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Biomedical subjects

R A Brown

Publications and source records attributed to R A Brown.

At least 19 recordsLinked to original sources

Gastrointestinal tract perforation in children due to blunt abdominal trauma.

Over a 14-year period 587 children under 13 years of age were admitted with blunt injury to the abdomen. Twenty-nine (4.9 per cent) of these were found to have bowel rupture. Evidence of peritonitis was present at initial evaluation in 11 children (38 per cent). Radiological evidence of perforation (pneumoperitoneum) was present in only five of 27 (19 per cent) with a further six of 27 (22 per cent) showing dilated loops of bowel or fluid levels. Thus 59 per cent of radiographs were not diagnostic. The mean time from admission to laparotomy was 17 h. Proximal bowel perforation was common and perforation at multiple sites occurred in five patients; 59 per cent had a concomitant injury which resulted in two deaths (from head injury). Initial clinical and radiological evidence of bowel perforation can be misleading and reliance on such indicators may result in significant diagnostic delay. Frequently repeated clinical examination is advocated; progression of abdominal signs should alert the clinician to proceed to laparotomy.

Abdominal Injuries

Reflux strictures of the esophagus in children.

Although the therapeutic approach to gastroesophageal reflux in children is well established, there are differences of opinion regarding the management of esophageal strictures, viz bougienage with medical therapy, fundoplication without dilatation, preoperative dilatation followed by fundoplication with intraoperative and postoperative dilatation, or resection and interposition. Sixteen consecutive children (mean age, 30.2 months) with reflux strictures were evaluated, constituting 12% of children operated on for gastroesophageal reflux. The strictures became clinically apparent 22.4 months (mean) from the onset of symptoms and were diagnosed by contrast studies and endoscopy. At first endoscopy all the patients had well-established fibrotic strictures. The strictures were mostly situated in the middle or lower esophagus and 7 were longer than 3 cm in length. All 16 were treated with antacids, H2-receptor blockers (Cimetidine), prokinetic agents, and intense nutritional resuscitation, together with preoperative stricture dilatations (average, 3.6 times). This was followed by fundoplication when nutritional parameters had been restored, esophagitis improved, and the strictures dilated to adequate size. Seven children required concomitant gastrostomies for prograde esophageal dilatations. Twelve children needed postoperative esophageal dilatations. The results were satisfactory in 14 (88%). Two required endoesophageal resection for localized unyielding strictures. One child responded only after failed reflux surgery was corrected at a second procedure. During an average follow-up of 8.2 years (range, 3 to 11) there has been no stricture recurrence and growth velocity was restored in all. We conclude that our preferred method is preoperative in-hospital management of gastroesophageal reflux with maximum nutritional support and careful evaluation of the degree and extent of esophagitis and fibrous scarring.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool

Colorectal carcinoma in children.

An increasing incidence of colorectal carcinoma has been noted at this institution. We report seven children with colorectal carcinoma. The average delay between onset of symptoms and diagnosis was 41/2 months, and in five patients distant metastases were present at the first operation. Initial symptoms were ignored in all cases and in only one was the serious nature of the condition realized at first presentation. In five lesions the histology was mucin secreting adenocarcinoma, a poor prognostic variant. All seven died on average 11 months after diagnosis. These three factors--delay in diagnosis, advanced stage of disease, and poorly differentiated histology--contribute overall to a poor prognosis in the young.

Adenocarcinoma

Regulation of growth plate cartilage degradation in vitro: effects of calcification and a low molecular weight angiogenic factor (ESAF).

Endothelial cell stimulating angiogenic factor (ESAF) is an activator of matrix metalloproteinases, including latent collagenase, and is released by chondrocytes during calcification. ESAF, added to cultured growth plate chondrocytes, elicited a time-dependent, 2.4-fold increase in matrix lysis (compared with 30% for IL-1). Matrix breakdown was suppressed by addition of tissue inhibitor of metalloproteinase (TIMP). Although calcification has been previously reported to stimulate ESAF production, no corresponding increase in cartilage lysis was seen in the present study. However, the level of ESAF that cultures produce during calcification is many times less than that added to the cultures in this series of experiments. We conclude that ESAF can produce dramatic increases in cartilage breakdown (apparently by activation of latent enzymes), but only at levels in excess of those stimulated by calcification. This indicates that ESAF may operate in concert with other initiators, perhaps from the invading endothelial cells.

Angiogenesis Inducing Agents

The superficial branch of the radial nerve: an anatomic study with surgical implications.

Twenty fresh cadaver extremities were dissected to delineate and quantify the course of the superficial branch of the radial nerve. This branch bifurcated from the radial nerve at the level of the lateral humeral epicondyle in eight specimens, and in all specimens the bifurcation was no more than 2.1 cm from the lateral epicondyle. It continued distally, deep to the brachioradialis and became subcutaneous a mean of 9.0 cm proximal to the radial styloid, traversing between the tendons of the brachioradialis and extensor carpi radialis longus. The superficial branch of the radial nerve branched a mean of 5.1 cm proximal to the radial styloid. Distally, at the level of the extensor retinaculum, the closest branches to the center of the first dorsal compartment and to Lister's tubercle were mean distances of 0.4 and 1.6 cm, respectively. In the hand, the superficial branch of the radial nerve most commonly supplied branches to the thumb, the index finger, and the dorsoradial aspect of the long finger. Knowledge of the course of the superficial branch of the radial nerve will help prevent injury during operative procedures on the radial side of the hand, wrist, and forearm and will aid in its localization in treatment of traumatic injuries or performance of nerve blocks in its distribution.

Anthropometry

Group treatment program for abusive husbands: long-term evaluation.

Long-term outcomes of a short-term group treatment program for abuse husbands were investigated in a controlled study. Recidivism rates, based on police reports, were found to be lower than those for a control group of untreated abusive husbands; they were also found to be lower for those men initially exhibiting greater depression. Implications for further research are discussed.

Adult

Interaction and aggregation of sodium aurothiomalate and poly L-lysine.

This report describes the interaction and aggregation of sodium aurothiomalate with polylysine, a potentially useful property, both as a model for drug-protein interaction and as a means of reversibly immobilizing sodium aurothiomalate. Sodium aurothiomalate formed stable precipitates with polylysine at neutral pH, ionic strengths below 1M NaCl, and optimally, at sodium aurothiomalate to lysine ratios of less than one. The interaction could be demonstrated both by precipitation (which was sensitive to the size of polylysine polymer) and by using polylysine immobilized to Sepharose. Precipitation could be inhibited by addition of the organic thiomalate moiety alone. These findings indicate that the interaction of sodium aurothiomalate with polylysine is by electrostatic bonding of the thiomalate (mercaptosuccinate) moiety and the epsilon-amino groups of lysine residues. At suitable molar ratios this will link together many polylysine chains leading to precipitation. This represents a potentially valuable interaction for immobilization of the drug and in the formation of conjugates.

Carbon Radioisotopes

Simplified method of grading primary carcinomas of the breast.

AIMS: To produce a simplified prognostic index for breast cancer. METHODS: A retrospective study of 105 cases of primary infiltrating breast adenocarcinoma (not otherwise specified) was performed. Mitotic counts and semiquantitative assessment of tumour necrosis, fibrosis tubule formation, nuclear pleomorphism were made in histological sections of the primary tumour. Statistical analysis was performed to determine which of these parameters best predicts the observed survival. RESULTS: Mitotic count and necrosis correlated best with survival. This allowed the formation of a simple prognostic index based on these two parameters. CONCLUSIONS: This new prognostic index, with four tumour grades, seemed to be superior to Bloom's grading method, with greater separation of the prognostic groups. In particular, there is clear segregation of a group of patients with a distinctly poor prognosis.

Adenocarcinoma

Central venous catheters. Technique and experience at Red Cross War Memorial Children's Hospital, Cape Town, 1987-1990.

Central venous catheters can be of major benefit to children in whom prolonged intravenous access is required. For their everyday use, however, the known associated morbidity needs to be at an acceptably low level. Experience with 44 central venous catheters in 31 children (3318 catheter days over a 40-month period) is reported. The complication rate of catheter sepsis (0.3/100 catheter days), thrombosis (1 catheter), and technical problems (17, of which 6 required removal) justified catheter usage. Provided catheters are correctly inserted and the patients meticulously nursed, these catheters offer major advantages to infants and children requiring long-term intravenous access, particularly for parenteral nutrition.

Catheterization, Central Venous

High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults.

Seventy consecutive adult patients with acute myelogenous leukemia (AML), median age 44 years, received high-dose cytarabine (3 g/m2 every 12 hours for 12 doses) followed by daunorubicin (45 mg/m2 daily for three doses) for remission induction. A single, identical course was planned for postremission therapy. Complete remission (CR) was achieved in 63 patients (90%, 95% confidence interval [CI] 83% to 97%), 60 after a single course. Eight patients were selected to undergo elective bone marrow transplantation (BMT) during first CR. Of the remaining 55 patients, 40 (73%) underwent planned post-CR therapy; 15 patients did not, owing to early relapse, excessive toxicity from the induction chemotherapy, or refusal. Nineteen patients, including 13 who received planned post-CR therapy, remain in continuous CR at a median follow-up of 5.2 years (range 3.0 to 7.1 years). The 5-year actuarial leukemia-free survival was 30% (95% Cl, 19% to 42%) for all patients achieving CR and 32% (95% Cl, 19% to 47%) for the 40 patients who received the planned post-CR chemotherapy. Analysis of various putative prognostic factors for CR and overall and leukemia-free survival showed significance for a previous history of myelodysplasia, higher initial leukocyte counts, certain French-American-British (FAB) types, and certain abnormal karyotypes. None of these factors was consistently significant regarding the above parameters, although small patient numbers in certain analyses may have obscured significant associations. Myelosuppression was occasionally prolonged after remission induction and especially post-CR therapy. Severe cerebellar toxicity was observed in 13 patients; in 11 cases, this toxicity was fully reversible. Other serious complications were infrequent. Intensive chemotherapy with high-dose cytarabine and daunorubicin has substantial antileukemic activity in adult AML, and may represent an improvement over conventional therapy. Relapses were common, however, even in patients who received planned therapy, and substantial toxicity was observed. The optimum use of this regimen in AML remains to be determined.

Adult

Bovine haptoglobin response in clinically defined field conditions.

In order to assess the usefulness of haptoglobin as a measure of the acute phase response in cattle, the concentration of serum haptoglobin was estimated in the non-infectious conditions of milk fever and ketosis, and in the infectious conditions of severe mastitis, acute severe metritis, retained placenta and chronic endometritis. Mean haptoglobin concentrations were normal in cattle with non-infectious conditions and chronic endometritis but significantly increased in cattle with infectious conditions.

Acute Disease

Plasma exchange and vincristine in the treatment of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura associated with bone marrow transplantation.

Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) is a rare and often fatal complication of bone marrow transplantation (BMT). In this study, we report eight such cases (seven allo and one auto) treated with plasma exchanges (PE), vincristine (six patients), and discontinuation of cyclosporin A (in allo BMT). This complication occurred in 6.3% of 112 allogeneic BMT and in 0.7% of 146 autologous BMT. In seven patients, the BMT preparatory regimens consisted of cyclophosphamide, etoposide, and total-body irradiation (TBI). Among the eight patients with HUS/TTP, one allogeneic BMT patient with reversible renal failure, but without central nervous system (CNS) involvement, or systemic mycotic infection, responded completely and is without evidence of disease for a period of greater than 3.5 years. Three patients showed hematologic improvement, and four did not respond. The median duration of survival was 17 days. Six of the seven deaths occurred in a setting of systemic infection, progressive renal failure, and worsening of graft-versus-host reaction. In spite of hematologic improvement to PE and vincristine, BMT patients in whom HUS/TTP developed usually succumbed to complications.

Adolescent

The fundal pile: bleeding gastric varices.

Bleeding from esophageal varices is a common cause of major upper gastrointestinal tract blood loss in children with portal hypertension but usually ceases spontaneously or is satisfactorily managed by nonoperative measures. Massive hemorrhage from gastric fundal varices may be difficult to control with compression and sclerotherapy; in these cases, a direct surgical approach may be indicated. Since 1984, 27 children have undergone aggressive injection sclerotherapy for bleeding esophageal/gastric varices. Nine (6 with portal vein thrombosis) bled from gastric fundal varices. In 5 of these, medical management and sclerotherapy failed to control the acute bleed. In all 5 there was "rupture" of a large gastric fundal varix or "pile" and bleeding was controlled at emergency laparotomy by underrunning the varices through a high anterior gastrotomy. Four have subsequently been successfully managed by continued sclerotherapy and one patient with cirrhosis has died of liver failure. In 3 of the survivors both esophageal and gastric fundal varices have been completely obliterated. No further life-threatening hemorrhage has occurred in any case during a follow-up period of 1 to 5 years. Bleeding from gastric varices is more common than previously recorded and more difficult to control by nonoperative management, including injection sclerotherapy. In uncontrolled hemorrhage from gastric varices, surgical underrunning offers a means of providing initial control. Thereafter, the inevitable variceal recurrence may be successfully treated with sclerotherapy.

Child

Nonspecific cytotoxic cells of rainbow trout (Oncorhynchus mykiss) kill YAC-1 targets by both necrotic and apoptic mechanisms.

Nonspecific cytotoxic cells (NCC) have been identified in a number of fish species and are thought to be evolutionary progenitors of mammalian natural killer cells. We show here that trout NCC are functionally similar to cytotoxic cells of higher vertebrates in that they mediate cytotoxicity through both mechanisms of apoptosis and necrosis. To demonstrate that trout NCC inflict apoptic and necrotic lesions in tumor target cells, DNA fragmentation and 51chromium release assays were conducted using leukocytes isolated from peripheral blood, spleen, and anterior kidney. At effector-target ratios of 25:1, 50:1, 100:1, and 200:1, the release of thymidine-labeled DNA fragments and the release of 51chromium from YAC-1 target cells paralleled one another. Percent chromium release and DNA fragmentation increased when effector:target incubation times were extended from 4 to 18 h. As evidenced in agarose gels, the pattern of fragmentation induced by trout effector cells was identical to that produced by BALB/c NK cells. Similar to human and murine NK cells, trout NCC were maximally inhibited by 50 mM mannose-6-phosphate. Morphologic characteristics of rainbow trout NCC were examined using light and electron microscopy. Photomicrographs of effector:target cell mixtures after a 1 h incubation show NCC binding to target YAC-1 cells. Transmission electron micrographs of the conjugates revealed that the cells responsible for killing are small (4.2-4.5 microns), agranular mononuclear leukocytes.

Animals

Chest trauma in a Canadian urban setting--implications for trauma research in Canada.

The trauma registry at the Montreal General Hospital was reviewed to provide basic epidemiologic data on chest trauma in Canada and to compare these data with the minimal data available in the literature. Chest trauma in multiply injured patients resulted in higher Injury Severity Scores (ISSs) than the average. This was reflected in higher mortality for patients with chest trauma. The majority of injuries were caused by blunt trauma. Less than 9% of patients admitted to the hospital required thoracotomy for thoracic vascular and cardiac trauma. Outcome (measured by mortality) was better than that predicted from the literature based on admission ISS. The etiology of trauma in this Canadian setting and the resulting injury profiles were substantially different from those obtained from the predominantly American epidemiologic data available in the literature. This suggests the need for gathering more Canadian population-based trauma data for the planning of trauma prevention and care in this country.

Adolescent