Variation in blood levels of inflammatory markers related and unrelated to smoking cessation in women

This study assessed the influence of short-term changes in smoking habit on blood levels of inflammatory markers, which have been associated with increased cardiovascular risk. Five inflammatory markers were measured before and 6 weeks after attempting smoking cessation in 138 healthy women. In the 48 participants who stopped smoking, white blood cell count (-0.7+/-1.2 x 10(9)/L; P<.001) and fibrinogen (-0.6+/-1.5 micromol/L; P<.01) decreased, but there was no significant (P>.1) change in the plasma level of C-reactive protein (median change +0.1; interquartile range -0.2, 0.9 mg/L), intercellular adhesion molecule 1 (+17+/-75 ng/mL), or CD40 ligand (+0.4+/-2.1 ng/mL). Most of the individual variation in inflammatory marker levels was unrelated to changes in smoking habit.     

The hand: a reflection of arthritis

Hand joint involvement in rheumatic diseases is often precocious and predominant as compared to other skeleton-muscular regions. Clinical examination not always allows for easy detection of fluid outpouring and synovial involvement, and undoubtedly does not allow to diagnose pathognomonic bone alterations of several rheumatic conditions. Articular ultrasonography is an innocuous methodology, easily reproducible and directly applied by a rheumatologist. The aim of this vignette is to present ultrasonography elementary lesions of the hand for a prompt diagnosis.     

Corticotroph axis sensitivity after exercise: comparison between elite athletes and sedentary subjects

Strenuous exercise activates the hypothalamic-pituitary-adrenal (HPA) axis. Several reports showed that physical training is associated with a decreased efficiency of the feedback control of HPA axis. The aims of the present study were: 1) to evaluate the differences in the mechanical, hormonal, and lactate responses to a high-intensity isokinetic exercise among different groups of competitive athletes (CA, no.=20) of power and endurance disciplines and sedentary controls (SED, no.=10); 2) to determine the effects of the training status on the HPA axis responsiveness following exercise, as indirectly evaluated by the rates of ACTH, cortisol, and DHEA recovery after exercise. CA and SED fulfilled eight sets of twenty concentric contractions of the knee extensors at 180 degrees/sec angular velocity throughout a constant range of motion (100 degrees). There was a rest period of 30 sec between each set and a 3-min rest period between the two legs. Before, immediately after the isokinetic exercise and at different times in the subsequent 120 min of recovery, blood and saliva were sampled to determine plasma ACTH, salivary cortisol, serum DHEA, and serum lactate concentrations. CA showed a higher cortisol response to exercise than SED, whereas no differences were found in the responses of ACTH, DHEA and lactate. In the athlete group the exercise-induced increases of ACTH, cortisol, and lactate were higher in power athletes with respect to endurance athletes. No differences were observed between athletes and SED in the rates of hormonal recovery after exercise: this finding does not support the concept that a reduced feedback control of HPA axis can represent a feature of trained individuals.     

Anaplastic thyroid carcinoma: clinical outcome of 30 consecutive patients referred to a single institution in the past 5 years

OBJECTIVE: Treatment options for anaplastic thyroid carcinoma (ATC), which is one of the most lethal human malignant tumors, include surgery, chemotherapy and radiotherapy usually combined in a multimodal approach, to improve survival and avoid death from local invasion. However, there is no standard protocol for ATC treatment and the optimal sequence within multimodal therapy is debated. We retrospectively report the clinical outcome of 30 ATC patients referred consecutively to the Oncological Endocrinology Unit of San Giovanni Battista Hospital (Turin, Italy) between 2000 and 2005. DESIGN: Patients were treated by one of the following approaches: i) surgery followed by adjuvant-combined chemoradiotherapy; ii) neo-adjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy; or iii) chemotherapy alone. The surgical procedures were classified as 'maximal debulking' or 'palliative resection'. Maximal debulking entailed total or near-total thyroidectomy and complete resection of all gross tumor or minimal residual disease adherent to vital structures, independently of the presence or absence of distant metastases. In palliative resections, macroscopic residual disease was left in the neck. Survival of patients stratified by treatment was assessed. RESULTS: Analysis of multivariate hazard ratios showed that maximal debulking followed by adjuvant chemoradiotherapy was the only treatment that modified survival of ATC patients (hazard ratio= 0.23, 95% CI: 0.07-0.79), even if factors determining poor prognosis or increased surgical risk were present. CONCLUSIONS: Despite the overall grim outcome of ATC, these results justify an attempt at maximal debulking surgery, followed by adjuvant chemoradiotherapy, possibly in all ATC patients.     

Key points in the management of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a relatively common condition with a prevalence ranging from 10% to 20% in Western countries and 5% to 10% in Asian populations [1]. In a recent evidence-based consensus [2], GERD was defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms or complications. This global definition emphasizes the syndromic nature of the disease and subdivides the patients in different groups depending on the presence of mucosal complications (ie, esophagitis, metaplasia, stenosis) and on the prevalent clinical manifestations (ie, typical reflux symptoms or extraesophageal/supraesophageal syndromes). General practitioners, gastroenterologists, and specialists from different branches of medicine generally share the management of GERD patients, and basically they need to address the following four issues.     

Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection with Brucella spp.

The ability of Brucella spp. to infect human osteoblasts and the cytokine response of these cells to infection were investigated in vitro. Brucella abortus, B. suis, B. melitensis, and B. canis were able to infect the SaOS-2 and MG-63 osteoblastic cell lines, and the first three species exhibited intracellular replication. B. abortus internalization was not significantly affected by pretreatment of cells with cytochalasin D but was inhibited up to 92% by colchicine. A virB10 mutant of B. abortus could infect but not replicate within osteoblasts, suggesting a role for the type IV secretion system in intracellular survival. Infected osteoblasts produced low levels of chemokines (interleukin-8 [IL-8] and macrophage chemoattractant protein 1 [MCP-1]) and did not produce proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor alpha [TNF-α]). However, osteoblasts stimulated with culture supernatants from Brucella-infected human monocytes (THP-1 cell line) produced chemokines at levels 12-fold (MCP-1) to 17-fold (IL-8) higher than those of infected osteoblasts and also produced IL-6. In the inverse experiment, culture supernatants from Brucella-infected osteoblasts induced the production of IL-8, IL-1β, IL-6, and TNF-α by THP-1 cells. The induction of TNF-α and IL-1β was largely due to granulocyte-macrophage colony-stimulating factor produced by infected osteoblasts, as demonstrated by inhibition with a specific neutralizing antibody. This study shows that Brucella can invade and replicate within human osteoblastic cell lines, which can directly and indirectly mount a proinflammatory response. Both phenomena may have a role in the chronic inflammation and bone and joint destruction observed in osteoarticular brucellosis.Brucella spp. are gram-negative facultative intracellular bacteria that infect domestic and wild animals and can be transmitted to humans, in whom they produce a debilitating and eventually chronic disease. The most common clinical features of human brucellosis are undulant fever, sweats, arthralgias, myalgias, lymphadenopathy, and hepatosplenomegaly (35). Osteoarticular brucellosis is the most common localization of active brucellosis, although its reported prevalence varies widely. The three most common forms of osteoarticular involvement are sacroiliitis, spondylitis, and peripheral arthritis (1, 15, 23, 28, 38).Brucellar arthritis is frequently polyarticular and usually affects knees, sacroiliac joints, shoulders, and hips (28). In some cases, brucellar arthritis may be destructive, with associated osteopenia and cartilage damage. Brucellar spondylitis, which is more destructive than arthritis and causes more serious complications than arthritis does (7), typically begins at the disco-vertebral junction but may spread to the whole vertebrae and to adjacent vertebral bodies (29, 50).While the clinical and imaging aspects of osteoarticular brucellosis have been described widely, the pathogenic mechanisms of joint and bone disease caused by Brucella have not been investigated at the molecular and cellular levels. Regarding brucellar arthritis, a septic form and a reactive form have been proposed (15). The septic form is supported by the isolation of Brucella spp. from synovial fluid or tissue.In osteoarticular infections by pathogens such as Staphylococcus aureus and Mycobacterium tuberculosis, bone and joint damage results mainly from the inflammatory reaction elicited by the infection. In the mouse model of S. aureus arthritis, polymorphonuclear leukocytes and macrophages are seen in the synovial tissue early in the infection (5, 44). Similarly, an infiltrate of highly activated polymorphonuclear leukocytes has been observed in posttraumatic infectious osteomyelitis in humans (45). These cells produce not only proinflammatory cytokines and chemokines but also a series of tissue-degrading enzymes, including metalloproteinases, which can contribute to joint and bone destruction (13, 48). High levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) are detected in the synovial fluid of patients with bacterial arthritis (34, 40). Increased local levels of TNF-α mRNA have also been detected in a rat model of osteomyelitis (27). These cytokines stimulate the release of proteases by inflammatory cells (41). In addition, TNF-α and IL-1β, together with IL-6, stimulate osteoclast differentiation and bone resorption in a synergistic fashion (19, 26). In human brucellar arthritis, synovial fluid usually presents an increased leukocyte count, and the synovial membrane frequently exhibits a nonspecific inflammatory change (28).Given the central role of inflammatory cells in bone and joint destruction in osteomyelitis and arthritis, the recruitment and activation of these cells are of utmost importance for the development of these pathological conditions. Besides their role in bone formation, osteoblasts have also been shown to respond to bacterial infection or bacterial products by secreting proinflammatory cytokines, such as IL-6 and IL-12 (2, 20), and chemokines, such as macrophage chemoattractant protein 1 (MCP-1), IL-8, IP-10, and RANTES (4, 31, 47, 49), which recruit macrophages, neutrophils, and T lymphocytes. Overall, these data point to an active role of osteoblasts in the immune responses elicited during osteoarticular infections.Staphylococcus aureus and Mycobacterium tuberculosis, which are common etiological agents of osteoarticular infections, can infect human osteoblasts in vitro (11, 12, 22, 46, 47). The intracellular persistence of these bacteria in bone cells may facilitate disease progression by protecting these organisms from extracellular host defenses and antibiotic therapy and may help to explain the recurrent nature of osteomyelitis (12). Brucella spp. are known to survive and replicate within mononuclear phagocytes (32) and also in nonphagocytic cells, including epithelial cells and fibroblasts (37). In contrast, there are no data on invasion and/or intracellular replication of Brucella spp. within osteoblasts.In the present study, we investigated whether Brucella spp. can infect and survive within human osteoblastic cell lines and whether this infection elicits the secretion of proinflammatory cytokines and chemokines that might be involved in the osteoarticular manifestations of brucellosis. Since many of these aspects have been described widely for S. aureus, which is a frequent etiological agent of septic arthritis and osteomyelitis, this bacterium was included in parallel in most experiments for comparison.     

Brain tumors and hormonal factors: review of the epidemiological literature

Background  

To date, the etiology of primary tumors of the central nervous system (mainly gliomas and meningiomas) is poorly understood. The role of sex hormones has been suggested, based on clinical, experimental, biological, and epidemiological data.     

Timing and significance of exercise-induced left ventricular outflow tract pressure gradients in hypertrophic cardiomyopathy

The relation of exercise-induced left ventricular (LV) outflow tract obstruction to functional capacity in hypertrophic cardiomyopathy (HC) is incompletely defined. Thus, we assessed the patterns of onset of physiologically provoked LV outflow gradients and exercise performance in 74 consecutive patients with HC (age 45 ± 16 years; 74% men) without LV outflow obstruction at rest. The subaortic gradients were measured serially using echocardiography in these 74 patients during maximum, symptom-limited, upright bicycle exercise testing. The time course of the provoked gradients and the relation to exercise performance were assessed. Of the 74 patients, 30 (41%) developed a dynamic LV outflow gradient of ≥30 mm Hg (mean 78 ± 37 mm Hg) during upright exercise testing that correlated highly with the gradients measured with the patients supine during the immediate recovery period (R2 = 0.97). The 16 patients in whom outflow obstruction developed rapidly at low exercise levels (≤5 METs) had a significantly reduced exercise capacity (6.1 ± 1.3 vs 8.0 ± 1.6 METs; p <0.01) compared to the other 14 patients in whom obstruction appeared later at greater exercise levels of >5 METs. The timing of the gradient onset was not predictable from the baseline clinical and echocardiographic features, peak exercise LV outflow tract gradient, or symptoms. In conclusion, in patients with HC without outflow obstruction at rest, the earlier onset of LV outflow tract gradients during physiologic exercise was associated with impaired exercise performance. These findings have provided insights into the determinants of functional impairment in HC and support the potential value of exercise echocardiography in the clinical assessment of patients with HC.