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The purpose of this study was to shed some light on labial synechiae, which is a common yet unfamiliar condition seen initially by the family physician and ultimately by the paediatric urologist. It is often diagnosed incorrectly, leading to undue anxiety and stress for the unsuspecting parents, and results in multiple unnecessary lab investigations, hence, putting a burden on the healthcare system in general. After IRB approval, a retrospective chart review was performed over a period of 15 years (2007-2021), at The Indus Hospital, Karachi, Pakistan. The records of all female children who underwent examination under anaesthesia (EUA) for labial synechiae (n=29) were included in the study. Our results indicate that the primary healthcare physicians were unable to recognise labial adhesions at the time of initial presentation. We conclude that labial synechiae is a benign condition affecting female infants, but is not very well understood by healthcare workers in our part of the world.

The present cross-sectional study sought to evaluate the Paediatric Penile Perception Score (PPPS) as a tool to assess parental perception of hypospadias repair in children. In all, 60 patients were enrolled in the study with median age of 3.9 years; of these 24 (40%) had proximal hypospadias and 36 (60%) had distal hypospadias. After hypospadias repair, parents/guardians were interviewed about meatus, glans, skin, and general appearance using a standardised questionnaire to report penile appearance and penile perception. Overall, the median PPPS score was 17 (IQR: 16-18) with no significant difference in the penile perception score between the type of hypospadias, relationship of the person interviewed with the child (mother, father or other), nor the children's age. The study revealed that penile perception score (PPPS) is a valuable tool that can be used to assess parental penile perception regarding the child's penile appearance and noted overall high satisfaction after hypospadias repair.

This study examined the combined effect of hydraulic retention time (HRT), organic loading rate (OLR) and heat pretreatment of manure (70 °C, 1 h) on the fate of E. coli, enterococci, C. perfringens, C. difficile, and on chemical parameters (volatile fatty acids and ammonia) that may inactivate pathogens. Semi-continuous mesophilic anaerobic reactors were fed with pig manure and horse feed. The operating conditions were 2, 3, 4 COD.L -1 .d -1 (OLR), 24, 35, 46 days (HRT) and use or not of a thermal pretreatment. The levels of the chemical parameters did not reach concentrations capable of inactivating the four bacteria. Anaerobic digestion led to a Log 10 removal > 3 (E. coli), 0.9-2.1 (enterococci), 0.1-0.6 (C. perfringens) and 0-1 (C. difficile). Increasing HRT only reduced the concentration of E. coli in the digestate. Increasing OLR reduced the Log 10 removal of enterococci and C. difficile. The heat pretreatment led to non-detection of E. coli in the digestate, reduced the concentration of C. perfringens by 0.8-1.3 Log 10 and increased the concentration of C. difficile by 0.04-0.7 Log 10 . Enterococci, not detected in the heated manure, were present in the digestate. The distribution of genes encoding virulence factors of C. difficile (tcdA and tcdB) and C. perfringens (cpa, cpb2 and cpb) was not impacted by anaerobic digestion or by the heat pretreatment. Enterococci, C. perfringens, C. difficile were present in the digestate at relatively stable concentrations regardless of the operating conditions, indicating that even with heat pretreatment, the biosafety of digestate cannot be guaranteed in mesophilic conditions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The unsteady flow of H 2 O saturated by tiny nanosized particles with various shapes (platelets, blades, cylinders, and bricks) over a thin slit is reported. For this novel analysis, the influences of the magnetic field and heat generation/absorption are incorporated into the governing model. The dimensionless nanofluid model is attained after the successful implementation of similarity transformations. Then, Runge-Kutta and homotopy analysis algorithms are implemented for mathematical analysis, and the results are obtained by varying the main flow parameters. A decrease in nanofluid motion is observed for a stronger magnetic field (M). Additionally, nanofluid temperature β(η) increases for higher values of M. Decreasing trends in the shear stresses Re x 0.5 C Fx are observed for the unsteadiness parameter S, and this declines with stronger M. Similarly, the local heat transfer rate Re x -0.5 N ux rises with the unsteady behavior of the fluid. It is observed that the nanofluid motion drops for variable thickness ( λ ) of the slit, whereas the motion becomes slower with stronger magnetic field effects (M).

Disorders of sex development, congenital conditions in which chromosomal, gonadal or anatomic sex is atypical at birth, require urgent assessment by a multidisciplinary team, to define whether there is a life threatening disorder of congenital adrenal hyperplasia or a healthy child with a complex condition. Uncertainty, stigma and taboo complicate counselling which must be knowledgeable, comprehensive and sensitive to different circumstances, religions and cultures. This articles will discuss clinical and genetic diagnosis, decisions regarding sex of rearing, ethical dilemmas, medical management of the infant and of the child or adolescent presenting for the first time with a DSD. Surgical options, timing and management are outlined., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Urothelial carcinoma is the third most prevalent malignancy in adults, accounting for 2.1 % of all cancerrelated deaths. The highest incidence in the 6th decade of life but it is rare in the paediatric population and its incidence is less than 1% constituting a very rare disease. We report the case of a 13 years old boy, who presented to the outpatient department at The Indus Hospital, Karachi, in May 2017, with the complaint of painless gross haematuria.

Poliovirus (PV) environmental surveillance (ES) plays an important role in the global eradication program and is crucial for monitoring silent PV circulation especially as clinical cases decrease. This study compared ES results using the novel bag-mediated filtration system (BMFS) with the current two-phase separation method. From February to November 2016, BMFS and two-phase samples were collected concurrently from twelve sites in Pakistan (n = 117). Detection was higher in BMFS than two-phase samples for each Sabin-like (SL) PV serotype (p<0.001) and wild PV type 1 (WPV1) (p = 0.065). Seventeen sampling events were positive for WPV1, with eight discordant in favor of BMFS and two in favor of two-phase. A vaccine-derived PV type 2 was detected in one BMFS sample but not the matched two-phase. After the removal of SL PV type 2 (SL2) from the oral polio vaccine in April 2016, BMFS samples detected SL2 more frequently than two-phase (p = 0.016), with the last detection by either method occurring June 12, 2016. More frequent PV detection in BMFS compared to two-phase samples is likely due to the greater effective volume assayed (1620 mL vs. 150 mL). This study demonstrated that the BMFS achieves enhanced ES for all PV serotypes in an endemic country., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate post-surgery pain relief in percutaneous nephrolithotomy cases., Methods: The case-control study was conducted at Indus Hospital, Karachi, from July 2014 to July 2015, and comprised patients undergoing percutaneous nephrolithotomy. The patients were randomized by snose protocol into two equal groups of cases and controls. The cases were given peri-tubal local anaesthetic infiltration of 0.25% bupivacaine, while the controls were given 10ml 0.9% normal saline infiltration. Post-operative pain was assessed using visual analogue scale., Results: Of the 68 patients, there were 34(50) in each of the two groups. Pain score was significantly less in the intervention group post-operatively at 6th and 12th hours (p<0.05). Also, total consumption of analgesics and demand of analgesic medication were also significantly low among the cases (p<0.05)., Conclusions: Bupivacaine infiltration into the peri-tubal track significantly reduced post-operative pain.

Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries. Among different RVA G types, humans are most commonly infected with G1, G2, G3, G4 and G9. During 2003-2004, G3 rotavirus termed as "new variant G3" emerged in Japan that later disseminated to multiple countries across the world. Although G3 rotaviruses are now commonly detected globally, they have been rarely reported from Pakistan. We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014. G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months. Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012. Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM. To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.

Background: To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation., Methods: Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community., Results: The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8-35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4-63.0), with significant variation in site-specific estimates (median varied from 33.3-79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2-98.7), assuming four samples per month for each site., Conclusions: ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance.

Objective: To develop and validate the Urdu version of the International Prostate Symptoms Score., Methods: The prospective study was conducted at Indus Hospital, Karachi, from January to April 2014, and comprised interviews of subjects at baseline and at 2 weeks for assessing the test-retest reliability. Patients presenting with lower urinary track symptoms and who were able to read Urdu were recruited as subjects. The reliability of the Urdu version of the International Prostate Symptoms Score was assessed by determining the internal consistency, and by assessing the test-retest reliability., Results: There were 58 subjects with a mean age of 61.53+/-9.99 years. There was no statistically significant difference in self-administered and assister filling total score (p=0.145) and quality of life (p=0.201). For reliability analysis, Cronbach's alpha coefficient was 0.756 total score and 0.622 for quality of life., Conclusions: The Urdu version of the International Prostate Symptoms Score stood validated for assessing lower urinary track symptoms.

Leiomyoma of urinary bladder is a rare tumour with an incidence of < 0.5% of all the bladder tumours. We report a case of leiomyoma of bladder after taking written and informed consent from a 38 years old female, after obtaining the permission of the institutional review board (IRB). She presented in November 2015, with symptoms of obstructive lower urinary tract for 1 year followed by acute urinary retention. Physical examination was unremarkable. Ultrasound showed well circumscribed polypoidal growth in the bladder with mild hydronephrosis on the left side. CT scan abdomen and pelvis with contrast was done, which revealed well circumscribed, rounded soft tissue lesion of 4.4 x 4.5 cm at the posterior inferior surface of the bladder near the bladder neck. Initially TURBT was done but after 6 months patient again went into urinary retention so local excision of the tumour was done. Histopathology confirmed the diagnosis of leiomyoma of the bladder. The diagnosis and management of leiomyoma of the bladder is presented along with review the literature.

Objective: To determine the mean difference in maximum urine flow rate and post-void residual urine volume in sitting as well as standing voiding position in healthy males., Methods: This descriptive, cross-sectional study was conducted at the Department of Urology, Indus Hospital, Karachi, from October 2013 to March 2014, and comprised healthy volunteers enrolled using non-probability, consecutive sampling technique. Each volunteer was asked to perform uroflowmetry in sitting and standing positions on two separate days, and a post-void residual volume was assessed after each test. The values of maximum flow rate, average flow rate, voiding volume, and post-void residue were compared between the different voiding positions., Results: A total of 50 volunteers were inducted. In standing position the maximum flow rate was 32.4±9.6 ml/sec, average flow rate 8.8±16.9 ml/sec, and post-void residue was 8.8±16.9ml. Similarly, in sitting position, the maximum flow rate was 14.8±5.4 ml/sec, average flow rate 14.8±5.4 ml/sec, and post-void residue was 6.6±9.4ml. A significant difference in both voiding positions was observed regarding the maximum flow rate, and average flow rate (p=0.001; p=0.003). However, the difference was not significant for voided volume (p=0.676), or post-void residual volume (p=0.771) in either position. Age-wise stratification of data showed significant difference in both younger and older age groups in terms of maximum flow rate (p=00.19). However, the average flow rate was only significantly different in younger age group (p=0.00). There was no difference in voided volume or post-void residue in either age group (p>0.05)., Conclusions: The standing voiding position in healthy people influenced uroflowmetry findings, and was associated with higher flow rates.

Objective: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patients., Methods: This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC)., Results: Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR., Conclusion: TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities..

Primary renal aspergillosis, though a rare entity, is still seen in immune compromised individuals. Renal aspergillosis may lead to formation of focal abscesses, fungal bezoars and may cause ureteric obstruction. Treatment involves stabilization of patient and removal of fungal bezoars along with administration of anti-fungal agents. This report describes the case of localized primary renal aspergillosis with fungal bezoars formation in a 55 years old female, diabetic, hypertensive, who presented with upper urinary tract obstruction and was successfully managed by endoscopic removal of fungal bezoars and intravenous amphotericin followed by oral itraconazole.

An approach is proposed for environmental surveillance of poliovirus by concentrating sewage samples with tangential flow filtration (TFF) followed by deep sequencing of viral RNA. Subsequent to testing the method with samples from Finland, samples from Pakistan, a country endemic for poliovirus, were investigated. Genomic sequencing was either performed directly, for unbiased identification of viruses regardless of their ability to grow in cell cultures, or after virus enrichment by cell culture or immunoprecipitation. Bioinformatics enabled separation and determination of individual consensus sequences. Overall, deep sequencing of the entire viral population identified polioviruses, non-polio enteroviruses, and other viruses. In Pakistani sewage samples, adeno-associated virus, unable to replicate autonomously in cell cultures, was the most abundant human virus. The presence of recombinants of wild polioviruses of serotype 1 (WPV1) was also inferred, whereby currently circulating WPV1 of south-Asian (SOAS) lineage comprised two sub-lineages depending on their non-capsid region origin. Complete genome analyses additionally identified point mutants and intertypic recombinants between attenuated Sabin strains in the Pakistani samples, and in one Finnish sample. The approach could allow rapid environmental surveillance of viruses causing human infections. It creates a permanent digital repository of the entire virome potentially useful for retrospective screening of future discovered viruses.

Adrenal myelolipomas are rare non functional benign tumours which are incidentally diagnosed in asymptomatic patients. Despite the fact that several theories have been discussed, the origin of myelolipoma remains unclear. Our patient, 19 years old male presented with history of abdominal pain for past 7 years. Computed tomography scan of abdomen with oral and intravenous contrast revealed well defined round heterogenous enhancing mass seen in right supra renal area involving the adrenal gland. Patient underwent surgery by open access through thoracoabdominal approach. Histopathology of resected mass showed myelolipoma along with trilineage haematopoesis with mature adipose tissues.

Objective: To evaluate the role of subdartos fascial tissue as watertight layer in improving outcome for 2-stage proximal hypospadias surgery., Methods: The experimental study was conducted at the Department of Urology, Indus Hospital, Karachi, and comprised an audit of patients with proximal hypospadias who underwent surgery from July 1, 2007, to December 31, 2011. The initial two-stage repair of proximal hypospadias led to a high rate of urethrocutanous fistula formation (Group A), and, thus, a modification was introduced and subdartos facial double layer was applied over the urethral suture line (Group B). The results were compared regarding age, type of hypospadias, graft failure and urethrocutanous fistula in these patients., Results: There were 27 patients in Group A and 16(59.3%) of them ended up having urethrocutanous fistula. Group B had 25 patients and only 2(8%) had fistula formation., Conclusions: The application of dartos facial flap waterproofing layer reduced fistula rate.

Objective: The phenotypic "ABO" blood groups are inherited antigenic substances which are found on the surface of red blood cells in addition to other tissues. Certain hypothesis advocates that genetic predisposition like "ABO" blood group would be associated with occurrence of diseases including type 2 diabetes. This study aimed to investigate the potential association between "ABO" and "Rhesus" blood groups with type 2 diabetes., Materials and Methods: We identified 47 research documents in a data based search including ISI-Web of Science, EMBASE and PubMed. Literature was explored using the key terms including "ABO blood groups" "type 2 diabetes". Studies in which "ABO" blood types and diabetes mellitus were discussed included without restrictions of research documents, types, status and language of the publications. Finally, 15 publications which matched our criteria were included, and remaining studies were excluded., Results: Blood group "B" was associated with high incidence of type 2 diabetes and blood group "O" has a minimum association with type 2 diabetes. Blood group "A" and "AB" were almost equally distributed in both diabetic and non-diabetic population. However, we were unable to find an association between "Rh+ve" and "Rh-ve" blood groups with type 2 diabetes., Conclusions: Subjects with blood group "B" are at high risk while individuals with blood group "O" are at low peril of evolving type 2 diabetes. It is suggested that subjects with blood group "B" should be closely monitored by physicians as these subjects have an increased risk of type 2 diabetes.

Background: Polio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV)., Objective: To assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV)., Methods: A double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0-14 days). Subjects were assigned to either receive 10mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status., Results: Overall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60 μg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p<0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3., Conclusions: There was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Adrenocortical oncocytoma is an exceedingly rare pathological variant of an adrenal neoplasm. The pathogenesis of oncocytic neoplasms is poorly understood. Females have been reported to be affected 2.5 times more frequently than males, and left-sided lesions are more common than those on right side. This case describes a 20 years old female with right lumbar pain. She found to have a right adrenal gland mass measuring about 6 x 5 cm. A computed tomogram showed hypodense mass lesion 6 x 4.2 cm involving right adrenal gland. Differential diagnosis of non-functional adrenal adenoma was made. A laparoscopic right adrenalectomy was performed using the 3-ports lateral transperitoneal approach. Histopathology showed adrenocortical oncocytoma of adrenal gland.

Primary Burkitt lymphoma of the central nervous system (CNS) is rare, with only few cases reported in the literature. An 18 year-old immunocompetent male presented with multiple cranial nerves palsies and was found to have a mass predominantly in the 4th ventricle of the brain. Tumor was surgically removed and showed morphological and immunohistochemical features consistent with Burkitt lymphoma. The patient responded very well to anthracycline based chemotherapy with high dose methotrexate (HD MTX) and intrathecal (IT) chemotherapy delivered by Ommaya reservoir. Primary Burkitt lymphoma of the CNS is a rare entity that poses differential diagnostic challenge with other small round blue cell tumors.

Objectives: This study aimed to compare the impact of Gross Domestic Product (GDP) per capita, spending on Research and Development (R&D), number of universities, and Indexed Scientific Journals on total number of research documents (papers), citations per document and Hirsch index (H-index) in various science and social science subjects among Asian countries., Materials and Methods: In this study, 40 Asian countries were included. The information regarding Asian countries, their GDP per capita, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the bibliometric indicators, including total number of research documents, citations per document and H-index in various science and social sciences subjects during the period 1996-2011. The main sources for information were World Bank, SCI-mago/Scopus and Web of Science; Thomson Reuters., Results: The mean per capita GDP for all the Asian countries is 14448.31±2854.40 US$, yearly per capita spending on R&D 0.64±0.16 US$, number of universities 72.37±18.32 and mean number of ISI indexed journal per country is 17.97±7.35. The mean of research documents published in various science and social science subjects among all the Asian countries during the period 1996-2011 is 158086.92±69204.09; citations per document 8.67±0.48; and H-index 122.8±19.21. Spending on R&D, number of universities and indexed journals have a positive correlation with number of published documents, citations per document and H-index in various science and social science subjects. However, there was no association between the per capita GDP and research outcomes., Conclusion: The Asian countries who spend more on R&D have a large number of universities and scientific indexed journals produced more in research outcomes including total number of research publication, citations per documents and H-index in various science and social science subjects.

Hematopoietic stem cell transplantation (HSCT) activity was surveyed in the 9 countries in the World Health Organization Eastern Mediterranean region that reported transplantation activity. Between the years of 1984 and 2007, 7933 transplantations were performed. The number of HSCTs per year has continued to increase, with a plateau in allogeneic HSCT (allo-HSCT) between 2005 and 2007. Overall, a greater proportion of transplantations were allo-HSCT (n = 5761, 77%) compared with autologous HSCT (ASCT) (n = 2172, 23%). Of 5761 allo-HSCT, acute leukemia constituted the main indication (n = 2124, 37%). There was a significant proportion of allo-HSCT for bone marrow failures (n = 1001, 17%) and hemoglobinopathies (n = 885, 15%). The rate of unrelated donor transplantations remained low, with only 2 matched unrelated donor allo-HSCTs reported. One hundred umbilical cord blood transplantations were reported (0.017% of allo-HSCT). Peripheral blood stem cells were the main source of graft in allo-HSCT, and peripheral blood stem cells increasingly constitute the main source of hematopoietic stem cells overall. Reduced-intensity conditioning was utilized in 5.7% of allografts over the surveyed period. ASCT numbers continue to increase. There has been a shift in the indication for ASCT from acute leukemia to lymphoproliferative disorders (45%), followed by myeloma (26%). The survey reflects transplantation activity according to the unique health settings of this region. Notable differences in transplantation practices as reported to the European Group for Blood and Marrow Transplantation over recent years are highlighted., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Circoviruses consist of highly prevalent and genetically diverse porcine and avian pathogens. The genomes of cycloviruses, a proposed new genus in the family Circoviridae, were recently identified in human and chimpanzee faeces. Here, six cyclovirus and four circovirus genomes from the tissues of chickens, goats, cows, and a bat were amplified and sequenced using rolling-circle amplification and inverse PCR. A goat cyclovirus was nearly identical to a cyclovirus from a cow. USA beef contained circoviruses with >99% similarity to porcine circovirus 2b. Circoviruses in chicken were related to those of pigeons. The close genetic similarity of a subset of cycloviruses and circoviruses replicating in distinct animal species may reflect recent cross-species transmissions. Further studies will be required to determine the impact of these highly prevalent infections on the health of farm animals.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. Although it can occur secondary to lymphoproliferative disorders and autoimmune or infectious diseases, CAD is rarely reported as secondary to solid tumors. We report a case of a woman aged 18 years diagnosed with a well-differentiated hepatocellular carcinoma of the fibrolamellar subtype, who was shown to have CAD also. Her general condition, including CAD, improved after targeted therapy with sorafenib for the hepatocellular carcinoma and only conservative measures for the CAD that consisted of avoidance of cold. In summary, although it is an extremely rare association and less common than lymphoproliferative disorders, CAD can be associated with solid tumors.

Acute promyelocytic leukemia (APL) is one of the most curable myeloid malignancies because of its great sensitivity to all-trans retinoic acid (ATRA) and response to anthracycline therapy. In an attempt to simplify post-remission therapy, deliver adequate dose of anthracycline and reduce treatment related toxicity, we entered 26 consecutively newly diagnosed, previously untreated APL patients in a pilot treatment program consisting of concurrent induction using idarubicin/ATRA followed by an exclusive outpatient post-remission therapy using single dose of idarubicin and intermittent ATRA, every 4 weeks. Of 25 evaluable patients, two (8%) died early during induction due to hemorrhagic complications, and 23 (92%) achieved complete remission. Overall survival at 4.2 years was 90% (CI 76.4-100), and 3.6 years disease-free survival was 78% (CI 60.6-95.4). The treatment outcome of this program is encouraging; however, the result of this study needs to be validated in larger cohort of patients and optimally in a randomized comparison with other current post-remission approaches.

Several centers are now performing allogeneic hematopoietic stem cell transplantation (HSCT) in the World Health Organization Eastern Mediterranean Region (EMRO) but the availability is still limited due to high cost and the need for multi-disciplinary team and an advanced laboratory support. Special issues including compatible donor availability, potential for alternate donor programs, differences in pattern of disease, pre-HSCT general status particularly for patients with BM failure, high sero-positivity for CMV, Hepatitis B and C infection and specific observations about GVHD with its relation to genetically homogeneous community are discussed. A total of 17 HSCT programs (performing five or more HSCTs annually) exist in nine countries of the EM region. Only six programs are currently reporting to EBMT or IBMTR. A total of 7617 HSCTs including 5701 allogeneic HSCTs have been performed. Due to low HSCT team density (1.5583 teams/10 million inhabitants versus 14.4333 in Europe) and very low HSCT team distribution (0.2729 teams/10,000 sq km area versus <1 to 6 teams in Europe) only 70.8% of total population has access to such a program in EM region. GNI/capita had no clear association with low HSCT activity; however improvement in infrastructure and establishment of EM regional HSCT registry need prioritization., ((c) 2010 Elsevier Ltd. All rights reserved.)

Circoviruses are known to infect birds and pigs and can cause a wide range of severe symptoms with significant economic impact. Using viral metagenomics, we identified circovirus-like DNA sequences and characterized 15 circular viral DNA genomes in stool samples from humans in Pakistan, Nigeria, Tunisia, and the United States and from wild chimpanzees. Distinct genomic features and phylogenetic analysis indicate that some viral genomes were part of a previously unrecognized genus in the Circoviridae family we tentatively named "Cyclovirus" whose genetic diversity is comparable to that of all the known species in the Circovirus genus. Circoviridae detection in the stools of U.S. adults was limited to porcine circoviruses which were also found in most U.S. pork products. To determine whether the divergent cycloviruses found in non-U.S. human stools were of dietary origin, we genetically compared them to the cycloviruses in muscle tissue samples of commonly eaten farm animals in Pakistan and Nigeria. Limited genetic overlap between cycloviruses in human stool samples and local cow, goat, sheep, camel, and chicken meat samples indicated that the majority of the 25 Cyclovirus species identified might be human viruses. We show that the genetic diversity of small circular DNA viral genomes in various mammals, including humans, is significantly larger than previously recognized, and frequent exposure through meat consumption and contact with animal or human feces provides ample opportunities for cyclovirus transmission. Determining the role of cycloviruses, found in 7 to 17% of non-U.S. human stools and 3 to 55% of non-U.S. meat samples tested, in both human and animal diseases is now facilitated by knowledge of their genomes.

Diarrhoea remains a significant cause of morbidity and mortality in developing countries where numerous cases remain without identified aetiology. Astroviruses are a recently identified cause of animal gastroenteritis which currently includes two species suspected of causing human diarrhoea. Using pan-astrovirus RT-PCR, we analysed human stool samples from different continents for astrovirus-related RNA sequences. We identified variants of the two known human astrovirus species plus, based on genetic distance criteria, three novel astrovirus species all distantly related to mink and ovine astroviruses, which we provisionally named HMOAstV species A-C. The complete genome of species A displayed all the conserved characteristics of mammalian astroviruses. Each of the now three groups of astroviruses found in human stool (HAstV, AstV-MLB and HMOAstV) were more closely related to animal astroviruses than to each other, indicating that human astroviruses may periodically emerge from zoonotic transmissions. Based on the pathogenic impact of their closest phylogenetic relatives in animals, further investigations of the role of HMOAstV, so far detected in Nigeria, Nepal and Pakistan, in human gastroenteritis are warranted.

Rotaviruses are among the major causes of gastroenteritis and diarrhea among children in developed as well as the developing countries. The rapidly evolving strain prevalence and circulation have resulted in the emergence of novel strains over the period worldwide. The introduction of G12 prototype in 1987 from Philippines and subsequently re-emergence among most of the Asian countries along with USA and Europe has provoked new research horizons to address the global distribution of rotavirus serotypes. These newly emerging subtypes and their sustenance among the population have posed tremendous challenge to the development of an effectual vaccine with heterotypic protective efficacy. In Pakistan, no data is available regarding the prevalent rotavirus serotypes; therefore, this is the first study to report the prevalence of G12 strain in Pakistan in hospitalized children with diarrhea addressing a dire need of further large-scale epidemiological surveys to resolve the underlying rotavirus isolates in both the hospitalized and the community neonatal and child population before formulating the vaccine introduction policies in the country's routine immunization program.

Using a simple metagenomic approach, we identified a divergent human parechovirus (HPeV) in the stool of a child in Pakistan. Genomic characterization showed this virus was distinct enough from reported HPeV types to qualify as candidate prototype for the seventh HPeV type.

Although several centers are now performing allogeneic hematopoietic SCT (HSCT) in the Eastern Mediterranean (EM) region, the availability is still limited. Special issues including compatible donor availability and potential for alternative donor programs are discussed. In comparison to Europe and North America, differences in patterns of diseases and pre-HSCT general status, particularly for patients with BM failure, are described. Other differences including high sero-positivity for CMV, hepatitis B and C infection, and specific observations about GVHD and its relation to genetically homogeneous communities are also discussed. We report that a total of 17 HSCT programs (performing five or more HSCTs annually) exist in 9 countries of the EM region. Only six programs are currently reporting to European Group for Blood and Marrow Transplantation or Center for International Blood and Marrow Transplantation Research. A total of 7617 HSCTs have been performed by these programs including 5701 allogeneic HSCTs. The area has low-HSCT team density (1.56 teams per 10 million inhabitants vs 14.43 in Europe) and very low-HSCT team distribution (0.27 teams per 10 000 sq km area vs <1-6 teams in Europe). Gross national income per capita had no clear association with low-HSCT activity. Much improvement in infrastructure and formation of an EM regional HSCT registry are needed.

Cytogenetic aberrations have long been recognized as the most important prognostic variable in acute myeloid leukemia (AML) and are now a major stratification tool for post-remission therapy. Cytogenetics-based stratification improves survival. Patients with AML and normal cytogenetics, the largest single subgroup, have had a very heterogeneous outcome with standard chemotherapy in multiple clinical trials. Hence it is difficult to recommend a "one size fits all" kind of treatment for this heterogeneous population of AML patients. New emerging data from preclinical, retrospective, and large, randomized controlled studies indicate that in addition to cytogenetic abnormalities, many other molecular aberrations are operative in the response to treatment as well as in the risk of relapse. Such molecular markers are being tested for developing targeted therapies and may help in improved stratification of patients in the selection of post-remission therapy. Emerging evidence reveals that at the submicroscopic level, AML with normal cytogenetics may carry poor prognostic genetic lesions or "molecular signatures" as is the case with FLT3 mutations and overexpression of BAALC, ERG or MN1, or may have aberrations that predict better risk as is the case with isolated NPM1 or CEBPA mutations. Later studies have tried to explore the interaction of various prognostically important genes in this group of AML patients. The utility of the evolving data for bedside management of such patients is expected to improve with the wider application of modern tools, using the proposed clinical outcome models, and probably by development of a risk-scoring system based on the relative risk associated with each molecular aberration. The goals include identifying those patients most likely to benefit from upfront allogeneic HSCT and sparing good-prognosis patients from unnecessary transplant-related morbidity. The following is an outline of the most common molecular changes, their impact on the outcome of AML patients with normal cytogenetics and challenges in their wide scale application in risk stratification.

Objective: To compare morbidity and stone clearance by ureteroscopy carried out under spinal anaesthesia with that carried out under general anaesthesia., Study Design: Quasi-experimental study., Place and Duration of Study: The study was conducted at the Kidney Centre, Postgraduate Training Institute, Karachi, from September 2005 to December 2006., Patients and Methods: A total number of 60 patients were enrolled for the study. All patients underwent ureteroscopic procedure for a calculus disease, using a semi-rigid ureteroscope of 10 Fr. These patients were divided in 2 groups of 30 patients, receiving general or spinal anaesthesia. Operative time, stone clearance, hospital stay, intra- and postoperative complications and visual analogue score for pain were noted in each case., Results: There were 30 patients each in both groups, with 73% males and 27% females in group A (general anaesthesia) and 93% males and 7% females in group B (spinal anaesthesia). Mean age of the patients were 33.9 and 36.9 years in groups A and B respectively. The average stone size was 0.79 cm in group A and 1.14 cm in group B (p=0.001). Duration of surgery was 41.4+/-1.29 minutes in group A and 30.5+/-2.13 minutes in group B (p=0.033). Mean hospital stay was 21.6 and 18.1 hours in group A and B respectively (p=0.073). Mean visual analogue score for pain in group A was 3.1 and group B was 1.8., Conclusion: Ureteroscopy under spinal anaesthesia resulted in decreased length of operative time and shortened hospital stay in this series and did not carry any additional risk of major complications.

Background: Eight genotypes of Hepatitis B virus designated A-H, have been known but in Pakistan, no such data is available on the prevalent HBV genotypes. Therefore, the subject study was conducted to determine HBV genotypes in the indigenous Pakistani population., Methods: A total of 690 individuals were enrolled for HBV screening with EIA and nested PCR. Positive samples were further analyzed to determine HBV genotypes (A-F) by multiplex-PCR using type specific primers., Results: 110 (15.94%) individuals were positive for HBV, including 64% males and 36% females. Out of these, 66 samples (65.34%) were classified into genotype D, 27 (26.73%) were of genotype B while 5(4.95%) had genotype A. In 3 (2.98%) samples, multiple genotypes were detected (genotype A+B; 2(1.99%) and genotypes B+D; 1(0.99%). Nine (8.18%) samples remained untyable., Conclusion: In Asia, genotypes B and C are the most prevalent but our study reveals that genotype D is predominant and HBV infection constitutes a significant health problem in Pakistan.

Background: The epidemiological significance of Hepatitis B virus genotypes has been well established and becoming an essential concern day by day however, much little is known about the mixed infection with more than one Hepatitis B virus genotypes and their clinical relevance., Methods: Intravenous drug abusers are considered as a major risk group for the acquisition and transmission of blood borne infections like hepatitis B, however, in Pakistan, no such data has ever been reported about the epidemiology of HBV and its genotypes in Injecting Drug Users. 250 individuals were analyzed for hepatitis B virus genotypes after prior screening with serological assay for the detection of HBsAg., Results: 56 (22.4%) individuals were found positive on ELSIA for HBsAg. The genotype distribution was found to be as: genotype D, 62.5%; genotype A, 8.92% while 28.57% individuals were found to be infected with a mixture of genotype A and D., Conclusion: There is an urgent need of the time to develop public health care policies with special emphasis towards the control of HBV transmission through high risk groups especially Injecting Drug Users.

Background: The infection rate of hepatitis B virus is continuously increasing in Pakistan. Therefore, a comprehensive study of epidemiological data is the need of time., Methods: A total of 1300 individuals were screened for HBV infection markers including HBsAg, anti-HBsAg, HBeAg and anti-HBcAg. The association of these disease indicators was compared with patients' epidemiological characteristics like age, socio-economic status and residential area to analyze and find out the possible correlation among these variables and the patients disease status., Results: 52 (4%) individuals were found positive for HBsAg with mean age 23.5 +/- 3.7 years. 9.30%, 33.47% and 12% individuals had HBeAg, antibodies for HBsAg, and antibodies for HBcAg respectively. HBsAg seropositivity rate was significantly associated (p = 0.03) with the residing locality indicating high infection in rural areas. Antibodies titer against HBsAg decreased with the increasing age reflecting an inverse correlation., Conclusion: Our results indicate high prevalence rate of Hepatitis B virus infection and nationwide vaccination campaigns along with public awareness and educational programs are needed to be practiced urgently.