A case-control study of risk factor for renal cell cancer in northern Italy

A hospital-based case-control study of renal cell cancer was conducted in northern Italy betwen 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various resproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR=1.34 for 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR=1.89) whereas carrot intake showed a negative association (OR=0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR=2.00, 95 percent confidence interval (CI) 1.07–3.73; and OR=1.60, 95 percent CI 0.95–2.70, respectively).Address reprint requests to Dr Talamini. The work was conducted with the contribution of the Italian Association for Cancer Research, Milan, Italy and the CNR (Italian National Research Council) Applied Projects Oncology (Contract n. 85.02209.44).Drs Talamini, Barón, Barra, Bidoli, Serraino, and Franceschi are in the Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ. 33081 Aviano (PN) Italy. At the time of this work, Dr Barón was a visiting biostatistician from the Department of Preventive Medicine and Biometrics, University of Colorado, Health Science Center, CO, funded by the National Cancer Institute (US) and the Italian National Research Council. Dr Franceschi is also chief of the Hormones and Sexual Factors and Cancer Working Group of the European Organization for Cooperation in Cancer Prevention Studies, Bruxelles, Belgium. Drs La Vecchia and Negri are in the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also in the Institute of Social and preventive Medicine, University of Lausanne, Switzerland.     

Rat Jejunal Permeability and Metabolism of μ-Selective Tetrapeptides in Gastrointestinal Fluids from Humans and Rats

Purpose. To study intestinal transport and metabolism of three new -selective tetrapeptide enkephalin analogues, LEF537, LEF553 and TAPP These peptides are stabilized against enzymatic hydrolysis by having a D-aminoacid in position 2 and a blocked COOH-terminal. Methods. We used a single-pass perfusion technique to study the transport of the peptides in rat jejunum. To reduce luminal and/or brush-border metabolism during the perfusion we used protease inhibitors (Pefabloc^® SC, bestatin and thiorphan). The rate of metabolism was studied by incubations in rat jejunal homogenate, rat jejunal fluid and human gastric and jejunal fluid with and without these inhibitors. Results. The jejunal permeabilities (P_eff) of the peptides were 0.43–0.78 10^–4 cm/s without inhibitors and 0.09–0.45 10^–4 cm/s in presence of the inhibitors. All three peptides were rather rapidly degraded by enzymes in rat jejunal homogenate with half-lives of between 11.9 ± 0.5 and 31.7 ± 1.5 min. The addition of inhibitors to the homogenate prolonged the half-lives substantially for LEF553 (167 ± 35 min) and TAPP (147 ± 2 min), but only slightly for LEF537 (16.4 ± 0.5 min). LEF553 and TAPP were both hydrolyzed in rat and human jejunal fluid, while LEF537 was metabolized less in these fluids. When LEF553 and TAPP were incubated with intestinal fluid in the presence of inhibitors, metabolism was almost completely inhibited. There was no metabolism for any of the peptides in human gastric juice. Conclusions. The replacement of the terminal free carboxylic group with an amide group did not increase the stability of the peptides in jejunal tissue enough to allow successful oral drug delivery.     

Poly (triethylenglycol monomethacrylate) and poly(glycerol monomethacrylate) cross-linked gel as potential viscoelastics for intraoperative use

Background: The highly swelling poly(glycerol monomethacrylate) gel (polyGLYMA) and hydrophilic polymer poly(triethylenglycol monomethacrylate (polyTEGMA) were tested as potential viscoelastics for intraopertive use in anterior segment surgery. Methods: PolyGLYMA was implanted into the anterior chamber in 5 rabbits, and 40% polyTEGMA in 16 rabbits. The eyes were enucleated 1 week to 3 months after the operation. The corneal endothelium was examined with specular microscopy, and then the whole eye histopathologically. Results: In all eyes of the polyGLYMA group, the clinical findings were characterized by a marked ciliary injection and severe secondary glaucoma, and the histologic ones by a marked inflammatory infiltration and thickening of Descemet's membrane in the anterior chamber angle. Specular microscopy revealed a decrease in the endothelial cell density and polymorphism of the endothelial cells. In the polyTEGMA group, the anterior segment and the fundus were physiologic all the time, and specular microscopy and histologic findings showed no degenerative and/or inflammatory changes. Conclusions: PolyGLYMA proved unsuitable for intracameral application in rabbits. The new polymer polyTEGMA is characterized by high biologic tolerance after its implantation into the anterior chamber of rabbits. PolyTEGMA 40% might be considered as a potential viscoelastic material in humans.     

Molecular Human Reproduction: Evidence for {gamma}-aminobutyric acid specific binding sites on human spermatozoa

The possible presence of -aminobutyric acid (GABA) specificbinding sites on human spermatozoa was investigated. Swim-uppreparations of human spermatozoa were incubated with radiolabelledGABA in the presence of unlabelled GABA, alternatively displacersof GABA_A/B receptors and GABA transport proteins. The resultsindicate that GABA specific binding sites are present on thesurface of human spermatozoa, and that these binding sites possiblyindicate the presence of GABA transport proteins. Furthermore,GABA at different concentrations was added to swim-up preparationsof human spermatozoa. Possible effects of GABA on sperm motility,hyperactivation and acrosome reaction were explored. No significantdifferences were observed between treated groups and controlsconcerning motility parameters and hyperactivation. Incubationwith GABA did not cause any increase in spontaneous acrosomereaction. However, spermatozoa treated with the calcium ionophoreA-23187 showed a small but significantly increased ability toundergo the acrosome reaction following preincubation in 10–⁴M GABA (P < 0.05).     

Effects of prolonged uniocular dark adaptation on the direct-current electroretinogram of pigmented and albino rabbits

The direct-current electroretinogram of seven pigmented and seven albino rabbits was recorded from both eyes for almost 4 h in response to repeated identical light stimuli. Stimulus duration was 10 s, light intensity was 6.8 × 10² lux, and the interval between the beginning of succeeding light stimuli was 3 min. The dark-adaptation period preceding light stimulation was 30 min for one of the eyes (unoccluded eye) and 150 min for the contralateral eye (occluded eye), which was patched during the first part (117 min) of the experiment. In pigmented animals, the b- and c-wave amplitudes of the unoccluded eye slowly increased during the first part of the experiment but not significantly during the second. The a-wave amplitude was not significantly changed. After removal of the cover, the a- and b-wave amplitudes of the occluded eye immediately attained but did not exceed the level of those in the unoccluded eye, irrespective of the light adaptation induced by the stimulus flashes previously presented to the unoccluded eye. (Control experiments on six pigmented rabbits confirmed that stimuli identical to those used in the main part of the study caused a light adaptation, since a decrease in a- and b-wave amplitudes occurred after the first light stimulus following an initial dark-adaptation period of 2 h for both eyes.) In albino rabbits, electroretinogram responses were clearly discernible in the occluded eye also during the first part of the experiment, probably because of transillumination of the head. In other respects, the results were essentially similar to those of pigmented animals. The observation that occluded eyes did not dark adapt better, as judged by the electroretinogram responses, than contralateral eyes given repeated light adaptive stimuli may indicate the presence of a mechanism for transfer of adaptation information between the eyes.     

Measles seroprevalence among pediatricians in a teaching hospital]

OBJECTIVE: A measles outbreak occurred in S. Paulo state, during 1996 and 1997, resulting in 20,921 cases. Forty seven percent of the cases occurred in people between 20 and 29 years of age, and one of the control strategies of the Department of Health was the vaccination of health care workers. The prevalence of antibodies against measles among the hospital pediatricians was investigated. METHODS: One hundred and fifty samples were taken from volunteer pediatricians to test for measles antibodies using ELISA. A questionnaire about their having had measles and the vaccine was filled out. RESULTS: Of the 150 doctors, 122 (81.4%) were female and 28 (18.6%) male, of between 23 and 46 years of age (mean and median 27 years). The majority (98%-147/150) had protective levels of antibodies against measles (>100 UI/ml); 118 (80.3%-118/147) without and 29 (19.7%-29/147) with a history of measles. Only 3 pediatricians (2%-3/150), had negative serology, 2 without and 1 with a history of measles. Out of the 118 without history of measles, 79 (67%-39/118) in spite of the protective level of antibodies against measles, did not know if they, had been vaccinated. Out of the 79 vaccinated pediatricians, 64 (81%-64/79), had been vaccinated 25 years before, and still maintained protective levels of antibodies. Of the 3 doctors with negative serologies only one declared that he had been vaccinated. CONCLUSIONS: Measles seroprevalence among pediatricians of this hospital is high, especially due to preceding vaccination. On the other hand, the 2% of pediatricians with negative serology, in an epidemic situation could constitute a significant population for the acquisition and dissemination of the disease.     

Interceptive effect of Lapachol in rats

Lapachol is a naphtoquinone with therapeutic potential against Chagas disease and is also used as an antimalarial agent. To study the reproductive toxicity potential of Lapachol, pregnant Wistar rats were treated with 0.5 mL of distilled water (control group), 0.5 mL of hydroalcoholic solution (vehicle group), or 20 mg of Lapachol in 0.5 mL of hydroalcoholic solution (treated group) by oral gavage from the 8th to the 12th day of pregnancy. The following variables were observed: maternal body weight on days 1, 6, 15, and 21; food intake on days 2, 6, 15, and 21 of pregnancy. The number of live and dead fetuses and the sites of resorptions were counted. The ovaries were weighed and the corpora lutea were counted. Data were analyzed by ANOVA one-way Dunnett test and chi 2 test. Results showed that mothers were uneffected but there was 100% fetal/embryo mortality, indicative of a strong interceptive effect of Lapachol in rats.     

Influence of serum albumin on renal function in nephrotic syndrome

 Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), determined by the clearances of inulin and para-aminohippuric acid, were evaluated in 119 children with different types of nephrotic syndrome and in different stages: the nephrotic stage (serum albumin <25 g/l), recovery stage (25–35 g/l), and remission (>35 g/l). GFR in the nephrotic stage was significantly lower than in remission and in controls, and was lowest at onset of the disease (84±6, 111±4, and 119±2 ml/min per 1.73 m²). ERPF was higher in the nephrotic stage than in recovery, especially in children with histological lesions. Thus the filtration fraction (FF) was greatly decreased in the nephrotic stage. In patients investigated both in the nephrotic and the remission phase, GFR and FF increased significantly. There was a direct correlation between the serum albumin concentration and FF and an inverse correlation between mean arterial pressure (MAP) and GFR and FF in all patients, a direct correlation between the serum albumin concentration and GFR in minimal change nephrotic syndrome patients, and an inverse correlation between ERPF and serum albumin in children with histological lesions. In conclusion, GFR and FF were decreased and ERPF increased in the nephrotic stage, normalizing in remission. The low GFR in the nephrotic stage was thus not dependent on hypoperfusion. We suggest that the low GFR is dependent on a very low ultrafiltration coefficient. The direct correlation between GFR and serum albumin and the indirect correlation between GFR and MAP suggest compensatory mechanisms that increase the ultrafiltration pressure to counteract the severely reduced ultrafiltration coefficient. Received: 19 November 1997 / Revised: 11 April 1998 / Accepted: 14 April 1998     

Meta-analysis by combining p-values: simulated linkage studies

Meta-analysis has been little explored to make an overall assessment of linkage from different studies. In practice, it is likely that published linkage studies will only report p-values. We compared the performance of the widely used Fisher method for combining p-values with that of pooling raw data. More loci were consistently found by pooling raw data. In the absence of further information, combining p-values can provide an overall, but limited, assessment of different linkage studies. However, meta-analysis would be better viewed as a preliminary step toward the goal of analyzing the pooled raw data.