Mohammad Khurshid

Crimean Congo-Haemorrhagic Fever treated with oral ribavirin

Crimean-Congo Haemorrhagic Fever (CCHF) is an often-lethal haemorrhagic fever caused by a tick-borne virus. There are no published data on ribavirin treatment of CCHF-infected patients, despite established in-vitro and in-vivo sensitivity. We report three health workers--two surgeons and a hospital worker--infected with CCHF virus in Pakistan who were treated with oral ribavirin 4 g/day for four days, then 2.4 g/day for six days. Intravenous ribavirin was unavailable. All three patients were severely ill with low platelet and white-cell counts, raised aspartate transaminase and evidence of impaired haemostasis. Based on published reports, all had an estimated probability of death of 90% or more. The patients became afebrile, and their haematological and biochemical abnormalities returned to normal within 48 h of ribavirin treatment; all made a complete recovery, and developed IgG and IgM antibody to CCHF virus. Our experience with ribavirin treatment is encouraging, but does not constitute evidence of efficacy. Given the difficulties in gathering adequate treatment data, we propose a consensus protocol for both intravenous and oral treatment of CCHF. This protocol could be distributed to key medical personnel in areas endemic for CCHF and used to provide a firm basis for effective treatment recommendations.

Comparative yield of salmonella typhi from blood and bone marrow cultures in patients with fever of unknown origin

Over three years, a comparative study on 100 selected patients with fever of unknown origin was undertaken to determine the yield of Salmonella typhi from their blood and bone marrow cultures. The results indicate that in patients who had an infection with S typhi the organism was isolated from the bone marrow in all of them and from the blood in only 66%. This suggests that bone marrow cultures may be attempted when blood cultures are negative for bacterial growth after three to four days of incubation.

Lipids and Membranes in the Organic Matrix of Urinary Calcific Crystals and Stones

Abstract. The ultrastructure of the organic matrix of demineralized urinary stones was examined by standard transmission and scanning electron microscopy as well as after malachite green-glutaraldehyde fixation. Crystal ghosts of both calcium oxalate and calcium phosphate were made of amorphous material and were dispersed in a matrix containing amorphous, fibrillar, and membranous substances. Malachite green positive material was seen to be associated with the ghosts, as well as with the membranous and fibrillar components of the organic matrix. Calcium oxalate and calcium-phosphate crystals, induced in human urine in vitro were also found to be associated with an organic matrix containing lipids and proteins. It is suggested that the intimate association between crystals and lipids is a result of the involvement of cellular membranes in the nucleation of these crystals.

Leukaemia Classification: a Study of the Accuracy of Diagnosis in 456 Patients

Summary. A panel of five haematologists has examined, without consultation or prior knowledge of the diagnosis, blood films and bone marrow smears from 456 patients with a diagnosis of leukaemia. A diagnostic classification which recognized various subtypes of acute myelogenous leukaemia was used but no attempt was made to subdivide acute lymphoblastic leukaemia.

Effect of general anaesthesia and surgery on neutrophil function

The effects of general anaesthesia and surgical trauma on neutrophil function were studied in 60 female ASA 1 and 2 patients undergoing anaesthesia for gynaecological surgery. Patients were divided into three groups depending on the degree of trauma and duration of surgery. Group 1 (n = 15) were patients for dilatation and curettage (minor surgical trauma) and were given 2% halothane. Group 2 (n = 30) had laparoscopic surgery (moderate surgical trauma) and received either 0.5% halothane or 1% enflurane. Group 3 (n= 15) were those having hysterectomy (major surgical trauma) and received 0.5% halothane for a longer duration. Venous samples were taken 30 min before anaesthesia (control value), 10 min after induction of anaesthesia, 10 min after the start of surgery, 30 min after the end of anaesthesia and 24 h later. Phagocytic index, nitroblue tetrazolium reduction test, total leucocyte count, and differential leucocyte counts were performed on each sample. Data were analysed by paired t‐test to compare findings in the same patient and by unpaired t‐test for differences between groups. Anaesthesia with halothane 0 5% to 2% caused a dose‐related depressant effect on leucocyte function which reversed. Enflurane 1% on the other hand caused significantly greater depression of leucocyte function compared with 0.5% halothane which persisted during the recovery period and recovered on the first postoperative day. Total leucocyte counts also showed a fivefold increase in the major surgery groups.

Population study of 1311 C/T polymorphism of Glucose 6 Phosphate Dehydrogenase gene in Pakistan - an analysis of 715 X-chromosomes.

BackgroundNucleotide 1311 polymorphism at exon 11 of G6PD gene is widely prevalent in various populations of the world. The aim of the study was to evaluate 1311 polymorphism in subjects carrying G6PD Mediterranean gene and in general population living in Pakistan.ResultsPatients already known to be G6PD deficient were tested for 563C-T (G6PD Mediterranean) and 1311 C-T mutation through RFLP based PCR and gene sequencing. A control group not known to be G6PD deficient was tested for 1311C/T only.C-T transition at nt 1311 was detected in 60/234 X-chromosomes with 563 C-T mutation (gene frequency of 0.26) while in 130 of normal 402 X-chromosomes (gene frequency of 0.32).ConclusionWe conclude that 1311 T is a frequent polymorphism both in general populations and in subjects with G6PD Mediterranean gene in Pakistan. The prevalence is higher compared to most of the populations of the world. The present study will help in understanding genetic basis of G6PD deficiency in Pakistani population and in developing ancestral links of its various ethnic groups.

Haemorrhagic manifestations and utility of haematological parameters in dengue fever: a tertiary care centre experience at Karachi.

A retrospective observational study of dengue fever was performed, including 210 patients (male:female ratio 1.6:1, ages 6–74 y, mean 29.7 y) attending the Aga Khan University Hospital, Karachi from January 2001 to December 2006. All included patients proved dengue IgM antibody positive. Of these, 19 (9%) showed increased haemoglobin/haematocrit levels on admission which remained elevated in 4 (2.1%) at the time of discharge. 56 patients (26.6%) had leucopenia and neutropenia and 77.1% (161) had thrombocytopenia at the time of admission; 2.5% (5) and 16.7% (35) had deranged PT and APTT, respectively. Atypical lymphocytes were seen in 109 patients (52%). Platelet transfusion was given in 45 (22.1%) cases. The majority of patients were discharged without any adverse sequelae. The fatality rate was 3.3% (n =7) and these patients died of dengue shock syndrome, while 196 (93.3%) recovered completely. Haematological parameters are an important clue and should be tested when a patient presents with symptoms suggestive of dengue fever.

Estimating window period blood donations for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus by nucleic acid amplification testing in Southern Pakistan.

Recently, strategic planning was initiated by the National Blood Transfusion Services Pakistan to improve its blood bank facilities. Emphasis has been placed on appropriate screening of blood products. Located in the southern region, Aga Khan University Hospital is a 700‐bed tertiary care academic institute with comprehensive blood banking. Screening of blood donors has been based on verbal screening and serologic testing to date. Additionally, the need of implementing nucleic acid testing (NAT) was considered in 2011 because of an upsurge in hepatitis epidemiology. The aim of this study was to analyze the efficacy of this additional donor screening program and to evaluate the impact of NAT on the yield and residual risk of transfusion‐transmissible viral infections.

Retrospective review of pediatric patients with acute lymphoblastic leukemia: A single center experience

OBJECTIVE We reviewed the clinical details and treatment outcome of children with newly diagnosed acute lymphoblastic leukemia (ALL) to determine the significance of already established prognostic factors in our patients. SETTING A tertiary care hospital in Karachi, Pakistan. STUDY DESIGN This is a retrospective study. MATERIALS AND METHODS Children diagnosed with ALL were evaluated over a period of 17 years (January 1, 1989 to December 31, 2006). Data was collected by reviewing the medical records of the patients and the prognostic factors analyzed by us include age, gender, white blood cell count, central nervous system and mediastinal involvement at presentation, morphology and immunophenotype of the blast cells, and response to induction therapy. RESULTS There were 46 patients diagnosed during the study period and on regular follow-up. Forty five (97.8%) of these were in complete remission after 28 days of induction therapy. Thirty patients (65.2%) were alive and doing well at the time of study. Of these 30 patients, 26 (86.6%) remained relapse free while only four (13.3%) had relapsed. The remaining 16 patients (34.7%) did not survive including 11 (68.7%) who had a relapse. Only significant variables in terms of prognosis were age and ALL phenotype with a P value 0.04 and 0.03 respectively. CONCLUSION We found that ALL is a frequent childhood hematological malignancy in our setting and is more prevalent in males and children less than ten years of age. Age and leukemia phenotype emerged as the important prognostic factors in pediatric ALL in our patients.

Chromosomal abnormalities in Pakistani children with acute lymphoblastic leukemia.

BACKGROUND Cytogenetic abnormalities have important implications in diagnosis and prognosis of acute leukemia and are now considered an important part of the diagnostic workup at presentation. Karyotype, if known at the time of diagnosis, guides physicians to plan appropriate management strategies for their patients. AIM AND OBJECTIVES To determine the cytogenetic profile of acute lymphoblastic leukemia (ALL) in Pakistani children in order to have insights regarding behavior of the disease. MATERIALS AND METHODS A retrospective analysis of all the cases of ALL (<15years old) diagnosed at Aga Khan University from January 2006 to June 2011 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. RESULTS A total of 153 patients were diagnosed as ALL during the study period, of which 127 samples successfully yielded metaphase chromosomes. The male to female ratio was 1.8:1. A normal karyotype was present in 51.2% (n=65) of the cases whereas 48.8% (n=62) had an abnormal karyotype. Most of the abnormal cases showed hyperdiploidy(13.4%) followed by t(9;22)(q34;q11.2) (7.08%). CONCLUSIONS This study revealed a relative lack of good prognostic cytogenetic aberrations in Pakistani children with ALL.