Prevalence of pulmonary nocardiosis in a tuberculosis hospital in Amritsar, Punjab

The prevalence of pulmonary nocardiosis in a tuberculosis and chest diseases hospital in Amritsar is reported. Of 1510 sputum samples cultured from 1016 patients, 67 sputa originating from 16 patients were found to be positive for the Nocardia asteroides species complex. Based upon repeated isolation of N. asteroides from the respiratory tract, its microscopic demonstration in KOH wet mounts or stained smears of sputum and clinical evaluation of patients, 14 cases of pulmonary nocardiosis were diagnosed. This gave a prevalence of 1.4% pulmonary nocardiosis in the tuberculosis hospital. The prevalence of the disease was found to be 1.3% in the males as against 1.5% in the females. Of the various clinical categories of patients investigated, pulmonary tuberculosis with sputum negative for acid-fast bacilli (AFB) yielded the highest prevalence of 3.2%, followed by 1.3%, 1.2%, 1.1% and 0.5% in pneumonia, chronic obstructive pulmonary disease (COPD), bronchiectasis and pulmonary tuberculosis with sputum positive for AFB, respectively. Type IV cutaneous hypersensitivity to nocardin was observed in 19 of 908 (2%) patients tested, whereas only a solitary positive reactor was found among 260 healthy volunteers. Twelve of 19 nocardin positive reactors (63%) had unequivocally proven pulmonary nocardiosis. The nocardin skin test gave false negative results in two nocardiosis patients. More comprehensive investigations are warranted in order to evaluate the nocardin skin test as an additional aid for the diagnosis of nocardiosis. Barring a solitary exception, the nocardiosis patients were successfully treated with sulphadiazine or trimethoprim-sulphamethoxazole (TMP-SMZ) combination. To the best of our knowledge, this is the largest series of pulmonary nocardiosis patients in a prospective study as yet reported from India. The observations underscore the point that nocardiosis warrants greater attention in the differential diagnosis of bronchopulmonary diseases.     

Dysregulation of the epigenome in triple-negative breast cancers: Basal-like and claudin-low breast cancers express aberrant DNA hypermethylation

A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers. The breast cancers that express this gene expression signature are enriched for triple-negative subtypes — basal-like and claudin-low breast cancers. Methylation analysis of primary breast cancers showed extensive promoter hypermethylation of epigenetic biomarker genes among triple-negative breast cancers, compared to other breast cancer subclasses where promoter hypermethylation events were less frequent. Furthermore, triple-negative breast cancers either did not express or expressed significantly reduced levels of protein corresponding to methylation-sensitive biomarker gene products. Together, these findings suggest strongly that loss of epigenetic biomarker gene expression is frequently associated with gene promoter hypermethylation events. We propose that aberrant DNA hypermethylation is a common characteristic of triple-negative breast cancers and may represent a fundamental biological property of basal-like and claudin-low breast cancers. Kaplan–Meier analysis of relapse-free survival revealed a survival disadvantage for patients with breast cancers that exhibit aberrant DNA hypermethylation. Identification of this distinguishing trait among triple-negative breast cancers forms the basis for development of new rational therapies that target the epigenome in patients with basal-like and claudin-low breast cancers.     

Use of Intravenous Thrombolysis in Acute Ischemic Stroke Management in Patients with Active Malignancies: A Topical Review

ObjectivesOur review aims to present existing data on the safety of Intravenous thrombolysis (IVT) use in acute ischemic stroke (AIS) patients with concomitant central nervous system or systemic malignancies, with attention to special circumstances pertaining to specific cancer subtypes to help in acute decision making, especially for neurologists and emergency medicine physicians.MethodsA literature search was conducted on electronic databases inclusive of Medline, EMBASE and CINAHL for articles published or available in English between January 1, 2000 to June 1, 2020 using the following search terms: “acute ischemic stroke,” “cerebrovascular disease,” “Intravenous thrombolysis,” “tissue plasminogen activator,” “cancer patients,” and “neoplasm”.ConclusionRecognition of stroke symptoms in patients with active cancer, in particularly those involving the brain, requires astute clinical judgement. Decision-making can be improved by understanding baseline functional status, cancer prognosis and expected disability from stroke, as well as utilizing diagnostic modalities such acute MRI where needed. While this article does not encourage use of IVT in patients with all malignancies, it lays the groundwork for decision making should thrombolysis be a consideration in a patient with AIS in a cancer patient.     

Delayed presentation of a large congenital laryngeal cleft in an adult

Laryngeal clefts are rare congenital malformations of the posterior laryngotracheal wall that lead to an abnormal communication between the airway and pharyngo-oesophageal tract. The condition is almost universally identified during infancy with minor laryngeal clefts very rarely diagnosed in adulthood. We present our tertiary centre’s experience of a large laryngeal cleft presenting at an advanced age, with the aim of increasing awareness of this correctible cause of respiratory distress and aspiration in adults.     

Multi detector CT Imaging of Abdominal and Diaphragmatic Hernias: Pictorial Essay

Diagnosis of abdominal wall hernia is often a clinical problem, especially in occult or in obese patients. Multidetector CT is an accurate method of detecting various types of abdominal and diaphragmatic hernias. It clearly demonstrates the anatomical sites of hernial sac, its contents and possible complications.     

Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.