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Biomedical subjects

D M Wilson

Publications and source records attributed to D M Wilson.

At least 217 records · Page 12Linked to original sources

The association of nephrolithiasis and autosomal dominant polycystic kidney disease.

Despite the frequency and morbidity of nephrolithiasis in autosomal dominant polycystic kidney disease (ADPKD), this association has not been subject to a detailed study. One hundred fifty-one of 751 ADPKD patients seen at the Mayo Clinic between 1976 and 1986 had nephrolithiasis. Seventy-four had passed calculi or had stones surgically removed. Stone analysis was available in 30 patients: uric acid, calcium oxalate, calcium phosphate, and struvite were present in 56.6%, 46.6%, 20%, and 10%, respectively. Calculi were observed in 71 of 79 patients with excretory urograms available for review. Faintly opaque and bull's eye stones, probably containing uric acid, were present in 12.7% and 14.1% of these patients, respectively. Precaliceal tubular ectasia was observed in 15.5%. Ninety-seven patients had preserved renal function (serum creatinine less than 1.5 mg/dL) at the initial evaluation. Six were excluded because they had other known causes of stone disease. The most common metabolic abnormality in the remaining 91 patients was hypocitric aciduria (ten of 15 patients with measurements). The urine pH in the first voided morning specimens (5.66 +/- 0.05) was significantly lower than that of an unselected control population (5.92 +/- 0.03, P less than 0.001). Hyperuricosuria, hyperoxaluria, and hypercalciuria were observed in six of 32 (18.8%), six of 31 (19.4%), and three of 39 (9.7%) patients with preserved renal function. The composition of the stones, the frequency of hypocitric aciduria, and the low urine pH (possibly related to the defect in excretion of ammonia described in ADPKD), suggest that metabolic, along with mechanical, factors are responsible for the frequent occurrence of nephrolithiasis in this disease.

Adult↗

Structural and immunohistochemical characterization of insulin-like growth factor I and II receptors in the murine central nervous system.

The description of the cellular localization of insulin-like growth factor (IGF) receptors in the central nervous system (CNS) remains incomplete, as do the descriptions of changes in their characteristics with respect to different developmental stages. We, therefore, performed affinity labeling studies in microsomal membrane preparations of adult and fetal rat brain and liver tissues with [125I]IGF-I and [125I]IGF-II. These studies demonstrated tissue- and developmental stage-specific structural variants of type I receptor alpha-subunits as well as type II receptors. The adult rat brain type I alpha-subunit had an apparent mol wt (Mr) of 127,000, whereas those of adult and fetal rat liver measured 140,000. Fetal rat brain microsomes, however, had two types of type I receptor alpha-subunits measuring 130,000 and 120,000 Mr. The larger subunit from fetal brain consistently migrated at an apparent Mr of 3,000, greater than subunits from adult brain. Both type I and II receptors were more abundant in fetal liver and brain than in adult tissues. Affinity labeling was also performed directly to monolayers of cultured fetal brain neurons and newborn astrocytes. These studies detected both type I and II receptors on the surfaces of both types of cells. However, only the high Mr (140,000) form of the type I alpha-subunit was detected in cultured CNS cells, suggesting that expression of low Mr variant receptors is altered in vitro. Type II receptors were demonstrated by immunohistochemistry in adult rat hypothalamic neurons. However, the majority of neurons did not react with type II receptor antibody. This finding implies that only a minority of hypothalamic neurons are capable of responding to IGF-II via type II receptors. On the other hand, all astrocytes had striking type II receptor immunoreactivity. This signifies a more general biological role for this receptor in astrocytes compared with neurons. These results suggest that different tissue-, developmental stage-, and cell-specific processes are mediated by IGF receptors and suggests new directions in which to explore potential biological actions for these receptor-ligand systems in the CNS.

Affinity Labels↗

Prostaglandin synthesis by osteoid osteoma and osteoblastoma.

Osteoid osteomas are characterized clinically by a pattern of nocturnal pain which is exquisitely sensitive to salicylates. Etiology for the pain has been ascribed by previous investigators to the presence of nonmyelinated nerve fibers or to the effect of prostaglandins. In an effort to corroborate the potential role of prostaglandins in mediating the pain associated with this tumor, we have determined the concentration of prostaglandins E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 utilizing radioimmunoassay of extracts of homogenated tumor tissue. Results were compared with similar extracts of normal bone and a variety of other osseous tumors. The increased concentrations of prostaglandin E2 found in cases of osteoid osteoma and osteoblastoma confirm studies of explants of these tumors previously recorded in the literature.

Bone Neoplasms↗

Melanogenuria: laboratory evaluation of the qualitative Thormählen and ferric chloride tests and their clinical utility.

Malignant melanoma, a disease that is increasing in occurrence and medical concern, is characterized by the excretion of melanogens. Two qualitative tests are recommended for melanogen detection, the Thormählen test and the ferric chloride test. We evaluated the laboratory and clinical performance of these tests by subsequently re-evaluating 201 urine samples that had been submitted for routine melanogen analysis. We used (a) Thormählen, (b) ferric chloride, (c) small-scale thin-layer chromatography, and (d) spectrophotometry. Nearly 30% of Thormählen test results were equivocal. The ferric chloride test was of no value in itself or in categorizing equivocal Thormählen results as positive or negative. The small-scale chromatography was irreproducible. Prompt scanning of the Thormählen reaction product was helpful in classifying equivocal results. History review of 121 histopathologically diagnosed melanoma patients indicated that these qualitative assays were of no clinical value in the diagnosis or monitoring of melanoma patients.

Chlorides↗

Identification of an apoC-II variant (apoC-IIBethesda) in a kindred with apoC-II deficiency and type I hyperlipoproteinemia.

Apolipoprotein (apo) C-II deficiency is characterized by elevated plasma triglycerides, chylomicrons, and very low density lipoproteins, as well as reduced levels of low density and high density lipoproteins. A subject with apoC-II deficiency has been identified with an apoC-II plasma level of less than 0.05 mg/dl. The plasma apoC-II in the proband was immunochemically similar to apoC-II in normal subjects when analyzed by Ouchterlony immunodiffusion, however the apoC-II had an apparently lower molecular weight and higher pI when analyzed by two-dimensional gel electrophoresis. This apoC-II variant, designated apoC-IIBethesda, was not affected by neuraminidase treatment or reduction. Two-dimensional gel electrophoresis of the plasma of the mother of the proband revealed both normal apoC-II and apoC-IIBethesda, whereas analysis of the father and two siblings revealed apoC-II of normal electrophoretic mobility. These results were interpreted as indicating that the proband was a compound heterozygote with one allele for apoC-IIBethesda inherited from the mother and an allele coding for an abnormality which results in the virtual or complete absence of plasma apoC-II from the father. This proband represents the first example of a compound heterozygote for an apolipoprotein defect associated with a dyslipoproteinemia.

Apolipoprotein C-II↗

Cation specificity for sugar substrates of the melibiose carrier in Escherichia coli.

A study has been made of the sugar substrate specificities and the cation specificities of the melibiose transport system of Escherichia coli. The following beta-galactosides were found to be transported: lactose, L-arabinose-beta-D-galactoside, D-fructose-beta-D-galactoside, o- and p-nitrophenyl-beta-D-galactosides. These beta-galactosides were cotransported with Na+ but not with H+. The alpha-galactosides raffinose, melibiose and p-nitrophenyl-alpha-galactoside were transported with either H+ or Na+. Of the monosaccharides tested D-galactose could use either Na+ or H+ for cotransport whereas D-fucose, L-arabinose and D-galactosamine could use only Na+. The sugar specificity requirements for H+ cotransport are therefore more exacting than those for Na+ cotransport.

Cations↗

Supportive follow-up for cigarette smokers in a family practice: issues of method, analysis and state of the art.

Kozlowski and Page have criticized a study published in 1982 in CMAJ on the effects of supportive follow-up on the rate at which patients quit smoking cigarettes. We agree with some of their general sentiments about the need for establishing a consensus on the evaluation of smoking cessation programs. More specifically, we defend the particular analysis originally used, given the state of knowledge and constraints on the study. We examine their main objections: the definition of successful cessation, the design of the study, the exclusion of patients lost to follow-up, the methods of statistical analysis used and the strength of more recent evidence on the usefulness of follow-up visits. We believe that the role of supportive follow-up deserves further evaluation.

Evaluation Studies as Topic↗

A smoking cessation intervention program for family physicians.

Family physicians are able to approach many patients who smoke but are often hesitant to help them quit. Lack of knowledge about effective interventions is a major reason for this hesitancy. The important components that have been tested in physician-initiated smoking cessation interventions are advice to quit, information about the risks of smoking and techniques for quitting, nicotine gum, setting a date for quitting and offers of supportive follow-up visits. We describe a cessation program developed for family physicians that incorporates these factors into three types of visits over a 2-month period: the challenge visit, which occurs during a regular office visit and focuses on advice and setting a date to quit; the quit-date visit, which involves instructing patients on the proper use of nicotine gum, if applicable, and confirming their desire to quit; and four supportive follow-up visits, which provide continuing encouragement for 2 months and allow physicians to monitor withdrawal symptoms, relapses and other problems. Such a program can be effectively incorporated into a general practice.

Chewing Gum↗

Growth curves and adult height estimation for adolescents.

Using data from the large number of adolescents studied in cycle III of the National Health Examination Survey, we utilized a sexual maturity index to develop a set of growth curves that reduce the distortion caused by commingling height data from adolescents maturing at different rates. We also created a set of correction tables to be used with these curves to permit the calculation of an adjusted height percentile that compensates for the effects of the differing rates of pubertal maturation. These adjusted height percentiles should remain more constant throughout puberty than height percentiles obtained from traditional growth curves; they may thus be used to estimate final adult height with only data obtained during routine physical examinations, by assuming that subjects maintain their adjusted height percentile through adolescence to adulthood. Height predictions made in this manner compare favorably with predictions made using two clinically tested algorithms.

Adolescent↗

Linear growth response to exogenous growth hormone in Prader-Willi syndrome.

Linear growth retardation and adult short stature are usual characteristics of Prader-Willi syndrome. Several lines of evidence suggest that a deficiency in growth hormone (GH) secretion may contribute to this abnormal growth pattern. We have recently reported observations in 4 children with Prader-Willi syndrome treated with GH. This report extends our observations in 2 of these cases. Both cases had abnormally low growth rate, normal stimulated GH levels, and low somatomedin-C levels prior to therapy. GH treatment led to significant increases in linear growth rate and somatomedin-C levels. An additive effect of oxandrolone therapy on linear growth rate was demonstrated in one case. Our results support the possibility of a neuro-secretory GH deficiency in Prader-Willi syndrome and suggest a need for further investigations.

Body Height↗

Semi-automated enzyme-linked immunosorbent assay (ELISA) for the quantification of apolipoprotein B using monoclonal antibodies.

A semi-automated competitive, double-antibody, solid-phase enzyme-linked immunosorbent assay for apolipoprotein B (Apo B) has been developed which utilizes microtiter plates with commercially available monoclonal antibodies and alkaline phosphatase-conjugated second antibody. The working range of the assay is 20-200 ng. The concentration of plasma Apo B was 0.88 +/- 0.20 g/l (n = 40) for a random sample of normal adults. The correlation coefficient for this assay, compared to a radial immunodiffusion assay, was 0.95 (slope = 1.13, intercept = -15). The quantification of the samples was not influenced by freezing and thawing, storage at -20 degrees C for up to 9 mth, or the lipoprotein particle on which the Apo B was present. The method is suitable for measurement of apolipoprotein B in either normal or pathological plasma, lipoprotein density classes, and is sensitive enough to quantify Apo B in cell biological and molecular biological investigations.

1-Propanol↗

The effect of smoke age and dilution on the cytotoxicity of sidestream (passive) smoke.

Decreases in the mortality of monolayer cultures of L-929 cells exposed to sidestream (passive) smoke with increases in smoke age and dilution have been reported. In the current study, the concentration of sidestream smoke (SS) to which cells were exposed was directly correlated with % mortality (r = 0.987) having 0% mortality at a concentration of 1.19% and a calculated mortality of 9562% at a concentration of 100%. The In of % mortality was correlated with increases in smoke age (r = -0.9999) and the regression equation was used to calculate 0 mortality at an age of 30 s and 393% mortality at the time of smoke generation. In addition, when sidestream smoke generated from a low-yield, filtered, modern design experimental cigarette was compared with that generated from a high-tar non-filtered reference cigarette, a lower number of puffs of smoke from the low-yield cigarette than from the high tar cigarette was necessary to yield 50% mortality of cells.

Animals↗

Emergency diagnosis of pituitary apoplexy.

A 60-year-old man, chronically anticoagulated for a prosthetic heart valve, suffered visual loss from hemorrhage into an unsuspected pituitary tumor. The diagnosis of pituitary apoplexy was made in the emergency department. The patient's coagulopathy was reversed, and he underwent an uneventful transsphenoidal hypophysectomy. Marked recovery of vision occurred over the next six months. The clinical features of this uncommonly diagnosed syndrome are reviewed, and the importance of recognizing this entity with the advent of computed tomographic scanning is emphasized.

Adenoma↗

Treatment of short stature and delayed adolescence.

The treatment of growth failure in children with documented GH deficiency remains the only noncontroversial indication for GH therapy. There are increasing data suggesting that GH may be useful in treating some children with Turner's syndrome and with NVSS. Further studies, however, are necessary to evaluate the long-term efficacy and safety of GH therapy in these children. The treatment of non-GH deficient children whose heights are within two standard deviations of the mean height for age is clearly inappropriate and should be avoided, despite parental protests.

Adolescent↗

Blood pressure determinants in living-related renal allograft donors and their recipients.

We studied 99 living related allograft donors with follow-up information of at least 10 years and the 50 recipients who had successful outcomes. Recipients were younger and had significantly lower blood pressures at follow-up than their donors. Borderline and definite hypertension were present in 22.2% and 4.0% of donors prior to donation, in 14.4% and 21.1% of donors at follow-up, and in 2.0% and 18.0% of the 50 recipients at follow-up. Age, relative weight, and mean arterial pressure (MAP) prior to donation were the key variables in predicting the follow-up ranked MAP of the donors. CPAH prior to donation was inversely correlated with the age of the donors and, indirectly, with the follow-up MAP. Donor CPAH prior to donation was significantly correlated with the renal allograft function of the recipients but not with the recipient ranked MAP at follow-up. No correlation of the ranked MAP or blood pressure outcome categories between donors and recipients was found. We conclude that donation of one kidney can accelerate the development of hypertension in those donors with predisposition to develop hypertension. In addition, the predisposition of the donors to develop hypertension and their age, within the range observed in the study, does not significantly influence the long-term blood pressure status of the recipient.

Adult↗

Transplantation of insulin-like growth factor-II-secreting tumors into nude rodents.

Restricted supplies of insulin-like growth factor II (IGF-II) have severely limited investigation of the in vivo actions of this hormone. To circumvent this problem, we have developed an in vivo rodent model in which rat (r) IGF-II-secreting cells (18, 54-SF) are transplanted into congenitally immunodeficient (nude) rats and mice. These cells proliferate and form discrete tumors that contain rIGF-II and abundant IGF-II receptors. The tumors also secrete rIGF-II into the circulation, resulting in plasma rIGF-II concentrations many-fold greater than those in control rodents (81 +/- 19 vs. less than 10 ng/ml, rats; 159 +/- 28 vs. 18 +/- 5 ng/ml, mice; P less than 0.05, both groups). There was no significant difference between the tumor-bearing and control rodents in either body weight or tail length. The tumor-bearing rodents did have significantly lower concentrations of IGF-I (296 +/- 23 vs. 527 +/- 67 ng/ml, rats; 300 +/- 26 vs. 482 +/- 70 ng/ml, mice; P less than 0.05, both groups), suggesting that the increased concentrations of rIGF-II may have inhibited IGF-I production or secretion. This animal model may be used to explore the biological effects of increased plasma IGF-II concentrations.

Adenoma↗

The Ames Clinitek 200/Multistix 9 urinalysis method compared with manual and microscopic methods.

We assayed 315 urine specimens by the Ames Clinitek 200/Multistix 9 semi-automated method and by corresponding standard methods (listed in parentheses) for the following analytes: protein (sulfosalicylic acid precipitation), glucose (Lilly Tes-Tape), ketones (Boehringer Mannheim Chemstrip K), leukocyte esterase (microscopic examination for leukocytes), blood (microscopic examination for erythrocytes), nitrite (microscopic examination for bacteria, Gram stain, or culture), and pH (pH meter). The Clinitek and standard methods agreed well at all concentrations for protein, ketones, and glucose. The Clinitek leukocyte esterase, nitrite, and blood methods were less sensitive than microscopic methods for detection of pyuria, bacteriuria, and hematuria, respectively. The Clinitek pH method produced falsely low pH values for urines with true pH less than 6.5, and falsely high values for urines with true pH greater than 6.5.

Autoanalysis↗

Testicular tumors with Peutz-Jeghers syndrome.

The case of a 6-year-old boy with Peutz-Jeghers syndrome (PJS), gynecomastia, and multifocal and bilateral testicular tumors is described. Females with PJS are known to be at increased risk for developing gonadal tumors. This case and other reports from the literature suggest that males, as well as females, with PJS are at risk for developing gonadal tumors.

Child↗