Anaplastic large cell lymphoma presenting as an endobronchial mass with lung involvement in an adolescent boy

Primary endobronchial presentation of anaplastic large cell lymphoma is rare in the paediatric age group. We present a 12-year-old boy with breathlessness, fever, cough and weight loss, who was misdiagnosed as a case of tuberculosis and started on antitubercular therapy, which showed no improvement. Chest X-ray showed a completely opacified left hemithorax and chest computed tomography revealed a mass encircling the left main bronchus with collapse– consolidation of the left lung. Fibreoptic bronchoscopy revealed a growth in the left main bronchus. Subsequently, fine-needle aspiration cytology and biopsy from the mass confirmed it to be a malignancy consistent with anaplastic large cell lymphoma. Metastatic work-up revealed no other sites of involvement. Chemotherapy resulted in rapid and complete regression of the tumour. No evidence of local or distant recurrence was reported after 18 months of follow-up. Clinicians and pathologists should be aware of this presentation as prompt diagnosis and treatment can give promising results. This case highlights the importance of timely tissue diagnosis in patients with non-resolving pyrexia and organ lesions on imaging.

Frequency of drug Induced Hyperglycemia during remission induction therapy in adults with Acute Lymphoblastic Leukemia

Objectives: To determine the frequency of drug induced hyperglycemia during remission induction and its associated risk factors in adult acute lymphoblastic leukemia [ALL] patients

Study Design: Cross sectional study

Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, from May 2017 to Nov 2017

Material and Methods: Fifty one adult patients of newly diagnosed ALL were enrolled in the study. Inclusion criteria included, eighteen years or older, treatment naïve. Patients with history of diabetes, on-going treatment or were taking drugs causing hyperglycemia were excluded from the study. Possible risk factors were recorded including age, body mass index [BMI], gender, family history of diabetes, history of hypertension and disease risk stratification for ALL. Patients were started on standard or augmented Berlin-Frankfurt-Münster [BFM] protocol according to risk category. Fasting and random glucose levels were done twice a week during induction chemotherapy. Hyperglycemia was diagnosed when patients experienced blood glucose greater than 126 mg/dL as fasting or greater than 200mg/dL as post prandial. Data were analyzed using SPSS version 23

Results: Eighteen of our fifty one enrolled patients [35.3 percent] experienced hyperglycemia during induction chemotherapy. There was also significant increase in fasting blood sugar levels from baseline readings after induction chemotherapy [p-value<0.001]. Univariate analysis demonstrated significant association between fasting high blood sugar after induction chemotherapy with age [p-value <0.001] and BMI [p-value=0.034]. While on multivariate analysis only age [p<0.001] was found to have significant association with hyperglycemia

Conclusion: Hyperglycemia was observed in less than half of our adult ALL patients during induction chemotherapy. Age was a significant risk factor associated with hyperglycemia

Early molecular response with Imatinib therapy in chronic Myeloid Leukemia and its association with baseline white blood cell count and Spleen size

Objectives: To determine the frequency of early molecular response in patients of chronic myeloid leukemia treated with Imatinib and its association with baseline white blood cell [WBC] count and spleen size

Study Design: Cross sectional study

Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, from May to Nov 2017

Material and Methods: Seventy eight patients of Chronic Myeloid Leukemia [CML] in chronic phase [CP] were included in the study. Inclusion criteria were: 18 years or older, diagnosed with CML in CP with positive BCR ABL1. Patients who were in accelerated/blast phase, or already taking any Tyrosine Kinase Inhibitors or chemotherapy were excluded from the study. Base line WBC count, spleen size and BCR-ABL1 is values were recorded. All the enrolled patients were placed on Imatinib therapy [400 mg/day] and RT-PCR for BCR ABL1 transcript was repeated after three months

Results: In our study, 60.15 percent of patients achieved EMR at 3 months after Imatanib therapy [p-value <0.001]. In univariate analysis, there was significant association of spleen size, baseline WBC count and percentages of blasts in bone marrow with BCR ABL1 [IS] at 3 months [p-value <0.001], while on multivariate regression model, significant association was found only in spleen size [p-value <0.001] with EMR

Conclusion: A significant number of patients achieved EMR with Imatinib therapy. Spleen size at diagnosis was the only significant factor associated with achieving EMR. It is imperative to identify patients at an early stage who are unlikely to achieve EMR and therefore have poor over-all survival

Evolutionary root defines the structural basis of high and low level vancomycin resistance in enterococci

D-alanyl-D-lactate [Dlac] and D-alanyl-D-serine [Dser] ligases respectively mediates high and low level vancomycin resistance among enterococci. To date, the evolutionary relationship of both ligases is largely unaddressed. Also poorly understood are the molecular differences in the magnitude of vancomycin resistance. To address the mention, we constructed the phylogenetic tree of all vancomycin resistance conferring ligases with the wild type ligases [Dala]. Multiple sequence alignment and tertiary structures of the structurally unresolved proteins were constructed by homology modeling. Phylogenetic tree revealed that both Dlac and Dser are profoundly different from Dala as a result of continuous selection pressure. Separate clustering of Dlac and Dser also highlighted the structural basis of molecule in maintaining different level of resistance as exhibited by the bacteria. This notion was further augmented as the functionally key region, omega loop [omega-loop], was found relatively more structured in only Dlac. Moreover, the critically active residue, His-243/244, was also noticed to be restricted in Dlac and found replaced by non polar residues in Dser. The present study not only provides protein structural explanation of the different intensities of vancomycin resistance among enterococci, but also presents yet another example for the scope of evolutionary science in biomedicine

Liquid antacids: a comparative study on palatability and cost effectiveness

To compare the palatability, acid consuming capacity and cost effectiveness of different brands of liquid antacids available in Karachi. Fifty healthy volunteers between the age of 20 to 59 years were recruited in the study. A total of seven antacid brands available in market were physically and chemically tested. The trial design was that of randomized, double blind and cross over study type. All fifty volunteers were individually asked to taste different brands of respectively classified antacids. All antacids were given during a period of 2-hour. Scoring/rating was conducted on the basis of aroma, taste, consistency and after taste using a scheme similar to wine tasting point scale methodology. Acid consuming capacity of antacid were determined according to British Pharmacopeias 2007. A total of 50 volunteers participated in the study after giving informed written consent. The taste rating scores deduced were independent of age and gender. Among all the antacids suspension B [Sodium Bicarbonate and Sodium Alginate] showed maximum palatability; however the overall palatability of the antacids was poor. Antacid containing sodium bicarbonate and sodium alginate was found least palatable. More over the extra strength antacid version showed highest acid consuming capacity entailing small dosage but shows reduced palatability. Antacid brand-B reveals lowest cost effectiveness and least palatability. While, based on the findings of this study G suspension can be one of the suitable antacid for the treatment of gastrointestinal disorders since it showed highest palatability scores and cost effectiveness

Osteochondral grafting of knee joint using mosaicplasty

Focal cartilage defects of articular surface-traumatic and degenerative are difficult to treat, thus a variety of surgical techniques have been developed and reported for treatment of such defects. Procedures such as Priddies perforations, microfracture, abrasion chondroplasty have shown long-term results which are often less than adequate. One of the reasons is that all these techniques lead to the formation of fibrocartilage which has inferior mechanical properties as compared to the native hyaline cartilage. Mosaicplasty is a procedure which aims at replacing the lost articular cartilage with hyaline cartilage including underlying bone support, thus providing adequate stability to the cartilage and better cartilage/bone integration. A young man underwent this procedure for recalcitrant knee pain at our institution. At 2 years follow-up, his knee pain has significantly improved. We hereby present medium term results [2 years] of this first case report in local literature

Microcephaly: tracing the evolutionary lineage of ASPM gene

Microcephaly, in the form of congenital autosomal recessive disorder [MCPH], is characterized by the reduced occipital frontal head circumference >3 standard deviation of otherwise normal population of matching age and sex. The disease is primarily associated with mild to severe mental retardation. Earlier studies have unravelled that among Pakistani population, mutations in ASPM gene is strongly associated in MCPH. In the present study, we have explored the ancestral root of this disease and the process involved in its evolution using tools of bioinformatics. Experimental Methods: cDNA gene and protein sequences of ASPM gene were retrieved from NCBI database and subjected to the non-redundant BLAST. Consensus phylogenetic tree was developed after multiple sequence alignment and bootstrapping of the protein sequences of ASPM gene from different mammals using Neighbour Joining method, selecting non mammals as an out group. Comparisons of the gene synteny and exon and intron patterns of ASPM gene were also undertaken to investigate chromosomal changes during the course of human evolution. Different statistical evolutionary models namely, Codon Based Z test and Maximum Composite Likelihood Estimate were used in order to estimate the nature of nucleotide substitution and the type of selection pressure the gene has undergone. Phylogenetic tree based on ASPM gene clearly segregated all non mammalian members as an out group. Mammalian in group holds the established evolutionary lineage, based on morpho-genetic attributes of mammalian evolution, segregating monotremes at the beginning followed by the members of rodentia and finally radiation of the primates including humans. Orientation of the ASPM gene remains conserved between human and chimpanzee, however, it was found reversed along with two flanking genes, a zinc finger binding domain 41 and coagulation factor XIII, which suggest relatively recent event of gene inversion. Some earlier and, in comparison, more intricate chromosomal changes have also been detected among the lower order of mammals. Aligning ASPM gene exons with the primates and lower order mammals indicates transitional bias of mutation over transversion [R value= 1.563]. Holistically, codon based Z test revealed positive selection pressure on of ASPM gene from rodentia to primates. Briefly, the studies highlights the evolutionary events of ASPM gene in mammals especially primates including humans. Further studies in connection to correlating the cranial cavity size and ancestral gene sequences and in depth sequence comparison would be more insightful in this regard and studies in this connection are ongoing and will be reported shortly

Herpes Simplex Virus-2 infection amongst urban male population in Pakistan

To describe the prevalence of Herpes Simplex Virus-2 [HSV-2] infection among males in six major cities of Pakistan. A cross sectional behavioural and biological survey of urban male population aged 16-45 years was conducted in Rawalpindi, Lahore, Karachi, Faisalabad, Peshawar and Quetta to measure the prevalence of five sexually transmitted infections and assess sexual behaviours. Respondents were selected through a multistage sampling technique. In each city 10 blocks demarcated by the Population Census Organization were selected based on probability proportional to socio-economic status. In each block 40 men were selected through systematic sampling with a random start. In total 2400 men were administered a behavioural questionnaire and 2396 provided biological specimens for laboratory testing. This paper discusses the overall and city wise prevalence of HSV-2 infection. The overall prevalence of HSV-2 infection in the six cities was 3.4 percent [95% Cl 2.8-4.3]. City wise the highest prevalence was reported in Karachi 6 percent [95% Cl 4.1-8.8], followed by Lahore and Quetta at 4.3 percent [95% Cl 2.7-6.7], and Faisalabad at 2.5 percent [95% Cl 1.4-4.5]. The lowest prevalence was in Rawalpindi at 1.8 percent [95% Cl 0.9-3.6]. Empirical evidence from this study suggests that there is city wise variation in the prevalence of HSV-2 infection across the major cities in Pakistan. Based on possible link between HSV-2 and HIV, future HIV control strategies must also focus on the better management of HSV-2 infections in Pakistan

Exercise tolerance test: a comparison between true positive and false positive test results

To study the factors which predetermine the coronary artery disease in patients having positive Exercise Tolerance Test [ETT] after comparing the ETT test results and coronary angiographic findings in true positive and false positive groups. This Cross-sectional study was conducted at Punjab Institute of Cardiology, Lahore from January 1, 2004 to December 31, 2004. All patients who had ETT done for chest pain diagnosis were studied. Patients were advised coronary angiography if ETT was positive for exercise induced ischaemia. One hundred and forty eight patients had coronary angiography done after positive ETT. Patients were divided into two groups depending upon the angiographic findings, i.e., true positive and false positive. Both groups were compared with each other. Results: Out of 148 patients, 126 [85.1%] patients had true positive ETT and 22 [14.9%] patients had false positive ETT. The mean age of patients in true positive group was 48.96 +/- 9.08 years and 50.9 +/- 7.85 years in false positive group. One hundred and eighteen [93.7%] male patients and 8 [6.3%] female patients had true positive ETT, whereas 14 [63.6%] males and 8 [36.4%] females had false positive ETT [p < 0.0001]. There was no statistically significant difference in the two groups in comparison of age and other conventional risk factors like diabetes mellitus, hypertension, smoking, family history and dyslipidemia. Abnormal resting ECG had a statistically significant difference between the groups [p < 0.04], likewise is hypertensive haemodynamic response during ETT [p < 0.003]. The symptom limited ETT as compared to no symptoms during ETT also conferred a statistically significant difference between the groups [p<0.0001]. Strongly positive ETT was also associated with true positive ETT [p < 0.002]. Amongst the vessels involved the most common was the LAD 113 [89.7%], followed by LCX 80 [63.5%] and the RCA 72 [57.1%]. Most of the patients 51 [40.5%] had three vessel disease as compared to SVD 34 [27%]. It can be concluded that amongst the patients who have positive ETT, females with abnormal resting ECG, who achieve target heart rate and have a hypertensive haemodynamic response with no symptoms are likely to have a false positive test result. Conversely male patients with normal resting ECG who do not achieve target heart rate, have a normotensive haemodynamic response and a strongly positive, symptom limited ETT are likely to have a true positive treadmill test result

Enterococci vs coliforms as a possible fecal contamination indicator: Baseline data for Karachi

Fecal contamination of drinking water is the major cause of water borne illnesses. For long time coliforms are exploited as fecal contamination indicator. However, recent studies indicate low survival rate of coliforms in stress conditions, hence it's use as indicator of fecal pollution is being abandoned in many parts of the developed world. Implementation of such strategy demands availability of local data in the cities like Karachi. The present study provides a comparison between coliforms and enterococcal load and its variation in sewage samples collected [June, August and November, 2006] from eighteen towns of Karachi. All the diluted samples were selective media to obtain colony-forming units [CFU] mainly for coliforms and enterococci. The bacteria isolated were identified on the basis of conventional microbiological methods. Observations thus obtained were subjected to rigorous statistical analysis. The total load of enterococci was found in range of 1.27-8.47 X 107 as compared to coliforms [3.03-13.9 X 107]. However, segregation of data reveals greater inter town variability in CFU/ml both in coliforms and enterococci as suggested by their cumulative standard deviation +1.5 X107. Furthermore, CFU/ml of both coliforms and enterococci also varies to variable scale when collected at different time intervals and at intra town level. Conclusively, the studies suggest high survival rate and lower variability of Enterococci compared to escherichia hence indicating its potential advantage to be used as fecal contamination indicator