Tehran University Medical Journal

Association studies in common endocrine diseases (review article)

Akrami SM

Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

HLA-DRB, DQA and DQB allele frequencies in Iranian patients with chronic hepatitis B by PCR-SSP

Amirzargar A

Background: The outcome of acute hepatitis B infection may be influenced by host genetic factors like human leukocyte antigen (HLA). To investigate the association between the HLA-DRB, DQA1 and DQB1 alleles and chronic hepatitis B infection, 50 patients with chronic hepatitis B (based on 6 months positive of HBsAg and HBc antibody and HBeAg and antibody by serological test), were selected from Turkman population in north east of Iran .Allele frequency in patients were compared with a 65 aged and sex match control group from healthy blood donor of that ethnic population.
Methods: HLA DRB, DQA1 and DQB1 alleles were determined using polymerase chain reaction based on sequence specific primer (PCR-SSP) method. Allele frequencies in patients and control subjects were compared by Epi-info statistical soft-wear.
Results: There was a significant increase and positive association in HLA-DRB1*0301, DQA1*0501 and DQB1*0604 allele frequency in patients group while the frequency of HLA-DRB1*1301, 1501 and DQB1*0401 and DQA1*0401, 0102 were lower in patients than control group and shows negative association.
Conclusion: In Iranian Torkman population, HLA DRB1*0301, DQA1*0501 and DQB1*0604 have an important role in susceptibility to chronic hepatitis B infection and HLA DRB1*1301, 1501, DQB1*0401 are associated with protection to chronic hepatitis B infection. Larger case control studies may be helpful to confirm our investigation.

Comparison of HCMV DNA load and antigenemia results in hematopoietic transplant recipients based on GVHD grade

Hashemi F B

Background: Human Cytomegalovirus (HCMV) infections are a significant challenge in patients with Hematopoietic Cell Transplant (HCT). Acute Graft vs. Host (GVHD) is recognized as a predisposing factor for increased incidence of HCMV reactivation. Availability of rapid and accurate tests for HCMV detection in HCT recipients is of foremost importance in developing countries, such as Iran.
Methods: A total of 201 peripheral blood leukocyte (PBL) and plasma specimens from 26 allogeneic HCT recipients were examined for HCMV DNA by polymerase chain reaction (PCR) assay. Densitometric analysis of 257bp PCR products from clinical samples and 101-106 "cloned plasmid" per µg DNA containing a HCMV specific fragment were analyzed using LabWorks software (v3.0.02). Optical density of amplicons was plotted, and calculated HCMV viral loads were compared with the patients' antigenemia results.
Results: HCMV viral loads ranged between <102 to 1.35×102 copies per µg DNA among 7 HCT patients. In addition, 14 episodes of positive antigenemia assay in 7 patients in which peak HCMV load were compared with GVHD grade II-IV patients. Significant correlation was also detected between HCMV DNA load in PBL and plasma samples, as well as HCMV DNA load in PBL samples and antigenemia results. Receiver–Operating Characteristic analysis determined that 2,200 HCMV copies in PBL samples as the threshold value for initiation of Ganciclovir therapy.
Conclusion: This report shows that rapid and sensitive assays, like quantitative PCR, are extremely valuable for detection of active HCMV infection, and life-threatening HCMV disease in HCT recipients during the post transplant period. Furthermore, high HCMV DNA load among GVHD grade II-IV patients confirms the high risk of HCMV reactivation among these HCT recipients. Tests such as quantitative PCR also helps physicians initiate timely preemptive therapy and for a shorter period, which may lead to better clinical outcome in HCMV-infected transplant patients.

Assessment of TPS tumor marker with ELISA for early detection and monitoring of gastrointestinal cancers

Salehi Nodeh A.R

Background: TPS is one of the tumor markers which has specially been considered due to its exclusive physiological characteristics like its easy measurement in serum of cancer patients. This study has been due to evaluate the efficiency of this tumor marker in the prognosis, treatment control and follow up of patients with gastrointestinal cancers including esophagus, stomach and colorectal.
Methods: TPS has been measured in 109 persons including 28 healthy people and 81 patients with different gastrointestinal malignancies which were composed of 38 patients with esophageal cancer, 20 ones with stomach cancer and 23 ones with colorectal cancer. Sampling has been done in three times depending on treatment methods. TPS has been measured with ELISA in samples which contend of 2 to 3 ml of serum from patients and the health.
Results: The obtained results, demonstrate the obvious changes in TPS serum level in patients underwent various treatment procedures.
Conclusion: The results have revealed that the serum TPS is not only as a measure of prognosis but also would be helpful in follow up and treatment control of the disease. Moreover the results has shown that serological analysis can be settled in the diagnosis and follow up with production of polyclonal antibody against TPS gene family and planning appropriate pattern.

Adjacent field dose modification in breast radiotherapy by use of half-blocks

Goodarzi A H

Background: During breast three fields radiotherapy, the problem is that the divergency of the field interferes with matching the edges. So the matching point of these supraclav and tangential field will suffer from over-dose and under-dose. To prevent these these divergency, a half- block is often applied at supracluv field. Also in some techniques like collimator and couch rotation, corner blocks and custom blocks are applied at tangential field which it renders its own problem. Hence, this research employ half-block in all three different radiotherapy scheme to some how radiate the cancerous tissue more appropriately to lessen the over exposure and yet deliver the needed dose to the tissue.
Methods: Ten breast cancer patients of Sohadaye Haftome-Tir hospital were considered for this study. The divegency of the fields at the matching point was blocked by using a half-block application and a slope, under patients. Dosimetery was measured by TLD at desired location on the skin before and after the half-block application. The measurement was carried out at 2 groups under 2 different irradiation methods (SSD, SAD).
Results: Dosimetery showed that the mean over-dose values at SSD method before applying half–block was 151% which reduced to 97% after half–block application, and in the SAD method the under-dose was improved from 41% to 80%.
Conclusion: Half–block can solve adjacent filelds problem efficiently, and since making the half-block at low cost is easily possible at any radiotherapy center, it is suggested to use block more often.

Cisplatin, cyclophosphamide versus taxol, carboplatin in epithelial ovarian carcinoma: a clinical trial

Modarres M

Background: Access to a safe and efficient chemotherapy regimen for improving the survival and live quality is a goal in ovarian carcinoma. Despite surgery is the base treatment of ovarian cancer, but in most patients chemotherapy is used due to progression of their disease. This study designed to compare two important chemotherapy regimens.
Methods: This historical cohort study compared two chemotherapy regimen cisplatin (75mg/m2)+ cyclophosphamide (750mg/m2), versus taxol (175mg/m2)+ carboplatinium (GFR+25)AUC between 1998-2005 in valiasr hospital. In this study toxicities of two regimes were compared. The survival function in these two groups were analysed with Kaplan-Meire curve.
Results: Gastrointestinal and mucosal toxicity were significantly higher in CP group compared TC group (p=0.02). Also there were no significant relation between decrease of serum CA125 and patient remission length in CP group but in other group with decrease of CA125 in lower than three cycle we had an increase in patient remission period. (P=0.02). Disease free interval in cisplatin group was longer versus taxol group (p<0.05), there was no significant difference in overall survival in two group.
Conclusion: This study revealed that cisplatin plus cyclophosphamide regimen can yet be used as a chemotherapy treatment in ovarian cancer. In this study there was no significant benefit in taxol regimen compared CP. In the adjuvant therapy of epithelial ovarian carcinoma.

The effect of influenza vaccination in the prevention of exacerbation of children asthma

Gharagozlou M

Background: Influenza epidemies which occur mosthly in cold seasons could be a risk factor for developing exacerbations and acute attacks of asthma. Although influenza vaccination is recommended for the asthmatic patients, there is a lack of sufficient clinical evidence that this annual vaccination prevents asthma exacerbation in children.
Methods: Prospective clinical trial study of 201 children with asthma, where 79 did, and 122 did not receive the influenza vaccine, was done. The two groups were compared with respect to use of bronchodilators, systemic corticosteroids, emergency department (ED) visits and hospitalizations for asthma. In multi variable analysis, adjustment was made for baseline asthma severity and demographic variables.
Results: After adjusting for other variables, the vaccinated group had a significant decreased in exacerbations frequency and duration. Also the frequency of used bronchodilators and the absence days of daycare center or school were lower in the vaccinated group (P<0.05). There was no significant difference between the two groups in relation to used systemic corticosteroids and ED or hospital admissions (P>005).
Conclusion: This study showed that influenza vaccination may be effective in prevention of some asthma exacerbation aspects.

Efficacy of megestrol acetate in treatment of 21 young patients with endometrial adenocarcinoma

Eftekhar Z

Background: Endometrial cancer is the most common malignancy of genital system which is commonly seen after menopause. Rises in the age of marriage non-surgical methods, using systemic progestins, have been evaluated to treat the young patients with well-differentiated endometrial cancer who wish to preserve their fertility.
Methods: Twenty one infertile patients with stage Ia well-differentiated endometrial adenocarcinoma were enrolled in a quasi-experimental study. The treatment initiated with 160mg/d of megestrol acetate then continued with 320mg/d for non-responsive cases. Patients follow up with FD&C and hysteroscopy. Patients divided in two groups on the basis of response to therapy and persistent. The responsive patients were introduced to IVF group and evaluated for later fertility and birth of alive newborns for three years.
Results: This study showed a response rate of 85.71% and 14.29% undergoing TAH. The mean duration of treatment was 5.85±2.00 month. The response to therapy was observed in 27.78% with dose of 160mg/d and the remaining patients with 320mg/d. Pregnancy occurred in 27.78%, 2 of which ended up in a term delivery and the others ended before term. Recurrence happened in 16.67% that 66.67% of them experienced remission again.
Conclusion: Use of 320mg/d seems to be associated with a better therapeutic response. Serious complications were not observed with this dose. Furthermore, continuance of the drug for three month following a normal pathology report was decreased the rate of recurrence.

Serum lipids and diabetic retinopathy

Shoja MR

Background: Diabetes Mellitus is the most common endocrinologic disease in human and retinopathy is one of the most common complications. Etiology of this complication is yet unknown but one of the factors that can be effective on its production or progression is serum lipid. We aim to study the relationship between different degrees of diabetic retinopathy and serum lipids levels.
Methods: An observational cross-sectional study designed to study over 37 patients with diabetes mellitus type one and 157 patients with diabetes mellitus type two. Former was selected as sensus and latter was selected randomly from diabetic patients attending the diabetes clinic in Yazd during 2002. Inclusion criteria was duration of diabetes at least seven years from diagnosis. Statistical analysis performed by SPSS package edition 11 and wit statistical tests as Chi square, Fisher Exact and ANOVA.
Results: Among 194 cases, 74 cases were males and 120 females. 90 cases (46.4%) have normal total serum cholesterol and 104 (53.6%) hypercholestrolemia. In case of triglyceride 94 cases (48.4%) have normal serum triglyceride and 100 (51.6%) hypertriglyceridemia. Distribution of different degrees of diabetic retinopathy was statistically significant due to cholesterol and triglycerides (P-Value<0.05). In different groups of sex, diabetic retinopathy was more prevalent if there was hypertriglyceridemia or hypercholesterolemia. This was correct about different groups of age and type of diabetes. This means that in different groups of age and type of diabetes, diabetic retinopathy was more prevalent if there was hypertriglyceridemia or hypercholesterolemia.
Conclusion: Prevalence of diabetic retinopathy is higher in cases with hypertriglyceridemia or hypercholesterolemia than cases with normal serum triglyceride or cholesterole.

Clinical characteristics and outcomes of pediatric germ cell tumors in Ali-Asghar Children’s Hospital 1990-2004

Ansari Sh

Background: Germ cell tumor (GCT) account for approximately 2-3% of all malignancies in childhood. About 20% of patients with GCT are still resistant to therapy.
Methods: This study was undertaken on 57 patients with Germ cell tumor who were admitted to Ali Asghar Children’s Hospital during 1990-2004. Through this study, information about sex, age type of pathology, clinical sign, treatment and survival (5-year period) was gathered in order to have better treatment and follow up. This study was carried out as across-sectional survey and the obtained data was analyzed via Spss 10 soft ware.
Results: The findings showed that the mean age of patients was 4/9 ± 0/1 (1mo -14y), male 54%, female 46%, male/female, ratio=1/1. Site of tumor: saccrococcygeal 57/8 %( 33), gonadal 42% (24). Pathological type is yolk sac 61/4% (35), dysgerminoma 12/2% (7), malignant teratoma 14% (8), embryonal carcinoma 10/5% (6). The most common clinical sign were buttock mass 31/5% (18), abdominal pain 10/5% (6), abdominal mass 17/5%(10), testicular mass 28% (16). All of the patients were treated with chemotherapy (bleomycine, vinblastin, cisplatinum) mean of duration follow up were 48/4 months. In all of patients 31/5% (18) of the cases were alive and 70% (40) of patients were relapse and 15/7% (9) no information, 52/6% (30) of cases were expired. Five years survival of patients was 62%.
Conclusion: The analysis of the patients treated shows that extragonadal location of primary tumor (specially sacrococcygeal), level of AFP above 10 ng/ml in patients ,6 or more months of age and metastatic disease were the most unfavorable factors for overall survival.

The comparison between monotherapy and combination therapy in Rheumatoid Arthritis

Khalvat A

Background: Rheumatoid arthritis (RA) is a chronic inflammatory condition. The condition can affected many tissues throught out the body, but the joints are usually most severely affected. The high incidence of RA, the conventional treatments and the experimental observation have shown by combination therapy, the disease symptoms of the patients reduce. To compare the efficacy and tolerability of single-agent Hydroxychloroquin (HCQ) with combination therapies composed of (HCQ) and Methotrexate (MTX) and (HCQ), (MTX) and Sulfasalazin (SSZ) in active rheumatoid arthritis patients with additive arthritis.
Methods: One hundred and twenty RA patients with active arthritis (male/female: 30/90) who were treated in rheumatology clinic between 2003 and 2005 were enrolled in this trial. Patients treated with (HCQ) alone(200 mg/day)were include in group (I), patients treated with combination of (HCQ) (200 mg/day)and (MTX) (7.5mg/week)in group (II),and patents treated with combination of (HCQ) (200mg/day),(MTX) (7.5mg/week)and (SSZ)(1 gr/day)in group (III), Forty patients (male/female:10/30) in group (I),(II) and (III)were eligible for statistical analysis at the end of study. Changes in variable were compared by the T-test.
Results: The combination of (MTX), (HCQ)and (SSZ) and the combination of (MTX) and (HCQ) were more effective regarding the clinical and laboratory parameters than (HCQ) alone (P<0.05). Moreover the combination of (MTX), (HCQ) and (SSZ) was more effective than the combination of (MTX) and (HCQ) (P<0.05). Combination therapies seem to be more effective and no more toxic than monotherapy in RA patients with additive arthritis.
Conclusion: Combination therapy with methotrexate, hydroxychloroquin and sulfasalazin is more effective than hydroxychloroquin alone or a combination of methotrexate and hydroxychloroquin in RA. We suggest starting combination therapy for the patients with early RA, when the diagnosis has been established.

Evaluation of libido in post hysterectomy patients

Zafarghandi N

Background: Hysterectomy is a common surgery as treatment for chronic and benign gynecologic problems. Eeach year more than half million women in USA undergo hysterectomy.
Methods: This analytical cross-sectional study, was done on 100 women who had underwent hysterectomy at least two years before the study and met inclusion criteria of study. During interview, the questionnaire were completed, then examination was done by gynecologist. Most of the information were collected from the patient’s files.
Results: In this study the most indication of hysterectomy was fibroma and the most common type surgery was total abdominal hysterectomy, and mostly were done without oophorectomy. 20% of cases were without or weak prior to operation and 80% with medium (or high) libido, after hysterectomy the figures changed to 41% and 59% respectively. After hysterectomy libido with P=0.001, frequency of coitus with P=0.001, and sexual satisfaction with P=0.013, significantly declined. Libido after hysterectomy declined with aging (P=0.01). There was no significant correlation between oophorectomy and libido.
Conclusion: Sexual function declines significantly after hysterectomy, with no association with oophorectomy and type of surgery.

Unilateral multifocal testicular biopsies in 320 patients with Germ Cell Aplasia

D Jamali Zavareii. M

Background: Germ cell aplasia (G.C.A) is one of the most important testicular causes of infertility and azospermia.In this condition the seminiferous tubules are only lined by a single layer of sertoli cell. In some cases, there is focal area with spermatogenic activity.
Methods: We studied infertile men with G.C.A referred to Jahade Daneshgahi of Iran during 1381-82, retrospectively. All the cases had more than one biopsy of one testis.
Results: In 11.6٪ of 320 cases, comparison of multiple biopsy sites of a testis revealed: when one site showed G.C.A, another site revealed areas with spermatogenic activity. Considering the cases who showed germ cells in both sites, 15.3٪ of cases multiple biopsy sites appeared to have focal spermatogenesis, better maturation of germ cells or higher scoring area for urologic operation.
Conclusion: According to new techniques in treatment of infertility with ICSI (intra cytoplasmic sperm injection) in which fertility is possible with one spermatozoa or even spermatid (after recovery), biopsy of multiple sites instead of only one site is highly recommended in azospermic patient.

Tranexamic acid in diffuse alveolar hemorrhage (case report)

Owlia MB

Background: Wagener's granulomatosis (WG) is a systemic necrotizing vasculitis characterized by upper and lower respiratory tract involvement and glomerulonephritis in most instances.
Case Report: We report a 36 years old man with DAH secondary to WG, as the presenting feature. He successfully treated with standard immune suppressive agents including pulse methylprednisolone and cyclophospha-mide, along with tranexamic acid as adjunctive therapy for control of active bleeding. Laboratory results showed mild to moderate anemia, increased serum lactate dehydrogenase and very high c-ANCA titer. Chest radiograph showed bilateral alveolar infilterates.
Conclusion: Diffuse Alveolar hemorrhage (DAH) is a dread complication of Wagener’s granulomatosis. Control of acute phase of hemorrhage with tranexamic acid can improve out come of patients.