Novel RAB3GAP1 Mutation in the First Tunisian Family With Warburg Micro Syndrome

Background@#and Purpose Warburg Micro syndrome (WARBM) is a rare autosomal recessive genetic disease characterized by ocular, neurologic, and endocrine anomalies. WARBM is a phenotypically and genetically heterogeneous syndrome caused by mutations in RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20. Here we present the clinical and genetic characterization of a consanguineous Tunisian family with a WARBM phenotype presenting two pathogenic variations, one of which is on RAB3GAP1. @*Methods@#We applied whole-exome sequencing (WES) to two affected young males presenting a WARBM-compatible phenotype. @*Results@#We reveal a new variation in RAB3GAP1 (NM_012233.3: c.297del, p.Gln99fs) and another variation in ABCD1 (NM_000033: c.896A>G, p.His299Arg). Each of these mutations, which in silico predictions concluded as being pathogenic variations, affects a critical protein region. Both affected males presented a WARBM-compatible phenotype, with severe intellectual disability, severe developmental delay, postnatal growth delay, postnatal microcephaly, congenital bilateral cataracts, general hypotonia, and a thin corpus callosum without a splenium. However, intrafamilial clinical heterogeneity was present, since only the oldest child had large ears, microphthalmia, foot deformities, and a genital anomaly, and only the youngest child had microcornea. Despite the mutation identified in ABCD1, our patients did not have any Xlinked symptoms of adrenoleukodystrophy disorder that are usually caused by ABCD1 mutations, which prompted our interest in clinical monitoring. @*Conclusions@#WES analysis of a consanguineous Tunisian family with WARBM revealed a novel variation in RAB3GAP1 (NM_012233.3: c.297del, p.Gln99fs) that is most likely pathogenic and allowed us to confirm the diagnosis of WARBM.

Genomic diversity of Clostridium perfringens strains isolated from food and human sources

Clostridium perfringens is a serious pathogen which causes enteric diseases in domestic animals and food poisoning in humans. Spores can survive cooking processes and play an important role in the possible onset of disease. In this study, RAPD-PCR and REPPCR were used to examine the genetic diversity of 49 isolates of C. perfringens type A from three different sources. The results of RAPD-PCR revealed the most genetic diversity among poultry isolates, while human isolates showed the least genetic diversity. Cluster analysis obtained from RAPD-PCR and based on the genetic distances split the 49 strains into five distinct major clusters [A, B, C, D, and E]. Cluster A and C were composed of isolates from poultry meat, cluster B was composed of isolates from human stool, cluster D was composed of isolates from minced meat, poultry meat and human stool and cluster E was composed of isolates from minced meat. Further characterization of these strains by using [GTG] 5 fingerprint repetitive sequence-based PCR analysis did not show further differentiation between various types of strains. In conclusion, RAPD-PCR method seems to be very promising for contamination source tracking in the field of food hygiene

Environmental Contamination by Echinococcus granulosus sensu lato Eggs in Relation to Slaughterhouses in Urban and Rural Areas in Tunisia

Hydatidosis has become a real concern for health care institutions and animal rearers in Tunisia. The Tunisian endemicity is aggravated by the growing number of dogs and the difficulty of getting rid of contaminated viscera because of the lack of equipment in most slaughterhouses. Therefore, microscopic and molecular tools were applied to evaluate the role of slaughterhouses in canine infection and Echinococcus granulosus sensu lato (s. l.) egg dissemination. Exposure risk to E. granulosus s. l. eggs in urban and rural areas was explored in order to implant preventive and adapted control strategies. Microscopic examinations detected taeniid eggs in 152 amongst 553 fecal samples. The copro-PCR demonstrated that 138 of 152 taeniid samples analyzed were positive for E. granulosus s. l. DNA. PCR-RFLP demonstrated that all isolated samples belonged to E. granulosus sensu stricto (s. s.). An important environmental contamination index (25.0%) by E. granulosus s. l. eggs was demonstrated. The average contamination index from the regions around slaughterhouses (23.3%; 95% CI: 17.7-28.9%) was in the same range as detected in areas located far from slaughterhouses (26.0%, 95% CI: 21.3-30.8%). Echinococcosis endemic areas were extended in both rural (29.9%, 95% CI: 24.8-34.9%) and urban locations (18.1%, 95% CI: 13.0-22.9%). The pathogen dissemination is related neither to the presence/absence of slaughterhouses nor to the location in urban or rural areas, but is probably influenced by human activities (home slaughtering) and behavior towards the infected viscera.

incidence of serious adverse events in a Tunisian hospital: a retrospective medical record review study

Aim: To describe the epidemiology of serious adverse events [SAE] reported in the division of internal medicine at the Mongi Slim university hospital in Tunis, to analyze their causes and contributing factors and compare them to that reported in literature so as to establish prevention strategies when these events were deemed preventable

Methods: This retrospective study collected the medical records of randomly selected 500 index hospitalizations. Records review was conducted in two stages: a primary review that aimed to detect hospitalizations where a SAE was likely to have occurred then a secondary review which purpose was to confirm the presence of the SAE, to determine its nature and its preventability

Results: SAE were detected in 5.2% of hospitalizations with a preventability of 57.7%. These events were responsible for a prolongation in 27.0% of hospitalizations and disability in 15.4% of cases. They were the cause of admission in 42.9% of hospitalizations in which a SAE occurred. The SAE consisted in adverse drug events in 73.0% of cases, healthcare-associated infections in 19.0% of cases, non-surgical procedures in 4% of cases and pressure ulcers in 4.0% of cases. Age and number of comorbidities were identified as the main risk factors for the occurrence of SAE

Conclusion: Awareness of the extent and severity of the problem of iatrogenesis is necessary because it is a prerequisite to establishing a culture of patient safety among caregivers

[Marshall syndrome: clinical, radiological and genetical features of a Tunisian family]

Marshall syndrome is a rare autosomal dominant skeletal dysplasia. It associates a particular facial dysmorphism with midface hypoplasia, ocular abnormalities and sensorineural hearing loss. It is caused by heterozygous mutations in COL11A1 gene coding the 1 chain of collagen XI. Stickler syndrome is the principal differential diagnosis of Marshall syndrome. Clinical and radiological study of Marshall syndrome in a Tunisian family with a linkage study of the COL11A1 gene to this disease. We report the clinical and the radiological findings of a Tunisian family including 8 members affected by Marshall syndrome. The linkage of the COL11A1 gene to this disease was tested using the polymorphic microsatellite markers of DNA. A variability of the clinical expression of Marshall syndrome was reported. Specific Marshall phenotype and an overlapping phenotype between the Marshall and Stickler syndromes were observed among the affected members of this family. The ocular manifestations were also heterogeneous. Marshall syndrome's specific radiological signs were found. The linkage study supports the linkage of the abnormal phenotype to the COL11A1 gene. There is a variability of the clinical expression among the affected members of the study's family. We will continue searching the causative mutation to establish a clear genotype- phenotype correlation

Entering the fractured tracheotomy tube into the left bronchus, a case report

Background and Purpose: Tracheostomy is a second selective approach to management the upper respiratory tract obstructions after intubation and used in patients who require long-term ventilation. This article reports a rare complication, entering the fractured tracheostomy tube into the left bronchus

The Patient: A 74-year-old man with a large hematoma in the right frontal lobe, Craniotomy surgery and evacuated of hematoma was done. A Patient's metal tracheostomy tube fractured and entered into the left bronchus that is a rare complication. The ICU staff immediately recognized and ENT specialist removed the fractured tube with rigid bronchoscopy

Conclusion: Fracturing of the Tracheostomy tube is one of the rare complications that need careful examination before the tubes used and applying the standard tracheostomy tube Should be considered

Clinical and laboratory findings of a group of Iranian patients with oral lichen planus

Statement of Problem: Lichen planus [LP] is a chronic disease that affects skin and mucous membranes. Lesions of oral lichen planus [OLP] can persist for a long time. Varying prevalence rates of oral lichen planus have been reported in different parts of the world, while information regarding the epidemiology of this disease in Iran is incomplete

Purpose: This study was designed to evaluate the characteristics of oral lichen planus in a group of Iranian patients and compare the results with similar conducted studies in other populations

Materials and Method: In this descriptive study data were collected from charts of 158 patients In Kerman, Iran [1997-2005] over 8 consecutive years. For each patient, age at presentation, gender, chief complaint, duration of chief compliant, previous treatment, current medications, skin involvement and a complete medical history has been recorded. A number of possible etiologic factors and possible presence of diabetes or liver disease also analyzed. Laboratory evaluations consisted of glucose tolerance test [GTT] and liver function tests [LFT]. This data were analyzed by SPSS version 12 statistical software

Results: The mean age of study population was 41.16 years. Subjects were predominantly female [65.1%]. Liver function tests [LFT] were abnormal in 19.6% of cases. Disturbance of glucose metabolism and fasting blood sugar was also higher than normal limit in10.8% and 2.9% of cases respectively. Atrophicerosive lesions were found in 17 of the cases. In 50 patients the lesions were exclusively keratotic and in 91 the lesions were atrophic-erosive and keratotic. Most oral lesions were multifocal [88.6%], with the buccal mucosa being the most common location in each clinical form [87.3%]. Duration of oral lesions ranged from 0.4 to 20 years with a mean of 1.54 year

Conclusion: This study showed that epidemiological and clinical features of the disease in Kerman are similar to those mentioned in literature. Also, in this study LFT and GTT were abnormal in 19.6% and 10.8% respectively

[ Comparison of clinical signs and symptoms presentation in men and women with myocardial infarction attending in Mashhad hospitals of Imam Reza and Ghaem]

Myocardial infarction is the leading cause of death in Iran and the world. Differences in signs and symptoms sometimes delay the diagnosis. This study aims at comparing clinical signs and symptoms of acute myocardial infarction in men and women. This analytic - descriptive research was carried out on 110 patients [36 women and 74 men] with MI experience who referring in emergency wards of Imam Reza [PBUH] and Ghaem hospitals. The subjects were selected randomly sampling. Data were collected from sample forms, individual information forms; the pain characteristics record forms, electrocardiogram and laboratory forms, pain numerical rating scale, Mc-Melzac pain questioner and electrocardiogram machine. The results showed that Chest pain was the most common initial symptom in both men and women so that 77% of women and 89% of men complained of chest pain. Intensity of infarction angina in women was more rigorous than men [P=0.04] .Quality of pain described as sharp pain by most women and burning pain by men [P=0.01]. Concerning accompanying signs, 63% of women and 75%, 55%of men reported sweat and nausea respectively which was not significant difference [P= 0.1].For other symptom [shortness of breath] chi square showed significant difference [P=0.03]. Pain was reported to spread to back and left shoulder in most women and to left shoulder in most men. findings showed that women who have MI are different on comparing by men from view of intensity, quality and location of pain.

Posterior mediastinal angiomyxolipoma with spinal canal extension

Angiomyxolipoma is a benign tumor considered as a variant of lipoma and that occurs mainly in the subcutis. The mediastinal location hasn't been previously reported. To describe the radiological features of this tumor in its posterior mediastinal location and to confront them to the pathological features. We report the case of a 49-year-old woman who was admitted for chest wall pain and neurologic disturbance of her two lower limbs. The chest X-ray showed a posterior mediastinal opacity. On CT examination, this mass contained some small areas of fat and enhanced intensily. Microscopic examination of the excised mass confirmed the diagnosis of posterior mediastinal angiomyxolipoma. Mediastinal location of angiomyxolipoma hasn't been previously reported. Clinicians and radiologists should be aware that this diagnosis should be suggested, among others, when there is a posterior mediastinal mass that contains fat and that intensely enhances with a possible spinal cord extension

Low incidence of colorectal cancer in Kerman province, Iran

In Iran colorectal cancer [CRC] incidence varies among various places. But we do not have any validate data that deeply explored the difference of CRC in Kerman province by national average. The aim of this study was to evaluate the incidence of colon cancer within a 12-year period in Kerman province and to find whether the incidence of CRC in Kerman compared with the total incidence found in Iran. Data on colorectal cancer was collected from all histopathology departments around the Kerman Province during 1991 - 2002 retrospectively. The crude and age-standardized incidence rates per 1 million populations were calculated based on the 1996 census data and the population growth rate. During this study total number of 551 new cases of colorectal cancer in Kerman province had been diagnosed. Age Standardized Rate of colon cancer in males and females were 50 [95% CI: 44-56] and 53 [95% CI: 46-59] cases per 1,000,000 population per year, respectively. The risk ratio in females relative to males was not significant in any type of colon cancer. We did not find any difference for each year during the entire study period. The ASR of colorectal cancer in Kerman province was quite lower than the average rate in the whole country. This study showed that, the risk of acquiring colon cancer was constant. We concluded that the risk of colorectal cancer in Kerman province was much lower than the entire country

[Neuroacanthocytosis: a diagnosis that should be considered]

Neuroacanthocythosis regroup heterogeneous neurodegenerative diseases. These conditions share neurological, hematological and even systemic features. In spite of the genetic progress, their pathogenesis is still unknown. To report a new case of neuroacanthocythosis. A 37-year-old woman was admitted for orofacial choreatic movement disorder. These movements were associated to dysarthria, lip and tongue mutilation, areflexia and raised plasma creatine kinase level. Examination of blood smear reveled 10% of acanthocytosis. Neuro-acanthocytosis diagnosis, precisely chorea-acanthocytosis, was done. Neuro-acanthocytosis should be considered in any movement disorder in order to attempt a genetic counseling

Hemorrhagic bowel syndrome in dairy cattle in Iran: a case report

Hemorrhagic bowel syndrome is a highly fatal intestinal disease of adult dairy cattle with uncertain cause. In a dairy herd in Khorasan Razavi province, Northeast of Iran, two cows showed depression, anorexia, decrease in milk production, ruminal hypomotility, bruxism and dehydration. At necropsy, massive hemorrhage and clot formation was observed within the jejunum and bacterial culture of the intestinal ingesta and lesions showed the presence of a large number of Clostridium perfringens. Subacute ruminal acidosis was detected in fresh and mid-lactation cows. This report shows the possibility of diagnosis of other hemorrhagic bowel syndrome cases in dairy cows in Iran

Epidemiological aspects of head and neck cancers in a group of Iranian population

Head and neck cancers occur in a wide variety of tissue types and sites, resulting in a complex range of malignancies cared y physicians in multiple specialties. Epidemiologic aspects of head and neck cancer in Iran have not been studied adequately. The aim of this study was to represent epidemiological aspets of head and neck cancers in Kerman province in Iran. In this retrospective epidemiological study, a total of 2211 cases of heads and neck cancers were diagnosed in period 11-year. Data on all malignant head and neck cancers were included in this study. Information was obtained from the records of the 18 departments of histopathology in Kerman province. The five most common sites were skin of the head and neck [46.81%], lymph nodes of head and neck [13.98%], larynx [13.48%], oral cavity and pharynx [12.2%], and thyroid [6.20%]. Paranasal sinuses were the least common. The incidence rate of head and neck cancers was 10.12/100000 cases. Geographical or regional variations in the prevalence of head and neck cancer indicate that the socio-cultural lifestyles of a population play an important role in head and neck carcinogenesis. This study showed that the incidence rate of head and neck cancers was lower than that in many other countries. However, comparison between our findings with some other studies shows a relation consistency

Acute pulmonary embolism: epidemiologic and tomodensitometric study

Acute pulmonary embolism is a common disease with substantial morbidity and mortality in untreated patients. It requires an urgent positive diagnosis. To assess the prevalence of acute pulmonary embolism and calculate the sensitivity and specificity of multidetector CT for the diagnosis of acute pulmonary embolism in a hospital specialized in cardio-thoracic diseases. This is a prospective study conducted at Abderrahmen Mami Hospital, which included 200 consecutive patients suspected of acute pulmonary embolism and explored by a multidetector CT pulmonary angiography [16 slices]. Prevalence of acute pulmonary embolism was calculated at 37.5%. The multidetector CT has enabled an alternative diagnosis in 46 patients [40%]. The sensitivity and specificity of multidetector CT were calculated respectively 89.6% and 100%. The prevalence of acute pulmonary embolism, in a hospital specialized in cardio-thoracic diseases, is higher than that found in general hospitals. High sensitivity and specificity of multidetector CT makes it the gold standard for the diagnosis of pulmonary embolism

Establishment of standard human fibroblast bank

Fibroblasts are mesenchymal cells that can be readily cultured in the laboratory and play a significant role in epithelial-mesenchymal interactions, secreting various growth factors and cytokines that have a direct effect on epidermal proliferation, differentiation and formation of extracellular matrix. They have been incorporated into various tissue-engineered and used for a variety of clinical applications, including the treatment of burns, chronic venous ulcers and several other clinical applications in dermatology and plastic surgery. Establishment of standard human fibroblast bank is the basis of some important researches. Foreskin was obtained aseptically from patient younger than 1 year old during surgical excision. Fibroblasts isolated by enzymatic treatment were cultivated successively in a culture medium to establish cell banking. The cells were checked to be negative for HBV, HCV, HIV, HSV-I, HSV-II, EBV, CMV, Treponema pallidum, Mycoplasma sp. and Chlamydia. First, 5[th] and 10[th] subcultured cells were processed for immunocytochemistry studies using a panel of monoclonal antibodies including antibodies to MHC class I and II antigens for checking of elimination of superficial cell antigens during cultivation. First, 5[th], 10[th] and 22[nd] subcultured cells were karyotyped to find any chromosomal abnormalities. The fibroblasts used in production of cell bank were checked for some bacteria and viruses by molecular methods and confirmed to be negative. The results of karyotyping of cultured fibroblasts after 22[nd] passages show abnormalities. Multiple centromeric fissions were present in the various metaphase spreads. There were multiple clones with variable rearrangements and chromosome fissions. Expression of HLA on the fibroblast surfaces was diminished during subculturing. Fifth to 10[th] subcultured fibroblasts were the best cells to establish a human fibroblast bank. To prevent chromosomal abnormalities in fibroblast passaging, the best colony that is chromosomally stable and has lower enzymatic separation time should be selected

[Anti TNF beneficial of harmful for the lung?]

The Tumor Necrosis Factor is a pro-inflammatory cytokine which plays a key role in the pathogenesis of many diseases. Therefore, the anti Tumor necrosis factors have been used for treating many inflammatory pathologies such as rheumatoid arthritis or Crohn's disease with success. However, the use of these drugs has revealed during the formal years many side effects dominated by the tuberculosis. Lung cancer and asthma might be other side effects of the drugs. More recently they have been used for other pulmonary indications such as sarcoIdosis. Their benefits for treating asthma is being studied. Therefore, a wise use of these drugs is mandatory to benefit from good effects and avoid hamful

[ comparative study of clinical diagnosis and histological reports of oral and jaw lesions]

Appropriate diagnosis in oral medicine requires expertise, experience and the use of several other related fields. One of the important fields in this domain is oral pathology. The purpose of this study was to investigate the consistency of clinical diagnosis and pathological reports of oral lesions in patients referring to oral pathological department of Kerman dentistry school during 1995- 2004. The present research is a descriptive- analytic and retrospective study in which all of the samples referred to the pathology department in Kerman dental school during 1995 to 2004 were considered. The corresponding data were analyzed by Chi-Squire and T tests using SPSS 13.5 program for statistical analysis. The histopathologic finding and clinical diagnosis were in the same line in 432 cases [64.87%] The highest percentage of proper diagnosis was found in the eight decade with the location in gingival lesions .The lowest percentage of agreement was found in the third decade and in the lesions of mouth floor. Based on the findings of the present research, it seems that the clinical diagnosis is not consistent with pathological finding in about one third of cases. Therefore, the students should be provided with sufficient information about the importance of careful recording of the patient's characteristics and documentation of oral lesions in the charts