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Biomedical subjects

J Weil

Publications and source records attributed to J Weil.

At least 91 records · Page 5Linked to original sources

Effects of a small bolus dose of ANF in healthy volunteers and in patients with volume retaining disorders.

Thirty-seven patients with volume-retaining disorders (liver cirrhosis with ascites, n = 8; heart failure NYHA III-IV, n = 12; endstage renal failure, n = 17) and twelve healthy age-matched controls were given a small dose (33 micrograms) of hANF (human atrial natriuretic factor). We tested the resulting hemodynamic and renal effects as well as the effect on plasma cyclic GMP levels and compared them with the properties of platelet ANF receptors. The ANF injection evoked an increase in cyclic GMP plasma levels of 19.3 +/- 2.2 nM in healthy controls. This increase tended to be smaller in the cirrhosis group (15.5 +/- 3.3 nM) and in the heart failure group (16.8 +/- 2.3 nM) than in the dialysis group (20.5 +/- 2.5 nM). The invasion rates of cyclic GMP were comparable in all groups, but the evasion rates increased more in the heart failure and endstage renal failure groups (27.9 +/- 7.7 min and 26.1 +/- 3.4 min, respectively) than in the cirrhosis and control groups (14.9 +/- 1.9 min and 14.2 +/- 1.9 min, respectively). Patients with endstage renal failure and congestive heart failure showed a smaller decrease in diastolic blood pressure than controls and patients with liver cirrhosis. Renal actions of ANF were diminished in cirrhosis and heart failure patients. Binding capacities of platelet ANF receptors were higher in the control group (12.2 +/- 1.5 receptors/cell) than in the patient groups (cirrhosis, 7.8 +/- 1.2; endstage renal failure, 8.0 +/- 0.9; heart insufficiency, 8.0 +/- 1.0 receptors/cell), with no differences among the patient groups. Binding affinities were not significantly different. Correlation analysis showed that the relationship between the actions of ANF and the increases in plasma cyclic GMP levels is loose and cannot predict the hemodynamic or renal effects of exogenous ANF in a given patient. Although the behavior of plasma cyclic GMP levels fails to predict the responsiveness of the body to ANF in a given patient, it does reflect the differences between the patient groups and the control group. In contrast, we found no correlation between the properties of platelet ANF receptors and ANF action.

Adult↗

Effect of prolonged physical exercise on fluid regulating hormones.

Sixteen well-trained young men performed a test marathon to study the behaviour of atrial natriuretic peptide (ANP) and its second messenger cyclic guanosine monophosphate (cGMP) in relation to changes in plasma volume (PV) and plasma proteins, arginine vasopressin (AVP), renin, aldosterone, potassium and sodium. Blood samples were drawn under standardized conditions before and immediately after the run, as well as 3 h and 31 h after the run. Directly after the run, a two-and-a-half fold increase of plasma ANP and a twofold increase of plasma cGMP level were found, whereas PV decreased significantly by 7.4%. At this time renin-, aldosterone- and AVP-secretion were much stimulated. Thirty-one hours after the run, PV was markedly greater (10%) than before the race, whereas plasma proteins had returned to pre-exercise values. The ANP and cGMP were not significantly altered compared to the pre-race values. We have concluded that ANP and the other volume-regulating hormones may play an important role during and immediately after prolonged physical exercise but not in the longer recovery period. It seems that an influx of plasma proteins into the vascular space is responsible for the increased PV at this time.

Adult↗

Captopril in children with dilated cardiomyopathy: acute and long-term effects in a prospective study of hemodynamic and hormonal effects.

Hemodynamic and hormonal effects of captopril were prospectively studied in 12 children (median age 5.8 years, range 4 weeks to 15 years) with dilated cardiomyopathy. A mean dose of 1.83 mg captopril/kg body weight was administered in three or four single doses depending on age. Left ventricular volume, ejection fraction (EF), cardiac index (CI), and systemic vascular resistance (SVR) were noninvasively determined by two-dimensional (2D) and Doppler echocardiography before and 2 days and 3 months after the onset of treatment. Blood pressure and heart rate were recorded as well. Additionally, on the day hemodynamic measurements were made, plasma renin activity (PRA), serum aldosterone, and plasma atrial natriuretic peptide (ANP) concentrations were determined. Plasma catecholamines were measured before and 2 days after captopril treatment. Concomitant medication was kept constant during the short-term phase of captopril treatment. During long-term therapy, diuretics were reduced according to the clinical status. Stroke volume (SVI) (-7%), end-systolic (ESVI) (-31%), and end-diastolic (EDVI) (-21%) volume indexes were significantly reduced (p less than 0.05) during short- and long-term therapy. The remaining hemodynamic parameters showed only minor, statistically not significant, changes. During short-term therapy, median serum aldosterone levels fell from 138-88.5 pg/ml (p less than 0.05), and plasma ANP decreased from 144-94 pg/ml (p less than 0.05). After 3 months these effects were less marked and statistically no longer significant. Changes in PRA and plasma catecholamines were not statistically significant at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Assessment of dry body-weight in haemodialysis patients by the biochemical marker cGMP.

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.

Atrial Natriuretic Factor↗

Helicobacter pylori infection treated with a tripotassium dicitrato bismuthate and metronidazole combination.

Seventy-two patients with H. pylori infection in their antral mucosa took part in the study. Forty-three received metronidazole 400 mg t.d.s. for two weeks, plus De-Nol tabs 2 b.d. for four weeks, and the remaining 29 patients received metronidazole 400 mg t.d.s. for two weeks plus De-Nol liquid 5 ml q.d.s. for four weeks. Seven of 57 H. pylori isolates were found to have pre-treatment metronidazole resistance. Success, in terms of eradication of H. pylori, was assessed using a one-month post-treatment 14C urea breath test. Successful eradication of H. pylori was achieved in 72% and 79%, respectively, of the metronidazole/De-Nol tablet and metronidazole/De-Nol liquid groups. These figures increased to 87% and 84%, respectively, if the patients whose organisms were known to be metronidazole-sensitive were considered in isolation. H. pylori was successfully eradicated in only one of seven patients with a metronidazole-resistant organism.

Aged↗

[Acute reduction of increased atrial natriuretic peptide level and cyclic guanosine monophosphate in patients with chronic heart failure caused by beta-adrenergic stimulation with dopexamine hydrochloride. Correlation with hemodynamic parameters].

In eight patients (63 +/- 8 years) with dilated cardiomyopathy, the acute effects of positive inotropic stimulation with dopexamine hydrochloride, a beta-2-agonistic and DA1-dopaminergic catecholamine, on the plasma levels of ANP and cGMP were tested. A four-point dose-response curve was prepared for dopexamine from 1 microgram/kg/min to 4 micrograms/kg/min. Each infusion stage lasted 15 min; ANP and cGMP were taken from the mixed venous blood. Hemodynamic parameters were determined by a Swan-Ganz catheter; cardiac output was determined by thermodilution. ANP dropped by 40% from 348 +/- 124 pg/ml to 208 +/- 70 pg/ml (p less than or equal to 0.01), while cGMP dropped by 25% from 4.8 +/- 1.6 pmol to 3.6 +/- 1.3 pmol/ml at the time of maximum hemodynamic effect after 1 h. Linear regression analyses revealed a significant relationship (p less than or equal to 0.01) between ANP as the independent variable and cGMP as the dependent variable. The hemodynamic determinants of the ANP concentration proved to be--independently of each other--the pulmonary capillary wedge pressure (p less than or equal to 0.01) and the mean right atrial pressure (p less than or equal to 0.01). The results show that chronically elevated ANP and cGMP levels can be strikingly reduced within a short time, whereby ANP and cGMP show similar kinetics. The results suggest a use of ANP and cGMP as humoral parameters in the therapy control of chronic heart failure.

Adrenergic beta-Agonists↗

[Renal effects of ibopamine in comparison with furosemide in patients with mild heart failure].

Ibopamine is a novel oral dopamine analogue with positive inotropy and diuretic effects. In a double-blind, randomized study, the drug was investigated in 10 patients (mean age 49 +/- 10 years, six male, four female) with mild heart failure (NYHA classes II: six patients, III: four patients). Effects of single oral doses of 200 mg ibopamine, of 40 mg furosemide, and of 200 mg ibopamine plus 40 mg furosemide were compared in each patient at 3-day-intervals. One h after application, systolic and diastolic blood pressure increased from 119 +/- 11 to 124 +/- 8, and from 75 +/- 4 to 80 +/- 6 mm Hg (p less than 0.01) in the ibopamine group, while changes in both other groups and changes of the heart rate were insignificant. During 2 h after drug ingestion urinary flow was raised from 124 +/- 81 to 227 +/- 166 ml/2 h in the ibopamine group (p less than 0.05), while the application of furosemide (with or without ibopamine) resulted in several fold increases of urinary flow. After ibopamine, the 2-h-creatinine-clearance rose from 123 +/- 73 to 130 +/- 85 ml/min (not significant). Sodium excretion remained unchanged by ibopamine, potassium excretion was increased from 2.9 +/- 1.7 to 4.0 +/- 3.3 mmol/h (p less than 0.05), while effects of furosemide were several fold of those of ibopamine. Atrial natriuretic factor concentrations in plasma increased significantly after ibopamine and after ibopamine plus furosemide (p less than 0.01), but remained constant after furosemide alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗

Effects of a bolus dose of atrial natriuretic factor in young and elderly volunteers.

We assessed the haemodynamic and renal effects as well as the effects on plasma cGMP levels of a small i.v. dose (33 micrograms) of human atrial natriuretic factor (99-126; hANF) in two age groups of healthy volunteers. Binding properties of platelet ANF receptors were also measured. The elderly (four males, eight females, mean age 52.3 years) showed increased haemodynamic (decrease in blood pressure) and renal responses (diuresis, natriuresis, calciuresis) as well as greater increases in plasma cGMP levels and urinary cGMP excretion than the young subjects (four males, 12 females, mean age 26 years). Binding capacities and affinities of platelet ANF receptors were identical in both groups. These data indicate that the sensitivity to ANF increases with age and that this increased sensitivity is reflected in the reactivity of plasma cGMP levels but not in the properties of platelet ANF receptors. The data may be important for the therapeutic use of ANF, for the understanding of the physiological regulation of ANF action and may underline the necessity of using age-matched control subjects for clinical studies on the possible therapeutic effectiveness of ANF.

Adult↗

Effects of clonidine and dihydralazine on atrial natriuretic factor and cGMP in humans.

The effects of a 1-wk treatment with clonidine (75 micrograms/day twice a day) and dihydralazine (25 mg/day twice a day) on base-line levels of plasma atrial natriuretic factor (ANF) and plasma and urinary guanosine 3',5'-cyclic monophosphate (cGMP) and their changes by acute saline infusion (2 liters) in eight normal subjects were evaluated. Basal ANF was decreased to 65% in the clonidine group compared with both the control and dihydralazine groups. Volume loading increased plasma ANF levels by 30-40% of base-line values in the control and the dihydralazine groups and by 15% in the clonidine group. Basal plasma and urinary cGMP levels were raised by 30 and 90% in the dihydralazine group compared with both other groups. Volume loading increased plasma cGMP levels by 40% in the control and clonidine-treated groups and by 25% in the dihydralazine-treated group. It is concluded that ANF may contribute to hemodynamic effects of clonidine but not to those of dihydralazine. Dihydralazine increases plasma and urinary cGMP, supposedly by direct activation of the soluble guanylate cyclase.

Adult↗

[Hemodynamic and medicamentous modification of stimulated atrial natriuretic factor secretion].

The secretion of atrial natriuretic factor (ANF) and its adaptation to pharmacologic and hemodynamic interventions were investigated in 36 patients with sinus rhythm. To provoke standardized secretion of ANF all patients underwent two periods of rapid right ventricular pacing for 4 min with a 15 min interval. Immediately after the first pacing eight patients received 5 mg verapamil, 10 patients 5 mg atenolol and 10 patients 4 mg molsidomine intravenously. Eight patients remained untreated and served as controls. The amounts of atrial pressure increments due to pacing were identical (70% over basal pressure) in all patients. After molsidomine, but not after the other drugs, basal right atrial pressure was lowered. In controls the secretion of ANF due to the second stimulation was significantly (2.5-fold) larger than the secretion induced by the first stimulation. In patients receiving verapamil the secretion response after the second pacing was blunted. Atenolol did not affect the release of ANF. After molsidomine the upward regulation of the ANF secretion rate - seen in controls - was abolished. Thus, the myoendocrine cells are capable for a fast upward regulation of their ANF secretion rate after repeated stimuli. Verapamil directly blocks stimulated ANF secretion, whereas beta-blockade shows no effect. Molsidomine seems to impair enhanced ANF release by lowering basal atrial pressure.

Adult↗

[Growth stimulation and growth treatment in patients with cleft lip, jaw and palate].

Both in animal-experimental and in clinical research it has been demonstrated that early, extensive surgery on cleft palate patients has a growth inhibitory effect. Study of skulls of non-operated cleft palate patients seems to confirm this experience. A method of conservative, multidisciplinary treatment of cleft palate patients for which the application of the 'growth stimulator' is essential, is described briefly. During 18 years experience has been obtained with this therapy. It is very important that treatment starts as soon as possible after birth. After the introduction of the treatment method as described the number and the severity of the anatomical deviations in the nasomaxillary complex has been reduced considerably. In literature the incidence of crossbite is often chosen as the criterion for the mutual comparison of the results of cleft palate therapies. Patients treated with 'growth stimulators' show more than 50% less crossbite than groups of patients treated with other methods as described in literature.

Cleft Lip↗

Verapamil impairs secretion of stimulated atrial natriuretic factor in humans.

The adaptation of the secretory rate of atrial natriuretic factor to repeated adequate stimuli and the influence of the calcium antagonist verapamil on the release of atrial natriuretic factor were investigated in 16 patients. In eight patients (Group 1) right atrial pressure was abruptly increased by rapid right ventricular pacing for 4 min (stimulation I). After a 15 min interval, the identical stimulation was repeated (stimulation II). Eight patients (Group 2) underwent the same protocol but received 5 mg of verapamil intravenously after stimulation I. Pacing increased right atrial pressure in both groups identically by 70%. In Group 1, release of atrial natriuretic factor caused by the second stimulation (median 290 pg/ml over basal) was significantly (2.5-fold) larger than atrial natriuretic factor release induced by the first stimulation (median 116 pg/ml over basal). In the verapamil-treated patients (Group 2), the effect of right atrial pressure increase on release of atrial natriuretic factor was abolished after stimulation II. In both groups, changes in plasma concentrations of cyclic guanosine monophosphate corresponded to changes in atrial natriuretic factor concentrations. Thus, the myoendocrine cells are apparently capable of a fast upward regulation of their response to repeated secretory stimuli. Verapamil appears to block the stimulatory effect of a sudden increase in right atrial pressure upon release of atrial natriuretic factor.

Adult↗

Replacement therapy for a homozygous protein C deficiency-state using a concentrate of human protein C and S.

A severe congenital deficiency of protein C was diagnosed in a 10-month-old girl who had been suffering from skin necrosis since the age of 7 months. The patient was treated initially with fresh frozen plasma, 10 ml per kg body weight, every 24 h. Following treatment, the mean plasma level of protein C was 0.1 U/ml after 30 min and less than 0.02 U/ml after 24 h. The child was then treated with a concentrate of human protein C and S, 100 U protein C per kg body weight, given every 48 h for a period of 9 months. The mean plasma level of protein C was 0.93 U/ml 30 min after administration of the concentrate and 0.13 and 0.08 U/ml after 24 and 48 h, respectively. The mean post-transfusional in vivo recovery of protein C was 44% and the half life was 8.3 h. The mean plasma level of 'free' protein S increased from 1.1 to 2.2 U/ml after administration of the concentrate. There was no increase in 'bound' protein S. The in vivo recovery of 'free' protein S was 49% and the half life was about 17 h. Since the start of this replacement therapy using a human protein C and S concentrate, the patient has not developed any thromboembolic complications. These results indicate the therapeutic value of human protein C and S concentrate in the treatment of severe protein C deficiency.

Female↗

Binding sites for atrial natriuretic peptide on platelets in patients with congestive cardiomyopathy.

The aim of the present investigation was to evaluate a possible down-regulation of atrial natriuretic peptide (ANP) binding sites on platelets in patients with chronically elevated ANP plasma levels. The assay procedure was proved to be able to measure the total number of binding sites even in the presence of high ANP plasma levels. We studied 15 adult patients with congestive cardiomyopathy in comparison to 18 healthy volunteers. In the patients the median ANP plasma level (median = 375, range: 155-900 pg ml-1) was about six-fold higher than in the healthy volunteers (median: 55.5, range: 20-90 pg ml-1). The median cyclic guanosine monophosphate (cGMP) plasma level (median: 6.2, range: 2.5-21.4 pmol ml-1) was about three-fold higher than in the healthy volunteers (median: 1.8 range: 1-2.8 pmol ml-1). Despite these markedly elevated ANP and cGMP plasma levels we did not find significantly less receptors per platelet in the patients (median: 19, range: 7.2-60.2) than in the healthy volunteers (median: 24.5, range: 14.8-41.1). Furthermore, there was no difference in the dissociation constants between the patients (median: 10.5, range: 7.9-27.4 pmol l-1) and the control subjects (median: 8.9, range: 5.4-17 pmol l-1).

Aged↗

Influence of AV synchrony on the plasma levels of atrial natriuretic peptide (ANP) in patients with total AV block.

ANP was determined in 13 patients with DDD pacemakers due to total AV block, at rest and during bicycle ergometry under both pacing modes, DDD and VVI (7O/min). Under DDD pacing, the mean ANP level (normal range 5-95 pg/mL) at rest was 36 +/- 18 pg/mL (mean +/- SD) and increased significantly by the factor of 3.5 to 1 27 pg/mL during exercise (p less than 0.01). By just changing the pacing mode to VVI, the ANP levels rose to 73 +/- 28 pg/mL (p less than O.0 1) at rest (= 203% of DDD resting level) and to 216 +/- 184 pg/mL (= 170% of DDD peak level) during exercise P less than 0.01). These results show that under AV synchronous pacing, the ANP levels we generally lower. A possible explanation for this increased release of ANP during asynchronous VVI pacing is the acute increase of the atrial wall tension which occurs when the atria contacts during the systole against closed AV valves.

Aged↗