[Current aspects of oncological rehabilitation]. / Onkologische Rehabilitation. So finden Krebspatienten in den Alltag zurück.

On completion of acute medical treatment oncological rehabilitation serves the purpose of re-integrating the patient into the everyday situation, family and working life, while at the same time improving his/her quality of life. The aims of outpatient or inpatient rehabilitation are based on an individual analysis of both physical and psychosocial problems and are implemented within the framework of an interdisciplinary therapeutic program. Not the least of the positive effects of rehabilitation is the saving of costs achieved by shortening the patient's time in hospital and reducing the number of working days lost.

Effect of metoprolol on 24-hour urinary excretion of adrenal steroids and kallikrein in patients with essential hypertension.

Treatment of fifteen patients with essential hypertension over four weeks using the beta 1-adrenoceptor blocking agent, metoprolol, resulted in a decrease in 24 h urinary excretion of kallikrein and aldosterone along with a decrease in plasma renin activity. There was no significant change in 24 h excretion rates of the free adrenal steroids deoxycorticosterone, 18-OH-deoxycorticosterone, corticosterone, cortisol or 18-OH-corticosterone during treatment, which were not significantly different from excretion rates of normal males, thus excluding inhibitory effects of adrenal steroids on urinary kallikrein activity. A positive correlation was found between plasma renin activity and urinary excretion of kallikrein during the control period and after 2 weeks on metoprolol, supporting the assumption of a preserved link between the renin-angiotensin-aldosterone system and the renal excretion of kallikrein in these patients. The decrease in kallikrein excretion during beta 1-adrenoceptor blockade in patients with essential hypertension may be explained by a reduction in sympathetic tone and by reduced activity of the renin-aldosterone system.

Removal of 14-C-palmitate during ventriculocisternal perfusion in conscious dogs in insulin-induced hypoglycemia.

A detailed description of a method is presented allowing continous ventriculocisternal perfusion of metabolites in the conscious dog. Using this preparation, the loss of the infused albuminbound 14-C-aplmitate, was studied in 14 conscious dogs during ventriculocisternal perfusion with artificial cerebrospinal fluid (CSF). Forty-five percent of the infused 14-C-palmitate was recovered from the cisternal effluent under equilibrium conditions after 60 min of perfusion. The effect of the injection of 2.0 U insulin/kg was also investigated in seven dogs. Plasma glucose concentration decreased to 40--50 mg% and the amount of 14-C-palmitate recovered was significantly higher one hour after insulin compared to the controls receiving saline injections. No significant changes in cerebral arteriovenous differences of glucose or oxygen or in venous 14-C-palmitate concentration were observed during the same time. It is concluded that the combined use of ventriculocisternal perfusion and the analysis of cerebral arteriovenous differences are useful in studying brain metabolism in the consciuos dog.

The determination of brain water content: microgravimetry versus drying-weighing method.

The microgravimetric technique and the drying-weighing method for the determination of brain water content are analyzed and compared. A new method has been devised for the automatic production of the gradient column. For gravimetry, tissue samples weighing more than 30 mg have proven adequate for measurement. Specific gravity (SG) should be determined as early as 1 minute after tissue is inserted into the gradient column. Calculations of cerebral blood volume (CBV) from changes in SG of both brain tissue and intravascular perfusate have shown that the SG of brain tissue is considerably influenced by changes in CBV. This is because the SG of blood is higher than that of brain tissue, and may lead to a decrease of SG of about 0.002 in anemic cortex and of 0.001 in anemic white matter, which will simulate a false increase in tissue volume as water of 4% and 2%, respectively. This methodological error may be relevant when the early stages of ischemic brain edema development are studied. Water content of brain tissue can also be determined with acceptable accuracy by vacuum freeze-drying samples of brain tissue weighing about 100 mg. In contrast to cortex, white matter shows a wide range of individual and regional differences in water content. Thus, conclusions on the presence of brain edema drawn from tissue water determinations should always be subjected to cautious analysis and criticism.

Teicoplanin pharmacokinetics and dosage recommendations in chronic hemodialysis patients and in patients undergoing continuous veno-venous hemodialysis.

Multiple-dose pharmacokinetics of teicoplanin, a glycopeptide antibiotic against gram-positive infections, were studied in 9 chronic hemodialysis (HD) patients and in 7 patients with an acute renal failure (ARF) treated by continuous veno-venous hemodialysis (CVVHD). After a loading dose of 800 mg i.v. the 400 mg maintenance doses were administered according to a target trough concentration of 5-15 mg/l. Using the Bayesian estimation method implemented in the computer program Abbottbase Pharmacokinetic System (PKS), we defined an open three-compartment kinetic model for teicoplanin and calculated the individual pharmacokinetics. The mean terminal elimination half-life was 176 +/- 41.3 h in the HD group and 99 +/- 22.3 h in the CVVHD group (p < 0.005). The total body clearance (CL) was 4 +/- 1.2 ml/min and 9.2 +/- 1.7 ml/min in the HD and CVVHD patients respectively (p < 0.001). The mean reduction of the serum levels during a HD session was 9.1% in the patients dialysed with a F8 filter and 20.2% with a high-flux F60 filter (p < 0.001). The resulting extraction rate was 10 +/- 3.6% (F8) which is similar to the unbound fraction. The elimination of teicoplanin during CVVHD therapy strongly depended on the ultrafiltration rate (UFR) (r = 0.923, p < 0.05). An UFR of 15.6 l/24 h resulted in a removal of 32%/24 h of a 400 mg dose and an UFR of 6.2 l/24 h in 9.5%/24 h respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of the PDGF-antagonist trapidil in patients with and without renal impairment.

The pharmacokinetics of the PDGF-antagonist trapidil and its major metabolite desethyl-trapidil (M 1) were studied in patients with and without renal failure after a single dose of 200 mg and following 4-day treatment with 200 mg t.i.d. Twenty patients were classified according to their renal function as assessed by creatinine clearance (C(Cr)) in group A: 133.7 +/- 30.3 ml/min (n = 8), group B: 63.6 +/- 15.4 ml/min (n = 6) and group C: 17.9 +/- 6.1 ml/min (n = 6), patients on hemodialysis were not enrolled. After the first dose maximal plasma concentrations of trapidil with 5.99 +/- 1.60 (A), 5.76 +/- 1.46 (B) and 5.63 +/- 1.53 micrograms/ml (C) were not different between groups, but somewhat lower on day 4 with 4.96 +/- 0.78 (A), 5.78 +/- 1.78 (B) and 5.47 +/- 1.42 micrograms/ml (C). Similarly, AUC0-infinity-values on day 1 with 16.9 +/- 4.8 (A), 20.2 +/- 6.7 (B) and 22.2 +/- 11.2 micrograms/ml x h (C) showed only modest (NS) differences between groups, but decreased markedly on day 4 to 10.8 +/- 1.8 (A), 13.6 +/- 5.8 (B) and 14.4 +/- 4.3 micrograms/ml x h (C). Linear regression analysis between AUC and C(Cr) demonstrated no relationship between these parameters. For plasma concentrations of M 1 no significant differences were seen between groups. At steady state maximal plasma concentrations of M 1 occurred earlier and were slightly increased. In one patient (group B) receiving tamoxifen comedication markedly elevated plasma concentrations of trapidil and desethyltrapidil occurred, suggesting a pharmacokinetic interaction. Trapidil may be safely given to patients with impaired renal function, the apparent decrease of trapidil plasma concentrations may suggest autoinduction of metabolizing enzymes.

Renal diseases in ankylosing spondylitis: review of the literature illustrated by case reports.

Ankylosing spondylitis (AS) can be accompanied by extraarticular manifestations in the cardiovascular, pulmonary, neurologic and renal organs. Secondary renal amyloidosis is the most common cause of renal involvement in AS (62%) followed by IgA nephropathy (30%), mesangioproliferative glomerulonephritis (5%) as well as rarely membranous nephropathy (1%), focal segmental glomerulosclerosis (1%) and focal proliferative glomeruleonephritis (1%). Treatment associated nephrotoxicity may result from non-steroidal anti-inflammatory drugs or disease modifying agents. The purpose of this paper was to alert for the possibility of renal damage in AS and to analyse the frequencies of different etiologies of renal involvement. Two typical case reports of renal involvement in AS are presented to illustrate the clinical course of such patients. Renal side effects and possible pre-existing renal diseases should be taken into account while choosing the appropriate medication for patients with AS.

Case report and review of the literature. Fatal pulmonary complication in ankylosing spondylitis.

A 44-year-old non-smoking patient with longstanding ankylosing spondylitis presented in marked respiratory distress with tachypnea, fever, cough, greenish sputum, night sweats, dyspnea and weight loss. Computed tomography showed traction bronchiectases and cavities associated with scarring. The findings were most pronounced in the upper lobes which contained multiple cavities up to 8 cm in diameter harboring fungus balls. The superior segment of the left lower lobe showed two additional cavities. Tuberculosis and atypical mycobacteria were ruled out. Antibiotic therapy resulted in transient improvement. Five months after this acute exacerbation the patient expired from massive haemoptysis. Pulmonary fibrosis is a rare manifestation of ankylosing spondylitis, may be complicated by infection and haemorrhage and determine the dismal prognosis of these patients.

[Long-term efficacy and side effect profile of a low-dose bemetizid-triamterene combination in patients with essential hypertension]. / Langzeitwirksamkeit und Nebenwirkungsprofil einer niedrigdosierten Bemetizid-Triamteren-Kombination bei Patienten mit essentieller Hypertonie.

As only few data are available on the antihypertensive effectiveness and pattern of adverse reactions to low-dose diuretic treatment, a multicenter study was designed in which 77 patients with essential hypertension (WHO grades I to II) were followed up for one year with a view to answering the above questions. In patients who, at the end of a two weeks' placebo period had diastolic pressure values of more than 90 mmHg treatment was initiated with one daily tablet of a new preparation containing 10 mg bemetizide and 20 mg triamterene, for eight weeks. If, at the end of this interval, the target pressure values of less than 90 mmHg had not been attained, the dose was doubled. Blood pressure measurements (in sitting position) were repeated fortnightly, serum electrolytes, metabolic parameters and urinary triamterene fluorescence determined every four weeks. 56 of the 77 patients stayed on 10/20 mg bemetizide-triamterene for twelve months running. In 13 cases the dose had to be raised. Eight patients dropped out of the study. Average blood pressure values of 56 patients decreased from 169/103 mmHg (at the end of the placebo period) to 145/83 mm Hg after 52 weeks. Diastolic pressure reductions averaged 18 mmHg in 27 patients below the age of 49, 19 mmHg in 22 patients aged between 50 and 65, and 22 mmHg in seven patients older than 65 years. At the end of the 52 weeks' therapy, total serum cholesterol, HDL and LDL cholesterol, triglycerides, glucose and uric acid were unchanged in comparison to the placebo period in the entire group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of erythropoietin therapy on alpha receptor density in chronic dialysis patients]. / Einfluss einer Erythropoetintherapie auf die alpha-Adrenozeptoren-Dichte bei chronischen Dialysepatienten.

The effect of a six months therapy with human recombinant erythropoietin (rHu-EPO) on blood pressure and on several parameters of sympathetic nervous activity was studied in chronic haemodialysis patients in a controlled and randomized trial in order to gain further insight into the mechanism of rHu-EPO-induced blood pressure elevation. Treatment was started at a dose of 3 X 80 IE/kg/week in eleven patients aiming to increase the initial hemoglobin concentration (7.0 +/- 0.3 [SEM] g%) to 10.0 g% by dose adjustments, while another untreated eleven patients served as a control group. Diastolic arterial pressure measured before and after haemodialysis increased on rHu-EPO treatment by 7 and 8 mm Hg respectively (p less than 0.05). Plasma noradrenaline concentration was increased (p less than 0.05) after the six months treatment period in the presence of unchanged dry weights. Conversely platelet alpha 2-adrenoceptor density (3H-yohimbine binding) and the fraction of high affinity binding sites for alpha 2-agonists (3H-UK 14.304) decreased (p less than 0.01) along with a decrease in reactivity to exogenous noradrenaline (p less than 0.05). None of these parameters changed in the control group compared to pretreatment values. The results obtained demonstrate that increased plasma noradrenaline concentrations may participate in rHu-EPO induced blood pressure increases. The decrease in platelet alpha 2-adrenoceptor densities and the decrease in noradrenaline reactivity in the presence of increased plasma noradrenaline concentrations suggest an intact regulation of alpha 2-adrenoceptors in chronic haemodialysis patients on chronic rHu-EPO therapy.

[Increased plasma endothelin concentrations in patients after liver transplantation and in liver cirrhosis]. / Erhöhte Plasma-Endothelin-Konzentrationen bei Patienten nach Lebertransplantation und bei Leberzirrhose.

Endothelin, one of the most potent vasoconstrictors known today, is released by the vascular endothelium. Patients after liver transplantation and patients with liver cirrhosis show significantly higher plasma endothelin concentrations and significantly reduced results in the quantitative liver function tests (ICG-HL, GEC, Lidocaine-HL, MEGX) compared with healthy control persons. The plasma endothelin concentrations were better correlated with the more liver bloodflow dependent function tests (ICG-HL, Lidocaine-HL) than with the more metabolic-capacity dependent function tests (GEC, MEGX). As cyclosporine A in vitro can increase the liberation of endothelin, we conclude that in patients after liver transplantation an endothelin mediated cyclosporine induced hepatotoxicity might be the reason for the demonstrated association.

[Cerebral hemodynamics in chronic hypoxic hypoxia].

The effects of chronic-hypoxic hypoxia on cerebral blood flow and its regulating mechanisms were investigated by means of intracardiac injection of radioactively labelled microspheres. In a gas chamber designed and constructed for the purpose, adult cats were exposed to stepwise decreasing inspiratory oxygen concentrations (for 4.5 months with a final O2 concentration of 8 vol%). Using animals adapted to hypoxic hypoxia, responsiveness of cerebral blood flow either to alterations in systemic arterial pressure (SAP) or to alterations in arterial blood oxygen tension (PaO2) were assessed. Flow measurement was done under three different conditions: normoxic normotension (PaO2 greater than 100 mmHg; SAP greater than 100 mmHg), hypoxic normotension (PaO2 = 30 mmHg; SAP greater than 100 mmHg), or normoxic hypotension (PaO2 greater than 100 mmHg; SAP = 60 mmHg). Hematocrit values continuously increased to 56% during the process of adaptation to hypoxia. There was also a remarkable increase in cardiac output of hypoxia-adapted animals subjected to hypoxia and to normoxia. Chronic-hypoxic hypoxia led to increased cerebral blood flow, which persisted even when animals were returned to normoxia. Under hemorrhagic hypotension, cerebral blood flow fell significantly in animals adapted to chronic-hypoxic hypoxia but did not fall short of the absolute values in controls. The relative reduction in cerebral blood flow might be attributable to the decrease in cardiac output and to altered blood viscosity. This implied that, even in animals subjected to long-standing graded hypoxic hypoxia, autoregulatory capacity might be partly preserved.

Regulation of alpha 2-adrenoceptor density in normotensive and hypertensive man.

We examined normotensive and hypertensive subjects in order to determine whether changes in platelet alpha 2-adrenoceptor density following alterations in plasma noradrenaline are related to changes in noradrenaline (NA) reactivity. Noradrenaline reactivity, plasma NA, alpha 2-adrenoceptor density, and adenylate cyclase activity were measured before and after a 24-h infusion of NA at a subpressor dose (0.02 micrograms/kg per min, n = 13), and also after application of drugs known to increase (nifedipine and furosemide) or decrease (clonidine) plasma NA. Measurements were obtained 60 min after nifedipine (20 mg in a single dose, n = 13), after 3 weeks on furosemide (30 mg twice a day, n = 8) and after 1 week on clonidine (150 micrograms three times a day, n = 5). Infusion of NA decreased alpha 2-adrenoceptor density (P less than 0.01) and NA reactivity (P less than 0.05). Nifedipine decreased alpha 2-adrenoceptor density and NA reactivity (P less than 0.01 for both) in patients with essential hypertension. The alterations in alpha 2-adrenoceptor densities were paralleled by a decreased adrenaline-induced inhibition of adenylate cyclase activity (P less than 0.01). Furosemide decreased alpha 2-adrenoceptor density (P less than 0.01), the fraction of high-affinity binding sites (P less than 0.01) and NA reactivity (P less than 0.05) in normotensive subjects. Following clonidine all three parameters, alpha 2-adrenoceptor density, the fraction of high affinity sites and NA reactivity, increased (P less than 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)