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Biomedical subjects

J Noseworthy

Publications and source records attributed to J Noseworthy.

16 recordsLinked to original sources

The influence of donor age on graft survival in renal transplantation.

The current supply of kidneys from cadaver and living related donor sources is not sufficient to meet the demand. As a result, alternative sources of renal allografts are being explored, including very young donors and anencephalic newborns. However, data on the success of transplanting kidneys from very young donors are limited and conflicting. The purpose of this study was to determine whether the function and survival of renal grafts obtained from newborns and very young donors is different from that for grafts obtained from older donors. Thirty-six cadaveric donors under the age of 3 years, including seven anencephalic newborns, were evaluated. Allograft recipients ranged in age from 12 months to 57 years. The clinical outcome for these donor organs was compared with the graft survival for 136 kidneys transplanted from cadaver donors over age 3 years at our institution. There was a 65% 6-month and 64% 1-year graft survival in recipients of kidneys from donors greater than or equal to 3 years. Survival of grafts from donors under 12 months of age (n = 16) was significantly decreased compared with donors age 3 years and older, with a 31% 6-month (P less than .01) and 19% 12-month survival (P less than .001). Grafts obtained from anencephalic donors did not differ in survival or function from kidneys obtained from other donors less than 12 months of age. Survival for renal allografts from donors age 13 months to 3 years was also decreased relative to older donors: 55% at 6 months (P greater than .1) and 40% at 1 year (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability.

The outcome of multiple sclerosis (MS), assessed according to the Kurtzke Disability Status Scale (DSS), was reviewed in 1,099 consecutive patients followed in London, Canada, between 1972 and 1984. A geographically based subgroup of 196 patients representing 90% of Middlesex County MS patients as well as a group of 197 patients seen from onset of disease were separately analysed. The clinical course was progressive from onset in 33% of the total population and in 28% of the Middlesex County subgroup. Of those with duration of 6-10 yrs, 30-40% with initially remitting disease developed progressive MS. The cross-sectional distribution of disability was bimodal with peaks at DSS 1 (no disability) and DSS 6 (assistance required for walking). Actuarial analysis showed that the median time to reach DSS 6 from onset of MS was 14.97 +/- 0.31 yrs in the total population and 9.42 +/- 0.44 yrs in the "seen from onset' subgroup. Survival was minimally altered; 87% of patients followed up to 40 yrs were still alive, although ascertainment of cases with this duration of MS was incomplete. Data describing the rate at which disability develops after the onset of a progressive phase of MS are also presented. The implications of these data in planning and interpretation of clinical therapeutic trials are discussed.

Canada

The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course.

Controversy exists regarding the predictive value of the early clinical course of multiple sclerosis (MS). Three parameters often considered are the attack rate, the first interattack interval and the rate at which disability develops in the early years of the disease. We have recorded the time to reach successive levels of disability defined by the Kurtzke Disability Status Scale (DSS) in 1,099 MS patients followed at University Hospital, London, Canada between 1972 and 1984. Our population is particularly suitable because of its size, the high degree of ascertainment of cases in the community, and the regular follow-up provided. Life table analysis was used to compare survival in patients stratified according to the above three parameters using DSS 6 as end point. Significant differences were evident in the survival distributions. Despite the extensive interindividual variation in the rate at which disability developed, the early course of MS may be useful in determining the relative risk of rapid progression.

Disability Evaluation

Neonatal cholestatic conditions requiring surgical reconstruction.

Obstructive jaundice in infancy and childhood can arise from a variety of causes. Recognition of the importance of persistent jaundice beyond 2 weeks of age in the infant or elevation of the conjugated bilirubin more than 2 mg/dl will allow the timely evaluation of neonates with possible biliary atresia prior to the development of irreversible hepatic damage. Episodes of intermittent jaundice or persistent conjugated hyperbilirubinemia should be investigated at any age to exclude obstructive lesions of the extrahepatic biliary tract. In all cases, a rapid but carefully coordinated evaluation can be undertaken by a pediatric gastroenterology and surgical team, allowing optimum economy of effort and preservation of hepatic function. In nearly all cases with obstructive lesions of the extrahepatic biliary tree, satisfactory hepatic function can be preserved through appropriate surgical intervention. Results with biliary atresia continue to improve but are dependent on early diagnosis and treatment. In cases in which hepatic function deteriorates and hepatic failure becomes inevitable, orthotopic hepatic transplantation can be lifesaving and should be undertaken prior to the onset of irreversible hepatic decompensation. Although the terminology may be somewhat confusing and its etiology uncertain, the entity of choledochal cysts, taken within the context of its modern classification, accurately describes a group of cystic anomalies of the extrahepatic (and intrahepatic) biliary tree, which have many common features. The vast majority can be expeditiously dealt with by surgical excision and hepaticoenteral reconstruction. Two particular associations with choledochal cysts are important to note. When it occurs with infancy, choledochal cysts can be difficult to diagnose, but very important to define and treat expeditiously in order to prevent serious impairment of hepatic function. In all patients, but particularly in adults, the risk of associated carcinoma necessitates extremely careful definition of the biliary tree and urges one to advocate complete excision of the cyst at initial operation.

Bile Ducts

Antiidiotypic antibody to reovirus binds to neurons and protects from viral infection.

A syngeneic monoclonal antiidiotype directed against the idiotype of an antireovirus type 3 hemagglutinin demonstrates several of the biological actions of the original viral hemagglutinin and binds to rat and murine cortical neurons grown in dissociated cell culture. Receptor-bearing neurons appear within 24 hours of plating in cultures from mouse or rat cortex taken on embryonic day 15; these neurons are demonstrable for the duration of the culture life span (4 to 8 weeks). When cortical cultures are incubated with antiidiotype before or during exposure to reovirus, the antiidiotype protects neurons from type 3 infection without inhibiting infection of nonneuronal cells with either type 3 or type 1. Thus an antibody directed against a viral receptor can prevent infection of receptor-bearing cells without directly neutralizing the virus.

Animals

Blunt liver injury in childhood: evolution of therapy and current perspective.

One hundred eighty-eight consecutive children with serious blunt abdominal or multisystem trauma were evaluated between August 1981 and July 1985. Of the 188 patients, 53 (28%) were found to have hepatic parenchymal injuries and are the basis of this report. Four of the 53 (8%) underwent emergency laparotomy for exsanguinating hemorrhage; two patients died, both of hepatic vein lacerations, and two are alive and well after right hepatic lobectomy. Forty-nine (92%) of the children with liver injuries did not require operation for hemorrhage. Four of these 49 patients developed serious complications; hemobilia occurred in one patient and bile peritonitis occurred in three. The one case of hemobilia was resolved without surgery. One child underwent a delayed operative biliary tract reconstruction that was successful. The other two children required a combination of debridement and drainage procedures. Fifty-one of the 53 children (96%) are currently alive without morbidity related to their liver injuries. Both children who died had multiple trauma including central nervous system injuries and had exsanguinating hemorrhage that required emergency laparotomy at initial evaluation. There were no children with "late" hemorrhage and none who developed septic complications. Nonoperative management of most childhood blunt abdominal trauma is possible. Widespread use of abdominal computerized tomography scanning has made this approach practical. This large series of consecutive liver injuries from a large pediatric trauma center illustrates the advantages and the risks of a selective but primarily nonoperative approach to liver trauma in children.

Alanine Transaminase

Multisystem trauma.

Several unique features of childhood anatomy and physiology mandate an approach to evaluation and treatment of multiply injured children that differs from that applied to adults. Details of this approach have been presented, with particular emphasis, on early, aggressive multimodal imaging, nonoperative management of splenic, hepatic, renal, and duodenal injuries, and specific aids in early precise definition of extent of injury (contrast-enhanced CT, serum levels of hepatic enzymes, and diagnostic peritoneal lavage). The outcome of this approach preserves maximum function and minimizes morbidity when performed in an institution having the requisite supportive resources.

Blood Transfusion

Adult ureteral ectopia.

We report on 6 women with ureteral ectopia to emphasize the need for careful endoscopic examination in evaluating the entity. The clinical histories are unusual in that 1 of the 6 patients had classical symptoms of urinary incontinence. A discussion of the diagnosis and treatment of ureteral ectopia in such patients is presented.

Abdomen

Protein and glycoprotein electrophoretic patterns of enriched fractions of primary and secondary granules from guinea pig polymorphonuclear leukocytes.

The postnuclear supernatant fraction of sucrose homogenates of guinea pig polymorphonuclear leukocytes (PMNL) was subjected to differential centrifugation to obtain a total particulate fraction, a particle-free supernatant fraction, highly enriched fractions of primary and secondary granules, and a membrane-rich fraction. The various fractions were solubilized in buffer containing sodium dodecyl sulfate (SDS) and analyzed for protein and glycoproteincomponents by SDS -polyacrylamide gel electrophoresis. The major glycoprotein components of the postnuclear supernatant fraction were found mainly associated with the enriched fraction of secondary granules and, to a lesser extent, with the membrane-rich fraction. No major glycoprotein components were visible in the polypeptide electrophoretic patterns of the primary granule fraction or of the particle-free supernate. Attempts at separation of guinea pig granules by zonal sucrose density gradient centrifugation were only partially successful. Data supporting a species difference in this regard between rabbit and guinea pig PMNL granules are presented.

Alkaline Phosphatase

Vitamin D requirement in infants receiving parenteral nutrition.

The adequacy of low dose vitamin D (25 IU/dl) parenteral nutrition (PN) solution was studied in 18 infants. All infants had surgical indications for PN. The birth weights were 2810 +/- 135 g and gestational ages 37.4 +/- 0.5 wk (mean +/- SEM). Duration of study ranged from 5 to 175 days. Thirteen infants were studied for up to 6 weeks and five infants for 71 to 175 days. Results showed that studied infants maintained growth along normal percentiles for weight, length, and head circumference. Vitamin D status as indicated by serum 25 hydroxyvitamin D (25 OHD) rose from 15 +/- 1.9 ng/ml to 26 +/- 2.8 ng/ml, mean +/- SEM (p less than 0.001) after 9 days, and remained normal up to 6 months. Five infants with biochemical liver dysfunction also had normal serum 25 OHD concentrations, indicating the hepatic 25 hydroxylation process was not severely impaired. Serum total and ionized calcium, phosphorus, and vitamin D-binding protein concentrations were normal. Serum magnesium was mildly elevated in five infants (2.6 to 3 mg/dl) on one occasion and resolved spontaneously. Serum alkaline phosphatase (AP) concentrations rose above baseline values in 12 of 17 infants, but remained within normal range (less than 400 IU/liter at 30 degrees C). Another infant with markedly elevated AP values died from liver dysfunction. Radiographs of the forearms were normal except for marked demineralization in one infant in spite of normal 25 OHD concentrations. We conclude that 25 IU vitamin D/dl of nutrient infusate is adequate to maintain normal vitamin D status, as indicated by normal serum 25 OHD concentrations in infants receiving PN for as long as 6 months.

Alkaline Phosphatase

Parenteral nutrition for infants: effect of high versus low calcium and phosphorus content.

Calcium (Ca) and phosphorus (P) homeostasis were determined in 18 infants (birth weight, 2,810 +/- 135 g; gestational age, 37.4 +/- 0.5 weeks; mean +/- SEM) who received high or low Ca and P content (Ca, P) parenteral nutrition (PN) with a fixed, low dose of vitamin D (25 IU/dl). Nine infants were randomized into low (standard) Ca, P (20 mg Ca and 15.5 mg P/dl) and nine into high Ca, P (60-80 mg Ca and 46.5-62 mg P/dl) PN, and then were studied for up to 6 weeks. The high Ca, P group had stable serum 1,25 dihydroxyvitamin D [1,25(OH)2D], which consistently remained within the normal range (less than 116 pg/ml). Tubular reabsorption of phosphorus (TRP) also was stable and remained consistently less than 90%. The low Ca, P group had elevated and higher 1,25(OH)2D (p = 0.03) than the high Ca, P group. The mean serum 1,25(OH)2D concentration rose from 32 to 112, 115, and 133 pg/ml over a period of 6 weeks. TRP also was higher (p = 0.02) and remained consistently greater than 90%. There were no significant differences between groups in serum parathyroid hormone, calcitonin, Ca, Mg, P, alkaline phosphatase, vitamin D binding protein, and 25 hydroxyvitamin D concentrations; urine Ca/creatinine and Mg/creatinine ratios, and fractional excretion of sodium (Na). Thus, a "high" Ca (60 mg/dl) and P (46.5 mg/dl) content in PN solutions can result in stable serum 1,25(OH)2D and TRP, presumably reflecting minimal stress to Ca and P homeostatic mechanisms without further increase in urinary Ca excretion.

Calcium