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Biomedical subjects

E K Smith

Publications and source records attributed to E K Smith.

At least 19 recordsLinked to original sources

Terminal loop cutaneous ureterostomy in renal transplantation.

Patients presenting for renal transplantation with urinary diversion abnormalities pose serious problems. The use of a terminal loop cutaneous ureterostomy (TLCU) in patients whose outcome was satisfactory was first described in 1977. Primary urinary drainage was achieved in 3 recipients of cadaver renal allografts by creating a TLCU. This method of drainage has been satisfactory in these patients with follow-up between four and thirty months. We suggest that this simple technique should be considered more frequently for selected patients who require supravesical urinary diversion.

Adult

The role of aluminum in the functional iron deficiency of patients treated with erythropoietin: case report of clinical characteristics and response to treatment.

The quantitative variation among patients in their response to erythropoietin can be explained, in part, by factors that can independently cause anemia in patients with end-stage renal disease. Aluminum can blunt the effect of erythropoietin, in part by interfering with iron bioavailability. This inhibitory effect cannot be completely overcome by aggressive ferrotherapy, but can be reversed with aluminum chelation therapy. A patient is described who developed hematological evidence of aluminum excess after being treated with erythropoietin. The biochemical evidence of functional iron deficiency and the response to aluminum chelation therapy support the hypothesis that the inhibitory effect of aluminum on erythropoiesis is mediated by the interference of aluminum with the bioavailability of iron.

Aluminum

Dialyzer re-use--a multiple crossover study with random allocation to order of treatment.

A multiple crossover research study was used to evaluate the effect of dialyzer re-use on fever, blood leaks, serum urea and creatinine values and symptoms. Each of 6 crossover periods consisted of 4 weeks on either single-use or re-use, 1 week washout, 4 weeks on the alternative treatment and 1 week washout. The re-use consisted of 6 uses of each dialyzer and the washout weeks consisted of 3 single-use sessions. Analysis of paired observations within rather than between patients showed no effects of time (i.e. among crossover periods 1 through 6) or number of re-uses (i.e. among uses 1 through 6). There was no significant difference for temperature change during dialysis, blood leak rate, or the serum urea and creatinine values before the first dialysis of each washout period. There were no differences for symptoms of pruritus, cramps, nausea, headache, chest pain, backache or fatigue. There were no clinical advantages or disadvantages associated with dialyzer re-use.

Cellulose

Production in vitro of antibodies directed against alloantigen-specific recognition sites on T cells and on lymphocytotoxic HLA antibodies.

We have examined the mechanism of immunological unresponsiveness in a recipient (P.S.) with a long-term functioning renal allograft. P.S., whose HLA type is A1, A30; B14, B18; DR1, w8; DRw52; DQw1 and in whose serum we had earlier demonstrated the presence of antiidiotypic antibodies, received a kidney from a cadaver donor of HLA type A1, A10, B8 in March, 1970. Peripheral blood B lymphocytes from the patient were transformed with Epstein-Barr virus (EBV), and by the cluster-picking technique a B cell line was propagated with continuous production of antibodies. Antiidiotypic antibodies with two distinct biological functions were demonstrable; one specifically inhibiting the lymphocytotoxic activity of anti-HLA-B8, B5, and DR3 reference typing sera, and the other specifically inhibiting proliferative responses in MLC of the recipient's lymphocytes and of third party cells sharing B14, DR1, DQw1 with the patient against stimulator cells carrying B8, DR3 antigens. Immunodepletion experiments demonstrated that the inhibitory activity was associated with the IgM fraction. Absorption experiments suggested that different antibodies may be responsible for the inhibition of lymphocytotoxic activity of anti-HLA sera and of the proliferative responses in MLC. Antiidiotypic antibodies have been postulated to be important in maintaining allograft tolerance in vivo, thereby enhancing renal allograft survival. The availability of such antibodies in large quantities, produced in vitro, could provide antisera for the immunochemical characterization of specific idiotypic receptors on immunoglobulins and T lymphocytes.

Antibody Specificity

Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine.

We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.

Antilymphocyte Serum

Factors underlying performance on written tests of knowledge.

The study compares two popular forms of written tests; the multiple choice test (MCQ) and the Modified Essay Question (MEQ). Two factors were varied in the experiment: the format of the questions (multiple choice, directed free response, or open-ended free response) and the context of the questions (in a patient problem or in random sequence). Six problems were developed in each version, and administered to a total of 36 medical students at three educational levels using a Latin-square design. The results showed a significant effect of each factor in the design, amounting to a difference of 8.7% between MCQ and directed free response, 4.2% between directed and open-ended free response and 4.3% between problem and random context. However, the correlation of scores based on content across the formats approached unity after correction for attenuation. A process score, based on the style and presentation in the undirected format, correlated more strongly with the free-response questions. The results suggest that, although the MCQ and MEQ may assess different skills, there is a very strong relationship between content scores derived from the two formats. The free response formats may present the opportunity for assessment of other factors related to presentation if scoring procedures are modified. Finally, the effect of randomizing questions is a deterioration of performance when compared to placing questions in the problem context.

Education, Medical, Undergraduate

Measurement of quality of life in end-stage renal disease: the time trade-off approach.

The quality of life of patients with end-stage renal disease was estimated using the time trade-off technique. The sample included 103 transplant, 60 hospital hemodialysis, 57 home/self-care, and 52 continuous ambulatory peritoneal dialysis patients. Test-retest reliability was high: intra-class correlation coefficient 0.81 (p less than 0.001). The correlations of the time trade-off with the Spitzer Quality of Life index and a visual analogue scale completed by the nephrologists, nurses, friends/relatives, and the patient were positive and statistically significant, but still relatively low (r = 0.22-0.43; p less than 0.01). The time trade-off demonstrated evidence for discriminative construct validity by ordering treatment groups according to a priori prediction. The mean time trade-off values and standard deviations (where death is 0 and full health is 1) were 0.43 (0.26) for hospital hemodialysis 0.49 (0.23) for home/self-care hemodialysis, 0.56 (0.29) for continuous ambulatory peritoneal dialysis, and 0.84 (0.24) for transplant. Analysis of variance showed transplant to be different from all other groups (p less than 0.001) with age, sex, time with end-stage renal disease, and work status making no significant independent contribution. The partial correlation coefficients between time trade-off score and items in the physical, social, and emotional functioning sub-scales of the Rand questionnaire showed that physical functioning was far more important than social or emotional functioning. The time trade-off is reliable, demonstrates evidence for validity, and suggests that the quality of life for patients with end-stage renal disease is much poorer than that reported previously.

Emotions

Effects of exercise on longevity of rats.

It has been postulated that life span is inversely related to energy expenditure. If this is correct, regularly performed exercise could accelerate the aging process. In two early studies, exercise shortened the life span of rats; the results of these studies have been cited as evidence for the concept that an increase in energy expenditure accelerates aging. However, subsequent studies have not confirmed this finding. Instead, the weight of evidence now indicates that rats that exercise regularly have a longer average life span than sedentary, ad libitum-fed controls. Freely eating sedentary rats become obese, indicating that their food intake is in excess of their energy requirements. Available evidence seems compatible with the interpretation that exercise results in improved survival in rats by countering deleterious effects of a sedentary life combined with overeating.

Aging

Modified essay questions: are they worth the effort?

The method chosen for important examinations strongly influences the nature of student learning. The Newcastle Medical School in Australia developed a 5-year problem-based curriculum and adopted the Modified Essay Question (MEQ) as the main written instrument for assessing students' problem-solving skills. Even with the best of intentions the MEQ has been abused by its over-use, as shown in this review of annual assessment for years 1, 3 and 5 of the course. Analysis of staff and students' dissatisfaction with this instrument showed some difficulties attributable to the nature of MEQ items. However, a number of problems also emerged as a result of subtle changes in the teaching staff's approach to learning and assessment. This paper concludes by acknowledging the strengths and limitations of the MEQ. It recommends ways in which the MEQ can be effective, as part of a balanced programme involving other suitable instruments.

Adolescent

Longevity of cold-exposed rats: a reevaluation of the "rate-of-living theory".

It has been postulated that increased energy expenditure results in shortened survival. To test this "rate-of-living theory" we examined the effect of raising energy expenditure by means of cold exposure on the longevity of rats. Male 6-mo-old SPF Long-Evans rats were gradually accustomed to immersion in cool water (23 degrees C). After 3 mo they were standing in the cool water for 4 h/day, 5 days/wk. They were maintained on this program until age 32 mo. The cold exposure resulted in a 44% increase in food intake (P less than 0.001). Despite their greater food intake, the cold-exposed rats' body weights were significantly lower than those of control animals from age 11 to 32 mo. The average age at death of the cold-exposed rats was 968 +/- 141 days compared with 923 +/- 159 days for the controls. The cold exposure appeared to protect against neoplasia, particularly sarcomas; only 24% of the necropsied cold-exposed rats had malignancies compared with 57% for the controls. The results of this study provide no support for the concept that increased energy expenditure decreases longevity.

Animals

Effect of voluntary exercise on longevity of rats.

The purpose of this study was to obtain information regarding the effects of exercise on longevity in rats. The exercise used was voluntary activity wheel running. The runners gradually decreased their running from approximately 4 to approximately 1 mile/day as they aged from 9 to 30 mo. The runners lived slightly but significantly longer than sedentary freely eating controls and sedentary pair-fed controls (1,012 +/- 138 vs. 923 +/- 160 and 928 +/- 186 days) but significantly less long than food-restricted paired-weight sedentary controls (1,113 +/- 150 days). Although the exercise improved survival, it did not result in an extension of life-span. In contrast, the food-restricted paired-weight sedentary rats showed a true increase in life-span. The paired-weight rats also had a significantly reduced incidence of malignancies compared with the other three groups. However, there was no significant difference between the runners and the freely eating or pair-fed sedentary controls in the cause of death. These results provide evidence that exercise improves survival but does not result in an extension of life-span in rats.

Animals

Polyclonal B cell hyperplasia associated with Epstein-Barr virus causing acute renal allograft failure.

Six weeks post cadaver renal transplantation, a patient developed a flu-like illness. Acute renal failure unresponsive to anti-rejection therapy occurred and he died four days later from Pneumocystis carinii pneumonia and Streptococcus viridans septicemia. Autopsy revealed a diffuse polymorphic polyclonal B cell infiltrate occupying most organs, including the allograft. Primary Epstein-Barr Virus (EBV) infection was established by 1) rising anti-EBV antibody titres; 2) the demonstration of EBV nuclear antigen in the infiltrate and 3) the presence of EBV specific DNA sequences in affected tissues. EBV associated polymorphic B cell hyperplasia can mimic rejection and result in acute allograft failure.

Antibodies, Viral

Direct solid-phase radioimmunoassay for screening 17 alpha-hydroxyprogesterone in whole-blood samples from newborns.

We describe a direct, solid-phase RIA for 17 alpha-hydroxyprogesterone (17-OH-P) that we are using to screen neonates for congenital adrenal hyperplasia. Phosphate buffer containing danazol and anti-17-OH-P is placed in tubes coated with antibody to IgG. The tubes also contain standards, controls, or blood samples on filter paper discs 3 mm in diameter. 125I-labeled 17-OH-P is added to each tube. The mixture is vortex-mixed and incubated overnight. The fluid and disc are removed, the radioactivity remaining in the tubes is counted, and the amount of 17-OH-P per disc is calculated by using a log-logit transformation of the standard curve. Results compare favorably with those by two extraction assays. Inter- and intra-assay CVs were less than 11% and less than 9%, respectively. Sensitivity was 2 pg per assay tube. There is no significant cross reactivity with structurally related steroids at their physiological concentrations. Analytical recovery of added 17-OH-P averaged 104%. 17-OH-P in whole blood spotted on filter paper is stable for at least six months.

17-alpha-Hydroxypregnenolone