Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis.

In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma.

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.

hMENA(11a) contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells.

Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients is indicative of a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA(11a) and hMENAΔv6 with opposite functions. A novel role for the epithelial-associated hMENA(11a) isoform in sustaining HER3 activation and pro-survival pathways in HER2-overexpressing breast cancer cells has been identified by reverse phase protein array and validated in vivo in a series of breast cancer tissues. As HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA(11a) is involved in these resistance mechanisms. The specific hMENA(11a) depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors, whereas PI3K inhibitors activated hMENA(11a) phosphorylation and affected its localization. At the functional level, we found that hMENA(11a) sustains cell proliferation and survival in response to PI3K inhibitor treatment, whereas hMENA(11a) silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultures, hMENA(11a) contributes to resistance to PI3K inhibition because its depletion drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that hMENA(11a) in HER2-overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA(11a) expression can be proposed as a marker of HER3 activation and resistance to PI3K inhibition therapies, to select patients who may benefit from these combined targeted treatments. hMENA(11a) activity could represent a new target for antiproliferative therapies in breast cancer.

Soft tissue depression at the iliac crest prominence: a new landmark for identifying the L4-L5 interspace.

BACKGROUND: One of the most common approaches to identifying the L4-L5 interspace is using the iliac crest as a landmark. We propose a new landmark to identify the L4-L5 interspace based on the soft tissue depression palpable at the iliac crest prominence. The aim of this study was to assess the reliability and time saving when using this new landmark compared to using the iliac crest to perform a lumbar plexus block. METHODS: Fifty-four patients scheduled for lower limb surgery were randomly allocated to have a lumbar plexus block performed using the iliac crest (Chayen's approach) or the soft tissue depression (Borghi's approach). The landmarks for both approaches were drawn on each patient prior to randomization (N.=27 per group). All the blocks were performed by an anesthesiologist familiar with both techniques using a nerve stimulator and 30 mL of 0.5% levobupivacaine. The time to achieve successful needle placement and the number of needle re-directions, as well as the onset time for the sensory and motor blockade, were recorded. RESULTS: All the blocks using Borghi's approach were performed successfully. With the Chayen's approach, there were 5 needle placement failures. The mean times to onset of a successful block after injection of the local anesthetic did not differ between the two groups: 17.8±3.9 min for the Chayen vs. 15.9±2.4 min for the Borghi's approach (P=0.14). However, the mean time to achieve correct needle placement was 7.6±3.2 min with the Chayen's approach compared to 5.1 (±2.6 SD) min with the Borghi's approach (P<0.01). The Chayen's approach also required a significantly higher median number of needle redirections (2 [inter-quartile range (IQR): 0-4] vs. 0 [IQR: 0-4], P<0.01). In obese patients (BMI ≥30 kg/m(2)), the mean placement time was 10.5±1.7 min vs. 4.8±2.1 min (P<0.01), and median number of needle re-directions was 2.5 (IQR: 2-3) vs. 0.5 (IQR: 0-3) (P=0.04), with the Chayen and Borghi's approach, respectively. CONCLUSION: Use of the palpable soft tissue depression at the iliac crest prominence for performing a lumbar plexus block offered several potential advantages over the standard inter-iliac crest approach.

[Stress in auto-transportation sector between prejudice and reality]. / Stress nel settore autotrasporti tra pregiudizio e realtà.

Every year in the EU about 800 drivers die in road accidents. In Italy the average is around 200 deaths per year. Based on this context the Occupational Medicine Department (OMD) of Bergamo Hospital has sponsored a new project dedicated to the healthcare and safety of all employees of road haulage in the province of Bergamo. Furthermore the collaboration between UMD and the Clinical Psychology Department of the hospital has allowed the fulfillment of another project aiming to evaluate the personality profile of around 80 drivers employed in the road haulage sector". The aims of the projects is to identify and to point out dangerous situations of significant psychological vulnerability; to know the current situation and to discriminate stress factors from protective ones; to make companies more aware of prevention activities; to inform the drivers about their companies' policy in order to grant safety in their job. The psychological tools used were: half open interview and Personality Inventory MMPI2. The population was selected randomly from volunteers. Now we know the results in 33 tested drivers. So far seven cases have been classified as psychological vulnerable and stress and protective factors have been identified. Results underline the relevance of an integrated approach able to take care of the employees and involving the companies in the prevention programs.

Stiff person syndrome and motor mononeuropathy with conduction block: a singular association.

The "Stiff person syndrome"(SPS) is a rare dysimmune chronic neurological disorder, sometimes paraneoplastic, characterized by progressive stiffness, painful persistent or spasmodic muscle contractions, mostly involving spine and lower extremities. In 60 to 90 percent of cases, non-paraneoplastic forms are associated to the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies in the cerebrospinal fluid and in the serum, while anti-amphiphysin antibodies are frequently associated to paraneoplastic types. The relevant treatment consists of three basic approaches: increase in the inhibitory processes in charge of muscle activity control, re-modulation of the immune response, removal of any associated neoplasia. Indications regarding the efficacy of high-dose intravenous immunoglobulin (IVIG) also in this dysimmune pathology are on the increase. We described an unusual case of autoimmune SPS associated with an exclusively motor left peroneal nerve neuropathy, with conduction block, treated with high-dose intravenous immunoglobulin (IVIG), oral cyclosporine, sodium valproate, baclofen and diazepam.

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study.

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.

[Exercise-induced left arm pain and thrombocytosis]. / Belastungsinduzierte Schmerzen im linken Arm und erhöhte Thrombozytenzahl.

We describe the case of a 45-year-old male smoker who presented with an acute anterior wall myocardial infarction and a platelet count on admission of 1030000/mm3. Emergent coronary angiography revealead left anterior wall akinesia caused by a spontaneously resolved thrombosis of the left anterior descending artery with residual stenosis. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was uneventful. He was diagnosed with essential thrombocythemia based on the findings of marked thrombocytosis of 1,030,000/mm3, splenomegaly and numerous clumping giant megakaryocytes on bone marrow biopsy. In addition to standard therapy with aspirin, heparin, betablocking agent, ACE-inhibitor and statine he received additional anti-platelet therapy with Clopidogrel. Cytoreductive therapy was not necessary.

Acroparesthesia and acral arterial occlusions as first manifestations of essential thrombocythemia.

Thrombocytosis is either caused by a reactive process (secondary thrombocytosis) or by a clonal bone marrow disorder The latter category includes essential thrombocythemia with bleedings and thrombotic complications as major causes of illness and death in this patients. We describe a 43-year-old man with a 6 months history of acroparesthesia in his toes. Half a year after onset of these symptoms, he noticed a bluish discoloration of digit V of his left foot. On first presentation physical examination revealed a bluish discoloration of all toes and a cold and blue digit V of the left foot. Peripheral pulses were all palpable, normal ankle systolic pressure measurements and normal pulse volume recordings except for digit V of the left foot were found. Laboratory tests revealed thrombocytosis of 800000/microliter. On treatment with acetylsalicylacid, prostanoids intravenously and low molecular weight heparin, the patient became asymptomatic and pulse volume recording of digit V was normalized. After exclusion of cardial or vascular sources of embolism by utrasonography bone marrow aspirate and biopsy supported the diagnosis of essential thrombocythemia.

Cancer precursor lesions in intact stomach Helicobacter pylori gastritis and in resected stomach gastritis.

Hemigastrectomy for benign disease and Helicobacter pylori infection are risk conditions for the development of gastric cancer. Aim of the study was to compare gastric histology and precursor lesions of malignancy in these two conditions. The hemigastrectomy group included 351 consecutively endoscoped subjects operated for gastroduodenal benign disease. Six to ten biopsy specimens were routinely taken from the residual gastric mucosa. The intact stomach group included 2097 consecutively endoscoped symptomatic subjects, who did not receive eradication therapy against H. pylori. The histological findings were classified as normal mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization. The age over fifty was a significant risk factor for the occurrence of IM (OR 2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or = 0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or = 0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P < or = 0.001). Both in males and females the risk for CNAG was significantly higher in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000). Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82, P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp-positive individuals evidenced a significant risk for metaplastic mucosal changes (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those with a longer postoperative follow up endoscopy presented an increased risk for CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000). CNAG and IM were the most frequently observed mucosal lesions both in subjects operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and 3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H. pylori infection may induce an increased incidence for histological precursor lesions for gastric malignancy and suggest that carcinogenesis in a resected stomach may be different from that in the intact stomach.

Functional changes of human quadriceps muscle injured by eccentric exercise.

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5 /s; range of motion from 40 to 110 of knee flexion). The isometric torque of the quadriceps (knee at 90 flexion) decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63%) and VMO (66%) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.

Functional changes of human quadriceps muscle injured by eccentric exercise

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5º/s; range of motion from 40º to 110º of knee flexion). The isometric torque of the quadriceps (knee at 90º flexion) decreased 52 percent immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63 percent) and VMO (66 percent) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3 percent (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109 percent on the 2nd day and were still increased by 32 percent on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals

Case control study on health-related quality of life in adult coeliac disease.

AIMS: To evaluate whether health-related quality of life in adult coeliac disease is related to: 1) adhesion to gluten-free diet; 2) manifestation of clinical features; and 3) associated diseases. PATIENTS AND METHODS: A total of 68 coeliac patients (54 female and 14 male) aged between 18 and 74 years, on gluten-free diet for at least two years were studied. The subjective health status was measured by means of the Short Form 36 Health Survey. A series of 136 subjects, matched according to sex, age and ethnic group, were evaluated as control group. RESULTS: Patients obtained worse scores with respect to healthy controls at all domains of Short Form 36 Health Survey (p<0.05); compliers showed better results than non-compliers. The lowest scores were obtained in patients with more than six symptoms, mostly in non-compliers, the highest in compliers with less than six symptoms. Patients with two or more associated diseases presented significantly worse scores than patients with only one associated disease. CONCLUSIONS: The importance of gluten-free diet in clinical management of coeliac disease is confirmed by results of the present study; moreover, the results seem to indicate that a complex interplay of factors should be taken into account in evaluating health-related quality of life in adult coeliac disease. Accordingly, our data show that health-related quality of life of coeliac patients is impaired not only by poor compliance but also by different negative factors such as severity of illness (in terms of number of symptoms) at diagnosis and comorbidity.

Modulation of lipid metabolism and vitamin A by conjugated linoleic acid.

The term conjugated linoleic acid (CLA) refers to a collection of positional and geometrical isomers of octadeca- dienoic acid with conjugated double bonds. CLA has been shown to possess several beneficial activities in different experimental models, however, out of 28 isomers only two, c9, t11 and t10, c12 have been thus far demonstrated to be biologically active. The discovery that it can be elongated and desaturated as a regular fatty acid in human and animal tissues brought a new possibility that its activity may be related to its properties as a peculiar unsaturated fatty acid. In fact, CLA is able to be incorporated in lipid classes as oleic acid, accumulating in those tissues rich in neutral lipids; to be metabolized as linoleic acid and so influencing linoleic acid desaturation and elongation; and to be beta oxidized in peroxisomes which may account for, through activation of PPARs, its ability to increase free retinol levels and influence gene expression. These activities are amplified where CLA accumulates more such as mammary and adipose tissues and may explain its peculiar beneficial properties, at relative low dietary concentrations, in these tissues. Furthermore, it has been demonstrated that CLA can be endogenously formed by delta 9 desaturation of vaccenic acid (t11 18:1) thus forming the isomer c9, t11. Either endogenously formed or through dietary intake, CLA showed to be metabolized in the same way and to exert the same biological properties. We may conclude that a regular intake of CLA, or/and vaccenic acid as its precursor, should work as an excellent preventive agent by modulating lipid metabolism in target tissues thus conferring protection against the attack of insults of different type.

Co-occurrence of psoriatic arthritis with collagenous colitis: clinicopathologic findings of a case.

A 58-year-old man developed psoriatic arthritis and, after 6 months, persistent watery diarrhoea. Biopsies from the colorectal mucosa showed thickened subepithelial collagen consistent with collagenous colitis. There also was an inflammatory cell infiltration (mainly lymphocytes and monocytes) in the chorion. These findings and the parallel course of articular and bowel complaints suggest a clinicopathologic correlation between arthritis and colic involvement.

Isolation and characterisation of the ylmE homologue of Thermus thermophilus.

Screening of a Thermus thermophilus genomic library led to the identification of a homologue of the ylmE gene. ylmE is highly conserved in widely divergent organisms from prokaryotes to mammals, suggesting an important, albeit currently unknown, cellular function. The 633 bp gene has a GC content of 69.2% overall and 90% in the third nucleotide position, while the gene product is predicted to be a soluble cytoplasmic protein of 23,441 Da. It belongs to a family of conserved proteins of unknown function and exhibits amino acid identities ranging from 45% to 28% to the Aquifex aeolicus and Saccharomyces cerevisiae family members, respectively. We speculate that the gene product may be involved in a cellular stress response in T. thermophilus.

[Predictive variables of mortality in elderly patients after hospitalization. Significance of multidimensional evaluation]. / Variabili predittive di mortalità negli anziani dopo il ricovero ospedaliero. L'importanza della valutazione multidimensionale.

Functional status evaluation in the elderly is stronger predictor of hospital outcomes than type and number of pathology. Multidimensional and functional assessment among hospitalized elderly allows to identify, as well as acute and chronic illness, disabilities of sanitary problems and socio-economical aspects that in the elderly can complicate illness. Our study has identified six-month mortality post hospitalization of 20.2%. The high mortality observed in our follow-up agrees with the literature and it is a marker of considerable frailty among elderly patients. The independent predictor variables of six month post hospital mortality in the study were: male gender, dependence DMI score, low serum albumin (2.8 g/dl), impaired IADL score, cancer illness and APACHE score < 13.7. These measures represent distinct domains: demographic, functional and clinical. Identifying predictors of high-risk patients is an important way in accurate targeting.

Cloning and characterisation of the Hint homologue of the thermophile Thermus thermophilus.

Screening of a genomic library of the thermophile Thermus thermophilus revealed a novel thermophilic hint gene, homologues of which are highly conserved in genera from archaea to mammals. Hint belongs to the HIT protein super-family, which contains two broad groups, Fhit, associated with tumour suppression in eukaryotes and Hint with putatitively protein kinase C inhibitory activity. In T. thermophilus the 321 bp gene has a GC content of 67% overall and 94.4% in the third nucleotide position, with unusually no thymine as a wobble base. The gene product, a small highly conserved 11,996 Da predicted soluble cytoplasmic protein, offers an ideal opportunity to investigate thermostabilising amino acid substitutions. Here we report on the characterisation of the novel hint sequence.

Correlation between a psychometric test and biochemical indices of hepatic encephalopathy in alcoholics.

BACKGROUND/AIMS: In alcohol abusers an alteration of responses to psychometric tests has been reported, even when clinical symptoms of hepatic encephalopathy (HE) are absent. Our research was intended to individualize a simple psychometric test, easy enough to be performed also at the patient's home, able to reveal an impending encephalopathy and, consequently, to facilitate earlier treatment. METHODOLOGY: Twenty-six consecutive male alcoholics were engaged and, after informed consent, the following schedule was applied: administration of a psychometric test, followed by a drawing of blood for the determination of many blood parameters. After 15 days of treatment to detoxicate patients, psychometric tests and blood examinations were repeated. RESULTS: The results confirmed that common blood examinations are not useful to monitor brain damage in chronic alcoholism, that a psychometric test is able to demonstrate a therapeutic improvement and that a positive and significant correlation has been observed between BBCA/AAA ratio and WAIS Score. CONCLUSIONS: These preliminary results suggest that it is possible to suspect dangerous biochemical changes by means of a simple psychometric test.

[Polypharmacy in the ambulatory care of aged patients]. / La politerapia nella pratica ambulatoriale del paziente anziano.

The aim of this study was to assess the prevalence and possible predictors of polypharmacy in a sample of the general population. The sample consisted of 638 subjects (267 males, mean age 54.7, and 371 females, mean age 55) taken from the records of three general practitioners in the city of Turin, Italy. The prevalence of polypharmacy, for prescription drugs, was 12.5% (80 subjects). The prevalence of polypharmacy, for non prescription drugs, was 17.4% (111 subjects). The number of prescription drugs per patient rises progressively with age, averaging 2.28 and 2.5 respectively in males and in female aged older than 80 years. The number of non prescription drugs was observed to decrease with age: in women, subjects that used two or more non prescription drugs were 35% in those aged under 50 years, 20% in subjects aged from 65 to 80 years and 12.5% in those aged older than 80 years. Subjects aged older than 65 years, an IADL score < 10, more than 20 physical exams performed by practitioner in the last year, a recent hospitalisation, presence of cardiovascular disease, and presence of genito-urinary disease, were significantly and independently associated to polypharmacy for prescription drugs. Only female sex was significantly associated to polypharmacy for non prescription drugs. Our conclusion is that although age should not be involved in polypharmacy as a variable, several phenomena that influence medical treatment goals become more prevalent with increasing age and explain the high drugs consumption in the elderly. A rational, essential therapy, helped by guidelines could reduce potential problems associated with polypharmacy in the elderly.