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Management of rare hematological disorders pose unique diagnostic and therapeutic challenges due to unusual occurrence and limited treatment options. We retrospectively identified 45 patients receiving matched related donor transplant for rare hematological disorders from 2006 to 2019. Patients were divided into two groups (1) malignant and (2) non malignant. The malignant disorder group included four patients while the nonmalignant group included 41 patients divided into immune dysregulation (n = 23), bone marrow failure (n = 10), metabolic (n = 5), and bleeding diathesis (n = 3). Twenty-six (57.8%) patients received myeloablative conditioning (MAC) and 16 (35.6%) received reduced intensity conditioning (RIC), while 3 (6.6%) patients with severe combined immunodeficiency received stem cell infusion alone without conditioning. The cumulative incidence (CI) of grade II-IV acute GVHD (aGVHD) was 39.1% (n = 18) and chronic GVHD (cGVHD) 15.2% (n = 7). There was no primary graft failure while CI of secondary graft failure was 9%. Overall survival (OS) and disease-free survival (DFS) was 82.2% and 77.8% respectively. Group wise OS was 75% in the malignant group, 82.6% in the immune dysregulation group, 80% in patients with metabolic disorders and bone marrow failure, while 100% in patients with bleeding diathesis. This retrospective analysis shows that hematopoietic stem cell transplant can be a feasible treatment option for rare hematological disorders.

Background and Purpose: Coronavirus disease 2019 (CO-VID-19) has an increased propensity for systemic hypercoagulability and thromboembolism. An association with cerebrovascular diseases, especially cerebral venous thrombosis (CVT), has been reported among these patients. The objective of the present study was to identify risk factors for CVT as well as its presentation and outcome in COVID-19 patients., Methods: This is a multicenter and multinational observational study. Ten centers in 4 countries (Pakistan, Egypt, Singapore, and the United Arab Emirates) participated in this study. The study included patients (aged >18 years) with symptomatic CVT and recent COVID-19 infection., Results: Twenty patients (70% men) were included. Their mean age was 42.4 years, with a male-to-female ratio of 2.3:1. Headache (85%) and seizures (65%) were the common presenting symptoms, with a mean admission Glasgow Coma Scale (GCS) score of 13. CVT was the presenting feature in 13 cases (65%), while 7 patients (35%) developed CVT while being treated for COVID-19 infection. Respiratory symptoms were absent in 45% of the patients. The most common imaging finding was infarction (65%), followed by hemorrhage (20%). The superior sagittal sinus (65%) was the most common site of thrombosis. Acute inflammatory markers were raised, including elevated serum D-dimer (87.5%), erythrocyte sedimentation rate (69%), and C-reactive protein (47%) levels. Homocysteine was elevated in half of the tested cases. The mortality rate was 20% (4 patients). A good functional outcome was seen in the surviving patients, with a mean modified Rankin Scale score at discharge of 1.3. Nine patients (45%) had a modified Rankin Scale score of 0-1 at discharge., Conclusion: COVID-19-related CVT is more common among males at older ages when compared to previously reported non-COVID-19-related CVT cases. CVT should be suspected in COVID-19 patients presenting with headache or seizures. Mortality is high, but functional neurological outcome is good among survivors., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objective: Prevalence of aplastic anemia (AA) is high in the Asian population. This study was done to explore the etiology and association of AA with various socio-economic and environmental factors. Study design and setting: Study included 1324 consecutive AA cases registered at Armed Forces Bone Marrow Transplant Centre Rawalpindi, Pakistan, from March 2001 to August 2016. The study questionnaire was completed through an interview. It included patients' socio-demographic details, personal and family medical history, environmental attributes and clinico-hematological features. Results: The median age of patients was 20 years, 997 were male and 327 female. Distribution of non-severe, severe and very severe AA was 230 (17.4%); 598 (45.2%) and 496 (37.4%), respectively. The majority of patients were from low ( n  = 761, 57.5%) or middle socioeconomic class ( n  = 543, 41%). Consanguinity among patients ( n  = 806, 61%) was slightly higher than the national statistics. History of chemical exposures included fertilizers ( n  = 116, 8.7%), pesticides ( n  = 56, 4.2%) and industrial chemicals ( n  = 37, 2.8%). PNH clone was found in 63 of AA patients. After excluding 298 patients undergoing HSCT and 660 deaths/lost to follow-up, disease evolution was observed in 38(10.4%) patients out of 366 evaluable patients. These included PNH = 18, MDS = 11 and AML = 9. Discussion: Due to lack of funding and adequate human resource at the center, age and sex-matched controls could not be included. Other limitations were a lack of molecular testing to exclude the possibility of inherited bone marrow failure syndromes on a genetic basis. Conclusion: Younger age, male predominance and higher consanguinity point toward genetic factors in AA etiology among the South Asian population.

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. All rights reserved.)

Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning regimens in such patients. We retrospectively analyzed 192 high-risk patients undergoing matched-related donor transplantation from July 2001 to December 2018. The median age was 19.5 (2-52) years. Patients were divided into 2 groups, Cy 200 anti-thymocyte globulin (ATG) 20 (Gp1 n = 79) or Flu 120-150 Cy 120-160 ATG 20 (Gp2 n = 113). The risk of graft failure was significantly higher in Gp1, and the majority occurred in patients with >2 risk factors ( p = 0.02). The incidence of grade II-IV acute graft versus host disease (GVHD) and chronic GVHD was not significantly different between the two groups. The overall survival (OS) of the study cohort was 81.3 %, disease-free survival (DFS) 76.6 % and GVHD-free relapse-free survival (GRFS) was 64.1%. DFS and GRFS were significantly higher in Gp2 as compared to Gp1: DFS 84.1% versus 68.4 % ( p = 0.02), GRFS 77.9% versus 54.4% ( p = 0.01), respectively. We conclude that Flu-based conditioning is associated with superior OS, DFS and GRFS as compared to the conventional Cy-based regimen in high-risk AA., Competing Interests: This manuscript contains original research not previously published or submitted for publication elsewhere while under consideration. The authors declare no conflict of interest with this manuscript., (© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.)

Cisplatin is used as a first line therapy in treating cancers. However, its use is often accompanied with the development of peripheral neuropathy. 6-Methoxyflavanone (6-MeOF) is a positive allosteric modulator at GABAA receptors and is known for attenuating diabetes-induced neuropathic pain. Neuropathy was induced in male Sprague-Dawley rats (150-250 g), via intraperitoneal injection of cisplatin (3 mg/kg) once a week for four consecutive weeks. 6-MeOF (25, 50 and 75 mg/kg, i.p) and gabapentin (75 mg/kg, i.p) were administered 30 min before each cisplatin injection. Static and dynamic allodynia were assessed using von Frey filaments and cotton buds. The anti-inflammatory activity was analyzed with plethysmometer. Body weights were also measured each week. The binding affinity of 6-MeOF with chloride channel, Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) was studied using docking approach. The in vitro COX-1 and COX-2 inhibitory effect of 6-MeOF was conducted with COX colorimetric assay. Administration of cisplatin for four consecutive weeks induced static (decreased paw withdrawal threshold; PWT) and dynamic allodynia (decreased paw withdrawal latency; PWL). Co-administration of 6-MeOF for four weeks significantly attenuated the cisplatin-induced expression of nocifensive behaviors observed as significant increase in PWT and PWL. Moreover, it also prevented the body weight loss induced by cisplatin administration. In silico studies depicted a good interaction of 6-MeOF with chloride ion channels and COX-1 and COX-2 enzymes. The in vitro study confirmed the inhibitory activity of 6-MeOF for COX-1 and COX-2. 6-MeOF may be effective in attenuating cisplatin-induced allodynia, probably through interaction with GABAergic receptors and reducing inflammation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Despite excellent transplant outcomes of aplastic anemia (AA) in developed countries, management in developing countries is challenging because of delay in the diagnosis, use of family donors for transfusions, and higher infection risk pretransplant. These factors can lead to allo-immunization, increased risk of graft failure, graft-versus-host disease (GVHD), and transplant-related mortality, leading to unfavorable outcomes. Conventional cyclophosphamide (Cy) and antithymocyte globulin (ATG) are associated with inferior overall survival in such high-risk patients. We conducted single-center retrospective analysis of high-risk AA patients (N = 147) enrolled consecutively and undergoing matched related donor transplant from March 2002 through October 2018. We included high-risk AA patients receiving fludarabine (Flu)-based conditioning. Median patient age was 20 years (range, 3 to 52). The median time from diagnosis to transplant was 11 months (range, 3 to 63). High-risk features included age ≥ 20 years in 55.8% of patients (n = 82), disease duration more than 3 months in 95 % (n = 140), RBC concentrates transfusions > 20 in 79.6% (n = 117), random donor platelet transfusion > 50 in 64.6% of patients (n = 95), and second hematopoietic stem cell transplant (HSCT) in 7.4% (11). We divided patients into 2 groups based on different conditioning regimens. Flu group 1 (Flu1) received Flu 120 to 150 mg/m 2 , Cy 120 to 200 mg/kg, and ATG 20 mg/kg, and Flu group 2 (Flu2) was given Flu 150 mg/m 2 , Cy 300 mg/m 2 , and ATG 20 mg/kg. Bone marrow stem cells were used as graft source in 97% of patients (n = 144) (alone in 52% and with peripheral blood stem cells in 45%). Cyclosporine alone was used for GVHD prophylaxis in 75% (n = 110) and cyclosporine plus methotrexate in 25% (n = 37). Median total nucleated cell dose was 5 × 10 8 /kg. Median days for neutrophil engraftment was 13 (range, 10 to 20) and platelet engraftment 20 (range, 14 to 43). Day 100 mortality was 7.5% (n = 11). Sustained successful engraftment was achieved in 87.8% of patients (n = 129). Most graft failures (40%) occurred in Flu2 conditioning (P = .000) and in patients with >2 risk factors (P = .000). Overall incidence of acute and chronic GVHD was 11.6% (n = 17) and 12.9% (n = 19), respectively, in Flu1 and Flu2 groups. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) was 83.7%, 78.2%, and 70.7%, respectively. A trend toward improved OS was observed in patients receiving Flu1 conditioning but was statistically nonsignificant (P = .256), whereas DFS and GRFS were significantly better in Flu1 versus Flu2 (P = .004 and .001, respectively). When stratified per number of risk factors (age > 20, RBC concentrate > 20 or platelet > 50 random, duration > 3 months, previous HSCT), OS and DFS decreased significantly with increasing number of risk factors (P = .000 and .001, respectively). Patients are able to tolerate Flu-based conditioning well with lower rates of rejection and excellent long-term survival in high-risk AA patients. Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. Use of Flu plus low-dose Cy conditioning is associated with inferior survival outcomes. A randomized trial of Flu-based versus conventional Cy-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. All rights reserved.)

Aplastic anemia (AA) is the most serious non-malignant blood disorder in Pakistan, ranked second in prevalence, after thalassemia. We investigated various epidemiological, clinical, and genetic factors of AA in a Pakistani cohort of 214 patients reporting at our hospital between June 2014 and December 2015. A control group of 214 healthy subjects was included for comparison of epidemiological and clinical features. Epidemiological data revealed 2.75-fold higher frequency of AA among males. A single peak of disease onset was observed between ages 10 and 29 years followed by a steady decline. AA was strongly associated with lower socioeconomic profile, rural residence, and high rate of consanguineous marriages. Serum granulocyte colony-stimulating factor and thrombopoietin levels were significantly elevated in AA patients, compared to healthy controls (P < 0.0001), while there was no statistical significance in other nine cytokine levels screened. Allele frequencies of DRB1*15 (56.8%) and DQB1*06 (70.3%) were predominantly high in AA patients. Ten mutations were found in TERT and TERC genes, including two novel mutations (Val526Ala and Val777Met) in exons 3 and 7 of TERT gene. Despite specific features of the AA cohort, this study suggests that epidemiologic and etiologic factors as well as host genetic predisposition exclusively or cooperatively trigger AA in Pakistan.

Primary myelofibrosis (PMF) is a clonal, BCR-ABL1 negative myeloproliferative neoplasm characterised by splenomegaly, leukoerythroblastic peripheral blood picture and bone marrow fibrosis. Different cytogentic abnormalities are documented in PMF which have impact on clinical outcome and overall survival. Del 5q31 is documented in only 0.8% of PMF patients and is associated with poor outcome and increased risk of progression to acute leukemia. Anemia with del 5q responds frequently to lenalidomide treatment. We are reporting case of a middle-aged male who presented with constitutional symptoms, myelofibrosis; and calreticulin type 2 mutation was present. His cytogenetics showed del 5q positivity. He was started on lenalidomide but developed toxic epidermal necrolysis, resultantly lenalidomide was stopped. Skin eruptions are a known entity in patients with lenalidomide therapy; but to date, there is no reported case of lenalidomide induced toxic epidermal necrolysis (TEN) in patients with myelofibrosis.

Levetiracetam is an antiepileptic drug used for the treatment of generalised or partial seizures, either alone or in a combination therapy. Adverse effects have been reported with its clinical use, including headache, dizziness, liver failure etc. A rare but an important adverse effect is an increase in creatine phosphokinase (CPK) levels with its use. Herein, we present a case of 43-year male, known intravenous (IV) drug abuser with a history of decompressive craniotomy. Patient presented with severe behavioural disorder for which risperidone was given. Five days later, he started having high grade fever, hyperventilation and uncontrolled generalised tonic-clonic seizures (GTCS). After initial management of seizures, levetiracetam was started in combination with topiramate for seizure control. Seizures remained subsided but CPK levels, which were normal at the start of therapy, began to rise and reached tremendous levels of 29,000 mg/dl within a span of a week. Levetiracetam, suspected as a cause of this increase CPK levels, was stopped immediately and the levels returned to baseline within one week. This report provided us with an important step in the management of seizures with levetiracetam.

A novel, sensitive and validated RP-HPLC-UV method was developed for simultaneous determination of moxifloxacin and ofloxacin using timolol maleate as internal standard in physiological fluids. Different experimental parameters were optimized and validated according to international guidelines. Complete separation of the analytes was achieved with Kromasil 100-5C18 analytical column (250mm×4.6mm×5μm), methanol and 0.05% trifloroacetic acid (TFA) (38:62v/v) were used as mobile phase, pumped at flow rate of 1.1ml/min in isocratic phase, column oven temperature maintained at 45°C and detection wavelength of 290nm. Protein precipitation method was applied to extract the drugs from human plasma and bovine aqueous humor samples using methanol as precipitating solvent. This method is linear in concentration range of 0.018-100μg/ml for moxifloxacin and 0.014-20μg/ml for ofloxacin. The recoveries of the method were 97.52 and 97.39% in human plasma for MX and OFN respectively, while in aqueous humor 94.48% for MX. The LOD values in plasma were found to be 10.0 and 8.00ng/ml for MX and OFN respectively, while their respective LOQ values were 18.0 and 14ng/ml. In aqueous humor the LOD and LOQ for MX were 16.0 and 24ng/ml respectively. In future, this method will be used to study the pharmacokinetic profile of moxifloxacin and ofloxacin in biological fluids and pharmaceutical products., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background Aims: Mesenchymal stromal cell (MSC) transplantation has immerged as promising therapeutic approach to treat spinal cord injury (SCI). In this pilot study, we investigated the safety of intrathecal injection of autologous bone marrow-derived MSCs in nine patients with SCI., Methods: Patients with complete SCI at the thoracic level were divided into two groups: chronic (>6 months, group 1) and sub-acute SCI (<6 months, group 2), according to time elapsed since injury. MSCs were isolated by density gradient separation of autologous bone marrow harvested from the iliac crest. Cells were cultured in a Good Manufacturing Practice-compliant facility to produce clinical scale dose. After quality control testing, MSCs were injected back to patients by intrathecal injection. Safety was defined as absence of adverse event and side effects after 1 month after receiving the injection., Results: Six patients had chronic SCI with a median duration of 33 months since date of injury (range: 10-55 months), and three patients were in sub-acute phase of disease. Each patient received two or three injections with a median of 1.2 × 10(6) MSCs/kg body weight. No treatment-related adverse event was observed during median follow-up of 720 days (range: 630-826 days) in group 1 and 366 days (range: 269-367 days) in group 2, respectively., Discussion: This pilot study demonstrated that autologous MSCs can be safely administered through intrathecal injection in spinal cord injury patients. Further investigation through randomized, placebo-controlled trials is needed., (Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose. Pancreaticopericardial fistula (PPF) is an extremely rare complication of acute or chronic pancreatitis. This paper presents a rare case of PPF and provides systematic review of existing cases from 1970 to 2014. Methods. A PubMed search using key words was performed for all the cases of PPF from January 1970 to December 2014. Fourteen cases were included in the study. The cases were reviewed for demographic characteristics, diagnostic modalities, and treatment. Descriptive analysis of these variables was performed. Results. Median age was 43 years. 78% were known alcoholics and 73.3% had chronic pancreatitis. Dyspnea was present in 78%. Cardiac tamponade was present in 53%; 75% of patients had known chronic pancreatitis (RR = 0.74). Surgery was associated with best treatment outcomes and 50% of patients who underwent endoscopic treatment survived. Conclusion. PPF is a rare disease. This paper indicates that acute cardiac tamponade in patients with history of alcoholism and chronic pancreatitis could be a sign of an existing pancreaticopericardial fistula and early surgical intervention could be life-saving.

Unlabelled: Validation study of the Mini-Mental State Examination in Urdu language for Pakistani population., Objective: This study was conducted primarily to validate and determine the optimal cutoff score in the diagnosis of dementia among Pakistani's and study the effects of gender and education on the MMSE performance in our population., Methods: Four hundred participants took part in the study. Patient with dementia recruited from five major hospitals from Pakistan. The MMSE was translated into Urdu., Results: There were 61 men and 39 women in dementia group and 225 men and 75 women in the control group. The mean score of Urdu MMSE were lower in patients with dementia 18.5 ± 5.6 (range 0-30) as compared to the controls 26.8 ± 2.6 (range 7-30). This difference between groups was statistically significant (p<0.001). Educational based MMSE score below 15 yielded perfect sensitivity and specificity for the diagnosis of dementia., Conclusions: These finding confirm the influence of level of education on MMSE score and education stratified cutoff scores should be used while screening for cognitive impairment in this population.

The objective of the current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for Insulin. Thermoreversible in-situ gel system was developed and evaluated both in-vitro and in-vivo comprising of pluronic F-127 alone or in combination with methylcellulose in different ratios. The drug release kinetics and mechanism was predicted by applying various mathematical models to the in-vitro dissolution data. Rabbits were used as animal model following subcutaneous injection to predict various pharmacokinetic parameters by applying Pk-Summit® software. The in-vitro and in-vivo data revealed that the formulation IPM 15/3 consisting of the pluronic F-127 (15% w/v) and methylcellulose (3% w/v) was the most robust and capable formulation for extending the drug release and maintaining basal plasma insulin level between 10 and 40 µU/ml for 240 h (10 d).

Nocardia is an uncommon Gram-positive organism. It typically appears as delicate filamentous Gram-positive branching rods. In the United States it was estimated to be approximately 500 to 1000 new cases per year. The organism causes disease in immunocompromised individuals with pulmonary infection representing the most common site of infection. Nocardia mikamii has been a recently isolated pathogen and not many cases of disseminated infection with this organism has been reported in the literature; we present a case of disseminated nocardiosis (mikamii sp.) in an immunocompromised patient. We also present a literature review on nocardiosis.

A simple, specific, precise and rapid RP-HPLC-UV method was developed for simultaneous determination of lumefantrine and its metabolite desbutyl lumefantrine in human plasma. Experimental parameters were optimized and the method was validated according to standard guidelines. The method showed adequate separation for lumefantrine and desbutyl lumefantrine and best resolution was achieved with Supelco Discovery HS C18 RP (150mm×4.6mm, 5μm) column using acetonitrile and 0.05% trifluroacetic acid (70:30, v/v) as a mobile phase pumped at a flow rate of 1.0ml/min and wavelength of 335nm. The method was linear over the concentration range of 10-12,000ng/ml. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for lumefantrine were 10.0 and 18.0ng/ml, while for desbutyl lumefantrine were 7.5 and 15.0ng/ml, respectively. The proposed method was efficiently applied for determination of lumefantrine and desbutyl lumefantrine concentrations in plasma samples for pharmacokinetic studies., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid., Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excell 2007 was used for statistical analysis., Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n = 8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement., Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition.

Objective: To analyze factors associated with survival, rejection and graft versus host disease in aplastic anaemia patients undergoing allogeneic haematopoietic stem cell transplantation (SCT) from HLA matched sibling donors., Study Design: Analytical study., Place and Duration of Study: Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to June 2010., Methodology: Consecutive aplastic anaemia (AA) patients undergoing haematopoietic stem cell transplantation from HLA-matched sibling donors at this centre were included in this study. Potential factors affecting overall survival, rejection, disease-free survival and graft versus host disease were analyzed. Survival analysis was done by Kaplan-Meier method. Cox regression model was applied for multivariate analysis., Results: Ninety male and thirty-five female patients with AA were included in the study. Median age was 18 years. Conditioning regimens used were cyclophosphamide (Cy) plus antilymphocyte globulin (ALG) or antithymocyte globulin (ATG), fludarabine (FLU) +Cy+ATG, Campath 1-H +Cy in 89, 30 and 6 cases respectively. GVHD prophylaxis used was ciclosporin (CSA) plus prednisolone and short methotrexate in 81 while 44 received CSA plus prednisolone. At a median follow-up of 1185 days OS and DFS were 84% and 78% respectively. Factors associated with better OS were male sex, Flu/Cy/ATG conditioning and use of bone marrow as stem cell source., Conclusion: Flu/Cy/ATG conditioning regimen, bone marrow as stem cell source and CSA, prednisolone and short methotrexate regimen were associated with better survival in AA.

The management of rupture of membranes at a nearly viability stage is still controversial. A case of a primigravida, who had rupture of membranes at 23 weeks of gestation, is reported. On conservative management, her pregnancy continued to 30 weeks and she delivered a normal fetus, who showed no abnormality till one year of follow-up.