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Biomedical subjects

H Groth

Publications and source records attributed to H Groth.

At least 37 records · Page 2Linked to original sources

Primary aldosteronism: treatment with trilostane.

Trilostane, an inhibitor of the 3 beta-hydroxysteroid dehydrogenase enzyme system of steroid biosynthesis, was applied to 18 patients with primary aldosteronism (9 patients with adrenal adenoma, 9 patients with bilateral adrenal hyperplasia) for 12 weeks. A marked decrease in plasma aldosterone was observed during therapy combined with a reduction in blood pressure and a rise in serum potassium levels. Except for slight diarrhea in 4 patients, which did not require cessation of trilostane medication, no further side effects were observed. Trilostane proved to be an effective inhibitor of aldosterone biosynthesis and was found useful in the treatment of primary aldosteronism both in patients with adrenal adenoma and in those with bilateral adrenal hyperplasia.

3-Hydroxysteroid Dehydrogenases↗

Unilateral parenchymatous kidney disease and hypertension: results of nephrectomy and medical treatment.

In the present study 43 patients with unilateral parenchymatous kidney disease and hypertension were investigated. 20 patients were nephrectomized, 23 treated with antihypertensive drugs. Both therapeutic approaches showed an excellent and sustained blood pressure-(BP)-lowering effect. BP fell from 185 +/- 27/116 +/- 13 to 138 +/- 20/86 +/- 10 mm Hg in the operated and from 194 +/- 32/116 +/- 13 to 149 +/- 22/95 +/- 12 mm Hg in the medically treated patients after 2 and 6 weeks, respectively (p less than 0.001). BP was 142 +/- 16/89 +/- 11 and 136 +/- 16/90 +/- 10 mm Hg at the long-term follow-up in the 2 subgroups. In the operated group 70% (n = 14) were cured, 20% (n = 4) were improved and 10% (n = 2) unimproved. In the medically treated group 65% (n = 15) were normotensive, 26% (n = 6) improved and 9% (n = 2) treatment resistant. No significant correlation between postoperative BP reduction and lateralization of renin secretion (PRA-ratio greater than or equal to 1.5) was found. Although cured patients showed a higher mean PRA-ratio, 4 patients with a PRA-ratio less than 1.5 were cured (n = 2) or improved (n = 2) postoperatively. Our results document an excellent and sustained antihypertensive effect of both nephrectomy and medical treatment in patients with unilateral parenchymatous kidney disease and hypertension. They further limit the predictive value of renal venous renin determination in the preoperative workup.

Adolescent↗

Does self-measurement of blood pressure improve patient compliance in hypertension?

Compliance with antihypertensive therapy was measured before and after distribution of non-automatic blood pressure devices. After 2 weeks of placebo treatment, 37 patients were treated with an antihypertensive combination drug containing triamterene. Adherence to therapy was assessed over 8 months by measuring urine fluorescence due to triamterene at intervals of 2-4 weeks, unknown to the patients. After 3 months of therapy, all patients, not just those with poor compliance, were given blood pressure devices and were carefully instructed in their use. The results showed that self-recording of blood pressure increased the compliance rate in the total group from 65% at the beginning of the study to 81% at the end. In those who initially showed poor compliance, there was an increase in compliance from 0 to 70% after self-measuring of blood pressure was introduced. We conclude that self-recording of blood pressure may be of value in patients with unsatisfactory blood pressure responses in whom poor compliance is suspected.

Antihypertensive Agents↗

The scored tablet--a source of error in drug dosing?

To determine the weight deviation of scored tablets after breaking we took 100 tablets of each of 34 brands of commercially available antihypertensive drugs and broke them into two, using the scored line. We graded the weights of the tablet halves according to their deviation from the expected weight (1 = less than or equal to +/- 5%, 11 = +/- 6-10%, 111 = greater than or equal to +/- 10%). The brands were ranked by the proportion of tablet halves (n = 200) in each category. Only seven brands divided very accurately and 11 brands divided reasonably accurately. Despite the scored line the remainder were either moderately (n = 10) or absolutely (n = 6) unsuitable for breaking, by hand or otherwise. A high proportion of these tablet halves showed weight deviations of 6-10% or more than 10% when compared to the expected weight. These findings show that a great number of antihypertensive drugs do not break evenly despite a scored line. This leads to inaccuracy of dosage.

Antihypertensive Agents↗

The spectrum of renovascular hypertension.

This review briefly summarizes pathological findings that may cause renovascular hypertension. Though atherosclerosis is the most common cause of renovascular hypertension, one third of all renovascular disorders has to be contributed to one of the arterial dysplasias. In contrast to atherosclerotic lesions which occur predominantly in older, male patients, fibrodysplastic alterations occur rather in younger, female patients. In very few cases malformations of the renal arteries or generalized diseases may cause renovascular hypertension.

Adult↗

Transdermal clonidine application: long-term results in essential hypertension.

Skin patches of a clonidine transdermal therapeutic system (clonidine-TTS) with a constant release rate of either 0.1 or 0.2 mg clonidine/24 h continuously over 7 days were used in 32 essential hypertensives. These self-adhesive drug delivery systems (3.5 cm2), which were affixed to the upper outer arm, were changed by the patients at weekly intervals. During a mean observation period of 7 months (range 1-19 months) transdermal clonidine reduced the blood pressure from 162 +/- 15/107 +/- 5 mmHg to normal values (diastolic less than or equal to 95 mmHg) in 63% of our patients. However, chronic use of clonidine-TTS was accompanied by a high frequency of contact dermatitis (type IV allergy) in nearly half of our patients (n = 15, 47%). In 11 of these 15 patients transdermal clonidine administration had to be stopped because of intolerable local skin reactions (pruritus, erythema, vesiculation, and/or infiltration). Subsequent patch testing with all components of clonidine-TTS was performed in eight cases. Whereas in seven cases an allergic contact dermatitis to clonidine was found, only one patient showed an allergy to another component of clonidine-TTS (polyisobutylene). We conclude that this strikingly high incidence of local allergic skin reactions limits the use of clonidine-TTS in essential hypertension.

Administration, Topical↗

Captopril in Cushing's syndrome.

To analyse the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome ten patients with hypercorticism (five with pituitary hypothalamic dysfunction, three with adrenal adenomas and two with adrenal carcinomas) received a single oral dose of 25 mg captopril. Mean arterial pressure was then determined at short intervals over periods of up to 240 min. Plasma renin activity (PRA) was measured immediately before the administration of captopril. Eleven patients with severe essential hypertension, who showed a comparable distribution of basal PRA values, served as a control. Patients with elevated basal PRA values (greater than 3 ng/ml X 3 h) showed, both in the subgroup of cases with essential hypertension and in that with Cushing's syndrome, a statistically significant fall (P less than 0.05-P less than 0.001) in mean arterial pressure, the decrease being slightly more pronounced in essential hypertensives. On the other hand patients with normal PRA values (less than or equal to ng/ml X 3 h) exhibited only a minor fall in mean arterial pressure reaching statistical significance (P less than 0.05) only after 60 min (essential hypertension) and 180 min (Cushing's syndrome), respectively. Our results document that in patients with Cushing's syndrome the effect of captopril seems to be determined by the activity of the renin angiotensin system. Thus, in a substantial number of patients with hypercorticism, the renin angiotensin system may be an important factor in the pathogenesis of hypertension, whereas in patients with low PRA values other factors like oversecretion of mineralocorticoids may be responsible for the observed blood pressure increases.

Adult↗

Human red blood cells--an ideal model system for the action of calcium agonists and antagonists.

To characterize the pharmacological properties of the slow calcium channel of human red blood cells, we studied the action of various calcium antagonists and two agonists on the 45Ca2+-influx. The Ca2+-ejecting ATPase was inhibited by vanadate. All dihydropyridine derivatives tested showed their inhibiting or stimulating effect on the channel at concentrations attainable in vivo (nitrendipine:Ki = 2.5; Bayer K 6244:Ki 5 microM; nicardipine:Ki = 15 microM, Ks = 0.5 microM; Ciba 28 392:Ki = 20, Ks = 0.3 microM; Ki = inhibition constant, Ks = stimulation constant). Of special interest was the biphasic behaviour (stimulation and inhibition) of the calcium antagonist nicardipine and the agonist Ciba 28 392. The maximum inhibition by the phenylalkylamine derivative verapamil was obtained at much higher concentrations (250 microM; Ki = 100). These data suggest that the calcium channel of human red blood cells has pharmacological properties very similar to the channel in heart and smooth muscle cells with respect to dihydropyridine action. Therefore, human red blood cells are an ideal model to study the action of calcium agonists and antagonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[Clonidine transdermal therapeutic system in essential hypertension: effect and tolerance].

The antihypertensive efficacy and side effects of a transdermal therapeutic system containing 2.5 mg clonidine (clonidine-TTS) was investigated in 21 patients with essential hypertension over a period of 10 weeks. The system was designed to release 0.1 mg clonidine/24 h. Mean systolic and diastolic blood pressure fell from 160 +/- 17/106 +/- 7 mm Hg to 139 +/- 16/91 +/- 8 mm Hg after 4 weeks and to 135 +/- 14/89 +/- 8 mm Hg after 10 weeks (p less than 0.001). Sufficient blood pressure control was achieved by one clonidine-TTS weekly in 24% and by 2 clonidine-TTS in 33% of the patients. 43% of all cases required additional oral therapy with 50 mg hydrochlorothiazide/day. However, antihypertensive action was accompanied by a high incidence of local skin reactions. These skin reactions with erythema, itching and red papules occurred in 6 of the 21 patients (29%) after treatment with TTS for at least 4 weeks. Patch testing with the various components of clonidine-TTS in 4 patients identified clonidine-allergy of delayed type in 3 cases. Typical clonidine side effects such as fatigue, dry mouth, constipation and sexual disturbances were moderate. It is concluded that clonidine-TTS has a good and continuous antihypertensive action. However, the high incidence of skin reactions limits its use in the treatment of essential hypertension.

Adult↗

[Deleterious course in tumor patients with ectopic ACTH secretion and secondary Cushing's syndrome].

Ectopic ACTH secretion with secondary Cushing's syndrome was observed in two patients with metastatic islet cell carcinoma and oat cell carcinoma of the lung respectively. Both patients were young (27 and 31 years), male, and developed severe hypokalemia, metabolic alkalosis and hypertension. Besides excessively increased ACTH-secretion, increased free urinary cortisol, 17-hydroxy- and 17-ketosteroids were found. The dexamethasone suppression test was negative. Inhibitors of adrenal steroid synthesis (aminoglutethimide, trilostan, o,p'-DDD) did not significantly change cortisol secretion and hypokalemia, and clinical symptoms persisted. Radiotherapy (5000 cGy) resulted in a partial remission of short duration in one patient. Both patients, however, died of metabolic complications 2 and 8 months after the diagnosis of Cushing's syndrome.

ACTH Syndrome, Ectopic↗

Altered calcium and sodium metabolism in red blood cells of hypertensive man: assessment by ion-selective electrodes.

Free intracellular calcium [Ca2+]i, sodium [Na+]i and potassium [K+]i were assessed in freeze-thawed human red blood cells (RBC) by ion-selective electrodes. After metabolic depletion by 30 mM 2-desoxy-glucose, [Ca2+]i increased faster and to significantly higher values in RBC from 16 patients with mild to moderate essential hypertension (mean diastolic blood pressure 111 +/- 10 mmHg) than in the RBC of 24 normotensives. The rate of [Ca2+]i increase was 7.0 +/- 3.6 versus 3.7 +/- 4.0 mumol/h/l cells (P less than 0.01) for the first 24 h and 8.1 +/- 4.8 versus 6.4 +/- 3.5 mumol/h/l cells for the following 24 h. [Na+]i before and after 24 h incubation was significantly higher in hypertensives, whereas basal [Ca2+]i and [K+]i before and after incubation were the same in both groups. After Ca loading by ionophore A 23187, the maximum rate of [Ca2+]i extrusion was not significantly lower in intact RBC from hypertensives than in those from normotensives (59.5 +/- 7.8 versus 87.9 +/- 18.1 mumol/min/l cells). These results indicate disturbances in RBC Ca metabolism similar to those observed earlier for Na and K. If generalized, the defect could lead to raised [Ca2+]i in smooth muscle and sympathetic nerve tissue, thus causing increased vascular tone and probably catecholamine release with subsequent arterial hypertension.

Adenosine Triphosphate↗

Influence of anoxia and dinitrophenol on the phosphorylase a activity and the cyclic nucleotide content of smooth muscle.

The effect of anoxia or 2,4-dinitrophenol (DNP) on the phosphorylase activity and the cyclic AMP and the cyclic GMP content was studied in smooth muscle preparations. When the aerobic conditions were changed to anaerobic in experiments on bovine mesenteric artery, there was a significant increase in the activity of phosphorylase a during the first 60 min. We had observed a reduction of the glycogen content of the artery during this time period, which accounted for about 2/3 of the increase in lactate production (Pasteur effect). Under anaerobic conditions the content of cyclic AMP in the vessel was not changed, and the increase in phosphorylase a activity was not inhibited by a blockade of adrenergic beta-receptors. DNP, which like anoxia inhibits the mitochondrial production of ATP, increased the phosphorylase a activity to the same extent as anoxia. Anoxia and DNP also enhanced the activity of phosphorylase a in pig thoracic aorta and rabbit colon smooth muscle. In thoracic aorta both anoxia and DNP produced a more transient and smaller increase in the phosphorylase a activity than in the mesenteric artery. The Pasteur effect was also relatively smaller (100%) in thoracic aorta than in mesenteric artery (400%). It is suggested that an anoxic increase in the phosphorylase a activity participates in the Pasteur effect in smooth muscle.

2,4-Dinitrophenol↗

Clonidine through the skin in the treatment of essential hypertension: is it practical?

The antihypertensive effects and side-effects of a clonidine transdermal therapeutic system (clonidine-TTS) were examined over 10 weeks in 22 patients with essential hypertension. The clonidine-TTS containing a 2.5 mg drug reservoir was designed to release 0.1 mg clonidine/24 h for seven days through a micropore rate-controlling membrane. In the total group mean systolic and diastolic blood pressure decreased from 162 +/- 14/106 +/- 4 mmHg to 137 +/- 17/92 +/- 8 mmHg after four weeks and 136 +/- 13/90 +/- 7 mmHg after 10 weeks (P less than 0.001). Five patients (23%) responded well to one clonidine-TTS (diastolic blood pressure less than or equal to 95 mmHg) and seven patients (32%) needed two clonidine-TTS. Additional oral therapy with 50 mg hydrochlorothiazide/day resulted in reduction of blood pressure to normal in six of the remaining 10 patients. This good pressure response was, however, accompanied by a high incidence of local allergic skin reactions of delayed type (type IV) in seven (32%) of the 22 cases. Patch testing with various components of clonidine-TTS which was performed in four of the seven patients showed in three cases allergic contact dermatitis to clonidine. Our results demonstrate a good and sustained antihypertensive action of clonidine-TTS. However, the extraordinarily high incidence of skin allergy to clonidine limits its use in the treatment of essential hypertension.

Administration, Topical↗