Rare and changeable as a chameleon: paraneoplastic syndromes in renal cell carcinoma.

INTRODUCTION: Paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) are important to be recognized by the treating physician, because they may lead to diagnosis of underlying malignant disease. On the other hand, PNS may dominate the clinical picture and can hide the true disorder like a chameleon. When realized, a PNS can be used as a 'neoplastic tumour marker', especially in case of recurrence. Their occurrence can even be linked to prognosis of disease. METHODS: A PubMed search combining the MeSH terms renal cell carcinoma and paraneoplastic syndrome was executed in April 2015. All hits concerning these MeSH terms have been taken into account when writing this review. RESULTS: There is a big gap between reporting and incidence of paraneoplastic syndromes in renal cell carcinoma. Most of the articles in Medline are case reports and reviews of research done in the 1950s-1990s. One problem is that a clear definition of a paraneoplastic syndrome is still lacking. The most important PNS in RCC are hypercalcemia. It is important that PNS are not only arising in advanced stages of renal cell carcinoma; in contrast, a PNS can often be the first symptom of RCC. CONCLUSION: Paraneoplastic syndromes are often unrecognized but are important biomarkers in RCC. Further research into the underlying pathomechanisms of PNS may improve our understanding of the RCC tumour biology and is urgently needed.

[TKI 2.0 - changes in the medical treatment of renal cell carcinoma]. / TKI 2.0 ­ Wandel in der medikamentösen Therapie des Nierenzellkarzinoms.

Only for renal cell carcinoma (RCC) in a local stage curative treatment option by surgical resection exists. For metastatic disease the 5­year survival rate decreases radically. A factor that contributes to this is the low sensibility to radiation and chemotherapeutics. Since the approval of the tyrosine kinase inhibitors in 2006 effective drugs for the treatment of mRCC is available. The specific inhibition of the vascular-endothelial-growth (VEGF)-receptor and the "mammalian Target of Rapamycin" (mTOR) leads to a prolongation of the progression-free survival as well as the overall survival rate. For a long time, the current target therapy with TKI appeared to be exhausted, but since recently research has gone a step further. Thus, Cabozantinib and Lenvatinib in the combination with Everolimus have been approved for second-line therapy in mRCC. For the first time a clinical study demonstrated positive results for an adjuvant treatment with sunitinib in patients with a high-risk RCC. Furthermore, in april 2016 the immune checkpoint inhibitor Nivolumab was approved for second-line therapy in mRCC in Germany. The following report examines briefly the current therapeutic recommendations, new findings and drug approvals and ongoing clinical trials.

Regional cerebral metabolic activity in the rat following experimental subarachnoid hemorrhage.

A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2-deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of less than 34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP.

Increased norepinephrine synthesis in the cerebral hemispheres of rats following subarachnoid hemorrhage.

Norepinephrine (NE) was assayed in rat brains 72 h after the creation of an experimental subarachnoid hemorrhage (SAH). NE in the cerebral hemispheres was found to increase by 64% when compared to controls. NE in the brainstem and cerebellum was unchanged. The kinetics of hemispheric NE metabolism were then studied in control and SAH rats. SAH caused a 3-fold increase in NE synthesis and a 44% reduction in turnover time when compared to controls. These results may reflect increased activity of central noradrenergic neuronal pathways in SAH.

Elevation of brain norepinephrine concentration after experimental subarachnoid hemorrhage.

Regional brain tissue catecholamine concentrations were measured in 5 control rats and in 10 rats 72 hours after experimental subarachnoid hemorrhage (SAH). Catecholamine levels were determined in the cerebral hemispheres, brain stem, and cerebellum of each animal using a radioenzymatic assay. Three days after SAH, the tissue concentration of norepinephrine (NE) in the cerebral hemispheres was 64% greater than that in control rats (P less than 0.001). NE levels did not change significantly in either the brain stem or the cerebellum. Most if not all of the NE in the brain tissue rostral to the brain stem is derived from neurons that originate in the locus coeruleus (LC). These data may therefore indicate that the LC is activated after SAH. The possible pathophysiological consequences of activation of the LC in relation to delayed cerebral ischemia after SAH will be discussed.

[Sex specific factors in recurrent idiopathic calcium urolithiasis]. / Geschlechtsspezifische Faktoren bei der rezidivierenden Idiopathischen Kalzium-Urolithiasis.

For question of sex dependency 24 h-urine samples of 165 patients with recurrent idiopathic calcium urolithiasis (100 men, 65 women) were obtained during regular diet and analyzed for differences in excretion rates of lithogenic and inhibitory constituents. Results were compared to values of 43 apparently healthy subjects (31 men, 12 women). Male stone patients revealed significantly higher excretion rates of lithogenic substances (calcium, uric acid, phosphate) and of the inhibitory agent magnesium than female patients. No differences were found for citrate and oxalate excretion values. Combination of an elevated rate of hyperuricosuria and significantly lower urine-pH in male patients results in a higher risk of stone formation in men. Similar differences between sexes were observed among controls but on a lower excretory level. Trying to explain the differing urinary excretion rates between sexes, the influence of sex differences in diet and body weight is discussed. An alteration of stone forming risk through action of sex hormones on urinary constitution appears unlikely.

[Magnesium excretion in recurrent calcium urolithiasis]. / Magnesiumausscheidung bei rezidivierender Kalziumurolithiasis.

Patients with recurrent non-infectious calcium urolithiasis were classified metabolically (122 patients). When the magnesium excretion was measured in the metabolic subgroups, a subset of patients (21.6%) could be identified with marked hypomagnesuria as the only metabolic abnormality. A significantly reduced rate of magnesium excretion was found in these normocalciuric stone formers while assessing the overall 24-h urine magnesium excretion or the 24-h urine and fasting urine magnesium to calcium ratio. These differences were apparently not due to factors that might modify renal magnesium excretion, such as parathyroid function, hypercalcemia, hypophosphatemia, alimentary sodium load, age and sex.

[Use of PGF2alpha and GnRH for estrus synchronization in cattle]. / Einsatz von PGF2alpha und GnRH zur Zyklussteuerung beim Rind.

Estrus detection has a tremendous impact on the reproductive efficiency in dairy farms. Recently the systematic use of hormones for synchronization of estrus and ovulation has been propagated. These programs are designed to facilitate estrus detection and/or increase its efficiency. Prostaglandin programs are used to improve estrus detection and reproductive management in dairy operations. All cows are treated up to three times in weekly or biweekly intervals at the end of the voluntary waiting period. This should lead to groups of cows in estrus within two to four days after PG treatment. Since PG programs cannot completely eliminate the need for estrus detection procedures for fixed time artificial insemination (AI) were developed. Fixed time AI not only requires control of the luteal phase of the cow but also synchronization of the follicular development. Treatment with GnRH will induce a new follicular wave and provide a dominant follicle in a defined growth phase at the time of PG administration seven days later. A second injection of GnRH given 48 hours after PG results in ovulation approximately 24 to 32 hours after GnRH (OvSynch-procedure). The pros and cons of hormone programs in dairy farming are discussed in the light of field trials and experiments performed in our department.

[The role of anaesthesiology in intensive care (author's transl)]. / Die Einordnung der Intensivbehandlung in die Anästhesiologie.

The German Society of Anaesthesia and Resuscitation was founded in 1953. The change of name to "German Society of Anaesthesia and Intensive Care" in 1977 reflects the development that this specialty has undergone since 1953; it is also an indication of the claim of anaesthesia to play a part in the care of the critically ill surgical patient. To the questions: what is the basis for this claim, what can anaesthesia contribute towards the care of these cases, where is the dividing line between anaesthesia and the other disciplines concerned in intensive care, what effect has intensive care work on the training of the anaesthetist, the answers are as follows: the concern of the anaesthetist is the care of the patient whose vital functions are impaired by surgery, anaesthesia or disease; he has therefore acquired techniques and means to maintain and assist these vital functions. His work in the intensive care ward is thus often no more than a continuation of the work he is doing in the operating theatre. This does not mean that he should replace the clinician of the traditional specialties working in the intensive care unit; rather that he should function as a co-ordinator as regards the type and course of treatment and nursing. For the anaesthetist there is the advantage that he can enlarge and consolidate the skill and knowledge acquired in the operating theatre, deepen his understanding of pathophysiological conditions and gain experience and assurance in evaluation of a variety of clinical situations. By becoming competent in diverse fields (at a time when the general trend is for ever more specialization) he will contribute towards raising the status of the anaesthetist who is still apt to be regarded as merely a technician.

Hereditary autosomal dominant form of bladder diverticula in male patients.

We report on 1 family in which 7 male patients had solitary bladder diverticulum. This family represents an autosomal dominant form of this disease by which only men are affected. Diverticula of the bladder can be classified as congenital (primary) or acquired (secondary). Vesical diverticula are uncommon in children and occur either primarily, when the vesical mucosa protrudes through a congenital defect in the bladder wall, or secondarily to bladder outflow obstruction. In adults the occurrence of multiloculated secondary diverticula is mainly due to subvesical obstruction. This seemingly autosomal dominant form of solitary diverticula in men was mostly associated with bladder outlet obstruction.

Pharmacokinetics of cyanide in poisoning of dogs, and the effect of 4-dimethylaminophenol or thiosulfate.

Cyanide in blood, plasma, and urine of dogs after administration of K14CN was determined with the isotope dilution technique. The addition of large amounts of inactive KCN as soon as possible to a sample to be analyzed inhibited the decrease of the original cyanide concentration. After administration of several lethal doses of cyanide into the stomach or by slow intravenous infusion a concentration of about 40 micron cyanide in plasma was found at the moment of respiratory arrest. Since 60% of the cyanide in plasma was bound to proteins the concentration of free cyanide which stopped respiration was about 16 micron. Quick formation of ferrihemoglobin by i.v. injection of 4-dimethylaminophenol after plasma cyanide had risen to or above 40 micron decreased the cyanide concentration in plasma and restored respiration, while cyanide was accumulated in red cells by formation of ferrihemoglobin cyanide. Equilibrium constants calculated for the reaction between ferrihemoglobin and cyanide in vivo indicated that the reaction approached equilibrium in a few minutes. Up to 60% of the radioactive cyanide absorbed was found as non-cyanide radioactivity in the urine.