THE ATP-BINDING CASSETTE TRANSPORTER A1 GENE POLYMORPHISMS AND TYPE 2 DIABETES MELLITUS.

Insulin resistance (IR), secretion of insulin, and abnormalities of lipid metabolism are all markers of type 2 diabetes (T2DM), which is a progressive and complex metabolic disorder. Major risk factors for the development of T2DM were identified as genetic, environmental, and lifestyle factors. Several studies found that many genes contribute to T2DM susceptibility after glucose tolerance. Adenosine Binding Cassette Transporter Proteins 1 is a member of the ABC gene superfamily that is involved in cholesterol transport and HDL cholesterol (HDL-C) biosynthesis. Abnormal cholesterol metabolism, particularly high-density lipoprotein, has been related to genetic variations in the ABCA1 gene (HDL-C). Previous research suggested that ABCA1 gene polymorphisms may a hereditary risk factor for type 2 diabetes, along with lower HDL levels in various populations.

EGFR and HER-2/neu expression in gallbladder carcinoma: an institutional experience

Background: Gallbladder cancer [GBC] is the most common malignancy of the biliary tract in India. Despite the recent advancement in the understanding of the cancer biology, the disease still remains a therapeutic challenge with poor prognosis and low survival. Surgery is the primary modality of treatment and rest of the modalities are basically adjuvant in nature. This study was performed to evaluate the epidermal growth factor receptor [EGFR] and human epidermal growth factor receptor-2 [HER-2/neu] expression in GBC

Methods: The present study was prospective and done in tertiary super-specialty institute of northern India. This was a pilot study, and at the time of completion, 29 samples were found suitable which were later submitted for EGFR and HER-2/neu evaluation. The sample includes both cases of GBC [n=18] and cholecystitis [n=11] as control. [Table 1] After performing necessary processing, slides were incubated with primary antibody [EGFR] ready to use [RTU] BioGenex, India and HER-2/neu dilution 1: 600, Dakopatts [Denmark]. Then slides were incubated with secondary antibody [Real Envision Detection Kit, Dakopatts, Denmark]. Finally in mounted slides, cell membrane staining was used to assess positivity for EGFR and HER-2/neu

Results: EGFR was positive in 21/29 [72.41%] overall, out of which 14/18 [77.78%] positive in cases and 7/11 [63.64%] positive in control. [Table 1, 3][Figure 2]. For HER-2/neu, it was positive in 21/29 [72.41%] overall, just like in EGFR mentioned above, but positive 12/18 [66.67%] in cases and 9/11 [81.82%] in control respectively. [Table 1, 3][Figure 3]

Conclusion: Despite the efforts by many investigators, GBC continues to represent a major challenge in oncology. Surgical resection remains the only curative treatment for this disease. The roles of radiation, chemoradiation, and chemotherapy in neoadjuvant and adjuvant settings remained to be defined in prospective studies. With further studies based on molecular understanding and developing new targeted therapies, we will be in better position to manage GBC and increase the survival rate

Treatment of ST Elevation Myocardial Infarction from Fibrinolysis to Primary PCI: In Terms of Risks and Benefits.

The treatment of ST elevation myocardial infarction (STEMI) has undergone significant advances over the past three decades. Current practice guidelines raise the importance of promptly restoring normal coronary blood flow and myocardial perfusion in the infarct zone after the onset of chest pain, through either pharmacologic or mechanical reperfusion strategies. Fibrinolytic therapy remains the most widely used reperfusion strategy worldwide. With the development of newer fibrinolytic agents and adjuvant potent anti-platelets therapies, this approach carries an increased risk of bleeding complications. The current research present up-date review of the use of reperfusion strategies for the treatment of STEMI, using data through the search of MEDLINE, PubMed, EMBASE, as well as related extracts from the annual report of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. We summarized data from the available studies conducted over the past last 30 years in relation to pharmacologic reperfusion therapy in regards to risks and benefits. Conclusion: Fibrinolytic therapy remains the main reperfusion strategy used for the treatment of STMI worldwide. In the current era, there is a lack of fibrinolytic therapy trials, mainly because of increased focus in mechanical reperfusion therapies’ studies in the developed world. Clinical trials on the use of the fibrinolytics with newer platelet agents are urgently needed.

Rheological studies on different oily vehicles for pharmaceutical preparations

The rheological properties of oily vehicles based on patents of non-aqueous vehicles for pharmaceutical suspensions were studied. The effects of different concentrations of suspending agents and different excipients on the flow curves were also investigated. A Rotovisko viscometer [Haake] fitted with concentric cylinder sensors, NV measuring head- 500 and a temperature controlled water jacket at 37°C was used. The results showed that Fractionated Coconut Oil [FCO] alone and with 0.7% w/v lecithin exhibited Newtonian behavior. Dispersions of aluminium stearate, hydrogenated castor oil, Cab-o-sil and sucrose in FCO exhibited pseudoplastic behavior. Aluminium stearate 1% w/v and above and the oily vehicle containing aluminium stearate, hydrogenated castor oil, lecithin and sucrose exhibited thixotropic pseudoplastic properties. The omission of lecithin from the later vehicle resulted in a decrease in the apparent viscosity and the loss of thixotropy. The thixotropic pseudoplastic behavior of oily vehicles is a desirable property in liquid pharmaceutical systems that ideally should have a high consistency in the container, yet pour or spread easily after they had been stirred vigorously. Possible reasoning and suggestions were discussed

Disease profile and treatment results of anal canal SCC: experience from AIIMS, New Delhi

Anal Canal squamous cell carcinoma [SSC] accounts for nearly 2% of all cancers of the alimentary tract. Over the past few years, the management of anal canal cancer has changed from primary surgery to primary chemoradiotherapy [CRT]. A total of 83 patients' [pts] records [62 males, 21 females] were retrospectively reviewed. Length of disease was <5 cm in 44 pts and confined to primary in 46 pts. Ten pts have anti-cancer therapy outside. We delivered radiotherapy [RT] alone to 16 pts, chemotherapy [CT] alone to 4 pts, CRT in 51 pts and pre-operative [pre-op] RT in 2 pts. RT dose was up to 30 Gray [Gy] =16; 30-50 Gy=12 and >50 Gy=41 pts. RT compliance was optimal in 64/69, grade [Gr] /= 2 in 13/69 pts. Thirteen pts [18.84%] were hospitalized during RT. No response [NR] was found in 4/83, <50% in 18/83, >50-<`00% in 39.83 and complete response [CR] in 22/83 pts. Recurrence at primary site was seen in 7 and loco-regional in 2 pts. Salvage therapy was done in all 9 pts [surgery =8 and CT=1]. Status at last follow up, alive without disease = 22/83 and with disease = 61/83. This retrospective analysis revealed that the advanced disease was in 47%, the optimal anti-cancer therapy could be delivered to 63.9%. Despite heterogeneity of patient population and management, the overall disease-free survival [DFS] with sphincter-preservation was achieved in 26.5% pts

Quantitative tumor volume vs. TNM staging: the impact on prognosis in head and neck cancer

To evaluate the prognostic value of tumor volume [TV] by clinical method [CM] and Computerized Tomography [CT] scan in head and neck [H and N] cancer. Total 25 patients' [pts] pretreatment tumor volume [PT TV] was assessed clinically by cuboid volume method. Afterwards contrast enhanced computerized tomography [CECT] images of the pts were transferred to workstation by DICOM software. The computerized tomography tumor volume [CT TV] was obtained on Radworks 6.0, using mouse control cursor. After assessment, the patients were given 3 cycles of neoadjuvant chemotherapy followed by radiotherapy by conventional method on Co-60 Theratron 780 C. After 1 month of treatment, TV was again measured. Statistical analysis was done on MSTAT statistical analysis software. Two-tailed student t test, chi square test and test for two proportions for significance had been used. Large variations in tumor volume were found both in intra as well as inter T-stages. As the tumor size increases with T stages, the differences in measurement of TV by both methods decreases. CT TV results pre as well as post-treatment were more consistent than clinical method. The use of TV as a prognostic factor by CT scan seems to be more useful parameter than the CM. TV should be included in the TNM [tumor, node, and metastasis] classification after setting the strict guidelines for tumor delineation, to solve the discrepancy of treatment outcome in the same clinical stage

Racial variation in clinical characteristic and outcome in patients presenting with acute myocardial infarction: comparison between Qatari and South Asian patients in Qatar

South Asians [SA] from the Indian Subcontinent are known to have coronary artery disease [CAD] at a very young age and also to have a more diffuse disease when compared to indigenous patients in the Western world. The aim of the study was to compare clinical characteristics and outcome of South Asian patients to Qatari patients presenting with acute myocardial infarction [AMI] in Qatar. The majority of SA residing in Qatar are manual workers of lower socioeconomic status when compared to the Qatari population. We conducted a retrospective analysis of a prospectively collected data of all patients diagnosed with acute myocardial infarction [AMI] in the State of Qatar during ten years [1991 -2001]. Patients were divided into two groups: Qataris [1598 patients] and South Asians [2606 patients]. Diagnostic classification of definite AMI was made in accordance with criteria based on the International Classification of Disease ninth revision [ICD-9]. The obtained information was based on the following parameters: age at the time of admission, gender, cardiovascular risk factor profiles [smoking, hypercholesterolemia, diabetes, and pre-existing coronary heart disease], and ECG. Data analyses were performed using univariate and stepwise logistic regression analysis. When compared to Qatari patients, SA patients were younger [47 yrs vs 61 yrs; p < 0.0001]. SA were more likely to be smokers [50.5% vs 23.4%; p < 0.0001] and male [96.9% vs 71.8% p < 0.0001]. SA were less likely to have: diabetes mellitus [24.8% vs 54.0%; p < 0.0001]; hypertension [19.9% vs 37.6%; p < 0.0001]; previous MI [8.1% vs 15.8%; p < 0.0001]; CABG [2.2% vs 3.9%; p = 0.002]. The number of patients who received thrombolytic therapy was significantly higher among SA when compared to Qatari [54.6% vs 25.9%; p < 0.0001], and this was significantly associated with lower in-hospital mortality rate [6.7% vs 16.8%; p < 0.0001]. SA patients who had AMI in Qatar had better outcome than Qataris. This may be explained by the patients' favorable baseline clinical characteristics such as younger age and less prevalence of diabetes and hypertension

Impact of fasting in Ramadan in patients with cardiac disease

To investigate whether Ramadan fasting has any effect on patients with heart disease. We prospectively studied 465 outpatients with heart disease who were fasting during the month of Ramadan from October 24 to November 24, 2003. These studied subjects were from various medical centers in the Gulf region; State of Qatar, Kuwait, United Arab Emirates, and Bahrain. We performed detailed clinical assessments one month before Ramadan, during Ramadan and one month after Ramadan and analyzed predictors of outcome. Overall, the mean age was 55.9 +/- 11.3 years [age range 32-72]. Of the 465 patients treated, 363 [78.1%] were males and 102 [21.9%] females. Among them, 119 [25.6%] patients had congestive heart failure, 288 [62%] patients with angina, 22 [4.7%] patients with atrial fibrillation and 11 [2.4%] patients with prosthetic metallic valves. Three hundred and seventy [79%] had prior myocardial infarction [MI], 195 [17.2%] had prior coronary artery bypass surgery [CABG], and 177 [38%] had prior percutaneous coronary interventions [PCI]. At the time of follow-up, we found that 91.2% could fast and only 6.7% felt worse while fasting in Ramadan. Of the studied subjects, 82.8% were compliant with cardiac medications and 68.8% were compliant with dietary instructions. We hospitalized 19 patients during Ramadan for cardiac reasons [unstable angina, worsening heart failure, MI, uncontrolled hypertension, subtherapeutic anticoagulation or arrhythmias]. The effects of fasting during Ramadan on stable patients with cardiac disease are minimal. Most patients with stable cardiac disease can fast

Comparison of plasma levels of anticardiolipin and antiphospholipid antibodies in male patients with or without response to streptokinase following acute myocardial infarction

Streptokinase therapy is a medical approach for reperfusion therapy but with variable responses among patients which may be associated with antistreptokinase antibodies or other antibodies such as antiphospholipid or anticardiolipin antibodies. To compare the blood levels of anticardiolipin and antiphospholipid antibodies and also responses to streptokinase in patients with acute myocardial infarction. In this case-control study, 52 male patients with myocardial infarction were studied in two groups marked as responsive and non-responsive to streptokinase. The patients' responses to streptokinase were measured according to their first ECG and the ECG taken 90-180 minutes following the administration of streptokinase. Reduction of more than half of the ST elevation was considered as being responsive to the treatment. The antibody titers against anticardiolipin and antiphospholipid were further checked by ELISA method. Correlation between each antibody and the response to streptokinase was analyzed using Mann Whitney test [T-test]. The relationship between the antibodies mean values and the responses to streptokinase was investigated. The Mean level of IgG anticardiolipin in responsive patients was significantly lower than the non-responsive group [P=0.009], however, the mean levels of other antibodies such as IgM anticardiolipin, IgG antiphospholipid and the IgM antiphospholipid were statistically insignificant respectively. Based on the results found in our study, it seems that the anticardiolipin antibody has an effect on the response to streptokinase. This antibody inhibits the fibrin