Tuberculosis in prisoners and their contacts in Chile: estimating incidence and latent infection.

SETTING: Contact investigation of tuberculosis (TB) patients in Chilean prisons. OBJECTIVE: 1) To estimate TB incidence and the prevalence of latent tuberculous infection (LTBI) among prisoners and their contacts; and 2) to determine factors associated with disease transmission. DESIGN: Cross-sectional study conducted in 46 prisons (51% of the total prison population) to assess the prevalence of and risk factors for LTBI among contacts of prisoners newly diagnosed with pulmonary TB. We used in vitro interferon-gamma release assays to establish LTBI and a questionnaire to address risk factors. RESULTS: During the 1-year follow-up, we studied 418 contacts of 33 active TB cases. We found high TB incidence (123.9 per 100,000 prisoners) and high LTBI prevalence (29.4%) among contacts. LTBI rates are significantly higher in prison inmates than in non-prisoners (33.2% vs. 15.6%). Male sex, illicit drugs, malnutrition, corticosteroid use, low educational level and sharing a cell with a case increase the risk of LTBI. Multivariate analyses showed that corticosteroid use, duration of incarceration and overcrowding are the most relevant determinants for LTBI among all contacts. CONCLUSIONS: Our results confirm that incarceration increases the risk of tuberculous infection and TB disease, and that it was associated not only with origin from vulnerable groups, but also with the prison environment. Reinforcing TB control is essential to prevent TB transmission in prisons.

[The hemodialysed patient and his/her family caregiver. Comparison of perceptions of the chronic illness]. / Il paziente emodializzato e il caregiver familiare. Percezioni a confronto sulla malattia cronica.

BACKGROUND: According to health psychology, the family caregiver (fc), i.e. the person who takes care of a hemodialysed patient, plays a pivotal role in coping with dialysis. This study explored and compared the lifestyle and the main needs of a cohort of hemodialysis patients, with reduced personal autonomy, to their fc, evaluating some psychological functional parameters, such as the perception of familial and social support, the psychological quality of life, the disability due to chronic illness, and the communication style. METHODS: An anonymous multiple versions questionnaire, administered according to the caregiver's family relationship, was given for self assessment to 54 couples of patients and related fc (spouse, son/daughter and brother/sister), mean age 66 and 60, respectively; mean dialytic patients' age: 8 years and 6 months. The questionnaire consisted of three different sections, demographics, renal disease and psychological evaluation, with 4 standard scales (Social Support Satisfaction, Marital Communication, Psychological General Well-Being Index and Evaluation of Needs). A multivariate variance analysis (MANOVA) was subsequently performed. RESULTS: Women have a higher perception of their lifestyle change after dialysis, and, in general, patients communicate more easily with their fc than vice versa. Communication problems are more common in patients with a recent diagnosis. Patients and fc mostly need a better dialogue with their nephrologists and urge some psychological help. CONCLUSIONS: The quality of the relationship between physicians, patients and their families is a key element in the process of healing.

Medical prevention and treatment of urinary stones.

Despite revolutionary developments in minimally invasive methods for the removal of stones in the last 15 years, the medical prevention of urinary stones remains very rewarding, due to the continual increase in the prevalence of nephrolithiasis in western countries, the high recurrence rate of the disease, its complications, discomfort and the costs of lithotripsy. Medical prevention is highly effective (50-95% efficacy in different series) and cost-convenient; its basic elements are appropriate metabolic evaluation, adequate hydration, "common sense" diet, and, in selected cases, drugs of proven efficacy. Clinical-metabolic evaluation should aim at the recognition of specific types of nephrolithiasis, and sort out secondary and/or remediable cases, define urinary risk factors, assess patients' compliance and the side effects of any therapy during follow-up. Hydration has proved effective in clinical trials and population-based observational studies; "fluids" may consist of water (any kind), coffee (caffeinated or decaffeinated), tea, beer and wine; grapefruit juice appears to have an unexplained ill effect. Despite the lack of clinical demonstration that dietary manipulations reduce the recurrences of stones, biochemical and epidemiological data suggest that high sodium, animal protein and sucrose intake increase the risk. Undue reductions in Ca intake also appear to be detrimental both for stone recurrences and bone mineralisation: "adequate" Ca intake (800-1000 mg/day) should be encouraged, but only in food since supplemental Ca, as drugs, appears to increase the risk of stones. Effective drugs are available for cystine, uric acid, infected stones and several secondary causes of Ca nephrolithiasis; in "idiopathic" Ca nephrolithiasis, thiazides, allopurinol, K and K-Mg citrate and possibly neutral K phosphate have been shown to be effective, at least in specific metabolic contexts.

Micronucleus frequencies in exfoliated buccal cells in normal mucosa, precancerous lesions and squamous cell carcinoma.

OBJECTIVE: To assess the value of micronuclei in the characterization of precancerous lesions of the oral cavity with reference to their likelihood of progressing to malignant lesions. STUDY DESIGN: The frequency of micronuclei was determined in exfoliated cells from normal oral mucosa, a preneoplastic condition (leukoplakia) and precancerous lesions with and without dysplasia, squamous cell carcinomas and sites of previous carcinomas that had been removed. RESULTS: Average micronucleus frequencies were increased in precancerous lesions as compared to normal mucosa and further increased in carcinomas, suggesting that micronuclei are a biomarker of neoplastic progression in this type of cancer. With all samples, micronucleus frequencies were systematically higher when cells were collected by vigorous than by light scraping, suggesting a decreasing gradient from basal to superficial layers of mucosa. The micronucleus frequency did not vary with the sex or age of patients, while it did vary with the anatomic site of the lesions. CONCLUSION: Although the gradual increase in micronucleus counts from normal mucosa to precancerous lesions to carcinomas suggests a link of this biomarker with neoplastic progression, the large overlapping of data prevents its use as a predictor of progression of precancerous lesions to malignancy in individual patients.

Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes.

Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.

Chromosome aberrations in hospital workers: evidence from surveillance studies in Italy (1963-1993).

Hospital workers are occupationally exposed to various agents known or suspected to induce chromosome damage, the most studied being ionizing radiation. To determine the extent of chromosome damage in peripheral blood lymphocytes in this population, taking into account temporal changes and job titles, a re-analysis of cytogenetic studies performed in four Italian laboratories in the period 1965-1993 was carried out. A total of 871 hospital workers and 617 controls, mainly coming from ad hoc studies or surveillance programs in occupational groups potentially exposed to ionizing radiation, were examined. The exposed to controls frequency ratio of chromosome aberrations was evaluated as the measure of effect within each dataset by job title, using multivariate Poisson regression analysis, which allowed an efficient control of confounding. Increased frequency of chromosome-type aberrations among exposed subjects was found in all datasets, especially in those dealing with older data. Significantly higher frequencies are reported for various job titles, particularly for orthopedists, radiologists, anesthesists, and nurses among paramedical occupations. Decrease in exposure to ionizing radiation in hospital workers was documented through a targeted study in the critical group of radiologists. A similar time-related reduction in the frequency of chromosome-type aberrations also has been reported by the surveillance studies carried out over the most recent decades. These data substantiate the use of chromosome-type aberrations as biomarkers of exposure in this occupational setting in the period evaluated. However, the increases observed also in workers with doubtful exposure to ionizing radiation indicate that other chromosome-damaging agents may be involved and, in turn, suggest the extension of surveillance to a larger number of occupations.

Abnormal reabsorption of Na+/CI- by the thiazide-inhibitable transporter of the distal convoluted tubule in Gitelman's syndrome.

Eleven patients with Gitelman's syndrome and 23 controls underwent acute administration of the thiazide diuretic hydrochlorothiazide and/or the loop diuretic furosemide (FUR) in order to indirectly evaluate the activity of the two electroneutral Na+/Cl(-)-reabsorptive systems of the distal nephron, namely the thiazide-sensitive Na+-Cl- symporter of the distal convoluted tubule and the FUR-sensitive Na+-K+-2Cl- symporter of the loop of Henle. The patients were characterized by hypokalemia, mild metabolic alkalosis, hypomagnesemia, hypocalciuria, and reduced free water generation during maximally diluted diuresis which indicated reduced distal nephron NaCl reabsorption. The plasma Na and Cl levels were similar in patients and controls. Hydrochlorothiazide induced a significantly lower increase of urinary Na and Cl excretions in 6 patients with Gitelman's syndrome than in 6 controls, indicating reduced NaCl reabsorption by the thiazide-sensitive Na+/Cl- symporter of the distal convoluted tubule in Gitelman's syndrome. FUR induced a slightly higher increase of urinary Na and Cl excretions in 11 patients with Gitelman's syndrome than in 17 controls, in keeping with reduced NaCl reabsorption in tubular sites past the loop of Henle during FUR effect or increased NaCl reabsorption in the loop itself (as a compensatory mechanism for NaCl-reabsorptive defect in the distal convoluted tubule) or both. Our results confirm that the functional activity of the renal thiazide-sensitive Na+-Cl- cotransporter (but not of the FUR-sensitive carrier) is deficient in patients with Gitelman's syndrome, in keeping with the recently described genetic link between the syndrome and a wide variety of nonconservative mutations of the gene encoding the protein; it is suggested that dynamic studies with diuretic administration may be of diagnostic help in this condition.

Staining of micronuclei in squamous epithelial cells of human oral mucosa.

OBJECTIVE: To evaluate the influence of methodologic variables, staining method and sampling, on the frequency of micronuclei scored in squamous epithelial cells of oral mucosa. Micronuclei were used as biomarkers of structural and numerical chromosome damage. STUDY DESIGN: Feulgen and Giemsa stain and fluorescent dyes Hoechst 33258 and propidium iodide were used for micronucleus staining. Cells were collected by either light or vigorous scraping of oral mucosa. RESULTS: Staining of micronuclei by Hoechst 33258 proved more handly, less time consuming and at least equally reliable to the more widely used Feulgen staining. Results with Giemsa stain and propidium iodide were unsatisfactory. Micronuclei were less frequent in superficial layers of the oral mucosa. CONCLUSION: Hoechst 33258 can be recommended for micronucleus staining in squamous epithelial cells of oral mucosa. Differences in scraping may affect the measurement of micronucleus frequency; scraping should therefore be carefully standardized in each laboratory.

Sister chromatid exchange induction in peripheral blood lymphocytes of traffic police workers.

Traffic police workers, as a population exposed to urban atmosphere, were compared with a control population exposed to indoor air pollution levels. Sister chromatid exchanges (SCEs) as a biomarker of effect were measured in peripheral blood lymphocytes of 54 exposed subjects and 35 controls, and environmental concentration of polynuclear aromatic hydrocarbon (PAH) tracer compounds was detected by personal air samplers. The mean exposure level to benzo[a]pyrene in our group of traffic policemen (3.4 mg/m3) was in the range that has been estimated in urban areas in Europe during the last 10 years. No difference in SCE levels was found between exposed workers (7.36, SD 1.35) and controls (7.47, SD 1.28). No correlation was observed between SCE/cell and airborne PAH concentration in the traffic worker population. A positive regression of SCE on exposure estimate was found only in the non-smoking group of police workers. Our findings suggest that exposure to urban air pollution does not induce relevant cytogenetic effects.

Aflatoxin exposure and cytogenetic alterations in individuals from the Gambia, West Africa.

Aflatoxin-albumin adducts in peripheral blood provide a measure of exposure to aflatoxin over the previous 2-3 months. In the present study, the levels of these adducts were determined in a group of individuals from The Gambia, West Africa and were compared in a cross-sectional study to the levels of various cytogenetic alterations (chromosomal aberrations, micronuclei, sister chromatid exchanges) in the same individuals to test whether an increase in genetic damage is associated with an increased exposure in this population. Of 35 subjects tested for aflatoxin-albumin adducts, all but 3 were positive. There were no correlations between the adduct level and the number of cytogenetic abnormalities at the individual level. A comparison of the cytogenetic alterations was made between Gambian individuals and a group of 22 healthy people from Italy where aflatoxin exposure is expected to be low. The levels of structural chromosomal aberrations, sister chromatid exchanges and micronuclei were all higher in the former group. Overall, these data are indicative of a higher exposure to genotoxins in Gambian subjects, one of which are aflatoxins, but suggest that more specific genetic markers of aflatoxin exposure are required to further examine the link between aflatoxin exposure and genetic alterations.

Influence of sex on cytogenetic end points: evidence from a large human sample and review of the literature.

The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupation exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease.

Cytogenetic biomonitoring of styrene-exposed plastic boat builders.

Earlier studies have produced evidence for an association between work-related styrene exposure and cytogenetic damage, while more recent studies have failed to show such an association. In the present study, chromosome aberrations (CA) and sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes of 46 male workers employed in a fiber-reinforced plastic boat building factory and exposed to styrene. Two groups of 23 workers each, characterized by different exposure levels (ranges: 2-120 mg/m3 and 86-1389 mg/m3 ambient air) were studied, fifty-one controls matched by sex, age and smoking habits were included. Randomized blood samples were analyzed for cytogenetic damage separately in two laboratories. Interlaboratory differences in the scoring of CA and SCE were noted. However, increases of the considered cytogenetic endpoints in exposed vs control groups were consistently observed in both laboratories. Multivariate statistical analysis of pooled data revealed increases of CA ranging between 19% (RR = 1.19; 95% C.I., 0.80-1.78; chromatid-type aberrations, low exposure group) and 144% (RR = 2.44; 95% C.I., 1.26-4.70; chromosome-type aberrations, high exposure group). Parallel excess of SCE in styrene exposed workers was also observed, although at a lesser extent (RR = 1.22; 95% C.I., 1.05-1.43, low exposure group; RR = 1.26; 95% C.I., 1.07-1.47, high exposure group). These findings suggest the presence of a causal association between occupational exposure to styrene and cytogenetic damage in the plastic boat building factory that was the object of the study.

Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study.

To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.

Correction of hypokalemia with antialdosterone therapy in Gitelman's syndrome.

Six adult patients (4 females and 2 males, age range 26-57 years) with Gitelman's syndrome (GS) were treated with spironolactone 200-300 mg/day (n = 5) and/or amiloride 10-30 mg/day (n = 3) for 1-18 months. The patients had hypokalemia, hyperreninemia, chloride-resistant metabolic alkalosis, renal hypomagnesemia (n = 5), and hypocalciuria (n = 5). Free water clearance studies during maximal water diuresis and furosemide administration were suggestive of a solute reabsorptive defect beyond the loop of Henle. Antialdosterone therapy induced a significant increase of PK (from 2.6 +/- 0.4 to 3.4 +/- 0.4 mM; p < 0.0001) and a decrease of CK (from 21.4 +/- 13.2 to 10.6 +/- 4.8 ml/min, p < 0.02) and FEK (from 21.0 +/- 13.6 to 13.4 +/- 5.7%; p < 0.03); PMg increased from 1.38 +/- 0.38 to 1.64 +/- 0.21 mg/dl (p < 0.03) with a parallel fall of CMg (from 5.5 +/- 2.3 to 2.9 +/- 1.5 ml/min; p < 0.02) and FEMg (from 5.7 +/- 2.6 to 2.9 +/- 0.6%; p < 0.05); arterial blood pH and HCO3- did not change (P = plasma, C = clearance, FE = fractional excretion). The creatinine clearance fell (from 90.5 +/- 16.8 to 65.8 +/- 20.9 ml/min; p < 0.05), and Prenin rose (from 16.6 +/- 8.9 to 35.3 +/- 25.3 ng/ml/h; p < 0.02, as did Paldo (from 26.1 +/- 12.3 to 109 +/- 82.6 ng/dl; p < 0.01), indicating extracellular fluid volume contraction; however no significant clinical symptoms of hypovolemia ensued.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac arrhythmias and electrolyte changes during haemodialysis.

Cardiac arrhythmias are a frequent event in chronic haemodialysis patients, and their pathogenesis is still poorly understood. We evaluated plasma K+ (PK), intraerythrocytic K+ (EK) and acid-base changes during haemodialysis in six patients with frequent arrhythmias (A-pts), and in six (used as controls) nonarrhythmic dialysis patients (C-pts). PK decreased significantly (P less than 0.01) during haemodialysis in both groups: A-pts (pre HD: 4.81 +/- 0.52 mM; 1st hour: 3.66 +/- 0.44; end HD: 3.17 +/- 0.38) and C-pts (4.75 +/- 0.80; 3.71 +/- 0.32 and 3.18 +/- 0.18 respectively) without any significant difference at any time between the two groups. Predialysis arterial pH and HCO3 were similar in A-pts (7.33 +/- 0.07 and 22.1 +/- 4.5 mM) and C-pts (7.29 +/- 0.04 and 19.7 +/- 2.6 mM) but an apparently better correction of acidosis within the treatment was seen in A-pts (arterial pH 1st hour: 7.38 +/- 0.07; end HD: 7.39 +/- 0.07) than C-pts (1st hour: 7.31 +/- 0.02, P less than 0.05 versus A-pts; end HD: 7.33 +/- 0.03, P less than 0.05 versus A-pts). EK was significantly (P less than 0.01) greater at all times in C-pts (pre HD: 90.6 +/- 15.7 mmol/l RBC; 1st hour: 93.3 +/- 11.7; end HD 96.6 +/- 10.7) than A-pts (72.1 +/- 9.0; 77.2 +/- 3.7 and 79.3 +/- 8.4, respectively). We conclude that haemodialysis patients with arrhythmias have a decreased intraerythrocytic K content in comparison with other patients despite similar PK values; this finding might constitute a predisposing factor for arrhythmias.

Pseudo-Bartter's syndrome from surreptitious diuretic intake: differential diagnosis with true Bartter's syndrome.

Five patients with pseudo-Bartter's syndrome from surreptitious diuretic abuse were compared with six patients with true Bartter's syndrome, diagnosed as a normotensive, hyperreninaemic, hypokalaemic metabolic alkalosis with normal urine chloride excretion, low CH2O/(CH2O+CCl) ratio during maximal water diuresis and negative urine screen for diuretics. The latter was positive for frusemide in four and for hydrochlorothiazide in the remaining pseudo-Bartter's patients. The two groups of patients did not differ as for plasma Na+, Cl-, K+, HCO3-, renin, and aldosterone, while uric acid and Mg2+ were greater in pseudo-Bartter's patients. Daily and fasting urine Na+, Cl- and K+ excretion were less in pseudo-Bartter's patients; however, there was substantial overlap of values between the two groups. Fractional distal solute reabsorption during maximal water diuresis was low in the six patients with Bartter's syndrome and in two pseudo-Bartter's patients; thus, this parameter could not be taken as a specific diagnostic marker of Bartter's syndrome. Frusemide administration, 40 mg i.v., induced a brisk increase of urine flow (11.7-21.8 ml/min), UOsm (148-186 mOsm/kg H2O) and FENa (14.6-24%) in Bartter's syndrome, but not pseudo-Bartter's patients; in all pseudo-Bartter's patients frusemide-induced changes of UOsm (13-97) and FENa (-0.5 to 10.2) were markedly less than in Bartter's syndrome patients. Frusemide resistance in pseudo-Bartter's patients was most probably related to diuretic-induced ECF volume contraction and increased proximal tubule solute reabsorption; in fact fractional lithium clearance (FELi, a marker of post-proximal solute delivery) was low in pseudo-Bartter's, but not in Bartter's syndrome patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytogenetic biomonitoring of an Italian population exposed to pesticides: chromosome aberration and sister-chromatid exchange analysis in peripheral blood lymphocytes.

Chromosome aberrations (CA) and sister-chromatid exchanges (SCE) were measured in lymphocytes of (A) 32 healthy individuals working in the flower industry and exposed to pesticides, (B) 32 individuals exposed as above and hospitalized for bladder cancer, and (C) 31 controls. Compounds to which floriculturists were exposed included 18 nitro-organic herbicides and fungicides, 9 nitro-organic fungicides, 12 organophosphate and organothiophosphate insecticides, 4 hydrocarbon derivative herbicides and 5 inorganic fungicides and insecticides. 150 and 70 metaphases per individual were scored for CA and SCE, respectively. A significant increase in the incidence of CA and SCE was observed in both exposed groups. Cancer patients showed the presence of rare rearrangements (dicentrics, rings and quadriradials) that were not observed in controls and were present at a lower frequency in healthy exposed people. Hyperdiploid and polyploid metaphases were also significantly increased in the 2 exposed groups compared to controls. Stratifying for age or smoking habits, although affecting the significance of individual data, did not change the substance of the results.