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Biomedical subjects

A Schmitz

Publications and source records attributed to A Schmitz.

At least 163 records · Page 9Linked to original sources

Kidney function in newly diagnosed type 2 (non-insulin-dependent) diabetic patients, before and during treatment.

Glomerular filtration rate, kidney volume, and urinary albumin excretion rate were studied in otherwise healthy newly diagnosed Type 2 (non-insulin-dependent) diabetic patients, untreated at diagnosis, after short-term treatment and after 3 months treatment. In 10 patients (Group A) glomerular filtration rate (measured by the plasma clearance of 51-Cr-EDTA) decreased from the time of diagnosis 106.2 +/- 14.6 ml.min-1.1.73 m2(-1) (mean +/- SD) to 95.9 +/- 13.7 ml.min-1.1.73 m2(-1) after 3 months treatment (p = 0.049). At the same time, mean plasma glucose was reduced from 13.3 +/- 3.2 mmol/l to 6.5 +/- 1.1 mmol/l. The fall in mean plasma glucose was correlated to the reduction in glomerular filtration rate, r = 0.76, p = 0.011. Kidney volume as measured by ultrasonic scanning was reduced from 264.0 +/- 33.7 ml/1.73 m2 to 210.8 +/- 23.8 ml/1.73 m2 (p less than 0.005). The relative decline in urinary albumin excretion rate was correlated to the fall in glomerular filtration rate, r = 0.69, p = 0.026. In 15 patients (Group B) 24-h urine collections were made during 9.5 +/- 3.2 days, urinary albumin excretion rate fell from the first to the last day in hospital from 14.0 x/divided by 3.0 micrograms/min (geometric mean x /divided by tolerance factor) to 7.0 x/divided by 2.7 micrograms/min p = 0.015. The relative decline was correlated to the change in mean plasma glucose, r = 0.65, p = 0.032. Thus, kidney function in Type 2 diabetic patients is influenced by metabolic control, although to a lesser extent than is seen in Type 1 (insulin-dependent) diabetic patients with comparable glycaemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

No microalbuminuria or other adverse effects of long-standing hyperfiltration in humans with one kidney.

Hypertrophy and hyperfiltration are characteristic features of single kidneys and kidneys of patients with insulin-dependent diabetes mellitus (IDDM). In both cases the hyperfiltration has been suggested to be involved in the pathogenesis of renal functional deterioration. We studied the effect of long-standing hyperfiltration on kidney function in 29 subjects with one kidney, three of whom were insulin-dependent diabetics. Four groups were studied: (1) uninephrectomized less than 10 years since uninephrectomy (UN) (n = 7; age, 30 +/- 6 years); (2) uninephrectomized greater than or equal to 10 years since UN (19 +/- 11 years, 10 to 52); n = 14; age, 38 +/- 15 years; (3) congenital unilateral renal agenesis (n = 5, age, 39 +/- 16 years); and (4) IDDM patients with one kidney (n = 3; age, 28 to 52 years; diabetes duration, 8 to 31 years; years with one kidney, 18 to 30). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique, kidney volume (KV) by ultrasonic scanning, and urinary albumin excretion rate (UAE) by radioimmunoassay. In all subjects GFR, RPF, and KV were within the normal range, representing a single kidney hyperfiltration of approximately 70% and hypertrophy of approximately 100%. Only one of the subjects with renal agenesis had an elevated UAE (117 micrograms/min); the remainder had a normal UAE, ie, less than 10 micrograms/min, and the diabetics were below the risk level of 20 micrograms/min. Serum creatinine was normal and BP was slightly elevated in only three subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glomerular filtration rate and kidney volume in normoalbuminuric non-insulin-dependent diabetics--lack of glomerular hyperfiltration and renal hypertrophy in uncomplicated NIDDM.

UNLABELLED: Glomerular filtration rate (GFR) and kidney volume were evaluated in 18 healthy normoalbuminuric non-insulin-dependent diabetic patients and compared to 12 healthy controls matched for sex, age and body mass index (BMI). The patients (12 males, six females) were 61.6 +/- 3.4 (mean +/- SD) years old, the known diabetes duration was 5 +/- 4.8 years, fasting plasma glucose 8.6 +/- 2.3 mmol/l, urinary albumin excretion rate 7.9 x/divided by 2.0 micrograms/min, BMI 26.8 +/- 2.8 kg/m2 and blood pressure systolic/diastolic 145 +/- 19/82 +/- 7 mmHg. The GFR was measured by the plasma clearance of [51Cr]EDTA, using a single shot procedure. The kidney volume was measured by ultrasonic scanning. The GFR was not increased in diabetics: 100.4 +/- 16.7 ml/min/1.73 m2 as compared to controls: 93.8 +/- 11.4 ml/min/1.73 m2. The kidney volume was similar in the two groups. Diabetics: 231.1 +/- 33.4 ml/1.73 m2. CONTROLS: 236.3 +/- 45.7 ml/1.73 m2. There was a borderline significant correlation between kidney volume and GFR (r = 0.40, p = 0.10) in diabetics. No correlation between glycosylated haemoglobin and GFR was found in diabetics. In contrast to the findings in insulin-dependent diabetes renal hypertrophy and hyperfunction were not characteristic features in this series of non-insulin-dependent diabetics. It is suggested that diabetic glomerulopathy is not always a consequence of long-standing hyperfiltration.

Aged↗

[Soft-tissue sarcomas. Review of 47 patients treated in 10 years in the same institute].

We have retrospectively examined the records of 47 patients treated in our department between 1977 and 1987 for soft tissue sarcoma of the extremities trunk, head or retroperitoneal space. We also reanalyze the histologic slides of 38 patients with respect to grade and necrosis. Surgery was performed for cure intent in 31 patients. Of these, 20 with a tumor of the extremities, trunk, or head underwent adjuvant radiotherapy. The patients with a high-grade sarcoma also received adjuvant chemotherapy. Local control was achieved in 95% of these 20 patients. These results compare favorably with other reported series. Out of the 8 patients with a tumor of the retroperitoneum, only one is alive without evidence of disease. The histological studies confirmed the relationship between grade and necrosis.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of pump versus pen treatment on glycaemic control and kidney function in long-term uncomplicated insulin-dependent diabetes mellitus (IDDM).

Glycaemic control on pump versus pen treatment was evaluated and the effects of optimised metabolic control on kidney function was studied in very long-term uncomplicated insulin-dependent diabetes mellitus (IDDM). Ten otherwise healthy patients participated, age: 36.5 yr +/- 7.9, diabetes duration: 23.7 yr +/- 2.9, urinary albumin excretion (UAE): 5.8 micrograms/min x/ divided by 2.2, se-creatinine and blood pressure were normal and only background retinopathy was present. A 2 x 6 months randomised cross-over study was performed using continuous subcutaneous insulin infusion (CSII) and multiple injection technique (MIT). Glycaemic control was evaluated by a six point profile every two weeks and by measuring HbA1c monthly. At 0, 6 and 12 months, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique, and UAE by radioimmunoassay. Glycaemic control was significantly better on CSII as compared to MIT (p = 0.01) or pre-study conventional treatment (CT), p = 0.03, whereas there was no difference between MIT and CT. There was no change in kidney function during either treatment. Thus, in these very long-term uncomplicated patients, glycaemic control was significantly improved during CSII. In spite of this, no change was found in GFR, which might suggest that in long-standing diabetes, kidney function is unaltered by changes in metabolic control.

Adult↗

Comparative renal pathophysiology relevant to IDDM and NIDDM patients.

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.

Diabetes Mellitus, Type 1↗

Microalbuminuria: a major risk factor in non-insulin-dependent diabetes. A 10-year follow-up study of 503 patients.

The impact of microalbuminuria on mortality as well as other risk factors was investigated in a 10-year follow-up study of 503 predominantly non-insulin-dependent diabetic patients of whom 265 had died. Using Cox's regression analysis the prognostic influence of age, sex, age at diagnosis, known diabetes duration, blood pressure, fasting plasma glucose, relative weight, serum creatinine, retinopathy, and treatment was evaluated as well as morning urine albumin concentration (UAC) in four categories, i.e. UAC less than or equal to 15 micrograms/ml (normal), 15 micrograms/ml less than UAC less than or equal to 40 micrograms/ml, 40 micrograms/ml less than UAC less than or equal to 200 micrograms/ml and UAC greater than 200 micrograms/ml. Age, UAC, known duration, and serum creatinine were the only significant risk factors. After correction for the other three independent risk factors, the hazard ratios in the elevated UAC categories relative to the group with UAC less than or equal to 15 micrograms/ml were 1.53 (p = 0.007), 2.28 (p = 0.000002), and 1.82 (p = 0.02). The statistically significant correlations with UAC were: age (r = 0.09, p less than 0.05), duration (r = 0.14, p less than 0.01), systolic blood pressure (r = 0.12, p less than 0.01), serum creatinine (r = 0.33, p less than 0.001), and fasting plasma glucose (r = 0.12, p less than 0.01). Increased UAC was associated also with retinopathy (p = 0.01). Fifty-eight per cent of the deaths were caused by cardiovascular disease or stroke; only 3% died from uraemia. A reinvestigation including blood pressure, fasting plasma glucose, and UAC was made on 208 survivors.

Aged↗

Acute and long-term renal effects of angiotensin converting enzyme inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients.

Glomerular filtration rate (GFR) (thalamate clearance), renal plasma flow (RPF) (hippuran clearance), and urinary albumin excretion rate (AER) were measured in 10 normoalbuminuric, normotensive insulin-dependent diabetic patients and 8 normal subjects before and during acute angiotensin converting enzyme (ACE) inhibition by means of enalapril (10 mg IV). The effect of placebo versus enalapril (30 mg day-1) was also studied for 3-month treatment periods in the insulin-dependent diabetic patients. Acute ACE-inhibition caused a decline in filtration fraction (FF) from 0.259 +/- 0.011 (+/- SE) to 0.237 +/- 0.013 (2p less than 0.01) in the diabetic patients, and from 0.210 +/- 0.010 to 0.188 +/- 0.006 (2p less than 0.02) in the normal subjects. Mean arterial blood pressure was lowered from 90 +/- 1 to 84 +/- 2 mmHg (2p less than 0.01) and from 91 +/- 1 to 86 +/- 2 mmHg (2p less than 0.05). No significant change in blood glucose, AER or fractional albumin excretion (theta Alb) was seen in either group. After 3 months of enalapril treatment FF was decreased from 0.253 +/- 0.011 to 0.235 +/- 0.011 (2p less than 0.05), AER from 5.6 x/ divided by 1.7 to 4.3 x/divided by 1.6 micrograms min-1 (2p less than 0.01) and theta Alb from 1.22 +/- 0.22 x 10(-6) to 0.92 +/- 0.12 x 10(-6) (2p less than 0.02). The decline in total renal resistance was not significant (0.175 +/- 0.013 to 0.165 +/- 0.012 mmHg ml-1 min-1) and significant changes in GFR, RPF, mean arterial pressure or HbA1c were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Glomerular morphology by light microscopy in non-insulin-dependent diabetes mellitus. Lack of glomerular hypertrophy.

We quantitated glomerular structure by light microscopy in 19 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and studied the possible connection between morphology and urinary albumin concentration. Autopsy material was collected retrospectively from diabetic subjects in whom urinary albumin concentration had been measured within 1.5 yr. Nineteen consecutive sex- and age-matched nondiabetic subjects were controls. A quantitative study of a random sample of glomeruli was performed blindly on periodic acid-Schiff (PAS)-stained sections. The main parameters obtained were 1) mean volume of open glomeruli, 2) frequency of glomerular occlusion, and 3) volume fraction of red-stained material (PAS-positive substance) in open glomeruli [Vv(R/G)]. There was no increase in glomerular volume in these NIDDM subjects, contrary to the glomerular hypertrophy found early as well as late in insulin-dependent diabetes mellitus. An increase in Vv(R/G) was found in diabetic subjects, demonstrating the presence of glomerulopathy as it is diagnosed by light microscopy. The frequency of glomerular occlusion was not significantly different between the groups. A high urinary albumin concentration did not necessarily reflect more advanced glomerulopathy.

Aged↗

Autonomic and somatosensory nerve function after 2 years of continuous subcutaneous insulin infusion in type I diabetes.

Autonomic and somatosensory nerve function was studied in 24 insulin-dependent diabetic subjects (aged 29 +/- 7 yrs, diabetes duration 8 +/- 4 yr) randomly allocated to either continuous subcutaneous insulin infusion (CSII; n = 12) or unchanged conventional insulin therapy (CIT; n = 12). Measures of glycemic control and somatosensory and autonomic nerve function were comparable in the two groups at the start. Glycemic control was significantly improved in the CSII group throughout study, whereas it remained unchanged in the CIT group. In the CIT group, vibratory perception threshold (VPT) of the great toe and the medial malleolus deteriorated, as did heart rate variation (HRV) at rest, at deep breathing (.05 less than P less than .06), and at standing. In contrast, CSII patients retained their VPT and HRV. Comparison of nerve function alterations during the 2-yr trial showed better preservation in CSII than in CIT patients of VPT in the great toe (0.8 +/- 1.7 vs. -1.4 +/- 1.9 V, P less than .01) and the medial malleolus (1.5 +/- 2.9 vs. -1.4 +/- 1.8 V, P less than .05) and of HRV at rest (10 +/- 24 vs. -13 +/- 22 ms, P less than .05) and at standing (-0.01 +/- 0.13 vs. -0.15 +/- 0.16 ms, P less than .05). We conclude that intensified glycemic control can favorably influence parasympathetic and somatosensory nerve function in insulin-dependent diabetes mellitus.

Adult↗

Low-dose dopamine infusion, renal haemodynamics and urinary albumin excretion rate in insulin-dependent diabetics and in normal man.

The effect of experimental renal vasodilatation by means of low-dose (2.0 micrograms/kg/min) intravenous dopamine infusion was investigated in 28 insulin-dependent diabetes mellitus (IDDM) patients with normal basal urinary albumin excretion rate (UAE) (less than 15 micrograms/min), 9 IDDM patients with UAE between 15-200 micrograms/min (microalbuminuria), and 7 normal subjects. Glomerular filtration rate (GFR) (thalamate clearance) showed a small increase with dopamine infusion, in the normoalbuminuric IDDM patients from 140 +/- 20 to 146 +/- 20 ml/min (2p less than 0.01), in the microalbuminuric IDDM patients from 146 to 151 ml/min (NS), and in normal subjects from 115 +/- 16 to 122 +/- 15 (2p less than 0.05). A marked increase in renal plasma flow (RPF) (hippuran clearance) was seen in all three groups--533 +/- 82 to 724 +/- 120 ml/min (2p less than 0.01), 574 +/- 69 to 777 +/- 140 ml/min (2p less than 0.01) and 523 +/- 87 to 749 +/- 145 ml/min (2p less than 0.05), respectively. Urinary albumin excretion rate (radioimmunoassay) increased from 5.3 x/divide 1.5 (tolerance factor) to 6.5 x/divide 1.8 micrograms/min (2p less than 0.05) in the normoalbuminuric IDDM patients and from 6.1 x/divide 2.1 to 7.8 x/divide 2.3 micrograms/min (2p less than 0.05) in the normal subjects, while no significant change was seen in the microalbuminuric group of diabetics. Kidney volume (ultrasonic scanning) was significantly enhanced in IDDM patients (294 +/- 73 ml vs. 196 +/- 49 ml). There was no significant correlation between kidney volume and the renal haemodynamic response to dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acute renal effects of oral felodipine in normal man.

The acute renal effects of a single oral dose of felodipine 0.15 mg/kg were studied in 8 healthy males. Thirty minutes after administration the mean plasma concentration was 25.7 nmol/l. There was a significant reduction in diastolic blood pressure (24%) and a concomitant rise in heart rate (38%), leaving the systolic pressure unchanged. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique using the clearance of 125I-iothalamate and 131I-hippuran respectively. GFR was unchanged and the filtration fraction (FF) was reduced, whilst there was a decrease in renal vascular resistance (RVR). The glomerular filter characteristics were unchanged, as estimated by the unchanged excretion rate of albumin. There was a significant rise in the clearance of sodium (176%) but only a small and insignificant increase in urine volume. Clearance of potassium was decreased. An increase in the clearance of uric acid and a rise in the beta-2-microglobulin excretion rate were found, both suggesting a proximal tubular effect of felodipine. The excretion rate of calcium was increased.

Adult↗

Possible role of c-fos, c-N-ras and c-mos proto-oncogenes in muscular development.

Time course analyses of various proto-oncogene transcripts compared with cytoskeleton-specific and muscle-specific messenger RNAs (mRNAs) were carried out during growth and differentiation of a clonal line of rat myoblasts that retain the capacity to form non-contractile fibres in vitro. Throughout their growth phase, these cells express consistent levels of c-fos, c-myc, c-Ki-ras and c-N-ras RNA and no c-mos RNA. When the cultures approach confluency the level of c-fos RNA rises sharply 3-4-fold, peaks, and rapidly declines when muscle-specific transcripts start accumulating, to become negligible in myotube-forming cells. These changes occur whatever the concentration in seric factors. By contrast, the level of c-N-ras RNA rises up to 3-fold and both c-myc and c-Ki-ras RNAs are slowly eliminated during the myogenic process, whereas no c-mos RNA is detectable. However, skeletal muscles from prenatal fetuses and adult animals were reproducibly found to contain both low and high levels of c-mos RNA respectively. These data and the demonstration that inactivation of the c-fos gene correlates with the loss of myogenic capability in six lines of neoplastic myoblasts, including four lines transformed by the v-fos oncogene, suggest a physiological function for this proto-oncogene during early stages of myogenesis and for the c-N-ras and c-mos genes in later stages of muscular development.

Animals↗

Clinical outcome of using insulin at 40 IU/ml and 100 IU/ml in pump treatment. Results of a controlled multi-center trial.

In three different diabetes centers the use of insulin at a strength of 40 IU/ml (U40) and 100 IU/ml (U100) in continuous subcutaneous insulin infusion (CSII) treatment of insulin dependent (Type I) diabetic patients was compared in a randomized cross-over design. Forty-six Type I diabetic patients, all previously treated with CSII for at least one year, completed consecutively two 13-week periods of treatment with U40 and U100. Body weight and insulin requirements were identical at the end of the two periods. Slightly higher levels of glycemia were recorded during U40 when compared to U100 treatment: mean blood glucose was 142 +/- 34 (SD) vs. 133 +/- 34 mg/dl (2 p less than 0.01). The same tendency was observed in the mean glycosylated hemoglobin value (6.84 +/- 1.35 vs. 6.65 +/- 1.13%, 2 p greater than 0.1). There were no significant differences between U40 and U100 in the number of catheters used and the number of catheter blockages reported, while the development of subcutaneous nodules at the insertion sites was significantly more frequent during U40 treatment. It is concluded that the implementation of insulin in the strength of 100 IU/ml is as effective as the use of insulin in the strength of 40 IU/ml for CSII therapy, and might even be associated with slightly improved glycemic control and less subcutaneous side-effects.

Adult↗

Repetitive natriuresis and blood pressure. Long-term calcium entry blockade with isradipine.

The long-term effects (3.5 months) of a new calcium entry blocker of the 1-4-dihydropyridine class, isradipine (PN 200-110), on renal hemodynamics and excretional parameters were investigated in 10 essential hypertensive subjects (World Health Organization Classes I and II). Blood pressure and renal vascular resistance fell significantly (p less than 0.001), and a slight increase in glomerular filtration rate and renal plasma flow was seen (p less than 0.05). Output of fluid from the proximal tubules, measured as clearance of lithium and uric acid, increased significantly (p less than 0.01 and p less than 0.05, respectively), and a compensatory increase in absolute reabsorption of sodium beyond the proximal tubular level accompanied by an increase in clearance of potassium was noted. A 40% increase in the resultant clearance of sodium (p less than 0.01) and an increase in diuresis (p less than 0.05) followed the morning dose of isradipine after 3.5 months of treatment. Changes in blood pressure were significantly correlated with changes in absolute proximal reabsorption of sodium (r = 0.81), excretion of sodium (r = -0.64), and diuresis (r = -0.80). Thus, the natriuretic properties of calcium entry blockers may be more important for the long-term antihypertensive effect than the vasodilator effect per se. A model for renal sodium handling following treatment with calcium entry blockers was proposed. Although a causal relationship is not implied, isradipine induced a sustained, repetitive postdose effect on proximal fluid output, net natriuresis, and diuresis, that was intimately related to the long-term blood pressure-regulating response.

Blood Pressure↗