Archives of Iranian Medicine
Volume:4 Issue: 4, Oct 2001

Background-Alpha-thalassemia is one of the most prevalent hemoglobin disorders in the world. The molecular basis of a -thalassemia is deletions of variable lengths involving one or both a -genes at the a -globin gene cluster. Functional point mutations leading to inactivation of the a -genes are less frequent. So far, no comprehensive population screening for a -thalassemia has been performed in Iran and no molecular diagnostic services are available for this disease. As a result, a considerable number of patients with microcytic, hypochromic anemia and normal Hb A2 levels might be misdiagnosed as silent b -thalassemia. The aim of the present study was to determine the spectrum of common a -thalassemia mutations in Iran.Methods-A total of 57 Iranian subjects were randomly chosen from a pool of patients with microcytic hypochromic anemia and negative b -thalassemia genotyping. They were tested for the 2 most frequent a -thalassemia deletions (-a 3.7, -a 4.2). Analysis was performed using deletion-specific PCR amplification followed by agarose gel electrophoresis of the resulting PCR fragments. Results- No -a 4.2 deletion was detected, however, 18 (31.6%) out of 57 analyzed cases demonstrated the -a 3.7 deletion, either in the homozygous or heterozygous state. Conclusion-This study suggests that the -a 3.7 deletion is a common cause of microcytic hypochromic anemia in Iran. The results are in accordance with previous studies, which report a remarkably high frequency of -a 3.7 in the Middle East. Routine screening for this mutation will improve the molecular diagnosis of anemia in Iran.

Background-Beta-thalassemia is the most common hereditary disorder in Iran and during the past 10 years, amplification refractory mutation system (ARMS) and restriction fragment length polymorphism (RFLP) were the sole molecular technique used for diagnosis of the disease. Although many beta-globin gene mutations exist in the Iranian multiethnic population, these techniques seem labor-intensive, time-consuming and expensive. This has urged us to use new techniques such as reverse hybridization and direct sequencing this issue. Methods-In this study, reverse hybridization was applied in parallel with ARMS to screen for the 10 most common beta-thalassemia mutations and hemoglobin S in 82 patients clinically diagnosed as beta-thalassemia minor and major.Results-From the 82 cases detectable by both methods, 80 had similar results. Compared to ARMS, reverse hybridization appeared to be more reliable, cost-effective, fast and applicable.Conclusion-Considering the vast spectrum of beta-thalassemia mutations in Iran, a fast and reliable technique such as reverse hybridization represents vital advantages in comparison with the traditional diagnostic methods. In fact, it is recommended as the technique of choice that can be employed by the National Thalassemia Project for the detection and prenatal diagnosis of beta-thalassemia in Iran.

Background-Leber congenital amaurosis (LCA) is a hereditary neonatal blindness. Congenital blindness is common among a specific branch of the Lore tribes in Kerman province, central Iran. This study was designed to identify all affected patients, construct a pedigree for obtaining the transmission pattern, establish definite diagnosis, and finally determine the genetic origin of the blindness among this tribe.Methods-Using several field studies, over a period of 2 years, and conducting interviews with senior members of the tribe, a total of 25 patients were identified. Electrophysiological tests and karyotyping were undertaken for appropriate cases. DNA samples collected from a group of affected individuals and their first-degree relatives were used to evaluate genetic linkage to a number of known loci on different chromosomes.Results-Autosomal recessive pattern of inheritance and neonatal visual impairment without any noticeable eye lesions was documented. Infantile nystagmus, keratoconus, narrowing of retinal vessels, retinal degeneration, mild pigmentary retinopathy and electrophysiological investigations were consistent with LCA. Only one locus on 17p13.1 was consistent with linkage in this kindred.Conclusion-We made a large pedigree of LCA for the first time in Iran. Mutation screening of the responsible gene is currently in progress.

Background-The aim of this study was to determine IS6110 banding pattern of Mycobacterium tuberculosis (MTB) isolates for evaluation of tuberculosis (TB) transmission. These isolates were obtained from intermediate laboratories of six major provinces of Iran; East Azarbaijan, West Azarbaijan, Khorasan, Kerman, Kermanshah and Fars.Methods-Restriction fragment length polymorphism (RFLP) was performed on 100 suitable isolates, which have been obtained from some laboratories thought Iran. Fingerprinting was done using the oligonucleotide 6110 a’ (5΄-GTGAGGGCATCGAGGTGGC) and 6110 b΄ (5΄-GCGTAGGCGTCGGTGACAAA) primers.Results-We observed two types of banding patterns among the typed strains: sixty-two percent of MTB strains had a high copy number of IS6110, whereas 33% had a low copy number. In addition, five MTB strains (5%) without any IS6110 banding pattern were detected. The analysis of banding pattern in MTB isolates revealed heterogeneous DNA fingerprinting. The computer-assisted dendogram system demonstrated 8% to 51% similarity among typed strains. According to the available data, similarity between 90% and 100% is considered as homogeneous DNA fingerprinting.Conclusion-Since two banding patterns (low and high) have been detected, it could be suggested that two or more lineage for TB strains might exist in Iran, which requires further analysis. This study also suggests that in these cases, tuberculosis is characterized by the absence of obvious focuses of transmission.

Background-Mashhad, a city in northern Iran, is a newly recognized endemic area for a retrovirus, the Human T-cell Lymphotropic Virus type I (HTLV-I). This virus is the causative agent of a chronic slowly progressive cord syndrome called HTLV-I associated with Human T-cell virus type I-associated myelopathy or/tropical spastic paraparesis (HAM/TSP) and has tropism for CD4+ T- cells, which results in T-cell activation that escape the autocrine pathway.Objective-The purpose of this study was to determine the immuno-phenotypic features of peripheral blood lymphocytes of HAM/TSP patients, especially differential expression of interleukin-2 receptor α (IL-2Rα) chain on the surface of the T-cells of HAM/TSP patients, HTLV-I carriers and healthy controls.Methods-Subjects in this case-control study included 20 HAM/TSP patients, 14 HTLV-I carriers and 12 healthy controls. The absolute white blood cell count and the differential cell count were determined by hematologic analysis and the relative and absolute number of peripheral blood CD3+ CD25+ T-cells were determined by flowcytometry.Results-The relative number of lymphocytes (36±9%), relative number of CD3+ cells (74±7%) and the relative and absolute number of CD25/3+ cells (21±8%, 0.309±0.155 x109/1) were significantly higher in HAM/TSP patients than healthy controls (29±7%, 68±4%, 13±3%, 0.187±0.065 x 109/1) (p<0.05). The relative lymphocyte (36±5%) and relative CD25/3+ (18±5%) cell counts were significantly higher in carriers in comparison with controls. No significant differences were present in these parameters between carriers and HAM/TSP patients.Conclusion-This differential pattern of T-cell activation markers among the study groups may have striking diagnostic and therapeutic implications.

Background-Aqueous extract of Teucrium polium has been used traditionally as an antidiabetic agent in many Iranian provinces. The goal of this study was to investigate the hypoglycemic effect and histopathological changes in the liver following the ingestion of an extract of T. polium in streptozocin-induced diabetic rats. Methods-An aqueous extract of Teucrium polium was fed intra-esophageally to healthy and streptozocin-induced diabetic rats for several days. Serum glucose levels of the case group were measured daily and compared to those of the healthy control. At the end of the extract ingestion period, parts of the animal liver were excised, fixed in formalin and studied histologically. Results-Treatment of diabetic animals with the aqueous extract resulted in a significant decrease (p<0.001) in the serum glucose level after 24h, which reached those of the normoglycemic animals in 8 days. Liver sections from T. polium-treated rats showed marked cytoplasmic hydropic changes in 1/3 to 2/3 of the liver lobule in perivenular and midzonal areas. Apoptopic bodies were also noted in the perivenular zone and Kupffer cells increased in number. Nuclear enlargement with anisonucleosis and prominence of 1 or 2 nucleoli suggestive of regenerative changes were also observed.Conclusion-Although the aqueous extract of T. polium has strong hypoglycemic properties in experimental animals, human application should be discouraged.

Objective-To carry out cytogenetics investigations on bone marrow and peripheral blood samples obtained from patients with leukemia.Methods-A total of 35 bone marrow or blood samples from all types of leukemia patients was referred to the Cytogenetic Laboratory of Tehran University of Medical Sciences. The referral centers were the Hematology and Oncology Centers in Shariati Hospital and the Children’s Medical Center. Cell culturing including high resolution (HR) and Giemsa banding (G-bands by trypsin using Giemsa strain; GTG) were carried out according to standard protocols. Chromosome analysis was performed following international system for human cytogenetics nomenclature (ISCN) guidelines (1995). Results-Among the 28 cases, chromosomal abnormality rate was 50% in acute myelogenous leukemia (AML), 80% in acute lymphocytic leukemia (ALL), 83% in chronic myelocytic leukemia (CML) and 100% in the Lymphoproliferative disease (LPD) groups. Two patients in the myeloproliferative disease (MPD)/CML group had normal karyotype and were therefore treated as MPD. The types of observed chromosomal abnormality were translocation 15/17 in AML-M3 patients, double trisomy 8 and 13 in an AML patient, hyperdiploidy of 50- 55 of chromosomes in a child with ALL, a double abnormality of Philadelphia and t 7/8 in a CML patient at blast stage and a complex variant Philadelphia translocation of a t4/9/22 in a CML patient. Conclusion-Despite being a pilot study with a small number of samples, the majority of patients demonstrated chromosomal abnormalities comparable to previously reported cases in other countries. The type of chromosomal abnormality was relevant to diagnosis and stage of the disease.

Objective-The high prevalence of esophageal cancer (EC) in northern Iran, along with its unknown etiology, continues to be a major public health problem. Ecological and case-control studies have discussed the probable role of dietary factors in this disease. The aim of this study was to determine the relationship between EC and the type and characteristics of consumed food and beverages at the time of the study as well as in the past. Methods-A total of 99 cases and 192 controls were enrolled in this study. Clinicians and pathologists referred the patients to the Babol Research Base, which is under the supervision of the Institute of Public Health Research of Tehran University of Medical Sciences. For each patient two controls were selected from their neighbors. Data were collected by means of a structured questionnaire concerning dietary habits.Results-There were no significant differences between the case and control groups in respect to the age, sex and ethnic origin. The case group showed significant differences in family history of cancer other than EC, history of gastroesophageal reflux, habit of rapid drinking of hot tea, and eating of hot foods. These factors were found to be related to the presence of EC, whereas eating cheese, vegetables, fresh fruits, black pepper and turmeric were found to be protective factors.Conclusion-This study showed some differences in the diet content and habits of patients suffering from EC in comparison to normal controls. Further elaborate studies are required to reveal the true pattern of dietary divergence in these patients. Besides, the authors are aware that recall bias might have distorted some of the results. More objective measures for assessment of diets are recommended.

Background-Diarrhea is a major cause of mortality in 15 to 20 percent of the under 5-year-olds, and among the bacterial agents causing diarrhea, the five most important are Shigella, Salmonella, E. coli, Campylobacter and Yersinia.Methods-In a one-year study conducted in cooperation with a local health center in Islamshahr, South of Tehran, rectal swabs were collected from children less than 5 years of age who presented with diarrhea. Frequency evaluations of Yersinia and Campylobacter along with other intestinal bacterial pathogens were made.Results-A total of 1600 samples were analyzed, 235 (14.7%) of which were positive. Most (119 cases; 50%) high-risk ages included children less than 2 years of age. Enteropathogenic Escherichia coli (EPEC) was the most common (109 cases; 6.8%) cause of diarrhea followed by Shigella (54 cases; 3.4%), Salmonella (46 cases; 2.9%), Campylobacter (15 cases; 0.9%) and Yersinia (11 cases; 0.7%). Seasonal investigations show that, with the exception of Yersinia, all pathogenic bacteria are the most frequently isolated organisms occurring in the summer. Conclusion-Better knowledge about the causes of infection and the epidemiological situation could help the management of intestinal infections.

We report two cases of a 17- and 19-year-old brothers from Rasht (North of Iran), who presented with actinic lichen planus lesions. The younger brother had typical annular patches on his forehead and neck and violaceous papules on his neck. The second brother presented with pigmented melasma-like lesions on his face. Histopathologic studies revealed lichen planus-like eruptions. Many reports describe the tendency of familial lichen planus (LP) developing at an early age and to becoming severe or chronic, and having widespread atypical manifestations. Our report probably is the first, which describes familial occurrence of actinic LP and adds further evidence to the possible role of genetic factors in triggering and determining different types of LP other than the disease itself.