Psychiatric disorders,acne and systemic retinoids: comparison of risks

Background: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids.

Materials and methods: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest.

Results: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin.

Conclusion: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.     

Fracture resistance of implant-supported screw- versus cement-retained porcelain fused to metal single crowns: SEM fractographic analysis.

OBJECTIVES: The present in vitro study aimed at evaluating the fracture resistance of both implant-supported screw- and cement-retained porcelain fused to metal (PFM) single crowns. A scanning electron microscope (SEM) evaluation of the mode of failure of the specimens was also performed. METHODS: Forty PFM premolar-shaped identical single crowns were realized. The restorations were divided into two groups: cement-retained (group 1) and screw-retained (group 2) prostheses. Compressive loading tests and SEM fractographic analyses were performed. The data were statistically analysed by means of the Student's t-test, with a confidence interval of 95%. RESULTS: The mean fracture load value was 1657 (+/-725) N in group 1 and 1281 (+/-747) N in group 2; the statistical analysis pointed out no significant differences between the two groups (p=0.115). The mean work at maximum load value was 0.775 (+/-0.619) J in group 1 and 0.605 (+/-0.526) J in group 2; the statistical analysis pointed out no significant differences between the two groups (p=0.355). All the samples were affected by cohesive fractures of the porcelain. Screw-retained crowns showed microcracks at the level of the occlusal access to the screw and extensive fractures in the whole thickness of the ceramics. On the contrary, cement-retained restorations were affected by less wide paramarginal fractures of the porcelain. SIGNIFICANCE: A stronger implant-prosthetic connection was noticed in cemented restorations group than in screw-retained single crowns. Even though negatively influenced by the presence of the occlusal access to the screw, the metal-ceramics bond can be considered predictable in both the implant-prosthetic connection systems analysed.     

Molecular mechanisms underlying airway smooth muscle contraction and proliferation: implications for asthma

Airway smooth muscle (ASM) plays a key role in bronchomotor tone, as well as in structural remodeling of the bronchial wall. Therefore, ASM contraction and proliferation significantly participate in the development and progression of asthma. Many contractile agonists also behave as mitogenic stimuli, thus contributing to frame a hyperresponsive and hyperplastic ASM phenotype. In this review, the molecular mechanisms and signaling pathways involved in excitation-contraction coupling and ASM cell growth will be outlined. Indeed, the recent advances in understanding the basic aspects of ASM biology are disclosing important cellular targets, currently explored for the implementation of new, more effective anti-asthma therapies.     

Lipid-lowering drug use in Italian primary care: effects of reimbursement criteria revision

Objective To assess whether the prescribing pattern of lipid-lowering drugs (LLD) changed after reimbursement criteria revision in a general practice in southern Italy. Methods From the Caserta-1 Local Health Service database, 93 general practitioners (GPs) who had consistently sent data about their patients during the years 2003-2005 were recruited. Prevalence of use and incidence of new treatments were calculated for each year, stratified by three drug cohorts: statins, omega-3 fatty acids, and fibrates. Subanalyses by gender, age, and indication of use were performed. Results Overall, 1-year prevalence of LLD use increased from 2003 to 2004. After reimbursement criteria revision (November 2004), a slight decrease was observed for statins, from 41.1 (95% CI: 39.9–42.2) per 1,000 inhabitants in 2004 to 40.3 (39.2–41.5) in 2005, while omega-3 utilization fell markedly: 14.6 (13.9–15.3) vs. 5.4 (5.0–5.8). The use of both statins and omega-3 fatty acids was reduced particularly for primary prevention. On the other hand, utilization of statins increased in diabetic patients and as secondary prevention from 2004 to 2005. Concerning individual molecules, 1-year prevalence of use of any statin declined from 2004 to 2005, except for rosuvastatin. Conclusions Revision of reimbursement criteria led to significant changes in the trend in LLD use in general practice in southern Italy: (1) statin utilization was slightly reduced in 2005, although it increased in certain categories, such as diabetic patients, and (2) omega-3 fatty acid use was strongly reduced even though a higher use in post-infarction cases was reported.     

Effect of application technique of luting agent on the retention of three types of fiber-reinforced post systems

The aim of this study was to evaluate retentive strengths of three adhesive/resin cement/fiber post systems to the apical third of post-space dentin varying the application method of the luting agent. ENA post (Micerium, Avegno, Genova, Italy), FRC Postec Plus (Ivoclar Vivadent, Schaan, Liechtenstein), and Anatomical Post (Dentalica, Milano, Italy) were luted in prepared root canals using the adhesive system and resin cement provided by the respective manufacturer. Each group was randomly divided into three subgroups (n = 10) according to the technique used to place the luting agent into post space: using a lentulo spiral, applying the cement onto the post surface, and injecting the material with a specific syringe. A push-out test was performed on sections from the post-space apical part of each specimen. All fractured specimens were observed using a stereomicroscope. Bond strength values were not significantly affected by the application technique of the luting agent (p > 0.05). The ENA post system showed the highest retentive strengths. The other two post groups exhibited similar bond strengths to each other. Microscopic analysis revealed a prevalence of post/cement and mixed failures.     

Independent prognostic role of p16 expression in lung cancer.

OBJECTIVES: The cyclin-dependent kinase p16 (also known as Ink4A, Mts1, Cdkn2, and Cdkn4i) has been proposed as a tumor suppressor gene mapped on chromosome segment 9p21. This study evaluated p16 protein expression in 135 lung cancer specimens and investigated potential genetic alterations occurring in this gene. RESULTS: We found altered p16 immunohistochemical expression to be a frequent event in lung cancer and to be independent of either the histologic type or any other clinical-pathologic feature. Western blot analyses performed on about one third of the specimens correlated highly with these results. In addition, we found p16 immunohistochemical expression to be a favorable prognostic factor in lung cancer in that its reduction or loss correlated with a worse outcome for the patients. Polymerase chain reaction amplification and direct sequencing of p16 exons 1 and 2 revealed no mutations, indicating that p16-altered expression in lung cancer is not necessarily linked to mutational events of these genes. CONCLUSIONS: We conclude that p16-altered expression is both an independent and frequent event in lung cancer and may have an important role in tumorigenesis and in malignant progression of a significant proportion of these cancers. However, the actual incidence and relevance of p16 mutations in this neoplasm continues to be debated, and its analysis seems inconclusive. Our results suggest a prognostic role for the immunodetection of this protein on formalin-fixed and paraffin-embedded specimens. They further suggest its routine use in the evaluation of the frequently unpredictable behavior of lung cancer.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.     

Cutaneous manifestations of HIV—a detailed study of morphological variants,markers of advanced disease,and the changing spectrum

Background

Cutaneous manifestations are early and easily identifiable markers of human immunodeficiency virus (HIV) infection. They can help in predicting severity and progress of the disease and can be correlated well with CD4 counts. This study was undertaken to study the cutaneous manifestations of HIV infection and to correlate them with CD4 counts. It also aimed to study the changing spectrum of these manifestations and describe cutaneous manifestations seen in advanced disease.

Method

A total of 234 HIV-positive patients not on anti-retroviral therapy, who attended the outpatient department or were admitted as inpatients at Military Hospital, Shillong during the period between May 2008 and October 2009 were included. Cutaneous, mucosal, and genitourinary manifestations in these patients were studied in detail and were correlated with CD4 counts.

Results

Infections were the most common group of mucocutaneous manifestations, while onychomycosis was the commonly observed individual manifestation. A different set of cutaneous markers for advanced HIV disease was observed and new parameters for therapy were also arrived at.

Conclusion

Specific morphological variants of cutaneous markers may provide a better clue to early diagnosis of HIV and can help in diagnosing advanced stages of the disease. Fresh cutaneous markers are required for indicating cut-off levels of CD4 count at 350/μL for starting therapy.