Detection of MDM2 gene amplification on tissue microarray-based Fluorescence In-Situ Hybridization (FISH) in well-differentiated and dedifferentiated liposarcomas, displaying a wide morphological spectrum: A validation study at a tertiary cancer referral centre

Background: Liposarcomas including atypical lipomatous tumors (ALT)/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPSs) display a histomorphological spectrum with their several diagnostic mimics. Murine double minute 2(MDM2) gene amplification characterizes ALT/WDLPS and DDLPS. Presently, there is no documented study from our subcontinent on the validation of MDM2 gene testing in these tumors. Material and Methods: Twenty-eight cases, diagnosed as ALT/WDLPS (n = 5) and DDLPSs (n = 23), along with 10 other tumors were tested for MDM2 gene amplification, using fluorescence in situ hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, diagnosed as ALT/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 immunostaining. Twenty tumors were tested for p16INK4a immunostaining. Results: FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as DDLPSs, 19 displayed MDM2 gene amplification. Among the 5 cases diagnosed as ALT/WDLPS, four showed MDM2 gene amplification. Finally, 19 cases were confirmed as DDLPS and 4 as ALT/WDLPS. Furthermore, 7/19 cases confirmed as DDLPS and all 4 cases as ALT/WDLPS tested for MDM2 immunostaining, displayed its diffuse immunoexpression, while a single case of DDLPS showed its focal immunostaining. None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 DDLPSs and 4 cases of ALT/WDLPS displayed p16INK4a immunostaining. The sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in ALT/WDLPS, and specificity was 100%. The sensitivity for MDM2 gene amplification was 94.7% in cases of DDLPS and 100% in cases of ALT/WDLPS. The sensitivity for p16INK4a was 100%. Conclusion: This constitutes the first sizable study on MDM2 testing in ALT/WDLPS and DDLPS from our subcontinent using TMAs. MDM2 gene amplification testing continues as the diagnostic gold standard for ALTs/WDLPSs and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 clone) and p16INK4a immunostaining, together seem useful for triaging cases for FISH.

Study of leukocytic hydrolytic enzymes in patients with acute stage of coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is a major killer worldwide. Atherosclerosis, which is the basis of CHD, is believed to be an inflammatory disorder. Though various aspects of atherosclerosis are extensively studied, leukocytic hydrolytic enzymes are not studied very well with respect to CHD. AIM: This study was planned to assess changes associated with leukocytic hydrolases in CHD patients. SETTING AND DESIGN: A tertiary care hospital; case-control study. MATERIALS AND METHODS: 106 patients with acute myocardial infarction, 60 patients with unstable angina and 45 healthy controls were included in the study. Acid phosphatase, lysozyme, adenosine deaminase (ADA) and cathepsin-G levels were estimated from leukocytes. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured. STATISTICAL ANALYSIS: Statistical comparison of data was done using student's t-test (unpaired). Correlation difference was calculated by using Pearson correlation coefficient. RESULTS: Significantly higher levels of acid phosphatase, lysozyme, ADA with lower levels of cathepsin G in leukocytes were observed in CHD group. We also found significantly higher levels of serum MDA with lower concentrations of blood GSH in CHD group. In diabetic CHD group, significantly higher levels of leukocytic acid phosphatase, lysozyme, ADA and serum MDA with lower levels of cathepsin G and blood GSH were observed. CONCLUSIONS: Our study indicates that leukocyte hydrolytic enzymes, mainly acid phosphatase, lysozyme and ADA were more active in CHD patients and may contribute to inflammation related with CHD. Its also indicates that leukocyte cathepsin-G may have antiinflammatory role.

Magnetic resonance urography (MRU) versus intravenous urography (IVU) in obstructive uropathy: a prospective study of 30 cases.

AIM: Intravenous Urography (IVU) as a diagnostic modality has limitations in patients of obstructive uropathy with impaired renal function. Our aim was to study the technique and diagnostic accuracy of Magnetic Resonance Urography (MRU) in obstructive uropathy and to correlate the findings with IVU. METHODOLOGY: Forty-eight patients, selected over a six-month period, based on mild to severe pelvicalyceal dilatation on screening ultrasonography, underwent an IVU; those having non-obstructive dilatation were excluded (18 patients). Thirty patients (age range 10 to 75 years) with definite obstructive dilatation underwent MRU. These were obtained using an open MRI unit (Siemens Magnetom Open Viva) with low-dose gadolinium-DTPA (0.01 mmol/kg body weight) using various MRI sequences. MRU studies were classified as 'excellent' or 'diagnostic' and data generated was compared with that of IVU. RESULTS: MRU studies were 'excellent' in twelve and 'diagnostic' in eighteen patients. Of the sixty pelvicalyceal systems (PCS) evaluated in thirty patients, there were thirty-seven calculi, nine pelvi-ureteric junction (PUJ) obstructions, six with impaired renal function, four malrotated kidneys and one each of horseshoe kidney, pancake kidney, pelvic mass (endometriomas), duplex moieties, ureterocele and vesico-ureteric reflux. MRU better depicted moderate-severe PCS dilatation, staghorn and urethral calculi, impaired renal function, extrinsic ureteric and PUJ obstruction. IVU better depicted small calculi and mild PCS dilatation. CONCLUSIONS: In these thirty patients of obstructive uropathy, low magnetic field, open MRI units and low-dose Gd-DTPA provided cost-effective MRU studies with excellent diagnostic utility. MRU scored over IVU in patients with moderate-severe dilatation, staghorn and urethral calculi, impaired renal function, extrinsic ureteric and PUJ obstruction.

Papillary carcinoma of thyroid presenting as posterior mediastinal mass with superior vena cava syndrome.

Enlarged thyroid with retrosternal extension presenting as anterior mediastinal mass is known. Superior vena cava (SVC) syndrome due to direct invasion from a primary thyroid malignancy is a rare phenomenon. We present a unique case of papillary carcinoma of thyroid extending into the posterior mediastinum with superior vena cava syndrome along with internal jugular and azygous vein thrombosis.

Role of multidetector CT virtual bronchoscopy in the evaluation of post-tracheostomy tracheal stenosis--a preliminary study.

AIM: To study the technique and utility of virtual bronchoscopy (virtual reality endobronchial simulation, VRES) as a tool to evaluate post-tracheostomy tracheal stenoses and to correlate the findings of virtual and invasive bronchoscopy and to follow-up treated lesions or those currently under treatment that were initially diagnosed with VRES. METHODOLOGY: This prospective study comprised nine patients in the age group 13 to 65 years presenting with breathlessness and stridor following one or multiple tracheostomies. They underwent plain CT using a multidetector CT (MDCT) scanner (Siemens Volume Zoom) using narrow (1 mm) collimation. These thin slice images were post-processed using an Irix-based workstation with a 'Fly-Through' endoscopy application. These patients also underwent a rigid (three patients) or fiberoptic (six patients) bronchoscopy. RESULTS: Of the nine patients that underwent VRES, five were found to have stenoses, three had obstructing granulation tissue, one had an obstructing membrane and one had synechiae. The invasive bronchoscopic findings supported the VRES diagnosis in all but one case of stenosis, one of granulation tissue and the case with synechiae. Membranes and synechiae were relatively difficult to diagnose without the corresponding axial and multiplanar images. VRES achieved a higher sensitivity, while invasive bronchoscopy a higher specificity. CONCLUSIONS: VRES proved to be comparable to invasive bronchoscopy in the depiction of post-tracheostomy tracheal stenoses, with a notable advantage in critical stenoses in that the airway distal to the stenosis could be assessed with VRES but not with invasive bronchoscopy. A preliminary VRES was found to be of assistance in the selection of patients for the more invasive therapeutic procedures such as laser ablation of granulation tissue and its follow-up.

An open clinical trial of benazepril--a new ACE inhibitor in mild-moderate hypertension.

Benazepril hydrochloride, a new non-sulfhydryl ACE inhibitor (ACEI) was studied in a titrated dose of 10 mg-20 mg once a day for 6 weeks in 42 mild to moderate adult hypertensive patients with sitting diastolic blood pressure (SDBP) 95-114 mm Hg. The pre-drug SDBP(mean +/- SE) of 102.5 +/- 0.8 mm Hg showed a significant reduction to 87.5 +/- 0.93 mm Hg at the end of treatment. BP was controlled (SDBP < or = 90 mm Hg) in 34 (81%) patients and a drop of at least 10 mm Hg from the pre-treatment SDBP value was noted in 34 (81%) patients. Common adverse reaction was cough in 8(19%) patients. Clinically significant changes in laboratory evaluations were not seen in any patient. Study showed that benazepril in a dose range of 10 to 20 mg per day is an effective agent for treatment of mild to moderate hypertension.

HIV in intensive care--a 3 years experience.

A three year prospective study of a total of 62 critically ill HIV patients in MICU showed a rising percentage from 0.86 in 1992 to 3.17 in 1994. Four major presentations were observed, neurological-20 patients (32.5%), sepsis syndrome-18 (29%), poisoning-10 (16.1%) and miscellaneous-14 (22.6%). Acute poisoning emerged as the most important preventable indication for MICU admissions. Interventions like CVP and haemodynamic monitoring-25 patients, endotracheal intubation-18, mechanical ventilation-14, tracheostomy-3, haemodialysis-3 were done when indicated. The mortality of the 14 ventilated patients was high at 92.9% compared to the overall HIV mortality of 46.8%. This study shows that critically ill HIV patients do deserve intensive care management with optimum infection control precautions. Survival of 53.2% is noteworthy in a resource stretched set up.

Nifedipine, captopril, metoprolol and nifedipine with metoprolol in hypertensive crisis in non-intensive care setting.

In 102 cases of severe hypertension (DBP > or = 115 mm Hg), with or without acute complications, efficacy and safety of SL Nifedipine 10 mg (NIF), SL Captopril 25 mg (CAP), IV Metoprolol 15 mg (MET) and SL NIF + IV MET were studied in an inpatient trial. Maximum mean percent reduction in SBP was 13.3, 9.7, 15.7 and 19.9 and in DBP was 21.2, 13.9, 12.5 and 20.4 with NIF, CAP, MET and NIF + MET respectively. A safe DBP of < or = 110 mm Hg (Kaplan) was achieved in 90, 61, 72.2 and 95.2 percent of patients. A statistically significant fall in DBP was observed at 5 minutes with all regimens except CAP which was at 15 minutes. Mild side effects observed were palpitations and flushing (NIF n = 4), taste disturbances (CAP n = 3), heaviness of head (CAP n = 1) and giddiness (MET n = 2, NIF + MET n = 2). The trial data suggest that hypertensive crisis can be managed, without intensive care facility, with all four regimens; this implies significant cost containment.

Amlodipine in mild and moderate hypertension: initial Indian experience.

In an open, non-comparative, variable-dose study, 20 outpatients with mild to moderate essential hypertension were treated with 5-10 mg amlodipine once daily for 4 weeks, after their blood pressures had stabilized on placebo. Amlodipine produced a significant decrease in blood pressure (P < 0.05) from the initial mean of 162/100 mm Hg to 139/85 mm Hg at 4 weeks. 80% of the patients reached the goal diastolic blood pressure of < or = 90 mm Hg with a once-daily dose of 5 mg amlodipine within 2 weeks. The remaining 20% also attained the goal diastolic blood pressure within 4 weeks, with a one-step increase in the dose to 10 mg at 2 weeks. Amlodipine maintained blood pressure reduction throughout the 24-hours dosing interval with a once-daily dose. Notably, no side effects were observed; pulse rate, electrocardiogram, and laboratory parameters were not significantly altered with therapy. Amlodipine in a single daily dose of 5-10 mg is effective and well tolerated in the treatment of patients with mild to moderate hypertension.

Sublingual nifedipine and captopril in hypertensive urgencies and emergencies.

Fifty two patients of severe hypertension, diastolic blood pressure > or = 115 mmHg, with or without acute complications, were treated with sublingual nifedipine 10 mg or sublingual captopril 25 mg in a randomized prospective in patient study with careful clinical monitoring. Both the drugs were safe and effective in rapidly lowering blood pressure. Nifedipine appeared to be superior to captopril with earlier onset of action, greater magnitude of response and longer duration of action. No significant side effects were observed in either of the two groups.

Familial hypercholesterolaemia--report of two cases.

Two young female patients aged 12 and 20 years with homozygous familial hypercholesterolaemia are presented with autopsy reports. Both had extensive coronary artery disease with myocardial infarction and tendon xanthomas. The first case had additional aortic stenosis.