Biomedical subjects

A Duncan

Publications and source records attributed to A Duncan.

At least 91 records · Page 5Linked to original sources

PubMed1993

Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis.

BACKGROUND: Mercaptides (sodium hydrogen sulfide and sodium methanethiol) and mercapto-fatty acid (sodium mercaptoacetate) are reducing agents that help to maintain anaerobic conditions in the colonic lumen. The metabolic effect of these agents on n-butyrate and glucose oxidation in human colonocytes is unknown. METHODS: Isolated human colonocytes were prepared from 31 colectomy specimens, and generation of oxidative metabolites from [1-14C]n-butyrate and [6-14C]glucose was measured in the presence and absence of reducing agents. Injury to cells was judged by diminished production of metabolites. RESULTS: The injurious action of mercaptides at all sites of the colon was of the order of sodium hydrogen sulfide > methanethiol > mercaptoacetate. Significant inhibition of n-butyrate (< 0.005) but not glucose oxidation was observed with sodium hydrogen sulfide in the ascending colon, splenic flexure, and rectosigmoid region. Hydrogen sulfide more significantly inhibited fatty acid oxidation in the rectosigmoid than in the ascending colon (P < 0.02). CONCLUSIONS: Metabolic effects of sodium hydrogen sulfide on butyrate oxidation along the length of the colon closely mirror metabolic abnormalities observed in active ulcerative colitis, and the increased production of sulfide in ulcerative colitis suggests that the action of mercaptides may be involved in the genesis of ulcerative colitis.

Colitis, Ulcerative↗

PubMed1993

Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical basis for ulcerative colitis?

1. Isolated colonic epithelial cells of the rat were incubated for 40 min with [6-14C]glucose and n-[1-14C]butyrate in the presence of 0.1-2.0 mmol/l NaHS, a concentration range found in the human colon. Metabolic products, 14CO2, acetoacetate, beta-hydroxybutyrate and lactate, were measured and injury to cells was judged by diminished production of metabolites. 2. Oxidation of n-butyrate to CO2 and acetoacetate was reduced at 0.1 and 0.5 mmol/l NaHS, whereas glucose oxidation remained unimpaired. At 1.0-2.0 mmol/l NaHS, n-butyrate and glucose oxidation were dose-dependently reduced at the same rate. 3. To bypass short-chain acyl-CoA dehydrogenase activity necessary for butyrate oxidation, ketogenesis from crotonate was measured in the presence of 1.0 mmol/l NaHS. Suppression by sulphide of ketogenesis from crotonate (-10.5 +/- 6.1%) compared with control conditions was not significant, whereas suppression of ketogenesis from n-butyrate (-36.00 +/- 5.14%) was significant (P = < 0.01). Inhibition of FAD-linked oxidation was more affected by NaHS than was NAD-linked oxidation. 4. L-Methionine (5.0 mmol/l) significantly redressed the impaired beta-oxidation induced by NaHS. Methionine equally improved CO2 and ketone body production, suggesting a global reversal of the action of sulphide. 5. Sulphide-induced oxidative changes closely mirror the impairment of beta-oxidation observed in colonocytes of patients with ulcerative colitis. A hypothesis for the disease process of ulcerative colitis is that sulphides may form persulphides with butyryl-CoA, which would inhibit cellular short-chain acyl-CoA deHydrogenase and beta-oxidation to induce an energy-deficiency state in colonocytes and mucosal inflammation.

Animals↗

PubMed1993

The early effects of radioiodine therapy for hyperthyroidism on biochemical indices of bone turnover.

OBJECTIVE: We investigated the early changes following radioiodine therapy for hyperthyroidism, in biochemical indices of bone synthesis and degradation, and their relationship to circulating thyroid hormone concentrations. DESIGN: Prospective follow-up over the first 12 weeks after radioiodine therapy. PATIENTS: Six women with clinical and biochemical evidence of hyperthyroidism. MEASUREMENTS: Serum concentrations of T4, free T3 and osteocalcin, and urinary excretion of the pyridinium cross-links, pyridinaline and deoxypyridinaline, measured before and weekly for 12 weeks after administration of radioiodine therapy. RESULTS: Biochemical indices of bone metabolism were elevated prior to treatment. There was a brisk reduction in circulating thyroid hormones levels paralleled by a similar fall in pyridinium cross-link excretion, which had returned to normal in five patients by the end of the study. There was a positive correlation between pyridinium cross-link excretion and thyroid hormone concentrations. There was no significant change in serum osteocalcin. CONCLUSIONS: Treatment of hyperthyroidism results in prompt correction of the associated increased rate of bone collagen degradation suggesting that effective early correction of hyperthyroidism is desirable to limit its detrimental effect on skeletal mass.

Adult↗

PubMed1993

Elevated D dimer in the lungs and blood of patients with sarcoidosis.

The hypothesis of this study was that D dimer, a specific degradation product of cross-linked fibrin, would be increased in the bronchoalveolar lavage (BAL) fluids of patients with sarcoidosis and that it would be related to other BAL parameters of disease activity. Eight of 10 sarcoidosis patients but none of 18 healthy volunteers had detectable BAL D dimer by enzyme immunoassay. Autoradiography revealed the presence of fibrinogen and D dimer in the BAL fluids from sarcoidosis patients. Bronchoalveolar lavage D dimer levels in sarcoidosis patients correlated with total BAL cells per milliliter, lymphocytes per milliliter, and total protein level, but not macrophages per milliliter. The D dimer in the BAL fluids from sarcoidosis patients did not correlate with D dimer in the blood. Our findings indicate that BAL D dimer parallels directly the lymphocytic alveolitis that characterizes pulmonary sarcoidosis.

Adult↗

PubMed1993

Diffuse leiomyomatosis of the uterus with local pelvic spread.

The clinical and pathological findings of a case of diffuse leiomyomatosis of the uterus are described. The unique feature of this case is the extension of the disease process to the pelvic mesocolon. The diagnostic difficulties encountered in the histological assessment of smooth muscle tumors of the uterus are discussed.

Adult↗

PubMed1992

Automated analysis of the pyridinium crosslinks of collagen in tissue and urine using solid-phase extraction and reversed-phase high-performance liquid chromatography.

A fully automated method for assaying the collagen crosslinking amino acids, pyridinoline and deoxypyridinoline, in human urine samples or tissue hydrolysates is described. Samples were processed using a Gilson ASPEC system with solid-phase extraction of the crosslinks on columns containing 100 mg of microgranular cellulose. Introduction of an additional solvent step during sample preparation allowed direct analysis by reversed-phase HPLC and elimination of the drying step used previously in a manual method. Use of a synthetic pyridinoline derivative as internal standard enabled accurate quantification of the crosslinks by correcting for recoveries through the whole assay. Samples were analyzed in sequential mode with a total assay time of 30 min. The automated assay showed close correlation with the manual method for both free and total crosslink determinations in human urine (r > 0.97). Reproducibility was improved, as seen from replicate analyses of human urine (CV < 3% for automated pyridinoline measurement compared with 8-12% previously observed for the manual method). Crosslink excretion is the most useful marker of collagen degradation in metabolic bone diseases and arthritic disorders. The automated assay which has been developed is rapid, convenient, and reliable and will greatly facilitate the monitoring of urinary collagen crosslinks and their tissue levels in clinical investigations.

Amino Acids↗

PubMed1992

The relation of prothrombin times to coronary heart disease risk factors among men aged 31-45 years.

Although levels of coagulation factor VII and fibrinogen are predictive of cardiovascular disease, relatively little data describe hemostatic characteristics in healthy populations. The cross-sectional associations between the prothrombin time, a measure of the activity of the extrinsic and common pathways of coagulation, and traits associated with the risk of cardiovascular disease were therefore examined among 3,604 white and 514 black, male, US Army veterans aged 31-45 years. The prothrombin time measurements, performed in 1985 and 1986, were precise, with an intraclass correlation of 0.98 (202 pairs). Overall, the mean prothrombin time was 12.4 seconds (standard deviation, 0.4 seconds), and 11 percent of the men had a value of less than 12 seconds. Many of the observed associations with the prothrombin time paralleled those that have been reported with clotting factor VII and fibrinogen. The mean prothrombin time was 0.15 seconds shorter among whites than among blacks and was 0.2 seconds shorter among current cigarette smokers than among men who had never smoked. Inverse associations were also seen with relative weight and with levels of total cholesterol and triglycerides (r = -0.09 to -0.16). All associations were statistically significant at the 0.01 level, and the examined characteristics could jointly account for about 12 percent of the variability in prothrombin times. Additional data on characteristics related to coagulation may help elucidate the natural history of cardiovascular disease and aid in the design of clinical trials.

Adult↗

PubMed1992

Limitations of the triolein breath test.

Patients being investigated for intestinal absorptive capacity were classified as normals or malabsorbers on the basis of three fat absorption tests. Malabsorbers were further classified as mild, moderate, severe or gross according to severity of malabsorption. Using this classification system the triolein breath test was evaluated in 53 patients. Seventeen patients were excluded because their graph of percentage breath [14C]carbon dioxide versus time was exponential indicating that the peak [14C]-carbon dioxide may be occurring later than the six hour duration of the test. The sensitivity and specificity of the triolein breath test were found to be 100% and 96%, respectively and moderate correlations with the individual fat absorption tests were found. However, the breath test was limited in its capacity to predict the severity of malabsorption. Carbon dioxide output was also measured in order to determine the applicability of using an assumed value. The respiratory quotient and variability of results were high in nineteen patients indicating possible hyperventilation. In 32 patients with reproducible results and normal respiratory quotients the average carbon dioxide output was 8.66 mmol/kg per hour with a wide range of 5-12.4 mmol/kg per hour. Consequently the use of an assumed carbon dioxide output can introduce considerable errors in the triolein breath test. This study highlights drawbacks of the triolein breath test, particularly problems in using an assumed carbon dioxide output for its calculation, its inability to predict the severity of malabsorption and the nature of the dietary load used.

Adolescent↗

PubMed1992

Myelination of regenerated axons in goldfish optic nerve by Schwann cells.

This study uses immunohistochemistry and EM to examine the site of injury in goldfish optic nerve during axonal regeneration. Within seven days of nerve crush axons begin to regrow and a network of GFAP+ reactive astrocytes appears in the nerve on either side of the injury. However, the damaged area remains GFAP-. By 42 days after nerve crush, the sheaths of new axons acquire myelin marker 6D2, and the crush area becomes populated by a mass of longitudinally-orientated S-100+ cells. Ultrastructurally, the predominant cells in the crush area bear a strong resemblance to peripheral nerve Schwann cells; they display a one-to-one association with myelinated axons, have a basal lamina and are surrounded by collagen fibres. It is proposed that these cells are Schwann cells which enter the optic nerve as a result of crush, where they become confined to the astrocyte-free crush area.

Animals↗

PubMed1992

Renal cell carcinoma in childhood.

The imaging features of renal cell carcinoma in 4 young patients (age 7 to 14 years) are described. A high proportion (75%) showed calcification on plain radiographs or computed tomography (CT). Both patients who underwent CT showed well defined high density tumours which were also echogenic on ultrasound examination. These findings are significantly different to those most commonly seen on studies of the tumour in adults.

Adolescent↗

PubMed1992

Age-related changes in the concentration of hydroxypyridinium crosslinks in functionally different skeletal muscles.

High-performance liquid chromatography methods were developed to measure the concentration of hydroxypyridinium crosslinks in the intramuscular collagen and tendinous parts of functionally different skeletal muscles at different ages. A significant increase in pyridinoline concentration took place during maturation reaching 0.32 +/- 0.07 (mol/mol collagen) in soleus (slow plantar flexor) and 0.28 +/- 0.07 in plantaris (fast "mixed" plantar flexor) at the age of 4 months. In medial and lateral gastrocnemius (fast "mixed" plantar flexors) the pyridinoline concentrations (mol/mol collagen) reached 0.24 +/- 0.06 and 0.19 +/- 0.04, respectively, similar to those in both the extensor digitorum longus (fast "mixed" dorsi flexor) and rectus femoris (fast "mixed" knee extensor) muscles, but higher than in the fast "mixed" dorsi flexor muscle, anterior tibialis (0.11 +/- 0.05 mol/mol). By comparison, pyridinoline concentrations of 0.33 mol/mol collagen (+/- 0.10) was measured from longissimus dorsi, a slow-twitch back posture muscle. After maturation the most significant increase in pyridinoline concentration was measured in soleus and gastrocnemius muscles. No differences in the crosslinking between different parts of muscle belly were noticed at any time-point. However, significantly fewer pyridinoline crosslinks were found in tendinous parts of soleus, extensor digitorum longus and anterior tibialis than in intramuscular collagen. The concentration of pyridinoline crosslinks tended to be highest in slow-twitch postural muscles, soleus and longissimus dorsi, and generally higher in plantar flexors which are exposed to higher stretch than dorsal flexors. The reasons for the unexpectedly low concentrations of pyridinoline crosslinks in the tendinous parts of muscles remain to be clarified.

Aging↗

PubMed1992

Percutaneous antegrade ureteral stenting as an adjunct for treatment of complicated ureteral injuries.

We report our use of percutaneous antegrade ureteral stenting (PAUS) as an adjunct for the management of dehisced ureteral repairs and delayed-presentation ureteral injuries secondary to penetrating trauma. This procedure was performed in treating six patients with ureteral injuries. Four patients had dehiscence of a lacerated ureter that had been primarily repaired. Two other patients had ureteral contusions that subsequently became full-thickness disruptions postoperatively. One of these patients developed a pancreaticoureteral fistula. The sepsis resolved in all six patients and in five of the six patients the ureteral disruption healed within 2 months after PAUS without operative intervention. In one patient the ureter healed with stricture, necessitating ureteral reanastomosis. All urinomas resolved with percutaneous drainage. The PAUS technique was used to successfully treat four dehisced ureteral repairs and was the primary method used to successfully treat two disrupted ureteral contusions that were associated with multiple collections and fistulas. These techniques can be utilized for complex ureteral injuries associated with pancreatic leaks, colon or duodenal injuries, and multiple abscesses.

Adult↗

PubMed1992

Packing and re-exploration for patients with nonhepatic injuries.

We retrospectively reviewed the clinical records of 11 patients admitted to the trauma service at Kings County Hospital who underwent packing and temporary closure for severe nonhepatic injuries. The mean ISS was 37 and the mean Abdominal Trauma Index value was 48. Operative findings included 17 major vascular injuries. Although the mean blood pressure was 105 mm Hg during the procedure, the patients required an average of 17 units of blood and all were acidotic, hypothermic, and coagulopathic. Acidosis persisted in all patients and the mean base excess was -13 at closure. A conscious decision was made to terminate the procedure when surgical bleeding was controlled. Patients were resuscitated and warmed in the ICU and returned to the operating room within 48 hours. Seven of the 11 patients survived. Of the eight patients who survived to return to the operating room, all required gastrointestinal procedures at re-exploration. This preliminary experience supports packing to control coagulopathic bleeding, use of temporary abdominal closure, and further ICU resuscitation with a planned second laparotomy for definitive management of gastrointestinal injuries in patients with severe nonhepatic injuries.

Abdominal Injuries↗

PubMed1992

Is Asacol as effective as sulphasalazine in maintaining remission of Crohn's disease and ulcerative colitis?

To compare the efficacy of Asacol (mesalazine coated with Eudraget-S) as a maintenance therapy with that of sulphasalazine, relapse rates of patients with ulcerative colitis and Crohn's disease, treated with sulphasalazine or Asacol were assessed in a retrospective study. A total of 164 patients were investigated, 127 on sulphasalazine and 37 on Asacol. None of the patients on Asacol was changed from sulphasalazine because of lack of efficacy to sulphasalazine. Relapse rates were measured over a 4 year period. In ulcerative colitis these were sulphasalazine 10/77 (13.0%), Asacol 5/20 (25.0%), NS; in all Crohn's disease patients, sulphasalazine 12/50 (24.0%), Asacol 11/17 (64.7%); P less than 0.0025. In patients with Crohn's disease with ileal involvement, relapse rates were sulphasalazine 9/28 (32.1%), Asacol 9/11 (81.6%), P less than 0.0125; without ileal involvement, sulphasalazine 3/22 (13.6%), Asacol 2/6 (33.4%), NS. This study suggests that Asacol is as effective as sulphasalazine in maintaining remission in ulcerative colitis and in patients with Crohn's disease without ileal involvement. Sulphasalazine seems to be more effective than Asacol in maintaining remission in patients with Crohn's disease with terminal ileal involvement.

Acrylic Resins↗

PubMed1992

Laxative induced diarrhoea--a neglected diagnosis.

A laxative screening service was established and offered to gastroenterologists in hospitals covering the West and Central belt of Scotland. The prevalence of laxative induced diarrhoea was assessed in two populations and was found to be 4% in new patients presenting to a gastroenterology clinic with diarrhoea and 20% in patients already under investigation of chronic idiopathic diarrhoea. A high rate of missed diagnosis of laxative induced diarrhoea (71%) and a low request rate (eight per annum) confirm the low clinical awareness of this diagnosis. We found potential savings of 80% of the cost of investigations subsequently ordered which could have been avoided by performing laxative screens on all patients presenting with diarrhoea. The introduction of such a screening policy is recommended as a cost-effective measure.

Cathartics↗

PubMed1992

Measurement of faecal ammonia.

A modified end-point enzymatic method for the measurement of ammonia in stool water is presented. A protein precipitation step was included in order to inactivate urease and faecal enzymes, which oxidise NADH. The modified method is reliable, with acceptable precision and accuracy, and is linear up to a concentration of 1.5 mmol/l.

Ammonia↗

PubMed1992

The fecal osmotic gap: technical aspects regarding its calculation.

The fecal osmotic gap is considered to be useful in the investigation of chronic diarrhea. However, two important questions regarding the calculation of the osmotic gap remain unanswered: the effect of the method of measuring osmolality and the most appropriate means for its calculation. In 41 patients with varying causes of diarrhea, stool osmolalities and electrolyte concentrations were measured. Measurement of stool osmolality by a dew point technique underestimated results by a variable factor, which makes it an inappropriate method. Fecal osmolality measured by freezing point depression gave reliable results and so was considered to be preferable. The osmotic gap was calculated by two methods: subtraction of the calculated osmolality from (1) stool osmolality and (2) plasma osmolality. The former approach was found to be inappropriate on the basis of large variations in results when consecutive stool samples were analyzed, a poor correlation with the severity of osmotic diarrhea, poor resolution between results from patients with secretory diarrhea and those with osmotic diarrhea, and practical difficulties in ensuring adequate collection of stool samples.

Chronic Disease↗

PubMed1992

The diagnosis of intra-abdominal abscesses in patients with severe Crohn's disease.

A series of 24 patients with severe relapses of Crohn's disease responding poorly to conventional treatment with corticosteroids was studied to determine the incidence of intra-abdominal abscesses and the best means to detect them. Ultrasound scans proved to be difficult to interpret and unreliable. Computed tomography demonstrated abnormal bowel thickening in most cases, and showed seven of the eight intraabdominal abscesses. 111In leucocyte scintigraphy always demonstrated inflamed areas of bowel, but underestimated the extent of disease in three patients and overestimated it in five. All eight abdominal abscesses were detected, and there were no false-positive results. It was always possible to distinguish the abscess from inflamed bowel wall. Intra-abdominal abscess is not uncommon in patients with severe relapses of Crohn's disease which are not responsive to corticosteroid therapy, being present in about one-third of patients. 111In leucocyte scintigraphy is a simple and helpful test for differentiating between active inflammatory bowel disease and complicating abscesses, contributing significantly to the management of patients with severe Crohn's disease.

Abscess↗