Chronic persistent surgical pain is strongly associated with COMT alleles in patients undergoing cardiac surgery with median sternotomy.

OBJECTIVES: Catechol-O-methyl transferase (COMT), a catechol-dependent enzyme, plays pivotal role in the development of pain. In different ethnic populations, it is associated with chronic persistent surgical pain (CPSP). In this context, the present study is aimed to assess involvement of COMT allele (Val158Met) in the development of CPSP. METHODOLOGY: The patients (n = 216) underwent cardiac surgery with median sternotomy were selected to assess the magnitude of the CPSP evaluated with pain questionnaires' after 3 months from surgery. The exon 4 of COMT gene was PCR amplified and sequenced. The quantitative gene expression of COMT using RT-PCR corroborated the COMT enzyme activity. RESULTS: Among 216 patients who underwent sternotomy procedure, 54 patients showed CPSP even after 3 months from surgery. The sequence analysis revealed that, in 25% (54/216) patients having following one or more alleles: c.472G>A (Val158Met) (reported), and novel c.382C>G;c.383G>C (Arg128Ala), c.373C>G (Arg125Gly), c.370G>A (Val124Met), c.359G>C (Gly120Ala), c.349G>A, c.350G>A(Ala117Ser), c.349G>C, c.351C>A (Ala117Pro), c.349G>A (Ala117Thr), c.350G>C (Ala117Gly), and c.405G>C (Ala135Ser) were observed for the first time in Indian population. Distinct CPSP (≥ 4 NRS pain score) was observed in these patients correlating with COMT enzyme activity (7.80 ± 0.92 units/mg) which is 14 times lowered when compared with non-CPSP patient's (n = 162) 110.15 ± 6.41 units/mg. The findings of COMT gene expression using quantitative RT-PCR corroborated the COMT enzyme activity. CONCLUSION: The dominant effect of mutant COMT alleles connecting with low enzyme activity resulted in CPSP, warrants COMT genetic analysis prior to surgery was useful to predict the occurrence of CPSP.

Association of G472A allele of membrane bound catechol-O-methyltransferase gene with chronic post-sternotomy pain.

Chronic persistent surgical pain (CPSP) is a complex disease with strong genetic component. The studies on revealed association of mutations in membrane bound catechol-O-methyltransferase gene with CPSP were reported indifferent ethnic populations across the globe. We identify that one out of four patients who underwent sternotomy procedure showed CPSP even after 3 months of surgery. The Mb.COMT gene sequence analysis revealed of the four patients, three patients had no mutation in Mb.COMT gene, while in one patient exhibited G472A mutation. Interestingly, this patient showed CPSP even after 90 days of surgery. The magnitude of the CPSP was evaluated with pain questionnaires' at the end of 3 months after discharge from the hospital. In this study 25% (1/4) showed presence G472A allele correlating with CPSP. Further the study suggested that evaluation of G472A allele of Mb.COMT gene in the patients undergoing sternotomy for monitoring pain in pre and post-surgical events.

Well-differentiated fetal adenocarcinoma of the lung in an adult male: report of an unusual tumor with a brief review of literature.

We report a case of a well-differentiated fetal adenocarcinoma (WDFA) of the lung in a 50-year-old male smoker. The literature regarding this uncommon tumor is limited. This rare variant of adenocarcinoma is more common in females, in the third and fourth decades. Microscopically it is composed of neoplastic glands and tubules that resemble the fetal lung. Well-differentiated fetal adenocarcinoma is a low-grade malignancy and surgery is the preferred mode of therapy. This uncommon case of a well-differentiated fetal adenocarcinoma in an adult male patient is reported, with relevant immunohistochemical findings, along with a discussion of the current literature.

The effect on post-operative pain of intravenous clonidine given before induction of anaesthesia.

BACKGROUND: Treatment of acute post-thoracotomy pain is particularly important not only to keep the patient comfortable but also to minimize pulmonary complications. AIM: This study was designed to test the effect of pre-induction administration of clonidine, given as a single intravenous dose, on post-operative pain scores and fentanyl consumption in patients after thoracic surgery. SETTING AND DESIGN: Tertiary referral centre. Prospective, randomised, double-blind, placebo-controlled trial. METHODS: Sixty patients were randomly allocated to receive clonidine (3 mcg/kg) or saline pre-operatively before induction of anaesthesia. The primary endpoint was pain on coughing (visual analogue scale (VAS) 0-100 mm) 120 min after surgery, time to first analgesic injection in the post-anaesthesia care unit (PACU) and 24-h fentanyl consumption. STATISTICAL ANALYSIS: For between-group comparisons, t-test and U-test were used as appropriate after checking normality of distribution. The incidence of complications between the groups was compared by Fisher's exact test. RESULTS: The post-operative VAS for the first 120 min and the fentanyl consumption at 24 h was significantly greater in the placebo group compared with the clonidine group (P<0.05). The sedation score was increased in the clonidine group during study drug infusion, but did not differ significantly on admission to the PACU. CONCLUSIONS: A single intravenous dose of clonidine (3 mcg/kg) given before induction of anaesthesia significantly reduced the post-operative VAS score in the initial period and fentanyl consumption during 24 h after thoracic surgery.

Aetiology of peripheral lymphadenopathy in adults: analysis of 1724 cases seen at a tertiary care teaching hospital in southern India.

BACKGROUND: In patients presenting with peripheral lymphadenopathy, excision biopsy of the most accessible lymph node provides material to establish an early diagnosis, and is important in the management of these patients. METHODS: A retrospective study was done of 1724 lymph node biopsy specimens obtained from adult patients and submitted for histopathological examination over a 12-year period. RESULTS: About one-third (n = 614; 35.6%) of these patients had non-specific lymphadenitis. This included a heterogeneous group of disorders comprising benign follicular hyperplasia, reactive hyperplasia, marked follicular hyperplasia and reactive sinus histiocytosis. Tuberculosis lymphadenitis (n = 540; 31.3%) and malignancy (n = 447; 25.9%) were the other common causes. Of the 540 patients with tuberculosis lymphadenitis, the human immunodeficiency virus (HIV) status was tested in 424 (78.5%) patients; of these, 34 patients (8%) were HIV-seropositive. Epithelioid granulomas with caseation necrosis were more frequently seen in HIV-seronegative patients compared with HIV-seropositive ones (chi2 = 54.66; p < 0.001 ). In HIV-seropositive patients, multiple sites of lymph node involvement (chi2 = 40.597; p < 0.001), suppurative type with adjacent necrosis and panniculitis (chi2 = 68.128; p < 0.001), and non-reactive histological types (chi2 = 109.234; p < 0.001) were more commonly seen compared with HIV-seronegative patients. Kikuchi-Fujimoto disease (n = 36), Kimura disease (n = 7), Rosai-Dorfman disease (n = 6), were rare aetiological causes that have been infrequently reported from India. CONCLUSION: Awareness of the characteristic histopathological findings and uncommon aetiological causes of peripheral lymphadenopathy may spare patients from unnecessary evaluation and treatment. In HIV-positive patients, lymph node tuberculosis may be histopathologically unusual and may be suppurative or non-reactive in nearly one-third of patients.

Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity.

BACKGROUND: The retinoblastoma tumor suppressor (Rb) acts in a conserved pathway that is deregulated in most human cancers. Inactivation of the single Rb-related gene in Caenorhabditis elegans, lin-35, has only limited effects on viability and fertility, yet causes changes in cell-fate and cell-cycle regulation when combined with inactivation of specific other genes. For instance, lin-35 Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene. RESULTS: We used the ORFeome RNAi library to identify genes that interact with C. elegans lin-35 Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes in lin-35 mutants as compared to rrf-3 and eri-1 RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the synthetic lin-35 interactor zfp-2 was found to suppress RNAi and to cooperate with lin-35 Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function similar to lin-35 Rb, as synMuv B genes that prevent inappropriate vulval induction. Partial inactivation of specific spliceosome components revealed further similarities with lin-35 Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules. CONCLUSION: We identified an extensive series of candidate lin-35 Rb interacting genes and validated zfp-2 as a novel lin-35 synthetic lethal gene. In addition, we observed a novel role for a subset of splicing components in lin-35 Rb-controlled processes. Our data support novel hypotheses about possibilities for anti-cancer therapies and multilevel regulation of gene expression.

Coronary artery bypass in patients with severe left ventricular dysfunction.

We retrospectively reviewed the case records of 82 patients with severe left ventricular dysfunction (ejection fraction < 30%) who underwent coronary artery bypass grafting between March 1993 and February 2000. They were aged 28 to 76 years (mean, 60 years), and 66 of them were male. Significant comorbid factors included hypertension (93%), diabetes mellitus (85%), and hypercholesterolemia (49%). The number of grafts used ranged from 1 to 3. The majority of the patients (91%) belonged to the Canadian Cardiovascular Society angina class III. Coronary angiography revealed single-vessel (in 16% of the patients), double-vessel (52%), and triple-vessel disease (32%), and left main stem disease (18%). Seven patients (9%) died within 48 hours after surgery. The mean duration of hospital stay was 7 +/- 2 days. The 75 patients who survived were followed up for 3 months to 7 years. At the 1-year follow-up, 61 of the 68 patients (90%) who were alive moved up from angina class III to class I. Our observations suggest that coronary bypass carries an acceptable mortality risk and may offer a better quality of life in patients with poor ventricular function.