Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke.

BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.

Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture' ?

BACKGROUND: Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. METHODS: A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). RESULTS: A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). CONCLUSION: Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure.

Profiling cancer risk in oral potentially malignant disorders-A patient cohort study.

BACKGROUND: Oral potentially malignant disorders harbour variable and unpredictable risk for squamous carcinoma development. Whilst current management strategies utilise histopathological diagnoses, dysplasia grading and targeted intervention for "high-risk" lesions, clinicians are unable to predict malignant potential. METHODS: Detailed, retrospective clinico-pathological analysis of potentially malignant lesions undergoing malignant transformation, from a 590 patient cohort treated by interventional laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was documented at study census date (31 December 2014). RESULTS: A total of 99 patients (16.8%) developed cancer: 71 (12%) seen "unexpectedly" upon excision and 28 (4.8%) progressing to malignancy at a median of 87.3 months post-surgery. Thirty "unexpected" excisions were micro-invasive (42.3%) arising primarily in severely dysplastic precursors (75%) at ventro-lateral tongue and floor of mouth sites (54.5%); 1 patient (1.4%) had a cancer-related death, whilst 58 (81.7%) were disease free. A total of 19 of 28 "progressive" cancers (67.9%) arose at new sites, with erythroleukoplakia a significant predictor of malignancy (P = .0019). Nine (32.1%) developed at the same precursor site, with 6 (77.7%) on the ventro-lateral tongue and floor of mouth. Three (10.7%) were micro-invasive, 9 patients (32.1%) died from metastatic disease and 12 (42.9%) were disease free (P < .001). CONCLUSION: Squamous carcinoma may arise at the site of a precursor lesion as transformation or new-site development via field cancerisation. Whilst interventional surgery facilitates early diagnosis and treatment of occult disease, thus reducing risk from same-site transformation, new-site cancer is a significant long-term risk for patients with potentially malignant disorder.

Efficacy of oral brush biopsy in potentially malignant disorder management.

BACKGROUND: Oral potentially malignant disorders (PMD) harbour unpredictable risk for squamous cell carcinoma development. Current management requires tissue biopsy for histopathology characterisation, dysplasia grading and targeted intervention to "high-risk" lesions, although evidence-based guidelines are limited and diagnoses subjective. This study investigated the use of adjunctive oral brush biopsy techniques during the management of PMD in a UK hospital population. METHODS: Retrospective review of a 310 PMD patient cohort presenting to Maxillofacial Surgery in Newcastle upon Tyne with new, single-site lesions between December 2009 and May 2014. Patients underwent Orcellex® brush biopsy and liquid-based cytology examination in addition to conventional biopsy techniques, with management proceeding along established care pathways. Patient demographics, cytology data, most significant histopathology diagnoses and clinical outcome were all documented at the study census date (31.12.15). RESULTS: A total of 170 male & 140 female patients (age range 18-91 years), exhibiting primarily leukoplakia (86.5%) at floor of mouth and ventrolateral tongue sites (44.9%), were identified. Management comprised: observation (49.7%), laser surgery (44.9%), antifungal treatment (3.5%) and Head & Neck clinic referral following cancer diagnosis (1.9%). Clinical outcomes were as follows: disease free (51.3%), persistent PMD (42.3%) and malignant transformation (6.4%). Histology and cytology diagnoses strongly correlated (r = .305). Treatment modality, lesion site, histology and cytology diagnoses were the best predictors of clinical outcome. CONCLUSIONS: Orcellex® brush cytology provides reliable diagnoses consistent with conventional histopathology and offers less invasive, adjunctive assessment appropriate for long-term monitoring of patients in specialist clinics.

Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water.

The blending together of synthetic chemistry with natural product biosynthesis represents a potentially powerful approach to synthesis; to enable this, further synthetic tools and methodologies are needed. To this end, we have explored the first Sonogashira cross-coupling to halotryptophans in water. Broad reaction scope is demonstrated and we have explored the limits of the scope of the reaction. We have demonstrated this methodology to work excellently in the modification of model tripeptides. Furthermore, through precursor directed biosynthesis, we have generated for the first time a new to nature brominated natural product bromo-cystargamide, and demonstrated the applicability of our reaction conditions to modify this novel metabolite.

Effects of dietary concentration of wet distillers grains on performance by newly received beef cattle, in vitro gas production and volatile fatty acid concentrations, and in vitro dry matter disappearance.

Three studies were designed to evaluate effects of wet distillers grains with solubles (WDGS) on health and performance of newly received beef cattle, in vitro gas production, molar proportions and total concentrations of VFA, and IVDMD. In Exp. 1 and 2, 219 (BW = 209 kg, SE = 2.2 kg; Exp. 1) and 200 beef steers (BW = 186 kg, SE = 3.2 kg; Exp. 2) were used in randomized complete block design receiving studies. The 4 dietary treatments (DM basis) were a 65% concentrate, steam-flaked corn (SFC)-based receiving diet without WDGS (CON) or diets that contained 12.5, 25.0, or 37.5% WDGS. There were no differences among the 4 receiving diets in BW (P ≥ 0.61), ADG (P ≥ 0.75), DMI (P ≥ 0.27), and G:F (P ≥ 0.35), or in the proportion of cattle treated for morbidity from bovine respiratory disease in either of the 2 experiments. In Exp. 3, in vitro methods were used to determine the effects of WDGS on IVDMD, total gas production, and molar proportions and total concentrations of VFA. Substrates used for the incubations contained the same major components as the diets used in Exp. 1, with ruminal fluid obtained from steers fed a 60% concentrate diet. Total gas production was less (P = 0.03) for the average of the 3 WDGS substrates than for CON, with a linear decrease (P = 0.01) in total gas production as WDGS concentration increased in the substrates. In contrast to gas production, IVDMD was greater for the average of the 3 WDGS concentrations vs. CON (P ≤ 0.05) at 6 and 12 h and increased (P ≤ 0.02) with increasing WDGS concentration at 6 (linear and quadratic) and 12 h (linear) of incubation. At 48 h, there was a quadratic effect (P = 0.05) on IVDMD, with the greatest value for 25% WDGS. Molar proportion of butyrate increased linearly (P < 0.01) as the concentration of WDGS increased in the substrate, and the average of the 3 substrates containing WDGS had a greater proportion of butyrate (P = 0.03) than CON. Performance data from Exp. 1 and 2 indicate that including WDGS in the SFC-based diets for newly received cattle can be an effective at concentrations up to 37.5% of the DM. In vivo measurements are needed to corroborate the in vitro fermentation changes noted with addition of WDGS.

Normalization of NF-κB activity in dorsal root ganglia neurons cultured from diabetic rats reverses neuropathy-linked markers of cellular pathology.

AIMS/HYPOTHESIS: Dorsal root ganglia (DRG) sensory neurons cultured from 3 to 5 month streptozotocin (STZ)-induced diabetic rats exhibit structural and biochemical changes seen in peripheral nerve fibers in vivo, including axonal swellings, oxidative damage, reduced axonal sprouting, and decreased NF-κB activity. NF-κB is a transcription factor required by DRG neurons for survival and plasticity, and regulates transcription of antioxidant proteins (e.g. MnSOD). We hypothesized that the diabetes-induced decrease in NF-κB activity in DRG contributes to pathological phenomena observed in cultured DRG neurons from diabetic rats. METHODS: NF-κB localization was assessed in intact DRG and neuron cultures using immunostaining. NF-κB activity was manipulated in sensory neuron cultures derived from age-matched normal or 3-5 month STZ-diabetic rats using pharmacological means and lentiviral expression of shRNA. The impact of diabetes and altered NF-κB activity on neuronal phenotype involved analysis of neurite outgrowth, neurite morphology, oxidative stress (lipid peroxidation) and expression of MnSOD. RESULTS: STZ-induced diabetes caused a significant decrease in nuclear localization of NF-κB subunits p50 and c-rel, but no change in p65 in intact DRG. Inhibition of NF-κB in normal neuron cultures significantly increased axonal swellings and oxidative stress, and reduced both neurite outgrowth and expression of MnSOD. These phenomena mimicked markers of pathology in cultured DRG neurons from diabetic rats. Enhancement of NF-κB activity in cultured diabetic DRG neurons ameliorated the sub-optimal neurite outgrowth and MnSOD levels triggered by diabetes. Exogenous insulin enhanced nuclear localization of p50 and c-rel but not p65 in diabetic neuronal cultures. CONCLUSION/INTERPRETATION: The diabetes-induced decrease of nuclear localization of NF-κB subunits p50 and c-rel in DRG contributes to development of in vitro markers of peripheral neuropathy, possibly through impaired mitochondrial ROS scavenging by deficient MnSOD.

Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab therapy in patients with multiple sclerosis (MS), which is often accompanied by an immune reconstitution inflammatory syndrome (IRIS) after removal of the drug. We describe a patient with MS who presented with simultaneous PML-IRIS 2 months after stopping natalizumab for other reasons. CASE REPORT AND RESULTS: The patient had widespread PML and severe IRIS. He received corticosteroids and displayed a vigorous JC virus-specific cellular immune response. Elevated myoinositol and lipid/creatine peaks measured in PML lesions by proton magnetic resonance spectroscopy ((1)H-MRS) corresponded to episodes of contrast enhancement on MRI scans and persisted after the enhancement subsided. He demonstrated steady clinical improvement, but developed marked residual atrophy in areas affected by PML and inflammation, as well as seizures. CONCLUSIONS: New enhancing white matter lesions, occurring after discontinuation of natalizumab, can be the manifestation of PML-IRIS rather than an MS exacerbation. Elevated myoinositol and lipid/creatine peaks appear to be more sensitive markers of inflammation in PML lesions than contrast enhancement. (1)H-MRS may become useful as a biomarker for PML-IRIS by helping clinicians determine the need for corticosteroid administration and anticipate continuing clinical recovery.

Performance of finishing beef steers in response to anabolic implant and zilpaterol hydrochloride supplementation.

Our objectives were to evaluate the dose/payout pattern of trenbolone acetate (TBA) and estradiol-17ß (E(2)) implants and feeding of zilpaterol hydrochloride (ZH) on performance and carcass characteristics of finishing beef steers. A randomized complete block design was used with a 3 × 2 factorial arrangement of treatments. British × Continental steers (n = 168; initial BW = 362 kg) were blocked by BW and allotted randomly to 42 pens (7 pens/treatment; 6 pens/block; 4 steers/pen). The main effects of treatment were implant [no implant (NI); Revalor-S (REV-S; 120 mg of TBA + 24 mg of E(2)); and Revalor-XS (REV-X; 200 mg of TBA + 40 mg of E(2))] and ZH (0 or 8.3 mg/kg of DM for 20 d with a 3-d withdrawal before slaughter). Blocks were split into 2 groups, and block groups were fed for either 153 or 174 d. No implant × ZH interactions were noted for cumulative performance data. Overall, shrunk final BW (567, 606, and 624 kg for NI, REV-S, and REV-X, respectively), ADG (1.25, 1.51, and 1.60 kg), and G:F (0.14, 0.16, and 0.17) increased (P < 0.05) as TBA and E(2) dose increased. Implanting increased (P < 0.05) DMI, but DMI did not differ (P > 0.10) between REV-S and REV-X (8.8 for NI vs. 9.4 kg/d for the 2 implants). From d 1 to 112 of the feeding period, implanting increased (P < 0.05) ADG and G:F, but REV-S and REV-X did not differ (P > 0.10). From d 112 to end, ADG increased by 19% (P < 0.05) and G:F was 18% greater (P < 0.05) for REV-X vs. REV-S. Carcass-adjusted final BW (29-kg difference), ADG (0.2-kg/d difference), and G:F (0.02 difference) were increased (P < 0.05) by ZH, but daily DMI was not affected by feeding ZH. Hot carcass weight was increased (P < 0.05) by ZH (19-kg difference) and implant, with REV-X resulting in the greatest response (HCW of 376 for NI vs. 404 and 419 kg for REV-S and REV-X, respectively; P < 0.05). An implant × ZH interaction (P = 0.05) occurred for dressing percent (DP). Without ZH, implanting increased DP, but DP did not differ (P > 0.10) between REV-X and REV-S. With ZH, REV-X increased (1.7%; P < 0.05) DP vs. NI and REV-S. Marbling score, 12th-rib fat, and KPH were not affected (P > 0.10) by implant or ZH. Overall, treatment increased steer performance and HCW in an additive fashion, suggesting different mechanisms of action for ZH and steroidal implants. In addition, a greater dose of TBA + E(2) and extended payout improved steer performance and HCW.

Carlo Moreschi (1876-1921): co-founder of the journal "La Medicina del Lavoro" and often forgotten pioneer of modern medicine.

BACKGROUND: Carlo Moreschi (1876-1921) was founding co-editor of the journal "Il Lavoro" (now known as "La Medicina del Lavoro"), together with Luigi Devoto in 1901. Despite this fact, many of his pioneering contributions to 20th century scientific debate are not well known outside Italy. OBJECTIVES: The aim of this paper therefore was to recall Moreschi' achievements and the groundbreaking work of this remarkable Italian physician. METHODS: A comprehensive analysis was conducted on scientific papers written by Carlo Moreschi between 1901 and 1920, extending the investigation to his original manuscripts and private correspondence with family and colleagues. RESULTS: Careful examination of Moreschi's work reveals several studies in the field of social medicine, epidemiology of infectious diseases, general pathology and oncology. In particular, his main interest in haematology and immunology enabled Moreschi to be one of the first to understand the mechanisms of complement fixation and the formation pathways ofantiglobulin sera. In this manner, Moreschi significantly contributed to the work of Wassermann regarding the diagnosis of syphilis, as well as contributing to the discovery of the "antiglobulin test", first described by Coombs in 1945. Furthermore, Moreschi co-founded "Il Lavoro" and "Haematologica", the oldest journals in their respective fields. CONCLUSIONS: According to Devoto, Moreschi can be remembered as the archetype modern researcher and clinician. His role in the 20th century scientific debate and his pioneering work in the field of immunology and haematology, that are often forgotten due to his premature death, deserve to be reconsidered and re-assessed by the Italian and international scientific community.

The latest endangered species in Australia: a tobacco-smoking veterinarian.

The results of a tobacco smoking survey conducted among veterinarians in Queensland, Australia, during 2007 are presented. Of the 567 participants only 3% reported being current smokers, 24% were ex-smokers and 73% had never smoked. The prevalence of smoking was similar among males and females, and the highest smoking rate was reported among veterinarians aged 31-40 years. However, the rate of never-smokers was strongly and negatively correlated with age, and the proportion of ex-smokers increased with age. Encouragingly, the results from this study suggest that tobacco use has all but disappeared from the Australian veterinary profession in recent years.

Prevalence and correlates of musculoskeletal disorders among Australian dental hygiene students.

INTRODUCTION: Although musculoskeletal disorders (MSD) have been identified as a significant occupational health issue for dental hygienists, few studies have explored this problem among the dental hygiene student population. AIM: The aim of this study was to investigate the prevalence and correlates of MSD among a selection of undergraduate dental hygiene students in Australia. METHODOLOGY: A self-reporting questionnaire was distributed to dental hygiene students at an Australian university during 2008, from which a response rate of approximately 72% was achieved. RESULTS: Musculoskeletal disorders were most commonly reported by students at the neck (64.29%), lower back (57.94%) and shoulder (48.41%) regions. Logistic regression indicated various correlations with MSD. Students who did not undertake regular exercise every week experienced an increased risk of lower back pain [Odds Ratio (OR): 4.88, 95% Confidence Interval (CI): 1.75-14.9]. Students undertaking 16-20 h of desk-based study per week were much more likely to report neck pain (OR: 19.7, 95% CI: 1.34-378.94). Working 6-10 h on a computer each week was a risk factor for shoulder (OR: 7.03, 95% CI: 1.42-39.49) and upper back pain (OR: 5.29, 95% CI: 1.21-25.56). CONCLUSIONS: Overall, this study suggests that MSD are a reasonably common problem for dental hygiene students in Australia. As such, further studies are required to establish epidemiological patterns of MSD, and our profession will need to carefully consider preventive strategies to help minimize the impact of this important occupational health issue on the next generation of dental hygienists.

Effects of ionophores and antibiotics on in vitro hydrogen sulfide production, dry matter disappearance, and total gas production in cultures with a steam-flaked corn-based substrate with or without added sulfur.

Effects of 3 ionophores and 2 antibiotics on in vitro H(2)S production, IVDMD, total gas production, and VFA profile with or without added S were examined. In Exp. 1, ruminal fluid from 2 ruminally cannulated steers fed a steam-flaked corn-based diet (75% concentrate) without ionophore and antibiotics for 28 d before collection was used to inoculate in vitro cultures. Treatments were control (no ionophore or antibiotic), 3 ionophores (lasalocid sodium and monensin sodium at 5 mg/L or laidlomycin propionate at 1.65 mg/L), and 2 antibiotics (chlortetracycline hydrochloride at 5 mg/L and tylosin tartarate at 1.25 mg/L). Cultures also had 0 or 1.75 mg of S/L (from sodium sulfate). No S x ionophore-antibiotic treatment interactions were noted (P > 0.53) for IVDMD, total gas production, and H(2)S production. Hydrogen sulfide (mumol/g of fermentable DM) was increased (P < 0.001), and total gas production tended (P = 0.09) to be increased with additional S; however, IVDMD was not affected by added S (P = 0.90). Production of H(2)S was not affected by ionophores or antibiotics (P > 0.18). On average, IVDMD (P = 0.05) was greater for ionophores than for antibiotics, whereas total gas production was less for ionophores than for control (P < 0.001) and antibiotics (P < 0.001). Molar proportions of acetate (P < 0.01) and acetate:propionate (P < 0.01) were decreased and propionate was increased (P < 0.001) in ionophore treatments when no S was added, but when S was added there were no differences (P > 0.20) in acetate, propionate, or acetate:propionate between ionophores and control (S x treatment interaction, P = 0.03). In Exp. 2, the effects of ionophore-antibiotic combinations with added S were examined using the same procedures as in Exp. 1. Treatments were control, monensin plus tylosin (MT), and lasalocid plus chlortetracycline (LCTC), with concentrations of the ionophores and antibiotics as in Exp. 1. No differences were observed among treatments for H(2)S production (P > 0.55). Treatments MT and LCTC tended (P = 0.06) to increase IVDMD and decreased (P = 0.02) gas production vs. control. Proportion of acetate (P = 0.01) and acetate:propionate (P < 0.01) were decreased and propionate increased (P = 0.01) for both MT and LCTC compared with control. These data suggest that when S is approximately 0.42% of substrate DM, the 3 ionophores and 2 antibiotics we evaluated did not affect production of H(2)S gas in an in vitro rumen culture system.

Adult cystic hygroma: successful use of OK-432 (Picibanil).

OBJECTIVE: We report an adult case of cystic lymphangioma treated with OK-432 (Picibanil). METHOD: A case report and review of the literature concerning the use of OK-432 to treat cystic lymphangioma is presented. RESULTS: A 31-year-old woman developed a cystic lymphangioma four weeks post-partum. This was treated initially by aspiration, for diagnostic purposes. Investigation suggested that surgery would be challenging. A review of the literature demonstrated success with OK-432 in the treatment of this condition, although primarily in the paediatric population. This patient was successfully treated thus, and at the time of writing remained symptom free. A suggested management plan is outlined. CONCLUSION: Treatment with OK-432 is useful in the management of cystic lymphangiomas in adults and should be considered as first line treatment.

Complete recovery of an isolated left vocal fold palsy associated with a benign mediastinal thymic cyst.

OBJECTIVES: To present a case of benign mediastinal thymic cyst, and to review the published information on these cysts, including their incidence, presentation, diagnosis and management. METHODS: We report the case of a 55-year-old man who presented with a unilateral vocal fold palsy subsequently found to be due to the presence of a benign mediastinal thymic cyst. A literature search was undertaken to identify the incidence, key features and management of this rare condition. RESULTS: Benign mediastinal thymic cysts are a rare cause of mediastinal masses. Usually diagnosed incidentally, their management is usually surgical. Vocal fold palsy in isolation has not previously been reported in association with mediastinal thymic cysts. CONCLUSION: This report describes what we believe to be the first published case of a completely reversible vocal fold palsy presenting in association with a rare benign mediastinal thymic cyst.

An international review of tobacco smoking among medical students.

We conducted a systematic international review of tobacco smoking habits among medical students. Particular attention was paid to countries where smoking rates have been historically well-documented in local journals, but were less often included in larger international review articles. The methodology involved a search of relevant medical subject headings, after which the reference lists of journal papers were also examined to find additional publications. A total of 66 manuscripts met the inclusion criteria. The most common countries previously studied included India, the United States, Australia, Japan, Pakistan, Turkey and the United Kingdom. Overall, our review suggests that the prevalence of smoking among medical students varies widely amongst different countries and also between male and female students within the same areas. Consistently low smoking rates were found in Australia and the United States, while generally high rates were reported in Spain and Turkey. Given their important future role as exemplars, more effective measures to help reduce tobacco smoking among medical students are clearly needed worldwide.

[Tobacco smoking among Italian physicians]. / Abitudine al fumo nei medici italiani.

A survey of the international literature published between 1985 and 2000 reveals high smoking rates among Italian physicians. Since 1985 smoking rates among physicians have gradually declined, similarly to those of general population. However, prevalence rates seem to vary between northern and southern Italy, with the highest rates in the southern regions. Studies examining smoking rates by gender reveal that, while smoking trends among males have declined somewhat, the latter remained relatively stable among female physicians. From an international perspective, declines in the absolute smoking rates of Italian physicians have not kept pace with those of many other countries, since at least one-quarter of Italian physicians currently smoke. Furthermore, most of the Italian physicians smoke while they are at work. This represents an occupational health problem that needs to be addressed by all levels of management. In meeting this challenge, occupational medicine has an important role to play in helping reduce the prevalence of smoking among health care workers.