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Biomedical subjects

E Grossi

Publications and source records attributed to E Grossi.

At least 37 records · Page 2Linked to original sources

Familial clustering of Helicobacter pylori infection: population based study.

OBJECTIVES: To assess the rate of intrafamilial transmission of Helicobacter pylori infection in the general population and the role of a family's social background. DESIGN: Population survey. SETTING: Campogalliano, a town in northern Italy with about 5000 residents. PARTICIPANTS: 3289 residents, accounting for 416 families. MAIN OUTCOME MEASURES: Prevalence of H pylori infection assessed by presence of IgG antibodies to H pylori. RESULTS: The overall prevalence of H pylori infection was 58%. Children belonging to families with both parents infected had a significantly higher prevalence of H pylori infection (44%) than children from families with only one (30%) or no parents (21%) infected (P<0.001). Multivariate analyses confirmed that children with both parents positive had double the risk of being infected by H pylori than those from families in which both parents were negative. Family social status was independently related to infection in children, with those from blue collar or farming families showing an increased risk of infection compared with children of white collars workers (odds ratio 2.02, 95% confidence interval 1.16 to 3.49). CONCLUSIONS: H pylori infection clusters within families belonging to the same population. Social status may also be a risk factor. This suggests either a person to person transmission or a common source of exposure for H pylori infection.

Adolescent↗

Inhibition of endothelial cell migration by gene transfer of tissue inhibitor of metalloproteinases-1.

BACKGROUND: Angiogenesis requires degradation of the vessel's basal lamina and endothelial cell migration into the tissue stroma. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play important roles in this process. MMP activity is tightly regulated during vessel growth. This work was designed to characterize the effect of TIMP-1 upregulation on endothelial cell invasion of the extracellular matrix. METHODS: We constructed replication-deficient recombinant adenoviruses that encode either TIMP-1 (Ad.TIMP-1) or Escherichia coli lac Z (Ad.beta gal) cDNA. Bovine aortic endothelial (BAE) cells were infected with 100 infectious particles/cell. Gene expression was assessed by Northern and Western blotting. TIMP-1 activity in cell-conditioned media was measured by a resorufin-labeled casein protease assay. BAE cell migration was measured by Boyden chamber assays with 0.2% gelatin-coated, 8. 0-mcm polycarbonate membranes. RESULTS: TIMP-1 was overexpressed by Ad.TIMP-1-infected BAE cells relative to control, Ad. beta gal-infected or uninfected cells. TIMP-1 activity in Ad.TIMP-1 cell-conditioned medium was 2.8-fold higher than in control cells. By Boyden chamber assays with gelatin-coated membranes, Ad. TIMP-1-infected BAE cells showed 89.97 +/-1.64% (mean +/- SEM) reduction in migration relative to Ad.beta gal-infected cells (P < 0. 02) and 90.53 +/- 1.12% relative to uninfected cells (P < 0.02). Without gelatin coating, migration was equivalent in all groups. CONCLUSION: The replication-deficient recombinant adenovirus we constructed affords rapid and efficient upregulation of functional TIMP-1 in endothelial cells. Infection results in a dramatic decrease in cell migration and invasion of extracellular matrix. Thus, such a recombinant vector may provide a useful tool for the gene therapy of vascular remodeling and inhibition of angiogenesis.

Animals↗

Bioequivalence of levothyroxine tablets administered to a target population in steady state.

Two parallel trials were carried out with levothyroxine sodium salt in 50 and 100 microg strengths, respectively, giving 100 microg day-1(50x2 microg day-1 or 100x1 microg day-1) in both trials in a repeated dose regimen. Twenty patients suffering from primary hypothyroidism under treatment with 100 microg day-1 of thyroxine sodium salt were enrolled in each trial. They were clinically and chemically euthyroid. Each trial lasted 114 days, with 57 days being devoted to the first treatment (test or reference) and 57 days to the other (reference or test), according to a two-period, two-sequence, two-formulation design in a steady state without wash-out. The test formulation was prepared with a technological improvement and is being produced to replace that at present on the market. Serum concentrations of free and total levothyroxine, and free and total levotriiodothyronine were assayed repeatedly during the treatment and in timed samples after the last dose of each formulation, using radioimmunoassays. Cmax and AUCss,tau were considered to be target parameters for bioequivalence which was assessed through 90% confidence intervals in the 0.80-1.25 range, as required by EU and US FDA operating guidelines. The results have shown that of these hormones, the free and total parent compound thyroxine is that which most clearly showed a peak after dosing, whereas its metabolite, free and total triiodothyronine, fluctuated around pre-dose concentrations. Bioequivalence was fully assessed with Cmax and AUCss,tau, with all four hormones tested and at both strengths administered. The two test formulations in 50 and 100 microg are thus bioequivalent with the two reference preparations. Tolerability was very good in all cases.

Adult↗

Prevalence of subclinical hypothyroidism in a population living in the Milan metropolitan area.

Subclinical hypothyroidism is a condition characterized by increased levels of thyroid-stimulating hormone (TSH) associated with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). The exact prevalence of this condition in Italy is not known. The aim of this study was to assess the presence of subclinical hypothyroidism in 1001 subjects living in the Milan area (age 17-89) and apparently free from thyroid pathology. This sample which had applied to a large laboratory centre (Centro Diagnostico Italiano, Milano) for a routine check-up was seen from April to July 1996. A serum TSH assay was performed using a highly sensitive immunoenzymatic method, while an FT3 and FT4 assay was performed by means of a radioimmunologic method using commercial kits. The prevalence of subclinical hypothyroidism in the total population proved to be 4.7% (95% CI-Confidence Interval: 3.4-6.0). Sex stratification showed a prevalence of 6.1% in females and 3.4% in males. Prevalence in patients up to 65 was 4.2%. This value increased up to 8.0% in subjects over 65. By combining these variables, in females >65 prevalence increased to 11.3%. Overall, symptoms typical of overt hypothyroidism were found in 58.3% of patients suffering from subclinical hypothyroidism and in 39.9% of healthy subjects (p<0.02). The results of this study show that there is a significant presence (about 5%) of subclinical hypothyroidism in this population and that its frequency is more than doubled in women over 65. Early treatment might reduce the progression to overt hypothyroidism. The benefits of such a procedure were recently suggested by a decision making modelling approach applied to the Italian environment.

Adolescent↗

Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy.

BACKGROUND: Stroke occurs in 1% to 7% of heart surgery. Aortic arch atherosclerosis is a risk factor for intraoperative stroke, and endarterectomy has been proposed to prevent stroke during heart surgery in patients with arch atheromas. METHODS AND RESULTS: Intraoperative transesophageal echocardiography was performed in 3404 patients undergoing heart surgery between 1990 and 1996. Use of transesophageal echocardiography was unselected and based on equipment availability. Aortic arch atheromas (>/=5 mm, or mobile) were seen in 268 (8%) patients. They were evaluated for intraoperative stroke (confirmed by a neurologist and cerebral infarction on computed tomography or magnetic resonance imaging). Arch endarterectomy was performed in 43 patients as an adjunct to their cardiac procedure in an attempt to prevent intraoperative stroke. The intraoperative stroke rate in all 268 patients with atheromas was high (15.3%). On univariate analysis, age, previous stroke, and arch endarterectomy were significantly associated with intraoperative stroke. On multivariate analysis, age (odds ratio 3.9, P =.01) and arch endarterectomy (odds ratio 3.6, P =.001) were independently predictive of intraoperative stroke. Mortality rate in all 268 patients was high (14.9%). These patients with atheromas also had a long recovery room, intensive care unit, and total hospital length of stay (48 days). CONCLUSIONS: Patients with protruding aortic arch atheromas are at high risk for intraoperative stroke, significant and multiple morbidity, prolonged hospital stay, and death resulting from heart surgery. Aortic arch endarterectomy is strongly associated with intraoperative stroke; its use should be carefully considered in light of these results.

Aged↗

Serum tumour necrosis factor-alpha is increased in patients with Helicobacter pylori infection and CagA antibodies.

BACKGROUND: Helicobacter pylori causes gastric inflammation secondary to the mucosal release of cytokines and tumour necrosis factor-alpha. AIMS: To investigate whether serum levels of tumor necrosis factor-alpha correlate with Helicobacter pylori infection, CagA antibodies, 13C-urea breath test results, endoscopic, and histological findings. METHODS: Endoscopy (with gastric biopsies), 13C-urea breath test, and serological assay of CagA antibodies and tumour necrosis factor-alpha were performed in 172 dyspeptic patients. RESULTS: A total of 126 patients (73.2%) were infected; of the 126 patients, 84 with CagA antibodies (66.7%) showed a higher prevalence rate of duodenal ulcer (p = 0.03), more severe neutrophil infiltration (p = 0.03) and higher bacterial colonization (p = 0.03) than those without antibodies. CagA+ and CagA- groups differed also in 13C-urea breath test results (p = 0.03). A significant difference in serum tumour necrosis factor-alpha levels was observed between infected and uninfected individuals (p = 0.03) as well as between CagA+ and CagA- patients (p = 0.002). CONCLUSIONS: Helicobacter pylori infection is associated with increased serum levels of tumour necrosis factor-alpha. Subjects who harbour CagA positive strains have more severe mucosal damage, higher bacterial colonization, higher probability of developing duodenal ulcer and higher serum levels of tumour necrosis factor-alpha than those infected with CagA- strains.

Adult↗

Immunostimulating effect of oral glutamine.

Glutamine represents the principal metabolic substrate for all rapidly proliferating cells. Since part of the glutamine efficacy could be related to immunoregulating properties, we assessed the effects of orally administered glutamine on serum interleukin-2 (IL-2) levels and intestinal T-cell populations in 48 athymic (nude) mice. Twenty-four mice received a standard diet enriched by glutamine (added to drinking water at a 4% concentration), while the other 24 served as the control group and received the same diet without glutamine. In glutamine-fed animals, we observed a marked increase in IL-2 concentrations after 10 days of treatment in comparison with control group and a modest but significant increase in intestinal T-cell counts. These results suggest that oral glutamine is able to exert local and systemic immunostimulating activity that could be of relevance in the prevention of gut integrity and immune defense loss associated, for example, with trauma, surgery, and starvation.

Adjuvants, Immunologic↗

Improvement of Pap smear sensitivity using a visual adjunctive procedure: a co-operative Italian study on speculoscopy (GISPE).

The present study evaluates whether speculoscopy, a magnified chemiluminescence examination, combined with Pap smear can improve the detection of cervical lesions, as compared with Pap smear alone. The investigation was a prospective practice-based research carried out as a multicentre cohort study throughout the Italian territory. The participants were 3,300 asymptomatic women age > or = 18 years undergoing routine pelvic and cytological screening. All participants were subjected to Pap smear, speculoscopy and colposcopy investigations in succession. The 646 women with positive colposcopy underwent biopsy. Of the 267 women with positive histology 25 were high-grade intraephitelial lesions (HGSIL) and 242 were low-grade intraephitelial lesions (LGSIL). The histological findings were correlated with the results of Pap smear and speculoscopy alone and combined (PPS). Pap smear alone detected 76% of HGSIL, speculoscopy alone identified 84% of HGSIL, and PPS indicated 100% HGSIL. Of the 242 women with LGSIL, Pap smear alone detected 37% of the cases, speculoscopy alone detected 54% of the cases, and PPS identified 91% of the cases. Together, the two tests missed 9% of the LGSIL. The combination PPS was found to increase sensitivity from 40% to 92%, but to lower specificity from 94% to 23%. Speculoscopy combined with Pap smear can yield a higher percentage of women with biopsy-confirmed cervical pathology than the use of Pap smear as a sole screening test. This is particularly true of patients with LGSIL. The mechanisms of pathological detection and the use of speculoscopy should be investigated further.

Adolescent↗

Cost effectiveness of screening for subclinical hypothyroidism in the elderly. A decision-analytical model.

OBJECTIVE: The value of early detection of subclinical hypothyroidism is the object of a long lasting debate. In this study, we assessed the cost effectiveness of a policy based upon screening for this condition through thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) serum level measurements in the elderly. DESIGN: A Markov model was developed where hypothetical elderly patients (i.e. > or = 60 years of age), who attend general practitioner (GP) clinics for periodic health examinations in a primary-care setting in Italy, made transitions between health states at annual interval for 15 years, thus allowing an estimation of the average cost and of the expected average number of quality-adjusted life-years (QALY). In this model, patients were assumed to be seen at annual intervals by GPs for clinical examination and serum cholesterol level measurement, to which a TSH, T3 and T4 serum measurement was added. In the base-case analysis, TSH was measured every 5 years and, if abnormal, T3 and T4 serum levels were also determined. Costs were analysed from the perspective of the Italian National Health Service (NHS) and reflected 1996 values. MAIN OUTCOME MEASURES AND RESULTS: In the base-case analysis, the additional benefit estimated from testing a female population for subclinical hypothyroidism every 5 years was 0.36 QALY, with a cost per QALY gained of 668,298 lire (L). The expected gain in QALY for men was 0.20 and the cost per QALY gained was L270,322. In general, the best cost-effectiveness profile was seen with testing every 3 years. Results were sensitive to variations in the prevalence of disease among the target population, both in men and women. CONCLUSIONS: Our study indicates that a screening policy for subclinical hypothyroidism in the elderly population could be worthwhile. However, as the costs could be significant when applied at the population level, this policy deserves further assessment through well-designed primary research.

Aged↗

Pregnancy outcome among HIV positive and negative intravenous drug users.

OBJECTIVE: To analyze determinants of pregnancy outcome, among HIV infected and uninfected intravenous drug users. STUDY DESIGN: A total of 315 pregnant current intravenous drug users, IVDU (151 HIV infected and 164 HIV uninfected subjects) were referred to the Center for Pregnant Drug Addicts of the Mangiagalli Clinic, Milan, Italy, for internatal care and delivery between 1985 and 1993. RESULTS: HIV uninfected and infected mothers did not differ significantly according to type of pregnancy, gestational age at childbirth, mode of delivery, pregnancy outcome and newborn weight, height, head circumference, sex and Apgar at 1 and 5 min. Out of 133 children (born to HIV infected mothers) for whom HIV status was available, 20 (15%) were HIV infected or developed AIDS-related signs and symptoms during a 24 months follow-up. The distribution of HIV infected and non infected infants was not significantly different as regards maternal CD4 lymphocyte count, week of gestation at birth, mode of delivery, infant weight, height, head circumference and Apgar at 1 and 5 min. CONCLUSION: Our data show that HIV infected women in the early stages of HIV infection are not at a higher risk of adverse course of pregnancy than HIV uninfected women. Vertical transmission rates were not associated to newborn characteristics.

Adult↗

Perioperative morbidity and mortality in combined vs. staged approaches to carotid and coronary revascularization.

Between 1986 and 1994 we identified 57 patients who underwent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) during the same hospitalization. Simultaneous CABG and CEA was performed in 28 patients (mean age 70.5 years, 58% male). Indications for CABG in these patients were myocardial infarction in two crescendo angina in 19, congestive heart failure in two and left main or triple-vessel coronary artery disease noted during carotid preoperative evaluation in five. Indications for CEA were transient ischemic attack (TIA) in 12, crescendo TIA in six, cerebrovascular accident (CVA) in five, and asymptomatic stenosis in five. There were no postoperative myocardial infarctions or perioperative deaths. Two patients developed atrial fibrillation, and four patients had CVAs (two were ipsilateral to the side of CEA). Twenty-nine patients underwent staged procedures (i.e., not performed concomitantly but during the same hospitalization). Indications for CABG and CEA were comparable to those in the group undergoing simultaneous procedures. In 17 patients CEA was performed before CABG. There was a single CVA, the result of an intracerebral hemorrhage. Five of the 17 patients had a myocardial infarction and two died; one patient had first-degree heart block requiring a pacemaker. Four additional patients developed atrial fibrillation, one of whom required cardioversion. The remaining 12 patients had CABG followed by CEA. There were no CVAs, myocardial infarctions, arrhythmias, or deaths in this subgroup. These data demonstrate that the performance of simultaneous CABG and CEA procedures is associated with increased neurologic morbidity (14.3%), both ipsilateral and contralateral to the side of carotid surgery in contrast to staged CABG and CEA (3.4%). In addition, when staged carotid surgery preceded coronary revascularization in those with severe coronary artery disease, the combined cardiac complication and mortality rate was significantly higher than when coronary revascularization preceded CEA. This evidence suggests that when CABG and CEA must be performed during the same hospitalization, the procedures should be staged with CABG preceding CEA.

Aged↗

The incidence of complications after caesarean section in 156 HIV-positive women.

OBJECTIVE: To investigate the risks of post-operative complications in HIV-positive mothers who undergo a caesarean section (CS) because the delivery cannot be safely accomplished by the vaginal route or to protect the infant from viral infection. DESIGN: In a multicentre study, we reviewed the incidence and type of post-operative complications in 156 HIV-positive women who underwent a CS. These results were compared with those observed in an equal number of HIV-uninfected women who matched for the indication requiring a caesarean delivery, the stage of labour, the integrity or rupture of membranes, and the use of antibiotic prophylaxis. SETTING: Seven teaching hospitals providing obstetrical care for mothers infected with HIV. RESULTS: We found that six HIV-infected mothers suffered a major complication (two cases of pneumonia, one pleural effusion, two severe anaemia and one sepsis) compared with only one HIV-negative woman who required blood transfusion after surgery. Minor complications like post-operative fever, endometritis, wound and urinary tract infections were significantly more frequent in HIV-positive women than controls. Multivariate analysis revealed that in HIV-infected women the only factor associated with a significant increase in the rate of complications was a CD4 lymphocyte count < 200 x 10(6)/l. CONCLUSIONS: The results of our study indicate that HIV-positive mothers are at an increased risk of post-operative complications when delivered by CS. The risk of post-operative complications is higher in HIV-infected women who are severely immunodepressed.

CD4 Lymphocyte Count↗

The effects of doxofylline versus theophylline on sleep architecture in COPD patients.

Theophylline is known to alter sleep architecture because of its affinity to adenosine receptors. One of the consequences of disrupted sleep is impaired cognitive performance. A single-blind, randomized cross-over study of eight male chronic obstructive pulmonary disease (COPD) patients was undertaken to evaluate the effects of theophylline versus doxofylline on sleep architecture. The patients, who were all ex-smokers, had been treated with theophylline. Mean age was 53 +/- 12 yrs, forced expiratory volume in one second (FEV1) 50 +/- 22% predicted and forced vital capacity (FVC) 70 +/- 18% predicted. Following a wash-out period, four patients were given oral slow-release theophylline (T) (300 mg b.i.d.) for one week, followed by a cross-over to doxofylline (D) (400 mg t.i.d.) for a second week. The other four patients were given the drugs in the reverse order. All patients underwent polysomnography at baseline and at the end of each week of treatment. The number of arousals per hour was 5.5 +/- 2.9 at baseline, 9.4 +/- 5.2 during T treatment and 5.4 +/- 4.4 during D treatment. During T treatment, sleep efficiency was 60 +/- 19% vs 75 +/- 13% recorded at baseline trial and 68 +/- 25 recorded during D treatment. Sleep quality, during T treatment, was poorer than at baseline, with a greater increase in the percentage of wakefulness and more stage 2 sleep than at baseline. Slow wave sleep was reduced with both treatments, particularly D. Neither drug affected the arterial oxygen saturation (Sao2) or respiratory rate during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Superiority of transesophageal echocardiography in detecting aortic arch atheromatous disease: identification of patients at increased risk of stroke during cardiac surgery.

It has been shown that transesophageal echocardiography (TEE) is useful in evaluating atheromatous disease of the aortic arch and that such disease is a risk factor for stroke in medical patients. Data obtained by traditional methods of evaluating the aortic arch prior to cardiac surgery, namely, chest x-ray (CXR) and cardiac catheterization (CATH), were compared with that detected by TEE. Images of the descending thoracic aorta and aortic arch seen on intraoperative TEE in 258 cardiac surgical patients were graded as I = normal, II = intimal thickening or plaques < 5 mm thick or with a mobile component (severe disease). The aortic knob seen on CXR in 209 of these patients was graded as normal, < 1/2 or > or = > 1/2 ring of calcification. Calcification in the aortic root (graded as 0, 1+, 2+) and irregularities in the aortic lumen seen at CATH in 33 patients were also examined. Data were analyzed with respect to age, gender, type of surgery, and stroke. Increasing age correlated strongly with increasing severity of aortic arch and descending thoracic aortic disease seen by TEE. Severe disease was not present in patients under age 50 but was present in about 20% of those over age 70. Atheromatous disease was found by TEE in 55% of patients with a normal CXR and 91% of those with heavily calcified aortic knobs. Ischemic strokes occurred in seven patients. Severe arch disease correlated significantly with stroke (P < .01). Other variables did not correlate with stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

The effect of intravenous doxofylline or aminophylline on gastric secretion in duodenal ulcer patients.

The aim of this study was to compare the effects upon gastric secretion of therapeutic doses of aminophylline, with doxofylline, a new xanthine derivative proposed for the treatment of chronic asthma. Twelve patients with endoscopically-proven healed duodenal ulcer were studied twice under double-blind conditions in cross-over experiments. In a 1-hour infusion, six patients received either 240 mg aminophylline i.v. or 200 mg doxofylline i.v., and six received either 240 mg aminophylline i.v. or 400 mg doxofylline i.v. Compared with basal gastric secretion, for the hour after the infusion 240 mg aminophylline i.v. stimulated gastric acid output by a mean 213% (P less than 0.01) and mean pepsin output by 129% (P less than 0.01). Intravenous doxofylline did not stimulate a significant increase of either acid or pepsin output (200 mg: acid output +4%, pepsin output +10%; 400 mg: acid output +25%, pepsin output +27%). These findings suggest that doxofylline, unlike aminophylline, has a low secretagogue activity and it may be more suitable for asthmatic patients with peptic ulcer disease.

Adult↗