Experience with telepathology in combination with diagnostic assistance systems in countries with restricted resources.

INTRODUCTION: We describe the use of telepathology in countries with restricted resources using two diagnosis assistance systems (Isabel and Memem7) in addition to the diagnoses made by experts in pathology via the iPath-Network. METHODS: A total of 156 cases, largely from Afghanistan, were analysed; 18 cases had to be excluded because of poor image quality. RESULTS: Of the remaining 138 cases (100%), a responsible physician provided a tentative diagnosis for 61.6% of them. With a diagnosis from a consultant pathologist, it was then possible to make a definite diagnosis in 84.8% of cases on the basis of images taken from hematoxylin and eosin staining sections alone. The use of the diagnosis assistance systems resulted in an ordered list of differential diagnoses in 82.6% (IsabelHealth) and in 74.6% (Memem7) of cases, respectively. Adding morphological terminology reduced the list of possible diagnoses to 52.2% (72 cases, Memem7), but improved their quality. DISCUSSION: In summary, diagnosis assistance systems are promising approaches to provide physicians in countries with restricted resources with lists of probable differential diagnoses, thus increasing the plausibility of the diagnosis of the consultant pathologist.

Association of Neo Angiogenesis by CD34 Expression and Clinicopathologic Features in Squamous Cell Carcinoma of Cervix.

Tumor angiogenesis is one of the most important factors in tumor progression. In this study, the angiogenesis of cervical squamous cell carcinoma (SCC) and its association with prognostic factors was assessed by using CD34 immunostaining marker. The microvessel density in 40 patients with cervical SCC was studied in three areas of the tumor; stromal and peripheral tumor area (combined) central stromal tumor area and peripheral tumor area and the relationship of microvascular density and survival was also evaluated. The count of CD34 is correlated with younger age, the presence of perineural invasion and metastasis to lymph nodes. High peripheral tumor angiogenesis is also correlated with lower disease-free tumor survival. According to the findings of the present study, CD34 expression, especially in peripheral tumor areas, can be used as a prognostic marker in cervical SCC.

Assesment, treatment and prevention of atypical hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is a heterogeneous group of hemolytic disorders. Different terminologies have been described in HUS, which are as follows: (1) D+ HUS: Presentation with a preceding diarrhea; (2) typical HUS: D+ HUS with a single and self-limited episode; (3) atypical HUS (aHUS): Indicated those with complement dysregulation; (4) recurrent HUS: Recurrent episodes of thrombocytopenia and/or microangiopathic hemolytic anemia (MAHA) after improvement of hematologic abnormalities; and (5) familial HUS: Necessary to distinct synchronous outbreaks of D+ HUS in family members and asynchronous disease with an inherited risk factor. aHUS is one of the potential causes of end-stage renal disease (ESRD) in children. It has a high recurrence after renal transplantation in some genetic forms. Therefore, recognition of the responsible mechanism and proper prophylactic treatment are recommended to prevent or delay the occurrence of ESRD and prolong the length of survival of the transplanted kidney. A computerized search of MEDLINE and other databases was carried out to find the latest results in pathogenesis, treatment, and prevention of aHUS.

Mycophenolate mofetil for treatment of idiopathic nephrotic syndrome in children.

INTRODUCTION: Management of frequently relapsing steroid-responsive or steroid-resistant idiopathic nephrotic syndrome (NS) in children has been a clinical challenge for pediatric nephrologists. In addition, adverse effects of long-term corticosteroids and cyclosporine administration emerge seeking a safe and effective treatment. The purpose of this study was to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in these patients. MATERIALS AND METHODS: This study reviewed the outcomes of children with frequently relapsing or steroid-resistant idiopathic NS who were treated with MMF. RESULTS: A total of 36 patients (23 boys and 13 girls) were included. Their mean age at the time of diagnosis of NS was 61.94 ± 43.9 months. Of the children, 91.6% of those who had frequent relapses and 8.3% of those with steroid-resistant NS responded to MMF significantly (P < .001), with no significant association between age and gender with response to MMF. The treatment was well tolerated with no significant complications. CONCLUSIONS: In children with frequently relapsing NS, MMF was a safe and useful drug for maintaining remission, while it was of low value in children with steroid-resistant NS.

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays.

BACKGROUND: c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. METHODS: In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. RESULTS: Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. CONCLUSIONS: c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

Passive smoking and nasopharyngeal colonization by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in daycare children.

Exposure to tobacco smoke may be associated with higher risk of nasopharyngeal colonization and infection by Streptococcus pneumoniae (SP), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC). This study was done to determine the influence of passive smoking on S. pneumoniae, H. influenzae, and M. catarrhalis colonization rates among children. This is a prospective cross-sectional study. Tertiary referral centers with accredited otorhinolaryngology-head and neck surgery and Microbiology Departments. In this cross-sectional study, 2-6 years old children in 10 randomly selected day-care centers in northeast of Iran (Mashad) were studied. Smoking exposure and medical history were recorded. Carriage rates for aforementioned bacteria were analyzed on the basis of smoking exposure. 1,125 children (Female/Male: 597/528) with the mean age of 5.05 ± 0.98 years were studied. Carriage rates of S. pneumoniae, H. influenzae and M. catarrhalis among children were 10.1, 8.8 and 6.7%, respectively. Mixed colonization was found in 2.7%. There was a significant difference in carriage rates between children who live in smoking families compare to those with nonsmoking families for M. catarrhalis (P = 0.001) but not for S. pneumoniae, and H. influenza (P = 0.798 and P = 0.117, respectively). It seems exposure to tobacco smoke is associated with increased carriage rate of M. catarrhalis in day-care children.

Treatment and prophylaxis in pediatric urinary tract infection.

Urinary tract infection (UTI) is the most common serious bacterial infection in early life. Appropriate diagnosis and treatment prevent complications such as hypertension, proteinuria and end stage renal disease. A computerized search of MEDLINE, Embase and other databases was done to find the latest results about the treatment and prevention in pediatric UTI. Randomized control trials, systematic reviews and original articles were assessed. Search terms were "UTI, treatment, prophylaxis, prevention, and children". All children with complicated or simple UTI were included in our search study from neonatal period to late childhood and medical aspects of treatment were reviewed. Recently, treatment approaches have been changed by simplification of drug administration. Oral treatment is recommended especially in older infants and children instead of strict intravenous treatment and patient admission. In addition, prophylactic treatment becomes easier and limited to certain cases. In this article, we review the recent information and approaches in this setting.

Immunogenicity of trivalent influenza vaccine in children with acute lymphoblastic leukemia during maintenance therapy.

PURPOSE: The aim of this study was to assess the immune response of children with acute lymphoblastic leukemia (ALL) to influenza vaccine and to compare it with healthy controls. PROCEDURE: Thirty-two children aged 1-18 years with ALL on maintenance therapy and 30 healthy sibling controls were enrolled in the study. All children were vaccinated with trivalent inactivated influenza vaccine. Hemagglutinin-inhibition (HI) antibody titers were determined in sera of both patient and control groups just before and 4 weeks after vaccination. The ability of each group to mount a protective (> or =40) and/or fourfold titer was measured. RESULTS: The protective response for virus subunits among patients and healthy controls were 43.4% versus 88% for H1N1 (P = 0.04), 63.3% versus 80% for H3N2 antigens (P = 0.06), and 26% versus 73% for B antigen (P = 0.001). Responses for H1N1 and B subunits were significantly lower in patients than controls. In the patient group, the significant response to each virus was demonstrated in the analysis of pre- and post-vaccination geometric mean titer (GMT) (P = 0.001). The percentage of patients and controls with fourfold increase in HI titers were 56.2% versus 80% for H1N1 (P = 0.04), 40.6% versus 53.3% for H3N2 (P = 0.31), and 59.4% versus 83.3% for B (P = 0.038). Immune responses for H1N1 and B subunits were significantly lower in patients than controls. CONCLUSIONS: Influenza vaccine is tolerated well in ALL patients with acceptable but limited immune response compared to healthy controls. These findings support the recommendation for annual influenza vaccination in children with ALL.

Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium.

BACKGROUND: Different molecular alterations have been described in endometrioid endometrial carcinoma (EECA). Among them the most frequently altered is loss of the PTEN protein, a tumor suppressor gene. The purpose of this study was to evaluate the expression pattern of PTEN gene in normal, hyperplastic and neoplastic endometrium. METHODS: In a study in a referral gynecologic hospital in Tehran, Iran, immunohistochemical (IHC) evaluation of PTEN was performed on 87 consecutive specimens to the following three groups; group A- normal proliferative endometrium(n = 29); group B- hyperplastic endometrium [including simple hyperplasia without atypia(n = 21) and complex hyperplasia with atypia (n = 8)] and group C- EECA(n = 29). Immunostaining of cells was analyzed by arbitrary quantitative methods according to both slide's area staining and intensity of color reaction. RESULTS: PTEN immunoreactivity was present in all normal proliferative endometrium, all simple hyperplasia, 75% of atypical complex hyperplasia and in 48% of EECA (P < 0.001). The intensity of PTEN reaction was significantly higher in group with proliferative endometrium than hyperplastic endometrium and EECA (P < 0.001). CONCLUSION: PTEN expression was significantly higher in cyclical endometrium than in atypical hyperplasia and endometrioid carcinoma.

The role of insulin like growth factor (IGF)-1 and IGF-binding protein-3 in diagnosis of Growth Hormone Deficiency in short stature children.

OBJECTIVE: The purpose of this study was to evaluate the role of IGF-1 and IGFBP-3 in diagnosis of short stature children and adolescents in whom Growth Hormone Deficiency (GHD) was found. METHODS: In this cross sectional study the referred short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in 2003-2005 were studied. The inclusion criteria were proved short stature based on the physical examination, weight, height, standard deviation score (SDS) of height < -2, with considering stage of puberty and predicted height in children without any genetic or chronic disorders. The exclusion criteria were any positive physical or laboratory data suggesting hypothyroidism, rickets or liver disorders. For all patients a provocative growth hormone test was performed with propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as peak(cutoff) serum GH level under 10 ìg/L and low IGF-1 and IGFBP-3 considered as cutoff serum level under -2 standard deviation. RESULTS: Eighty one short stature patients (39 boys and 42 girls) with mean age of 10.6 +/- 3.5 years completed the study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3. There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3 in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3, respectively. CONCLUSION: No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests in assessment of GHD were poor.

Diagnostic utility of autopsy in a university hospital in Iran.

OBJECTIVE: The objective of this study were to evaluate the diagnostic utility of the autopsy in University hospital in Tehran, Iran. METHODS: In this retrospective descriptive-analytic survey during a six years period from 1998 to 2003, autopsies in the Bahrami Children Hospital, a teriary care hospital in Tehran, were studied. The clinical and autopsy diagnoses were compared and categorized as follows: 1. Change (clinical and autopsy diagnoses discordant), 2. Add (significant unexpected findings noted on the autopsy, although the clinical diagnosis was not altered), 3. Confirm (clinical and autopsy diagnosis concordant), 4. Autopsy inconclusive. RESULTS: Eighty four autopsies were studied. Out of 350 neonatal deaths in the period, autopsy was performed in 74 neonates (21%) and of 249 under 5 year deaths (except neonates) autopsy was performed in only 10 cases (4%). In 61 cases (73%) the autopsy diagnoses confirmed the clinical diagnosis, in 10 cases (12%) it changed the clinical diagnosis, in 11 cases (13%) it significantly added to the clinical diagnosis and in 2 cases (2%) it was inconclusive. CONCLUSION: This study demonstrated that neonatal and infantile autopsy continued to provide clinically useful data in 25% of cases and remains an invaluable tool in pediatric medicine.

Validation of initial serum creatinine as a predictive factor for development of end stage renal disease in posterior urethral valves.

OBJECTIVE: The aim of this study was to determine the value of initial serum creatinine in prediction of End-stage renal disease (ESRD) in children with posterior urethral valves PUV. METHODS: In this retrospective study, patients diagnosed with PUV admitted in Aliasghar Children's Hospital in Tehran, Iran from 1991 through 2001 were studied. Based on the development of ESRD (need for dialysis) they were classified in two groups and their demographics, initial presentations, laboratory data, imaging findings and outcomes were reviewed and compared. RESULTS: Thirty six male patients with PUV, treated with valve ablation (13), vesicostomy (13), or high ureterostomy (10) were followed for developing ESRD. Sixteen of the 36 patients developed ESRD at their last follow-up. There was no significant difference in age at initial presentation, presence of urinary tract infections, incidence of vesicoureteral reflux, renal dysplasia or type of primary surgical intervention between the patients with or without ESRD. Patients who progressed to ESRD had serum creatinine concentration > 1.0 mg/dl at diagnosis as compared to those without ESRD (P = 0.001). CONCLUSION: Initial serum creatinine is a valuable factor for prediction of renal outcome in patients with PUV.

Intravenous immune globulin versus intravenous anti-D immune globulin for the treatment of acute immune thrombocytopenic purpura.

OBJECTIVE: The purpose of this study was to compare the efficacy and side effects of intravenous immunoglobulin (IVIG) with intravenous anti-D immunoglobulin for treatment of newly diagnosed acute childhood Idiopathic thrombocytopenic purpura (ITP). METHODS: Children (6 months to 14 years) with newly diagnosed acute ITP and platelet count below 20,000/ microL were randomized to receive single dose intravenous 75 microg/kg anti-D or 1g/kg IVIG for two consecutive days (total dose 2 g/kg). Response rate defined as a platelet count over 20,000 / microL 72 hours after initial treatment. RESULTS: Eighty one patients (52 male and 29 female) with mean age of 5 years and 3 months randomly divided in anti-D group (n=42) and IVIG group (n=39). Mean baseline (pretreatment) platelet counts were 15406 / microL and 15230/ microL in anti-D and IVIG group, respectively. The response rate in IVIG group (98%) was more significant than anti-D group (76%); (P = 0.017). After 7 days the platelet counts of all patients in IVIG group were more than 20,000/ microL while in anti-D group 12% had platelet counts below 20,000/ microL. CONCLUSION: In acute childhood ITP, initial treatment with IVIG (2g/Kg in divided dose) increased platelet count more rapidly and more significant than intravenous anti-D (single dose of 75 microg/kg) within the first 72 hours.

Sweat test in asthmatic children; a single center study.

Asthma and Cystic Fibrosis (CF) have some identical manifestations. In the present study, the frequency of positive sweat test was assessed in asthmatic children. This cross-sectional study was performed in asthmatic children, who were referred to Bahrami Children Hospital, Tehran, during July 2003 to July 2005. Sweat test was performed for all children. One hundred and thirty five (95 males and 40 females) asthmatic were studied. Sweat test was positive in 35 (26%) patients. Major signs and symptoms among these 35 patients were: Cough (35/35), Dyspnea (7/35), Chronic Diarrhea (6/35), and steatorrhea (1/35). Failure to thrive was found in 31 of 35 patients. The mean duration of asthma in patients with positive test was 49.3 months, which was significantly higher than 18.1 months in the group with negative test (P=0.001). Significant relations between recurrent respiratory tract infections (P=0.029), chronic diarrhea (P=0.001), failure to thrive (P=0.0001), and positive sweat test were found. Sweat test should be recommended in asthmatic children with recurrent upper respiratory tract infections, long duration of asthma, chronic diarrhea, and failure to thrive.