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Biomedical subjects

E Hommel

Publications and source records attributed to E Hommel.

At least 55 records · Page 3Linked to original sources

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.

Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mm Hg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 micrograms/min (geometric mean 688 micrograms/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml.min-1. (1.73 m2)-1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open + occluded) was estimated by combined light-and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r = 0.77, p less than 10(-4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r = -0.78, p less than 10(-5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects. Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.

Adult↗

Effects of acetazolamide on kidney function in type 1 (insulin-dependent) diabetic patients with diabetic nephropathy.

We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a double-blind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection 51Cr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108 +/- 11 vs 82 +/- 9 ml/min, p less than 0.02, diabetic patients: 71 +/- 19 vs 54 +/- 14 ml/min, p less than 0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22 +/- 6 vs 27 +/- 8, NS, diabetic patients: 14 +/- 5 vs 15 +/- 4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one-third (control subjects: 85 +/- 11 vs 56 +/- 7, p less than 0.02, diabetic patients: 55 +/- 17 vs 37 +/- 6, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79 +/- 5 vs 67 +/- 8, p less than 0.02, diabetic patients: 79 +/- 5 vs 72 +/- 6, p less than 0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unchanged. Extracellular fluid volume declined by 10% in both groups (p less than 0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy.

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and urinary albumin excretion in incipient diabetic nephropathy (defined as urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) in two out of three sterile ketone-free 24-h urine collections in patients having insulin-dependent diabetes mellitus (IDDM) without hypertension or other kidney disease). The urinary excretion of prostaglandin E2 was significantly elevated in 8 insulin-dependent diabetic patients with incipient nephropathy as compared with 9 normoalbuminuric IDDM patients and 11 healthy controls: 317 (182-1273); 95 (67-225); 132 (54-263) pg/min, respectively (2p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within 2 weeks in 8 females having IDDM with incipient nephropathy. The study design was a randomized double-blind trial with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%) (2p less than 0.01), urinary albumin excretion rate diminished from 207 (63-253) to 87 (49-147) mg/24 h (2p less than 0.01), fractional clearance of albumin declined (70%) (2p less than 0.01). Glomerular filtration rate remained stable (108 (88-133) versus 110 (95-142) ml/min). Blood glucose and blood pressure were comparable during the placebo and indomethacin treatment (12.6 +/- 3 versus 13.4 +/- 5 mmol/l and 122/79 +/- 3/9 versus 122/82 +/- 4/10 mmHg, respectively). Our results suggest that enhanced glomerular synthesis of vasodilating prostaglandins may accelerate microalbuminuria in incipient diabetic nephropathy.

Adult↗

Fluorescein and fluorescein glucuronide in plasma after intravenous injection of fluorescein.

After intravenous injection of fluorescein the time-course of the plasma concentrations of fluorescein (F) and fluorescein glucuronide (FG) was studied in 18 insulin-dependent diabetics with various degrees of nephropathy, and in two non-diabetic subjects. Fifteen minutes after injection the molar concentrations of free (non-protein bound) F and FG were almost identical. After one hour the concentration curve integrals of the two substances were of the same magnitude. There was, however, considerable interindividual variation. In diabetic patients with renal insufficiency an increase was found in both integrals, the F integral being less increased (27%) than the FG integral (44%). It appears from the variation in absolute and relative concentrations of F and FG that a separate determination of the two fluorophores in plasma is desirable, when F is used by intravenous administration as an indicator of blood-ocular barrier function. Previous observations of an increase with time after injection of the free fraction of plasma fluorescence are explained by the finding of a higher free fraction of FG (34%) than of F (11%) and a change in relative concentrations of the two fluorophores.

Adult↗

Effect of antihypertensive treatment on kidney function in diabetic nephropathy.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

Adult↗

Effects of indomethacin on kidney function in type 1 (insulin-dependent) diabetic patients with nephropathy.

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albuminuria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253 pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95 pg/min) and 11 non-diabetic women (132 pg/min), respectively (p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized double-blind trial, with the patients receiving either indomethacin (150 mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%, p less than 0.01), glomerular filtration rate diminished from 120 +/- 18 to 106 +/- 17 ml/min/1.73 m2 (p less than 0.05), albuminuria declined from 148 to 69 micrograms/min (median and range) (p less than 0.05) and fractional clearance of albumin diminished 42% (p less than 0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4 +/- 4 versus 14.2 +/- 3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.

Adult↗

Prevalence and causes of microscopic haematuria in type 1 (insulin-dependent) diabetic patients with persistent proteinuria.

The prevalence and causes of microscopic haematuria were examined in all Type 1 (insulin-dependent) diabetic patients with persistent proteinuria (diabetes duration greater than or equal to 5 years) attending the outpatient clinic at Hvidöre Hospital during 1985. One hundred eighty-four patients (69F/115M) out of 1024 Type 1 patients had persistent proteinuria (18%). Microscopic haematuria was defined as greater than or equal to 3 erythrocytes per high power field in two or more sterile urine samples. Twenty-three Type 1 patients with persistent proteinuria (7F/16M, aged 35.4 +/- 13 years) had microscopic haematuria (12.5%). No significant changes were found between the group with and without microscopic haematuria: blood pressure 148/89 +/- 22/11 versus 145/91 +/- 20/11 mmHg, duration of diabetes when persistent albuminuria occurred 17 +/- 8 versus 20 +/- 10 years, serum creatinine 99 +/- 24 versus 98 +/- 31 mumol/l, simplex retinopathy 61 versus 54%, proliferative retinopathy 39 versus 42%, and no signs of retinopathy 0 versus 4%. Kidney biopsy was performed in 13 out of the 23 patients with microscopic haematuria. Diabetic glomerulosclerosis was present in all 13 patients, but 9 patients had a non-diabetic renal disease superimposed (mesangioproliferative glomerulonephritis (n = 5), membranous glomerulonephritis (n = 3) and sarcoidosis (n = 1). Microscopic haematuria is a rare finding, frequently reflecting superimposed non-diabetic glomerulopathies, in Type 1 diabetic patients with diabetic nephropathy and well preserved kidney function.

Adolescent↗

Measurement of colloid osmotic pressure in body fluids: errors caused by preheparinized glass capillaries and by CO2 loss.

The effect on colloid osmotic pressure (COP) of heparinizing body fluids was estimated with a low compliant osmometer, using Diaflo PM-30 or PM-10 membranes (Amicon, Lexington, Mass., USA). It was found that collecting and storing samples in preheparinized glass capillaries may increase COP by up to 4.0 mmHg. Measurements on heparin and protein solutions, separately and mixed, show that these macromolecules have a mutually potentiating effect on COP, probably by excluding part of the water as distribution space for the other molecular species. While this 'heparin error' varies among various types and batches of capillaries (Vitrex, Modulohm I/S), the content of heparin in some batches appears to be two to three times greater than the declared minimum. Alternatively, the excess COP may result from addition of other water-soluble macromolecules in the heparinization process. Even if some batches do not give appreciable error, we recommend to avoid preheparinized capillaries for measurement of COP. Both defibrination, and the amount of heparin needed to anticoagulate macro blood samples, have insignificant effect on COP. Loss of CO2 by diffusion from separated plasma may increase pH towards 9.5. Concomitantly, COP increased by 2.1 mmHg per pH-unit. If plasma or serum samples are capped within some minutes after separation, they may be stored for weeks at 4 degrees C in polyethylene tubes without appreciable change of COP.

Animals↗

Prognostic value of an electrocardiogram at rest and exercise test in patients admitted with suspected acute myocardial infarction, in whom the diagnosis is not confirmed.

The prognosis following discharge in 217 patients admitted with suspected acute myocardial infarction (AMI) due to chest pain, but in whom AMI was not confirmed, was related to the electrocardiogram (ECG) at rest and a symptom-limited exercise test. The patients were followed for 12 to 24 months, (median 14 months). The end-point was a cardiac event, i.e. non-fatal AMI or cardiac death. The prognosis after discharge was only slightly better than in a comparable group of patients with confirmed AMI (P = 0.05). The percentages without a cardiac event after one year were 91.3 and 86.1, respectively. Impaired prognosis was found in patients with negative T waves or ST depression at rest or with ST--T abnormalities or angina pectoris during exercise. Patients with ST depression or elevation, Q wave or intraventricular block at rest. ST abnormalities during exercise or both constituted a high-risk group. The prognosis was significantly better for patients without these entities. The percentage without a cardiac event after one year was 86.9 and 97.6, respectively. It is concluded that patients in whom AMI is not confirmed have a high risk of cardiac events following discharge. Signs of ischaemic heart disease in the ECG at rest and during exercise can be used to identify high and low risk patients.

Coronary Disease↗

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy.

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.

Adult↗

Acute reduction of arterial blood pressure reduces urinary albumin excretion in type 1 (insulin-dependent) diabetic patients with incipient nephropathy.

The effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus 51Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 micrograms) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79 +/- 13/8 to 104/68 +/- 9/7 mmHg (p less than 0.01), urinary albumin excretion rate from 68 (31-369) to 46 (6-200) micrograms/min (median and range) (p less than 0.01), and fractional clearance of albumin in all patients (median 29%) (p less than 0.01). Glomerular filtration rate was 110 +/- 11 before and 106 +/- 13 ml/min/1.73 m2 after clonidine injection. The blood glucose concentration was 15 +/- 4 mmol/l before and 14 +/- 5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.

Adult↗

Prevalence of microalbuminuria in children with type 1 (insulin-dependent) diabetes mellitus.

The prevalence of microalbuminuria was determined in children aged 7 to 18 years with Type 1 (insulin-dependent) diabetes of more than 2 years' duration. All patients (n = 102) attending 2 diabetes clinics were asked to collect 2 overnight timed urine samples for albumin analysis by radioimmunoassay. Complete urine collection was obtained in 97 patients (95%). Overnight urinary albumin excretion rates were also measured in 36 healthy children matched for age and sex. Nineteen of the 97 patients (20%) had microalbuminuria, i.e. overnight urinary albumin excretion rates above the upper normal level (14 micrograms/min) in both urine collections. Microalbuminuria was only demonstrated in patients aged greater than or equal to 15 years, prevalence 37% (19/52 patients). Arterial blood pressure was elevated, mean 122/84 +/- 11/9mmHg, in the microalbuminuric group (19 patients) compared to the age-matched normoalbuminuric diabetic group (33 patients), mean 117/74 +/- 10/10mm Hg, p less than 0.001. The prevalence of simplex retinopathy was identical in these two groups, i.e. 25%. Glycosylated haemoglobin was slightly higher in the microalbuminuric patients, p less than 0.10. Our cross-sectional study reveals a high prevalence (37%) of persistent microalbuminuria, a stage highly predictive of later development of diabetic nephropathy, in Type 1 diabetic children aged greater than or equal to 15 years.

Adolescent↗

Prevalence of hyperglycaemia and undiagnosed diabetes mellitus in patients with acute myocardial infarction.

The prevalence of hyperglycaemia and undiagnosed diabetes mellitus was assessed in 214 consecutive patients admitted to the coronary care units with acute myocardial infarction (AMI). On admission, 16 patients (7.5%) had known diabetes, and 19 patients, not previously known to be diabetic, had blood glucose concentrations of greater than or equal to 9 mmol/l. Fifteen patients survived for 2 months at which time a 75 g oral glucose tolerance test showed diabetes in 9 (60%) and impaired glucose tolerance in 4 (27%). Ten of these 13 patients (77%) with abnormal glucose tolerance had elevated glycosylated haemoglobin (HbA1c) on admission, indicating pre-existing glucose intolerance or diabetes. The prevalence of undiagnosed diabetes was 4.5% (9/198). However, we may have overlooked undiagnosed diabetes in a small number of patients on admission, since only a random blood glucose less than 8 mmol/l rules out diabetes, WHO criteria. Elevated blood glucose in patients with AMI is more likely to reflect a stationary pre-existing abnormal glucose tolerance than a temporary stress-induced phenomenon.

Adult↗

Urinary excretion of unconjugated and conjugated 3,5-diiodothyronine.

A radioimmunoassay for the estimation of 3,5-diiodothyronine (3,5-T2) in human urine has been established. The urinary excretion of both glucuronide and sulfate conjugates of 3,5-T2 were estimated after enzymatic deconjugation. In 19 healthy controls the median excretion of unconjugated 3,5-T2 was 276 pmol/d, whereas the median excretion of glucuronidated and sulfated 3,5-T2 in 7 healthy subjects was 448 and 451 pmol/d, respectively. The median excretion of 154 pmol/d in 9 hypothyroid patients did not differ from that found in controls. In contrast 12 patients with hyperthyroidism had an enhanced excretion, 1312 pmol/d (P less than 0.01). Compared with previous data on the daily degradation of 3,5-T2, it is concluded that approximately one-sixth of degradated 3,5-T2 is excreted in the urine.

Adult↗

The effect of a new ergoline derivative, CU 32-085, in the treatment of acromegaly. A controlled study.

The effect of a new dopamine agonist, CU 32-085 (8 alpha-amino-ergoline), on pituitary function in acromegaly was evaluated by a controlled, single blind study of 12 acromegalics. The study included a single dose placebo/drug (0.5 mg CU 32-085) trial and a long-term crossover trial with 3 month periods (placebo/CU 32-085 8 mg daily). The patients were evaluated clinically and biochemically (oral glucose tolerance (OGTT), TRH- and LHRH-tests) before and after each 3 month period. Nine patients completed this long-term trial; one died from myocardial infarction during the placebo period, and two dropped out because of side effects. The release of GH, judged from more than 9 h suppression of serum GH following the single dose, and from the response to OGTT after the long-term treatment, was significantly inhibited by CU 32-085. Serum GH reached normal values in 4 of 9 patients. Serum PRL was also markedly suppressed, to subnormal values after the 3 months in all but one hyperprolactinemic patient. Serum TSH, cortisol, FSH and LH were generally unaffected. Glucose tolerance was not significantly altered, although an improvement was found in six of nine patients. A semiquantitative evaluation of subjective symptoms showed a significant improvement following the long-term treatment, while objective signs of acromegaly were unaffected. The blood pressure was slightly lowered, both after a single dose and after 3 months' treatment. Seven patients experienced nausea and dizziness, two of them with vomiting, after a single dose of the drug. Four of these had similar symptoms initially during the long-term treatment, which forced two to interrupt the trial. We conclude that CU 32-085 caused a marked suppression of the release of GH and PRL and an improvement of the major symptoms of acromegaly, a therapeutic effect that is comparable to the previous experience with bromocriptine.

Acromegaly↗

Cell surface mannosyl transferase activity in the liver of embryonic chick. A mannose containing glycolipid as intermediate in glycoprotein synthesis.

Trypsin dissociated intact cells of embryonic chick liver catalyze the transfer of mannose from exogenous GDP-mannose to glycoprotein in vitro. In cells of 8 day old embryos a surface bound mannosyltransferase-system forms several mannose containing isoprenoid-lipids in a primary step. One of these compounds serves as a substrate in the highly specific second step of the overall reaction, the transfer of mannose to glycoprotein. The isoprenoic intermediate has been isolated and its effectivity as substrate for the incorporation of mannose into glycoprotein has been examined.

Animals↗