Lung Function and Health Status in Patients of Chronic Obstructive Pulmonary Disease on Treatment with Tiotropium

Introduction: Chronic obstructive pulmonary disease (COPD) is a group of chronic and slowly progressive respiratory disordercharacterized by reduced maximum expiratory flow during forced exhalation. Tiotropium, a long-acting antimuscarinic agent,has well-known documented effect on improving lung function and quality of life (QOL). There are many studies globally ontiotropium and its effect on lung function, but limited studies available in our Indian set up. Hence, we planned this study.Materials and Methods: Patients were recruited from chest clinic and outpatient department from the Department of Medicineof University College of Medical Sciences and GTB Hospital. It was a prospective observational cohort study conducted fromNovember 2017 to April 2019. Tiotropium was given as meter dose inhaler in dose of 18 µg per dose, in schedule as prescribedby the Global Initiative for Chronic Obstructive Lung Disease-2017 guidelines. Patients were followed up for 3 months withperiodic assessment of lung functions, Saint George’s Respiratory Questionnaire (SGRQ) score, and symptoms assessment.Results: A total of 65 patients were recruited for study which included 57 (87.7%) males and 8 (12.3%) females. Among thepulmonary function tests measured, there is a significant change in mean forced expiratory volume (FEV1) at the end of followup period compared to FEV1 at baseline. There is a significant change in mean forced vital capacity at the end of follow-upstudy compared to start of the study. There was no significant change in mean SGRQ score after 1 month of start of drug,but significant statistical change observed at end of the 3rd month of the study compared to the 1st month that implies SGRQscore decreased and patients health status and QOL improved. There is a significant change in mean SGRQ score at the endof follow-up study compared to baseline. In our study, 16 patients (24.6%) complained of dry mouth, 7 (10.7%) complained ofpharyngitis or throat irritation, and 3 (4.6%) patients complained of constipation.Conclusion: There was a statistically significant change in lung functions and improvement in QOL scores as assessed bySGRQ at the end of the study compared to baseline by use of inhaled tiotropium in COPD patients

Mainstreaming genetic counseling for BRCA testing into oncology clinics – Indian perspective

BReastCAncer (BRCA) susceptibility genes BRCA1 and BRCA2 are mainly associated with hereditary breast and ovarian cancer (HBOC) syndrome and present an estimated 45%–65% cumulative lifetime risk of developing breast cancer and an 11%–39% risk of ovarian cancer. HBOC is also linked to triple-negative breast cancer (TNBC). BRCA1 mutations in TNBC are observed in 36% of women age <40 years and 27% of women age <50 years. In India, the prevalence of BRCA1/2 mutation varies from 2.9% to 38% among families with genetic predisposition toward hereditary cancers. With HBOC being linked to early-onset breast cancer and increased susceptibility to other cancers, early screening for BRCA mutations has become a pressing need. Though genetic counseling (GC) for BRCA mutation testing is common in most of the developed countries, India still faces several challenges in mainstreaming the same. Many barriers to effective GC for BRCA testing are unique to India. There is a dearth of trained geneticists which puts the pressure on oncologists to give GC for which they neither have the time or training. Presence of multiethnic/linguistic population acts as a major hindrance along the way toward development of robust predictive and effective GC models for BRCA testing. The current review discusses the need and benefits of GC in breast cancer prevention, through BRCA testing, from an Indian perspective. The functional framework of GC and the role of genetic counselors are discussed in detail. In addition, importance of GC training and role of a multidisciplinary team approach for mainstreaming pre- and post-BRCA test GC is highlighted.

An uncommon case of an adult with del(5)(q) in acute lymphoblastic leukemia.

Del(5)(q) is a common chromosomal abnormality with favourable prognosis in Myelodysplastic Syndrome (MDS) and Acute myeloid leukemia (AML). However, del(5)(q) is also seen rarely in Acute lymphoblastic leukemia (ALL) and its significance remains poorly understood. We present here, a case report of diagnosis of an adult 75 year old patient of ALL with a cytogenetic abnormality of del(5)(q32). His clinical features, morphology and immunophenotyping findings were suggestive of T-ALL. Relevant literature has been reviewed and discussed.

Cancer biomarkers - Current perspectives.

In the recent years, knowledge about cancer biomarkers has increased tremendously providing great opportunities for improving the management of cancer patients by enhancing the efficiency of detection and efficacy of treatment. Recent technological advancement has enabled the examination of many potential biomarkers and renewed interest in developing new biomarkers. Biomarkers of cancer could include a broad range of biochemical entities, such as nucleic acids, proteins, sugars, lipids, and small metabolites, cytogenetic and cytokinetic parameters as well as whole tumour cells found in the body fluid. A comprehensive understanding of the relevance of each biomarker will be very important not only for diagnosing the disease reliably, but also help in the choice of multiple therapeutic alternatives currently available that is likely to benefit the patients. This review provides a brief account on various biomarkers for diagnosis, prognosis and therapeutic purposes, which include markers already in clinical practice as well as various upcoming biomarkers.

Targeting protein acetylation for improving cancer therapy.

Acetylation is one of the most important post-translational modification of proteins determining the structure, function and intracellular localization that plays an important role in the signal transduction pathways related to diverse cell functions, both during unstimulated and stress conditions. Protein acetylation in cells is regulated by a co-ordinated action of histone acetyl transferases (HAT) and histone deacetylases(HDAC) that ensures the maintenance of homeostasis and execution of activities related to damage response viz. DNA repair, cell cycle delay, apoptosis and senescence. Since inhibition of histone deacetylation, stalls the progress of many nuclear events including proliferation and damage response events on the one hand and the levels of deacetylases are elevated in many tumours on the other. Histone deacetylase has been among the targets for the development of anticancer drugs and adjuvant. The recent observation showing acetylation of proteins by calreticulin (an endoplasmic reticulum resident protein) with a high efficiency when polyphenolic acetates are the acetyl group donating molecules and acetyl CoA as weak substrate extends the realm of protein acetylation beyond HAT/HDAC combination. Elucidation of the relative roles of HAT/HDAC mediated acetylation viz. a calreticulin mediated acetylation in cell function under a variety of stress conditions would hold key to the design of drugs targeting protein acetylation system.

Magnetic resonance imaging changes in a case of extra-pyramidal syndrome after acute organophosphate poisoning.

Distal symmetrical polyneuropathy and neuromuscular weakness is common neurological problem in recovery phase of acute organophosphate (OP) poisoning. Various types of extra pyramidal syndromes are uncommon sequel after OP poisoning. These are reported to be reversible within few weeks and characteristically associated with normal magnetic resonance imaging (MRI). In this report we are presenting a case with extra pyramidal syndrome after acute OP poisoning with few interesting MRI changes in striatum.

Engineered antibodies act as targeted therapies in cancer treatment.

Over the last two decades cancer cure rates have not gone up as expected, and the effectiveness of chemotherapy has reached a plateau. This has prompted a search for targeted therapies with higher efficacy and lesser toxicities. Monoclonal antibodies against cancer cells offer targeted therapies with little or no toxicities against normal tissues. In this review we will discuss the concepts behind the development of monoclonal antibodies in cancer and their present status in the clinic. Specifically, we will discuss the clinical use of Rituximab (RituxanO), Trastuzumab (HerceptinO) and Bevacizumab (AvastinO) in various cancers and the key clinical trials that have led to their incorporation in cancer therapeutics.

Kinase inhibitors translate lab discoveries into exciting new cures for cancers.

Genetic mutations can lead to abnormal activation of certain kinases that in turn lead to excessive cell division seen in cancers. Inhibitors of over activated kinases can theoretically inhibit cancer causing pathways and result in tumor shrinkage. These discoveries have sparked a revolution in drug discovery with many small molecule kinases inhibitors now being used in cancer clinical trials. The amazing success of Imatinib, a blocker of the bcr-abl kinase in chronic myeloid leukemia has shown that the drugs based on these strategies can improve cure rates in cancer. In this article, the authors review the concepts of kinase inhibition in cancer and principles behind the success of imitanib. The authors also review other promising kinase inhibitors being used in clinical trials that are expected to aid the fight against cancer.