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Biomedical subjects

F C Goetz

Publications and source records attributed to F C Goetz.

At least 73 records · Page 4Linked to original sources
PubMed1985

Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus.

To distinguish metabolic from genetic factors in the development of microangiopathy in diabetes, we evaluated biopsy specimens of kidney and quadriceps muscle from seven pairs of identical twins who were discordant for Type I (insulin-dependent) diabetes mellitus. Two of the diabetic patients had clinical diabetic nephropathy, including hypertension, marked albuminuria, and a substantially reduced creatinine clearance; the other five had normal renal function and only minor clinical indications of complications. All the twins of the diabetic patients had normal glomerular basement membrane widths and normal fractional volumes of the glomerular mesangium. Values for glomerular basement membrane width, tubular basement membrane width, and mesangial volume in each diabetic twin exceeded the values in the respective sibling (P less than or equal to 0.0035), even if the value in the diabetic twin lay within established normal ranges. Values for muscle capillary basement membrane width in the diabetic twins did not differ from those in their siblings (P = 0.5). Our observations suggest that the metabolic abnormalities of diabetes are necessary, if not sufficient, for the development of glomerular abnormalities. We also conclude that in diabetic patients, alterations in muscle capillary basement membrane width do not necessarily accompany pathologic lesions in the kidney.

Adult↗
PubMed1985

Relationship of renal size to nephropathy in type 1 (insulin-dependent) diabetes.

Thirty-five patients with Type 1 (insulin-dependent) diabetes mellitus and 90 normal subjects had renal size (renal area index) determined by X-ray and also had examination of renal biopsies by light and electron microscopy. Renal area index of 206 +/- 32 cm2/1.73 m2 (mean +/- SD) in the Type 1 diabetic patients exceeded that in the normal subjects (180 +/- 25 cm2/1.73 m2, p less than 0.001). In the diabetic patients, the renal area index correlated with creatinine clearance (r = +0.43, p less than 0.05), but did not correlate with urinary albumin excretion, or the electron microscopic measurements of percentage total mesangium and glomerular basement membrane width. In diabetic patients with clinical nephropathy or severe glomerulopathy on biopsy, the kidneys may remain large. Thus, renal size does not indicate the severity of diabetic renal lesions on biopsy.

Adolescent↗
PubMed1985

One institution's experience with pancreas transplantation.

The University of Minnesota has the largest experience with pancreas transplantation of any institution, with 130 cases since 1966, including 116 in 98 patients between July 1978 and June 1985. Currently, 30 patients are insulin-independent, 19 for greater than one year, the longest for seven years. One-year patient and graft survival rates overall are 87% and 30%, respectively. Of 98 recipients, 49 had had previous kidney transplants, while 49 had not, and currently most of the pancreas recipients do not have uremia and have not had a kidney transplant but have early complications of diabetes. A total of 44 of the grafts were procured from related and 72 from cadaver donors. Although 32 of the 116 grafts (28%) failed for technical reasons, the most common cause of graft failure has been rejection. Various immunosuppressive regimens have been used in attempts to reduce the rejection rate, and one combination, low-dose cyclosporine-azathioprine-prednisone (triple therapy), has been particularly effective, with a one-year functional survival rate of 73% in recipients of technically successful grafts from human leukocyte antigen-mismatched cadaver or related donors (N = 20). The pancreas graft survival rates have improved gradually (43% for 1984 to 1985, N = 30; versus 27% for 1978 to 1983, N = 86) for transplants from both related and cadaver donors. Metabolic studies from most recipients with functioning grafts (insulin-independent) show normal or nearly normal results. Preliminary observations on secondary complications suggest a more favorable course in recipients whose grafts have functioned long term than in those whose grafts failed early.

Actuarial Analysis↗
PubMed1984

Quantitation of the sweating deficiency in diabetes mellitus.

This report introduces quantitative tests for the evaluation of sweating and the results obtained in 81 diabetic and 30 control subjects. The tests rely on the ability of pilocarpine, introduced into the skin by iontophoresis, to stimulate sweating from fully or partially innervated sweat glands but not from denervated glands. Many diabetic patients had a reduced number of excitable sweat glands and a low volume of sweat per square centimeter of skin. The results of the sweat tests correlated best with the clinically determined perception of pain from pinprick. The similar degree of involvement of sudomotor axons and pain-conveying axons may be related to the known similarity in size and reinnervation patterns. There was poor correlation of the sweating deficiency with alpha motor conduction velocity and with denervation of foot muscles as determined by the evoked muscle action potential. The number of excitable sweat glands was usually normal if the muscle action potential was above 0.5 mv, and often normal even when a muscle action potential was unobtainable. Every diabetic patient with abnormal sweating and several with normal sweating had reduced heart rate fluctuation during a standard Valsalva maneuver or during slow respiration.

Adult↗
PubMed1984

Recent experience with 89 pancreas transplants at a single institution.

Of 89 pancreas transplants performed in 77 diabetic patients (43 with and 34 without previous kidney transplants), 53 were from cadaver and 36 from related donors. To date, 64 patients (83%) are alive and 27 (35%) have functioning grafts (14 greater than 1 year), including 0 out of 3 duct-ligated, 3 out of 15 open-duct, 17 out of 32 enteric-drained, and 7 out of 39 duct-injected. Of technically successful allografts, 8 out of 16 (50%) in the azathioprine- and 17 out of 47 (36%) in the cyclosporin-treated recipients are functioning (eight cyclosporin patients also take azathioprine). Seven of the nine (78%) non-kidney-transplants recipients of technically successful pancreas allografts from HLA-identical siblings have functioning grafts. Causes of graft failure include allograft rejection, fibrosis secondary to duct injection, or selective beta-cell destruction independent of rejection. Of the 24 recipients who are currently insulin-dependent, 14 have normal or near-normal glucose tolerance test results, while 10 have abnormal results, even though they are otherwise euglycaemic. The patient population to whom pancreas transplantation is applied is gradually changing, and non-uraemic, non-kidney-transplant patients currently comprise the majority of our cases (17 out of 24 in 1983; nine of the 17 currently have functioning grafts). We now prefer the enteric drainage technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Pancreas transplantation.

Clinical pancreas transplantation is a procedure being applied with increasing effectiveness for the treatment of diabetes. The authors examine, through the Pancreas Transplant Registry, all known cases of islet transplantation since 1970 and all pancreas transplantation since 1977 and then summarize their own work on pancreas transplants at the University of Minnesota.

Diabetes Mellitus↗
PubMed1984

One hundred pancreas transplants at a single institution.

Clinical pancreas transplantation at the University of Minnesota began in 1966. An initial series of 14 whole pancreas grafts was reported in part to the American Surgical Association in 1970. Only one patient survived for more than 1 year with a functioning graft. Twenty attempts at islet allotransplantation in the mid-1970s were unsuccessful. In 1978 we resumed performing pancreas transplants by the segmental technique, allowing the use of related donors. The current series (July 25, 1978 to December 20, 1983) includes 86 pancreas transplants (51 cadaver, 35 related) in 75 patients (41 with and 34 without previous kidney grafts). Variations in management of the pancreatic duct include three ligated, 15 duct-open, 39 duct-injected, and 29 pancreaticojejunostomies. The latter technique is currently preferred. Currently (April 1984) 61 patients are alive (81%), 24 have functioning grafts (32%), and 21 are insulin-independent (28%), three with open-duct grafts for 4.4 to 5.7 years, seven with silicone-injected grafts from 10 to 39 months, and 14 with pancreaticojejunostomies for 3 to 31 months; 15 of the grafts have functioned for greater than 1 year. Twenty-two of the grafts (25%) failed for technical reasons (thrombosis, infection, or ascites); 35 grafts functioned for 1 to 13 months before totally failing from either rejection, fibrosis, or recurrent disease; five patients died with functioning grafts. The graft survival rate has been higher for pancreases from related (15/35, 43% functioning) than from cadaver (9/51, 18% functioning) donors. The success rate has increased, e.g., 11/22 recipients of pancreas transplants in 1983 currently have functioning grafts (50%). Metabolic studies show most patients with functioning grafts to be euglycemic; however, three of 24 have chronic hyperglycemia unless supplemented with insulin, but they are no longer ketosis-prone. Glucose tolerance test results are normal or nearly normal in 12 and abnormal in 12 of the recipients with currently functioning grafts. Regression of diabetic nephropathy has been documented in two long-term recipients. Pancreas transplantation is currently applicable as treatment for selected diabetics who have demonstrated their propensity to develop serious secondary complications.

Adult↗
PubMed1984

Pancreas transplants from related donors.

Of 89 pancreas transplants performed at the University of Minnesota between July 1978, and March 1983, 36 have been segmental grafts from living-related donors (17 HLA-identical siblings, 6 identical twins, 13 HLA-mismatched relatives). All recipients had been diabetic for at least 10 years and all donors were at least 10 years older than the ages of onset of diabetes in the recipients; in the case of sibling donors, no other siblings or family members other than the recipient were diabetic. Changes in plasma glucose and serum insulin levels occurred in most donors postoperatively, but glucose tolerance tests usually remained normal. Of the 36 grafts from related donors, 16 are currently functioning (12 were technical failures), as compared with 10 of 53 from cadaver donors (10 were technical failures). The pancreatic ducts were left open, injected with synthetic polymers, or anastomosed to a Roux-en-Y limb of recipient jejunum. All techniques have been associated with successes and failures, but we currently prefer the enteric-drainage technique. The patient survival rates for recipients of transplants from related versus cadaver donors were 94% versus 78% (P less than .013); the respective graft survival rates were 43% versus 20% (P = .25). When only technically successful grafts were considered, the one-year function rates were 65% for pancreas grafts from related donors (n = 29) versus 25% for those from cadaver donors (n = 43) (P = .005). The highest success rate has been in azathioprine-treated recipients of technically successful pancreas transplants from related donors of a previous kidney (3 of 3 grafts from HLA-identical siblings and 3 of 3 from HLA-mismatched relatives are functioning). However, 7 of 9 technically successful grafts from HLA-identical siblings in nonuremic, non-kidney-transplant recipients treated with cyclosporine are also functioning (one-year graft survival rate of 76%). The results in nonuremic, non-kidney-transplant recipients of mismatched related grafts have not been so good, and only one of 5 technically successful grafts in this category is currently functioning. However, this patient has been treated with cyclosporine, azathioprine, and prednisone (triple therapy)--an immunosuppressive regimen we have recently applied with success in nonuremic, non-kidney-transplant recipients of cadaveric grafts.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗
PubMed1984

Structural-functional relationships in diabetic nephropathy.

Renal biopsies in 45 patients with insulin-dependent diabetes mellitus (IDDM) were examined by semiquantitative light microscopy and quantitative electron microscopic stereologic morphometry. In these 14 males and 31 females, aged 13-52 yr, who had had IDDM for 2.5-29 yr there was no strong relationship between either glomerular basement membrane (GBM) thickness or mesangial expansion and duration of IDDM. There was only a weak relationship between the thickness of the GBM and expansion of the mesangium. Thus, GBM thickening and mesangial expansion in IDDM occur at rates that often differ from one another and that vary greatly among patients. The clinical manifestations of diabetic nephropathy, albuminuria, hypertension, and decreased glomerular filtration rate related poorly or not at all to GBM thickening. In contrast, all light and electron microscopic measures of mesangial expansion were strongly related to the clinical manifestations of diabetic nephropathy, although in the absence of these clinical findings, it was not possible to predict the severity of any of the diabetic glomerular lesions. Mesangial expansion had strong inverse correlations with capillary filtering surface area density. It is hypothesized that mesangial expansion could lead to glomerular functional deterioration in IDDM by restricting the glomerular capillary vasculature and its filtering surface. However, capillary closure, glomerular sclerosis, and interstitial fibrosis could also contribute to the clinical manifestations of this disorder.

Adolescent↗
PubMed1984

The sweating deficiency in diabetes mellitus: methods of quantitation and clinical correlation.

A method that measures the amount of sweat evaporating from the skin was used to quantitate the sweating deficiency that accompanies diabetic neuropathy. The decreased amount of sweat secreted after pilocarpine stimulation was proportional to the reduction in number of excitable sweat glands, and to the decrease in water measured by the summed volume of all sweat droplets secreted. The results also correlated favorably with the degree of sensory loss to painful stimuli, but not to the alpha motor nerve conduction velocity or motor axon loss evaluated by muscle action potentials evoked from foot muscles. Respiratory-cardiovascular reflexes, as measured by the Valsalva ratio, were always abnormal in patients with demonstrated sweating deficiency and often in patients with normal sweat function.

Adult↗
PubMed1983

Postprandial glucose and insulin responses to meals containing different carbohydrates in normal and diabetic subjects.

To examine whether the form of dietary carbohydrate influences glucose and insulin responses, we studied the glucose and insulin responses to five meals--each containing a different form of carbohydrate but all with nearly identical amounts of total carbohydrate, protein, and fat--in 10 healthy subjects, 12 patients with Type I diabetes, and 10 patients with Type II diabetes. The test carbohydrates were glucose, fructose, sucrose, potato starch, and wheat starch. In all three groups, the meal containing sucrose as the test carbohydrate did not produce significantly greater peak increments in the plasma concentration of glucose or greater increments in the area under the plasma glucose-response curves than did meals containing potato, wheat, or glucose as test carbohydrates. Urinary excretion of glucose in patients with diabetes was not significantly greater after the sucrose meal. The meal containing fructose as the test carbohydrate produced the smallest increments in plasma glucose levels, but the differences were not always statistically significant. In healthy subjects and patients with Type II diabetes, peak serum concentrations of insulin were not significantly different in response to the five test carbohydrates. Our data do not support the view that dietary sucrose, when consumed as part of a meal, aggravates postprandial hyperglycemia.

Adult↗
PubMed1983

Urinary C-peptide: a simple measure of integrated insulin production with emphasis on the effects of body size, diet, and corticosteroids.

C-Peptide is secreted from the beta-cell in equimolar quantities with insulin. Since a fraction of C-peptide is excreted in the urine, measurement of C-peptide in timed urine collections is a simple indirect measure of integrated insulin production. Normal subjects were studied to determine the effects of diet and oral prednisone on urinary C-peptide excretion. In subjects on a defined diet, there is a positive correlation of urinary C-peptide with body weight. When insulin production is increased after oral prednisone, there is also a positive correlation with body mass index and percent ideal body weight. Prednisone increases plasma glucose, immunoreactive insulin, and serum and urinary C-peptide levels beginning 8-12 h after oral administration. This effect of prednisone is most marked in the postprandial state. Diets high in carbohydrate and protein result in significantly more insulin production, as measured by urinary C-peptide, than isocaloric diets with low protein or carbohydrate composition.

Adolescent↗
PubMed1983

Diabetic nephropathy. A perspective.

The earliest manifestations of clinical diabetic nephropathy, including proteinuria, hypertension, and declining GFR, represent very advanced diabetic glomerulopathy with especially prominent mesangial expansion. Mesangial expansion, by restricting glomerular capillary filtration surface and lumenal volume, stimulates compensatory mechanisms analogous to those resulting from a marked reduction in nephron number. These compensatory mechanisms involve alterations in glomerular hemodynamics designed to maintain glomerular filtration but which ultimately injure the kidney. These hemodynamic perturbations are not specific to diabetes but represent a final common pathway toward endstage renal failure that also characterizes the remnant kidney. This thesis concludes that the onset of clinical diabetic nephropathy augurs inevitable decline in kidney function, and that only studies and interventions exercised before clinical nephropathy develops can influence understanding and outcome of diabetic nephropathy.

Basement Membrane↗