Smoking Following Renal Transplantation in Hungary and Its Possible Deleterious Effect on Renal Graft Function

Smoking is a known risk factor for kidney damage and also influences graft function following renal transplantation. Because smoking habits following kidney transplantation are not systematically evaluated, we analyzed them in a single center in Hungary. The survey was conducted among 402 randomly selected kidney graft recipients. We assessed smoking-related questions as well as clinical kidney disease and transplantation data. Posttransplantation renal function was analyzed based on serum creatinine values at 1 month and at 3 years after transplantation. In our study 25% (n = 102) of patients continued to smoke after transplantation. Smokers who received grafts displayed a significantly younger age compared with nonsmokers (40.1 ± 13.4 vs 47.1 ± 12.7 years; P < .001) independent of underlying kidney disease. Posttransplantation kidney function in smokers did not differ at 1 month after engraftment, but was significantly impaired at 3 years as assessed based on serum creatinine levels: 138.9 ± 42.4 versus 128.4 ± 48.5 μmol/L (P < .05). Decrease of renal function correlated with smoking intensity defined in pack-years (r² = 0.102; P < .05). Smoking is common following kidney transplantation in Hungary and might represent a risk factor for kidney damage following renal transplantation. Therefore, effective tobacco-dependence treatment is necessary in this patient population.     

Late hyponatremia in premature infants: role of aldosterone and arginine vasopressin

To assess the possible involvement of arginine vasopressin in the pathogenesis of late hyponatremia in preterm infants, serial measurements of sodium balance, fractional sodium excretion, plasma and urine osmolality and sodium concentration, and urinary aldosterone and arginine vasopressin excretion were performed at weekly intervals in nine healthy preterm infants. During the course of late hyponatremia, there was a significant increase in urinary aldosterone and arginine vasopressin excretion, from 0.94 +/- 0.16 to 4.30 +/- 0.76 micrograms/day and from 0.38 +/- 0.08 to 1.19 +/- 0.26 ng/day, respectively, from the first to the fourth to fifth weeks. A significant negative correlation was found between fractional sodium excretion and urinary aldosterone excretion. Aldosterone excretion, however, correlated positively with urinary arginine vasopressin excretion in seven of the nine infants. The parallel increase in urinary aldosterone and arginine vasopressin excretion in salt-losing premature infants may occur in response to the protracted contraction of the extracellular fluid compartment, and may contribute to the restoration of volume in the body fluid compartments and to the development of late hyponatremia.     

Food-induced thermogenesis in obese children

In 11 obese children aged 12.5 (±0.7) years with normal glucose tolerance and 7 lean, control children aged 11.9±0.7 years the preload resting energy expenditure and thermogenic response to a standardised meal was measured by indirect calorimetry. Preload energy expenditure was higher in obese children when expressed in absolute terms than in controls, but was not different when corrected for lean body weight. Four children with obesity of recent onset had lower food-induced thermogenesis and insulin response then seven overweight children with long-standing obesity. Food-induced thermogenesis and insulin response showed a significant positive correlation.It is concluded that food-induced thermogenesis is reduced in the early phase of childhood obesity but increased in the later phase when hyperinsulinaemia develops, pointing towards an important role of insulin in food-induced thermogenesis.Abbreviations EE energy expenditure - LBW lean body weight - FIT food-induced thermogenesis - IRI immunoreactive insulin - GH growth hormone - FFA free fatty acids - LR low responder - HR high responder - RO respiratory quotient     

Immunohistochemical demonstration of the co-expression of vimentin and cytokeratin(s) in the guinea pig cochlea

Summary Using a decalcification procedure for guinea pig petrous bones, we were able to prepare cryostat sections for immunohistochemical studies. A panel of monoclonal antibodies against intermediate filament proteins was then used to show a co-expression of cytokeratin and vimentin in the epithelial cells of the stria vascularis.     

Antinuclear factor, smooth and striated muscle antibodies in Duchenne-type muscular dystrophy

Antinuclear factors and antibodies to smooth and striated muscle were studied by the indirect immune fluorescence method in the sera of 19 children suffering from progressive muscular dystrophy. In 47% of the patients antinuclear factor positivity, in 65% anti smooth muscle antibody positivity, and in 26% antistriated muscle antibody positivity was found. Antibody to striated muscle was present in patients with serious advanced dystrophy and in patients unable to walk, while anti-smooth muscle antibody occurred in less serious cases, too. On the basis of the results, it is concluded that in genetically determined progressive muscular dystrophy a secondary autoimmune process develops owing to the degeneration of muscles as the disease progresses.     

Inhibition of proliferation of PC-3 human prostate cancer by antagonists of growth hormone-releasing hormone: lack of correlation with the levels of serum IGF-I and expression of tumoral IGF-II and vascular endothelial growth factor

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) such as JV-1-38 can inhibit androgen-independent prostate cancer directly by several mechanisms and/or indirectly by suppressing growth hormone/insulin-like growth factor-I (GH/IGF-I) axis. To shed more light on the mechanisms involved, the effects of JV-1-38 on PC-3 human prostate cancer were compared with those of somatostatin analog RC-160 in vivo and in vitro. METHODS: Nude mice bearing PC-3 tumors received JV-1-38 (20 microg), RC-160 (50 microg) or a combination of JV-1-38 and RC-160. The concentration of IGF-I in serum and the expression of mRNA for IGF-II and vascular endothelial growth factor (VEGF) in tumor tissue were investigated. RESULTS: In vivo, the final volume of PC-3 tumors treated with JV-1-38 was significantly lowered by 49% (P < 0.01), whereas RC-160 exerted only 30% inhibition (NS), compared with controls. Combined use of both compounds augmented tumor inhibition to 63% (P < 0.001). Serum IGF-I levels were decreased only in mice treated with RC-160. JV-1-38 suppressed mRNA for IGF-II in PC-3 tumors by 42%, whereas RC-160 alone or in combination with JV-1-38 caused a 65% reduction. JV-1-38 and RC-160 used as single drugs decreased the expression of VEGF by 50%, and their combination caused a 63% reduction. In vitro, JV-1-38 inhibited the proliferation of PC-3 cells by 39%. This effect could be partially reversed by addition of IGF-I to the serum-free medium. RC-160 alone did not affect the PC-3 cell growth in vitro, but in combination with JV-1-38 it augmented the antiproliferative effect of the GH-RH antagonist to 72%. Exposure to JV-1-38 in vitro reduced the expression of mRNA for IGF-II in PC-3 cells by 55% but did not change VEGF mRNA levels, whereas RC-160 had no effect. CONCLUSIONS: The antiproliferative effect of JV-1-38 was not associated with the suppression of serum IGF-I and was only partially correlated with the expression of IGF-II and VEGF in PC-3 tumors, suggesting that other mechanisms play a role in the antitumor action of GHRH antagonists. Nevertheless, the stronger inhibition of tumor growth after combined treatment with JV-1-38 and RC-160 indicates that the interference with multiple local stimulatory factors leads to an enhanced inhibition of prostate cancer.     

Experimental studies and first clinical experience with a new Lithoclast and ultrasound combination for lithotripsy

OBJECTIVES: A new lithotriptor for intracorporeal lithotripsy was developed combining the two most effective lithotriptors. A combination of the mechanically driven Lithoclast Master and a new ultrasonic device was constructed. Efficacy was tested in standardized model stones and in patient treatment. MATERIAL: The new lithotriptor is composed of a Lithoclast Master and an ultrasonic device (EMS, Nyon, Switzerland). The 1.0 mm Lithoclast probe is advanced off-center through the hollow 3.3 mm ultrasonic probe and protrudes about 1 mm. Five different artificial stones of defined hardness and density were used as model stones for disintegration. Time until first fragmentation and complete fragmentation (particles smaller than 2.2 mm to fit through the ultrasonic probe), percent disintegration after 1 min and time until 50% disintegration were determined for the new device as well as lithoclast and ultrasound alone. A total of 68 patients were treated by percutaneous nephrolitholapaxy (PNL) with the new device from February 1999 to August 2001. Lithotripsy was performed after fluoroscopically guided puncture of the lower calix and dilatation of the nephrostomy tract with coaxial bougies. Thirty-five patients had complete and 33 patients partial staghorn calculi. RESULTS: First fragmentation was reached 25-200 times faster with the combination as with either mode alone. Disintegrated stone mass after 1 min was 1.5-4 times larger in combined lithotripsy and 50% disintegration time 30-50% shorter. Clinically, complete stone free rate (KUB and ultrasound) was 66% after the first PNL. Sixteen out of 68 patients had a second look PNL with an overall stone free rate of 89.7% by dismission. Stone composition was calcium-oxalate-monohydrate in 13%, Ca-ox-monohydrate/uric acid in 35%, apatite in 20% and cystine in 11%. CONCLUSION: In in vitro experiments and clinically the new lithotriptor provides easy handling and high effectivity in fragmentation of all stones regardless of their composition.     

Dexloxiglumide Rotta Research Lab

Dexloxiglumide, the (R)-isomer of loxiglumide, is a selective and highly potent CCK1 receptor antagonist. It is twice as potent as the racemic compound. because the anti-CCK activity is specific to the (R)-form, whereas the (S)-isomer is almost ineffective. It has been developed by Rotta Research Lab SpA for the treatment of diseases in which CCK1 receptor activity is potentially involved, including gastrointestinal motility, food intake and pancreatic disorders [218696]. Its receptor-mediated actions have been described in multiple in vitro and in vivo pharmacological systems. Results from both preclinical and clinical studies indicate that it is an effective inhibitor of gallbladder contraction, improves lower esophegal sphincter (LES) function, accelerates gastric emptying, accelerates colonic transit and significantly decreases symptoms in IBS and functional dyspepsia patients, and therefore has potential as an effective treatment for constipation-predominant IBS. functional dyspesia, constipation, LES function, gastric emptying disorders and biliary colics. Forest Laboratories has entered into an agreement with Rotta for the development and marketing of dexloxiglumide for the treatment of constipation-predominant IBS and phase III studies are currently ongoing in the US. In August 2000, Merrill Lynch expected that dexloxiglumide would not be launched until 2004 [379892], and in June 2001, predicted a US filing date in 2003 [413928].