Interaction of genetic and exposure factors in the prevalence of berylliosis.

Prevalence of berylliosis, a lung disorder driven by the activation of beryllium-specific T cells, is associated with a major histocompatibility complex (MHC) class II marker (HLA-DPB1Glu69) and with the type of industrial exposure. We evaluated the interaction between marker and exposure in a beryllium-exposed population in which the prevalence of berylliosis was associated with machining beryllium. The presence of the marker was associated with higher prevalence (HLA-DPB1Glu69-positive machinists 25%; HLA-DPB1Glu69-negative machinists 3.2%, P = 0.05) and predicted berylliosis independent of machining history (odds ratios 11.8 and 10.1). The study shows that in berylliosis the carrier status of a genetic susceptibility factor adds to the effect of process-related risk factors.

The bright liver syndrome. Prevalence and determinants of a "bright" liver echopattern.

BACKGROUND: "Bright" liver at ultrasonography predicts fatty liver. AIM: To assess prevalence and predictors of a bright liver. METHODS: Prevalence arm--Prospective collection of records of unselected patients undergoing liver ultrasound. Protocol arm--A sample of patients with bright liver underwent routine laboratory investigations, liver tests, HBsAg (EIA) and anti-HCV (ELISA). Equipment--Grey scale real-time scanner. Bright liver diagnosed through the liver-kidney contrast. Statistics--Student's t-test; chi-square test; one-way analysis of variance; stepwise multiple logistic regression analysis, forward and backward. RESULTS: Prevalence arm--72 out of 363 (19.8%) cases had bright liver. Protocol arm--100 cases underwent laboratory evaluation. No difference was found in mean values of fasting plasma glucose, LDL cholesterol, apo A, Lp(a), uric acid, total bilirubin, GOT, GPT, AP, GGT, and serum bile acids or in the prevalence of serum HBsAg and anti-HCV in bright liver vs control groups. Univariate analysis showed body mass index, age, total cholesterol triglycerides, apo B, albumin, HDL cholesterol to be significantly different between cases and controls. However, the last 2 variables dropped out when logistic regression analysis was applied. CONCLUSIONS: 1. Roughly 20% of Italian patients undergoing US for routine clinical practice will have a bright liver. 2. Body mass index, age, serum cholesterol, triglycerides, and apo B levels are the independent predictors of a bright liver.

Effects of lipiodol retention on MRI signal intensity from hepatocellular carcinoma and surrounding liver treated by chemoembolization.

Opinion is divided regarding the influence of iodized oil on MRI signal intensity of hepatic tumours treated with transcatheter arterial chemoembolization (TACE), in which lipiodol deposits. The aim of our study was to ascertain whether or not lipiodol directly influences the MRI signal intensity of hepatocellular carcinoma (HCC) treated by TACE and that of the surrounding liver. Thirteen patients with HCC were studied retrospectively. CT and MRI scans were performed both before and 3 months after TACE. The CT scan was performed to check whether embolized nodules contained lipiodol and how lipiodol was distributed within them. In addition, eight patients were examined prospectively within 7 days after TACE. In these patients a CT scan was performed to see how lipiodol was distributed in the neoplastic nodules and in normal hepatic parenchyma. In the first group of patients the contrast-to-noise (C/N) ratio on T1-weighted (T1W) images and the T2 relaxation time on T2-weighted (T2W) images were calculated for both neoplasm and surrounding liver. In the second group of patients we also measured the signal intensity of non-neoplastic liver that was either permeated or not permeated by lipiodol. The data were analysed with Wilcoxon's test. On T1W images we observed that the retention of lipiodol increased the C/N ratio in all the tumours studied within 1 week after TACE. In the patients studied 3 months after TACE the C/N ratio was not significantly increased. On T2W images lipiodol retention did not change tumour signal intensity. The iodized oil did not change the signal intensity of the liver surrounding the tumour, in comparison with the liver not permeated by lipiodol, on either T1W or T2W images. The results indicate that lipiodol does not modify the signal intensity in non-neoplastic hepatic parenchyma in which it is deposited; after 3 months it does not significantly affect the signal of the tumours that accumulated it. Lipiodol produces a high signal on T1W images over the first few days following TACE in those tumours in which it is deposited.

Serological markers predicting tuberculosis in human immunodeficiency virus-infected patients.

SETTING: Human immunodeficiency virus (HIV)-positive patients retrospectively identified at the Hospital of Bari, Italy, with diagnosis of tuberculosis (TB) (n = 30) or non-tuberculous pneumonia (n = 29). Serum samples drawn at the time of diagnosis and one year before. Anti-purified protein derivative (PPD) and anti-diacyltrehalose (DAT) serum antibodies quantified by ELISA assay. OBJECTIVE: Since TB patients with HIV infection may present with elevated serum antibodies against Mycobacterium tuberculosis, we hypothesized that TB-specific antibody markers might predict TB in these subjects. DESIGN: A retrospective study was designed to assess the presence of M. tuberculosis-specific antibodies in HIV-positive patients developing TB. RESULTS: Of 30 HIV-positive TB patients, 24 (80%) had anti-PPD or anti-DAT antibodies at the time of TB diagnosis, and 20 (67%) one year before. In a sub-population of 16 of the 30 HIV-positive subjects, positivity for anti-PPD or anti-DAT antibodies one year before TB diagnosis was higher (11/16, 69%) than for the PPD skin test (4/16, 25%, P < 0.01). Antibody tests were specific for TB since positivity rates were lower both in patients with non-tuberculous pneumonia (P < 0.01) and in those with M. avium infection (P < 0.05). CONCLUSION: Antibody markers may predict TB in HIV-positive subjects, including those with negative PPD skin test.

Influence of antimalarials chloroquine, quinine, primaquine and mepacrine on the evolution of Ehrlich ascites tumour.

Substances like imidazoles, benzimidazoles and also quinolines, whose chemical structure includes a heterocyclic nitrogen, are known to interfere with the microsomal oxidation and, in some cases, with the metabolism of drugs. Since chloroquine and primaquine exert this effect in vivo and in vitro, we studied the influence of other antimalarials (quinine and mepacrine) in mice with induced Ehrlich ascites tumour (EAT) to find out whether variations in oxygen consumption affected the course of the disease. In vitro data, obtained by a polarographic technique, indicate that primaquine and, in particular, mepacrine increase EAT-cell oxygen consumption, while in vivo data, obtained in mice injected with an inoculum of about 1 x 10(6) tumour cells per mouse, show that both drugs, but notably mepacrine, accelerate tumour growth, as monitored by Cox's statistical method for body weight, and lead to earlier death. In cases of existing neoplasia, therefore, the potentially toxic effects of certain antimalarials must be borne in mind.

In vivo biological response following low-dose interleukin-2 in complete remission B-cell non-Hodgkin's lymphoma patients. Italian Lymphoma Study Group (GISL).

The aim of the present study is to verify whether recombinant interleukin-2 (rIL-2) at low doses is well tolerated in aggressive lymphoma in complete remission (CR), and if there may be a biological justification for its use as a remission-maintenance therapy able to reduce the percentage of relapses. We treated 6 patients with B-cell non-Hodgkin's lymphoma (B-NHL) in CR following PM-Cytabom with rIL-2 3 IMU s.c. x 5 d per wk, every other wk for 8 wk. Our results show that this treatment provokes statistically significant changes in the absolute number of lymphocytes, eosinophils, CD25+ and CD122+ cells and soluble IL-2 receptors; these doses, however, are not sufficient to modify CD3+, CD16+ and CD56+ cell values or natural killer and lymphokine activated killer cell activity. Thus these findings do not appear to constitute a biological rationale for the use of rIL-2 at this dose and schedule as a remission-maintenance therapy in B-cell NHL. Nevertheless, the results are a valid basis for further study of the use of the same rIL-2 doses for a longer period of time in combination with other cytokines, in the hope that the biological effects can be augmented without increasing the toxic side effects.

Synthesis and secretion of B-100 and A-I apolipoproteins in response to the changes of intracellular cholesteryl ester content in chick liver.

We investigated in the chick whether the diet-induced changes of the hepatic content of cholesteryl esters (CE) influence the synthesis and the secretion of apoB- and apoA-I-containing lipoproteins. Control chicks received a low cholesterol diet for 2 (SD-1), 4 (SD-2), or 7 (SD-3) weeks; the chicks in the experimental groups received a cholesterol-rich diet for 2 weeks and were killed at the end of the cholesterol feeding (CH-F), and after 2 (CH-D) or 5 (CH-DD) weeks of a low cholesterol diet. Hepatic CE content in CH-F chicks was 30-fold that observed in controls, but returned to the control level after 5 weeks of cholesterol depletion (CH-DD). The incorporation of 35S-labeled amino acids into cell and medium apoB and apoA-I was measured in liver slices. Intracellular 35S-labeled apoB was similar in all groups whereas medium 35S-labeled apoB was 2-fold higher in CH-F than in controls (SD-1). Pulse-chase experiments showed that radioactive apoB secreted by CH-F chicks at 120 min of chase was 2 times that of SD-1 chicks. This increased secretion of apoB was not found in CH-D chicks. In CH-F chicks, the intracellular and medium 35S-labeled apoA-I were 2-fold the values found in controls (SD-1); apoA-I production returned to the control level only after 5 weeks of cholesterol depletion (CH-DD). The increased secretion of apoB and apoA-I in CH-F chicks was associated with an increased secretion of very low, intermediate, and low density lipoproteins containing newly synthesized apoB and apoA-I and of high density lipoproteins containing predominantly apoA-I. Thus, in response to hepatic CE accumulation induced by cholesterol feeding, a larger proportion of newly synthesized apoB is driven to the secretory pathway and more apoA-I is synthesized. This promotes an increased secretion of plasma lipoproteins that contribute to the removal of CE from the liver.

Evaluation of a western blot serum test for the diagnosis of Mycobacterium tuberculosis infection.

This study was designed to evaluate the possibility of monitoring Mycobacterium tuberculosis infection using a serological assay. A discriminant score comprising antigen fractions of 38, 28, 24 and 19 kDa, identified in western blots using the Mycobacterium bovis bacille Calmette-Guérin (BCG) A60 antigen complex was established in a sample of 57 purified protein derivative (PPD)-negative and 47 PPD-positive individuals. It was then tested in a group of 140 subjects undergoing BCG vaccination as a model of tuberculosis complex infection and in a group of human immunodeficiency virus (HIV)-infected individuals as a model of cell-mediated immunodeficiency-related risk of tuberculosis. The discriminant score identified 57 out of 57 (100%) PPD-positives and none (0%) of the 47 PPD-negatives. In the BCG vaccinated subjects, 1.4% tested positive before vaccination and 90% after vaccination. In the HIV-positive subjects, 90% of the PPD-positive and 5% of the PPD-negative subjects had a positive score. This study suggests that the western blot discriminant score is an accurate test to survey M. tuberculosis infection in serum samples.

Evaluation of a novel tuberculosis complex-specific 34 kDa protein in the serological diagnosis of tuberculosis.

Tuberculosis (TB) serological testing with antigen complexes, although very sensitive, is not always as specific due to reactive serum antibodies in patients with inactive TB or nontuberculous infections. Since the use of recombinant M. tuberculosis proteins may enhance specificity, this study was designed to evaluate a novel 34 kDa tuberculosis complex-specific protein as a component of an antigen panel of recombinant proteins. Seventy patients with active TB (41 positive and 29 negative for acid-fast bacilli (AFB) in sputum) were evaluated, in comparison with 30 tuberculin purified protein derivative skin test positive (PPD+) and 30 PPD- normals, 20 subjects with inactive TB and 20 PPD+ subjects with nontuberculous pneumonia as controls. Serum antibody levels were quantified using enzyme linked immunosorbent assay (ELISA) tests with MS2-34, a fusion protein comprising the NH2-terminal 16 kDa of the 34 kDa protein, a recombinant 38 kDa protein (p38), and PPD. Using MS2-34 and p38 as an antigen panel in active TB patients yielded higher sensitivity and negative predictive value (sensitivity 86%; negative predictive value 91%) than using PPD (sensitivity 66%; negative predictive value 81%). Importantly, the MS2-34+p38 panel yielded a higher sensitivity (83%) than PPD (66%) in the subset of AFB- active TB patients. Thus, this novel protein increases sensitivity and specificity of serological testing for TB when used in panels of recombinant proteins.

Role of peripheral CD8 lymphocytes and soluble IL-2 receptor in predicting the duration of corticosteroid treatment in polymyalgia rheumatica and giant cell arteritis.

OBJECTIVES: To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA). METHODS: 38 PMR/GCA patients were followed up prospectively. Serum levels of sIL-2R and peripheral blood CD8 lymphocytes were measured before the start of corticosteroid treatment, after six months of treatment and at the last visit. Phenotypical analysis of lymphocyte subpopulations was performed with a two colour technique, and assay of sIL-2R was performed using an enzyme-linked immunosorbent kit. Forty four healthy people matched for age and gender comprised a healthy control group. RESULTS: The median duration of follow up was 28 months (range 7-65). Corticosteroid treatment lasted a median of 23.5 months (7-65). Eleven patients (29%) were in remission at the end of follow up; 45% of the patients had at least one relapse or recurrence. Compared with controls, patients with active disease had a significantly lower percentage of CD8 cells and significantly increased sIL-2R levels. Erythrocyte sedimentation rate, C reactive protein, and sIL-2R values were significantly less after six months of steroid treatment compared with before treatment. The percentage of CD8 cells remained significantly lower at six months and the end of follow up compared with controls, while sIL-2R levels remained significantly greater. Patients in whom the percentage of CD8 cells at six months was lower than one SD of the mean of normal controls (26%) had a significantly longer duration of corticosteroid treatment, a greater cumulative dose of prednisone and more relapses or recurrences compared with patients in whom the percentage was in the normal range. The duration of treatment and the cumulative dose of prednisone were not influenced by the percentage of CD8 cells before treatment therapy or by the levels of sIL-2R after six months of treatment. CONCLUSIONS: A reduced percentage of CD8 cells after six months of treatment may be a useful outcome parameter which would identify a group of PMR/GCA patients likely to experience more severe disease, defined as longer duration of corticosteroid treatment, higher cumulative dose of prednisone, and relapse or recurrence of disease.

Influence of glycyrrhizin on the evolution and respiration of Ehrlich ascites tumour cells.

It has been demonstrated that 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid and glycyrrhizin effectively inhibit the inception and growth of skin tumours. Moreover, glycyrrhizin and its aglycone act on the growth and differentiation of mouse melanoma cells in culture. In this study we investigated the effect of glycyrrhizin, 18 alpha- and 18 beta-glycyrrhetinic acids on the evolution of Ehrlich ascites tumour in mice. A prolonged glycyrrhizin treatment proved to be effective in modifying the animals' survival pattern.

Gait analysis of the donor foot in microsurgical reconstruction of the thumb.

Clinical and step evaluations by a piezoelectric system board were performed in 54 patients who underwent microsurgical reconstruction of the thumb by great or second toe transfer. Forty-four patients were male and 10 were female. In 13 cases, the thumb was reconstructed by the Morrison wrap-around technique. In 27 cases, an extended variant of the Morrison technique was used in which the whole distal phalanx was harvested with skin and nail apparatus. Four patients were treated by great toe transfer and 10 were treated by second toe transfer. Follow-up ranged from 2 to 144 months. The group of patients treated by the wrap-around technique presented hallux rigidus in 38.5% of cases. The group of patients treated by the extended variant of the Morrison technique presented a lesser tendency to hallux rigidus but a clear reduction of the pushing phase of hallux. The group of patients treated by second toe transfer presented a third and fourth metatarsal bone overload that was confirmed by a statistical Wilcoxon test: overload was linked to a plantar hyperkeratosis at the third metatarsal (20%), fourth metatarsal (10%), or fifth metatarsal bone (20%). A claw deformity of the third and fourth toes was observed in 20% of these patients. The four patients who underwent microsurgical reconstruction of the thumb by great toe transfer exhibited an overload of central and lateral metatarsal bones. Second toe transfer is not associated with the functional or cosmetic changes seen in great toe transfer and is therefore preferred.(ABSTRACT TRUNCATED AT 250 WORDS)

Body size perception and dissatisfaction in female subjects of different ages.

The relationships between age and both body size estimation and body dissatisfaction were assessed by Distorting Television Image Method (DTIM) and Body Cathexis Scale (BCS) in a sample of 96 female subjects of ages ranging from 7 to 65 years. We found that there were no significant body distortion differences between different age ranges, although the most accurate perception seemed to occur during adolescence. As far as DTIM assessment of body dissatisfaction was concerned, adolescents showed no significantly greater aesthetic preoccupation than subjects of other age groups. On the other hand, using BCS, body dissatisfaction appeared to increase proportionally with age. The low, although significant, correlations between these two techniques of measuring body dissatisfaction suggest that, in addition to evaluating aesthetic features, BCS also assesses the degree of satisfaction with functional body aspects which are exposed to unavoidable decline with ageing.

Quantitation of HIV-1 p24 antibody expressed as relative binding capacity p24 antigen (p24 RBC) in infants born to HIV-1 seropositive mothers: correlation of this serological marker with the HIV-1 maternal antibody course and p24 antigenemia detection.

The antibody content to HIV-1 p24 Ag expressed as relative binding capacity to the target antigen (p24 RBC) was retrospectively quantified in serum samples from 20 HIV-1-uninfected infants born to HIV-1 seropositive mothers. p24 RBC values quantified at birth were included either in a low (0-20%) or high (80-100%) range of values, classified as group A (11 infants) and group B (9 infants), respectively. The course of maternal antibodies to HIV-1 antigens p17, p24, p31, gp41, p51, p66, gp120, and gp160 was studied in each group. A substantial difference in the amount and subsequently in the decline of maternal antibodies to gag proteins p17, p24, and p55 and to pol proteins p51 and p66 was observed in the two infant groups in contrast with a similar content and decline of the remaining antibodies. In 7 HIV-1-infected infants of whom 4 resembled infant group A and 3 infant group B for p24 RBC values, a relationship appeared between p24 antibody decline and p24 antigenemia detection.

A prospective comparison between treatment with phlebotomy alone and with interferon-alpha in patients with polycythemia vera.

Interferon alpha (alpha-IFN) is increasingly used for the treatment of patients affected by polycythemia vera (PV). As prior studies are difficult to interpret in view of the lack of appropriate controls, we undertook a randomized comparison of lymphoblastoid alpha-IFN (alpha n-1 IFN) treatment against venesection treatment alone. In a crossover trial, we treated 22 PV patients alternatively for 5 months each with 3 MU/day sc of alpha n-1 IFN and phlebotomy alone. During IFN treatment, red blood cell count and hematocrit level were well controlled in both trial groups, reducing or eliminating the need for phlebotomy in all patients; furthermore, platelet number and white blood cell count declined during alpha-IFN therapy. In addition, the number of symptomatic patients was greatly reduced, and in six patients a reduction in splenic size was observed. Finally, the only patient with chromosomal abnormalities showed a complete cytogenetic conversion after 5 months of alpha-IFN therapy. Thus, for the first time, our results provide the unequivocal demonstration that alpha-IFN is superior to phlebotomy in controlling the pathologic expansion of erythroid elements and all the clinical aspects of this disease.

Prevalence rates of gallstone disease in Italy. The Chianciano population study.

The prevalence of gallstone disease and associated factors in the entire population of subjects aged 15-65 years born and resident in Chianciano Terme (Siena - Tuscany) was examined in the years 1985 and 1986. The investigation included gallbladder ultrasonography, administration of a questionnaire on personal and family history, physical examination and blood chemistry. A total of 1809 subjects (attendance rate 87.7%) participated in the study. Personal history and physical examination showed that Chianciano inhabitants have a low prevalence of obesity (4.3%) and only 4.4% of the female population had more than two pregnancies. Overall prevalence of gallstone disease (cholecystectomy+cholelithiasis) was 5.9% (3.7% for males and 8.4% for females). Age standardized relative risk of gallstone disease for females was 2.25 (95% confidence limits = 1.68-2.68). Prevalence of cholelithiasis was 3.5% (2.7% for males and 4.2% for females). Prevalence of gallstone disease increased with increasing age in both sexes, being extremely low in the age interval of 15-29 years (0.25%). The overall gallstones/cholecystectomy ratio was found to be lower (1:1) in females than in males (2.7:1). Although subjects with gallstones reported more frequently biliary colics and non-specific dyspeptic symptoms, the diagnostic power of all symptoms in identifying cholelithiasis was very poor due to low sensitivity. Only one third of subjects with gallstones was aware of having the disease. Age, obesity and number of pregnancies were positively associated with gallstone disease in univariate analyses. The association with obesity and parity disappeared in multivariate analysis. Blood lipids and glucose were not associated with the disease both in univariate and multivariate analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of survival in subjects with chronic obstructive pulmonary disease treated with long-term oxygen therapy.

We examined 166 patients with advanced chronic obstructive pulmonary disease (COPD) treated with long-term oxygen therapy (LTOT) in order to evaluate the prognostic factors of such patients. The mean observation period was 24 months (range 2-50 months) and the following variables were considered: age, forced expiratory volume in 1 s (FEV1), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), hematocrit, right ventricular systolic pressure (RVSP; evaluated by Doppler echocardiography), number of hospitalizations in the 2 years prior to prescription of LTOT and body mass index. The overall survival rate was 78.3% at 24 months and 67.1% at 36 months. A univariate analysis identified three variables as significant predictors of survival: FEV1, PaO2 and RVSP. A multivariate analysis, using Cox's model, showed an independent predictive power for RVSP, age and FEV1. RVSP higher than 35 mm Hg, age greater than 70 years and FEV1 lower than 30% of the predicted value were associated with shortened survival. The importance of pulmonary hypertension as a predictor of death suggests that LTOT could be prescribed earlier for COPD patients with cor pulmonale, as oxygen has been shown to be the only effective therapy for improving the survival probability of these patients.

Chloroform in alveolar air of individuals attending indoor swimming pools.

Alveolar air samples were collected from 163 subjects at indoor swimming pools and from 77 nonexposed subjects. Chloroform was present in all samples collected from exposed subjects (median = 695.02 nmol/m3). It was found at very low levels in 53% of samples from nonexposed subjects. Alveolar air chloroform levels from people attending indoor swimming pools (mean value within each sampling session) were correlated with environmental air concentration (r = 0.907, p = .002). Analysis of variance showed that levels of chloroform in alveolar air depend on environmental air concentration, age, intensity of the sport activity, and kind of swimming. Chloroform levels in samples collected from competitive swimmers versus nonswimming visitors were different (F = 10.911, p = .001). Moreover, their pattern of swimming may affect chloroform concentration in alveolar air. The analysis of chloroform in alveolar air assesses indoor exposure in healthy subjects simply and at low cost.

Identification of homogeneous geographical areas of mortality for tumours from cluster analysis.

This paper attempts to demonstrate the utility of cluster analysis as a descriptive method of studying mortality in epidemiology. In order to verify which algorithms of clustering best fit the data structure, the method of cophenetic correlation was implemented. Furthermore the probabilistic algorithm proposed by Beale was used to assess the partition. The results show the presence of some striking clusters between Local Sanitary Units of the Emilia Romagna Region for four types of tumour in men.