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Biomedical subjects

J N Thompson

Publications and source records attributed to J N Thompson.

At least 109 records · Page 6Linked to original sources

Peritoneal fibrinolytic activity and intra-abdominal adhesions.

The mechanisms leading to reduction of peritoneal fibrinolytic activity in conditions that are associated with the formation of intra-abdominal adhesions were studied. Tissue plasminogen activator was found, by antibody inhibition techniques, to be the activator of fibrinolysis in homogenates of control peritoneum (n = 6). Homogenates of control (n = 10) and inflamed peritoneum (n = 10) were analysed. Plasminogen activating activity was much lower in inflamed peritoneum (median 0.07 IU/cm2) than in control tissue (median 12.0 IU/cm2) (p less than 0.001). Levels of tissue plasminogen activator and alpha 2-antiplasmin were similar in both control and inflamed tissue. Plasminogen activator inhibitor-1, not detectable in control peritoneum, was present in inflamed tissue and might be the reason for the reduction in functional fibrinolytic activity.

Abdomen↗

Parental age in the blepharophimosis, ptosis, epicanthus inversus, telecanthus complex.

Maternal and paternal age and birth order of 14 sporadic cases of the autosomal dominant blepharophimosis-ptosis-epicanthus inversus-telecanthus (BPEI) phenotype were compared to similar statistics from control individuals. Correlation coefficients were determined for paternal age and incidence, maternal age and incidence, and birth order and incidence. The partial correlation coefficient of the father's age and incidence with maternal age and birth order held constant was -0.02 and that for the mother's age and incidence with paternal age and birth order held constant was 0.57. Maternal age seems to have a stronger influence than the paternal age in this group of BPEI patients.

Abnormalities, Multiple↗

Evaluation of fine catheter aspiration cytology of the peritoneum as an adjunct to decision making in the acute abdomen.

Fine catheter aspiration cytology of the peritoneal cavity was performed successfully in 61 patients admitted with acute abdominal pain. Aspirates were examined microscopically and the percentage of neutrophils in the specimen counted. In patients in whom the clinical need for operation was certain (n = 25) all patients required surgery and the peritoneal neutrophil count was greater than 50 per cent. In patients in whom the clinical need for operation was uncertain (n = 36) 19 patients required operation: the peritoneal neutrophil count was greater than 50 per cent in 18 and in one patient with ectopic pregnancy fresh blood was aspirated. Of the 17 patients not requiring operation the peritoneal neutrophil count was less than 10 per cent in 15 and greater than 50 per cent in two patients (both had acute pelvic inflammatory disease). This study confirms peritoneal cytology as a useful adjunct to decision making in those patients with acute abdominal pain in whom the decision to operate is in doubt.

Abdomen, Acute↗

N-acetylglucosamine-6-phosphate deacetylase in hepatocytes, Kupffer cells and sinusoidal endothelial cells from rat liver.

The activity of N-acetylglucosamine-6-phosphate deacetylase, a key enzyme in the pathway of N-acetylglucosamine catabolism, was measured in hepatocytes, Kupffer cells and sinusoidal endothelial cells from rat liver and cultured human skin fibroblasts. Kupffer cells and endothelial cells had similar high levels of deacetylase activity that were more than twice the level observed in fibroblasts. In contrast, hepatocytes had extremely low activity (several hundredfold less than Kupffer cells and endothelial cells). A major implication of deacetylase deficiency in hepatocytes is that N-acetylglucosamine generated as a result of the catabolism of complex carbohydrates in these cells cannot enter glycolysis and must be largely reused for the synthesis of plasma glycoproteins and other N-acetylglucosamine-containing macromolecules.

Amidohydrolases↗

Sarcoidosis of the upper respiratory tract in patients with nasal rim lesions: a pilot study.

Lupus pernio has been associated with sarcoidosis of the upper respiratory tract. The semantic differences in the use of the designation "lupus pernio" are such that American dermatologists may not consider patients with nasal rim papules of sarcoidosis to have lupus pernio. During a 12-month period, we referred each new patient with sarcoidosis and nasal rim lesions for direct and indirect laryngoscopy. Three of our four patients had sarcoidosis of the upper respiratory tract. We recommend a large prospective study to assess the incidence of this disorder in patients with nasal rim lesions of sarcoidosis. Until such a study is undertaken, however, we believe that consideration should be given to otolaryngologic examination of these patients, regardless of their symptoms.

Adult↗

Quantitative morphometric analysis of brain growth using magnetic resonance imaging.

Using a simple image analysis system, we have established normative data obtained from magnetic resonance imaging (MRI) scans for the relative size and growth of the major structural domains of the brain. Midsagittal scans of the head were analyzed in 95 subjects aged 0 to 20 years. Only scans with no demonstrable structural abnormalities of the brain were utilized. Age-related changes in the relative growth of specific structures were calculated by dividing patients into 5-year age increments. No age-related changes were found in the size of the posterior fossa, supratentorial intracranial space, or cisterna magna relative to the total intracranial vault space. A significant (P less than .01) increase in the size of the corpus callosum relative to that of the supratentorial structures and relative to the total intracranial vault space was noted to occur between the 6- to 10-year-old and 11- to 15-year-old age groups. This may reflect an increase in myelination of the corpus callosum that occurs during this period. A small reduction in the ratio of the posterior fossa to the supratentorial space was found between the 0- to 5-year-old and the 6- to 10-year-old age groups, but the biological significance of this difference is uncertain. It appears from these data that quantitative analysis of MRI scans can be used to draw objective conclusions about the relative sizes and growth of the major brain structures. The development of normative data for these structures and the simplicity of the methodology should have many clinical applications in the assessment of aberrant brain development.

Adolescent↗

A screening method for mucopolysaccharidoses with increased urinary excretion of sulfated N-acetylhexosamines.

Patients with mucopolysaccharidosis have been reported to excrete elevated amounts of sulfated N-acetylhexosamines in their urine. Based on this finding, a new and simple colorimetric screening test for these disorders is presented. Chromatography of whole urine on Dowex AG 1-X8, from each of 23 normal controls, 5 patients with mucopolysaccharidosis and one patient with multiple sulfatase deficiency, was used to separate the sulfated hexosamines. The fractions eluted with 2M NaCl were analyzed according to the method of Reissig. Patients with Sanfilippo syndrome, type A, Sanfilippo syndrome, type D, Maroteaux-Lamy syndrome, Morquio syndrome, type A, and multiple sulfatase deficiency were clearly distinguished from normal controls. The procedure appeared most sensitive for Sanfilippo syndrome, type D, and multiple sulfatase deficiency, each of which involves deficient activity of N-acetylglucosamine 6-sulfate sulfatase.

Chromatography, Ion Exchange↗

Questionnaire identification of surgical patients at risk of HIV infection.

The prevalence of human immunodeficiency virus (HIV) infection is increasing. Risks of hospital transmission, though small, will consequently also increase. Precautions taken during invasive procedures, particularly surgery, and in the handling of specimens from patients diminish this risk. As HIV antibody screening is not permissible, we have assessed the possible efficacy of a routine questionnaire to identify high-risk groups. Of 525 questionnaires given to routine surgical patients, 506 (96%) were completed. Twenty-eight (5.5%) indicated that they were in a high-risk group. High-risk patients were more likely to present with anorectal disease, to be male and to be young compared with patients from the remainder of the sample. The questionnaire was acceptable to 97% of patients although to a significantly smaller number (82%) of high-risk patients. Routine HIV antibody testing would be acceptable to 88% of low-risk patients but to only 60% of high-risk patients. Questionnaire assessment is an acceptable and perhaps more reliable method of assessing HIV risk status than the other currently available options. It has to be accepted that it will never result in complete identification but we recommend this method as one approach to the problem faced by the surgical team.

Adolescent↗

Enzymic pathways of hyaluronan catabolism.

The enzymic degradation of hyaluronan in mammalian tissues takes place in two phases, encompassing breakdown of the polysaccharide to its monosaccharide constituents and subsequent utilization of the monosaccharide products. Degradation to the monosaccharide components is effected by the concerted action of three enzymes, hyaluronidase, beta-D-glucuronidase and beta-N-acetyl-D-hexosaminidase. The relative contributions of hyaluronidase and the two exoglycosidases to the physiological catabolism of hyaluronan are not yet known but consideration of the kinetic properties of the three enzymes clearly indicates that hyaluronidase is best suited for the initial attack on the polysaccharide, inasmuch as its Km for hyaluronan is 1000- to 10,000-fold lower than that estimated for beta-D-glucuronidase. Recent investigations in the authors' laboratories have been focused on the catabolism of hyaluronan and other complex carbohydrates in liver, since the sinusoidal endothelial cells in this organ are the main sites for degradation of circulating hyaluronan. Assay of ten lysosomal hydrolases in isolated rat liver cells showed considerably higher activities in Kupffer cells and endothelial cells than in hepatocytes for nine of the enzymes, including beta-D-glucuronidase and beta-N-acetyl-D-hexosaminidase. The activity of N-acetylglucosamine-6-phosphate deacetylase, a key enzyme in the metabolism of the N-acetylglucosamine released by the lysosomal degradation of hyaluronan and other complex carbohydrates, has also been determined. High deacetylase activities were observed in both Kupffer cells and endothelial cells but, surprisingly, virtually no activity was detected in hepatocytes. This finding implies that N-acetylglucosamine cannot be degraded in hepatocytes and must be largely reutilized in the synthesis of new macromolecules. Further studies of the enzymes involved in hyaluronan degradation and N-acetylglucosamine utilization in the liver are under way.

Animals↗

Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation.

A unifying pathophysiological hypothesis states that the plasminogen activating activity (PAA) of the peritoneal mesothelium determines whether the fibrin which forms after peritoneal injury is either lysed or organized into permanent fibrous adhesions. The PAA of human peritoneal biopsies was measured using a fibrin plate lysis technique to assess the changes that occur in inflammation and ischaemia, conditions which both produce fibrous adhesions. Activity was found in all biopsies from normal parietal and visceral (appendix, bowel and omentum) peritoneum with no significant site-to-site variation. Inflamed peritoneum (parietal, appendicular and mesenteric) had significantly less PAA compared with normal peritoneum; visceral ischaemia also resulted in a significant decrease of PAA. These reductions in human peritoneal PAA observed in inflammation and ischaemia support the view that mesothelial PAA plays a key part in the prevention of events leading to the production of fibrous adhesions.

Appendicitis↗

Clinical decision making and laparoscopy versus computer prediction in the management of the acute abdomen.

A prospective study has been undertaken of 321 patients with acute abdominal pain admitted to hospital under one surgical firm over a period of 21 months. During the first 10 months patients were classified on admission according to the perceived need for operation, with laparoscopy being performed on all those in whom the need for operation was uncertain. In addition, all women with suspected appendicitis underwent laparoscopy because previous studies by us and others have demonstrated a high error rate in this group. During the second 11 months of the study a similar system of classification and procedure was used but the patient's initial assessment was entered on a structured data sheet. After the patient had been discharged home this information was entered into a computer-aided diagnosis program. Hypothetical retrospective computer-aided decisions were then made about patient management. The final management error rate (correct decision to operate or not) was compared with the actual error rate using the clinical system. The final overall error rate in the first 10 months was 11 out of 163 patients and this was improved to 3 out of 158 in the second 11 months of the study by the addition of the structured data sheet to selective laparoscopy. A management policy based entirely on diagnostic probabilities taken from the computer-aided diagnosis program would have produced an error rate of 26 out of 158. We conclude that in the management of the acute abdomen a policy based on clinical decision combined with selective laparoscopy may be superior to one based on diagnostic probabilities alone. Further improvement in results follows the introduction of a structured data sheet for initial data collection.

Abdomen↗

Sanfilippo syndrome, type D: a spectrophotometric assay with prenatal diagnostic potential.

Sanfilippo syndrome, type D (MPS IIID), is characterized by moderate physical abnormalities, progressive mental deterioration, and deficient activity of N-acetylglucosamine 6-sulfate sulfatase, a lysosomal hydrolase involved in the degradation of heparin, keratan sulfate, and heparan sulfate. To date, demonstration of the enzyme deficiency typically relies on a radiolabeled trisaccharide substrate derived from heparan sulfate. In our study, we have developed a spectrophotometric assay for the determination of N-acetylglucosamine 6-sulfate sulfatase activity using the monosaccharide, N-acetylglucosamine 6-sulfate, as substrate. The reaction mixture was incubated for 6 h at 37 degrees C and, after Dowex chromatography, released N-acetylglucosamine was measured by a modification of the method of Reissig. Assay conditions were optimized for cultured skin fibroblasts and primary cultures of amniotic fluid cells. The pH optimum for each was 5.5. The assay was linear for 24 h and up to 0.1 absorbance units. Activities of the three known MPS IIID skin fibroblast cell lines were more than 4 SD below the skin fibroblast control mean and more than 5 SD below the control mean for amniotic fluid cells. An enzyme deficiency in cultured amniotic fluid cells of the same magnitude as the skin fibroblasts of the known patients would be detectable and, therefore, prenatal diagnosis by this method is feasible.

Amniotic Fluid↗

The perioperative changes in glomerular filtration and renal blood flow in patients with obstructive jaundice.

Experimental alterations in renal haemodynamics have been observed in obstructive jaundice and these may be the pathophysiological mechanism of increased renal susceptibility to injury in obstructive jaundice. Dynamic 99mTc-DTPA renal scintigraphy was done before and eight weeks after elective hepatobiliary surgery in six patients with obstructive jaundice (bilirubin greater than 100 mumol/l) and in six non-jaundiced control patients to assess changes in glomerular filtration and renal blood flow. Glomerular filtration was lower preoperatively in the jaundiced patients than in the control patients. Glomerular filtration increased postoperatively in jaundiced patients, but decreased in control patients. Renal blood flow was reduced postoperatively in control patients, but not in jaundiced patients. The changes in renal blood flow were different for each group of patients. These results provide clinical evidence of altered renal haemodynamics and a reversible impairment of glomerular filtration in obstructive jaundice. The changes seen in renal blood flow may be the underlying mechanism of increased renal susceptibility to injury.

Adult↗