lenalidomide induced toxic epidermal necrolysis and del [5q]: co-occurrence of rarities

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

Anatomical outcome following indocyanine green assisted internal limiting membrane peeling for stage 3 and 4 macular hole surgery

Objective: To evaluate the anatomical success of stage 3 and 4 macular hole surgery after removal of internal limiting membrane [ILM] with the help of Indocyanine green [ICG]

Study Design: An experimental study

Place and Duration of Study: LRBT Tertiary Care Eye Hospital, Karachi, October 2015 to August 2016

Methodology: Twenty patients with stage 3 and 4 macular hole [confirmed by spectral domain optical coherence tomography] underwent standard 3 ports pars plana vitrectomy. Staining of ILM was performed with the help of 0.5% ICG to aid in visualization. ILM was removed by using intraocular forceps in circular fashion. Finally, gas fluid exchange with internal tamponade of SF6 20% was performed. Postoperative face down posture was maintained for seven days. Patients were followed-up for 8 months and assessment of macular hole closure was done using SD-OCT

Results: After a follow-up of 8 months, macular hole was closed in 17 eyes [85%] and vision had improved in 6 patients. Postoperative complications included cataract, hyphema and vitreous hemorrhage

Conclusion: Surgery for stage 3 and 4 macular hole with ILM peeling has high anatomical success rate. Final visual acuity is dependent on preoperative macular hole stage and visual acuity at presentation

Comparison of problem based with case based learning: a cross-sectional study

Background: Problem-based learning [PBL] and case-based learning [CBL] are teaching methodologies, which regulate self-directed learning skills. In medical schools of Pakistan either or both are being consistently used in the undergraduate and postgraduate curriculum. The objective of our study was to compare CBL with PBL on the basis of perception of those students who have observed this transition of learning methodologies in the undergraduate medical curriculum

Methods: It was a cross sectional comparative study, conducted from February to May 2016 whereby all 3rd year medical students who were exposed to PBL in the third year of education after two years experience of CBL were included. Response of students on the usefulness of PBL was acquired on 5-point Likert scale. Results were compared by chi square test

Result: The complete response was obtained from 212 students. Eighty four percent students preferred PBL over CBL [p<0.01]. PBL significantly assisted students to; identify gaps in knowledge, improve their areas of weakness, manage time, make decisions, solve problems, use critical reasoning skills and communicate with each other [p<0.01] in comparison to CBL. It enhanced the ability to find information from internet and libraries. Students recommended that PBLs were time consuming and proper training of facilitators was required as compared to CBL. They were convinced with system of education of CBL followed by PBL

Conclusion: The PBL was effective in terms of retention of concepts, critical reasoning and problem-solving approaches yet satisfaction with the current system of education elucidated role of CBL in the first two years of undergraduate medical curriculum to prepare students through guided enquiry and presentation of clinical scenarios. Proper training of facilitators will be a key point to improve learning of students through PBLs

Design and in-vitro evaluation of sustained release floating tablets of metformin HCL based on effervescence and swelling

An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology [RSM]. Seventeen [17] trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio [A], amount of sodium bi-carbonate [B], and amount of SSG [C] were adopted as independent variables. Floating lag time in sec [Y[1]], cumulative percent drug released at 1 h [Y[2]] and 12 h [Y[3]] were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition [40°C and 75% RH] for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties

Hysterosalpingographic evaluation of primary and secondary infertility

To determine the pathological patterns of fallopian tubes and uterus on hysterosalpingogrphy [HSG] examination in cases of infertility. Two years retrospective charts review of patients referred to our centre for HSG evaluation of infertility, from July 2008 to July 2010. Four thousand one hundred eight hysterosalpingograms were carried out at our centre during the study period. Out of these, 1999 [48.6%] were primary infertility cases while the 2109 [51.3%] were of secondary infertility. Mean age of presentation for primary infertility was 30 years and 35 years for secondary infertility. Bilateral free peritoneal spill was noted in 60% of cases. Unilateral tubal blockage was present in 15% and bilateral tubal blockage in 10% of patients. Bilateral hydrosalpinx was present in 10% of patients and unilateral loculated spill was found in 5% of patients with primary infertility. Patients with uterine congenital anomalies were also evaluated and the frequency of bicornuate uterus was 4%, unicornuate uterus was 2% and uterine didelphys was 0.2%. Infertile patients who underwent HSG were mostly in older age group with secondary infertility being slightly more common emphasizing early work up and care. Most of the patients with primary infertility had normal HSG examination. To our knowledge this is the largest data for HSG to be presented from Pakistan

Determination of neuron specific enolase [NSE] in small cell lung carcinoma [SCLC] and non-small cell lung carcinoma [NSCLC] patients

Neuron specific enolase [NSE] is routinely used as tumor marker in Small cell lung carcinoma [SCLC], and to some extent in non-small cell lung carcinoma [NSCLC]. In Pakistan, tumor marker technology is not a new one. It is however mostly directed towards uses in hepatic, breast, ovarian, uterine and colorectal cancers, whereas availability and general practice of its use for diagnosis of respiratory metastasizing disease such as lung cancer is seldom and rare, especially the SCLC/NSCLC specific NSE. The aim of present study is to determine the potential usefulness of NSE in diagnosis and prognosis of SCLC and NSCLC patients in our setting. Fifty-eight patients of lung cancer were identified and selected, between January 2004 to December 2007, and divided into various groups depending upon their clinical stage of disease. NSE level was determined in all patients and clinical history data and related pathophysiological components of all selected patients were carefully assessed and compulsorily followed to avoid any bias. Cancer status of patients were evaluated by data available from multiple bronchoscopies, X rays, cytology and histopathology examinations and grouped as SCLC with all five stages [I, II, IIIA, IIIB and IV] and NSCLC with only stage IV. NSE level was also determined in Healthy subjects and patients with non-malignant lung diseases [NMLD] for comparison. We observed significant elevation in levels in NSE for different stages of SCLC and NSCLC in comparison with healthy and NMLD groups. Most significant increase was noted in SCLC stage IV not only in comparison with healthy [P <0.001] and NMLD groups [P < 0.001] but also with stage I [P <0.001] within the group. Elevated difference in NSE levels was also correlated with stage II, IIIA and IIIB of SCLC group. As regard NSCLC, where patients belonged only to stage IV of disease, significant difference was observed with healthy [P <0.01] when compared with NSCLC, whereas non-significant difference in NSE levels was noted in group-SCLC stage II, IIIA and IIIB. In comparison, all stage IV patients [n=7] of SCLC exhibited higher levels of NSE with a range of 136.19 ng/ml to 175.01 ng/ml, higher than detected in patents of stage IV in NSCLC. The result of our study suggests that NSE appears to be a useful tumor marker for SCLC and to some extent, NSCLC. Moreover, NSE exhibits higher levels in some stages of SCLC suggesting, its specificity, not only for advanced stage of SCLC but also for SCLC in general as compared to NSCLC. Its determination, therefore, is beneficial in the diagnosis, treatment and a possible follow-up for patients survival

Comparative analysis of vitamin B 12 levels and effects of its deficiency in selected adult population diagnosed with various clinical conditions

Back ground: vitamin B12 deficiency has been associated with various clinical conditions and co-morbidities however none of the individual symptom, or group of symptoms could be ascertaining directly to its declined status. Mostly older population is affected and documented causes of deficiency are hematologic or neurological, followed by gastrointestinal and a possible altered vascular symptoms

Aim: the present prospective observational study was initiated to compare analytical levels of vitamin B12 and evaluation of underlying clinical condition and symptoms associated with possible vitamin B12 deficiencies. Materials and Methods: The study was prospective observational and carried out for the assessment period of 1st January 2000 till 30th Dec 2010. After two years of assessment, 290 patients [males, n = 156 and females, n = 134] were inducted in the study and finalized during the period 1st January 2002 to 30th December 2009. Age ranges were from 16 to 70 years, and categorized in two groups as > 60 yrs. and < 60 years. Several blood parameters [serum folate, B12, CBC, LDH, creatinine, Hb] were analyzed by standardized methods on automated analyzers

Results and Conclusion: vitamin B12 deficiency was found to be more prevalent in females and when compared with other groups the percentage increased up to 58.20% in individuals with vitamin B12 <150 pg/ml. The most common condition was malnourishment followed by anemia [n = 75; 46.01 %] and weakness [n = 55, 33. 74%] as the more frequent clinical findings. Other clinical conditions were neuropsychiatric, whereas less frequent findings were paresthesia and gastrointestinal symptoms. Moreover, hypertension was more prevalent in vitamin B12 deficient individuals followed by diabetes, dementia, stroke, ischemic heart disease and Parkinson's disease

Short title: vitamin B12 deficiency in clinical conditions

Pediatrics mandibular fractures: a study on the involvement of canine region

This study was conducted to compare the frequency of mandibular canine region fractures with fractures of other regions of mandible in patients with un-erupted canines at the Department of Oral and Maxillofacial Surgery, Abbasi Shaheed Hospital Karachi form January 2002 to March 2004. A Non Probability Convenience sample of all patients with age 6-12 years presenting with mandibular fracture were included. The sample was categorized into two groups: Age 6-9 years with un-erupted canines and Age 10-12 years with erupted canines. The fracture site parameter was categorized into two groups: Fractures in Canine Region and Fractures in other regions of the mandible. Total study sample was 76 subjects. Mean age of the subjects was calculated as 8.57 years [SD 1.94]. Male to Female ratio was 2.6:1. The most common cause of injury was recorded as fall 51.3% followed by road traffic accident 35.5%, assault and sports injuries accounted for 6.6%. The most common overall site of fracture was canine region 44.7%. In the age group [6-9 yrs] the fractures occurring in canine region were 51.3% and 15.8% in [9-12 years group]. Significant association was found to exist between the age groups [6-9 Years, 9-12 years] and fracture groups [canine region fractures, other region fractures] pvalue< 0.05. This study clearly demonstrates that mandibular fractures occur commonly in children in the region of un-erupted canines supporting the evidence of an area of weakness in the mandibular canine region, especially during the mixed dentition period

Histological patterns and clinical presentation of oral squamous cell carcinoma

The objective of our study was to identify the different histological patterns of Oral Squamous cell carcinoma [OSCC] in relevance to demographic variables and to evaluate histological patterns according to various clinical presentations at the joint department of Oral Surgery, Karachi Medical and Dental College and Abbasi Shaheed Hospital Karachi. This descriptive study was conducted from December 2005 to November 2006 at Oral Surgery Department of Karachi Medical and Dental College and Abbasi Shaheed Hospital Karachi. A total of 60 cases presenting with OSCC were included in this study. Their demographic details, habit profile, clinical information of lesion were recorded on a proforma. All the patients underwent biopsy and their histological information was also noted on the same proforma. This study included 60 patients of OSCC. Fifty eight percent of patients were from age group between 41 -60 years. Approximately 63.3% males and 36.7% females were affected and male to female ratio was 1.7: 1. Approximately 48.3% of lesions involved alveolus. Nearly 86.7% of patients were indulged in habits of tobacco chewing. Clinical appearance of lesion showed that 66.7% of lesions were ulcerative type and histologically 48.3% were well-differentiated OSCC. Majority of patients were indulged in habit of tobacco chewing, Ulcerative type was the dominant clinical presentation whereas histologically well-differentiated OSCC was the most common presentation. Infiltration was a consistent finding in all cases

Evaluation of Carcino-embryonic antigen [CEA] and diagnostic significance in adult patients suffering from Colorectal Carcinoma [CRC] and GIT malignancies

Carcinoembryonic antigen [CEA] is a classic tumor marker for CRC, and has been used to monitor CRC recurrence and as a prognostic factor for CRC patients. The CEA molecule is an onco-development human tumor marker and bears the cluster differentiation designation of CD66e. It has a molecular weight of 180 kDa. Due to considerable clinical merit of CEA for diagnosis, prognosis and treatment, a study was carried out to assess its levels in patients suspected of or diagnosed with GIT cancers, with special reference to colorectal carcinoma [CRC]. A total of 106 patients, 71 [66.98%] males and 35 [33.01%] females, were included in the study with age range of 46 to 79 years. Out of 71 males, 33 [46.47%] have malignant conditions and exhibited elevated levels of CEA whereas 38 have non-malignant complications with normal or non-significant CEA concentrations. The malignant conditions in males [n = 33] are sub-grouped and were determined to be pancreatic [n = 2, 6.06%], gastric [n = 10, 30.30%], colorectal [n = 18, 54.54%] and hepatic [n = 3, 9.09%] cancers. Furthermore, in female group of 35 patients, 15 [42.85%] were diagnosed with malignant condition of pancreatic [n = 1; 6.66%], gastric [n = 5; 33.33%], colorectal [n = 7; 46.66%] and hepatic [n = 2; 13.335] cancers and exhibited elevated levels of CEA. In present study all malignant conditions, either metastasizing or not, showed significantly elevated levels of CEA. In male-malignant cancer patents' groups, average CEA values were 102.20 40 ng/ml, 298.40 21 ng/ml, 451.65 16 ng/ml and 176.10 5 ng/ml for pancreatic, gastric, colorectal and hepatic cancers, respectively. Similarly in females elevated levels of CEA were noted in pancreatic [99 ng/ml], gastric [169.25 22 ng/ml] CRC [441.15 16 ng/ml] and hepatic [128.54 20 ng/ml]. At present, serial CEA-monitoring is considered the best non-invasive technique for detecting CRC and its recurrence. It is also substantiated that intensive follow-up CEA assays facilitate the identification of treatable recurrence at an early stage

Estimation of Total, Bio-available and Free Testosterone levels in various age groups of men

In recent years several studies recommended the estimation of total as well as bio-available and free testosterone levels to assess the variations provided by the measurements and thus developing the foundation for interpreting hormone status in all groups of men. Therefore present study documents the current testosterone status i.e. total, free and bio-available, including sex hormone binding globulin [SHBG] in variable age groups of men [n = 78] between 14 years to 65 years. They were grouped as male aged 14-24 yrs [young] [n = 24], 25-35 yrs [adult] [n = 20], 36-50 yrs [middle aged] [n.= 29] and 51-65 yrs [older] [n - 15]. Scrum total testosterone and SHBG were measured by Electro Chemiluminescence's [ECL] technology whereas bio-available and free testosterones were calculated from pre-described calculation methods. Total testosterone levels are comparable to each other in adult and middle age groups, however significantly differ [P < 0.001] among older and younger group. Moreover, highest level of significant difference in free testosterone values were obtained for younger men in comparison with middle age group [P< 0.001] and moderate level of significance was noted when same was compared with adult and middle aged groups [P < 0.05]. The assessment of data was gave similar outcome for bio-available testosterone as well; accept when older group was compared with middle aged men, which was found to be non-significant, in conclusion, the levels of total, free, bio-available testosterone and SHBG were compared with their normal ranges and noted to be match-able with their respective age groups accordingly

Radiographic evaluation of aetiology of mandibular third molar impactions

To determine the role of various factors in the etiology of lower third molar impaction by using measurements on conventional panoramic radiograph. Orthopantomograms of 100 patients having full dentition with bilateral mandibular third molars were included in the study ranging between ages of 18-39 years. All the patients were divided into erupted and impacted groups on the basis of status of lower thirdmolar on Orthopantomogram. All Radiographs were traced on overlying acetate paper and analyzed by measuring retromolar eruption space [from Xi-7 and AER-7] mesiodistal width of lower third molar, space width ratio and angulations of lower third molar, In erupted group, retromolar eruption space measured from Xi-7 was 31.79 +/- 3.38 where as in the impacted group, it was 26.93 +/- 4.11. Retromolar space measured from AER-7 was I 6.09 +/- 2.35 mm among erupted group whereas for impacted group, it was 11.06 +/- 3.64 mm. Mesiodistal width of mandibular third molar among erupted group was 13.29 +/- 1.41 mm while among impacted group, it was 13.70 +/- 1.72 mm. Space width ratio among impacted group was 0.83 +/- 0.36 whereas among erupted group, it was 1.22 +/- 0.20. Mean angulations of lower third molars was 7.79° +/- 9.15 among erupted group, where as among impacted group, mean angulations of lower third molars was 34.68° +/- 27.68. Both the groups were statistically different in all the tested variables except mesiodistal width of lower third molar

Comparative study of postprandial hypertriglyceridemia in diabetic patients with occurrence of microalbuminuria

It has been demonstrated that Type 2 Diabetes Mellitus [T2DM] patients, with the presence of microalbuminuria [MA] had higher postprandial triglyceride than those without MA. The present study further investigates this potential association and to elaborate the degree of dependence of T2DM with MA condition on onset of high postprandial [PP] triglyceridemia in our setting. A total of 32 patients with T2DM were included in the study during February 2007 and December 2008 and were divided into two groups according to the presence [n = 15, MA+ve] or absence of MA [n=l 7, MA-ve]. Blood was drawn in the fasting state and at 2 and 6 h after the standard mixed breakfast test meal for biochemical analysts. Plasma ApoA, triglycerides, glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, creatinine and Glycosylated hemoglobin Ale [HbAlc] levels were determined using standard methods. 24 hr albumin and urinary micro albumin showed highly significant difference [P<0.001] in values in MA-ve and MA+ve groups, whereas glycosylated HbAlc and duration of T2DM doesn't exhibit any significant difference. Biochemical constituents such as glucose, total cholesterol and HDL-cholesterol exhibited mild [P<0.05] to moderate [P<0.01] significance when compared within the groups of MA-ve and MA +ve patients in fasting and postprandial conditions. Comparatively highest level of constantly significant difference in values was noted only in triglycerides when MA +ve were compared with MA-ve, which remains high not only at 2 hrs. Postprandial [P<0.001] but also after 6 hrs. Under same conditions [P<0.001]. The data strongly support the theory and observations that in patients with T2DM and co-existence of MA, hypertriglyceridemia prevails, which further complicates the already co-morbid hyperlipidemic state in these patients

Diagnostic utility of Amino-terminal pro-B type natriuretic peptide [NT pro BNP] in adult patients with chronic kidney diseases

In recent studies, suggestions were made that the diagnostic utility of Amino-terminal pro-B type natriuretic peptide [NT-proBNP] a known biomarkers of myocardial dysfunction, be extended to chronic kidney disease [CKD] patients that are devoid of any cardiovascular abnormalities or disease, however may develop same in future. The goal of present study was to further evaluate the relationship between CKD and NT-proBNP concentration in patients with varying levels of renal dysfunction including End Stage Renal Disease [ESRD]. Stable adult patients of both gender [n = 76] with CKD were included in the study during January 2007 to September 2008, who had been on hemodialysis [HD]. The patients were divided into two groups depending on Left ventricular ejection fraction [EF]<50%. Other parameters such as mean arterial pressure [MAP], NT proBNP and biochemical parameters were measured using standard procedures. The result strongly presents a correlation between of NT-proBNP levels in CKD patients, who were without a definite onset of LVD. Furthermore, NT pro-BNP significantly correlated with an elevated protein to creatinine ratio and blood urea nitrogen [P < 0.01] suggesting that onset and presence of CKD influenced the concentration of natriuretic peptides. The present study regarding assessment of NT proBNP in CKD patients, provide evidence that renal dysfunction and natriuretic peptides, especially NT-proBNP are correlated with each other. In addition, further prospective studies are underway to validate and better define this relationship

Diagnostic utility and Assessment of C - reactive protein [CRP] in patients with community acquired pneumonia

It has been researched and agreed upon that pneumonia elicits a powerful inflammatory response with the release of inflammatory mediators or biomarkers, such as acute-phase proteins, inteleukin-6 and C-reactive protein [CRP] from activated mononuclear phagocyte cells. It is also known and recommended that the early analysis of serum concentrations of CRP is a significant tool for the diagnosis and monitoring of different acute inflammatory processes. Community-acquired pneumonia [CAP] is documented to be the major cause of death in the western world and effects increasing number of population annually. In present study we have investigated the suggested usefulness of serum CRP levels in patients with CAP at the time of diagnosis and compared it with CRP of healthy controls. One hundred and seventy one [n = 171] patients were included in the study and classified according to presence of pathogens/ etiology in individual capacity as well as in combination with other organisms. All microbiological assays were performed according to standardized procedures, whereas CRP was measured in serum samples by an automated turbid metric method with normal reference of

Diagnostic importance of C-reactive protein [CRP] analysis in tuberculosis pleural effusions

One of the acute-phase biomarkers that have recently been investigated for its clinical utility in tuberculosis pleural effusion is C-reactive protein [CRP] which has already been commonly used as a marker of inflammation and tissue injury. Therefore, the present study was undertaken to analyze the viability of CRP as a diagnostic aid for tuberculosis in lymphocytic pleural effusions. Fifty two [n = 52] patients with lymphocytic pleural effusion with definite diagnosis of a disease condition, were taken into the test group and classified into no tuberculosis [n = 28] group and tuberculosis pleurisy group where sputum culture was positive for Mycobacterium tuberculosis in pleural effusion [n = 24]. CRP in pleural fluid was analyzed by automated turbid metric immunoassay method as per description of the manufacturer and normal reference value in serum is

Evaluation of vitamin B12 and folic acid deficiencies in selective middle aged and elderly male and female patients

Significant prevalence of vitamin B12 and folate deficiencies supported by biochemical evidence has been reported in the world. It was indicated that these biochemical evidences are associated with prevalence of anaemia in elderly. The major reasons of vitamin deficiencies, especially that of B-12, was reported to be inadequate dietary intake and, in the elderly, malabsorption of the vitamin from food. Vitamin deficiencies especially that of B-12 are usually diagnosed on the basis of serum or plasma vitamin concentrations. Due to dilemma of management and diagnoses of mal-nutrition and vitamin deficiencies in elderly population, the present study was undertaken to ascertain vitamin B12, folate and RBC folate status in selected middle aged and elderly male and female patients. A total of 132 patients [period March 2004 to November 2007], were selected according to gender and age. For males [n = 72]; age groups were 50-60, 61-70, 71-80 yrs and greater than 80 yrs and for females [n = 60]; age groups were 52-61, 62-69, 70-79 and greater than 80 yrs. The results clearly depicts that elderly patients in both gender between the age groups of 71 and greater than 80 had significantly low vitamin concentrations [p < 0.001] than the middle age groups of 61 to 70 [P < 0.01]. Correspondingly, their hemoglobin levels were also relates to the overall picture of either normal or low concentrations of vitamins in all groups. In males the lowest concentration of 3.5 ng/ml for folate, Vitamin B12 of 228 pg/ml and 168 ng/ml for RBC folate were observed in > 80 years group preceded by 6.2 ng/ml, 278 pg/ml and 170 ng/ml respectively, in 71 to 80 years group, whereas in females, the observations were 2.5 ng/ml for folate, 220 pg/ml for B12 and 110 ng/ml for RBC folate concentrations in > 80 years age group of patients. In conclusion few management strategies were suggested for therapy of vitamin deficient older patients