مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال شصت و نهم شماره 4 (پیاپی 124، تیر 1390)

Cell-therapy provides a promising alternative for the treatment of type 1 diabetes. Monocytes which have a reprogramming or differentiation potential and are more available than any other types of stem cells, have been recognized as candidates for such investigations. The aim of the present study was to evaluate the differentiation potential of rat peripheral blood monocytes into insulin-producing cells by the use of rat pancreatic extract (2 days after a 60% pancreatectomy). Rat peripheral blood monocytes were isolated and cultured. Adherent monocytes were induced to differentiate into programmable cells in RPMI supplemented by 10% FCS, β-mercaptoetanol, M-CSF and IL-3 for six days. The dedifferentiated cells were analyzed by invert microscopy. Cultures of Programmable Cells of Monocytic Origin (PCMOs) were continued in RPMI, containing 10% FBS, pancreatic extract and 5 mmol/L glucose for 15 days. The medium was replaced every three days. At the end of the protocol, insulin and c-peptide excreted by the differentiated cells were tested by radioimmunoassay on days 6, 14, and 21. In order to verify insulin production in the cells, dithizone-staining, which is a method for insulin identification, was employed. The results showed that the cells cultured in rat pancreatic extract secreted insulin and c-peptide relative to the control group. Dithizone-staining was positive in the aforesaid cells (P<0/05). The results of the current study showed that pancreatic extract treatment can differentiate rat peripheral blood monocytes into insulin-producing cells which can be regarded as a potential source for the treatment of diabetes.

With respect to the importance of hepatitis B vaccination of high-risk groups such as prisoners, this study was performed to assess the comparability of a short-course double-dose vaccination schedule with the standard 3-dose schedule. Within a randomized clinical trial, a short-course vaccination (at months 0 and 1) with 20 microgram (double-dose) doses of the vaccine was compared to the standard method of hepatitis B vaccination (at months 0, 1 and 6, with 10-microgram doses) in 100 prisoners in Zahedan city in Iran in 2009. We made sure the sera from all the individuals were negative for markers of previous hepatitis B infection. Subsequently serum from all the participants was tested for anti-HBs antibody 1, 2 and 7 months after the first dose of vaccination. Seroconversion rates (HBsAb>10 mIU/ml) 1, 2 and 7 months after the first dose of vaccination were similar in the routine (11%, 79% and 94%, respectively) relative to the double-dose group (26%, 95% and 93 %, respectively). The mean values of anti-HBs antibody titers were similar in the 1st and 2nd months for the two groups but it was significantly higher (P=0.002) in the routine dose (514 mIU/ml) versus the double-dose group (130 mIU/mL), in the 7th month. Demonstrating comparable results with the standard 3-dose schedule, it seems that short-term double-dose vaccination for hepatitis B is a safe and acceptable method for use in high-risk groups such as prisoners.

Intrauterine insemination (IUI) is a less expensive and less invasive treatment in comparison with other assisted reproductive techniques, and it has been widely used for a variety of indications as well as in the treatment of couples with infertility. The outcome of IUI may be affected by numerous factors but in this study, we evaluated the effects of cervical mucus removal undertaken before IUI on clinical pregnancy rates. In this randomized clinical trial study, all infertile women who were candidates for IUI and attended Shahid Akbar Abadi Hospital during 2009 and 2010 were recruited. The participants were randomly assigned into two groups. Cervical mucus was removed prior to IUI in patients in group A but in group B, a classic IUI was done without removing the cervical mucus. Pregnancy rates were assessed in the two groups by serum levels of β-HCG and detection of fetus in the uterus. 291 women including 143 in the classic IUI group and 148 in cervical mucus removal group completed the study. The pregnancy rates were 14.2% (21 pregnancies upon 148 cycles) in the cervical mucus removal group and 7% (10 pregnancies upon 143 cycles) in the control group (P=0.04, OR: 2.199; CI 95%: 0.997-4.85). The findings showed that cervical mucus removal could result in a two-fold increase in pregnancy rate in comparison with classic IUI. Thus, we suggest this practical and noninvasive method to improve pregnancy rate in these patients.

In the last two decades, cryptococcosis has been gaining a distinct public health importance due to the growing number of AIDS cases. Considering the low sensitivity of direct examination with India ink and culture, use of sensitive techniques is crucial in the diagnosis of cryptococcal meningitis. Polymerase Chain Reaction (PCR) can be used to directly detect Cryptococcus neoformans in CSF samples to increase the diagnostic power in cases where conventional methods are unable to detect the organism.

In this cross-sectional study, CSF samples were obtained from 25 patients suspected of having neurocryptococcosis. The patients were referred to the Medical Mycology Laboratory of the School of Public Health affiliated to Tehran University of Medical Sciences from March 2009 to February 2010. Three different methods, direct India ink examination, culture and PCR were used to evaluate the CSF samples. Two 102 and 106 of Cryptococcus neoformans dilutions in 1ml of CSF were prepared and examined by the three methods. In PCR method, two primer pairs were selected to amplify the Cryptococcus neoformans URA5 gene. The sequences of primers were for A, B, C and D serotypes.

Only in one case PCR, as well as direct examination and culture were positive. All the other samples were negative in PCR, direct examination or culture. Both CSF dilutions were positive in the three tests in the mentioned patient and the positive control.

PCR method can efficiently identify both control and positive samples of Cryptococcus neoformans.

Cancer of uterine cervix is the second cause of death in women in the world and the most common cause in developing countries. Because the majority of women with invasive cervical cancer of the uterine have not previously undergone screening, many clinicians assume that Pap smear has a high degree of accuracy; but problems such as false positive and false negative interpretations, as well as interobserver variability have questioned its validity. We retrieved 162 positive cervical smears that had been originally interpreted as ASC-US, ASC-H, LSIL, HSIL, SCC, AGC and adenocarcinoma from the cytology archives of Women's Hospital in Tehran, Iran. The slides were rescreened by an experienced pathologist and reclassified in the mentioned categories. All the 162 slides were reviewed by three more pathologists in a blind study using interpretative criteria utilized in their daily routine to evaluate interobserver reproducibility. To increase the level of interobserver agreement, the diagnostic categories were reduced to squamous Vs. glandular abnormalities and invasive (SCC and adenocarcinoma) Vs. non-invasive abnormalities. The results obtained in this study indicated slight interobserver agreement (k=0.26). The most reproducible category was the invasive category (SCC in addition to adenocarcinoma) and the least agreement was seen for HSIL (k=0.19). This study showed that reproducibility of cytological interpretation of conventional Pap smears varies among interpretive categories and the overall interobserver agreement is slight. Since convening on the reduction of interobserver discrepancy in Pap smear interpretations necessitates more reliable information of interpretative variability, larger studies need to be undertaken.

Recurrent miscarriage is defined as the loss of three or more pregnancies. Recurrent Pregnancy Loss (RPL) is traditionally investigated after three or more consecutive losses. Although some believe that the investigation must be launched after two miscarriages, there is not enough compelling evidence to draw conclusion. In this cross-sectional study, we studied 58 women with two or more consecutive abortions (37 women with two and 21 women with three or more miscarriages) from 2005 to 2009. The following risk factors were analyzed and compared between the two groups: endocrine dysfunctions, genetic abnormalities, uterine anomalies, infections, thrombophilia, polycystic ovary syndrome, autoimmune disorders, sperm characteristics, and advanced maternal age. We did not find any known factor for pregnancy losses in 18 (31.03%) patients but in the rest, the most common cause of Recurrent pregnancy loss was endocrine disorders (41.4%). The other causes were uterine abnormalities (12.1%), infections (12.1%), maternal age more than 35 years (12.1%), thrombophilia (8.6%), abnormal semen analysis (8.6%), genetic defects (6.9%) and autoimmune disorders (1.7%). There were no significant differences between the two groups in regards with the causes of abortion except uterine abnormality (P=0.039) which was more frequent in women with three or more three miscarriages (23.8%) relative to women with two abortions (5.4%). There were no significant differences between women with two or women with three or more three abortions in regards with the causes of abortion except uterine anomalies. Therefore, it seems quite reasonable and perhaps beneficial to start the investigation in patients with two abortions.

Obesity is a major health problem all around the world. On the other hand, few people, especially women, are physically active to the levels recommended by Healthy People 2010 web site managed by the U.S. Department of Health and Human Services. The objective of this study was to compare the potential effects of intermittent and continuous exercise programs combined with concurrent calorie restriction diets on lipid profile and fasting blood sugar in overweight and obese females.

Forty-five women with a sedentary life style and a BMI greater than 25 kg/m2, were randomly assigned to one of the three groups (15 subjects in each group): a) 40 minutes of medium-intensity intermittent exercise (64-76% of maximal heart rate), 3 bouts per day for 5 days a week, b) a single bout of a 40-minute continuous exercise per day for 5 days a week, C) the non-exercising control group. A self-monitored calorie restricted diet was recommended to all participants by a dietitian. The lipid profile, fasting blood sugar and blood pressure of all participants were assessed at baseline and 12 weeks after the intervention period.

After the intervention, there were no significant differences among the groups in terms of lipid profile [cholesterol (P=0.94), triglyceride (P=0.62)] fasting blood sugar (P=0.054), systolic blood pressure (P=0.84) or diastolic blood pressure (P=0.30).

There seems to be no significant differences between short term continuous and intermittent aerobic exercise programs in improving lipid profile, fasting blood sugar or blood pressure both in overweight and obese women.

Psoriasis is a chronic, inflammatory disease of the skin. Recently, nicotinic cholinergic receptors have been demonstrated on keratinocytes, stimulating calcium influx and accelerating cell differentiation. Therefore, smoking and nicotine seem to influence inflammatory processes in psoriatic skin. The aim of this study was to determine the frequency of cigarette smoking as an independent risk factor in patients with psoriasis who attended the department of dermatology at Razi Hospital in Rasht during the years 2008 and 2009. In this descriptive-inferential study, we recruited 96 patients with psoriasis vulgaris and 96 individuals as the controls. The participants were adjusted for sex, age and body mass index. The collected data related to smoking status, duration of smoking habit, smoking intensity, pack-year smoking history, and passively exposure to smoking were documented in a researcher-devised questionnaire. Subsequently, the data were analyzed by descriptive and inferential statistics such as χ2, t-test and Mann-Whitney U test by SPSS software. The smoking rate was 33.3% in the patients and 19.4% in the controls. Pack-year history, regarded as the intensity and duration (years) of smoking, significantly increased the risk of psoriasis vulgaris (P<0.05, OR=2.07, 95% CI=1.17-3.68). Being a passive smoker did not make significant differences between the cases and the controls. Our study demonstrated that psoriasis vulgaris had a relationship with duration and intensity of cigarette smoking and revealed the importance of smoking cessation, particularly among patients with psoriasis.

Diabetes insipidus is a rare disease which can be considered as a part of broad spectrum of preeclampsia manifestations. A 39-year old primigravid woman, with an unremarkable past medical history, was admitted in the 33rd week of gestation for elevated blood pressure. On admission, her blood pressure was 140/90 mmHg and the only abnormal laboratory findings were trace proteinuria and elevated liver enzymes. During the following days her blood pressure rose to 150/100 mmHg with deterioration of clinical and paraclinical status of the patient characterized by excessive thirst, polydipsia and excretion of large amounts of diluted urine. Having considered the patient's aggravating status, termination of pregnancy was planned. Fortunately, all the clinical and paraclinical presentations, including those related to the probable diabetes insipidus disappeared on the second day of postpartum period. Sign and symptoms of diabetes insipidus should be considered in all cases admitted for preeclampsia.

The combinations of antiretroviral (ARV) drugs have proven effective in controlling the progression of AIDS, but these benefits can be compromised by drug resistance. Thus, drug-resistance testing has become an important tool in the management of HIV-infected individuals.1 Drug resistance develops when mutations in the HIV virus proteins occur due to amino acid substitutions.2 Drug resistance testing is done in two ways: phenotypic test and genotypic test.3 In the first method, virus proliferation is measured in the presence of different concentrations of the drugs. In the second, the genetic structure of viral genome sequences are investigated.4 Although, the first case of HIV infection in Iran was identified 23 years ago (1988), there is still no study published on its drug resistance. The main purpose of this study was to determine the prevalence of drug resistance mutations in patients with HIV/AIDS attending Imam Khomeini Hospital in Tehran. The secondary objectives of the study were to determine the frequency of drug resistance to specific drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PI). We collected plasma samples from 25 patients with HIV/AIDS and immunological failure. After the extraction of the viral RNA from plasma, genomic sequencing was performed. Finally, the data for determining drug resistance were analyzed by the Stanford HIV Drug Resistance Database (http://hivdb.stanford.edu) software. Out of the 25 patients under study, 20 were male (80%) and five were female (20%). Routes of HIV transmission were: 56% by needle sharing among injecting drug users (IDUs), 20% through sexual contact, 12% through blood transfusions and 12% by unknown routes. High-level drug resistance for ARV drugs included: 24% to NRTIs, 28% to NNRTIs and zero percent to PI drugs. In addition, 15 patients had been infected with genotype A and 10 patients with genotype B of the virus subtypes. More than half of the patients (56%) had HCV co-infection and 44% had prison histories. Overall, the prevalence of drug resistance was 28% which is lower to those of other countries which range from 30% to 90%. Among NRTI drugs, 24% had high-level drug resistance to Lamivudin while no resistance was witnessed against Tenofovir. Among NRTI drugs, 8% had high-level and 68% had low-level resistance to Stavudine. Among NNRTI drugs, 24% and 28% of the patients showed high-level resistance to Efavirenze and Nevirapine, respectively, although the resistance rate in the present study was much lower in comparison to similar studies in China, Venezuela and Chile with respective resistance rates of 61%, 38% and 84%. In this study, no resistance was seen against PI drugs, while the resistance rates in other countries, such as Venezuela, Chile, Brazil and the U.S. have been respectively reported to be 47%, 45%, 45% and 41%.5 With higher genetic barriers than NNRTI drugs, and lack of resistance to them, PI drugs can be used effectively in health care systems in triple drug regimens. With a compliance rate of 32% in our study, 2NRTI+PI combination seems to be preferable to 2NRTI+NNRTI combination for the treatment of HIV/AIDS patients