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Biomedical subjects

R A Gutman

Publications and source records attributed to R A Gutman.

At least 37 records · Page 2Linked to original sources

Optimizing glycemic control: can insulin dependent diabetic patients rely on their perception of blood glucose fluctuations in order to make therapeutic decisions?

30 insulin dependent diabetic (IDD) patients without clinically evident autonomic neuropathy were asked on 128 occasions to estimate quantitatively what they believed their capillary blood glucose (CBG) to be (predicted blood glucose--PBG) immediately before an actual CBG measurement was performed (real blood glucose--RBG). A statistically significant correlation was found between the pooled RBG's and PBG's of our patient population (r = 0.57, p less than 0.001). However, there was a notable skewing of the RBG/PBG curve, evidencing a tendency of our patients' predictions to be closer to normality. This is further documented by the fact that the mean M value of the RBG's of each of the 11 patients with more than 6 predictions was significantly greater than the mean M value of the corresponding PBG's. Within the ranges of hypoglycemia (RBG less than or equal to 3.3 mmol/l) and of normoglycemia (3.4-7.8 mmol/l) there was no correlation between RBG's and PBG's. With RBG's greater than or equal to 7.8 mmol/l the correlation was statistically significant (r = 0.41, p less than 0.01). When the pooled predictions were analyzed according to qualitative accuracy for different ranges of RBG the following trend emerges: for RBG's less than or equal to 3.3 mmol/l (60 mg%), 2/11 predictions were accurate (18%), for RBG's greater than or equal to 12.3 mmol/l (221 mg%), 30/37 (81%) and for RBG's between 3.4 and 12.2 mmol/l (61-220 mg%), 44/80 (55%). In conclusion, our patients as a whole showed an ability to discriminate between high, normal and low levels of blood glucose, albeit with a strong bias to predict values closer to the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hypophosphatemia in long-term renal transplant recipients: effects on bone histology and 1,25-dihydroxycholecalciferol.

The effects of long-term hypophosphatemia were studied in 10 renal transplant recipients with persistent hypophosphatemia. The renal transplant recipients are 3-14 years (mean 8.7 +/- 4 years) post transplantation. The mean (+/- SD) serum calcium, phosphate, and creatinine levels are 9.66 +/- 0.42, 2.29 +/- 0.16, and 1.47 +/- 0.23 mg/dl, respectively. Carboxy (C)-terminal parathyroid hormone (PTH) is elevated in 8 hypophosphatemic renal transplant recipients. The mean 1,25-dihydroxycholecalciferol [1,25(OH)2D3] level is 33 +/- 20 pg/ml (normal 19-55 pg/ml) compared to 42 +/- 0.6 pg/ml (NS) in 4 normophosphatemic renal transplant recipients with comparable renal function. The 1,25(OH)2D3 level correlates with C-PTH (p less than 0.01) but not serum phosphate. Anterior iliac crest bone biopsies were obtained in all 10 hypophosphatemic renal transplant recipients. Histomorphometric analysis of osteoblastic osteoid, total surface osteoid, bone-osteoclast interface, total resorption, osteoclasts/mm2, osteoid seam width, and relative osteoid volume are not significantly different from normals. Trabecular bone volume is decreased (15.6 +/- 5.7 vs. 23 +/- 5%, p less than 0.01). Comparison of dynamic parameters with normal reveals no differences in appositional and bone formation rate. In summary, in hypophosphatemic renal transplant recipients: hypophosphatemia does not produce osteomalacia; hyperparathyroidism is often observed, and plasma 1,25(OH)2D3 levels, in general, remain in the normal range.

Adult↗

The quality of life of patients with end-stage renal disease.

We assessed the quality of life of 859 patients undergoing dialysis or transplantation, with the goal of ascertaining whether objective and subjective measures of the quality of life were influenced by case mix or treatment. We found that 79.1 per cent of the transplant recipients were able to function at nearly normal levels, as compared with between 47.5 and 59.1 per cent of the patients treated with dialysis (depending on the type). Nearly 75 per cent of the transplant recipients were able to work, as compared with between 24.7 and 59.3 per cent of the patients undergoing dialysis. On three subjective measures (life satisfaction, well-being, and psychological affect) transplant recipients had a higher quality of life than patients on dialysis. Among the patients treated with dialysis, those undergoing treatment at home had the highest quality of life. All quality-of-life differences were found to persist even after the patient case mix had been controlled statistically. Finally, the quality of life of transplant recipients compared well with that of the general population, but despite favorable subjective assessments, patients undergoing dialysis did not work or function at the same level as people in the general population.

Adult↗

[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↗

Controlled comparison of hemodialysis and peritoneal dialysis: Veterans Administration multicenter study.

We measured mortality and morbidity among 114 patients assigned randomly to home hemodialysis (HD) and home intermittent peritoneal dialysis (IPD). Data were collected during the time of home training and for 12 months after initiation of home dialysis. Training time was shorter for the IPD than for the HD patients (P less than 0.001) with median time 1.8 months for IPD and 3.9 months for HD. Switching to the alternative mode of treatment was more frequent for the IPD group (29/59 vs. 5/55, P less than 0.001). Survival time was not different, perhaps because of the modality change. More IPD patients were hospitalized in the first 6 months (20 for IPD vs. 9 for HD, P = 0.02), but they had fewer troublesome cardiovascular events in the first year (0 vs. 12, P less than 0.001). The HD patients maintained better nutritional status as reflected in body weight and arm muscle circumference and possibly in urea appearance rate. Thus, these data suggest that for most patients, IPD is a less satisfactory form of therapy than HD, but certain advantages of IPD did emerge. Applications of this information to the currently more popular mode of CAPD await further study.

Clinical Trials as Topic↗

Postparathyroidectomy hypocalcemia as an accurate indicator of preparathyroidectomy bone histology in the uremic patient.

19 chronic renal failure patients underwent iliac crest bone biopsy prior to total parathyroidectomy with autotransplantation. The preoperative serum calcium concentration did not correlate with the number of osteoclasts/mm2 present on the preparathyroidectomy iliac biopsy. However, the postparathyroidectomy decrement in serum calcium (mg/dl and percent change) and the osteoclasts/mm2 were strongly correlated (p less than 0.001). In addition, the postoperative fall in serum calcium also correlated with the postoperative change in serum alkaline phosphatase (p less than 0.001). The nadir in postparathyroidectomy serum calcium was attained in a mean of 4.4 +/- 2.7 days. Our results indicate that the preoperative serum calcium concentration does not necessarily reflect active bone resorption, but the postoperative decrement in serum calcium provides an accurate index of preoperative histologic activity. The available data do not provide information with respect to the mechanism of postparathyroidectomy hypocalcemia since either the cessation of bone resorption, continued bone deposition, or a combination of both may be operative.

Adult↗

Characteristics of long-term (14 years) survivors of maintenance dialysis.

The characteristics of 25 men and women who have been maintenance dialysis patients for at least 14 years (average 15.7 years) were tabulated on the basis of a survey instrument. In addition to repeated problems with vascular access surgery, the most common medical problems surround difficulties with musculoskeletal system. The most severe manifestation of this was a fibrosing arthropathy and repeated pathologic fractures. Cardiovascular morbidity was less prominent. As a group, these patients were characterized largely as 'independent, organized and cheerful'. The average calculated dose of dialysis for this group was 27 m2. h/70 kg body weight per week.

Adult↗

Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis.

Fungal peritonitis is a rare complication in patients on continuous ambulatory peritoneal dialysis. We report five recent cases and their management. The fungi isolated were Candida albicans, C. parapsilosis, Exophiala jeanselmei, Drechslera spicifera, and a Fusarium species. Chemotherapy was attempted with various regimens including oral ketoconazole, intravenous or intraperitoneal amphotericin B, and oral flucytosine. Pharmacokinetic studies were done in two patients receiving treatment with one of these drugs. Three patients were cured of their fungal infection. Three patients whose Tenckhoff catheters were left in situ died, whereas two patients whose catheters were removed survived. Our experience suggests that removal of the peritoneal catheter should be considered once the diagnosis of fungal peritonitis is established.

Adult↗

Transient glucose intolerance in rats after a single injection of serum from a diabetic patient with an unusual insulin resistance.

The single intravenous injection to rats of 1 ml of serum from an insulin resistant patient without an excessive titre of insulin antibodies (total extractable insulin levels: 0.8 U/l, serum insulin binding capacity: 1.58 U/l) and no demonstrable insulin receptor antibodies, produced fasting hyperglycemia in the animals on the fourth day following the injection (FPG: 212 +/- 35 mg %). On the 7th day the FPG returned to normal but the IVGTT was still pathological. After 14 days there was complete normalisation of the IVGTT. Glucose intolerance did not occur when rats were injected with 1 ml of the following control sera: the patient's serum following 6 months of treatment with cyclophosphamide when her insulin resistance was in remission, pooled sera from IDD's without insulin resistance, serum from an insulin resistant IDD with a high titre of insulin binding capacity (greater than 40 U/l) or with serum from a normal human subject. There were no alterations on light microscopy of the pancreatic islets of rats sacrificed on the 4th or 21st days. The above data suggest that our patient carried an uncharacterised substance which was capable of inducing glucose intolerance in rats. Hypothetically, it may be postulated that it was an immunoglobulin or some other protein acting via downregulation of insulin receptors or interfering with a post-receptor event mediating insulin action.

Animals↗

A quantitative histomorphometric comparison of 40 micron thick Paragon sections with 5 micron thick Goldner sections in the study of undecalcified bone.

The value of quantitative histomorphometric analysis of undecalcified stained sections of bone is widely recognized. Five micron thick sections have been regarded as essential to carry out this analysis, but their production requires expensive equipment. Our laboratory was equipped initially only for the production of Paragon-stained 40 micron thick sections. These thicker sections have been used traditionally to guide the planimetric analysis of microradiographs. However, we found that they could be used for the simpler eyepiece graticule histomorphometric analysis in the same way that 5 micron sections have been examined. Sequential sections from iliac bone biopsy of 12 different patients with renal osteodystrophy were examined using each method. For 7 histologic features, the analysis of the thick sections compared very well with that of the Goldner-stained thin sections. The correlation coefficients varied from 0.88 for osteoid volume to 0.99 for osteoid surface. Other features compared included active and inactive osteoclastic surface activity. Further evidence of the usefulness of these thicker sections come from three other analyses. The expected close coupling of osteoblastic and osteoclastic activity was demonstrated (N = 56, r = 0.87, P less than 0.001). For 19 additional patients, two forms of histologic evidence of the degree of hyperparathyroidism correlated very well with the measured immunoreactive PTH (r = 0.93 and 0.93). Finally, normal values obtained with our method compare favorably with published normal values.

Benzopyrans↗

Osteomalacia in chronic renal failure: a syndrome previously reported only with maintenance dialysis.

Osteomalacia without marked elevations of parathyroid hormone (PTH) has been described in maintenance dialysis patients. The proposed etiology has centered upon the transfer of an environmental agent (aluminum) from the dialysis water system. The present report describes an azotemic patient, who, prior to the initiation of dialytic therapy, presented with severe osteomalacia and low PTH concentrations for the severity of renal failure. The osteomalacia was documented by bone histology on two occasions 1 year apart, and aluminum deposits at the osteoidmineralized bone interface were demonstrated with histologic techniques. PTH concentrations were within the normal range (less than 0.1 ng/ml) on three widely spaced intervals. No definite statement can be made regarding the etiology of the osteomalacic syndrome in this patient, but maintenance dialysis does not appear to be necessary for its expression.

Aged↗

Acquired cytomegalovirus retinitis. Four new cases and a review of the literature with implications for management.

49 cases of acquired cytomegalovirus retinitis were reviewed including three new cases in renal allograft recipients and one in a patient with Hodgkin's Disease. Diagnosis in over 90% of cases was based on the distinctive funduscopic appearance of cytomegalovirus (CMV) retinitis. When performed, urine, subretinal fluid, and blood buffy coat cultures were positive for CMV in 97, 67 and 39% of cases, respectively. More than two-thirds of these patients were organ transplant recipients who received chronic immunosuppressive therapy. Attempted therapy of CMV retinitis with a variety of regimens has not been proven to be effective. At present, no specific treatment is recommended unless it is given under a controlled therapeutic trial.

Acyclovir↗

Osteomalacia after parathyroidectomy in patients with uremia.

Five patients on maintenance dialysis had symptoms of osteomalacia, proven by biopsy, after parathyroidectomy. In all five patients clinical and radiographic manifestations of secondary hyperparathyroidism were present before surgery, and in two patients preoperative biopsy of bone confirmed the existence of osteitis fibrosa. Like previously described patients with osteomalacia all five had multiple fractures and normal or high serum calcium concentrations that rose to abnormally high values on treatment with vitamin D or dihydrotachysterol. Quantitative histomorphometry of biopsy after parathyroidectomy showed no residual parathyroid hormone effect and nearly complete cessation of mineralization. Four patients had forearm autografts of parathyroid tissue that appeared to be functioning at very low rates according to paired venous sampling, and all five patients had relatively low circulating concentrations of parathyroid hormone. This and earlier experiences reported by others suggest that secondary hyperparathyroidism may have an important facilitative role in the mineralization of bone in uremic patients.

Adult↗

Physical activity and employment status of patients on maintenance dialysis.

Existing data on the clinical outcome of maintenance dialysis for end-stage kidney disease focus mainly on the duration of life. We surveyed 18 dialysis centers to gain a broader overview of the current status of 2481 patients on dialysis, irrespective of the type or location of dialysis. The results suggest that 12 per cent of dialysis patients are diabetics and that 53 per cent are 50 years of age or older. There was considerable variation among centers in the degree of rehabilitation; nevertheless, only 60 per cent of the nondiabetic patients and 23 per cent of the diabetic patients were capable of a level of physical activity beyond that of caring for themselves. Only one quarter of the patients worked outside the home, whereas one third worked at home. These results suggest that a larger proportion of dialysis patients than previously suspected are severely debilitated. There is a need for improved data on the quality and length of life of patients on maintenance dialysis.

Activities of Daily Living↗

Inhibitor of marrow thymidine incorporation from sera of patients with uremia.

A low-molecular-weight fraction of serum samples from 14 patients with uremia inhibited tritiated thymidine incorporation (18 +/- 2%) by cultured rabbit marrow whereas an identical fraction from nonazotemic subjects did not. A similar effect on ferrous 59 incorporation into heme was observed. A significantly smaller inhibition (8 +/- 2%) was noted in serum samples from patients on maintenance dialysis. The fraction containing inhibitory activity was filterable through a membrane that had a nominal mol-wt cutoff at 10,000 daltons (Amicon UM-10) and was retained wholly or in part on a membrane that had a 500-dalton cutoff (UM-05). On Sephadex G-50 and G-15 filtration, the inhibitory substance appeared in the first absorbance peak. This substance from 2 patients maintained on dialysis was studied further for its inhibitory activity. Dose-responsiveness was noted. The inhibitor was stable when it was heated to 56 degrees C for 60 min, but the activity was lost immediately when it was heated to 100 degrees C. Significant inactivation was observed following incubation with protease and papain. The inhibitor was partially soluble in chloroform. Taken together, these data suggest that uremic serum contains an inhibitor of marrow DNA synthesis in vitro, which may consist of peptides with mol wt less than 10,000 daltons and probably greater than 1,000 daltons. PTH or a mixture of urea, creatinine, methylguanidine, and guanidosuccinic acid did not show such inhibition on the marrow. This in vitro system offers a simple and reproducible method of testing various fractions of serum to allow further characterization of some toxic materials in uremic serum.

Adult↗