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Introduction: The Herbst device is widely used for correction of class II malocclusions; however, most of the researches carried out on the Herbst appliance in literature do not take into account patients with a different mandibular divergence. The aim of this study was to investigate the effects of Herbst on dental and skeletal structures and to evaluate possible influence of vertical facial growth patterns., Methods: A retrospective study was conducted on lateral cephalograms of 75 growing patients (mean age: 9.9 ± 1.9 years) with class II malocclusion treated with Herbst. Subjects were divided into 3 groups using the mandibular divergence index (SN and GoMe angle). Cephalometric parameters were evaluated using the modified SO (sagittal occlusion) Pancherz's analysis. A statistical analysis was conducted to evaluate differences among groups using ANOVA., Results: Our study showed differences in response to treatment depending on patient's facial vertical growth pattern. Cranial base angle and mandibular rotation were significantly different ( p < 0.05) between hypodivergent patients and normodivergent patients and between hypodivergent and hyperdivergent subjects., Conclusion: Hypodivergent patients increased their mandibular divergence during treatment to a greater extent than normodivergents; moreover, hyperdivergent patients exhibited a decreased mandibular divergence at the end of the treatment., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Maria Rita Giuca et al.)

Background/aim: The optimal therapeutic use of metronomic vinorelbine has not yet been defined. We aimed to assess the safety of metronomic oral vinorelbine in first-line treatment of elderly patients with advanced lung cancer who were unfit for polychemotherapy. Progression-free survival, response rate and overall survival were secondary end-points., Patients and Methods: Seventy-six patients received 50 mg of oral vinorelbine three times per week, until disease progression, patient refusal or unacceptable toxicity. Patients were evaluated for response and toxicity after one cycle of chemotherapy. The treatment was considered feasible with a grade 3/4 toxicity rate lower than 20%., Results: Clinical benefit was observed in 50% of patients. Median overall survival was 8.0 months. Grade 1/2 toxicity was observed in 53 patients (69.7%), grade 3 toxicity in eight patients (10.5%). One patient had grade 4 diarrhea., Conclusion: Metronomic oral vinorelbine is safe in elderly patients, allowing for long-term disease stabilization with optimal patient compliance., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Deferasirox (DFX) is used to reduce iron levels in patients with myelodysplastic syndrome (MDS) who develop iron overload after chronic red blood cell infusions. However, DFX can be associated with renal and gastrointestinal toxicities, which may cause treatment interruption or discontinuation. This study aimed to determine the effectiveness and safety of DFX in patients with MDS., Methods: This multicenter, retrospective, observational study was conducted at two hospitals in Italy. Elderly patients with transfusion-dependent MDS received DFX for up to 12 months and were divided into two groups: group A comprised patients who were not under multidisciplinary assessment; group B comprised patients under multidisciplinary control. Treatment effectiveness was estimated by monitoring the serum ferritin (SF) levels throughout the study. Any treatment-related adverse events (AEs), clinically relevant analytical alterations, and reasons for treatment discontinuation were monitored., Results: The study included 44 patients (13 female, 31 male; median age 77.0 years). At 3 months, SF levels decreased by ≥20 % in 29 and 31 % of patients in groups A and B, respectively, in 17 and 36 % of patients at 6 months, and in 22 and 58 % at 12 months. The most common AEs were diarrhea and increased serum creatinine, which were more frequent in group A. The discontinuation rate after renal AE was 15 and 5 % in groups A and B, respectively., Conclusion: Multidisciplinary evaluation can be an effective strategy for monitoring renal function in patients on DFX therapy, to improve treatment adherence and overall efficacy in elderly patients with MDS.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a treatment after first-line chemotherapy in patients with advanced NSCLC. We assessed the predictive and prognostic role of EGFR and Kras mutations in NSCLC patients treated with TKIs after progression, not included in clinical trials. Gefitinib 250 mg or Erlotinib 150 mg per os were administered to 70 patients. Radiological assessment was performed every six weeks. EGFR and Kras mutations were found in 21.4% and 24.3% of patients, respectively. At multivariate analysis, Kras mutation was positively associated with progression-free survival (PFS; HR=0.71, 95% CI: 0.53-0.96; p=0.027) and, less clearly, with response (OR=1.84, 95% CI: 0.98-3.45; p=0.057) and survival (HR=0.74, 95% CI:0.54-1.02; p=0.066). EGFR mutation influenced positively PFS (HR=0.69, 95% CI: 0.47-1.02; p=0.06), but not survival. In conclusion, in our unselected patients mutation of Kras correlated with a better outcome. The small number of patients may explain some discrepancies with data in literature.

Background: Malignant pleural mesothelioma is a problematic condition due to poor prognosis and difficulties in management. We evaluated the treatment and outcome of 378 mesothelioma patients referred to 6 Italian Oncology Departments., Methods: Demographic and clinical data were collected. Treatment was assessed in terms of chemotherapy (line of treatment, pemetrexed-based regimen, other therapies), surgery, and radiotherapy. Response to therapy, progression-free survival, and overall survival were evaluated., Results: 36 and 342 patients received best supportive care and active treatment, respectively; 86 patients underwent surgery, and 26 received trimodal therapy. Disease control after first-line chemotherapy was achieved in 74.2% of patients (75.7% in patients treated with pemetrexed combined with other drugs and 69% with pemetrexed as monotherapy). The disease control rate was 82.6% in pemetrexed re-challenged individuals. Median survival time was 11.6 months with supportive care, 16.2 months with chemotherapy only, 32.4 months with surgery plus chemotherapy, and 47.2 months with trimodal therapy. A more favorable prognosis was observed in responders to first-line therapy who were then actively treated with second-line (24.8 vs. 11.8 months in non-responders, p < 0.001) and third-line chemotherapy (28.9 vs. 17.8 months in non-responders, p = 0.005)., Conclusion: Mesothelioma patients benefited from chemotherapy alone only when retreated in the second line after response to first-line therapy., (© 2017 S. Karger GmbH, Freiburg.)

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients., Methods: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed., Results: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively)., Conclusions: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers., Methods: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay., Results: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l)., Conclusions: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year., (© 2013 S. Karger AG, Basel.)

Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It is widely used in combination with polychemotherapy regimens for the treatment of hematological disorders. There is no evidence of direct cardiotoxicity of the drug but a few cases of cardiovascular adverse events have been reported in the literature. We report on two patients affected by stage IV non-Hodgkin lymphoma with bone marrow infiltration and peripheral blood involvement who experienced cardiovascular accidents temporally related to rituximab infusion. In both cases the monoclonal antibody was administered in association with a polychemotherapy regimen but administration was postponed several days later in order to avoid severe cytokine release syndrome because of the high tumor burden. The first case concerns an episode of atrial fibrillation in a patient with a diagnosis of small B-cell lymphoma. The episode happened immediately after rituximab infusion. In the second case there was an episode of chest pain associated with fever and chills during rituximab infusion in a patient with a diagnosis of mantle cell lymphoma. In both cases we noticed an unusual correlation between symptom recurrence and the speed of rituximab infusion. Both patients presented several cardiovascular risk factors but preliminary cardiac function assessment excluded signs of heart dysfunction. The pathogenesis of cardiovascular events during rituximab infusion remains unclear. A key role might be played by cytokine release from B cells as a consequence of rituximab activity. Moreover, pre-existing silent cardiac damage could be co-responsible for the clinical manifestations we reported. We consider our clinical experience relevant because it raises an issue of good clinical practice: despite rituximab's good tolerability profile, patients with cardiovascular risk factors should undergo accurate cardiac assessment so that silent heart disease can be detected. If the suspicion of cardiac damage is high, more extensive cardiac assessment is recommended.

The soluble mesothelin-related peptide (SMRP), a candidate marker for screening of subjects with asbestos exposure, is influenced by some individual and clinical factors. The aim of this study was to quantify the role of age, smoking, weight, presence of diseases and exposure to asbestos on serum SMRP levels in a large series of subjects exposed to asbestos, possible candidates for mesothelioma screening. One thousand seven hundred and four participants underwent clinical examination and were interviewed on medical anamnesis, occupation, smoking and weight. SMRP was measured by an ELISA assay. Overall, median SMRP was 0.4 (IQR 25-75: 0.3-0.7) nmol/l. It was higher in current smokers and in subjects with a cumulative asbestos exposure >50 ff/cc/years than in all the other subjects (p < 0.001 and p = 0.002, respectively). SMRP was positively correlated with age (ρ = 0.11, p < 0.001) and, inversely, with BMI (ρ = -0.15, p < 0.001). SMRP was lower in healthy subjects (n = 1,217: median 0.4 nmol/l) than in subjects with malignant tumors (n = 118: 0.5 nmol/l; p = 0.01), asbestos-related pleural lesions (plaques or thickenings, n = 152: 0.6 nmol/l; p < 0.001) and other benign diseases (n = 182: 0.5 nmol/l; p = 0.04). Multivariate analysis revealed significant predictors of increased SMRP: age >57 years, current smoking, a positive anamnesis for cancer and for asbestos-related pleural lesions, and BMI < 25. Some clinical and demographic variables are associated with serum SMRP levels. The degree of these associations is low, nevertheless they should be accounted for in the interpretation of SMPR as a candidate marker predictive of mesothelioma. The potential predictive value of serum SMRP in screening/surveillance programs must be validated in prospective studies.

For more than 20 years erythropoietin (rHEPO) has largely been used to treat anemia in myelodysplastic syndromes (MDS). Early clinical trials showed erythroid responses in no more than 15-25% of patients. In the last decade, a better selection of MDS patients suitable for a therapeutic challenge with rHEPO, alone or in combination with G-CSF, allowed for an increased response-rate, averaging around 40%. More recently, an even higher percentage of responses have been obtained using higher-doses of rHEPO (up to 80,000 IU/weekly) in lower-risk MDS patients. This treatment however, especially at such high doses, is costly and not easily affordable for prolonged periods. The aim of this study was to verify if the use of "standard" doses of rHEPO could induce a satisfying response-rate with a less expensive treatment schedule in IPSS-defined "lower-risk" MDS anemic patients. From January 2005 to December 2009 a total of 55 consecutive anemic (Hb ≤ 10 g/dL) patients (29 males, 26 females, median age 78 years) with low-intermediate-1 risk MDS were treated after informed consent with rHEPO (40,000 IU once a week subcutaneously) for at least 3 months; at the end of this period, erythroid response was assessed, and responders were allowed to continue the treatment indefinitely, whereas non-responders were considered "off study". Both efficacy and safety of the treatment were recorded and evaluated. After 3 months of treatment, 36 out of 55 (65.5%) patients achieved an erythroid response to rHEPO according to IWG 2006 criteria. Higher response-rates to rHEPO were related with both lower IPSS and particularly WPSS scores. Treatment was safe, and only 1 patient had to discontinue the treatment because of unmanageable side-effects. Among the 36 responders, 28 (77%) maintained the response after a median follow-up of 46 months. Our data indicate that standard doses of rHEPO are at least as effective as higher-doses for correcting anemia in lower-risk MDS patients; in this clinical scenario, this schedule allows for a consistent reduction of costs without precluding the achievement of a durable erythroid response., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Recently, new indices related to erythrocytes and platelet counts have been provided by hematological analysers. The purpose of the study is to investigate these new parameters in the elderly to define their normal values and to compare them with the range provided by the manufacturer., Experimental Design: a comparative study., Setting: general community, geriatric and internal medicine ambulatories., Patients: sixty healthy free-living elderly (cut-off: 65 years) and 66 healthy young-adults, as a control group., Measures: we measured the common and the new hematological parameters by H.1 Bayer technology. The new hematological parameters are red diameter width-RDW, hemoglobin distribution width-HDW, mean platelet volume-MPV, platelet diameter width-PDW, platelet hematocrit-Pct. We then compared the values of our population with the Bayer range., Results: The confidence interval width of the new indices define very faster limits than the Bayer range. Statistical differences were significant only in male groups: young-adults (Y) versus elderly (E) with higher values in Y than E in RBC p=0.002, in Platelet count p=0.050 and in MPV p=0.026; and higher values in E in MCV p=0.008, MCH p=0.006 and PDW p=0.004., Conclusions: In the literature a wide range of common hematological parameters are reported in the elderly, while the new hematological values have not been discussed till now. Our results may contribute to define the laboratory limits of the new hematological values in the healthy elderly.

Background: Recently blood reduced glutathione (GSH), an important cellular antioxidant, has been proposed as an indicator of health, particularly in the elderly. To date, a gold standard unit for the expression of GSH concentrations is not known. The aim of the study is to define the most sensitive laboratory expression of GSH., Experimental Design: a comparative study among some laboratory expressions of GSH., Setting: Geriatric and Internal Medicine Units; General Community., Patients and Participants: forty-eight inpatients from Geriatric and Internal Medicine Units and 82 healthy subjects recruited among medical students and residents, people from preventive medicine services and from local senior centres. EXCLUSION CRITERIA FOR HEALTHY SUBJECTS: use of drugs in the year prior to the study., Interventions: neither treatment nor interventions., Measures: the laboratory expression of GSH, compared in this study, were mg/dl, packed cell volume (PCV), mg/1010 RBC, mM/gHb., Results: We noted statistically significant differences only if GSH was calculated as mg/1010 RBC; higher values were found in healthy subjects than in inpatients, apart from age. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb. Instead, the ratio GSH mg/1010 RBC expresses the true GSH concentrations inside each erythrocyte. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb.

Background: Blood concentrations of copper, zinc and magnesium were determined in healthy elderly to assess whether aging interferes with mineral and micronutrient status., Experimental Design: case series., Setting: Internal Medicine and Geriatrics ambulatories in a University Hospital in Pisa, a city of Central Italy., Participants: 143 healthy outpatients of both sexes, who underwent a cardiological examination., Intervention: no treatment and intervention were performed., Measures: copper (Cu), zinc (Zn) and magnesium--both intraerythrocytic (iMg) and extracellular (eMg)--were measured., Results: The concentrations of Cu and eMg were found significantly higher in the elderly: Cu 117.5 +/- 17.0 micrograms/dl in the elderly vs 102.5 +/- 19.6 micrograms/dl in the younger (p < 0.001); eMg 1.8 +/- 0.2 in the elderly vs 1.7 +/- 0.2 mEq/l in the younger (p < 0.05). On the other hand, the levels of Zn and iMg did not differ in the two groups: Zn 113.3 +/- 14.9 micrograms/dl in the elderly vs 118.0 +/- 17.3 micrograms/dl in the younger, p = n.s.; iMg 4.3 +/- 0.4 mEq/l in the elderly vs 4.2 +/- 0.4 mEq/l in the younger, p = n.s. No correlation was found between age and single elements., Conclusions: These results suggest that the healthy free-living elderly have an adequate mineral intake. Nutrient supplements may by useful in the elderly with chronic diseases, comorbidities, and polypharmacy to prevent further age dysfunctions.

The authors report a 7 year follow-up of Takayasu's arteritis (TA) type III, group 1, in a young Italian woman. At diagnosis, at the age of 25, the echotomographic and angiographic studies showed narrow subclavian arteries, narrow abdominal aorta (diameter of 0.6-0.8 cm) below the renal arteries, stenotic left common carotid and renal arteries, and occluded upper mesenteric artery. With steroid therapy, (prednisone 50 mg/day per os), the erythrocyte sedimentation rate (ESR) normalized within 12 days. With a maintenance dosage of 7.5 mg/day per os, the patient achieved remission as documented by the absence of symptoms, the persistent normalization of ESR, and the improving of the diameter of the abdominal aorta (1.3-1.4 cm). On steroid therapy, the patient had a normal pregnancy and delivered a healthy baby girl. The disease has been stable for seven years. Recently, diabetes mellitus occurred and it has been treated with insulin therapy. The rising of ESR after tapering of steroid therapy (prednisone 5 mg per os on alternate days) suggests an alternative treatment with a cytotoxic agent.

A case of Congenital Hypopituitarism (CH) in an untreated 48 yr-old-man is reported. The hormonal studies demonstrated a panhypopituitarism and MR imaging revealed absence of pituitary stalk, small anterior pituitary remnant on the sella floor and ectopic neurohypophysis at the tuber cinereum. The pattern of hormonal responsiveness suggests that CH encompasses findings typical of primary anterior pituitary disease and those of hypothalamic dysfunction.

A case of Congenital Hypopituitarism (CH) in an untreated 48 yr-old-man is reported. The hormonal studies demonstrated a panhypopituitarism and MR imaging revealed absence of pituitary stalk, small anterior pituitary remnant on the sella floor and ectopic neurohypophysis at the tuber cinereum. The pattern of hormonal responsiveness suggests that CH encompasses findings typical of primary anterior pituitary disease and those of hypothalamic dysfunction.

The case of a 70 year-old woman with a chronic gastrointestinal blood loss due to a stromal tumor located in the middle third of the small intestine is reported. The peculiarities of the case are the characteristic immunohistochemistry of the neoplasm and, particularly, the mimetic clinical presentation, a kind of ''phantom tumor'' confirmed only with celiotomy and surgical excision.

The etiology of carotid abnormalities is both congenital than acquired. The aim of this study was to clarify the role of aging and atherosclerosis in the acquired cases, and the role of these abnormalities in hemodynamic alterations and neurologic symptoms. Over a 1-year period the authors studied all the subjects undergoing carotid examination by continuous-wave and color-coded Doppler sonography at an Angiology Unit. They evaluated neurologic symptoms; risk factors for atherosclerosis; number, sites, and kinds of carotid abnormalities; atherosclerotic lesions; stenosis; hemodynamic alterations of the carotid; and other localizations of atherosclerotic diseases. There were 469 subjects: 272 (58%) with abnormalities (group 1) and 197 (42%) without abnormalities (group 2). The total number of abnormalities was 479 (104 tortuosities, 262 kinkings, and 113 coilings). The abnormalities were more prevalent in the elderly (P<0.001) and in women (P<0.001). In group 1 they found significant prevalences of hyperlipemia (P<0.001), hypertension (P<0.01), chronic cigarette smoking (P<0.01), and ischemic heart disease (P<0.05). Carotid atherosclerotic lesions were more prevalent in group 1 than in group 2 (P<0.001); among the patients with atherosclerotic carotid lesions, those in group 1 were older than those in group 2 (P<0.001). Tortuosity seemed to be associated with fewer hemodynamic alterations. The authors conclude that atherosclerosis, hypertension, and aging may play an important role in producing carotid abnormalities. The aging seemed more important than atherosclerosis. Only a prospective study of patients with carotid abnormalities and no atherosclerotic lesion will clarify the role of hemodynamics and neurologic symptomatology.

Materials and Methods: Eighteen elderly patients (mean age 76.3 +/- 6.9 years) with fever of unknown origin (FUO) are studied sequentially and prospectively from January 1994 to December 1996. The classic Petersdori's criteria of FUO are no more valid for the elderly. The fever of more than 3-4 weeks duration is the only criterion to be considered, the fever is frequently under 38.5 degrees C and the elderly patient is often studied for more than 1 week outside the hospital., Results: The most frequent underlying conditions were: malignancies in particular haematological diseases, followed by multisystem diseases and infections, tuberculosis "in primis"., Conclusions: Selected investigations directed to the most frequent underlying conditions of FUO in the aged individuals overcome the financial cost and the patient discomfort of the tests since an identified curable disease can improve the life expectancy and quality.

Cardiac mixoma in the elderly. A clinical study. The clinical features of 13 cardiac myxomas surgically resected are presented. The mean age at presentation was 68 years. Ten were in the left atrium, 5 near the fossa ovalis, 3 at the base of the atrial septum, 1 at the inferior wall and 1 on the anterior leaflet of mitral valve, 3 were in the right atrium, 1 of these was accompanied with a myxoma at the apex of left ventricle. The ECG and the chest X-ray were normal in 9 and in 8 patients, respectively. In 3 patients, the diagnosis was occasionally made by routine 2-dimensional echocardiography. 5 patients presented with fever of unknown origin, arthralgias, weakness, weight loss. None had intracardiac or extracardiac recurrence in the 73 months follow-up. The presentation with constitutional symptoms only like fever of UO, may mimic collagen and neoplastic diseases, vasculitis, lymphomas: the 2-dimensional echocardiography is mandatory to esclude a cardiac myxoma in the elderly.

We studied the hypothalamic-pituitary-thyroid function in two groups of healthy elderly subjects: group A (n = 23, age range 65-80 years), and group B (n = 11, age range 81-92 years), and in 32 controls, aged 20-60. A TRH test for TSH and prolactin was performed in all subjects, while the TSH circadian modulation was evaluated in elderly subjects only. Group B showed significantly lower fT3 and TSH, and higher fT4 levels with respect to controls (fT3: 4.4 +/- 0.2 vs. 5.2 +/- 0.2 pmol/l, p < 0.05; fT4: 13.1 +/- 0.9 vs. 11.4 +/- 0.4 pmol/l, p < 0.05; TSH: 1.07 +/- 0.21 vs. 1.46 +/- 0.13 mIU/l, p < 0.05). Morning TSH showed an inverse correlation with age (r = -0.42; p < 0.02) among the 34 elderly subjects, but not among controls. Evidence for TSH circadian modulation was found only in group A (nighttime TSH: 1.60 +/- 0.17, vs. daytime: 1.25 +/- 0.13 mIU/l, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 +/- 0.64 mIU/l, p = 0.01; B: 5.02 +/- 0.58 mIU/l, p < 0.01). The maximal PRL response was also blunted (A: 25.7 +/- 2.6 micrograms/l, B: 27.7 +/- 5.2 micrograms/l, p < 0.0005). In conclusion, a resetting of the pituitary threshold of the TSH feedback suppression, along with complex alterations in peripheral thyroid hormone levels, may progressively develop in older people, becoming apparent only with extreme senescence. Moreover, the TSH nocturnal surge may be lost with increasing age, thus providing evidence also for hypothalamic dysfunction.

Aim of Study: To evaluate the efficacy of 5-aminosalicylic acid (5-ASA) in preventing recurrences of Crohn's disease., Patients and Methods: Between January 1988 and December 1989 a total of 60 patients (37 men, 23 women, mean age 34.8 years) were selected in whom the diagnosis of Crohn's disease had been known for at least 2 years. A further criterion for inclusion was remission for at least one year in patients who had been operated or for one month in the nonoperated ones. Furthermore, the latter must have had at least one recurrence during the last year. They were in turn assigned to be treated with 5-ASA (2.4 g daily by mouth) or not treated (control). The activity and localization of Crohn's disease were defined according to the "Crohn's disease activity index" (CDAI) and the "laboratory index" (LI), as well as by endoscopy and (or) radiology. The patients were examined every 6 months for 4 years. A recurrence was diagnosed if the CDAI was more than 150 or had increased to at least 60 points above the initial value and the LI was above 100., Results: 29 recurrences were noted, 72.4% within the first 2 years. 15 recurrences (46.9%) were in the treated patients and 14 (58.3%) among the untreated controls. The Kaplan-Meier curve (statistical comparison of the probability of recurrence) showed no significant difference between the two groups (P = 0.23): the recurrence rate was the same in the two groups, among the patients with or without previous operation and for different primary localizations. There were no notable side effects., Conclusion: Treatment with 5-ASA was not found to influence the likelihood of recurrence. Age, duration of the disease, primary localization and previous operation were not prognostic factors.

Chronic exposure to asbestos can induce malignant peritoneal mesothelioma (PMM) without pulmonary or pleural involvement (PIMM). The localization to the peritoneum depends on the different susceptibility of the two mesotheliums and, perhaps, on the length of asbestos fibers which can facilitate their direct translocation.

Aging is a multifactorial process still incompletely known. The role of oxidative damage to cell membranes, as an important phase of the process, is underlined by the recent literature. We emphasize the value of vitamin E as an antioxidant agent supplied by suitable diets in middle age and by cheap tablets in the aged.

Objective: To evaluate the causes of non-pathologic traumatic fractures in the elderly and their consequences on quality of life., Design: A prospective trial., Follow-Up: 12 months for the inpatients and 3 months for the outpatients., Setting: Basal assessment in orthopaedic hospital; follow-up in geriatric unit., Patients: Both inpatients and outpatients, 65 years and over, both sexes, both living in a nursing home and in their own home, admitted to an orthopaedic hospital because of a fall, with diagnosis of a subsequent fracture. Criteria of exclusion: patients with pathologic fracture. 121 patients were enrolled, 108 had a complete follow-up., Surveys: Health and functional status prior to the fracture, causes and concomitant causes of the fall, site of the fracture, complications and functional disabilities., Results: The most frequent cause of fracture is an accidental fall, especially in younger elderly, other causes being acute cardiovascular and neurological diseases. Fractures occur more frequently in females. The most serious injuries affect frailer subjects, with advanced age, neurologic and multiple chronic diseases. Fracture of femur is the most frequent fracture and it has the highest risk complications, functional disabilities and death., Conclusions: Because of the high frequency of accidental falls, the authors emphasize the necessity of primary prevention, especially the removal of architectural barriers both at home and in public environment.

Normal aging does not induce impotence, but only modifies the physiology of the erection which, however, allows good sexual intercourse. Impotence, found in 55.0% of the over 75 men, is due to organic or psychogenic causes: above all, penile arterial insufficiency and the collateral effects of drugs for the diseases which often affect the elderly, are the main factors.

Aim of this study was to evaluate the aging of aorta with respect to atherosclerotic modifications: abdominal aorta echotomography is the preferred approach for this study. In 354 elderly patients, 65 and over, we have evaluated the diameter and the course of the aorta, the presence of atherosclerotic plaques in the aorta and iliac vessels, and the presence of aneurysms. Two kinds of findings could be identified by echotomography: age-related physiologic modifications, represented essentially by an increase of the aortic diameter; pathologic changes, characteristic for atherosclerosis, of which aneurysms are the most dangerous complications.

The authors describe a case of Takayasu's arteritis in a twenty-five-year-old Italian woman, characterized by nonspecific symptoms (weakness, arthralgias, fever) and elevated erythrocyte sedimentation rate early onset of these symptoms at the age of about twenty-three years early diagnosis, only eighteen months after the onset of symptomatology absence of progression of the disease under corticosteroid therapy with a follow-up of three years uneventful pregnancy ending in cesarean section and birth of a baby without maternal and neonatal complications.

Objective: To compare efficacy and tolerance of recombinant interferon alfa-2b in the treatment of anti-HCV-positive chronic active hepatitis (CAH) in subjects aged 65 years and above with those less than 65., Design: A randomized controlled trial., Setting: Outpatients in two hospitals., Patients: 65 consecutive outpatients with anti-HCV-positive CAH for 1 to 30 years, having basal aminotransferase levels at least twice the normal value. Those 65 and over were randomized to an interferon group (A, n = 22) or a no-treatment group (B, n = 22). All those under 65 received interferon (group C, n = 21)., Intervention: Interferon at a dose of 3 mU 3 times a week for a 6-month period. A normalization of serum aminotransferase levels was considered a positive response to therapy., Results: Response to therapy was positive in 62% of the treated elderly compared to 57% of the adults (P = 0.85). The two groups of responders showed a common highly significant reduction of aminotransferase (P < 0.001). Side effects were similar in elderly and young. Two untreated elderly showed spontaneous normalization of aminotransferase., Conclusion: Interferon in anti-HCV-positive CAH is useful in the elderly, allowing normalization of aminotransferase, improvement of the histology and remission of the disease in 62% of the cases. Side effects seem to be independent of age. Further studies are required to assess both duration of remission and usefulness of cyclic therapy in previous responders.

This is the case report of a forty-seven-year-old man with an ostium secundum atrial septal defect and a very high grade of pulmonary hypertension, associated with a large bilateral perinephric fluid accumulation. The fluid accumulation was remarkably reduced after eleven phlebotomies over a twelve-month period. A pathogenetic relation with the Eisenmenger's syndrome is discussed. No previous report of this association has been found in a survey of the literature.

Ten elderly patients with heart failure and frequent hospital readmission within 12 months before the study, were submitted to clinical radiologic, electrocardiographic and echocardiographic evaluation in order to find the causes of readmission. The most frequent factors were found to be non compliance with drug prescriptions and therapy inadequate for the etiology of the heart failure and the kind of cardiac dysfunction.

We report the natural history, the clinical, radiological, echocardiographic and hemodynamic pattern of a living sixty-three year old man with tetralogy of Fallot and cyanosis since birth. We discuss the possible circulatory adaptations which allowed exceptional survival up to the seventh decade: it is the sixth case reported in the literature.

There are several states of reversible dementias. Among these, electrolyte imbalance--especially hyponatremia--can determine transitory modification of cognitive functions. The purpose of this study is the evaluation of the relationship between cognitive disorders and serum sodium concentrations in the elderly. In a sample of 70 elderly people, the Authors reported a prevalence of hyponatremia in 28 patients (40%); only 4 (5.7% of total population) had impaired cognitive functions or mood disturbances. In the symptomatic patients hyponatremia was severe and had a fast onset; the symptoms disappeared by means a proper and ready treatment. This observation stresses out the importance of routine serum sodium determination in the elderly in coincidence with the sudden onset of a pattern of dementia.

Of 533 patients over 65 years old (153 males and 380 females), admitted to geriatric units for various medical diseases, 111 (20.8%) were anemic. Among males the prevalence of anemia was 30.1%, among females 17.1%. Three principal causes of anemia were revealed. The most frequent (42.3%) was microcytic, hypochromic anemia, with low levels of serum iron concentrations, related to gastrointestinal diseases (with chronic occult blood loss). 38.7% of anemic elderly people was affected by chronic diseases. In 19.0% a folate (16 case) and iron (5 cases) deficiency was revealed. These results suggest that anemia in the elderly is always pathological; hemoglobin values lower than 12 g/dl should be considered abnormal and investigated.

The authors describe a case of venous thrombosis of the legs, complicated by pulmonary embolism, in a 71 year-old man, following desmopressin therapy for hypothalamic diabetes insipidus. They suggest a role of desmopressin in stimulating the release of Von Willebrand's factor (VWF) from endothelial cells. VWF facilitates platelet adhesion by forming a bridge between platelet membrane and vascular subendothelium, followed by development of a large thrombus.

A 44 year old woman with upper limb skeletal malformations and endocardial cushion defect is described. This congenital heart disease was rarely reported in association with Holt-Oram syndrome.

In recent years, epidemiological and clinical patterns in infective endocarditis are changed: mean age of patients, sex, underlying cardiac diseases, source of bacteremia, availability of better diagnostic methods--specially two-dimensional and doppler echocardiography--and surgical options. The Authors report a paradigmatic case of a young man without cardiac disease, who developed a destructive endocarditis complicated by refractory congestive heart failure; the cause was an organism of low pathogenicity, Streptococcus sanguis, that entered the bloodstream after gastroduodenoscopy.

High total serum cholesterol and low HDL levels are major risk factors for cardiovascular disease before the age of 65. Currently in older populations their role has not yet been defined. In the elderly a low-cholesterol diet is therefore preferable to pharmacological treatment, in view of the absence of collateral effects. In this study 40 elderly patients with hypercholesterolemia were divided at random into two groups. They were respectively fed their usual diet and a legume-supplemented normal caloric diet for 8 weeks. Total serum cholesterol levels significantly decreased in the latter group from the 2nd week onward.

In dystrophia myotonica clinical evidence of cardiac involvement usually appears several years after the onset of neuromuscular symptoms. In more than 90% of cases there is damage to the specialized cardiac tissues and in about 7% of cases there are alterations to the myocardium. We report a case characterized by early and spread deterioration of the pump function developing into refractory congestive heart failure. The contemporary involvement of the smooth muscle of gallbladder and colon confirms the hypothesis that dystrophia myotonica is a pan-muscle disease.

Triiodothyronine (T3) kinetic studies were carried out using 126I-T3 and the single injection technique in eight clinically euthyroid patients with autonomous thyroid nodules and the metabolic results were compared to those obtained in a group of 12 healthy control subjects. Plasma labeled T3 concentration was measured by a chromatographic method based on the extraction of the hormone on Sephadex G-25 columns, followed by its elution with a specific anti-T3 antiserum. The analysis of the experimental plasma disappearance curves of the labeled hormone was performed using the noncompartmental method. The results obtained showed a significantly increased metabolic clearance rate of T3 in the patients with autonomous thyroid nodules, as compared to the control group. On the average, the T3 production rates were increased more significantly than the corresponding circulating levels of the hormone, therefore, suggesting that the significant TSH inhibition observed in the euthyroid patients with autonomous thyroid nodules could be related with an increased peripheral utilization of triiodothyronine.

In 40 subjects, 15 mean age 70.7 +/- 5.6 with systolic-diastolic hypertension, 15 mean age 75.5 +/- 6.8 years with systolic hypertension and 10 mean age 73.6 +/- 5.1 normotensive control group we have analyzed with M-mode 2D echocardiography and echophonocardiography the following parameters: diastolic--EDD--and systolic diameter--SD--of left ventricle, diastolic thickness of septum--SSD--and posterior wall--SPPD--of left ventricle, left ventricular ejection fraction--EF--(Theicholtr. formula), radius posterior wall thickness--R/SPPD--, left ventricular mass--LVM--(Devereux' formula), and systolic time intervals (Q-A2, LVET, PEP and PEP/LVET). The differences between groups are: systolic-diastolic hypertensive patients have increased EDD, SPPD and LVM, reduction of EF and increased PEP/LVET ratio in comparison with B and C groups; systolic hypertension doesn't increase EDD; SSD and PEP/LVET increase, while the EF remains within normal limits. In the healthy aged subjects SSD, SPPD and LVM are normal.

Approximately one year after the onset of chronic myeloid leukemia, a 66-year-old patient had multiple recurrent blast crises with the morphological, cytochemical, and immunological features of lymphoblasts. The lymphoblastic eruptions proved always highly sensitive to small doses of vincristine only (1.5 mg), which at variable intervals, of at first 3 months and later 20 days, brought about the immediate disappearance of blast cells from the peripheral circulation as well as from bone marrow blood. Some variable clinical aspects of the case during the crises are described; the crises recurred until the patient's sudden death due to cardiac causes.

Serum concentrations of TSH, TT4, TT3 and rT3 were monitored for one month after excision of ten autonomous thyroid adenomas which had suppressed TSH secretion. Basal serum TSH levels start to increase between 30 hr and 20 days after surgery reaching normal and steady levels by the 24 day. Serum TT3 concentrations rapidly decrease in the first 20 hr to values near the lower limit of the normal range. Thereafter TT3 levels change little until pituitary TSH secretion recovers. Serum TT4 levels also fall, but much more slowly than TT3. Rising TSH levels stimulate residual extranodular thyroid tissue secretion of both TT3 and TT4. However, serum TT3 levels rise more rapidly than TT4 levels. Preoperative serum concentrations of both TT4 and TT3 are related directly to the time required until the beginning of the postoperative rise in TSH levels, and inversely with the maximal postoperative serum TSH concentration achieved. Throughout the study period, for all patients, serum TSH concentrations were inversely related to serum TT4 concentrations. These data suggest that, although the time required until the onset of recovery of TSH secretion is directly related to preoperative levels of TT4 and TT3, the regulation of postoperative TSH levels is dependent upon serum TT4 levels. Also, the serum TT3 levels constant at the lower limit of the normal range before recovery of TSH secretion, and the preferential rise in serum TT3 concentrations associated with rising TSH secretion, may prevent or abbreviate temporary postoperative hypothyroidism.

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.