Long-term outcome of peripheral T-cell lymphomas: Ten-year follow-up of the International Prospective T-cell Project.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs.

Reference ranges of late-night salivary cortisol and cortisone measured by LC-MS/MS and accuracy for the diagnosis of Cushing's syndrome.

PURPOSE: International guidelines recommend salivary cortisol for the diagnosis of Cushing's syndrome. Despite mass spectrometry-based assays are considered the analytical gold-standard, there is still the need to define reference intervals and diagnostic accuracy of such methodology. METHODS: 100 healthy volunteers and 50 consecutive patients were enrolled to compare LC-MS/MS and electrochemiluminescence assay for the determination of late-night salivary cortisol and cortisone. Moreover, we aimed to determine reference intervals of salivary steroids in a population of healthy individuals and diagnostic accuracy in patients with suspected hypercortisolism and in a population including also healthy individuals. RESULTS: Method comparison highlighted a positive bias (51.8%) of immunoassay over LC-MS/MS. Reference intervals of salivary cortisol (0.17-0.97 µg/L), cortisone (0.84-4.85 µg/L) and ratio (0.08-0.30) were obtained. The most accurate thresholds of salivary cortisol for the diagnosis of hypercortisolism were 1.15 µg/L in the population with suspected hypercortisolism (AUC 1) and 1.30 µg/L in the population including also healthy individuals (AUC 1). Cut-off values of salivary cortisone (7.23 µg/L; Se 92.9%, Sp 97.2%, AUC 0.960 and Se 92.9%, Sp 99.1%, AUC 0.985 in suspected hypercortisolism and in overall population, respectively) and cortisol-to-cortisone ratio (0.20; Se 85.7%, Sp 80.6%, AUC 0.820 and Se 85.7%, Sp 85.5%, AUC 0.855 in suspected hypercortisolism and in overall population, respectively) were accurate and similar in both populations. CONCLUSION: LC-MS/MS is the most accurate analytical platform for measuring salivary steroids. Obtained reference intervals are coherent with previously published data and diagnostic accuracy for diagnosis of overt hypercortisolism proved highly satisfactory.

[Working and health conditions and preventive measures in a random sample of 5000 workers in the Veneto Region examined by telephone interview]. / Condizioni di lavoro e di salute e attività di prevenzione in un campione di 5000 lavoratori del veneto esaminati con questionario mediante intervista telefonica.

BACKGROUND: A survey was carried out in 2000 by the European Foundation for the Improvement of Living and Working Conditions in a random sample of workers from 15 countries of the European Union in order to obtain information on occupational exposure, health problems and preventive measures taken at the workplaces. OBJECTIVES: To obtain similar information in workers in the Veneto Region and compare the results with those of the third European Survey on Working Conditions (ESWC). The results of the survey on Veneto Region workers were further analyzed, investigating the distribution by risk factors in each work sector, and the association between risk factors and reported health problems. METHODS: The ESWC questionnaire was adapted to the requirements of a telephone interview and a sample of 5000 workers (size based on the budget) between 15 and 64 years of age was randomly extracted from the regional list of telephone subscribers. The questionnaire was administered by trained interviewers. No statistical tests were used in the comparison between ESWC and Veneto Region results due to the lack of a priori hypotheses. Odds ratio (OR) was calculated in estimating the association between risk factors and symptoms; and p-value for OR trend across the increasing level of exposure was also obtained. RESULTS: Workers reported to be exposed for more than a quarter of their work time to: vibrations (20%), noise (19%), dusts, fumes vapours, chemicals (18%), repetitive hand/arm movements (50%), tiring/painful positions (46%); working at very high speed or tight deadlines (60%). 54.4% of the subjects reported working with computers. Taking as a reference the third ESWC in 2000, among Veneto Region workers in 2005 exposure was lower as regards physical, chemical and ergonomic risk factors, and similar as regards working at very high speed. The more frequently reported work-related health problems were: stress (26.9%), backache (17.8%), overall fatigue (11.9%), muscular pains in upper limbs (6.8%), headache (6.1%), sight problems (5.4%), anxiety (5.5%), muscular pain in lower limbs (4.3%), irritability (4.0%), hearing problems (2.3%). Except for stress, all symptoms/health problems were two-three times more frequently reported in the ESWC than in the Veneto Region survey where, conversely, the number of persons with at least one new sick- leave spell was higher. Lastly, there was no difference as regards preventive measures taken at the workplace: information on risks (78.2%), wearing personal protective equipment (28.7%), training paid by employer (28.7%). Among the Veneto Region workers, the most often reported risk factors were exposure to physical and chemical risk factors in industry/agriculture, and shift-work and working at very high speed in the services. The most commonly adopted preventive measures were information on risks and wearing of personal protective equipment in industry, and training in services. Moreover, among the Veneto Region workers, a significant exposure-dependent increase was reported for respiratory problems, allergies, dermatitis, hearing loss, accidents, back pain, pain in the upper and lower limbs, and headache. The risk of stress, anxiety, sleeping problems, stomach pain and headache increased when skills were not adequate to cope with job demand. In contrast, the perception of improved health conditions increased with increasing skill discretion, decision authority, social support (which are dimensions of control of job demand), but not with information on risk, training, or use of personal protective equipment. CONCLUSIONS: Data from the present survey provide useful insights on working and health conditions of workers in the Veneto Region, revealing problems that were subsequently investigated using other sources of information, as reported in the studies published elsewhere in this volume.

[Comparison of four measurements of sickness absence in workers in the Veneto Region: interpretation and applicability. Data from Italian National Social Security Institute, 1997-2002]. / Quattro misure di assenze dal lavoro per malattia nei lavoratori del veneto, dati INPS 1997-2002: interpretazione dei risultati e applicabilità.

BACKGROUND: In 2005, 52% of workers in the Veneto Region reported one or more sick leave spells in the previous 12 months, compared with 16% reported in the European Survey on Working Condition in 2000 (ESWC), although health conditions were better in the Veneto Region than in the ESWC. OBJECTIVES: Since the above findings were based on answers to a questionnaire, we used an objective source of information in order to further investigate the problem. METHODS: The source of data consisted of the sick leave records of workers in the Veneto Region, 1997-2002, which were obtained from the Italian National Social Security Institute (INPS). Four measurements were used: (1) frequency = number of sick-leave spells during the study period/number of insured persons at risk for sickness absence during the study period; (2) cumulative incidence = number of persons with at least one new sick-leave spell during the study period/number of insured persons at risk for sickness absence during the study period; (3) sick-leave rate = number of sick-leave days during the study period/number of insured persons at risk for sickness absence during the study period; (4) duration of absence = number of sick-leave days in new sick leave spells during the study period/number of new sick-leave spells during the study period. Cumulative incidence could only be analyzed by statistical methods (binomial regression). RESULTS: The first three measurements gave overlapping results. The values were highest in industry, lowest in agriculture, and intermediate in crafts and services; they were highest in middle-aged subjects and lowest in younger and older individuals; the time trend increased up to 1999 and then decreased slowly. Cumulative incidence was 52.0%, 38.0%, 36.4% and 22.9%, in industry, services, crafts, and agriculture, respectively, and 42.8% in the total population. The results of binomial regression confirmed the above pattern, as well as an excess in women, in white collar workers, and in various occupational categories which, however, were probably not due to occupational exposures since in each occupational category the risk was always higher in industry than in crafts. By contrast, the sick-leave rate was higher in crafts and agriculture and lower in services and industry; it increased exponentially with age and did not show real differences between males and females. CONCLUSIONS: The choice of measurements influences the results; duration of absence could be used to detect areas of suspected work-related diseases, while cumulative incidence might be more helpful to detect areas of suspected absenteeism/presenteeism.

[Occupational injuries and sickness absence: association with job demand, decision latitude, and life style in 2174 workers in the Veneto Region]. / Infortuni sul lavoro e assenze dal lavoro per malattia: associazioni con carico lavorativo, autonomia decisionale e stili di vita in 2174 lavoratori del veneto.

BACKGROUND: Stress was the most frequent (26,9%) health problem reported in a survey on the perception of working and health conditions in 5000 workers in the Veneto Region. OBJECTIVES: The aim of the study was to investigate in the Veneto Region the association between occupational stress and events occurred in the previous 12 months: occupational accidents, or sickness absence for 10 or more consecutive days. METHODS: Perceived occupational stress is correlated, according to Karasek's model, to high job demand (JD) and low decision latitude (DL). Using Karasek's questionnaire (to which questions on smoking and alcohol consumption were added), we examined 2174 subjects working in 30 companies with between 10 and 500 employees, who belonged to the occupational categories of industry and services that are more prevalent in the Veneto Region. The questionnaire was administered by the occupational physician during health surveillance. The subjects were classified on the basis of current exposure to psychosocial factors or, for subjects reporting an event, their exposure at that time. We identified the tertiles of JD and DL; data were submitted to the analysis of multiple logistic regression, estimating odds ratio (OR) and 95% confidence interval (CI). The population attributable risk (PAR) was calculated using the formula (pc (OR-1)/OR), where pc is the fraction of exposed cases. RESULTS: An elevated risk of occupational accidents was found in subjects with regular consumption of alcohol (OR = 2.0; IC = 1.2-3.5), in smokers smoking 10-20 (2.3; 1.3-3.8) or >20 cigarettes/day (3.8; 1.8-7.9), in the highest tertile of JD (2.29; 1.35-3.89) and in the lowest tertile of DL (1.6; 1.0-2.6). PAR was 37.6% for occupational factors (high JD and low DL), 44.5%for non-occupational factors (cigarette smoking and alcohol consumption), and 82.1% overall. The risk of sickness absence increased in subjects smoking 10-20 cigarettes (1.63 = 1.1-2.40), in the highest tertile of JD (1.5; 1.0-2.2) and in the lowest tertile of DL (1.6; 1.1-2.2). PAR was 26.1% for occupational factors (high JD and low DL), 7.6% for non-occupational factors (smoking), and 30.4% overall. While the risk of sick absence increased mainly with the reduction of DL, the risk of occupational accidents increased with increasing JD and, to a lesser extent, with decreasing DL. The current approach to accident prevention is based only on technical and administrative aspects, in spite of the fact that 80% of accidents are not attributable to malfunctioning of machinery. Injury prevention should address technical, personal and psychosocial risk factors together as a whole.

[Association between causes of lNPS compensated disability and occupational category (Veneto Region, 1994-2002): a surveillance method for occupational diseases?]. / Associazione tra causa di invalidita pensionabile INPS e comparto lavorativo (Veneto, 1994-2002): un metodo di sorveglianza delle malattie professionali?

BACKGROUND: According to Italian law, workers are insured against disability through the National Social Security Institute (INPS), whose records contain information on diseases causing disability and occupational histories. OBJECTIVES: Using the INPS data, our objective was to identify any excess risk of disabling diseases in relation to the occupational categories. METHODS: Insurance covers all private sector employees, a small proportion of public sector employees, agricultural labourers, domestic workers, self-employed workers (craftsmen, commercial dealers,farmers), and few other occupational categories. For each insured worker, a database was created containing registry data, occupational history and, for compensated workers, the disease code, for each year from 1994 to 2002. A cohort study design was adopted, in which references were self-employed workers (with mixed exposure) to whom different categories of employees in agriculture, industry, crafts, and services were compared. Data were analyzed by means of Poisson regression, estimating the Incidence Rate Ratio (IRR) and confidence interval (CI) at 99.99%, instead of 95%, in order to set the threshold of error for the entire study at 0.05. RESULTS: In the construction industry there were significantly high risks of disability in both industry and crafts for tumours (industry: IRR = 2.07; IC = 1. 67-2.57; crafts: 2.57; 1.89-3.18), circulatory disorders (industry: IRR = 2.24; IC = 1.65-3.04; crafts.: 3.06; 2.16-4.32), and bone and joint diseases (industry. IRR = 5.0; IC = 3.15-7.94; crafts: 6.58; 5.04-8.59). CONCLUSIONS: The advantage of this approach is to recruit a large number of subjects at limited cost. The procedure here proposed is a mainly exploratory approach aimed at establishing new study hypotheses: disability, in fact, is acknowledged by INPS when its cause is not occupational according to the current literature.

[Safety and health in workers employed in industry. Data from Industrial Accidents Compensation Board (INAIL) and National Social Security Institute (INPS), Veneto Region, 1994-2002]. / Sicurezza e salute dei lavoratori dell'Industria attraverso i dati INAIL e INPS, Veneto, 1994-2002.

BACKGROUND: A decreasing time trend for occupational injuries and sickness absence would be the effect of the new legislation (D.Lgs. 626/94 and successive laws) on prevention in occupational settings. Conversely, the reduction of INPS disability would reflect a health improvement due to non-occupational causes. OBJECTIVES: The aim of the study was to investigate the efficacy of the new legislation among employees in industry (where the law was mainly applied), via the time trend of three standardized rates in the Veneto Region. METHODS: The numerator for the rate of occupational accidents (cases occurring in industry workers in the Veneto Region, broken down for sex, age and calendar years) was supplied by INAIL. The denominator for the above rate, as well as numerators and denominators for disability and sickness absence were supplied by INPS. Data were available from 1994 to 2002 for accidents and disability, and from 1997 to 2002 for sickness absence. In every year from 1994 to 2002, the rates were standardized for age and sex with the direct method, using an internal "standard" population. The time trend of year-specific standardized rates was analyzed by Joinpoint regression software. RESULTS: Among industrial workers in the Veneto Region, occupational accidents increased by 0.4% yearly, while disability decreased by 2.56% from 1994 to 2002. Sick absence increased up to 1999, then decreased. CONCLUSIONS: This epidemiological pattern is difficult to explain. The increase in accidents could be due to the increase of non-European Union workers and/or to the fact that accidents on the way to or from work were recognized as occupational accidents by INAIL starting from 2000. Both these phenomena could have contributed to increase the rate that was otherwise diminishing. On the other hand, this same situation could be due to insufficient efficacy of the legislation (D.Lgs. 626/94 and successive laws) for preventing occupational accidents and diseases.

Dual effect of methylprednsolone pulses on apoptosis of peripheral leukocytes in patients with renal diseases.

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis.

Elevated lung cancer risk shortly after smoking cessation: is it due to a reduction of endotoxin exposure?

Several reports indicate that the risk of lung cancer increases slightly for a short period of time after cessation of smoking while the risk of adverse cardiovascular events drops immediately. Recent studies on subjects occupationally exposed to organic dust-containing endotoxin have revealed lower than expected rates of lung cancer. There is experimental evidence that stimulation of the immune system by endotoxin has a protective effect against cancer. Tobacco smoke has been shown to contain high levels of endotoxin. We therefore postulate that cessation of smoking eliminates the protective effect of endotoxin. Any benefit conferred by endotoxin does not, however, justify smoking. As the inverse relationship between exposure to endotoxin and the risk of lung cancer is a strong one, endotoxin-like substances could form the basis of vaccination strategies.

Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia.

Bone fibrous dysplasia is one of the main features of McCune-Albright syndrome, a rare genetic condition caused by constitutive activating mutations of Gs-protein and defined by skin dysplasia, bone fibrous dysplasia, and autonomous multiple endocrinopathies. Raised serum alkaline phosphatase (ALP) and urinary hydroxyproline levels indicating bone metabolic hyperactivity have been reported in these patients. Encouraging therapeutic results have been achieved, mainly in adults, with pamidronate, an aminobisphosphonate. In this study we investigate newer bone metabolic indices in a cohort of 11 children and adolescents treated with pamidronate. Tenfold increases of bone ALP and urinary pyridinoline cross-links were found and osteocalcin levels were twofold higher compared with reference values. After treatment, significant decreases in bone ALP and cross-links (Wilcoxon test P < 0.06) were found. Bone mineral density (BMD) significantly increased during treatment. There were signs of radiological healing as thickening of the cortical bone was found in some cases.

Clinical relevance of hemochromatosis-related HFE C282Y/H63D gene mutations in patients on chronic dialysis.

BACKGROUND: The actual prevalence and the clinical relevance of gene mutations of HFE (which are linked to hemochromatosis) have not yet been established in patients on chronic dialysis. On the basis of theoretical premises, it could be hypothesized that these genetic determinants might influence the response to iron intake and the susceptibility for iron overload in patients in parenteral iron therapy. Furthermore, carriers for these mutations might be prone to develop sporadic porphyria cutanea tarda and cardiovascular events. METHODS: C282Y/H63D mutations of HFE gene were evaluated in 132 patients (34 in peritoneal dialysis, 98 in HD) and correlated with biochemical parameters of iron status (ferritin (FER) concentration and transferrin saturation (TSAT)), red cell parameters (red cell size and hemoglobin content), erythropoietin (EPO) dosage, major cardiovascular events and C-reactive protein as marker of chronic inflammation, in patients without iron therapy and after i.v. iron supplementation (< or = 60 mg/week) and with the presence of biopsy-proven porphyria. RESULTS: C282Y heterozygous mutation was found in 8/132 (6.6%); H63D homozygous and heterozygous mutations were found in 3/132 (2.3%) and 22/132 (16%) patients, respectively. Two patients (1.5%) showed double heterozygosis. No differences in baseline serum FER and TSAT and the other biochemical and clinical parameters were found in patients bearing mutations alleles nor after continuous iron therapy at low dosages. However, the prevalence of patients capable of maintaining normal hemoglobin (Hb) level without EPO therapy is increased in the C282Y-mutated patients. Only 1 patient out of the 4 with biopsy-proven porphyria cutanea tarda was bearing gene mutations (H63D heterozygosis). CONCLUSION: C282Y/H63D HFE gene mutations do not seem to be related to major abnormalities in biochemical parameters of iron status in dialysis patients without iron therapy or after i.v. iron supplementation, granted that low dosages are employed. Obviously, as our patients were exposed to a relatively uniform iron regimen in our clinical center (< or = 60 mg/week), it is unclear if other dosing regimens will unmask clinically significant differences between the heterozygotes and normals. The fact that the C282Y-mutated patients more frequently maintain high Hb values without EPO is interesting as could suggest a better use of available iron for erythopoiesis, but needs to be confirmed in larger samples. No clear association is demonstrated with porphyria cutanea tarda and major cardiovascular events.

Bladder tumor antigen assay as compared to voided urine cytology in the diagnosis of bladder cancer.

BACKGROUND: The study was aimed at comparing the diagnostic accuracy of the quantitative bladder tumor antigen (BTA) TRAK immunoassay with exfoliative urine cytology in the detection of primary and recurrent bladder cancer. METHODS: The analysis was carried out on 194 high risk patients undergoing a diagnostic cystoscopy, 279 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy, and 45 healthy controls. Urine cytology was performed by a skilled cytopathologist on three consecutive samples. RESULTS: BTA TRAK values resulted significantly higher in tumor positive cases than in absence of bladder tumor for both groups of patients. Non neoplastic urothelial diseases as well as the absence of mucosal abnormalities were associated with a marked increase in BTA TRAK levels with respect to the control group. Overall sensitivity and specificity was 63 and 63% for BTA TRAK (cut-off 34 U/ml), and 68.3 and 73.4% for urine cytology, respectively. The diagnostic advantage of urine cytology was maintained when patients were stratified by tumor grade. CONCLUSIONS: The clinical performance of the BTA TRAK in the detection of primary or recurrent bladder cancer is acceptable and reproducible as shown by similar results with previous reports, although urine cytology performed on three samples showed the highest sensitivity and specificity.

BTA quantitative assay and NMP22 testing compared with urine cytology in the detection of transitional cell carcinoma of the bladder.

PURPOSE: Both BTA TRAK and NMP22 urine concentrations have shown a sensitivity superior to urine cytology in the detection of bladder cancer. We compared these tumor markers with urine cytology performed on 3 consecutive samples and evaluated by an expert cytopathologist. PATIENTS AND METHODS: The investigations were conducted on 94 patients undergoing a diagnostic cystoscopy for a high suspicion of bladder cancer (group 1) and on 102 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy (group 2). Biopsy specimens were obtained also from tumor negative patients. Immunoassays for BTA TRAK and NMP22 were carried out according to standard methods. The choice of the cut-off was based on the ground of sensitivity and specificity curves intersection. Urine cytology results were expressed as positive, negative and 'dubious'. RESULTS: Overall sensitivity was 56% for NMP22 (cut-off 11 U/ml) and 57% for BTA TRAK (cut-off 60 U/ml). When dubious results were considered as positive cases, urine cytology achieved a sensitivity of 73.3%. Assuming dubious cases as negative results, urine cytology sensitivity resulted 59.3%. When the 2 groups of patients were evaluated separately with different cut-off, there was no significant gain in sensitivity for BTA TRAK and NMP22 over urine cytology. CONCLUSIONS: Urine cytology performed on 3 samples showed the highest sensitivity and specificity. The diagnostic advantage of urine cytology over BTA TRAK and NMP22 was maintained when patients were stratified by tumor grade.

Efficacy and efficiency of oral microemulsion cyclosporin versus intravenous and soft gelatin capsule cyclosporin in the treatment of severe steroid-refractory ulcerative colitis: an open-label retrospective trial.

We have used cyclosporin to treat patients with acute steroid-resistant ulcerative colitis since the beginning of 1991. Of the 55 patients so far elected for treatment, 40 received the drug intravenously at 2 mg/kg/day for 14 days, with the responders being maintained on traditional soft-gelatin-capsule cyclosporin at a dose of 6-8 mg/kg/day for 6 months; the remaining 15 received oral microemulsion cyclosporin, 5 mg/kg/day, for 3 months. The doses were titrated to ensure whole-blood drug concentrations of 60-240 ng/ml, with levels of approximately 200 ng/ml being attained by both regimens. One-hundred percent of the patients receiving oral microemulsion cyclosporin and 65% of those receiving the intravenous regimen achieved a short-term response (p = 0.011). Both the responder subsets received additional azathioprine and relapsed on treatment with the same frequency of 40%. However, 17% of the patients who received intravenous cyclosporin developed major toxicity (including one fatality), whereas no major toxicity was observed in the oral microemulsion cyclosporin group. The microemulsion formulation was therefore more effective than intravenous cyclosporin in achieving the short-term remission of steroid-unresponsive ulcerative colitis. As the maintenance drug, it led to the same frequency of disease relapse as traditional oral cyclosporin. However, because it did not involve invasive in-hospital procedures or cause major toxicity, it was more efficient than the combination of the intravenous and traditional oral drug.

Spontaneous release of interleukin 1 beta from human blood monocytes in thyrotoxic osteodystrophy.

Hyperthyroidism is a well documented cause of impaired bone turnover characterized by increased osteoblastic and osteoclastic activity, resulting in predominance of bone resorption and in decreased bone mass. Thyroid hormones can carry out a direct effect on osteoblasts which express specific receptors on their surface membrane; differently effect on osteoclast seems to be mediated by local factors, cytokynes released by activated osteoblasts or by bone monocytes cells. Interleukin 1 beta is the first purified cytokyne shown to have bone resorbing activity. In ten thyrotoxic female patients IL 1 beta in the cellular medium of the monocytes blood cells culture has been measured, compared to PYD/cr urinary excretion, and FT3, BGP serum levels, before and after thyrostatic treatment. Ten normal females were studied as control group. The results before treatment showed osteopenia in 20% (DEXA densitometry), increased values of FT3, BGP, IL 1 beta and PYD/cr in patients versus controls (p < 0.001). The thyrostatic therapy obtained normalization of IL 1 beta, PYD/cr, BGP, and FT3 levels. Our data demonstrate that increased thyroid hormone levels in vivo are associated to increased secretion of monocytes cytokynes in vitro and suggest that alterations in local production of bone acting cytokyne may underlie to thyrotoxic osteodistrophy.

[Computed tomography evaluation of urothelial carcinomas of the upper urinary tract]. / Valutazione con Tomografia Computerizzata dei carcinomi uroteliali delle vie escretrici urinarie superiori.

Computed Tomography (CT) is an indispensable noninvasive method for staging transitional cell carcinomas of renal pelvis and ureter. Twenty-seven patients with upper urinary tract tumors were examined and the CT results correlated with histopathologic findings. These tumors exhibit three different development patterns: in our series we identified 17 intraluminal sessile lesions, 6 focal or concentric wall thickenings and finally 7 infiltrating masses; soft-tissue density lesions exhibited in all cases mild contrast enhancement (mean density increase: 38 HU). Even though the attenuation values of tumors do not allow the accurate demonstration of the depth of renal pelvis and ureteral wall invasion, CT can differentiate the lesions which are still confined within the external wall layers (CT1, 17 cases) from those invading the peripelvic-ureteral fat (CT2, 9 cases) or spreading to other organs as well as distant metastases (CT3, 4 cases). Delayed scans can also demonstrate intraluminal lesion extent and sometimes changes of patients' position allow better differentiation of wall outlines from peripheral fat. The overall staging accuracy of CT was 76.66% and its sensitivity was 93.33%. The assessment of lymph node metastases was the major cause of error in the CT evaluation of these tumors.