Clinical and equipment-related factors associated with the adequate peripheral blood stem cell collection in autologous transplant at a tertiary cancer center in Kerala - A retrospective cohort study.

BACKGROUND: PBSC collection using apheresis is the preferred source of hematopoietic stem cells transplantation. However, apheresis procedures fail to harvest adequate CD34 yield in 5 to 40% of patients during the first collection. Therefore, this study aimed to study both the clinical- and equipmentrelated factors influencing CD34 yield among the autologous patients and to compare the collection efficiency of two apheresis equipments(Haemonetics MCS+ and Terumo Spectra Optia). METHODS: Retrospective analysis of 69 patients underwent PBSC collection from 2015 to 2018. Frequency, clinical- and equipment-related factors responsible for adequate CD34+ cells (≥2 x106 cells/kg) yield during the first collection was studied. Factors such as collection efficiency, percentage platelet loss and percentage hemoglobin loss were considered to compare the two apheresis system. RESULTS: Two-third (72%) patients of the study population had adequate CD34 stem cells yield during the first collection. Factors such as exposure to lenalidomide-based pretreatment regimen, peripheral blood WBC count and CD34 count are associated with the adequate CD34 yield. Optia had a slightly better collection efficiency than MCS+ (50 and 44; p=0.37). Optia had lower product volume (237 vs 298 ml) and lesser procedure duration (277 vs 360 min), whereas the median Hb loss (3.0% and 2.3%) and mean platelet loss (49% and 34%) were higher with MCS. CONCLUSION: This study infers that the collection efficiency of both the equipments in collecting CD34 stem cells was similar. However, during PBSC collection, procedures using Optia can be preferred to MCS+ on the patients with risk of anemia and thrombocytopenia.

Historical and current perspectives on therapeutic potential of higher basidiomycetes: an overview.

Mushrooms are macroscopic fungi which can be either epigeous or hypogeous and is estimated to be 140,000 on earth, yet only 10% are known. Since ancient time, it played a diverse role in human history for mycolatry, mycophagy and as medicine in folklore and religion. Many Asian and western countries consider mushrooms as panacea for a large number of diseases and utilized for consumption as a gourmet food for its taste as well as flavor. In recent years, scientific research fraternities have confirmed that various extracts and metabolites of mushrooms used traditionally are able to treat a wide range of diseases due to their balanced modulation of multiple targets thereby providing a greater therapeutic effect or equivalent curative effect to that of modern medicine. Medicinal mushrooms especially those belonging to higher basidiomycete groups are reservoir of bioactive compounds with multiple therapeutic properties. The present review provides historical importance as well as an updated information on pharmacologically relevant higher basidiomycetes belong to the genus Agaricus, Auricularia, Phellinus, Ganoderma, Pleurotus, Trametes and Lentinus and their biologically active secondary metabolites. This will help the researchers to understand various type of secondary metabolites, their therapeutic role and related in vivo or in vitro work at a glance. The mounting evidences from several scientific community across the globe, regarding various therapeutic applications of mushroom extracts, unarguably make it an advance research area worth mass attention.

Tumor control by hypoxia-specific chemotargeting of iron-oxide nanoparticle - Berberine complexes in a mouse model.

AIM: To evaluate the therapeutic efficacy of hypoxic cell-sensitizer Sanazole (SAN) -directed targeting of cytotoxic drug Berberine (BBN) and Iron-oxide nanoparticle (NP) complexes, to solid tumor in Swiss albino mice. MAIN METHODS: NP-BBN-SAN complexes were characterized by FTIR, XRD, TEM and Nano-size analyzer. This complex was orally administered to mice-bearing solid tumor in hind limb. Tumor regression was analysed by measuring tumor volume. Cellular DNA damages were assessed by comet assay. Transcriptional expression of genes related to tumor hypoxia and apoptosis was evaluated by quantitative real-time PCR and morphological changes in tissues were analysed by histopathology. Also levels of antioxidants and tumor markers in tissues and serum biochemical parameters were analysed. KEY FINDINGS: Administration of NP-BBN-SAN complexes reduced tumor volume and studies were focussed on the underlying mechanisms. Extensive damage to cellular-DNA; down-regulated transcription of hif-1α, vegf, akt and bcl2; and up-regulated expression of bax and caspases, were observed in tumor. Results on tumor markers, antioxidant-status and serum parameters corroborated the molecular findings. Histopathology of tumor, liver and kidney revealed the therapeutic specificity of NP-BBN-SAN. SIGNIFICANCE: Thus SAN and NP can be used for specific targeting of drugs, to hypoxic solid tumor, to improve therapeutic efficacy.

Anorectal melanoma: experience from a tertiary cancer care centre in South India.

Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months. None of the 22 patients survived for two years. Nine patients (29%) had curative surgery, in the form of abdominoperineal resection (six patients), abdominoperineal resection with bilateral inguinal node dissection (one patient), abdominoperineal resection with liver resection (one patient) and posterior exenteration (one patient). In patients who underwent curative surgery, the median overall survival was 15 months and disease-free survival was nine months, with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an aggressive disease with a poor prognosis. The majority of patients present with distant metastases. Prognosis depends on stage at presentation. Early diagnosis and surgical resection may improve the overall outcome. Newer modalities such as immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and anti-programmed cell death protein 1 monoclonal antibodies have radically changed the management of mucosal melanoma and may, in the future, improve the overall prognosis of anorectal melanoma.

Spring-loaded Syringe for Multiple Rapid Injections.

Mesotherapy refers to multiple injections of small quantity of the drug over a large area. The mesoguns available are expensive and the motor-driven models tends to waste the expensive material to be injected since the plunger stops after injecting without recoil. We searched for a less expensive device which would inject like the mesogun and still not waste the solution. On searching the web, we identified a spring-loaded syringe. We describe the assembly and use of this inexpensive syringe for delivering multiple injections with minimal wastage.

Diagnostic and prognostic significance of exercise-induced premature ventricular complexes in men and women: a four year follow-up.

Two hundred eighty patients (197 men and 83 women) with normal rest electrocardiograms and no history of prior myocardial infarction were referred for evaluation of chest pain. It was found that exercise-induced premature ventricular complexes had a lower sensitivity, specificity, positive predictive value and negative predictive value in predicting significant coronary artery disease than exercise-induced ST segment depression greater than or equal to 1 mm. The incidence of exercise-induced premature ventricular complexes was not significantly different in patients with no significant coronary artery disease, single vessel disease or multivessel disease. The site of origin of exercise-induced premature ventricular complexes was not helpful in predicting the presence or severity of coronary artery disease. At a mean follow-up period of 47.1 months, exercise-induced premature ventricular complexes did not predict coronary events (cardiac death or nonfatal myocardial infarction) in men or women.

Retrospective audit of clinico-pathologic features and treatment outcomes in a cohort of elderly non-Hodgkin's lymphoma patients in a tertiary cancer center.

INTRODUCTION: There is limited data from India regarding elderly non-Hodgkin's lymphomas (NHL) patients. Hence, this audit was planned to study the clinic-pathological features and treatment outcomes in elderly NHL patients. METHODS: Retrospective analysis of all NHL patients above age of 59 years treated at the author's institute, between December 2010 and December 2013 was done. Case records were reviewed for baseline details, staging details, prognostic factors, treatment delivered, response, toxicity and efficacy. SPSS version 16 (IBM, Newyork) was used for analysis. Descriptive statistics was performed. Kaplan-Meir survival analysis was done for estimation of progression-free survival (PFS) and overall survival (OS). Univariate analysis was done for identifying factors affecting PFS and OS. RESULTS: Out of 141 NHL patients, 67 patients were identified subjected to the inclusion criteria. The median age was 68 years (60-92). Majority were B-cell NHL (86.6%). The commonest subtype in B-cell was diffuse large B-cell lymphoma (55.2%). Fifty-four patients took treatment. The treatment intent was curative in 41 patients (61.2%). Among the patients receiving curative treatment, 16 patients couldn't receive treatment in accordance with NCCN guidelines due to financial issues. Two years PFS was 55%. Two years PFS for B-cell NHL and T-cell NHL were 55% and 50% respectively (P = 0.982). Two years PFS for standard Rx and nonstandard Rx were 62% and 50% respectively, but it didn't reach statistical significance (P = 0.537). Two years OS for the entire cohort was 84%. CONCLUSION: Standard treatment in accordance with guidelines can be delivered in elderly patients irrespective of age. There is a need for creating financial assistance for patients, so that potentially curative treatments are not denied.

Patterns of care in geriatric cancer patients - An audit from a rural based hospital cancer registry in Kerala.

BACKGROUND: There is deficit of data from India on elderly patients with cancer. Comprehensive geriatric assessment may lead to a better decision making capacity in this population. However, routine implementation of such assessment is resource consuming. AIM: The aim of this study was to determine the patterns of care in elderly patients treated at a tertiary rural cancer center in India. MATERIALS AND METHODS: All patients with age 70 or above with solid tumors without any definitive treatment prior to the registration at our center and registered between 01/01/2010 and 31/12/2011 were selected for this study. The baseline demographic pattern and the pattern of care of treatment were analyzed. SPSS version 16 (IBM Inc, Armonk, New York, U.S.) was used for analysis. Descriptive data are provided. RESULTS: A total of 761 patients were evaluable subject to the aforementioned inclusion criteria. The median age of this cohort was 75 years (70-95 years). The most frequent primary sites of malignancies in 451 males were head neck (32.4%), lung (23.3%) and gastrointestinal (23.3%). In 310 females, the most common sites were head neck (31.6%), gynecological (18.4%) and gastrointestinal (24.5%). 228 (30%) of the patients had localized disease, 376 (49.4%) had loco-regionally advanced disease and 145 (19.1%) had distant metastases at presentation. 334 (46.32%) of patients were treated with curative intent. On logistic regression analysis the factors that predicted use of curative intent treatment were age <75 years, performance status 0-1, primary site and clinical extent of disease. CONCLUSION: Routine comprehensive geriatric assessment needs to be implemented in our setting as almost 50% of our geriatric patients undergo curative intent treatment.

Clinical significance of exercise-induced bundle branch block.

To evaluate the diagnostic significance and long-term follow-up data of patients with exercise-induced bundle branch block (BBB), 10,176 consecutive patients' exercise test data were reviewed and 50 patients found to have exercise-induced BBB. Clinical, exercise test and arteriographic data were analyzed along with follow-up data during a mean of 43 months. Of the 50 patients, 37 had exercise-induced left BBB and 13 had exercise-induced right BBB. Significant coronary artery disease (CAD) was diagnosed in 26 of 37 patients (70%) with exercise-induced left BBB and in all 13 patients (100%) with exercise-induced right BBB. In patients who underwent coronary arteriography, data demonstrated a high prevalence of proximal left anterior descending disease (17 of 20, 85%). Follow-up data revealed that exercise-induced BBB was associated with a 36% (18 of 50) incidence of coronary events, including 16 patients who underwent coronary artery bypass grafting and 2 hospitalized for congestive heart failure. Results indicated that exercise-induced BBB was infrequent and occurred primarily in association with CAD, had a high prevalence of proximal left anterior CAD, infrequently had similar onset and offset heart rates, was reproducible and associated with a greater incidence of coronary artery bypass grafting than had been previously reported, although the incidence of cardiac events was similar to those investigations.

Clinical characteristics of patients younger than 60 years with mitral anular calcium: comparison with age- and sex-matched control subjects.

The clinical characteristics of 107 patients younger than 60 years with mitral anular calcium (MAC) were compared with those of 107 age- and sex-matched control subjects. The patients with MAC included 55 men and 52 women, mean age 51 years. The control group included 55 men and 52 women, mean age 51 years. Patients with MAC had a higher prevalence of cardiomegaly on chest x-ray (p less than 0.0001), left atrial and left ventricular enlargement by echocardiography (p less than 0.0001), precordial murmurs (p less than 0.0001), diabetes mellitus (p less than 0.0001), systemic hypertension (p less than 0.025) and total conduction defects on surface electrocardiograms (p less than 0.0001) compared with the age- and sex-matched control subjects. The mean serum phosphorus and product of serum calcium and phosphorus were higher in patients with MAC (p less than 0.0025) than in the control subjects. The prevalence of coronary heart disease, aortic stenosis and hypertrophic cardiomyopathy and the mean serum cholesterol, triglyceride, total protein, albumin, creatinine, alkaline phosphatase and calcium levels were not significantly different between patients with MAC and the control subjects.

Cardiac conduction defects in patients older than 60 years with aortic stenosis with and without mitral anular calcium.

The prevalence of conduction defects was investigated in 51 patients older than 60 years with aortic stenosis (AS) who underwent aortic valve replacement. Thirty one of the 51 patients, (61%) had associated mitral anular calcium (MAC). The mean age and prevalence of coronary artery disease, systemic hypertension and diabetes mellitus were similar in both groups. The prevalence of conduction defects (atrioventricular block, sinoatrial disease, bundle branch block, left anterior hemiblock or intraventricular conduction defect) was 18 of 31 (58%) in patients with MAC and 5 of 20 (25%) in patients without MAC (p less than 0.025). We conclude that patients older than 60 years with AS have a high prevalence of MAC, and that the prevalence of conduction defects is higher in patients older than 60 years with combined AS and MAC than in patients with AS without MAC.

Digoxin-induced positive exercise tests: their clinical and prognostic significance.

To evaluate the influence of digoxin on the results of exercise testing and the prognostic significance of digoxin-induced positive exercise tests, 98 healthy men, aged 22 to 70 years, were studied. All had normal initial exercise test results. All took digoxin, 0.25 mg daily, for 14 days, and then performed daily exercise tests until each had a negative test response. Five years after these initial tests, a medical history was obtained from 92 of the 98 subjects, and 76 subjects performed repeat exercise tests. Six subjects were lost to follow-up study. Twenty-five percent of subjects (22 of 98) had a digoxin-induced positive exercise test. There was a direct relation between age and the incidence of digoxin-positive tests. The incidence of digoxin-positive tests in men over age 60 years was 100 percent. By 30 seconds after exercise no subject had greater than 1.9 mm S-T depression. No test remained positive for more than 6 minutes after exercise was discontinued. No test was positive 12 days after digoxin was withdrawn. With logistic regression analysis, it was possible to estimate the probability that a subject would have a digoxin-induced positive test. No subject had had a cardiovascular event at follow-up study, but five subjects had a positive repeat exercise test. Four of these subjects had had a digoxin-positive test initially. It is concluded that (1) useful information can be obtained from exercise studies of patients who receive digoxin, (2) the probability that a positive exercise test is due to digoxin can be estimated, (3) to remove the exercise-induced electrocardiographic effect, the drug should be withdrawn for 12 days, and (4) digoxin may unmask subclinical coronary arterial stenosis.

Long-term follow-up of patients with echocardiographically detected mitral anular calcium and comparison with age- and sex-matched control subjects.

One hundred seven patients with echocardiographically documented mitral anular calcium (MAC) and 107 age- and sex-matched control subjects without MAC were studied and followed for a mean of 4.4 +/- 2.4 (standard deviation) years. Fourteen (7%) patients were lost to follow-up. Compared with the control group, patients with MAC had higher frequency of precordial murmurs (p less than 0.0001), cardiomegaly (p less than 0.0001), left atrial enlargement (p less than 0.0001), and rhythm and conduction disturbances (p less than 0.0001). During the follow-up, patients with MAC had higher incidence of valve replacement (p less than 0.0025), permanent pacemaker implantation (p less than 0.0025), congestive heart failure (p less than 0.0001), thromboembolic cerebrovascular event (p less than 0.01), sudden death (p less than 0.001) and total cardiac death (p less than 0.0001). However, the frequencies of myocardial infarction, coronary artery bypass surgery and angioplasty, endocarditis or noncardiac death were not significantly different between patients with MAC and the control subjects. Thus, patients with MAC have higher frequencies of precordial murmurs, cardiomegaly, left atrial and ventricular enlargement, rhythm and conduction disturbances. They more frequently undergo valve replacement and permanent pacemaker implantation, develop congestive heart failure and die of cardiac causes than age- and sex-matched control subjects.

Clinical and echocardiographic characteristics of patients with mitral anular calcification. Comparison with age- and sex-matched control subjects.

The clinical and echocardiographic features of 104 patients (53 women and 51 men) with mitral anular calcification (MAC) were compared with those of 121 age- and sex-matched control subjects (62 women and 59 men) without MAC. The incidence of coronary artery disease, rheumatic heart disease, systemic hypertension, and diabetes mellitus was similar in both groups. Patients with MAC had a greater incidence of cardiomegaly (p less than 0.001), cardiac conduction defects (p less than 0.001), and aortic outflow tract murmurs (p less than 0.005) than did control patients. Patients with MAC and without aortic root calcification had a higher incidence (p less than 0.001) of conduction defects than did patients with aortic root calcification without MAC. Control patients with and without aortic root calcification had a similar incidence of conduction defects. A higher incidence of atrioventricular block (p less than 0.025) and bundle branch block or left anterior hemiblock or intraventricular conduction defect (p less than 0.05) was present in anterior MAC than in posterior MAC. In conclusion, patients with MAC have a higher incidence of cardiomegaly, cardiac conduction defects, and aortic outflow tract murmurs than a control group.

Calcific valvular aortic stenosis with and without mitral anular calcium.

Seventy-six consecutive patients, mean age 66 +/- 9 years (+/- standard deviation), with isolated aortic valve replacement for calcific valvular aortic stenosis (AS) were studied. Mitral anular calcium (MAC) was detected by echocardiography in 45 patients (59%). Patients with MAC were older (p less than 0.01), had greater peak systolic aortic valve gradients (p less than 0.025), lower cardiac indexes (p less than 0.025) and smaller valve areas (p less than 0.05) than patients without MAC. Thirty-three percent of patients (15 of 45) with MAC required permanent pacemaker implantation after aortic valve replacement, compared with only 10% of patients (3 of 31) without MAC (p less than 0.025). During the follow-up of 7 years (mean 3.8 +/- 1.6), 27% of patients (12 of 45) with MAC died from cardiac causes, compared to only 7% (2 of 31) without MAC (p less than 0.025). Thus, patients with AS and MAC are older, have more severe AS, more frequently undergo permanent pacemaker implantation after aortic valve replacement and more frequently die of cardiac causes than patients with AS and no MAC during follow-up.

Ten-year results with the St. Jude Medical prosthesis.

Although the hemodynamic characteristics and durability of the St. Jude valve prosthesis have been reported, the need for and the degree of anticoagulation in patients who receive these valves remain uncertain. Our 10-year experience with 165 patients (100 men and 65 women, mean age of 58 +/- 13 years), who underwent valve replacement with St. Jude prostheses, is reported. Of the 165 patients, 147 were treated with warfarin. A prothrombin time 1.3 to 1.8 times control (range 15 to 20 seconds) was maintained in 134 patients with single valve and 1.8 to 2 times control (range 20 to 25 seconds) in 13 patients with double valve prostheses. The 10-year actuarial event-free incidence from thromboembolic and hemorrhagic complications was 84 and 95%, respectively. Of the 8 patients receiving antiplatelet therapy alone, 4 had thromboembolic events. Of the 10 patients on neither warfarin nor antiplatelet therapy, 3 had thromboembolic events. The 10-year actuarial event-free incidence from valve failure was 95%. The 10-year actuarial patient survival was 55%. Thus, the St. Jude valve is a safe and reliable prosthesis with acceptable overall long-term performance in patients given a modest anticoagulation regimen. Patients who receive St. Jude prosthetic valves without anticoagulants have a high incidence of thromboembolic events despite therapy with antiplatelet agents.

Previously unreported adverse reaction to encainide.

We describe a patient with recurrent atrial fibrillation who suffered a previously unreported adverse reaction to encainide therapy manifested by fever, chills, diaphoresis and myalgia. The patient had a similar response upon rechallenging with encainide, which resolved on discontinuation of therapy.

Safety of nifedipine in subjects with bronchial asthma and COPD.

This prospective study was undertaken to evaluate the safety of nifedipine, a calcium channel blocking agent, on 60 subjects with asthma, chronic obstructive pulmonary disease (COPD), angina, and normal subjects. All subjects received nifedipine, 20 mg, sublingually. Spirometry was done pre-drug administration and every 20 minutes after for two hours. Parameters measured were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow at 25 percent to 75 percent of total volume (FEF25-75%). Subjects with asthma and COPD were also given nifedipine 20 mg three times daily, orally for two weeks, and tested biweekly during this period. All bronchodilators, beta-blockers, and long acting nitrates were withheld for five half-lives of the drug prior to test day. There was no adverse effect on the pulmonary function. We found a statistically significant improvement (p less than 0.05) in FEV1 after nifedipine. There was no tachyphylaxis at the end of two weeks. Nifedipine is safe in patients with asthma and/or chronic bronchitis.

Diagnostic and prognostic value of Holter-detected ST-segment deviation in unselected patients with chest pain referred for coronary angiography: a long-term follow-up analysis.

OBJECTIVE: To evaluate the diagnostic and prognostic significance of ST-segment deviation detected by ambulatory Holter monitoring in unselected chest pain patients referred for coronary angiography. METHODS: Two hundred seventy-seven patients (71% were men) who underwent coronary angiography for evaluation of chest pain were studied with 24-h ambulatory Holter monitoring within 72 h of angiography. A lumen diameter reduction of > or = 50% was considered coronary artery disease. The ST-segment deviation was defined as > or = 1-mm deviation from the baseline lasting > or = 1 min separated by a minimum of 1 min. The patients were followed up for 65 +/- 21 months (mean +/- SD) for occurrences of death, myocardial infarction, hospitalization for unstable angina, and need for revascularization. RESULTS: Of the 277 patients, 223 (80%) had coronary artery disease. The prevalence of coronary artery disease was not significantly different in patients with (43 of 48 patients; 90%) and without (180 of 229 patients; 79%) Holter-detected ST-segment deviation. The diagnostic accuracy of Holter-detected ST-segment deviation in predicting the presence of coronary artery disease was poor (33%), with a sensitivity of 19% and a specificity of 91%. The presence of Holter-detected ST-segment deviation was not predictive of future cardiac events or death. CONCLUSION: The ST-segment changes detected on ambulatory Holter monitoring are of limited value in identifying coronary artery disease and predicting the future adverse cardiac events or death in unselected patients with chest pain.

Redox reactions and fluorescence spectroscopic behaviour of trifluoperazine at the surface of colloidal silica.

Fluorescence spectroscopic behaviour and redox reactions of trifluoperazine (TFP) were studied in aqueous solutions in the presence of silica (SiO2) particles. The effect of surface heterogeneity on the secondary reactions of the transients was determined using optical absorption and fluorescence techniques. It appears that electrostatic interaction is the driving force for adsorption of TFP over SiO2 particle. Contrary to the change in fluorescence intensity with time observed in an aqueous solution, fluorescence intensity of TFP did not change significantly with time over the surface of SiO2. Fluorescence microscopic observations of spleen cells treated with TFP over SiO2 showed that the drug got distributed in cells similar to that observed in homogeneous aqueous solution.