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Biomedical subjects

K Rickard

Publications and source records attributed to K Rickard.

At least 37 records · Page 2Linked to original sources

Modern treatment of haemophilia.

Many rapid advances have been made in the diagnosis and therapy of haemophilia. Nevertheless, the condition still poses problems and challenges (e.g., joint disease, transfusion-transmitted diseases, inhibitors, provision of care in developing countries, and education and cost issues). WHO and the World Federation of Hemophilia held a joint meeting in Geneva, on 21-23 March 1994, to discuss and review current and future approaches to the management of haemophilia and its complications, including prospects for genetic technology and gene therapy in developed and developing countries. The present review article summarizes the discussions and recommendations made by the participants.

Consumer Product Safety↗

Isolated limb perfusion with urokinase for acute ischemia.

PURPOSE: Isolated limb perfusion with urokinase was used to salvage an acutely ischemic lower limb. METHODS: Isolated limb perfusion with urokinase over a 90-minute period was used in the treatment of a 69-year-old female patient with acute ischemia of the left leg after thrombosis of a femoral artery bypass graft. Previous balloon embolectomy and heparin therapy had failed. The flow rate was able to be increased progressively without rise in the line pressure during the course of the perfusion, indicating an increase in capacity of the peripheral arterial bed. Fibrinogen and plasminogen levels in the isolated circulation remained low throughout the perfusion. The concentration of cross-linked fibrin degradation particles (d. dimer) rose progressively in the isolated circulation but remained at normal levels in the systemic circulation during perfusion. RESULTS: Completion angiography demonstrated clearance of thrombus in the popliteal artery and appearance of arteries not seen on preperfusion films. Clinical improvement paralleled the angiographic appearances, with restoration of limb viability. CONCLUSION: We concluded that isolated limb perfusion with use of urokinase is safe and worthy of further investigation.

Acute Disease↗

Serum-free culture of fractionated bovine bronchial epithelial cells.

Procedures for the serum-free culture of a density fractionated population of bovine bronchial epithelial cells have been established. Epithelial cells dispersed by protease digestion were fractionated by density equilibrium centrifugation, followed by plating of the small basal-like population on type I collagen-coated culture dishes. Two or three passages of 1:4 split enriched for a population of actively dividing cells, which could be stored in liquid nitrogen for subsequent use. Clonal growth assays revealed optimum proliferation using a 1:1 mixture of medium RPMI 1640 and LHC-9, a medium employed for human bronchial epithelial cells. Cellular growth rate, which was 0.6 to 1.3 doublings per day depending on the cell preparation, was conveniently decreased by supplementing LHC-9 medium with less than 50% RPMI. In contrast to airway epithelial cell cultures from other species, serum stimulated the growth of bovine bronchial epithelial cells in this system. Transforming growth factor beta 1, however, inhibited growth and induced differentiation into a squamous phenotype. Also in contrast with other systems, the bovine cells were resistant to growth inhibition by 100 nM tetradecanoyl phorbol acetate or 1 microM calcium ionophore A23187. Combination of phorbol ester with ionophore decreased mitotic activity, although induction of squamous morphology was not observed. Therefore, growth inhibition and squamous differentiation were not tightly coupled in this system. Finally, biologically synthesized matrix deposited by these cells stimulated growth rate. This culture system will therefore be useful in assessing the activities of both soluble and matrix-associated factors in the absence of serum.

Animals↗

Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome.

This study reports that thrombocytopenia is a universal phenomenon post hepatic transplantation. In 53 consecutive adult patients undergoing liver transplantation the platelet count fell by a mean of 63% (157 x 10(9)/l to 50 x 10(9)/l). The platelet count reached a nadir at Day 5 post-transplant but returned to pre-operative levels by Day 14. Non-parametric regression analysis found that pre-operative platelet count, blood transfusion requirements and maximum post-operative ALT values were independent predictors of the percentage fall in platelet count. No correlation was seen with length of graft cold ischaemic time or the use of University of Wisconsin (UW) solution. The nadir day correlated with maximum post-operative bilirubin and ALT, graft ischaemic time and use of UW solution. Maximum post-operative ALT was also an independent predictor of nadir platelet count. It was observed that patients who did not survive the hospital admission had lower post-operative platelet counts and these did not return to pre-operative levels by Day 14. The percentage fall in platelet count was an independent predictor of survival. Severe thrombocytopenia was associated with cerebral haemorrhage in 3 patients. This report provides evidence that allograft dysfunction (maximum post-operative bilirubin and/or AST/ALT) was the most consistent independent predictor of the nadir platelet count, nadir day and percentage fall in platelet count post liver transplantation although the exact mechanism(s) of the platelet changes remain uncertain.

Blood Transfusion↗

Effectiveness of enteric coated pancreatic enzymes given before meals in reducing steatorrhea in children with cystic fibrosis.

In vitro data indicate that length of enzyme incubation with food critically affects enzyme dissolution and presumably effectiveness. This study compared the effectiveness of enteric coated (EC) pancreatic enzymes given before meals with those given during meals (15 minutes after beginning of meal) in reducing steatorrhea in well-nourished children with cystic fibrosis. Eight children (6 years 11 months old to 14 years 7 months old) were studied in the General Clinical Research Center at Indiana University Hospital, Indianapolis. A crossover study design randomly assigned enzymes before or during meals during two consecutive 7-day treatment periods for each child. No difference in fat excretion was documented for the total group when the children who took enzymes before meals were compared with those who took enzymes during meals. However, a stepwise multiple regression analysis of the difference (before minus during) in fat excretion on sex, age, enzyme number, and treatment order documented a positive correlation of age with fat excretion (r = .83). Mean fat excretion in younger children (less than 10 years old) decreased significantly when enzymes were given before meals (7.14 +/- 1.95%) rather than during meals (9.92 +/- 1.61%) (P = .004). The difference in fat excretion (mean = 2.78 +/- 0.55%, range = 1.4% to 4%) translates into a half to one full year's growth potential. Younger children with cystic fibrosis may benefit clinically from taking EC enzymes before meals.

Adolescent↗

Effectiveness and safety of small vs. large doses of enteric coated pancreatic enzymes in reducing steatorrhea in children with cystic fibrosis: a prospective randomized study.

Among cystic fibrosis (CF) centers, usual doses of enteric coated (EC) pancreatic enzymes vary from one to six capsules per meal based upon arbitrary criteria for stool and growth patterns. Large doses of non-EC enzymes are associated with increased serum urate (SU) and urinary uric acid (UUA) but data are unavailable for EC enzymes. This study compared the effectiveness and safety of a relatively large dose (patient's usual dose) versus a small dose (1/4 usual dose) of EC enzymes in nine nourished children with CF, regarding decreasing fecal fat and stool nitrogen losses and maintaining normal SU and UUA concentrations. A crossover study design randomly assigned large or small doses to two consecutive 7 day treatment periods within each child. Large doses of EC enzymes reduced steatorrhea and increased SU and UUA. SU was normal with both treatments and UUA was normal, i.e., 17 of 18 values were between the 10th and 95th percentiles for healthy children eating a normal diet. When fat excretion was greater than 10% with small doses of EC enzymes, large doses resulted in reduced fat excretion and normal UUA. These data suggest that large doses of EC enzymes reduce steatorrhea and are safe in patients who have malabsorbtion with small doses.

Celiac Disease↗

Glycemic response to sucrose-containing mixed meals in diets of children of with insulin-dependent diabetes mellitus.

Our pilot study compared the short-term glycemic effects of a traditional "sucrose free" diet (Suc-Free, 2% total calories from sucrose) to a sucrose-containing diet (Suc-Con, 10% total calories from sucrose) in a clinical research center. Both weighed diets were isocaloric and included 50% carbohydrate, 30% fat, and 20% protein in three meals and three snacks; glucose, fructose, and dietary fiber were identical. Sucrose isocalorically replaced complex carbohydrate at each meal and for the afternoon snack. Ten children (7 to 12 years of age; mean total hemoglobin A1 level 8.9 +/- 0.3%) were randomly assigned, in a crossover design, to one of the two orders (Suc-Free followed by Suc-Con or Suc-Con followed by Suc-Free) for consecutive 2-day diet periods; insulin doses remained constant. Preprandial and postprandial blood glucose levels were measured for each meal and snack (18 measurements per day). To account for baseline differences, we calculated the change in blood glucose levels from baseline to 30 minutes and 1 hour for each meal and snack (mean +/- SEM). No differences were detected between diets. Total area under the glucose response curve (levels measured hourly from 8 AM to 9:30 PM in milligrams per deciliter) was not significantly different for the two diets (Suc-Free 3672 +/- 240; Suc-Con 3574 +/- 285; p = 0.74). No difference in 24-hour urinary glucose levels (measured in grams per day) was detected between the two diets (Suc-Free 35.6 +/- 7.5; Suc-Con 34.5 +/- 7.5; p = 0.84). Incidences of hyperglycemia that required supplemental short-acting insulin and of mild hypoglycemia were similar for both diet periods. Thus, in a controlled setting and during a short study period, children with insulin-dependent diabetes mellitus had a similar glycemic response to diets with and without a moderate amount of sucrose.

Blood Glucose↗

Protease injury in airways disease.

In summary, proteases are present in the airway in inflammatory airways disease. These enzymes can damage the airway epithelium. As a consequence, airway function can be altered, and long-term changes in airway anatomy can result. Although the exact cellular and biochemical mechanisms that lead to these changes are incompletely described, it seems likely that they will play important roles in clinical airways disease. As such, these pathways may represent novel opportunities for therapeutic intervention.

Animals↗

Liver transplantation: an Australian experience.

During a 4 and a half-year experience, 283 patients were referred to the Australian National Liver Transplant Unit. Sixty (21%) were children. The major causes of liver failure in the adults were chronic active hepatitis (27%), primary biliary cirrhosis (13%), primary sclerosing cholangitis (12%), fulminant hepatic failure (9%), alcoholic cirrhosis (9%), and malignancy (9%). In the children they were biliary atresia (43%) and inborn errors of metabolism (18%). One hundred and ninety-seven (69%) were accepted for liver transplantation. Of 111 (39%) accepted for early transplantation, 18 (16%) died before a donor became available. There were 319 possible organ donors. Ninety patients (24 of them children) received 100 grafts. Sixty-three (70%) patients survived. For all recipients, 1-year survival was 73%. Two-, 3- and 4-year survivals were 67%. One- to 4-year survivals for adults with benign conditions were 76%, contrasting with results for those with hepatic malignancy (20% 1-year survival). Children weighing greater than 8 kg did well whether they received whole grafts (80% 1- to 4-year survival) or reduced grafts (75% 1- to 4-year survival). Infants weighing less than 8 kg who received reduced adult grafts did significantly worse (20% 1- to 4-year survival). All 8 (100%) patients with fulminant hepatic failure who received grafts survived, including 3 who received ABO-incompatible grafts, though 2 of these subsequently required retransplantation. Rehabilitation of survivors was excellent with 91% of adults and 94% of children pursuing normal activities. Only 2 (2%) grafts failed with primary nonfunction, both in infants because of infarction. Graft survival was significantly worse (p less than 0.01) in patients with a positive direct crossmatch test against the donor. We calculate that the need for liver transplantation in Australia is approximately 7 per million of population per year. Increased donor offers are required to avoid deaths of patients on the waiting list. Reduced-size adult livers are successful for children and have alleviated considerably the critical shortage of pediatric donor livers. Liver transplantation is a highly satisfactory treatment for patients with benign liver disorders but not for those with malignant conditions. Patients with fulminant hepatic failure not responding to conservative therapy should be treated by liver transplantation. In this and other urgent circumstances, an ABO-incompatible liver may be lifesaving though retransplantation with an ABO-compatible liver may subsequently be required. The results of liver transplantation for nonmalignant conditions have improved steadily with clinical experience, with 1- and 2-year patient survivals during the past 28 months of 85%.

Adult↗

Human cardiolipin as the antigen in an ELISA to detect anticardiolipin antibodies.

Human cardiolipin was purified from cadaver heart tissue and used as the antigen in an enzyme-linked immunoassay (ELISA) for anticardiolipin antibodies. The correlation between assays using human and bovine cardiolipin was r = 0.90. Of the lupus anticoagulant positive patients 88% had antibodies to the human antigen and 75% had antibodies to the bovine antigen. Six of 45 samples contained antibodies which only reacted with the human antigen. All six samples remained positive when retested with a different human cardiolipin preparation and were negative when tested against a preparation of sheep cardiolipin. These studies suggest that there was increased specificity when human cardiolipin was used as the phospholipid antigen.

Animals↗

Decision-making in 100 patients referred to the Australian National Liver Transplantation Unit.

One hundred patients were referred to the Australian National Liver Transplantation Unit between January 1986 and August 1987. The commonest disorders for referral were chronic active hepatitis in adults (22 cases), fulminant hepatic failure (14), primary biliary cirrhosis (PBC) (12) and primary sclerosing cholangitis (PSC) (10). Of the 100 patients 31 were activated for transplantation while 35 were deferred and 34 were found to be unsuitable. The decision-making in these patients is discussed according to disease category. Timing of transplantation in PBC and PSC seemed clearcut, with 50% of referred patients being activated. However, major difficulties in timing of transplantation were found, particularly in patients with chronic active hepatitis (CAH) and fulminant hepatic failure (FHF). Of 36 patients with CAH (22) or FHF (14) only five were put on the active waiting list and only two were transplanted. Overall, 25 of the 31 patients underwent orthotopic liver transplantation, with 16 alive two-30 months later.

Adult↗

Absorption of calcium and magnesium from fortified human milk by very low birth weight infants.

Absorption of calcium and magnesium endogenous to human milk, as well as calcium and magnesium added as an exogenous supplement to human milk, was determined in 9 very low birth wt infants. Human milk, intrinsically labeled with stable isotopic tracers of calcium and magnesium, was prepared by administering isotopic tracers intravenously to a lactating woman. Different isotopic tracers, which were representative of calcium and magnesium in the supplement (Enfamil Human Milk Fortifier, Mead Johnson Nutritional Div.), were added to the intrinsically labeled milk. The fortified milk, which was labeled with two calcium tracers and two magnesium tracers, was given orally to the test subjects in a single feeding. True absorption of calcium and magnesium was determined from differences between the doses of tracer ingested and the quantities of tracer excreted in the feces. Stable isotopic tracers were quantified by fast atom bombardment mass spectrometry. These results demonstrate that the fractional absorptions of calcium in the human milk and the added mineral supplement are 80 and 82%, respectively. A total of 89% magnesium endogenous to human milk and 86% of magnesium derived from the mineral supplement was absorbed by the VLBW infants.

Biological Availability↗

The occurrence of maladaptive health-related behaviors and teacher-rated conduct problems in children of chronic low back pain patients.

Chronic low back pain (CLBP) is often associated with a complex of behaviors in the patient which cause interference in adaptive functioning of both the patient and the patient's family. This study examined a group of children of CLBP patients, a control group of children of diabetic patients, and a general control group of children. The study supported the hypothesis that, as a group, children of CLBP patients would exhibit a higher frequency of behaviors hypothesized to be learned through observation of and interaction with a CLBP parent than would children in either of the control groups. Significant differences between the pain group and the control groups on each of the nine teacher-reported and child self-report measures were observed. Implications and limitations of the study are discussed.

Back Pain↗

Nutritional management of the chronically ill child. Congenital heart disease and myelomeningocele.

We have presented some of the nutritional complications encountered in two major pediatric congenital disorders. Although these conditions represent two more common major defects, it is unlikely that many health care providers will manage large numbers of these patients. Nevertheless, the nutrition principles apply to other nutritional dilemmas of chronically ill children. When an infant consumes a low volume intake, regardless of etiology, concerns such as provision of adequate nutrition, within the confines of the infant's water balance, become paramount. Methods have been discussed for increasing caloric density and for monitoring dietary safety and adequacy. When an infant has a propensity for becoming obese one needs to consider preventive measures such as providing sound nutrition information, support, and follow-up for both patient and family. Nutritional problems can become magnified unless adequate support is provided for total health and social needs of the family. The role of the dietitian must be one active participation within the the framework of an interdisciplianry team so that appropriate innovative nutrition programs can be developed and implemented.

Child, Preschool↗