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Biomedical subjects

R A Gutman

Publications and source records attributed to R A Gutman.

18 recordsLinked to original sources

Variable mortality rates among dialysis treatment centers.

OBJECTIVE: To examine the variation in the risk for mortality among patients treated at renal dialysis facilities within a defined geographic area. SETTING: All free-standing and hospital-based dialysis facilities in a single southeastern state reported to the registry. DESIGN: Cohort of dialysis patients followed for 1 year by an end-stage renal disease registry. PATIENTS: Patients (n = 3612) aged 20 years and older receiving treatment at the dialysis facilities reporting to the registry during 1987. MEASUREMENTS: Demographic, comorbid, and severity of illness indicators were abstracted from patient records. Facility-specific risk estimates were derived from a Cox proportional hazards model. RESULTS: Facility-specific mortality rates ranged between 2.0 and 10.5 deaths per 10,000 patient days. Mortality rates were higher among older persons; whites; those with a history of diabetic nephropathy, angina, or congestive heart failure; and patients with either nutritional or functional status impairment. Facility-specific prevalence of each mortality risk factor varied widely. The unadjusted risk for death in a facility at the 75th percentile of risk was 1.3 times that of a facility at the median, whereas at the 25th percentile, it was 0.68 times as likely--a twofold range of risk. Controlling for differences in the prevalence of patient characteristics did not change the interquartile range in risks, and a facility's adjusted risk estimate showed a strong correlation with its unadjusted estimate (R2, 0.566; P less than 0.0001). CONCLUSIONS: Patient attributes associated with increased risk for mortality vary widely among dialysis facilities. Adjustment for these differences did not, however, substantially change either the degree of variation in mortality risks or the relative ranking of a facility's mortality.

Adult

[Intensified insulin therapy in the management of gestational diabetes].

A total of 35 pregnancies in 28 Pregestational Diabetic Patients (PDP) were followed with the goal of achieving and maintaining near normoglycemia (as many pre-postprandial glycemias as possible between 60-140 mg/dl); 13 patients (16 pregnancies) were assigned to Subcutaneous Continuous Preprogrammed Insulin Infusion (SCII) because of high risk pregnancies (HRP) (at least one of the following: former history of spontaneous abortions, stillbirths, premature deliveries and/or sterility). The remaining 12 PDP's (15 pregnancies with no past history of the above nature) were treated with Multiple Conventional Insulin Injections (MCII). Both groups were comparable regarding the following clinical parameters: age, time of onset and class of diabetes. All patients were instructed in performing 3 to 7 daily Self Capillary Blood Glucose controls (SCBG). Mean follow-up observation period was (mean +/- SEM) 28.5 +/- 2.5 weeks for SCII and 3.2 MCII and 28.8 +/- 3.2 weeks for MCII. All the 3 PDP drop out's (4 pregnancies) belonged to the CMII group. No drop out's were recorded in the SCII group. Both insulin therapy approaches were similarly effective in improving metabolic control in that comparable levels of mean blood glucose (MBG) and HbA1 were attained by SCII and MCII (Fig. 1). Compliance, as evidenced by average of daily SCBG was also similar in both groups (Fig. 2). Such satisfactory metabolic control was achieved mostly because of an increase in the percentage (65%) of "fair" glycemias (60-139 mg/dl) and not because of an increase in hypoglycemias (< 60 mg/dl) which could have canceled out an undesirable degree of hyperglycemias thus rendering "false satisfactory" MBG's and HbA1 (Fig. 1). With the above degree of metabolic control obtained there occurred no severe hypoglycemic episodes requiring medical intervention. All newborns to the PDP's who remained under treatment showed an adequate APGAR (X +/- SEM, 9.5 +/- 0.2) regardless of the modality (SCII or MCII) of insulin delivery used (Tables 1, 2). The single malformed baby found in this series was born to a patient on SCII who happened to start on the intensified insulin treatment rather late in her pregnancy (21st week) and, in addition, the patient self medicated with high doses of chlorpromazine because of recurrent vomiting episodes. Incidence of neonatal hypoglycemia (HY) or macrosomy (MS) was comparable in both groups (Tables 1, 2). It is to be pointed out, however, that PDP's who bore the babies with no HY or MS had presented a larger number of low glycemic values than mothers who bore the babies with HY and/or MS.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

H-ras protooncogene mutations in human thyroid neoplasms.

Structural alterations of protooncogene sequences may be involved in the pathogenesis of human neoplasms. We screened 54 thyroid tumors (36 benign and 18 malignant) for gene rearrangements of the protooncogenes c-myc, c-myb, c-fos, c-erb-B1, c-erb-B2, c-erb-A, N-ras, K-ras, and H-ras. Only mutations of H-ras were observed. None of the 15 colloid adenomas examined had detectable H-ras rearrangements. Of the remaining tumors, we observed mutations of H-ras in 4 benign and 4 malignant neoplasms. Gene amplification was found in 5 tumors. An aggressive recurrent papillary carcinoma had a marked amplification of one of the H-ras alleles. The amplified allele was truncated, in that the 3' variable tandem repeat was not a part of the amplification unit, and contained a codon 12 point mutation leading to a valine for glycine substitution. We also observed the association of low copy gene amplification with a codon 12 valine for glycine mutation in a follicular adenoma. Two tumors contained H-ras EcoRI polymorphisms not present in the DNA of normal thyroid from the same individuals, and one follicular carcinoma showed loss of an H-ras allele. Ras protooncogenes may become transforming by quantitative mutations, leading to increased expression, or qualitative mechanisms, through activating point mutations. Both of these appear to coexist in thyroid neoplasms, and it may be that a combination of both mechanisms is capable of inducing a more complete spectrum of neoplastic phenotypes.

Base Sequence

[Immune response in rabbits to tumoral tissue extracts of human colon].

Carcinoembryonic antigen (CEA) was purified after perchloric acid extraction of glycoprotein from human normal and tumoral colon. Antibodies against those extracts as well as purified CEA were raised in rabbits. Sera obtained from animals immunized with tumoral extract in protracted schemes showed disperse behavior on polyacrylamide gel electrophoresis (PAGE) for proteins in the area with gamma, mobility which were markedly increased. In addition, a large increase of proteins with a mobility comparable to alpha 2 proteins was observed. The latter increase was not present in sera of rabbits immunized with normal colon extracts. Low titer antisera were obtained after immunization with either antigen as revealed by immunodiffusion. The relatively highest titers were seen against the glycoprotein fraction of tumor extracts which had previously been enriched by isoelectric focusing. Immunoelectrophoresis of tumor extracts against homologous antisera revealed bands with beta mobility due to the presence of CEA antibodies only in the sera of animals injected with tumor extracts. Antibody titers assayed by radioimmunoassay (RIA) revealed that the highest titers were obtained from tumor glycoprotein extracts was used as an immunogen. Measurements of CEA concentrations in serum of patients with low and high levels of CEA showed non significant differences by statistical analysis, when antisera obtained from different bleedings of the same animals were used. It is concluded that in order to establish a CEA RIA for clinical purposes it is necessary to purify up to the isoelectric focusing step the material to be labelled as tracer or used as standard. Antibody reagent may be obtained by immunizing schemes or protracted schemes using crude perchloric acid extracts of colon tumor.

Adult

Cytomegalovirus infection and chronic hemodialysis.

Serologic and virologic studies of cytomegalovirus (CMV), a virus infection often disseminated in immunosuppressed patients, were initiated among hemodialysis patients, home dialysis partners, hemodialysis center personnel, and several groups of patients. No evidence was found of activation or persistence of CMV infections in connection with chronic renal disease or in association with hemodialysis. Evidence of increased CMV activation and/or infection was found among individuals who had re-entered the dialysis program following renal allograft rejection. The data indicate that dialysis personnel and home dialysis partners are not at increased risk for CMV infection. The findings of this study, which contrast with those pertaining to hepatitis B infection, suggest that different mechanisms are responsible for establishing both infection and persistence of CMV and hepatitis B.

Adult

Automated peritoneal dialysis for home use.

In order to provide an alternative to maintenance home dialysis for patients remotely situated or who had vascular access failure, a parallel peritoneal dialysis (PD) program was developed in March 1972. Over four years, 36 patients started PD with the intention of carrying out home treatments. Thirty of the 36 succeeded and 22 completed at least six months of home treatments, seven have so far been treated for over one year. No neuropathy developed except in diabetic patients. No patient, including four who had undergone bilateral nephrectomy, was depenedent on blood transfusions. Predialysis serum creatinine values were questionably higher (p less than 0.07) in a group of six patients who at another time had been maintained on hemodialysis (HD). In this group serum albumin was (mean +/- 1 S.D.) 3.3 +/- 4 g/100 ml on PD and 3.8 g/100 ml on HD (p less than 0.05). Sixteen of the 36 patients had bacterial peritonitis on 22 occasions; the average incidence was once every 14 months of patient exposure. An epidemic of sterile peritonitis involving 40 episodes in 16 patients was resolved after machine techniques were changed. Catheter failure occurred in 15 of the 22 patients in the long-term group, but catheter replacement was not difficult.

Adult

Renal intracortical blood flow distribution, function and sodium excretion in response to saline loading of anesthetized and unanesthetized dogs.

In order to study the effect of anesthesia on the canine response to saline loading, experiments were performed on 10 dogs, first while awake and then during pentobarbital anesthesia. Individual kidney function and intrarenal blood flow response to saline loading (7.5% body weight) were measured in each condition and all data are reported as the average of a single kidney. CIN is considerably reduced under anesthesia (24.7 +/- 3.2 vs. 43.2 +/- 3.9 ml/min, P less than 0.01). A directionally similar reduction of PAH clearance was noted (89 +/- 17 vs. 122 +/- 13 ml/min). The natriuretic response to saline loading of the dogs reached 290 +/- 61 muEq/min while awake, but only 70 +/- 27 muEq/min while anesthetized. No measurable increase of CIN or CPAH occurred in response to saline loading either in the anesthetized or unanesthetized state. The natriuresis was entirely due to a rise of CNA/GFR in both circumstances. The change of CNA/GFR in response to saline load was also appreciably larger while awake (1.2 leads to 4.7% vs. 0.7 leads to 1.8%). Although the fraction of blood flow to the outermost quarter of the kidney was initially the same (31 +/- 3 vs. 29 +/- 3%) awake or anesthetized, the changes with saline loading were in the opposite direction and the values reached were significantly different (37 +/- 3, awake, vs. 27 +/- 3%, P less than 0.05). We conclude that while increased outer cortical blood flow is not necessary for natriuresis, it may occur during sodium loading and may facilitate sodium excretion.

Animals

Renal transplantation between HL-A haploidentical donor-recipient pairs: functional and morphological evaluation.

Fifty-nine recipients received renal allografts from an HL-A haploidentical family member. Immunogenicity of the incompatible haplotype was measured by skin grafts exchanged within each family when possible, and renal allograft recipients were assigned prospectively to two groups depending on the skin graft survival time (Group 2A greater than 15 days; Group 2B less than 15 days). If skin grafts could not be accomplished, the patients were place in an unclassified group, Group 2. Renal function at one and 2 years following engraftment did not differ between the two groups. Mixed lymphocyte stimulation of recipient lymphocytes by mitomycin-treated donor lymphocytes also was comparable in the groups. Histopathological evaluation by light, immunofluorescence, and electron microscopy at least 6 months following allografting did not distinguish between the groups. The only differentiating characteristic was that Group 2A patients did not experience their primary rejection episode until an average of 18 days following transplantation, whereas Groups 2B and unclassified 2 had their initial primary rejection episode at average days 9 and 5, respectively. In our clinical program, matching for HL-A halotypes continues to be the best predictor for long-term renal function in consanguineous renal transplantation.

Antibody Formation

Renal intracortical blood flow distribution, function, and sodium excretion in unanesthetized dogs following vena caval ligation.

We studied the renal function and the intrarenal blood flow of nine dogs whose thoracic inferior vena cava had been previously ligated (caval dogs) and nine other dogs. Following preparative surgery which included placement of a left atrial catheter, a femoral artery catheter, and bilateral ureteral catheters, the caval dogs gained an average of 2.1 kg of fluid weight, whereas the normal dogs gained no weight. Although neither the caval dogs' blood pressure (114 plus or minus 7 vs 120 plus or minus 4 mm Hg) nor their inulin clearance (0.64 plus or minus 0.06 vs. 0.79 plus or minus 0.06 ml/min g-1 kidney weight) was significantly reduced, their estimated renal blood flow (Cpah/[1-hematocrit]) was considerably lower (2.30 plus or minus 0.24 vs. 3.25 plus or minus 0.15 ml/min g-1). During the clearance study, the caval dogs' excretion of sodium (79 plus or minus 18 vs. 158 plus or minus 17 muEq/min) and their fractional clearance of sodium (2.0 plus or minus 0.4 vs. 3.4 plus or minus 0.5%) were reduced. Studies with microspheres failed to demonstrate a selective decrease in blood flow. However, comparison studies of nine other dogs (five caval and four normal) demonstrated that microsphere results were less reproducible in caval dogs than they were in normal dogs. We have concluded taht reduced blood flow is the only consistent alteration of renal function in this edematous animal model and that previous suggestions of altered distribution are not supported by these studies.

Aminohippuric Acids

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