Current perspectives of catabolic mediators of cancer cachexia.

The development of cancer cachexia is perhaps the most common manifestation of advanced malignant diseases and has been recognized as a poor prognostic sign. The abnormalities associated with the condition include progressive weight loss, anorexia, asthenia, and anemia. The degree of cachexia is inversely correlated with the survival time of the patient and always implies a poor prognosis. Currently there is no established mechanism for cancer cachexia, but the severe metabolic disturbances and marked alterations in carbohydrate, lipid, and protein metabolism in the host finally lead to an increased energy deficiency. Weight loss, the key feature of cachexia, is due to a reduction of food intake, an increase in energy expenditure, or a combination of the two. A variety of changes in nutrient metabolism have been described in patients with cancer cachexia. Patients frequently exhibit a relative glucose intolerance and insulin resistance with increased activity of the Cori cycle. The cancer-bearing state affects protein synthesis and breakdown in different tissues of the body in a different manner. An acute-phase protein response can be presented in a significant proportion of patients with cancer with disease progression. A variety of proinflammatory cytokines appears to play a role in aspects of cachexia and a complex network of cytokines in combination with other factors might be involved. Aside from potential humoral mediators of cachexia, tumor-derived biologically active molecules have been reported recently.     

Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists.

A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.     

Impaired water metabolism and cerebral oedema following experimental subarachnoid haemorrhage in rats1

The acute phase of subarachnoid haemorrhage (SAH) is frequently associated with an impaired water metabolism and a disposition to cerebral oedema. For study of the pathogenesis of brain oedema following SAH, an experimental model of SAH was created in the rat The diuretic curves after water loading, the brain water and electrolyte contents and the plasma and cerebrospinal fluid arginine vasopressin (AVP) levels were examined in rats with SAH. Following a water load, a significant water retention and increases in brain water and sodium contents were observed after subarachnoid bleeding. Plasma and cerebrospinal fluid AVP levels were also elevated following SAH. It can be concluded that AVP plays important roles in the development of antidiuresis after water loading and in the disturbance of the brain water and electrolyte balance following experimental SAH.     

Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of^99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of^99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. This phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion,^99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.     

Neuroplastic effects of neonatal capsaicin on barrel cortex of adult rat. An electrophysiological and autoradiographic study

Capsaicin (50 mg/kg s.c./25 μl) was administered to rats on the 2nd and 5th days after birth. The animals were raised, and from the age of 3 months the properties of the evoked activity were tested in the contralateral barrelfield. This neonatal capsaicin treatment was found to induce profound changes in the responsiveness of the barrel cortex in the adult rats: (1) the receptive field of the neurons in the Cl barrel was expanded; units within a particular barrel were driven by a significantly larger number of vibrissae than in the controls. (2) The rate of discharge evoked by the related vibrissa deflection was enhanced, while (3) the angular sensitivity of the neurons was decreased. (4) The most prominent change in cortical activity was observed by autoradiography: capsaicin-treated rats exhibited an enhanced labelling of different types of neurons throughout the hemisphere (surpassing the cortical representation of stimulated vibrissae). The present observations indicate that neonatal capsaicin affects the functional activity of the rat somatosensory cortex. It is suggested that unmyelinated sensory afferents play a role in the development of the rat somatosensory system.     

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Endoscopic correction of vesicoureteric reflux--our thirteen years' experience.

AIM OF THE STUDY: We review our thirteen years' experience with the endoscopic treatment of primary vesicoureteric reflux (VUR). METHODS: We retrospectively reviewed the charts of 81 patients with primary vesicoureteric reflux who were treated endoscopically. The study included 61 girls and 20 boys aged 3 - 15 years. Twenty-eight patients had unilateral reflux, and 53 patients had bilateral reflux. Endoscopic correction with Teflon paste was done in 64 patients, and endoscopic treatment with Deflux was done in 17 patients. A total of 134 ureters were treated. RESULTS AND CONCLUSION: Reflux was corrected in 87 ureters (64.9 %) after the first injection. The second injection resolved reflux in an additional 20 ureters (14.9 %). Reimplantation was necessary in 4 patients (4.9 %). Overall success rate of the endoscopic treatment was 85.0 %. Reflux was completely absent in 79.8 % of the treated patients, and 5.2 % of the patients had a decreased grade of reflux after the procedure. Treatment was unsuccessful in 3.0 % of the patients. In seven patients spontaneous resolution of the persisting reflux occurred. Endoscopic correction should be performed in all patients with grade two, three and four reflux. Grade one reflux should be treated conservatively, and grade five reflux should be treated surgically. Since Deflux is a biodegradable material, most of the patients should be treated bilaterally, even if they have only grade one reflux. Endoscopic correction of primary vesicoureteric reflux is an easy, simple, fast and safe procedure that, in most cases, prevents regurgitation of urine from the bladder to the upper parts of the urinary system.