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Biomedical subjects

A Schmitz

Publications and source records attributed to A Schmitz.

At least 145 records · Page 8Linked to original sources

Normoalbuminuria ensures no reduction of renal function in type 1 (insulin-dependent) diabetic patients.

Recent reports have suggested that impaired renal function in type 1 diabetic patients may be present despite normal urinary albumin excretion (UAE). We have studied kidney function by means of a constant-infusion technique in normoalbuminuric type 1 diabetic patients without antihypertensive medication (UAE less than 20 micrograms min-1, n = 134), in microalbuminuric patients (20 greater than or equal to UAE less than 200 micrograms min-1, n = 50) and in 27 non-diabetic control subjects. Mean UAE was 4.5 micrograms min-1 (range 1.0-19.3 micrograms min-1) in normoalbuminuric patients, 53.1 micrograms min-1 (range 20.8-147.5 micrograms min-1) in microalbuminuric patients, and 4.0 micrograms min-1 (range 2.1-17.9 micrograms min-1) in controls. Glycosylated haemoglobin A1c was significantly higher in microalbuminuric patients (8.9%, range 5.9-12.6%) than in normoalbuminuric patients (7.9%, range 5.5-11.5%) (P less than 0.0001). Glomerular filtration rate in normoalbuminuric patients (135 ml min-1, range 97-198 ml min-1) was significantly higher than in controls (118 ml min-1, range 94-139 ml min-1) (P less than 1 x 10(-6), and significantly lower than in microalbuminuric patients (142 ml min-1, range 100-186 ml min-1) (P less than 0.05). Mean arterial blood pressure was lower in normoalbuminuric patients (91 mmHg, range 78-108 mmHg) than in microalbuminuric patients (98 mmHg, range 82-131 mmHg) (P less than 1 x 10(-6), but not significantly different from that of controls (89 mmHg, range 73-103 mmHg). We conclude that normal UAE is a reliable indicator of well-preserved renal function. Glomerular hyperfiltration, elevated blood pressure and poor metabolic control are characteristic features of microalbuminuric patients.

Adolescent↗

Cloning and sequence analysis of genes for dehalogenation of 4-chlorobenzoate from Arthrobacter sp. strain SU.

Strains of Arthrobacter catalyze a hydrolytic dehalogenation of 4-chlorobenzoate (4-CBA) to p-hydroxybenzoate. The reaction requires ATP and coenzyme A (CoA), indicating activation of the substrate via a thioester, like that reported for Pseudomonas sp. strain CBS3 (J. D. Scholten, K.-H. Chang, P. C. Babbit, H. Charest, M. Sylvestre, and D. Dunaway-Mariano, Science 253:182-185, 1991). The dehalogenase genes of Arthrobacter sp. strain SU were cloned and expressed in Escherichia coli. Analyses of deletions indicate that dehalogenation depends on three open reading frames (ORFs) which are organized in an operon. There is extensive sequence homology to corresponding gene products in Pseudomonas sp. strain CBS3, suggesting that ORF1 and ORF2 encode a 4-CBA-CoA-ligase and a 4-CBA-CoA dehalogenase, respectively. ORF3 possibly represents a thioesterase, although no homology to the enzyme from Pseudomonas sp. strain CBS3 exists.

Amino Acid Sequence↗

Enhanced urinary excretion of albumin in congestive heart failure: effect of ACE-inhibition.

Urinary excretion of albumin and beta 2-microglobulin were measured in 13 patients with congestive heart failure, NYHA class II-IV, before and after captopril treatment for 4 weeks, and in 13 healthy control subjects. The urinary excretion of albumin was enhanced in heart failure patients compared to control subjects (12.0 micrograms min-1 vs 2.8 micrograms min-1; medians, p less than 0.01), whereas beta 2-microglobulin excretion was normal. No significant change in urinary excretion of albumin was observed after captopril. Using Spearmann's test the urinary excretion of albumin was correlated to the NYHA class (Px = 0.681, p less than 0.05, plasma renin (Px = 0.886, p less than 0.01) and plasma angiotensin II (Px = 0.5840, p less than 0.05). Correlations with atrial natriuretic peptide (rho = 0.412, p = 0.153) and aldosterone (Px = 0.487, p = 0.106) did not reach significance. By multiple linear regression analysis only plasma renin activity was correlated to albumin excretion. In conclusion, patients with congestive heart failure had an increased urinary excretion of albumin. It is suggested that the enhanced transglomerular passage of albumin in congestive heart failure is partly due to an increased intra-renal angiotensin II generation, but elevated plasma level of atrial natriuretic peptide and increased renal venous pressure may also be important pathogenetic factors.

Adult↗

Microalbuminuria in non-insulin-dependent diabetes.

According to international consensus, microalbuminuria is defined as an elevated urinary albumin excretion rate (UAER) of 20-200 micrograms/min, which is below the proteinuric range. Nephropathy is a major complication in IDDM, seen in about 30% of patients after many years of diabetes. Increasing microalbuminuria is an excellent marker of subsequent nephropathy in these patients. End-stage diabetic nephropathy is also important in NIDDM, but in most Western countries this serious complication eventually develops in only 5 to 10% of cases, whereas the majority of patients die before this from cardiovascular disease. In completely healthy individuals there is no clear correlation between age and UAER, at least up to about 70 years of age. The mean excretion rate is around 5 micrograms/min, with a considerable range, but excretion only rarely exceeds 15 micrograms/min. In population studies among middle-aged and elderly individuals, higher values are seen. In newly diagnosed NIDDM about 40% of patients show an excretion rate above 15-20 micrograms/min. There is a significant but not precise correlation between albumin excretion rate and glycemic control, and usually UAER is reduced by standard antidiabetic treatment. In a considerable number of patients, high values cannot be reduced. In the course of NIDDM about 20-30% of patients show microalbuminuria. In patients with known diabetes, microalbuminuria is related not only to subsequent diabetic proteinuria, but even more strongly to early death, mainly from cardiovascular disease. Even slight microalbuminuria (15-40 mg/l in early morning urines) is clearly associated with increased mortality. In subjects with newly detected elevated blood glucose (by screening) microalbuminuria also predicts early mortality. The mechanisms are not established, but several arteriosclerosis-related risk factors are seen more frequently in patients with microalbuminuria, e.g. lipid abnormalities, elevated systolic blood pressure (BP), hemostatic measures, as well other markers of cardiovascular disease. Usually there is a significant but not precise correlation between BP and UAER in groups of patients throughout the course of diabetes. New studies document that also in the elderly background population microalbuminuria is a significant risk factor for early death, maybe even stronger than the established risk markers, which thus may be confounded with the presence of microalbuminuria.

Adult↗

Appendiceal mucoceles and pseudomyxoma peritonei.

Mucoceles of the appendix and associated pseudomyxoma peritonei are a heterogeneous group comprising various histopathologic lesions with differing prognoses. Between 1983 and 1990, we treated eight patients with appendiceal mucocele, three cystadenomas and five cystadenocarcinomas, three of which had accompanying pseudomyxoma peritonei. All patients were more than 50 years of age. Women outnumbered men by seven to one. Preoperative diagnosis was acute appendicitis or appendiceal abscess in all instances of mucocele unaccompanied by pseudomyxoma peritonei. Ultrasound of the abdomen, together with paracentesis, diagnosed pseudomyxoma peritonei in two of three patients. Elevated carcinoembryonic antigen levels were found in six of the eight patients and monitoring of this parameter was useful in the early detection of the two recurrences observed. The three patients with cystadenomas remain free of disease after appendectomy. Of the five patients treated for cystadenocarcinoma by right colectomy, two underwent reoperation after recurrence of disease. One patient died 41 months later of intestinal obstruction caused by pseudomyxoma peritonei. Pseudomyxoma peritonei significantly decreases survival of patients with appendiceal mucocele. In these patients, aggressive initial surgical management, repeated if need be, is indicated.

Aged↗

[Unexplained fever or inflammatory syndrome. Diagnostic value of liver puncture-biopsy].

The value of transcutaneous biopsy of the liver was assessed in a series of 110 cases of fever of unknown origin or of unexplained inflammatory syndrome. Liver histology was useful to the ultimate etiological diagnosis in 12 cases (11 per cent). The result of a transcutaneous biopsy of the liver was considered an essential aid to the ultimate diagnosis in 7 of these 12 cases. A hepatic lesion regarded as useless for the ultimate diagnosis was present in 16 cases (14.5 per cent). In the other cases, hepatic histology was normal or showed a non-specific reactive hepatitis. Unicteric cholestasis was present in 73 per cent of the cases but was of no predictive value for the detection of a useful hepatic lesion. On the other hand, serum transaminase levels were significantly higher when a useful lesion of the liver was observed.

Adolescent↗

The structure of murine interleukin-1 beta at 2.8 A resolution.

The three-dimensional structure of recombinant murine interleukin-1 beta has been solved by X-ray crystallographic techniques to 2.8 A resolution and refined to a crystallographic R factor of 0.192. Although murine interleukin-1 beta crystallizes in the same space group as human interleukin-1 beta with almost identical unit cell dimensions, the packing of the molecules is quite different. The murine interleukin-1 beta structure was solved by molecular replacement using the refined structure of human interleukin-1 beta as trial structure, and found to be related to the human structure by a nearly perfect twofold rotation about the crystallographic y-axis and a 14 degrees rotation about the z-axis, with no translation. The folding of murine interleukin-1 beta is similar to that found for the human variant, consisting of 12 beta strands wrapped around a core of hydrophobic side chains in a tetrahedron-like fashion. Significant differences with respect to the human structure are seen at the N terminus and in 4 of the 11 loops connecting the 12 beta strands.

Amino Acid Sequence↗

Enhanced urinary excretion of albumin and beta 2 microglobulin in essential hypertension induced by atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) was given as an intravenous bolus injection (2.0 micrograms kg-1) to 12 essential hypertensive patients (EH) and 10 normotensive control subjects (C) in order to study the effect of ANP on urinary excretion of albumin and beta 2-microglobulin, and on glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF). After the ANP injection, urinary excretion of albumin increased significantly (p less than 0.01) in EH from 7.3 micrograms min to 125 micrograms min (medians) and in C from 2.9 micrograms min-1 to 8.1 micrograms min-1 (p less than 0.05). Urinary excretion of beta 2-microglobulin increased in EH from 70 ng min-1 to 1022 ng min-1 (p less than 0.01) and in C from 118 ng min-1 to 170 ng min-1 (p less than 0.01). The increase in urinary excretion of both albumin (p less than 0.01) and B2-microglobulin (p less than 0.01) was significantly more pronounced in EH than in C. GFR and RPF were almost unchanged in both groups. FF rose to the same degree in the two groups. The increase in fractional excretion of sodium and in urine volume after ANP was enhanced in EH. It is concluded that ANP in pharmacological doses increased urinary excretion of albumin and beta 2-microglobulin to a considerably larger extent in essential hypertensive patients than in normotensive control subjects.

Adult↗

Ambulatory blood pressure measurement in type 2 diabetic patients: methodological aspects.

Ambulatory blood pressure was measured over 24 h on two occasions in 29 Type 2 diabetic patients age 65 (range 52-74) years, and the reproducibility compared with that of ordinary clinic measurements recorded by Hawskley's random zero sphygmomanometer. The variability of the difference between blood pressure measurements on the two occasions was twice as large for clinic measurement as for ambulatory measurement (2p less than 0.01). If applied to clinical trials this would allow a fourfold reduction of patient numbers without losing test power. In the group of patients treated with antihypertensive medication (n = 16) the spontaneous decline in blood pressure after leaving the hospital proved to be most prominent in those patients with the highest clinic blood pressure, a phenomenon with importance for the management of hypertension. The individual difference between clinic measurements and ambulatory day-time measurements from the same day was unpredictable. Ambulatory blood pressure measurement in the outpatient clinic may be a practicable approach for optimizing antihypertensive treatment in Type 2 diabetic patients.

Aged↗

Effects of felodipine on urinary albumin excretion and metabolic control in hypertensive non-insulin-dependent diabetics.

The effect of a blood pressure reduction by 10 mg extended release felodipine once daily on urinary albumin excretion (UAE) as well as the possible diabetogenic effect of felodipine was studied. A 2 X 12 week placebo-controlled double-blind crossover study was performed in 12 hypertensive non-insulin-dependent diabetic (NIDDM) patients without nephropathy on concomitant treatment with beta-blocker and/or a diuretic agent. Metabolic control as estimated by fasting plasma glucose, hemoglobin A1c and fasting plasma C-peptide was unaltered after felodipine. Blood pressure was significantly reduced by felodipine: systolic 166 +/- 26 mm Hg (placebo) v 153 +/- 26 mm Hg (felodipine) (P less than .05) and diastolic 95 +/- 7 mm Hg v 90 +/- 8 mm Hg (P less than .05). Heart rate was unchanged. There was no correlation between blood pressure and UAE, but the relative change in UAE expressed as UAE placebo/UAE felodipine was significantly correlated to the fall in systolic blood pressure (r = 0.64, P = .03) and mean blood pressure (r = 0.66, P = .02). Since microalbuminuria predicts proteinuria and reduced survival, early antihypertensive treatment may be beneficial in NIDDM as it is in IDDM. Long-term consequences on kidney function and mortality remains, however, to be elucidated.

Aged↗

Kidney function and cardiovascular risk factors in non-insulin-dependent diabetics (NIDDM) with microalbuminuria.

Microalbuminuria in non-insulin-dependent diabetes (NIDDM) is a strong predictor of increased mortality. The major causes of death are cardiovascular, whereas end-stage renal failure is of low frequency. To define kidney function and the presence of some assumed cardiovascular risk factors, we compared a group of 19 microalbuminuric NIDDM patients (M), of mean age (+/- SD) 65 +/- 4 years, and known duration of diabetes 8 +/- 7 years, with 19 randomly selected matched normoalbuminuric patients (N). Seven microalbuminuric patients (P) were also studied. Glomerular filtration rate (GFR) did not differ between N and M, whereas kidney volume was increased in M (260.3 +/- 54.1 ml 1.73 m-2) compared to N (220.4 +/- 44.8 ml 1.73 m-2; P = 0.018). The frequency of cardiac disease increased with increasing albuminuria. Glycaemic control did not differ between the groups, but fasting plasma C-peptide levels increased from 2.8 +/- 1.1 micrograms l-1 in N, to 3.7 +/- 1.7 micrograms l-1 in M (P = 0.08), and to 4.2 +/- 1.9 micrograms l-1 (P = 0.03) in P. The lipoprotein profile showed no significant differences, although the LDLcholesterol/HDLcholesterol (LDL-C/HDL-C) ratio tended to rise. A significant correlation was found between C-peptide and LDL-C/HDL-C (r = 0.5; P less than 10(-3]. In conclusion, GFR was not increased, and did not differ between N and M, whereas kidney volume was enhanced in M. Several assumed cardiovascular risk factors showed values of M intermediate between those of N and P.

Aged↗

Haemostatic measures in type 2 diabetic patients with microalbuminuria.

The major cause of disability and early mortality in Type 2 diabetes is cardiovascular disease. An enhanced urinary albumin excretion is strongly predictive of increased mortality, but the causal relationship behind this association is unclear. Abnormalities in the haemostatic system may be involved in the vascular pathology. We therefore studied the level of von Willebrand factor (vWf:Ag), factor VIII (VIII:Ag), fibrinogen, and fibronectin in male diabetic patients 50-70 years of age, with normal albumin excretion (n = 14), microalbuminuria (n = 14), and frank albuminuria (n = 7). Fourteen healthy age-matched males served as a reference group. There were no significant differences between normo- and micro-albuminuric patients but vWf:Ag (p less than 0.01), VIII:Ag (p less than 0.01), and fibrinogen (p less than 0.05) were increased in those with frank albuminuria. Urinary albumin excretion rate was significantly correlated to vWf:Ag (r = 0.46, p = 0.005), VIII:Ag (r = 0.45, p = 0.007), and fibrinogen (r = 0.49, p = 0.003). The known duration of diabetes was correlated to vWf and F VIII. The increased level of vWf:Ag in Type 2 diabetes and the significant association to the urinary albumin excretion rate may suggest a linkage between albuminuria and cardiovascular disease. However, the present study demonstrated no increase in haemostatic variables in patients with microalbuminuria as compared with those with normal albumin excretion.

Aged↗

Increased urinary haemoglobin in diabetics with microalbuminuria--measured by an ELISA.

A solid-phase sandwich enzyme immunoassay for the determination of urinary haemoglobin is described. A screening study was performed to establish whether occult haematuria/haemoglobinuria is present in diabetic patients with elevated urinary albumin excretion. Non-insulin-dependent diabetic patients (145) aged 66.5 years +/- 5.6 with a known duration of diabetes of 10.4 years +/- 6.8 were studied. They delivered a first morning urine sample at consecutive outpatient visits. Erythrocytes were lysed by freezing of the urine samples. The patients were categorized into three groups according to urinary albumin concentration (UAC) as measured by radio-immunoassay. Forty-five patients with microalbuminuria i.e. UAC greater than 20- less than or equal to 200 micrograms/ml had an elevated urinary haemoglobin concentration (UHC) of 38.5 micrograms/l compared to 90 patients with normal UAC and a UHC of 7.7 micrograms/l, p less than 10(-4). A further increase was seen in 10 proteinuric patients, UHC 161.8 micrograms/l, p less than 0.05. The urinary concentration of albumin and haemoglobin were significantly correlated, r = 0.49, p less than 10(-8). In 32 insulin-dependent diabetics the findings were similar. There was no correlation between either age or known duration and the haemoglobin concentration. In 42 normal subjects, the UHC was 3.6 micrograms/lx/divided by 6.1. Haematuria has formerly been described in patients with diabetic nephropathy alone. The present findings suggest that occult haematuria/haemoglobinuria is already present in patients with microalbuminuria.

Adolescent↗

[Ridge stabilization with adhesive inlays in MOD cavities].

The flexural rigidity of the buccal cusps of upper premolars was determined under a vertical load of 100 N by use of displacement transducers. The stiffness of the cusps was higher when the cavities were restored with cast gold onlays or with composite or ceramic inlays luted with composite resin. In most cases a decrease in cusp stiffness was observed after thermocycling of the teeth restored with composite or ceramic inlays. With amalgam restorations or cast gold inlays, the flexural rigidity of the cusps was not higher than that of the unrestored cavities.

Bicuspid↗

[Hypoxic hepatitis. Prospective, clinical and hemodynamic study of 45 cases].

The authors report 45 episodes of centrilobular liver cell necrosis, called ischemic hepatitis, in 43 cardiac patients. In 75 percent of the episodes, centrilobular liver cell necrosis was preceded by a period of progressive deterioration of myocardiac function. In 100 percent of the episodes, liver cell necrosis occurred after an acute clinical event inducing a transient fall of cardiac output. Shock was observed in only 47 percent of the episodes. The biological hallmarks of this centrilobular liver cell necrosis were a massive increase in serum aminotransferase levels and in 85 percent of the episodes, a decrease in the prothrombine time below 50 percent of control level. The mortality rate, 15 days after admission, was 42 percent. Prognosis was mainly related to cardiac function. The hemodynamic comparison between the 45 episodes of centrilobular liver cell necrosis and 22 cases of cardiogenic shock without liver cell necrosis showed that, besides hepatic ischemia, passive venous congestion of the liver and arterial hypoxemia were also involved in the onset of liver cell necrosis in these cardiac patients. Among these 45 episodes of liver cell necrosis of cardiac origin, a unique case of hepatic necrosis secondary to major hypoxemia and passive venous congestion, despite an high cardiac output was observed and is reported in detail. Accordingly, the appellation "hypoxic hepatitis" seems to be more appropriate than "ischemic hepatitis".

Adult↗

Glomerular volume in type 2 (noninsulin-dependent) diabetes estimated by a direct and unbiased stereologic method.

Glomerular volume was estimated in 20 type 2 diabetic patients (age 64 +/- 6 years, duration of diabetes 6 +/- 5 years) compared with 14 sex- and age-matched controls, as well as in a group of 11 very long-term type 1 diabetic patients (age 61 +/- 12 years, duration of diabetes 44 +/- 11 years). One whole autopsy kidney was obtained prospectively, and a known fraction (approximately equal to 1/140) was sampled systematically and embedded in plastic (JB-4 glycolmetacrylate), thereby essentially eliminating shrinkage. Sections 15-microns thick were stained with periodic acid-Schiff. Mean glomerular volume was estimated on a random sample of glomeruli using the disector method. Frequency of glomerular occlusion and mean volume of open glomeruli was estimated. Mean glomerular volume was not different between type 2 diabetic patients and controls (5.3 +/- 1.7 M mu3/1.73 m2 versus 5.3 +/- 1.9 M mu3/1.73 m2) nor was total glomerular volume or kidney weight. Frequency of glomerular occlusion was 4.8 +/- 5.7% in controls, 8.9 +/- 7.8% (p = 0.10) in type 2 patients, and 16.8% +/- 20.7 (p less than 0.05) in type 1 patients. In type 2 patients there was a correlation between frequency of glomerular occlusion and mean volume of open glomeruli (r = 0.44, p = 0.05), and the same tendency was seen in type 1 patients (r = 0.49, p = 0.12). By the present method the absolute level of glomerular volume was increased by at least a factor of two compared with previous studies. This illustrates the problems arising from shrinkage of tissue in paraffin and stresses the importance of using an unbiased stereological method. The lack of increase in total glomerular volume is in accordance with clinical findings of lack of glomerular hyperfiltration in type 2 patients, findings in contrast to those in type 1 diabetes. It is suggested that hyperfiltration per se is not the cause of glomerulopathy.

Aged↗