Search PubMed⌕ Search

Biomedical subjects

C Gennari

Publications and source records attributed to C Gennari.

At least 73 records · Page 4Linked to original sources

Most Helicobacter pylori-infected patients have specific antibodies, and some also have H. pylori antigens and genomic material in bile: is it a risk factor for gallstone formation?

Bile may contain a 130-kDa protein endowed with aminopeptidase activity and the ability to promote cholesterol crystallisation. As >90% of H. pylori strains have a similar peptidase activity, and half the isolates express a 110- to 140-kDa antigen, the CagA protein, we investigated a possible association between H. pylori infection and gallstones, and the presence in bile samples of factors related to H. pylori that could increase cholesterol crystallization. The prevalence of H. pylori infection was 82.1% in 112 patients with gallstones and 80.3% in 112 controls (NS). Fifteen bile samples out of 23 specimens from infected patients (65.2%) contained anti-CagA antibodies. A approximately 60-kDa antigen only reacting with an anti-CagA antibody was found in five bile samples (21.7%) from 23 infected patients. One bile sample (4.1%) contained ureA and cagA genes of H. pylori. The homology of CagA with the N-terminal sequence of aminopeptidase N was very low. We concluded that the presence of specific antibody to H. pylori in most bile samples tested and of an H. pylori putative antigen in a discrete number of cases may represent factors that increase the risk of gallstone formation.

Antibodies, Bacterial↗

cagA positive and negative Helicobacter pylori strains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage.

BACKGROUND/AIMS: Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with different cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation. METHODS: Well separated H pylori colonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined for cagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients' sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically. RESULTS: Of the 747 colonies examined, 45.3% were cagA+. All colonies from four patients were cagA+, and all colonies from two patients were cagA-. In 13 patients (68%) both cagA+ and cagA- colonies were found. CagA expression of isolates corresponded to their cagA status. H pylori strains with different CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p < 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites. CONCLUSIONS: Most patients with nonulcer dyspepsia are infected by both cagA+ and cagA- H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia.

Adult↗

Effect of ipriflavone--a synthetic derivative of natural isoflavones--on bone mass loss in the early years after menopause.

OBJECTIVE: We studied whether oral administration of ipriflavone, a synthetic derivative of naturally occurring isoflavones, could prevent bone loss occurring shortly after menopause. DESIGN: Fifty-six women with low vertebral bone density and with postmenopausal age less than five years were randomly allocated to receive either ipriflavone, 200 mg three times daily, or placebo. All subjects also received 1,000 mg elemental calcium daily. RESULTS: Vertebral bone density declined after two years in women taking only calcium (4.9 +/- 1.1%, SEM, p = 0.001), but it did not change in those receiving ipriflavone (-0.4 +/- 1.1%, n.s.). A significant (p = 0.010) between-treatment difference was evidenced at both year 1 and year 2. At the end of the study, urine hydroxyproline/creatinine excretion was higher in the control group than in the ipriflavone group, as compared to no difference at baseline. Five patients taking ipriflavone and five taking placebo experienced gastrointestinal discomfort or other adverse reactions, but only one and four subjects, respectively, had to discontinue the study. CONCLUSIONS: Ipriflavone prevents the rapid bone loss following early menopause. This effect is associated with a reduction of bone turnover rate.

Administration, Oral↗

Weill-Marchesani syndrome: report of an unusual case.

We report a single case of Weill-Marchesani syndrome, typically characterized by progressive joint stiffness, brachiymorphy, brachydactyly, and ectopia lentis. The clinical case appears particularly interesting as the patient also had primary osteoporosis, which until now has not been considered as a possible manifestation of Weill-Marchesani syndrome.

Adult↗

A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss.

One hundred ninety-eight postmenopausal women (aged 50-65 years) with vertebral bone density (VBD) 1 SD below the mean value for normal, age-matched, postmenopausal subjects were enrolled in six Italian centers and 134 completed 2 years of treatment. All subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d.) or a matching placebo, according to a double-blind, parallel group design. All patients also received an oral daily calcium supplement of 1 g as calcium carbonate. VBD and markers of bone turnover were measured at baseline, and every 6 months. A complete routine analysis of liver and kidney functions along with hematological parameters were measured before and at the end of treatment period. The valid completers analysis showed a significant increase of VBD in ipriflavone-treated women with average percent changes of +1.4 after 1 year, and +1% at the end of treatment period (P < 0.05). The placebo group presented a significant decrease of VBD after 2 years of treatment (P < 0.05). The difference between treatments was significant (P < 0.01). The intention to treat analysis confirmed the significant decrease of VBD in the placebo group, with no changes in ipriflavone-treated women. Skeletal ALP significantly decreased in ipriflavone-treated women (P < 0.05). Serum BGP and urine HOP/Cr showed a significant decrease only in ipriflavone-treated women, suggesting an inhibitory effect on bone turnover rate. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups. The evaluation of patients' compliance, assessed by residual tablets count, revealed a drug intake of more than 80% after 2 years in 92.5% and 92.8% of patients treated with ipriflavone or placebo, respectively. This study demonstrates that ipriflavone can prevent bone loss in postmenopausal women with low bone mass.

Aged↗

Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients.

Prolonged corticosteroid administration, as often required in the treatment of sarcoidosis, increases the risk of osteoporosis and fracture. The aim of the present study was to evaluate the usefulness of alendronate, a third generation bisphosphonate, in preventing corticosteroid-induced osteoporosis. Forty-three consecutive, previously untreated, sarcoid patients (17 men and 26 premenopausal women) were included in the study: 13 needed no treatment and served as controls (Group 1) and 30 needed glucocorticoids (prednisone) and were randomly selected to also receive either placebo (n = 15, Group 2) or alendronate 5 mg/day (n = 15, Group 3). Bone mineral density (BMD) at the ultradistal radius by dual photon absorptiometry (Osteograph 1000, NIM, Verona, Italy) and biochemical markers of bone turnover were measured at baseline and after 6 and 12 months of glucocorticoid therapy. No significant difference was found between Groups 2 and 3 in the mean cumulative dose of prednisone (4945 +/- 1956 mg and 5110 +/- 2013 mg, respectively). At the end of the study period, BMD increased by 0.8% in the alendronate-treated group; in the placebo-treated group, BMD decreased by 4.5%. The difference between groups was significant (P < 0.01, ANOVA). A significant decrease in markers of bone formation was found in all patients treated with prednisone (Groups 2 and 3), independently of alendronate. Alendronate, however, counteracted the increase in markers of bone resorption induced by glucocorticoid therapy. Our data suggest that alendronate is effective in preventing glucocorticoid-induced bone loss in sarcoid patients. Further studies on alendronate use in steroid-induced osteoporosis are needed.

Absorptiometry, Photon↗

Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass.

We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.

Absorptiometry, Photon↗

Design for an ipriflavone multicenter European fracture study.

In order to investigate the efficacy of ipriflavone (i.p.) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large multicentric European study was designed and is presently ongoing. Included in the study were 460 Caucasian, nonobese postmenopausal women aged > 45 and < 75 years, menopaused for at least 12 months. Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD compared with healthy women aged 50 years, corresponding to values below 0.860 g/cm2 (antero-posterior measurement) by Hologic QDR 1000. Women with prevalent vertebral fractures were excluded as well as those presenting secondary osteoporosis or having been treated with medications that could affect bone metabolism. This study was designed as a 3-year, double-blind, placebo-controlled, parallel group study that randomized the women to the oral administration of either 3 x 200 mg/day of i.p. or placebo. All patients received a daily supplement of 500 mg calcium. The primary purpose of the study was to evaluate the efficacy of i.p. in preventing vertebral nontraumatic fractures. Fracture is defined here as a > or = 20% decrease in any anterior, central, or posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral morphometry have been centralized in an independent Center, with standardized evaluation of two experts. Power calculations have been based on the hypothesis that 21% of placebo-treated patients would fracture within 3 years and that treatment with i.p. would lead to a 50% reduction in the incidence of fracture. Statistical tests have been designed to have a power of 80%, with a type I error equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD readings. This study should verify the hypothesis that i.p. significantly decreases the risk of vertebral fracture in postmenopausal, osteoporotic women.

Absorptiometry, Photon↗

Paget's disease.

Explore the source record for details and available documents.

Alleles↗

Treatment of post-menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: a placebo controlled study.

OBJECTIVE: The usefulness of GH in the treatment of post-menopausal osteoporosis (PMO) is still debated. We have studied the effects of recombinant human GH (rhGH) given alone or in combination with salmon calcitonin (sCT) in the treatment of PMO. PATIENTS: Thirty women with established PMO (aged 61.1 +/- 4.4 years) were divided into 3 groups of 10 and randomly assigned to 3 treatment sequences: rhGH (12IU/day) s.c. for 7 days, followed by sCT (50 IU/day) s.c. for 21 days and by 61 days without treatment (group 1); placebo for 7 days, followed by sCT for 21 days and by 61 days without treatment (group 2); rhGH for 7 days, followed by placebo for 21 days, and by 61 days without treatment (group 3). Each cycle was repeated 8 times (24 months). MEASUREMENTS: At days 0, 8, 29 and 90 of each cycle, serum IGF-I, calcium, phosphate, osteocalcin, alkaline phosphatase and urinary excretion of calcium, hydroxyproline and pyridinoline cross-links (Pyr) were measured. At months 0, 6, 12, 18 and 24, bone mineral density (BMD) was measured by dualphoton absorptiometry (DPA), at lumbar spine (LS), femoral shaft (F) and distal radius (DR). RESULTS: A significant increase in serum osteocalcin and urinary calcium, hydroxyproline and Pyr was detected after each rhGH period. In group 1, BMD at lumbar spine increased by 2.5% at year 2; in contrast, significant (P < 0.05) decreases in BMD-LS values were found in patients treated with CT and placebo (group 2) and with GH and placebo (group 3). BMD-F did not show any significant change in patients of group 2, but a significant (P < 0.05) decrease was found in groups 1 and 3. BMD-DR did not show any significant change with respect to baseline in any of the three groups. No significant difference between the three groups was found in bone mass at the three different regions. CONCLUSIONS: Our study demonstrates that treatment with rhGH increases bone turnover in postmenopausal osteoporotic women. Combined treatment with rhGH and CT over a period of 24 months is able to maintain bone mass at lumbar spine and distal radius, but induces a decline at femoral shaft; therefore, it does not seem particularly useful in the therapy of post-menopausal osteoporosis.

Amino Acids↗

The combined use of ultrasound and densitometry in the prediction of vertebral fracture.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density for evaluating the probability of vertebral fracture. 397 postmenopausal women (59.1 +/- 6.0 years) with (n = 178) or without (n = 219) atraumatic vertebral fractures were studied. In all women, bone mineral density (BMD) of the lumbar spine was evaluated by dual X-ray absorptiometry (DXA) and speed of sound (SOS); broadband ultrasound attenuation (BUA) and Stiffness in the calcaneus were evaluated by an Achilles unit (Lunar Corporation). Ultrasonographic parameters and BMD were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals (CI) to show which estimate of odd ratio is the most precise. The relative risk of vertebral fracture, after adjusting for potential confounders, was 3.5 (CI 2.6-4.8) for BUA; 4.5 (CI 3.2-6.2) for SOS; 5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound (US) parameters were still significant independent predictors of vertebral fracture, even after adjusting for BMD. The relative risk of fracture for a simultaneous decrease by 1 SD of BMD and by 1 SD of each ultrasound parameter was 17.3 (CI 9.4-39.6) for BMD and SOS; 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7) for BMD and Stiffness. Our data suggest that US and BMD provide complementary information which can be combined to improve estimates of vertebral fracture risk.

Age Factors↗

The usefulness of bone turnover in predicting the response to transdermal estrogen therapy in postmenopausal osteoporosis.

Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17 beta-estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual-energy X-ray absorptiometry [DXA]) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross-links) were assessed at baseline and after 1 and 2 years. In the estrogen-treated group, BMD showed a significant increase (p < 0.001) both after 1 and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2-year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.

Administration, Cutaneous↗