In-patient vs. day-hospital withdrawal treatment for chronic migraine with medication overuse and disability assessment: results at one-year follow-up

Chronic headaches have increasingly become a focus within the field of head pain. Most patients with frequent headache eventually overuse their medications. The diagnosis of medication-overuse headache is clinically important, because patients rarely respond to preventive medications whilst overusing acute medications. Properly treating medication overuse and preventing relapse require specific therapeutic strategies and the recognition of the different factors that contribute to its development and perpetuation, including some behaviours and psychological elements that are important in sustaining the overuse of medication. Abrupt withdrawal is considered the first step for helping these patients to stop medication overuse. The possibility of withdrawal within a day-hospital setting is considered a therapeutic alternative for these patients and compared to in-patient withdrawal. Long-term results are discussed.

     

2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 microM), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.     

Vaccination: role in metastatic melanoma

Based on the poor impact on overall survival obtained by systemic chemotherapy in metastatic melanoma and the identification of many melanoma antigens recognized by T cells, in the last decade many efforts have been devoted to the development of active specific immunotherapy as a promising systemic treatment for this neoplastic disease. A number of Phase I-II clinical trials have been performed with different vaccination approaches that included whole tumor cells, antigen peptides, antigen-pulsed dendritic cells, recombinant viruses, plasmids or naked DNA, and heat-shock proteins. Despite some promising immunological and clinical results obtained in these studies, melanoma-specific vaccines have altogether failed to prove their efficacy in the few large Phase III randomized clinical trials performed. Nonetheless, the possibility of activating the human immune system to recognize and destroy tumor cells remains a challenging investigative field, considering that the new knowledge of the intricate cellular and molecular mechanisms that regulate the immune function and tumor-host interactions may allow the development of new clinically relevant melanoma vaccination strategies.     

Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD

OBJECTIVE: The objective of this study was to investigate the association between antioxidant nutrients and markers of oxidative stress with pulmonary function in persons with chronic airflow limitation. DESIGN: Cross-sectional study exploring the association of antioxidant nutrients and markers of oxidative stress with forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%). SETTING/SUBJECTS: The study data included 218 persons with chronic airflow limitation recruited randomly from the general population of Erie and Niagara counties, New York State, USA. RESULTS: After adjustment for covariates, multiple linear regression analysis showed that serum beta-cryptoxanthin, lutein/zeaxanthin, and retinol, and dietary beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, vitamin C, and lycopene were positively associated with FEV1% (P < 0.05, all associations). Serum vitamins beta-cryptoxanthin, lutein/zeaxanthin, and lycopene, and dietary beta-cryptoxanthin, beta-carotene, vitamin C, and lutein/zeaxanthin were positively associated with FVC% (P < 0.05, all associations). Erythrocytic glutathione was negatively associated with FEV1%, while plasma thiobarbituric acid-reactive substances (TBARS) were negatively associated with FVC% (P < 0.05). CONCLUSION: These results support the hypothesis that an imbalance in antioxidant/oxidant status is associated with chronic airflow limitation, and that dietary habits and/or oxidative stress play contributing roles.     

Training the adult amblyopic eye with "perceptual learning" after vision loss in the non-amblyopic eye

We recently reported acuity development in the amblyopic eye of a 60-year-old patient after loss of vision in her non-amblyopic eye. Here, we focus on the training that we implemented, based on new insights from psychophysical procedures aiming at functional visual improvement of adults ("perceptual learning"). We alternately used the following procedures: grating acuity (Teller-Cards); contrast sensitivity (Vistech-Charts); two spatial localization tests (vertical alignment, pointing); and labyrinth patterns for a eye-hand coordination exercise. One month without intervention was followed by six months of training and two blocks of pleoptic treatment. Clinical parameters were assessed monthly. Besides acuity gain, we observed enhanced grating resolution and contrast sensitivity, decreased alignment distortions, pointing shifts, mainly after pleoptics, and more efficient labyrinth tracing. A questionnaire reflected the patient's perception of the changes. These data confirm the plasticity of the adult amblyopic system, be it spontaneous due to the loss of the non-amblyopic eye or caused by the intervention or both. Further experience is necessary to isolate the role of the intervention. Our results also underline the limitation of adult plasticity, emphasizing the importance of early diagnosis and treatment of amblyopia.     

Anorectal function problems after left hemicolectomy

BACKGROUND: The aim of this study was to evaluate the subjective anorectal function in patients with left hemicolectomy and to clarify the clinical factors influencing postoperative anorectal function problems. MATERIALS AND METHODS: One hundred and twenty one patients who underwent left hemicolectomy from April 2002 to December 2003 were enrolled in this study and sent questionnaires concerning anorectal function. Left hemicolectomy in patients with cancer was performed by high ligation of the inferior mesenteric artery; in patients with diverticulitis or polyposis, the inferior mesenteric artery was cut just below the branch of the left colonic artery. One hundred patients replied to the questionnaire: 52 men and 48 women, aged 37 to 85, with a mean age of 66.6 years. Differences were analyzed for statistical significance by the Chi square test and by logistic regression. RESULTS: Anorectal function problems was present in 33% of patients: female gender (P = 0.02), laparoscopic surgery (P = 0.04), and postoperative diarrhea (P = 0.04) had significant independent effects on anorectal function problems. Transient early fecal incontinence was observed in 16% of patients and laparoscopic surgery had significant independent effects on this problem (P = 0.04). Inability to discriminate between gas and stool, tenesmus, or urgency were present in 21%, 18%, and 17% of cases, respectively, and were independently associated respectively with laparoscopic surgery (P = 0.005) and postoperative diarrhea (P = 0.019) (P = 0.015). CONCLUSION: In our study the following two issues were clarified: anorectal function problems are frequent after left hemicolectomy, and the laparoscopic technique is linked to poor postoperative anorectal function. The technical methods of high ligation of the inferior mesenteric artery could explain this result.     

ACE inhibitors and angiotensin II receptor blockers in IgA nephropathy with mild proteinuria: the ACEARB study

Few studies have investigated IgA nephropathy patients presenting with 'favorable' clinical features at onset, such as normal renal function, proteinuria<1 g/24 hours and the absence of hypertension, and no controlled clinical trials have tested the effects of treatment in such patients who may nevertheless develop end-stage renal disease. It is therefore important to find a well-tolerated and economic therapy capable of decreasing their risk of high proteinuria and blood pressure levels. The aim of this multicenter open-label randomized clinical trial is to test whether blocking the renin-angiotensin system (RAS) decreases the risk of progression in patients aged 3-60 years with biopsy-proven benign IgA glomerulonephritis, proteinuria levels of 0.3-0.9 g/24 hours, and normal renal function and blood pressure. The RAS is blocked by first using a single drug class (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker), and then combining the 2 classes as soon as the 1-drug blockade has become ineffective. We plan to enroll 378 patients over the next 3 years and randomize them to receive ramipril 5 mg/day (3 mg/m2 in children) (group A), irbesartan 300 mg/day (175 mg/m 2 in children) (group B) or supportive therapy (group C); if an increase in proteinuria of at least 50% from baseline is detected after 6 months of treatment, the other RAS inhibitor will be added. The observation period will be at least 5 years (except in the case of the development of the primary end point).     

DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress-induced apoptosis

The DHCR24 gene encoding for the 3beta-hydroxysterol delta24-reductase, an oxidoreductase involved in cholesterol biosynthesis, was isolated by subtractive hybridization as highly expressed in a short-term melanoma cell line derived from a cutaneous metastases (S/M2) compared to that obtained from the autologous primary tumor (S/P). DHCR24 (alias seladin-1, diminuto/dwarf1 homolog) has been reported to act as an antiapoptotic factor in neurons. Gene expression analysis by Northern blot confirmed that DHCR24 was 5-fold upregulated in S/M2 compared to S/P cells. High levels of DHCR24 gene expression were detected in 13/25 melanoma metastases and in 1/7 primary melanomas by real-time PCR, indicating that upregulation of this gene may occur in melanoma progression. In S/M2 cells, high DHCR24 gene expression associated with resistance to apoptosis triggered by oxidative stress induced by exposure to hydrogen peroxide. DHCR24 gene transfer was shown to protect melanoma cells from H2O2-induced cytotoxicity. Although higher cholesterol levels were shown in S/M2 cells compared to S/P cells, DHCR24 gene transfer did not increase cholesterol content. To evaluate whether DHCR24 acts as an antiapoptotic factor in melanoma metastases, the cytotoxic effect of chemotherapeutic agents was tested in DHCR24 transfectants and in the presence of a DHCR24 inhibitor, U18666A. High DHCR24 gene expression in transfectants did not result in a higher resistance to cytotoxic agents; treatment with U18666A was cytotoxic in S/P cells with a lower DHCR24 content and showed additive cytotoxic effect only when associated with H2O2 and not with cysplatin or etoposide, indicating that the DHCR24 protective effect is exerted through an oxidative stress-specific mechanism.     

Intercorrelations between serum, salivary, and hair cortisol and child-reported estimates of stress in elementary school girls

To evaluate the impact of stress on children's well-being, it is important to have valid and reliable stress assessment methods. Nevertheless, selection of an appropriate method for a particular research question may not be straightforward, as there is currently no consensus on a reference method to measure stress in children. This article examined to what extent childhood stress can be estimated accurately by stressor questionnaires (i.e., Coddington life events scale) and biological markers (serum, salivary, and hair cortisol) using the Triads (a triangulation) method in 272 elementary school girls. Salivary cortisol was shown to most accurately indicate true childhood stress for short periods in the past (i.e., last 3 months), whereas hair cortisol may be preferred above salivary measurements for periods more distant and thus for chronic stress assessment. However, applicability should be confirmed in larger and more heterogeneous populations.