as Hirschsprung's disease.

Acetylcholinesterase

Reducing polypharmacy in extended care.

In this 5-year prospective study, we determined the feasibility of reducing polypharmacy in a long-term care institution by a systematic review of the pharmacy records. At 6-month intervals, the computer printout of all medications prescribed to patients in a 550-bed institution was reviewed. After patients taking more than 10 different drugs were identified, their physician was notified and was asked to review their medications according to specific guidelines. The number of patients taking 10 or more medications was reduced from 67, when the program was started, to 9. The average number of medications per patient was reduced from 5.5 to 4.6. This program reduced the prevalence of polypharmacy and had long-lasting effects on the physicians' prescribing habits. We also believe it led to improved patient care by reducing the potential for drug interactions and to cost savings for the pharmacy.

Aged

The dorsal involuting marginal zone stiffens anisotropically during its convergent extension in the gastrula of Xenopus laevis.

Physically, the course of morphogenesis is determined by the distribution and timing of force production in the embryo and by the mechanical properties of the tissues on which these forces act. We have miniaturized a standard materials-testing procedure (the stress-relaxation test) to measure the viscoelastic properties of the dorsal involuting marginal zone, prechordal mesoderm, and vegetal endoderm of Xenopus laevis embryos during gastrulation. We focused on the involuting marginal zone, because it undergoes convergent extension (an important and wide-spread morphogenetic process) and drives involution, blastopore closure and elongation of the embryonic axis. We show that the involuting marginal zone stiffens during gastrulation, stiffening is a special property of this region rather than a general property of the whole embryo, stiffening is greater along the anteroposterior axis than the mediolateral axis and changes in the cytoskeleton or extracellular matrix are necessary for stiffening, although changes in cell-cell adhesions or cell-matrix adhesions are not ruled out. These findings provide a baseline of data on which future experiments can be designed and make specific, testable predictions about the roles of the cytoskeleton, extracellular matrix and intercellular adhesion in convergent extension, as well as predictions about the morphogenetic role of convergent extension in early development.

Animals

A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis.

BACKGROUND: It is uncertain whether patients with proximal deep-vein thrombosis should be treated with streptokinase followed by intravenous heparin or with intravenous heparin alone. Published reports indicate that streptokinase plus heparin increases the risk of bleeding, including central nervous system bleeding and death, but decreases the risk of postphlebitic syndrome. Previous recommendations regarding these treatments have not considered patients' preferences or the values they attach to the possible outcomes of therapy. METHODS: We used decision analysis to combine published estimates of the probabilities of various adverse outcomes of treatment (bleeding, pulmonary embolism, postphlebitic syndrome, and death) with the values patients placed on these outcomes. We questioned 36 patients about the values they attached to each outcome. Sixteen patients had had deep-vein thrombosis, and 20 had not. RESULTS: By the values they attached to the outcomes, all 36 patients indicated that they were unwilling to accept an increased risk of death to avoid postphlebitic syndrome. According to the decision analysis, heparin alone was the better treatment for all 36 patients. As compared with streptokinase plus heparin, heparin alone provided 29 days of additional life expectancy over the predicted life expectancy of 20 years. Although the difference between the two treatments was small, heparin alone remained the better treatment in sensitivity analyses that examined the reasonable ranges of probabilities of the clinical outcomes. CONCLUSIONS: The values patients placed on the outcomes of treatment for deep-vein thrombosis support the use of heparin alone over the combined use of streptokinase and heparin.

Cerebral Hemorrhage

Conservative initial treatment for liver abscesses in children.

A total of 124 children aged less than 14 years with a liver abscess were seen in a 16-year period (1974-1990) and treated by non-operative initial management. Of the abscesses 98 occurred in the right liver and 26 in the left. The abscesses were solitary in 93 patients. Overall, 77 of the solitary and 21 of the multiple abscesses were confined to the right liver. In 78 of the right-sided and 20 of the left-sided abscesses the infection was primarily pyogenic in nature with Staphylococcus aureus being the usual organism cultured. The remainder were of amoebic origin. Clinical features were similar in patients with amoebic and pyogenic abscesses. Clinical and ultrasonographic follow-up demonstrated successful non-operative management and healing in 37 per cent of all patients submitted to an initial protocol of medical supportive care and antibiotic therapy. Of the multiple abscesses 60 per cent responded to non-operative management. Fourteen of the 16 solitary left-sided liver abscesses required drainage and three left-sided abscesses ruptured before drainage. Patients with a solitary left-sided abscess warrant early operative intervention.

Anti-Bacterial Agents

Long-term clinical, manometric, and histological evaluation of obstructive symptoms in the postoperative Hirschsprung's patient.

One hundred seventy-eight of 326 patients had surgery for Hirschsprung's disease at Red Cross Children's Hospital (1957 to 1990) agreed to participate in a recall follow-up study. Assessment of the postoperative outcome of the Swenson, Duhamel, and Soave procedures included manometric evaluation in 43 patients by perfused-tube and balloon-series techniques. Rectal suction biopsies were performed for patients who had persistent problems with stool evaluation. One hundred fifteen of the 178 patients were more than 4 years of age, and long-term functional outcome could be assessed. Although good results were obtained in 94% overall, 16 had clinical evidence of a degree of persisting obstruction. Results of manometric assessment of anorectal function in these patients were not significantly different from those of 28 patients who had normal stool evacuation. A biopsy was performed in 14 of the 16 patients who had symptoms of obstruction postoperatively, and abnormal histological features were noted. There was aganglionosis in four, features of neuronal intestinal dysplasia in nine, ganglioneuromatosis of the colon in one. The results of two biopsies were entirely normal. Implications of postoperative dysfunction after surgery for Hirschsprung's disease are discussed, and a protocol for investigation and management is proposed.

Child, Preschool

Fenestrated duodenal membranes: an analysis of symptoms, signs, diagnosis, and treatment.

Duodenal obstruction typically occurs in the ampullary region and presents in the early neonatal period. If the obstruction is incomplete, as with a fenestrated duodenal membrane, the presentation may be delayed and the diagnosis overlooked. Sixteen patients with fenestrated duodenal membranes presented over a 23-year period. Six presented in the neonatal period, with vomiting; an abdominal x-ray was diagnostic in four. Ten presented later (5 weeks to 14 years) with nonspecific symptoms, ie, failure to thrive, postprandial epigastric distension, and recurrent chest infections. Vomiting occurred in all, but was of short duration (< 1 week). Two patients in the delayed group had Down's syndrome. Diagnosis was confirmed on barium meal, and optimal surgical treatment was a bypass duodeno-duodenostomy. The diagnosis of fenestrated duodenal membrane must be considered in all cases with symptoms and signs suggestive of upper gastrointestinal tract obstruction, and excluded by contrast radiology.

Adolescent

A histological grading system for the evaluation of co-existing NID with Hirschsprung's disease.

The significance of dysplastic features in the surgical pullthrough segment of bowel in patients with Hirschsprung's disease (HD) has not yet been clarified. The aim of this study was to evaluate prospectively the ganglionated proximal bowel in 26 patients with HD (January 1988 through January 1991). The significance of dysplastic features and their influence on post operative outcome were evaluated by means of a newly devised histological scoring system based on the morphological features. Functional outcome was assessed clinically at follow-up interview. Comparison was with control specimens from 22 patients undergoing unrelated bowel surgery and a further 5 patients with neuronal intestinal dysplasia (NID). Results indicated a wide spectrum of histologically identified dysplastic features in patients with NID, the ganglionated bowel of HD and controls. Although individual abnormal features were noted in the control group, significant degrees of dysplasia were absent. The overall degree of dysplasia was less striking than that observed in NID and in the 5 patients in whom NID co-existed with HD. Dysplasia of the ENS in residual bowel could be correlated with postoperative dysfunction in 4 out of 5 patients (80%) with HD and features of co-existing NID. In addition, milder symptoms were noted in 50% of patients having a borderline score (5-6/12). This study emphasizes the relationship between clinical obstructive symptoms and a high degree of dysplasia within the ENS. A histological grading system is of value in evaluating the spectrum of abnormal findings and prospectively identifying those with functional significance in patients with NID co-existing with HD.

Acetylcholinesterase

A fiber optic system for measuring dynamic mechanical properties of embryonic tissues.

Dynamic mechanical properties of embryonic tissues, including viscoelasticity and active motility, play a major role in morphogenesis. Mechanical abnormalities resulting from altered cytoskeletal chemistry presumably contribute to spina bifida and other birth defects, but research in this area has been limited by inadequate mechanical measurement techniques. This paper discusses aspects of embryo tissues that make them difficult to measure and describes a versatile new system developed and used to study the biomechanics of morphogenesis in amphibian embryos. It incorporates a flexible optical-fiber probe driven by piezoceramic elements to impose and measure feedback-controlled, two-dimensional, time-varying patterns of stress or strain in the tissue. Compression, tension, and shear geometries are possible. Capacitive displacement sensors provide the precision and low drift rates required for these measurements. Software control permits the system to perform both standard and customized rheological tests, including interactive ones in which test parameters change in response to measured tissue behavior. Sample size range is 50 microns to 5 mm. Displacement range is 60 microns with a resolution of 0.1 microns. Force range is 10 microN with a resolution of 0.02 microN. Frequency range is DC to 20 Hz.

Amphibians

Left-sided liver abscess in childhood.

Abscesses occur less frequently on the left side of the liver than on the right, and are implicated in a higher incidence of complications. Of a total of 124 children with liver abscesses seen at Red Cross War Memorial Children's Hospital from 1974 to 1990, 26 had left-sided and 98 right-sided lesions. A similar spectrum of organisms was cultured, and 20 (77%) of the left-sided abscesses were found to be caused by pyogenic organisms as opposed to 78 (79%) of those on the right. The remainder were of amoebic origin. In 5 patients with multiple abscesses involving predominantly the left side of the liver, the right side was also involved. These were excluded from further comparison of left and right liver abscesses. Of the remainder, 16 (62%) left-sided and 77 (83%) right-sided abscesses were solitary. Clinical features were similar in both groups but epigastric mass was more frequent in left-sided lesions. After an initially conservative management policy, surgical drainage was necessary in 87.5% of solitary left-sided liver abscesses as opposed to 64% of solitary right-sided abscesses. No intrapericardial ruptures were noted, but 2 pericardial effusions required drainage. There was no mortality but 3 patients with solitary left-sided abscesses ruptured. The important role of ultrasound in the diagnosis and follow-up period is stressed. Patients with solitary left-sided abscesses are identified as being at risk. Abscess drainage is recommended in this group.

Child

Secondary effects of prolonged intestinal obstruction on the enteric nervous system in the rat.

Motility disturbances following prolonged intestinal obstruction have been attributed to secondary effects. This study aimed to demonstrate the effects of incomplete obstruction on the enteric nervous system (ENS) of a rat model. Surgical placement of a nonstrangulating ligature encircling the distal bowel was performed in 41 freshly weaned rats. Anesthetic protocol included Ketamine, ether, or Xylazine (an alpha 2-adrenergic agonist). Histological evaluation was by ganglion cell morphology, histochemical staining for acetylcholinesterase (AChE) and tyrosine hydroxylase (TOH) immunocytochemistry. Forty-one freshly weaned LE rats were divided into controls (8), sham procedures (8), intestinal obstruction (16), and a group of rats with colonic biopsy performed prior to and following experimental obstruction (9). The rats were sacrificed at periods varying between 14 and 45 days post experimental obstruction (median survival, 27 days). Histological changes included elongation of ganglion cells and a decrease in the number per 5-mm slide in obstructed animals. No other obstruction specific differences were detected. A significant (P < .01) increase in AChE in the submucous plexus was recorded in Xylazine-anesthetized animals. No obstruction-specific effects could be demonstrated in the ENS, suggesting that prolonged obstruction without ischemia does not result in any significant alterations in the ENS. Pharmacological stimulation of the alpha 2-adrenergic receptor appeared to result in an increase in AChE. This mechanism may help to explain a possible role for the adrenergic system in the increased AChE levels in affected bowel in patients with Hirschsprung's disease.

Acetylcholinesterase

Degenerative leiomyopathy in African children: a review of current perspectives.

The syndrome of degenerative leiomyopathy causing intestinal obstruction clinically manifests in young indigenous African children as massive megacolon without aganglionosis. Eighteen children have been seen over a 16 year period from a localized geographic area. There were 10 males and 8 females having a mean age of 9.5 years at presentation and a mean duration of symptoms of 4.3 years. The youngest was 6 months old. All had progressive abdominal distension and infrequent stooling but 11 had intermittent diarrhoea and 9 had colicky abdominal pain. Gross gaseous distension of the large bowel with extension into small intestine occurred in 9 and this extended into stomach and oesophagus in 4. Biopsy of the dilated, thin walled bowel showed smooth muscle degeneration and necrosis with replacement by fibrous tissue. Neuronal cells of Auerbach's plexus tend to be displaced into the circular layer of smooth muscle with mild inflammatory changes. Some small arteries show medial fibrosis with subintimal fibroblastic proliferation. Acetylcholinesterase and immunohistochemical staining with neural and muscle markers are within normal limits. One child died while 14 have been maintained on prokinetic agents, low residue diets, laxatives and enemas. Nine children have required surgical intervention of whom 4 had volvulus and 3 adhesive bowel obstruction. Degenerative leiomyopathy is a distinctive entity with classical clinical and histological features. The aetiology is still obscure.

Biopsy

Is tube cecostomy safe in the surgery of Hirschsprung's disease?

The use of concomitant tube cecostomy remains an option for decompression after distal large-bowel surgery but has been criticised because of a reported high complication rate. Two hundred and three patients who underwent a Soave endorectal pull-through procedure for Hirschsprung's disease (1974-1990) were evaluated. Operative technique included a modified sutured Soave endorectal pull-through procedure and a Stamm tube cecostomy utilising a large-lumen catheter. One hundred and twenty patients who had a modified two-stage procedure plus concomitant tube cecostomy were compared with 83 patients who underwent a three-stage procedure with colostomy cover. Early postoperative complications occurred in 8 patients (6.6%) in whom cecostomies were performed. A distal cuff abscess developed in 1 patient (0.8%), an anastomotic leak in 1 (0.8%) and 3 patients (2.5%) had colo-anal stenosis. The cecostomy tube dislodged in 2 patients and 1 required operative closure of a faecal fistula at the cecostomy site. Colonic venting was adequate and little nursing care was required. In 2 instances colonic distension developed after cecostomy clamping. Decompression was achieved by opening the cecostomy tube; this resulted in relief of symptoms and a good subsequent recovery. In contrast, there were 11 postoperative complications in the 83 patients undergoing a three-stage procedure (13.2%). In 2 patients (2.4%) an anastomotic leak occurred and 5 distal cuff abscesses (6%), 3 (3.6%) early strictures and 1 (1.2%) neorectal retraction developed. The use of a concomitant tube cecostomy with a two-stage Soave procedure is an effective and safe means of providing proximal colonic venting and did not add to mortality or morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cecostomy

Familial aspects of Hirschsprung's disease.

Twenty-eight of 370 patients (14 families) treated for Hirschsprung's disease (HD) over a 34 year period had a family member with histologically proven HD. These 14 represented 4% of the 351 families: more than one affected child per family in 10 (2.8%) and both parent and child in 2 families. Neuronal intestinal dysplasia (NID) in a parent was associated with total colonic aganglionosis in two siblings of one family which suggests a similar genetic inheritance pattern to HD. Aganglionosis extended beyond the rectosigmoid in 61% of the familial group as opposed to 27% of the non-familial group. A significantly higher number of total colonic aganglionosis (TCA) was noted in those with a family history; 11 out of 28 (39%) as opposed to 19 out of 342 (5.6%) without a family history (p less than 0.001). Fifty percent of males with TCA had a family history but in only 2 cases was this transmitted through a female sibling. Although no significant difference was noted between male and female probands, a three times higher incidence of familial occurrence was noted in females with rectosigmoid disease than in males. Progression of length of segment in succeeding generations was noted in two families. Associated anomalies occurred in 16% without familial occurrence and 11% of the familial group.

Adult

Ultrasonic features of pyogenic and amoebic hepatic abscesses.

Pyogenic liver abscesses are not infrequent in some developing countries. Amoebic abscesses may also occur in endemic areas and differentiation may be difficult. The ultrasonic data of proven cases of both conditions were compared and we are now more more confident in predicting the aetiology of these lesions.

Child

Variable speech control vs Varispeech: does newer mean better?

Normal-hearing volunteers (N:30, aged 19-28 yrs) yielded intelligibility scores for W-22 word lists and CID sentences at 40 db re each S's SRT, and judgments on a 7-pt scale ("very pleasant"----"very unpleasant") for Sentence 3 of Fairbanks' "Rainbow Passage". Normal and time-altered speeds (60%: compression; 140%: expansion) were compared between the widely-used but obsolescent Lexicon Varispeech (VSp) unit vs the commercially available Variable Speech Control Model A-7 which incorporates a time-sampling technique similar to the VSp. With both VSp and VSC, intelligibility was nearly perfect at all three speeds, and thus both appear equally suitable for intelligibility studies, but at the 60% and 140% speeds the signal clarity was significantly preferable for the VSp system (p less than .01 in both cases), by .6 of a scale interval at 60% and 1.8 interval at 140%. Furthermore, the VSC does not operate beyond the 60-140% range, as occasionally may be desirable in research on the effects of time alteration on speech reception.

Adolescent