Polymorphism of vitamin D receptor gene start codon in patients with calcium kidney stones

BACKGROUND: A linkage has been detected between vitamin D receptor (VDR) locus and calcium kidney stone disease. In order to assess the eventual role of VDR gene start codon polymorphisms in stone production, we analyzed the genotype-phenotype association in a group of patients with calcium kidney stones. METHODS: One hundred and fifty-five patients were studied. VDR genotypes were characterized at the translation start site by restriction fragment length polymorphism analysis, using endonuclease FokI. Phenotypes of calcium-phosphate metabolism were compared in patients with different genotypes: strontium enteral absorption (used as a surrogate marker for calcium absorption), bone mineral density (BMD), calcium and phosphate excretion were measured. RESULTS: Genotype distribution was not different in hypercalciuric and normocalciuric stone formers. Enteral strontium absorption, calcium excretion and BMD did not vary with the patient's genotype. Serum concentrations of phosphate (p=0.022) and renal threshold for phosphate excretion (p=0.026) were lower in patients with genotype FF (homozygous for the absence of the FokI site) than in those with genotype ff (homozygous for the presence of the FokI site). The lower phosphatemia was confirmed in FF hypercalciuric patients, but not in normocalciuric ones. Serum concentrations of phosphate and calcitriol in the group of hypercalciuric patients were inversely correlated with the genotype FF. CONCLUSIONS: The FokI genotype does not appear to be involved in the causes of idiopathic hypercalciuria and kidney stones. Hypercalciuric patients with FF genotype may be a subgroup with low plasma concentrations of phosphate, predisposed to tubular leakage of phosphate.     

Cardiovascular risk in hypertensive patients: results of the Pandora project

BACKGROUND: The aim of the Pandora project is to collect epidemiological information, check diagnostic and therapeutic pathways, and assess outcomes in a large hypertensive population. This report presents the results on patients enrolled in the study between 1997-1999. METHODS: Twenty-one general practitioners working in the Ravenna Local Health Service took part in the study. They were supplied with IBM compatible PCs and were trained to enter the patient's data (age, gender, familiarity for cardiovascular diseases, smoking, hospitalisations for cardiovascular disorders, diabetes, blood pressure, total cholesterolemia, creatininemia, antihypertensive therapy) on So.Ge.Pa. software. Cardiovascular risk factors were assessed according to the WHO - ISH joint committee recommendations. RESULTS: 2,608 treated hypertensive patients were enrolled, 65% of whom showed inadequate blood pressure control. The prevalence of inadequate BP control was higher in patients on multiple-drug antihypertensive therapy compared with those on monotherapy (71.9% vs. 47.9%), in older than in younger patients (70.7% vs. 56.1%) and in patients with three cardiovascular risk factors, or diabetes, or affected target organs, compared to those with two or less risk factors (72.4% vs. 63.3%), (p < 0.001 for all). 63.6% of patients were at risk for age, 36.6% for family history of cardiovascular diseases and 31.7% for severe hypercholesterolemia. CONCLUSIONS: BP control was inadequate in a large percentage of patients, but it was particularly unsatisfactory in the elderly and in patients with high cardiovascular risk. A cluster of cardiovascular risk factors was found in both adequately and inadequately controlled hypertensive patients.     

Alpha(2)-macroglobulin levels are high in adult patients with congenital antithrombin deficiency

Antithrombin is responsible for about 80% of the progressive inhibitory activity of thrombin in human plasma. The role of other protease inhibitors known to inhibit thrombin is not completely clarified. However, their contribution may become relevant when antithrombin is low. We elected to investigate adult patients with congenital antithrombin deficiency to assess the concentration of other naturally occurring thrombin inhibitors such as alpha(2)-macroglobulin, alpha(1)-antitrypsin, heparin cofactor II, and C(1)-inhibitor. The study included 59 patients with congenital antithrombin deficiency with and without a previous history of thrombosis, together with an equal number of control subjects matched for age and sex. Statistically significant differences (patients vs. controls) were observed only for alpha(2)-macroglobulin (i.e., 120 vs. 102%, p<0.01). Further analysis of antithrombin-deficient carriers with and without a past history of thrombosis showed that alpha(2)-macroglobulin levels were higher than the 90th percentile of control distribution more often in asymptomatic than symptomatic men (odds ratio=0.04; confidence interval=0.003-0.60), but not in women (odds ratio=2.14; confidence interval=0.35-13.1). In conclusion, results from this cross sectional study showed that alpha(2)-macroglobulin levels were high in patients with congenital antithrombin deficiency. Furthermore, the high levels were found more often in asymptomatic than symptomatic men. Whether this increase provides protection against thrombosis should be evaluated in a prospective study.     

Proenkephalin A-derived peptides in invertebrate innate immune processes

Lipopolysaccharides (LPS) injection into the coelomic fluid of the leech Theromyzon tessulatum stimulates release of proenkephalin A (PEA)-derived peptides as determined by immunoprecipitation and Western blot analyses. This release occurs in the first 15 min after LPS exposure and yields a 5.3-kDa peptide fragment corresponding to the C-terminal part of the precursor. This fragment is then cleaved to free an antibacterial peptide related to mammals arginine phenylalanine extended enkelytin: the peptide B. These PEA processing peptides were characterized using a combination of techniques including reversed-phase HPLC, microsequencing and mass spectrometry. The isolated invertebrate peptide B presents a high sequence homology with the bovine's and the same activity against Gram+bacteria. Titrations revealed the simultaneous appearance of Methionine-enkephalin (ME) and peptide B in invertebrates after stimulation by LPS (in a dose-dependent manner), surgical trauma or electrical stimulations to neural tissues of the mussel. Furthermore, peptide B processing in vitro yields Methionine-enkephalin arginine phenylalanine (MERF), which exhibits via the delta receptors, immunocyte excitatory properties, i.e., movement and conformational changes, but no antibacterial activity. We surmise that this unified response to the various stimuli is a survival strategy for organism by providing immediate antibacterial activity and immunocyte stimulation, thereby reducing any immune latency period needed for an adequate immune response.     

Volatiles from the venom of five species of paper wasps (Polistes dominulus, P. gallicus, P. nimphus, P. sulcifer and P. olivaceus).

The venom volatiles of five paper wasp species, four European belonging to the subgenus Polistes sensu stricto (P. dominulus, P. gallicus, P. nimphus, P. sulcifer) and one belonging to the Asian subgenus Gyrostoma (P. olivaceus), have been sampled by headspace solid phase micro-extraction and analysed by gas chromatography-mass spectrometry. The venom volatile components of Polistes wasps have never been fully investigated before, although the presence of some spiroacetals has been previously reported in literature. The composition of the venom was qualitatively and quantitatively different among the analysed species with the major substances tentatively identified, on the basis of their mass spectra, as: spiroacetals, mainly 2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, two amides, N-(3-methylbutyl)acetamide and N-(3-methylbutyl)propanamide and acetates of saturated, mono- and di-unsaturated 2-alcohols with an odd number of carbon atoms in the chain. The acetate of a di-unsaturated 2-alcohol, present in two isomeric forms, identified as (E)- and (Z)-5-tangerinol has never been reported in literature for insects. Propanoates of the same 2-alcohols were only found in the venom of P. gallicus. Both the amides and the above-mentioned spiroacetal have been already shown to be alarm pheromones in other social wasps, while the acetates and propanoates have ever been reported in this taxon.     

The echo-guided interstitial laser photocoagulation of malignant liver tumors. The authors' personal technic, immediate results and short-term complications in patients with normal and altered liver function

PURPOSE: The literature studies about interstitial laser photocoagulation of liver tumors mainly deal with the treatment of liver metastasis in patients with normal liver function. We report our personal experience with interstitial laser photocoagulation in patients with liver tumors (mostly cirrhotics with hepatocellular carcinoma). Our aim was to evaluate the short term efficacy of percutaneous interstitial laser photocoagulation in inducing focal ablation of liver tumors and the possible complications in patients with normal and impaired liver function. MATERIAL AND METHODS: Sixty-six patients (52-80 years; 42 men), 47 with 51 hepatocellular carcinoma nodules (diameter = 1.6-6.6 cm; mean 3.1 cm) on cirrhosis (18 in Child-Pugh A class, 24 in B e 5 in C class) and 19 patients with single liver metastasis (17 from colon, 2 from lung carcinoma; diameter = 3.9 cm; mean: 4.5 cm) underwent interstitial laser photocoagulation under ultrasound guidance. Depending on tumor size up to four needles were inserted in the tumor and multiple laser illuminations were performed: in nodules < or = 2 cm a single optical fiber and a single needle insertion were used, in nodules > 2 < 3 cm, 2-3 fibers were used with a single laser illumination, in nodules > 3 < 4 cm, 4 fibers were inserted and two laser illuminations were performed in the same session after 1.5 cm withdrawal of all fibers in the tumor, in nodules > 4 cm 2 sessions with 2 laser illuminations per session were performed. Necrosis of the nodules was evaluated with triphasic Helical CT 7 days after treatment. Patients with incomplete necrosis at CT were treated with additional interstitial laser photocoagulation sessions to attain complete necrosis. RESULTS: Fifty-eight patients underwent a single interstitial laser photocoagulation session, 7 patients 2 session and 1 patient 3 sessions. The range of administered energy per patient was 1200-32,000 Joules (mean: 6700 J). CT showed complete necrosis of 47 nodules in 43 patients with hepatocellular carcinoma and in 15/18 patients with metastasis. Three Child C class patients with mild ascites and hyperbilirubinemia before procedure (nodules O: 1.9, 3.5 and 5.8 cm) dropped out of CT follow-up because of severe liver function impairment with increased ascites and hyperbilirubinemia, associated with transient ileum paraliticus in 1 case. One of these patients died two months after treatment. Two patients with metastasis dropped out of treatment because of complications occurred after the interstitial laser photocoagulation session (1 ileum paraliticus, 1 gastric hemorrhage) and another one refused to continue the treatment.     

Yolk sac tumor in a young girl: a case report.

BACKGROUND: Yolk sac tumor is a rare neoplasm characterized by high malignancy given its premature metastasis, that is frequent in adolescence. CASE REPORT: A 21-year-old woman came to our observation for an ovarian cyst (13 cm in diameter). Following salpingo-oophorectomy, it was revealed as a yolk sac tumor by histological diagnosis. The patient exhibited a highly elevated level of alpha1-fetoprotein (AFP) (1156 UI/ml). She is now undergoing chemotherapy treatment. CONCLUSION: This is an interesting case of yolk sac tumor in a young girl, at an age typical for germ cell tumor. AFP represents a valid marker resulting in a useful diagnostic tool.     

Imaging axonal damage in multiple sclerosis by means of MR spectroscopy

Axonal damage in multiple sclerosis has become an important issue. This has been emphasized by recent in vivo proton magnetic resonance (MR) spectroscopy and in vitro pathology studies that have found axonal damage in both lesions and the surrounding normal-appearing white matter. In particular, proton MR spectroscopy, by monitoring levels of N-acetylaspartate (a putative marker of axonal integrity), has been particularly illuminating, as the extent of axonal injury associated with white matter inflammation and demyelination had not been well appreciated from classical pathology studies. Recent MR data demonstrate that cerebral axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of axonal damage and loss in the pathogenesis of the disease should be given due importance, and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards axonal protection.     

环氧合酶2基因多态性作为一种预防心肌梗死和卒中的遗传保护因素

背景：目前认为，心肌梗死（myocardial infarction，MI）和缺血性卒中与金属蛋白酶（metallopmteinases，MMPs）消化基质，导致动脉粥样斑块破裂有关。环氧合酶2（COX-2）和前列腺素E2合成可诱导巨噬细胞MMPs和MMP-9的产生。尽管COX-2的表达由遗传决定，但是COX-2多态性与MI和卒中发病危险的关系仍不清楚。     

Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin.

PURPOSE: We sought to demonstrate that a single systemic administration of L19mTNFalpha (a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and tumor necrosis factor alpha, TNFalpha) in combination with melphalan induced complete and long-lasting tumor eradication in tumor-bearing mice and triggered the generation of a specific T cell-based immune response that protects the animals from a second tumor challenge, as well as from challenges with syngeneic tumor cells of different histologic origin. Experimental Design and RESULTS: Treatment with L19mTNFalpha, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also rejected challenges with syngeneic tumor cells of different histologic origin. In adoptive immunity transfer experiments, the splenocytes from tumor-cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. CONCLUSIONS: The results show that the selective targeting of mTNFalpha to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFalpha to the tumor vasculature.