Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: a single-blind,randomized clinical trial

Brucellosis is associated with a high recurrence rate and requires more than one course of standard treatment; therefore, more research is required to find more effective treatments that lead to prompt recovery, and reduce the relapse of disease. This single-blind, randomized study was designed to evaluate the effect of the standard treatment for brucellosis in combination with hydroxychloroquine.A total of 177 patients with acute brucellosis were randomly assigned to one of two treatment groups: doxycycline-streptomycin (DS) and doxycycline-streptomycin-hydroxychloroquine (DSH). Clinical symptoms and signs, serological tests, and side effects of therapy were compared between the two groups during the treatment course and at three and six months after the end of drug therapy. Of the 177 patients, with a mean age of 40.5?±?16.9 years, 66.1% were males. The mean duration of clinical signs prior to admission was 43.4?±?41.1 days. Appropriate clinical responses, relapse, treatment failure, and adverse drug reactions were seen in 98.9%, 1.2%, 0.0%, and 12.6% of patients, respectively, in the DSH group vs. 86.7%, 11.6%, 2.3%, and 19.8% of patients, respectively, in the DS group. There were significant differences in clinical response and relapse rates between the two groups. The addition of hydroxychloroquine to a doxycycline-streptomycin regimen appears to increase the efficacy of treatment, accelerate improvement of clinical symptoms, and significantly reduce the rate of relapse of brucellosis.     

The PedsQL™ Oral Health Scale in Iranian children: reliability and validity

International Journal of Paediatric Dentistry 2011 Objective. The primary objective of the study was to translate and evaluate the psychometric properties of the Pediatric Quality of Life Inventory? (PedsQL?) Oral Health Scale in over 1000 Iranian children. Methods. A standard forward and backward translation procedure was used to convert the US English dialect version of the PedsQL? Oral Health Scale into the Iranian language (Persian). The Iranian version of the PedsQL? Oral Health Scale, in combination with the PedsQL? 4.0 Generic Core Scales, was then subsequently administered to 1053 Iranian children and 1026 parents. The reliability of the PedsQL? Oral Health Scale was evaluated using internal consistency and test‐retest methods. Known‐groups discriminant validity, exploratory factor analysis (EFA) of the Oral Health and the four Generic Core Scales combined, and confirmatory factor analysis (CFA) of the Oral Health Scale alone were conducted. The Benjamini–Hochberg procedure was used to correct P‐values for multiple comparisons. Results. Good to excellent internal consistency and test‐retest reliabilities were demonstrated. The PedsQL? Oral Health Scale demonstrated discriminant validity for subgroups of children across different decayed, missing and filled teeth (DMFT) index categories and gender. The EFA supported the a priori factor model of the combined five scales. The CFA analysis confirmed the unidimensional factor structure of the Oral Health Scale. Conclusions. The PedsQL? Oral Health Scale demonstrated excellent psychometric properties in combination with the PedsQL? 4.0 Generic Core Scales. These five scales combined can be utilized to assess the multidimensional oral‐health‐related quality of life of Iranian children.     

High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC

Significant rational is available for specific targeting of PI3K/AKT/mTOR pathway in the treatment of non-small cell lung cancer (NSCLC). However, almost all clinical trials that have evaluated Pi3K pathway-based monotherapies/combinations did not observe an improvement of patient’s outcome. The aim of our study was therefore to define combination of treatment based on the determination of predictive markers of resistance to the mTORC1 inhibitor RAD001/Everolimus. An in vivo study showed high efficacy of RAD001 in NSCLC Patient-Derived Xenografts (PDXs). When looking at biomarkers of resistance by RT-PCR study, three genes were found to be highly expressed in resistant tumors, i.e., PLK1, CXCR4, and AXL. We have then focused our study on the combination of RAD001 + Volasertib, a PLK1 inhibitor, and observed a high antitumor activity of the combination in comparison to each monotherapy; similarly, a clear synergistic effect between the two compounds was found in an in vitro study. Pharmacodynamics study demonstrated that this synergy was due to (1) tumor vascularization decrease, increase of the HIF1 protein expression and decrease of the intracellular pH, and (2) decrease of the Carbonic Anhydrase 9 (CAIX) protein that could not correct intracellular acidosis. In conclusion, all these preclinical data strongly suggest that the inhibition of mTORC1 and PLK1 proteins may be a promising therapeutic approach for NSCLC patients.     

Antenatal corticosteroids for preterm birth

A single course of antenatal corticosteroids is a rare example of a treatment that yields both a health benefit and a cost savings. This article reviews the history and background of antenatal corticosteroids, its use in clinical practice and the controversy today regarding the use of multiple courses of antenatal corticosteroids.     

Relationship of sperm DNA fragmentation, apoptosis and dysfunction of mitochondrial membrane potential with semen parameters and ART outcome after intracytoplasmic sperm injection

Purpose

The objective of this study was to assess the relationship of DNA damage, apoptosis and dysfunction of mitochondrial membrane potential (MMP) in ejaculated spermatozoa with semen parameters (sperm concentration, motility and normal morphology) and to evaluate their effects on assisted reproductive technology (ART) outcomes after intracytoplasmic sperm injection (ICSI).

Methods

Semen parameters in 120 infertile couples who underwent ICSI treatment were routinely analyzed and examined for the incidence of sperm DNA fragmentation (DF) by the sperm chromatin dispersion test (SCD). Whereas the incidences of sperm apoptosis and dysfunction of MMP were assessed by flow cytometry. The correlation among different sperm factors and ART outcomes was evaluated statistically.

Results

Sperm parameters were negatively related to DF (motility and normal morphology, p?<?0.01), apoptosis (concentration, motility and normal morphology, p?<?0.01, p?<?0.05 and p?<?0.05, p?<?0.01 respectively), and dysfunction of sperm MMP (concentration, motility and normal morphology, p?<?0.01). DF also showed a positive correlation with apoptosis and dysfunction of sperm MMP (p?<?0.05, and p?<?0.01 respectively). However, there was no significant correlation among DF, apoptosis and dysfunction of sperm MMP with ART outcomes, except early apoptosis which showed significant (p?<?0.05) negative correlation with pregnancy rate.

Conclusion

In the present study; DF, apoptosis and dysfunction of sperm MMP indicated negative relationship with sperm parameters. Although there was a negative correlation between early apoptosis and pregnancy rate, no significant correlation was observed between these parameters and ICSI outcomes.     

Risk factors for intraventricular hemorrhage in very low birth weight infants in Tehran, Iran

Intraventricular hemorrhage (IVH) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants; 80-90% of cases occur between birth and the third day of life. In a retrospective case control clinical study, files of all premature infants with birth weights <1500 grams admitted between April 2004 and October 2005 to the Neonatal Intensive Care Unit (NICU) of Akbar Abadi Hospital were reviewed. We determined risk factors that predispose to the development of high-grade IVH (grades 3 and 4) in VLBW infants. Thirty-nine infants with IVH grade 3 and 4 were identified. A control group of 82 VLBW infants were also selected. Prenatal data, delivery characteristics, neonatal course data and reports of cranial ultrasonography were carefully collected for both groups. Those variables that achieved significance (p<0.05) in univariate analysis were entered into multivariate logistic regression analysis. A total of 325 VLBW infants were evaluated. Mortality rate was 21.5%. Multivariate logistic analysis showed that the following factors are associated with greater risk of high-grade IVH occurrence: lower gestational age (OR: 3.72; 95% CI: 1.65-8.38), birth weight (OR: 3.42; 95% CI: 1.65-8.38), mechanical ventilation (OR: 4.14; 95% CI: 1.35-12.2), tocolytic therapy with magnesium sulfate (OR: 4.40; 95% CI: 1.10-24.5), hyaline membrane disease (HMD, OR: 3.16; 95% CI: 1.42-7.45), symptomatic hypotension (OR: 2.32; 95% CI: 1.06-5.42), hypercapnia (OR: 1.9; 95% CI: 1.1-3.4) and Apgar score at 5 minutes (OR: 1.58; 95% CI: 1.59-6.32).     

Term delivery following successful treatment of choriocarcinoma with brain metastases, a case report and review of literature

Background  Cerebral metastases from choriocarcinoma are a poor prognostic indicator of outcome in both the World Health Organization and FIGO classification systems. Although gestational trophoblastic neoplasia has become the most curable of gynecological malignancies, failure rate among “high-risk” patients is still high despite of the use of aggressive multidrug regimens. Case  A 27-year-old woman (G₄P₂Ab₁) presented with hemiplegia due to brain metastases of choriocarcinoma 1 year after spontaneous abortion. She underwent craniotomy and was treated with nine courses of multiple agent etoposide, methotrexate, actinomycin- etoposide, and cisplatinum (EMA-EP) regimen combined with whole brain irradiation. She delivered a term healthy child 2 years after termination of treatment. Conclusion  Multiagent EMA-EP chemotherapy and whole brain irradiation with craniotomy in selected patients preserves fertility and may improve a patient overall prognosis.