Implication of DNA repair genes in prostate tumourigenesis in Indian males.

Background & objectives: Prostate cancer (CaP) is the fifth most common cancer among Indian men. Tumour protein p53 (TP53) gene increases the fidelity of DNA replication and homologous recombination by transcriptional transactivation of mismatch repair (MMR) genes. DNA repair thus has a potential role in molecular carcinogenesis of CaP. The aim of the present study was to identify mutations, and polymorphisms in TP53 gene and MMR protein expression in CaP in Indian male population. Methods: TP53 codon 72 polymorphism was analysed in 105 CaP, 120 benign prostatic hyperplasia (BPH) cases and 106 normal controls. Mutational analysis of TP53 was done in DNA extracted from formalin fixed paraffin embedded tissue of 80 CaP and 24 BPH cases. Expression of MMR proteins viz. hMLH1, hMSH2, hPMS1 and hPMS2 was studied in 80 CaP, 15 prostatic intraepithelial neoplasia (PIN) and 15 BPH cases. Results: A somatic C/A variation at the intronic boundary of exon 7 in TP53 gene was observed in one each biopsy samples from CaP and BPH. A significant association of codon 72 TP53 Pro/Pro genotype was observed with the risk of CaP (OR, 2.59, P=0.02) and BPH (OR, 6.27, P<0.001). Immunohistochemical analysis of MMR proteins showed maximum loss of hPMS1 expression in cases of CaP and PIN while no loss in expression of MMR proteins was observed in BPH cases. The study also identified a significant loss of hPMS2 protein in poorly differentiated tumours (Gleason score >7) than in well differentiated tumours (Gleason score 3-6) (P<0.05). Interpretation & conclusions: The results of the present study demonstrate that TP53 codon 72 polymorphism plays significant role in the pathogenesis and susceptibility to CaP and BPH. Also, an aberrant MMR protein expression could be involved in progression of prostate cancer through PIN, early CaP to aggressive CaP. The loss of hPMS2 protein expression may serve as a marker for progression of CaP.

Myocardial dysfunction in rheumatic carditis--does it really exist?

OBJECTIVES: Acute rheumatic fever (ARF) continues to affect millions of children in developing countries. Aim of the present study was to evaluate the role of myocardial dysfunction in the genesis of heart failure in patients with rheumatic carditis. There are limited studies on this subject. METHODS AND RESULTS: In this prospective study, 108 consecutive patients of ARF were evaluated by echocardiography and assay of cardiac troponin I blood levels. The patients were divided into three groups. Group A (n = 30): patients with no evidence of carditis; Group B (n = 45): patients with first attack of carditis; and group C (n = 33): patients with recurrent attacks of carditis. Left ventricular dimensions tended to be larger in Group B and C patients. Left ventricular ejection fraction did not differ between the groups (Group A: 63 +/- 8.1%, Group B: 58 +/- 7.9%, Group C: 61.2 +/- 9%, p = ns). Heart failure was present in 37.7% patients of Group B, and in 60.6% patients of Group C (p = < 0.05). Ejection fraction was normal in majority of heart failure patients (75.7%). It was reduced in 29.4% of patients in Group B and in 20% of Group C patients with heart failure (p = ns). All patients with low ejection fraction had hemodynamically significant regurgitant valvular lesions. Mean cardiac troponin I values, an index of myocardial damage, did not differ between the three groups (Group A: 0.062 +/- 0.027 ng/ml, Group B: 0.068 +/- 0.019 ng/ml, Group C: 0.071 +/- 0.031 ng/ml, p = ns). CONCLUSION: The present study did not demonstrate any echocardiographic abnormalities or cardiac troponin I elevation suggesting significant myocardial involvement during acute rheumatic fever. This lends credence to the view that myocardial involvement does not play any significant role in the genesis of heart failure in patients with rheumatic carditis.

Screening of prostate cancer in males with prostatism.

Comparison of different screening methods including digital rectal examination (DRE) and estimation of serum prostate specific antigen (PSA) had been done for detection of cancer prostate at initial stages in 186 patients presenting with prostatism. The detection rate of raised serum PSA (> 4 ng/dl) was found significantly higher than that of abnormal DRE because it could detect cases of prostate cancer at very early stages. On the other hand using abnormal DRE alone as criteria for biopsy, large number of these cases, specially at early stages, would have remained undetected (36.9%) thereby giving false low incidence. Serum PSA was found raised in pre neoplastic conditions (73.9%) like PIN and AAH also, majority of which were missed on DRE (65.2%). Raised serum PSA was found in many benign conditions (36.7%, false positive) also, hence prostatic biopsy is advised to confirm malignancy.

Prevalence of bacterial prostatitis in benign prostatic hyperplasia.

To define the prevalence of bacterial prostatitis and urinary tract infection (U.T.I) among benign prostatic hyperplasia patients (B.H.P) undergoing prostatectomy trans urethral resection of prostate (T.U.R.P.), 100 consecutive patient has their preoperative and post-operative urine cultures along with tissue culture of the resected prostatic tissue. Our data suggests that significant incidence (42%) of bacterial growth in prostatic tissue-occurs in patients with B.H.P. Pre-existing U.T.I. is not a reliable indicator by which this group could be identified pre-operatively and prostatic infection could be treated.

Incidence of anaerobic bacterial infection following transurethral instrumentation.

Total 300 patients undergoing transurethral instrumentation had their urine culture for aerobic and anaerobic organism pre-operatively and post-operatively. An increase in the incidence of anaerobic urinary tract infection from 2% pre-operatively to 14% post-operatively following transurethral instrumentation was documented. It was concluded that transurethral instrumentation increases the incidence of anaerobic urinary tract infection and patients having symptoms of urinary tract infection following such procedures with sterile urine for aerobic bacteria should be studied and treated appropriately for anaerobic urinary tract infection.

Primary adenocarcinoma of the urinary bladder--a case report with review of literature.

Primary adenocarcinoma of the urinary bladder is a rare neoplasm. We present the clinicopathological and immunohistochemical analysis of a case in a 50 year old male. The histogenesis of the tumour and a review of literature is also discussed.