Psychological distress and adjustment to disease in patients before and after radical prostatectomy. Results of a prospective multi-centre study.

The aim of this prospective multi-centre study was to evaluate the level of psychological distress (PD) and adjustment to disease in patients who underwent radical prostatectomy. Furthermore, the impact of urinary incontinence and erectile dysfunction on PD was assessed. Anxiety, depression and PD were evaluated using the Hospital Anxiety and Depression Scale in 329 prostate cancer patients before surgery as well as 3, 6 and 12 months after surgery. These results were compared with those of a male German general population reference group. Adjustment to disease was assessed using the Perceived Adjustment to Chronic Illness Scale. Patients reported low levels of PD at all points of assessment similar to population norms of age-matched German men. Persistent PD was seen in about 8% of the patients and 20% had PD at least two of the measurement points. Relevant predictors for PD after surgery were urinary symptoms and baseline PD. Adjustment to disease was highest before surgery and had significantly reduced at 3 and 6 months after surgery. In general, men are resilient to the experience of localised prostate cancer and adjust well psychologically after surgery. However, between 8% and 20% of patients could possibly benefit from mental health support.

[Salvage prostatectomy. Principles of diagnostics and operative therapy]. / Salvage-Prostatektomie. Grundlagen der Diagnostik und operativen Therapie.

Organ-confined prostate cancer can be treated with curative intent by different types of radiotherapy or by radical surgery. Regardless of improvements in radiotherapy about 60% of patients with prostate cancer develop biochemical recurrence (BCR) which is defined by the progressive increase in serum prostate-specific antigen (PSA) and necessitates further diagnostic procedures. If non-organ-confined cancer and metastasis are categorically excluded by cross-sectional imaging using computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography CT (PET-CT) and bone scintigraphy, a prostate biopsy should be performed. Biopsy proven detection of recurrent or persisting prostate cancer after irradiation is essential prior to a salvage prostatectomy. The function of the lower urinary tract should be evaluated prior to surgery. Preoperative PSA measurement is the best prognostic indicator prior to surgery. Salvage prostatectomy in irradiated patients is more challenging and requires extensive skill. The most common complications are incontinence, rectal injury and anastomotic strictures. Both functional and oncologic outcome have improved due to better irradiation techniques and surgical skills. Provided post-radiotherapy recurrence of prostate cancer is diagnosed early enough, curing is possible by salvage prostatectomy.

Erectile dysfunction after radical prostatectomy: the impact of nerve-sparing status and surgical approach.

The core question of the study was whether the nerve-sparing status and surgical approach affected the patients' sexual life in the first year after surgery. In addition, determinants of erectile function (EF) and the extent of sexual activity were investigated. We conducted a multicentric, longitudinal study in seven German hospitals before, 3, 6 and 12 months after radical prostatectomy (RP). A total of 329 patients were asked to self-assess the symptoms associated with erectile dysfunction (ED). These symptoms were assessed using the International Index of Erectile Function and EORTC QLQ-PR25 questionnaires. A multiple regression model was used to test the influence of clinical, socio-demographic and quality-of-life-associated variables on the patients' EF 1 year after RP. Before surgery, 39% of patients had a severe ED (complete impotence). At 3, 6 and 12 months after surgery, it was 80, 79 and 71%, respectively. Although the surgical approach had no significant effect on EF, patients who had undergone nerve-sparing surgery had significantly lower ED rates. Nevertheless, 1 year after RP, 66% of these patients had severe ED. Age, nerve-sparing status and the burden of urinary symptoms had the greatest impact on the patients' EF. Regardless of nerve-sparing status and surgical approach, postsurgical improvement of EF does not mean a full convalescence of presurgical EF. Instead, it may rather reduce the degree of postsurgical ED in time. Consequently, urologists should disclose to the patient that ED is a likely side effect of RP.

[Radical prostatectomy - pro laparoscopic]. / Radikale Prostatektomie - pro laparoskopisch.

Recent publications have failed to demonstrate significant differences in perioperative oncological and functional outcomes between laparoscopic radical prostatectomy (LRPE) and R-LRPE. Reports suggesting better functional results, in particular better potency rates for R-LRPE, are rare. However, to date no large prospective, randomized, multicenter studies have compared the two methods. With an experienced operator both methods produce comparably good results. The monopoly of the intuitive system with extremely high cost of purchase and maintenance are the major disadvantages of R-LRPE.

[Medical decision making in hospital--results of an exploratory study on the value of shared decision making from the physicians point of view]. / Medizinische Entscheidungsfindung im Krankenhaus--Ergebnisse einer explorativen Studie zum Stellenwert des shared decision making aus der Sicht der Arzte.

The changes in the relationship between doctors and patients and the transfer of shared decision making into medical treatment has often been discussed. The role and the perspective of the patients are primarily described. The aim of our study is to examine the attitudes of physicians regarding the shared decision making concept, based on 15 interviews with clinical doctors. Our findings show that most doctors know the content of the concept and mostly agree with it. Practical barriers for the realisation of shared decision making are often stressed. The meaning of the concept of shared decision making for the physicians is in some respects different from the meaning of this concept for the patients. It is important to examine this concept more particularly with standardised instruments. It will be necessary to explore not only the role of patients and physicians in the medical decision making process but also the position of other relevant persons like the relatives of the patients or the nursing staff.

Effects of tolbutamide on insulin binding to isolated fat cells of the rat.

In isolated fat cells of the rat the in vitro and in vivo effects of tolbutamide on insulin binding and insulin response were studied. 450 mg tolbutamide/kg/day given for 7 days significantly increased the binding of insulin to isolated adipocytes. The binding curves reflected an increase in the number of receptor sites rater than in the affinity. The effect was associated with an enhanced response to insulin of the adipose tissue, since the fat cells obtained from animals treated with tolbutamide converted significantly more glucose to lipids in the presence of insulin than those obtained from the control group. However, the augmentation of insulin binding sites was observed only at a large tolbutamide dosage, which reduced the pancreatic insulin content, the secretory response of the isolated pancreas, and the serum insulin levels. Smaller doses, sufficient to produce metabolic effects via a stimulation of insulin secretion, did not provide additional insulin binding sites. When added in vitro to the binding assay or to adipose tissue incubated for 16 h, tolbutamide failed to increase insulin binding of the fat cells. It is suggested, therefore, that the effects produced by tolbutamide after in vivo treatment reflect an indirect rather than a direct action of the sulphonylurea.

Quantification of cells in islets of Langerhans using DNA determination.

DNA content seems to be an ideal reference parameter for data on secretory function or metabolism of pancreatic islets. The approved fluorometric DNA assay with diaminobenzoic acid (DABA) of Kissane and Robins comprises repeated ethanol extractions of the tissue for removal of lipids from which some DABA-reactive aldehydes may originate. In the present study it is demonstrated that only negligible amounts of DABA-positive material are extractable from islets of Langerhans. Furthermore, it is shown that various substances used in experiments on the endocrine pancreas do not interfere with the DABA-DNA reaction. A modification of the original DABA procedure which does not include ethanol extractions and which is thus more simple and accurate is described for application to pancreatic islets in the absence as well as in the presence of incubation medium. A close linear correlation between islet dry weight and islet DNA content is demonstrated. Islets from rats, normal mice, and ob/ob mice contain 38.3-39.2 ng DNA per microgram dry weight.

Inhibitory effect of deuterium oxide on glucose oxidation by pancreatic islets.

The inhibition of insulin release by deuterium oxide has been interpreted by its stabilizing action on the microtubular system of the beta-cell. Because only indirect information exists about beta-cell metabolism in the presence of D2O, the effect of D2O (99.7%) on glucose oxidation by pancreatic islets was studied. Heavy water reduced 14CO2 formation from [U-14C]glucose (16.7 mM) by ob/ob mouse and rat islets by 50 and 30%, resp. Omission of calcium from H2O-containing media resulted in a 40% diminished glucose oxidation by ob/ob mouse islets. In the absence of calcium, D2O led to a further decrease in 14CO2 production (60%). Erythrocytes oxidized similar amounts of glucose in the absence and presence of D2O. Effects of D2O on glucose transport and mitochondrial respiration are discussed as possible causes of the decreased 14CO2 formation in islet tissue. It is concluded that the inhibition of insulin release by D2O need not necessarily be ascribed to its stabilizing effect on microtubules, but may also be due--at least in part--to the reduction of islet glucose oxidation.

Changes of function and metabolism of the pancreatic B-cell caused by amino acids and related compounds.

Evidence is presented that, to explain the insulin releasing capacity of L-leucine, b-BCH or alpha-ketoisocaproate (KIC), the following alternatives must be considered: 1. Interaction of the unchanged molecules with specific B-cell membrane receptors triggers insulin release. Stimulation of metabolism is a consequence of these events. 2. Primary enhancement of intramitochondrial hydrogen production triggers insulin secretion which could modulate metabolism. 3. Combination of mechanism 1 and 2: a) Additive effects of 1 and 2. b) Potentiation of 1 by 2. c) Potentiation of 2 by 1. 4. Different control of first phase or second phase of insulin release by 1, 2, or 3.

Studies on the role of beta-cell metabolism in the insulinotropic effect of alpha-ketoisocaproic acid.

alpha-Ketoisocaproic acid has been shown to be a potent insulin secretagogue but the mechanism has not been elucidated. To define the role of beta-cell metabolism in the insulinotropic activity of alpha-ketoisocaproic acid the utilization of glucose and the oxidation of alpha-ketoisocaproic and isovaleric acid by incubated islets of obese hyperglycemic mice were measured. Glucose metabolism was never enhanced by alpha-ketoisocaproic acid. The same 14CO2 amounts were released from the non-secretagogue [1-14C]isovaleric acid (10 mM) or from alpha-keto[2-14C]isocaproic acid (5--20 mM). Pyruvate (20 mM) did not inhibit alpha-ketoisocaproic acid-induced insulin secretion in spite of reduction of decarboxylation of alpha-ketoisocaproic acid by more than 40%. The results indicate that stimulated insulin release in response to alpha-ketoisocaproic acid is not mediated by an indirect increase in glucose metabolism and further suggest that isovaleryl-CoA and following CoA-esters in alpha-ketoisocaproic acid degradation are not likely recognized as signals. The possibility, however, remains that enhanced intramitochondrial production of reducing equivalents elicits insulin secretion.

Uptake of tolbutamide by islets of Langerhans and other tissues.

3-H-tolbutamide was distributed in a volume exceeding the space occupied by 14-C-sucrose in islets as well as in liver, kidney, muscle, and fat. In contrast to previous reports, the findings suggest that tolbutamide is not restricted to the extracellular space of islets.

Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine (Periactinol, Nuran).

The tricyclic compound cyproheptadine (Periactinol, Nuran) inhibited glucose-induced insulin release from the perfused rat pancreas. Tolbutamide-stimulated insulin release was significantly reduced in the presence and completely suppressed in the absence of a substimulatory glucose concentration (5 mM). Arginine produced a slow rise of insulin release, which was completely abolished by cyproheptadine. Furthermore the biphasic glucagon release due to the stimulus was inhibited. Oxidation of 14C-glucose in isolated islets was unaltered in the presence of cyproheptadine, and pyruvate added to the perfusion medium failed to reverse the inhibitory effect on glucose induced insulin release, indicating that impaired glucose metabolism is not responsible for the inhibition. In addition, the inhibition remained unchanged when phentolamine was present, suggesting that the effect is not mediated by inhibitory adrenergic alpha receptors. Theophylline, in contrast, partly overcame the inhibition. When the calcium concentration of the medium was enhanced, the inhibitory effect of cyproheptadine was still visible, although the relative inhibition had become smaller. The results suggest that cyproheptadine blocks insulin release by affecting a fundamental step of the stimulus-secretion coupling common to peptide hormones. A participation of a calcium-antagonizing effect in the inhibition is discussed.