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Biomedical subjects

S Quaranta

Publications and source records attributed to S Quaranta.

At least 19 recordsLinked to original sources

Pilot study of the efficacy and safety of a modified-release magnesium 250 mg tablet (Sincromag) for the treatment of premenstrual syndrome.

BACKGROUND: Magnesium deficiency has been implicated as a possible contributing factor to some symptoms of premenstrual syndrome (PMS) and several studies have reported a lower intracellular magnesium concentration in women with PMS. Thus, it has been suggested that magnesium supplementation may improve certain symptoms in women with PMS. OBJECTIVE: This open-label study assessed the efficacy and safety of a patented modified-release magnesium 250 mg tablet for improving symptoms in women affected by PMS. METHODS: After a 3-month observational period, women aged 18-45 years with a regular menstrual cycle (from 25-35 days) who were affected by PMS (determined by a score of > or =25 points on a PMS questionnaire) [n = 41] were given the modified-release magnesium tablet over three menstrual cycles, beginning 20 days after the start of their last menstrual period and continuing until the start of their next menstrual period. RESULTS: PMS symptoms improved during magnesium treatment. After 3 months, the mean total PMS score (primary endpoint), as assessed by the investigator using Moos' Modified Menstrual Distress Questionnaire, was significantly lower than before therapy (p < 0.0001). During the same period, the mean PMS scores, as recorded in patients' diaries (secondary efficacy variables), also showed significant improvements (p < 0.0001 for all subscales). The relative decreases in total PMS scores, as assessed by investigator and patient, were 35.1% and 33.5%, respectively. The magnesium tablet was well tolerated, with vertigo the only treatment-related adverse event reported (one patient). CONCLUSIONS: We concluded that modified-release magnesium was effective in reducing premenstrual symptoms in women with PMS in this preliminary study.

Administration, Oral↗

Ethnic differences in the distribution of CYP3A5 gene polymorphisms.

The genetic polymorphism affecting the CYP3A5 enzyme is responsible for interindividual and interethnic variability in the metabolism of CYP3A5 substrates. The full extent of the CYP3A5 genetic polymorphism was analysed in French Caucasian, Gabonese and Tunisian populations using a polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) strategy. In the three populations, eight, 17 and ten single nucleotide polymorphisms (SNPs), respectively, were identified, among which nine correspond to rare new mutations. Also identified were 16 alleles including eight new allelic variants. Significant differences were observed in the distribution of these alleles. Particularly, the frequency of the CYP3A5*3C null allele in French Caucasians (81.3%) and in Tunisians (80.0%) is higher than in the Gabonese population (12.5%) (p < 0.001). Considering the CYP3A5 genotypes of the tested individuals, only 10.4% of French Caucasians and 30.0% of Tunisians were identified as CYP3A5 expressors. In contrast, 90.0% of Gabonese subjects appear to express the CYP3A5 protein.

Alleles↗

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Age Distribution↗

Human proteome enhancement: high-recovery method and improved two-dimensional map of colostral fat globule membrane proteins.

The human milk fat globule membrane protein composition is still largely unknown, although it counts for 2-4% of the total milk protein content and contains several important biologically active components. The aim of this work was to create a two-dimensional electrophoresis (2-DE) map of the human milk fat globule membrane proteins, both integral and membrane-associated, and to identify and characterize as many protein components as possible. A new protocol for the solubilization and extraction of the human milk fat globule membrane proteins with a double extraction procedure is presented, and the results compared with the extraction methods reported in the literature. The proteins were separated, in the first dimension, by isoelectric focusing (IEF) in the pH range 3-10 on strips of 13 cm length and, in the second dimension, by Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on 11.5% T homogeneous gels. A reproducible 2-DE map of integral and membrane-associated proteins was obtained and the first 23 spots, representing the major components, were identified by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometric analysis and/or by amino acid sequencing.

Electrophoresis, Gel, Two-Dimensional↗

Identification of the human beta-casein C-terminal fragments that specifically bind to purified antibodies to bovine beta-lactoglobulin.

The presence of foreign proteins in human milk after the ingestion of bovine dairy products is thought to be one of the possible causes of allergic sensitization in exclusively breast-fed predisposed infants. The immunologic determination of bovine beta-lactoglobulin (LG) concentration in human milk has been reported by several researchers, but the results are conflicting. Moreover, a strong cross-reactivity between antibodies to bovine beta-LG and human milk proteins and peptides was reported, throwing doubt on the reliability of radioimmunoassay and enzyme-linked immunosorbent assay detection and quantification assays for bovine beta-LG in human milk. Thus, the goal of this study was to isolate human milk peptides with a molecular mass >or= 1,000 Da cross-reactive with antibodies to bovine beta-LG in order to identify possible common epitopes between human and bovine milk proteins. The proteins were first isolated by affinity chromatography with purified polyclonal antibodies to bovine beta-LG, followed by gel filtration fast phase liquid chromatography and reverse phase-high performance liquid chromatography purification of the components specifically bound in the affinity separation step. Affinity-bound peptides were identified by determining their amino acid sequence. All the sequenced peptides belonged to the C-terminal part of human beta-casein, which confirms the cross-reactivity of human milk proteins and peptides with antibodies to bovine beta-LG and allows the identification of possible common epitopes between the two proteins. No bovine beta-LG peptides with a molecular mass >or= 1,000 Da were found in our milk samples from healthy mothers on a diet rich in bovine milk and dairy products.

Journal Article↗

Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation.

Primary biliary cirrhosis (PBC) and graft-versus-host disease (GVHD) are thought to have common immunopathologic features and previous studies have reported that 5.2 to 81% of patients with chronic GVHD after allogeneic hematopoietic cell transplant have antimitochondrial antibodies (AMA). We studied a total of 89 patients with chronic GVHD and 60 controls for AMA reactivity by ELISA and immunoblotting using recombinant PDC-E2, BCOADC-E2, and OGDC-E2, immunoblotting of beef heart mitochondrial proteins, and reactivity to nuclei, smooth muscle (ASMA), ribonucleoprotein JO-1, extractable nuclear antigen, nuclear proteins SSA/ SSB, ribonucleic P proteinase III, cardiolipin (ACA), liver kidney microsomal, thyroid microsomal, myeloperoxidase, and the reactivity of rheumatoid factor. A subset of 60 chronic GVHD sera were tested for reactivity to gp210 and LBR. Finally, liver tissue from patients with chronic GVHD and PBC was studied by immunohistochemistry to determine whether there was comparable abnormal apical staining of biliary epithelial cells using PDC-E2-specific monoclonal antibodies. Surprisingly, there were no AMA found in the sera from the 89 patients with chronic GVHD. Review of published data on AMA in GVHD suggests that previous results were primarily false positives. In contrast, sera from the patients with GVHD did have a variety of other autoantibodies and, in particular, 20/89 (22.4%) positive ANA, 23/89 (25.8%) positive ASMA, and 9/89 (10.1%) positive ACA. The other autoantibodies assayed were not statistically different from controls. Finally, abnormal biliary epithelial luminal staining of bile ducts was found, as expected, in liver tissue of patients with PBC but was absent in chronic GVHD.

Adult↗

The tumor necrosis factor-alpha promoter correlates with progression of primary biliary cirrhosis.

BACKGROUND/AIMS: There have been many studies attempting to identify genes that determine susceptibility to primary biliary cirrhosis (PBC), but few studies have attempted to define the genes that modulate the natural history of the disease. There is a biallelic polymorphism, coined TNF1 and TNF2, in the TNFalpha promoter region at -308. We investigated the relative frequency of the TNF1 and TNF2 alleles in patients with PBC, based on the hypothesis that a polymorphism of the TNFalpha promoter region may be associated with the rate of progression and prognosis of PBC. METHODS: Seventy-one Caucasoid patients with PBC and 133 healthy and unrelated Caucasoid individuals were studied. Genomic DNA was extracted from blood, and the mutation at position -308 of the TNFalpha gene analyzed by PCR and NcoI digestion. RESULTS: In 71 patients with PBC, 56/71 (78.9%) patients were TNF1/TNF1 homozygotes, 14/71 (19.7%) were TNF1/TNF2 heterozygotes and 1/71 (1.4%) were TNF2/TNF2 homozygotes. In 133 healthy individuals, 109/133 (80.5%) patients were TNF1/TNF1 homozygotes, 24/133 (18%) were TNF1/TNF2 heterozygotes. No control individuals were TNF2/TNF2 homozygotes. The difference between the two groups was not statistically significant (p = 0.3684). However, in patients with TNF1/TNF1 the Mayo score for disease severity was 4.596+/-0.157 (mean +/- SEM), compared to 5.637+/-0.420 for patients with TNF1/TNF2. This Mayo score was significantly higher in patients with the TNF1/TNF2 genotype than those with TNF1/TNF1 (p = 0.0140), with an odds ratio of 4.9. CONCLUSIONS: Our data demonstrate that the presence of the TNF2 allele may be associated with a higher Mayo score, and thus with patients in a more advanced clinical stage. These data have both theoretical and clinical implications.

Alleles↗

Characterization of antimitochondrial antibodies in health adults.

The detection of antimitochondrial antibodies (AMAs) is an important criterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequenced, and identified as members of the 2-oxo-acid dehydrogenase pathway, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), branched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate dehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagnostic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early disease, we investigated the prevalence of AMA, by enzyme-linked immunosorbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunoblotting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 and BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with histologically proven PBC in most of the sera. However, 1 sera of a 72-year-old female with a normal alkaline phosphatase had an AMA profile identical to typical PBC. After a variable follow-up period (8-14 months), sera from 8 of 9 of these people were re-obtained for AMA and relative epitope mapping. Interestingly, the reactivity had a wider AMA pattern than before.

Adult↗

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study.

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.

Administration, Oral↗

Benign recurrent intrahepatic cholestasis. Some reflections on a case followed for 20 years.

Benign recurrent intrahepatic cholestasis (BRIC) is a form of cholestasis of obscure aetiology characterized by recurrent episodes of jaundice and itching associated with a morphological picture of pure intrahepatic cholestasis. No effective treatment has yet been found among the many that have been proposed and the invariably benign nature of the condition has been questioned. A case of BRIC followed for a period of 20 years is described. This case is of great interest from these two points of view: 1) the histologic and electron microscopic findings 23 and 41 years after the first episode of cholestasis, respectively, failed to reveal evidence of the possible future development of cirrhosis; 2) treatment with ursodeoxycholic acid proved ineffective both therapeutically and in the prevention of episodes of bile stasis: on the contrary, calculosis of the common bile duct appeared after 8 months from the onset of the treatment.

Age Factors↗

[Renal insufficiency due to cholesterol embolism. 4 cases].

Atheroembolic disease is a complication of atheromatous disease and is quite often misunderstood. A precise diagnosis can be made difficult, by the lack of specific tests. The first case, in which we identified this disease, resulted from a bladder biopsy, in the instance of a patient with a suspected carcinoma. The experience, with this initial patient, led us to identification of a further 3 cases, within our previous 2 years case histories. One must consider the possibility of atheroembolic disease during the differential diagnosis of acute renal failure in geriatric patients, given the serious prognosis.

Acute Kidney Injury↗

Immunotactoid glomerulopathy (ITGP): a not fully defined clinicopathologic entity.

Immunotactoid glomerulopathy is characterized by the ultrastructural finding of fibrillary or microtubular deposits in patients without systemic diseases such as SLE, diabetes, paraproteinemias, cryoglobulinemia, or amyloidosis. These deposits correspond in most (but not all) cases to immunoglobulin and complement deposits as shown by immunohistochemical techniques. Different light microscopic patterns (mesangioproliferative, membranous, membranoproliferative, and crescentic) have been reported. Clinical presenting feature is characterized by proteinuria (often of nephrotic range), hematuria, and hypertension in most cases. Chronic renal failure requiring hemodialysis or transplantation is described in more than half the patients. Pathogenesis has not yet been elucidated and only some speculative hypotheses have so far been suggested. At present there is no clear evidence that we are dealing with a new pathologic entity, but larger series must be collected and studied in order to find a correct taxonomic collocation of this glomerulopathy.

Adult↗

Membranous glomerulonephritis (MGN) in transplanted kidneys: morphologic investigation on 256 renal allografts.

Twenty-two cases of membraneous glomerulonephritis (MGN) were identified among 256 bioptically investigated transplanted patients. MGN was defined as de novo in 15 patients and recurrent in three. The type of MGN could not be ascertained with certainty in the other four. Several morphologic features unusual for the idiopathic form of MGN were found. Most cases disclosed focal segmental distribution of subepithelial deposits and showed the contemporaneous presence of different stages of the disease according to Ehrenreich and Churg classification. In addition mild-to-moderate mesangial cell proliferation was found in about one third of de novo MGN biopsies. Endocapillary hypercellularity was observed in 14 specimens and held to be due to an excess of mononuclear blood cells, related to a concomitant episode of rejection. Chronic transplant glomerulopathy was found in 47% of patients with de novo MGN and in 66% of those with recurrent MGN, being more frequently observed in specimens with diffuse distribution of deposits. Repeated biopsies showed progression of the stage and extension of deposits to a large number of capillary loops in four out of six patients. De novo MGN was documented 1 to 54 mo (mean value 20.2 mo) after transplantation, and the recurrence was observed after 12, 15, and 42 mo. All but two patients (who were anuric) complained of proteinuria, which was in the nephrotic range in 12. Apart from the significantly higher frequency in de novo MGN patients of DR4 antigen, whose significance must in any case be re-evaluated in a larger series, none of the factors so far suggested to be linked to the onset of de novo MGN has found further support in our study. On the contrary, relevance in favoring the appearance and the evolution of MGN has to be attributed to transplant glomerulopathy, which, moreover, seems to be more important than MGN itself in causing the unfavorable outcome of the graft.

Adult↗

Intertubular capillary changes in kidney allografts: a morphologic investigation on 61 renal specimens.

A total of 61 kidney allograft specimens (51 biopsies and 10 nephrectomies) from 44 patients were investigated. Transplant glomerulopathy (TGP) was found in 38 specimens. Electron microscopy disclosed peculiar intertubular capillary changes (ITCC) in 47 specimens (all those showing TGP and nine without TGP). They were characterized by splitting and multilayering of the basement membranes. TGP and ITCC were graded and found mild (in 23 and 22 specimens), moderate (in 11 and 16 specimens), and severe (in four and nine specimens). Both worsened with time lapse from transplantation. When both were compared in single specimens, their grading was similar or, with a few exceptions, more severe for ITCC. TGP and ITCC were more frequent in biopsies with morphologic evidence of rejection and less frequent in patients treated with Cyclosporine A. Repeated biopsies and nephrectomies were studied in 10 patients and a somewhat more precocious appearance of ITCC than of TGP was found. Earlier and more severe ITCC were found in two patients who had had two transplants as compared to those with one. Morphologic similarities between TGP and ITCC suggest a common pathogenetic mechanism related to endothelial damage. The association to the histological evidence of rejection as well as the apparently protective activity of Cyclosporine A could support the involvement of an immune-mediated mechanism in agreement with what is reported in literature. The constant association of ITCC and TGP and its possible more precocious appearance enforce the diagnostic value of the former, which allows to infer the presence or the subsequent development of TGP even in biopsies where glomeruli are lacking.

Adult↗

[Epidemiologic and diagnostic observations on hemorrhage of the upper gastroenteric tract].

Acute upper gastrointestinal (GI) bleeding causes, according to the authors' experience, 1.65% of all annual hospitalizations. Mortality rate among high risk patients is about 20% and cirrhotic patients have a particularly poor outcome (70% of deaths caused by gastrointestinal hemorrhage). Endoscopy has been performed in 329 cases to identify the active site of bleeding (7.22% of 4791 "EGDS" performed from 1984 to 1988). In this retrospective study gastric and duodenal peptic diseases, have been observed more frequently than esophageal varices ruptures (11.8%) and in 25% of patients Gl bleeding was associated with the use of potentially dangerous drugs (NSAID and/or Steroids). A prompt endoscopy is fundamental to recognize the etiology and for a better management of the patient; unfortunately, even if improvements have been obtained in the diagnosis and therapy, the mortality caused by gastrointestinal hemorrhage is not significantly reduced.

Acute Disease↗