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Biomedical subjects

J Palmer

Publications and source records attributed to J Palmer.

At least 19 recordsLinked to original sources

Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of rheumatoid arthritis.

Peptidyl fluoromethyl ketones (FMKs), with the amino acid sequence Phe-Ala held constant but with variable N-terminal groups, were synthesized and tested for inhibition of the cysteine proteinase cathepsin B. The FMKs were effective in inhibiting cathepsin B activity in vitro. The inhibition was time dependent and was not reversed by dialysis, suggesting covalent modification of the enzyme. Cathepsin B activity present in livers and kidneys of rats treated with FMKs was reduced by 22-91% 4 hr after a single oral dose of 25 mg/kg. The FMKs inhibited the severity of inflammation and the extent of cartilage and bone damage in adjuvant-induced arthritis. These effects were seen during the late-stage of the disease with no effect on onset or incidence of disease. This is consistent with inhibition of protease-mediated damage. These FMKs or derivatives may be of clinical value in the treatment of arthritis.

Animals

Effects of growth hormone administration in pediatric renal allograft recipients.

The efficacy of recombinant human growth hormone (rGH) was assessed in five pediatric allograft recipients with severe growth retardation despite successful renal transplants. rGH 0.05 mg/kg per dose was given six times weekly by subcutaneous injection to five prepubertal children (mean age 15.2 +/- 2.0 years) all of whom had bone ages less than or equal to 12 years (10.0 +/- 1.4 years), a height standard deviation score of less than -2.5 (-4.9 +/- 1.5), no evidence of catch-up growth, a calculated glomerular filtration rate (GFR) of more than 40 ml/min per 1.73 m2 (51 +/- 6.8 ml/min per 1.73 m2), and stable renal function on alternate-day prednisone (16.7 +/- 2.6 mg/m2 per dose). Growth hormone profiles were abnormal in all children before treatment. rGH administration led to a significant increase in both growth rate (3.5 +/- 1.6 cm/year pre therapy, 8.5 +/- 1.4 cm/year post therapy, P less than 0.001) and percentage of expected growth velocity for bone age (67 +/- 31% pre therapy, 163 +/- 27% post therapy, P less than 0.001) with evidence of true catch-up growth. During the study period, three children had the appearance of secondary sexual characteristics, and one had premature advancement of his bone age. GFR decreased in three children, and in one rGH was discontinued due to a steady rise in serum creatinine. No significant changes were seen in serum calcium, phosphorus, cholesterol, triglycerides, glucose, or thyroid function, although a significant increase in alkaline phosphatase was found. In summary, growth-retarded pediatric renal allograft recipients may have abnormal endogenous GH production and respond favorably to rGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Urinary tract infections in children with posterior urethral valves after kidney transplantation.

The records of 14 boys with posterior urethral valves who had renal failure and subsequently underwent renal transplantation were reviewed to determine the postoperative incidence of urinary tract infection relative to that of 29 male transplant children without valves, who served as controls. There were no significant differences between the posterior urethral valve patients and controls with regard to age, donor source, immunosuppression, followup after transplantation or mean calculated creatinine clearance. Vesicoureteral reflux was found in 1 child with posterior urethral valves and 3 of the children in the control group (p not significant). A total of 15 urinary tract infections occurred in 5 children (36%) with posterior urethral valves, for a rate of 1 per 30 patient-months of followup, and 6 urinary tract infections occurred in 2 controls (7%), for a rate of 1 per 216 patient-months of followup (p < 0.05). However, only 1 of 26 controls (4%) without vesicoureteral reflux had urinary tract infection, for a rate 1 per 1,144 patient-months (p < 0.01). Conversely, the rate of urinary tract infections in controls with vesicoureteral reflux was similar to that of children with posterior urethral valves. Of the 5 children with posterior urethral valves 4 had the initial urinary tract infection within 2 months of transplantation and 10 of 15 episodes occurred within the first 4 months. Antimicrobial prophylaxis did not appear to decrease the rate of infection in children with posterior urethral valves. A history of posterior urethral valves increases the frequency of urinary tract infection after renal transplantation but the usefulness of antimicrobial prophylaxis and the relationship to long-term graft function remain to be determined. Urinary tract infection rarely develops in other transplanted boys without vesicoureteral reflux.

Adolescent

Energy metabolism and aging: a lifelong study of Fischer 344 rats.

Metabolic rate is widely regarded as an important component of aging processes, but variation of metabolic rate with age has not been well characterized. The purpose of the present study was to measure daily metabolic rate under usual living conditions over the lifespan of barrier-maintained Fischer 344 rats. In addition, effects of life-prolonging food restriction were assessed. Metabolic rate was measured indirectly by analysis of gas entering and leaving standard rodent cages over a 24-h period. Group A rats were fed ad libitum. Group B rats were fed 60% of ad libitum intake from 6 wk of age. Both group A and group B rats exhibited variation of metabolic rate per unit lean mass over the lifespan, with metabolic rate decreasing from 6 to 18 mo and then increasing from 18 to 24 mo of age. Results show estimates of lifetime energy expenditure in rats should take account of variability of metabolic rate and confirm the life-prolonging action of food restriction is not a consequence of reduced metabolic rate per unit metabolic mass. Rather, restricted rats are able to sustain appropriate fluxes of nutrients and appropriate metabolic rate under conditions of fuel utilization which promote maintenance of cellular homeostasis.

Aging

Measuring the effect of multiple eye fixations on memory for visual attributes.

Because of limited peripheral vision, many visual tasks depend on multiple eye fixations. Good performance in such tasks demonstrates that some memory must survive from one fixation to the next. One factor that must influence performance is the degree to which multiple eye fixations interfere with the critical memories. In the present study, the amount of interference was measured by comparing visual discriminations based on multiple fixations to visual discriminations based on a single fixation. The procedure resembled partial report, but used a discrimination measure. In the prototype study, two lines were presented, followed by a single line and a cue. The cue pointed toward one of the positions of the first two lines. Observers were required to judge if the single line in the second display was longer or shorter than the cued line of the first display. These judgments were used to estimate a length threshold. The critical manipulation was to instruct observers either to maintain fixation between the lines of the first display or to fixate each line in sequence. The results showed an advantage for multiple fixations despite the intervening eye movements. In fact, thresholds for the multiple-fixation condition were nearly as good as those in a control condition where the lines were foveally viewed without eye movements. Thus, eye movements had little or no interfering effect in this task. Additional studies generalized the procedure and the stimuli. In conclusion, information about a variety of size and shape attributes was remembered with essentially no interference across eye fixations.

Adult

Clinical comparison of two- and three-wavelength systems for continuous measurement of venous oxygen saturation.

OBJECTIVE: To evaluate clinically the accuracy of continuous SvO2 systems to reflect reference SvO2 values over a 24-hour period. DESIGN: Randomized clinical trial. SETTING: Six-bed cardiac surgical intensive care unit of a 540-bed federal facility. POPULATION: Sixty postoperative cardiac patients. INTERVENTIONS: Random assignment to a two- or three-wavelength continuous SvO2 catheter for postoperative SvO2 monitoring. At 4-hour intervals over a 24-hour period, mixed venous blood samples were analyzed with a reference cooximeter and compared with the monitor value of the SvO2 catheter. MAIN OUTCOME MEASURES: A reference cooximeter method to measure SvO2 in mixed venous blood; SvO2 as measured by the in-line, SvO2 catheter system. RESULTS: SvO2 measured by the three-wavelength system did not differ significantly from the reference SvO2 measurement. In contrast, SvO2 measured by the two-wavelength system was significantly lower than the reference SvO2 measurement within 4 hours of admission to the critical care unit and remained significantly lower throughout the 24-hour study period. CONCLUSIONS: The results of this clinical study confirmed a previous study in dogs, showing that SvO2 is measured more accurately by the three-wavelength continuous monitoring system.

Adult

[Respiratory support techniques in foals in a newborn intensive care unit for large animals].

Various techniques for support and control of respiration in neonatal foals are described. It is crucial to evaluate respiration through frequent arterial blood gas analysis. Details for blood sampling from the metatarsal arteries and interpretation of results are provided. Typical diseases in newborn foals, which cause hypoxemia and/or hypercapnia and can be indications for respiratory support are apnea, hypopnea, pulmonary atelectasis, surfactant deficiency, meconium-, fetal fluid- and milk aspiration, maladjustment syndrome, cardiovascular abnormalities, anemia, airway obstruction, compromised lung expansion, increased abdominal pressure and pneumonias. Oxygen insufflation can be delivered through an intranasal tube. Positive pressure ventilation is best accomplished via an endotracheal tube. A nasogastric tube is inserted for enteral nutrition, application of drugs and checking for gastric reflux. Details for insertion of endotracheal and nasogastric tubes are given. Positive pressure ventilation can be achieved by manual ventilation with a rebreathing resp. resuscitator bag and mechanical ventilation with a respirator. Management and control of mechanical ventilation as well as intensive care and monitoring of foals are described.

Animals

Successful use of Orthoclone OKT 3 for steroid-resistant acute rejection in pediatric renal allograft recipients.

Use of Orthoclone OKT 3 for the treatment of steroid-resistant acute rejection in kidney transplant recipients is well described in the literature. Our experience with the use of OKT 3 in 16 pediatric kidney transplant recipients supports the use of this therapy in the pediatric population by reporting efficacy and lack of major complications. Monitoring of OKT 3 antibodies is recommended because of potential need to reuse OKT 3 in subsequent transplants. In addition, techniques of improving medical compliance, particularly in the adolescent population, is an area identified as needing further study. The combination of improving rejection therapies and specific nursing interventions in preparing children and their families in the use of OKT 3 as well as in enhancing compliance will improve the outlook of pediatric transplant recipients.

Adolescent

Effect of recipient's race on pediatric renal allograft survival: a single-center study.

One hundred twenty-seven children (83 males, 44 females, 86 white, 41 nonwhite; mean age 12.1 years) who received 160 renal transplants between 1980 and 1989 were retrospectively studied. Variables such as age, sex, primary diagnosis, type, HLA-DR mismatching, and repeated transplants were compared between races and found not to be significant. However, HLA-A and -B cadaveric-graft mismatching, which was equivalent between whites and nonwhites prior to 1985 (pre-cyclosporine A era), has significantly favored whites (49% with 0 to 2 HLA-A and -B mismatch vs 16% in nonwhites) since 1985 (P less than .05), and a significantly higher proportion of nonwhite patients (59%) were receiving medical assistance (P less than .0001). Graft survival was evaluated with significantly poorer results in nonwhites as compared to whites (P less than .05). Although no difference was found between white and nonwhite cadaveric-graft survival before 1985, nonwhites had significantly worse graft survival since 1985 (72% vs 59% for 1 year and 61% vs 24% for 3 years in whites and nonwhites, respectively; P less than .05). Subpopulations such as nonwhite adolescents, nonwhite females, nonwhites with repeated transplants, and all low socioeconomic patients were identified as high-risk children with poor long-term survival. It is concluded that secondary to poorer matching since 1985 there has been decreased graft survival in nonwhites despite cyclosporine A. Attempts to improve matching and attention to high-risk groups are needed for equivalent survival.

Adolescent

Chylous ascites following retroperitoneal lymphadenectomy: report of 2 cases with guidelines for diagnosis and treatment.

Two cases of chylous ascites following retroperitoneal lymphadenectomy are presented. The first case, a 3-year-old girl, undersent a right radical nephrectomy and retroperitoneal lymph node dissection for Wilms' tumor. Chylous ascites developed postoperatively and resolved after 3 months of supportive therapy. The second case, a 45-year-old woman, underwent a right radical nephrectomy and retroperitoneal lymph node dissection for renal carcinoma. Chylous ascites occurred postoperatively and resolved after a single paracentesis. Diagnosis, evaluation, and therapeutic modalities are outlined and the literature is reviewed.

Adenocarcinoma

Panniculectomy and the difficult ileostomy for urinary diversion.

This paper describes a helpful operation for revision of the difficult ileal stoma for urinary diversion. By using the standard technique of panniculectomy or abdominal lipectomy, the ileal loop can be left in the same position on the abdominal wall and healthy, viable tissue can be mobilized and repositioned to enable the urological surgeon to perform the cutaneous portion of the procedure again and to refashion the ileal loop. This saves the patient an operation of greater magnitude and risk.

Abdominal Muscles