Archives of Iranian Medicine
Volume:15 Issue: 7, Jul 2012

Several systems have been proposed to rank academic institutions worldwide. We aimed to introduce a new method of Health Research System (HRS) evaluation in Iran. In this cross-sectional study, a specific questionnaire has been used to assess stewardship, capacity building, and knowledge production through annual evaluations of HRS in Iran. This article has explored the results of the 5-year evaluation (2003 – 2008) and aims to introduce this method to other developing countries. According to our study, in the stewardship axes, all medical science universities designed strategic plans by 2008 and 70% of the approved projects were based on priorities. In the domain of capacity building, the trend in the number of arranged workshops and held congresses is ascending. In the domain of knowledge production, the number of Iranian biomedical research articles increased from 2996 in 2003 to 8816 in 2008.The proportion of ISI Web of Science/Pub Med indexed articles per academic members also increased from 0.09 to 0.33. We conclude that HRS evaluation in Iran has supported knowledge production and has strengthened evidence-based policy making. The adapted ranking system for evaluation of medical research activities is an effective strategy for HRS promotion.

Data regarding the influence of minor changes in thyroid function on body mass index (BMI) are scarce and conflicting. This study aims to evaluate the association between normal levels of serum TSH and BMI, taking into consideration the effect of smoking tobacco. In this cross-sectional community-based survey, 1581 randomly selected subjects who had no histories of thyroid disorders were studied within the framework of the Tehran Lipid and Glucose Study. Serum TSH and TPOAb were measured from the fasting serum samples. Weight and height were measured and BMI was calculated. TSH concentrations within the reference range were positively associated with BMI (P < 0.002). Each unit increase of 1 µU/ml in TSH was associated with an increase in mean BMI of 0.31 kg/m2 (95% CI: 0.1 – 0.5, P < 0.002), an association which remained significant after adjustments for sex, physical activity, and smoking and in the subgroup with negative thyroid autoimmunity. The association between BMI and TSH remained significant only in nonsmokers (P < 0.004). The results suggest that a significant positive association exists between TSH and BMI in euthyroid nonsmokers.

The role of nitric oxide (NO) in many well-known effects of morphine is well defined. NO is involved in the signaling pathway of the N-methyl-D-aspartate (NMDA) receptor, which is proposed to mediate some of morphine's effects. This research studies the effect of morphine and NMDA on lipopolysaccharide (LPS)-stimulated NO production by clonal rat pheochromocytoma (PC12) cells. We used the Griess reaction to measure NO concentrations in cell culture medium. PC12 cells that were incubated for 24 h with varying concentrations of morphine (0.1, 1, 10, 100, and 1000µM) plus LPS (1 µg/ml) did not significantly alter the concentration of NO in the medium. However, NO production increased when cells were treated for both 48 h with 100 and 1000 µM morphine and for 72 h with 10,100, and 1000 µM of morphine. After 72 h, 1 µM naloxone significantly decreased NO concentration. Naloxone, at doses of 0.1, 1, and 10µM prevented NO production by 1000 µM of morphine. NMDA (0.1, 1, and 10 µM) did not alter NO concentrations after 24, 48 or 72 h. Morphine (1 µM)-induced NO production was inhibited by 10 µM NMDA after 48 h. Inhibition of NO was also noted with1 and 10 µM concentrations of morphine after 72 h. Chronic treatment of PC12 cells with morphine significantly increases LPS-stimulated NO production via naloxone-sensitive receptors.The cells seem to release endogenous morphine in medium. NMDA does not affect NO production, which may be due to the lack of functional NMDA receptor expression in PC12 cells.

Isotretinoin (13-cis retinoic acid) is used for treatment of nodular cystic acne unresponsive to conventional therapy. It is an expensive, potent teratogenic drug with serious adverse drug reaction (ADRs). Recently, use of this drug has increased in Iran. To date, there are no published data about the use of isotretinoin in Iran; therefore, this study aims to assess its use in this country. This was a prospective, drug utilization evaluation (DUE) study conducted in an institutional community pharmacy affiliated with Tehran University of Medical Sciences (TUMS). Drug prescription, administration, and evaluation of appropriateness were recorded and compared with standard protocols. Collected data were analyzed by SPSS software. A total of 274 outpatients treated with isotretinoin enrolled in the study. Of these, 51.3% were prescribed isotretinoin under the usual recommended daily doses of 0.5mg/kg/day. Data also indicated that 33.5% of the patients were given total doses of less than 100 mg/kg (72.4 ± 17.2 mg/kg) and 12.2% received more than 150 mg/kg. With regards to the teratogenic effects of isotretinoin, only 6.8% of couples simultaneously used two methods of contraception (P = 0.001). In addition, we detected improper use of isotretinoin for mild and moderate acne in about 20% of cases. The most important finding of this study is that the doses of isotretinoin are incorrect in many cases. Incorrect dosages would decrease drug efficacy and increase the risk of relapse. In addition, patients have not been adequately counseled about isotretinoin's teratogenicity and the seriousness of its adverse effects.

Oral mucositis is a serious complication of chemotherapy that results in painful debilitating inflammation, necessitating the administration of analgesics. There is no cure for mucositis. Some studies have evaluated the effect of zinc sulfate on mucositis. The present study aims to evaluate the effect of oral zinc sulfate on prevention of mucositis, xerostomia, and pain induced by chemotherapy. This double-blind, randomized controlled trial was carried out on 50 adult patients who underwent chemotherapy during 2008-2009. Patients were divided in two groups. Patients in the intervention group were administered three, 220 mg zinc sulfate capsules daily until the end of their chemotherapy treatment. Patients in the placebo group received three placebo capsules daily, which were similar in shape, taste, and color to the zinc sulfate capsules.Data were analyzed by SPSS version 17 software, using the independent samples t-test, Mann-Whitney U and Friedman tests. The incidence of grade 3 mucositis was lower in the zinc sulfate group. In the first follow up, grade 3 mucositis was detected in 10% of patients. In the placebo group, grade 3 mucositis was seen in 46.6% of patients. By the fourth follow up, grade 3 mucositis was detected in 3.33% of patients in the intervention group and in 20% of patient in the placebo group. At the end of the study there was no grade 3 mucositis detected in the zinc sulfate group, whereas there were 3.57% of patients in the placebo group with grade 3 mucositis. The results also showed that zinc sulfate decreased the effects of xerostomia and pain in patients under chemotherapy treatment. It can be concluded that zinc sulfate might decrease the intensity of mucositis.

Many clinical trials and natural history studies on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rely heavily on liver histology to define their endpoints. There are many indications that the liver is not uniformly involved in NAFLD thus sampling error is a major concern. This study aims to evaluate the uniformity of various histologic features in livers affected with NAFLD.Samples from a forensic autopsy series were studied and subjects with NAFLD identified. We took specimens from three different parts of each liver and recorded the degrees of steatosis, hepatocyte ballooning, lobular inflammation, portal inflammation, and fibrosis. A NASH activity index (NAI) which is the sum of scores of histologic features was also calculated. The agreement between the 3 samples from each liver was studied. There were 945 autopsies performed; 896 were suitable for histologic evaluation and 283 had NAFLD. Of these, 146 livers were available to our study from which 438 samples were taken. Fibrosis[intra-class correlation (ICC) = 0.87], lobular inflammation (kappa = 0.83), and portal inflammation (kappa = 0.83)were fairly uniformly distributed in the damaged liver. Steatosis was less uniform (kappa = 0.64), and hepatocyte ballooning was least uniformly distributed (kappa = 0.57). The ICC for NAI was 0.86, which indicated good agreement. The individual histologic features of NAFLD and NASH are not uniformly distributed in the liver. Hepatocyte ballooning is especially non-uniform. Such non-uniformity should be taken into account when interpreting results of studies that rely on paired biopsies. A summary score such as NAI is less affected by sampling error.

Osteoarthritis (OA) is a progressive disorder of the joints caused by gradual loss of articular cartilage, which naturally possesses a limited regenerative capacity. In the present study, the potential of intra-articular injection of mesenchymal stem cells (MSCs) has been evaluated in six osteoarthritic patients. Six female volunteers, average age of 54.56 years, with radiologic evidence of knee OA that required joint replacement surgery were selected for this study. About 50 ml bone marrow was aspirated from each patient and taken to the cell laboratory, where MSCs were isolated and characterized in terms of some surface markers. About 20-24×106 passaged-2 cells were prepared and tested for microbial contamination prior to intra-articular injection. During a one-year follow-up period, we found no local or systemic adverse events. All patients were partly satisfied with the results of the study. Pain, functional status of the knee, and walking distance tended to be improved up to six months post-injection, after which pain appeared to be slightly increased and patients’ walking abilities slightly decreased. Comparison of magnetic resonance images (MRI) at baseline and six months post-stem cell injection displayed an increase in cartilage thickness, extension of the repair tissue over the subchondral bone and a considerable decrease in the size of edematous subchondral patches in three out of six patients. The results indicated satisfactory effects of intra-articular injection of MSCs in patients with knee OA.

Because resistance to antifungal drugs is seen in patients, susceptibility testing of these drugs aids in choosing the appropriate drug and respective epidemiology. This study has investigated and compared susceptibility patterns of the Aspergillus specie sisolated from patients by the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution (MD) assay and Etest method. The minimum inhibitory concentrations (MICs) of various antifungal agents (amphotericin B, ketoconazole, itraconazole, and voriconazole) for 108 Aspergillus species isolated from patients were determined by CLSI M38-A broth MD and Etest. The isolates were obtained from clinical samples that included tissues, sputum, bronchoalveolar lavage, abdominal tap, and cerebrospinal fluid. As revealed by the MD method, 63.9% of the isolates were sensitive to amphotericin B and 36.1% were resistant.Etest revealed that 61.1% were sensitive to amphotericin B and 38.9% were resistant. As for ketoconazole, 108 isolates (100%) were shown to be sensitive through the MD method; while the Etest revealedan 88.9% sensitivity and 11.1% were resistant. All species were susceptible to voriconazole, according to both methods. The measure of agreement (Kappa Index) for these three drugs was satisfactory (≥0.6). According to the MD method, 69.4% of the species were susceptible to itraconazole, whereas 30.6% were not. For this drug, the Etest showed 86.1% susceptible and 13.9% resistant. Voriconazole was the most effective agent against isolates. Using RPMI agar, we found the Etest to behelpful, readily available, and easy to use for determining invitro susceptibilities of Aspergillus species to voriconazole, amphotericin B, ketoconazole, and itraconazole in the region of this study.

The transient receptor potential vanilloid receptor 1, TRPV1 [previously termed the capsaicin or vanilloid receptor 1 (VR1)] is a nonselective cation channel that has been cloned and is expressed predominantly in sensory neurons. TRPV1 is activated by protons as well as capsaicin. Despite extensive research, the physiological function of TRPV1 in the gastrointestinal tract and other tissues remains elusive. We have examined the effect of the selective TRPV1-receptor ligand, capsaicin, on intestinal peristalsis by studying migrating motor complexes (MMCs). We performed experiments on Knockout mice (KO) in which the TRPV1 gene was disrupted using standard gene targeting techniques and their wildtype (WT) littermates. Jejunal contractile activity was recorded from in vitro segments of the jejunum, 4 – 5cm in length. When distended to 2 – 3 cm with H2O, the segments generated regular MMCs that were recorded as changes in intraluminal pressure. Capsaicin (1 – 100 nM) caused a dose-dependent inhibition of motility manifested as an increase in the interval between motor complexes (MCs) in the WT animal only, a response abolished by pre-treatment with TRPV1 antagonist capsazepine (Capz), ruthenium red (RR), and L-NAME. At higher doses of capsaicin (1 – 100 μM), periodic MCs were replaced by tonic increases in pressure upon which were superimposed continuous phasic contractions. This stimulation occurred in both KO and WT mice and was unaffected by pre-treatment with Capz, RR, and L-NAME. These data demonstrate the potential role of TRPV1 receptors in organized peristalsis in the mouse jejunum. These findings also suggest that inhibition of contractions in mouse jejunum by TRPV1-receptor activation does involve a nitric oxide synthetase (NOS) pathway.

The growing prevalence of heart failure and the cost associated with its management has become a major burden for most health care systems worldwide.We review the evidence from randomized studies of innovative models of care delivery for patients with heart failure, refer to some of the most influential non-randomized studies, and discuss the implications of the available evidence for practitioners, policy makers and researchers. Acknowledging that the relevance of evidence depends on the user’s needs, we conclude that the likely impact ofmost models of care on health outcomes and resource utilizationis likely to be modest. New approaches for design and evaluation are therefore required. Given the dynamic complexity of the health service environments in which any such models of care must be implemented, the future development of innovative models of care delivery would benefit from closer collaboration between service users, providers, policy makers andmulti-disciplinary researchers,as well asmore rigorous evaluation.

The aim of this study was to investigate, for the first time, the genotype of hepatitis B virus (HBV) among hepatitis patients in Eastern Azerbaijan Province, Northwest Iran. A total of 100 HBV-infected patients were enrolled in this study. Among these, 40 samples were positive for both HBsAg and HBeAg, whereas 60 samples were HBsAg positive and HBe Agnegative. Patient's sera were subjected to DNA extraction and the genotype determined by PCR using type-specific primers. The results of genotyping revealed that genotype D was the only identified genotype in both acute and chronic patients in the study region. Analysis of sequencing results showed 98% – 99% homology with the previously reported HBV genotype D sequences. Genotype D was recognized as the predominant HBV genotype in the studied area. There was no significant relationship between genotype D of HBV and different types of infections.

Cystic fibrosis (CF) is one of the most common severe autosomal recessive genetic disorders, characterized primarily by chronic obstructive lung disease and maldigestion disorder. The disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Here we present a case of a fetus with hyperechogenic bowel, in which compound heterozygosity was established for the mutations p.IIe1000fsX1001 and p.Asp110His subsequent to amniocentesis. The mutations were most likely disease-causing, and pregnancy was terminated.

Although fungal brain infections are not uncommon, intracranial granulomas due to fungi are rare. Immunodeficiency is considered to be the main predisposing factor. We have presented the case of a 21-year-old lady admitted to the emergency ward with the clinical picture of impending brain herniation. She was a known case of chronic mucocutaneous candidiasis (CMCC) since childhood and had been under oral topical nystatin treatment which she had arbitrarily discontinued for the past ten years. The patient underwent emergent craniotomy and resection of the lesion. Pathologic exam revealed its fungal granulomatous nature. Cultures documented Candida albicans as the offending pathogen. The history of immunodeficiency was a useful clue in this case. To the best of our knowledge, this was the first case of fungal granuloma of the brain in the setting of chronic mucocutaneous candidiasis.