Asthma in COVID-19: Mitigating or exacerbating? An interesting case report.

Introduction: Bronchial asthma is an age-old disease whereas COVID-19 is an officially declared pandemic on March 11, 2020 by WHO. Since both are primarily a disease of the respiratory system, researchers across the globe tried to explore the potential relationship between them; to date, there is no convincing data. Here, we tried to present a case to explore potential relationships between these two, if present. Case presentation: A 30-year-old male patient with well-controlled cough variant asthma was diagnosed with a case of covid-19 infection 12 months back. All other sign symptoms subsided except dry cough. The patient is treated with an inhaled bronchodilator, oral and inhaled steroid, Tab montelukast as well as other conservative management like hot water vapor, lozenge, honey, etc but symptoms were not controlled for the last 12 months. The patient could not do his job because of this problem. All examination and investigation findings were normal. After long-term use of inhaled steroids, he is now 50-60% improved and gradually improving. Discussion: Covid can exacerbate cough in an asthmatic patient. Neuronal activation and neuroinflammatory mechanisms may aggravate this cough after covid. Diagnosis confirmed clinically with the relevant improvement of symptoms. Other important differentials were excluded by appropriate history, examinations, and investigation. Cough is improved by steroids in this case. Conclusion: Summary of conclusion: Cough variant asthma may be aggravated with covid 19 infection and meticulous history, treatment, and follow up needed for an asthmatic patient who is infected with covid 19.

Results of Laparoscopic Cholecystectomy in Acute Cholecystitis in Diabetic Patients: A Study with 50 Cases.

Acute cholecystitis (AC) is a common surgical condition requiring emergency hospitalization. Diabetic patient with gall stones disease is more prone to develop acute cholecystitis and its complications e.g. mucocele, empyema, gangrene and perforation. Early laparoscopic cholecystectomy (ELC) has proved to be an effective and safe day case surgical procedure for AC and their complications. This cross sectional study of diabetic patients admitted with acute cholecystitis, at the Department of Surgery of Bangladesh Institute of Researcher of Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM) General Hospital, Dhaka, Bangladesh from March 2016 to January 2017. A total number of 50 patients of known diabetes of acute cholecystitis were recruited irrespective of their age and sex and by excluding pregnant woman, obstructed jaundice and severe cardiopulmonary disease. More than half (52.0%) of the cholecystitis patients belonged to 31-40 years with mean age was 52.5±12.1 years. Females were predominant in this study (68.0%) with male: female ratio was 1:2.1. All (100%) patents had pain in right hypochondrium but relatively lower than non-diabetic patient due to diabetic neuropathy followed by majority 74.0% had nausea/vomiting, 70.0% had history of flatulence and dyspepsia, 62.0% had Murphy's sign positive. Thirty (60.0%) patients had glycaemic control and 20(40.0%) had uncontrolled DM. Insulin received patients were 35(70.0%) and 15 took oral hypoglycemic drug. Regarding postoperative complication, 8.0% had severe vomiting, right hypochondriac pain, 4.0% had wound sepsis and 2.0% had decreased pulmonary function and mild chest infection. In this study among laparoscopic finding during operation age and sex were not statistically significant. There was no mortality; laparoscopic cholecystectomy is the safe, accepted and preferred method of treatment for acute cholecystitis.

Role of Immune Cells and Cytokines for Immune Response in Kala-Azar.

Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, central to which is the activation of targeted T-cell populations for appropriate cytokine production and activation of infected cells. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-l response and IFN-γ production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. Experimental evidence and clinical studies indicate multifaceted role of various factors leading to parasite survival and multiplication. In early stage of infection, generation of reactive oxygen and nitrogen intermediates play significant role in curtailing the parasite multiplication. In later phase, hepatic resistance is expressed by the dominant role played by nitric oxide synthase (NOS)-2 gene regulation and on the other hand, production of inhibitors of NOS-2 gene expression, interleukin 10 (IL-10) and transforming growth factor-ß (TGF-ß) correlate well with reduced parasite killing. The hepatic infection is usually self-limiting due to production of multiple cytokine responses including moderate level of tumour necrosis factor (TNF) but in spleen excess TNF mediates destructive pathology. CD8+ T cells appear to play multiple roles comprising both cytotoxic activity and secretion of cytokines and chemokines. A better understanding of the innate and acquired immune functioning of the host could aid in rational control and better therapeutic intervention of the disease.

Sudden Intrathecal Drug Delivery Device Motor Stalls: A Case Series.

BACKGROUND AND OBJECTIVES: Intrathecal (IT) drug delivery systems (IDDSs) have been valuable in managing refractory chronic cancer and noncancer pain for more than 3 decades. These devices, time tested and overall reliable, have lately been noted at this institution to cease infusing unexpectedly. If not immediately recognized and rectified, this abrupt malfunction may lead to significant patient harm. METHODS: A series of 13 patients from 1 academic center whose Medtronic SynchroMed II pumps malfunctioned from 2013 to 2015 is described. Data from the patient population with regard to variables that may increase the rate of IDDS malfunction are analyzed. The risk factors for IDDS malfunction, Medtronic-issued recalls, and current literature on IT device failure are reviewed. RESULTS: The total prevalence of device motor stall among the population of this institution is 9.03%. The incidence rate of IDDS failure is calculated at 0.04 device failures per patient per year. Increased length of time from implant was the only statistically significant (P = 0.00009) risk factor for device failure identified in this population. Dysfunction in the motor gear train was found after destructive analysis of several devices in this series. CONCLUSIONS: Higher rates of device failure are associated with the use of off-label IT drugs. However, device failure may still occur while infusing only approved medications. Implanted patients should be properly informed and educated to differentiate and recognize the critical error alarm of their device as well as the signs and symptoms of IT medication overdose and withdrawal.

Contact radiotherapy boost in association with 'watch and wait' for rectal cancer: initial experience and outcomes from a shared programme between a district general hospital network and a regional oncology centre.

AIM: Recent data have highlighted the potential of more intensive neoadjuvant protocols to increase and sustain the rate of complete response in rectal cancer managed nonoperatively. This study aimed to review the outcome of all patients from our district general hospitals network who had received standard neoadjuvant therapy and were additionally referred to a centre of excellence for contact X-ray brachytherapy or high-dose-rate brachytherapy boost. METHOD: A retrospective, chart-based review of all patients co-managed in this manner was performed. Patient details were retrieved from a prospectively maintained departmental database. Indications for treatment, patient outcome and serial data from follow-up clinical and radiological assessment were analysed. RESULTS: Seventeen patients treated over a 6-year period were identified. Median follow-up was 20 (5-54) months. Fourteen patients were clinically staged as T2 or T3 and eight were clinically node positive. Three patients died, of whom only one was initially a surgical candidate but refused an exenteration. Of the 14 patients who remain alive, 11 (79%) have a sustained complete (n = 8) or partial (n = 3) response. Two patients had an incomplete response, one is being palliated and the other awaits salvage surgery. One patient underwent abdominoperineal excision for suspected local recurrence. Currently 13 (93%) surviving patients are stoma free. CONCLUSIONS: This series shows that the addition of a radiotherapy boost offered sustained responses and stoma-free survival even in advanced disease and adverse patient populations whilst providing the majority of care closer to home.

Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl.

AIMS/HYPOTHESIS: It is not clear how small tyrosine kinase inhibitors, such as imatinib mesilate, protect against diabetes and beta cell death. The aim of this study was to determine whether imatinib, as compared with the non-cAbl-inhibitor sunitinib, affects pro-survival signalling events in the phosphatidylinositol 3-kinase (PI3K) pathway. METHODS: Human EndoC-ßH1 cells, murine beta TC-6 cells and human pancreatic islets were used for immunoblot analysis of insulin receptor substrate (IRS)-1, Akt and extracellular signal-regulated kinase (ERK) phosphorylation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] plasma membrane concentrations were assessed in EndoC-ßH1 and MIN6 cells using evanescent wave microscopy. Src homology 2-containing inositol 5'-phosphatase 2 (SHIP2) tyrosine phosphorylation and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) serine phosphorylation, as well as c-Abl co-localisation with SHIP2, were studied in HEK293 and EndoC-ßH1 cells by immunoprecipitation and immunoblot analysis. Gene expression was assessed using RT-PCR. Cell viability was measured using vital staining. RESULTS: Imatinib stimulated ERK(thr202/tyr204) phosphorylation in a c-Abl-dependent manner. Imatinib, but not sunitinib, also stimulated IRS-1(tyr612), Akt(ser473) and Akt(thr308) phosphorylation. This effect was paralleled by oscillatory bursts in plasma membrane PI(3,4,5)P3 levels. Wortmannin induced a decrease in PI(3,4,5)P3 levels, which was slower in imatinib-treated cells than in control cells, indicating an effect on PI(3,4,5)P3-degrading enzymes. In line with this, imatinib decreased the phosphorylation of SHIP2 but not of PTEN. c-Abl co-immunoprecipitated with SHIP2 and its binding to SHIP2 was largely reduced by imatinib but not by sunitinib. Imatinib increased total ß-catenin levels and cell viability, whereas sunitinib exerted negative effects on cell viability. CONCLUSIONS/INTERPRETATION: Imatinib inhibition of c-Abl in beta cells decreases SHIP2 activity, which results in enhanced signalling downstream of PI3 kinase.

Islet perturbations in rats fed a high-fat diet.

The islet response to a high-fat diet, which induces insulin resistance, was investigated in Sprague-Dawley rats. It was found that the insulin response to glucose (15 or 25 mg/min, i.v.) was not different between rats given a high-fat diet and control rats after 2 weeks but was significantly reduced in rats fed high-fat diets after 4 (by 46+/-9%; p<0.001) and 8 weeks (by 68+/-12%; p<0.001). However, after 2 weeks of a high-fat diet, stimulated insulin secretion from isolated islets incubated for 60 min in 5.6, 8.3, and 11.1 mM glucose was impaired. When islets isolated from rats given a high-fat diet for 2 weeks were perifused, it was evident that the first-phase insulin secretion was impaired (seen during the first 6 min after increase of glucose from 3.3 to 8.3 mM). Insulin gene expression, examined by quantitative in situ hybridization, was impaired after 2 weeks of high-fat diet (52% decrease in mRNA-labeling; p<0.001). Islet hypertrophy was not evident in rats given high-fat diet, as determined by areas of either islet profiles in dark-field images or isolated islets. Islet innervation, as revealed by immunostaining for vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was increased after 2, 4, and 8 weeks of high-fat diet. Thus induction of insulin resistance by high-fat diet in Sprague-Dawley rats results after 2 weeks in impaired glucose-stimulated insulin secretion in vitro, impaired insulin gene expression, and hyperinnervation of the islets without any sign of islet hypertrophy, whereas the in vivo insulin response to glucose, although normal after 2 weeks, is impaired after 4 weeks.

Frequency of clonal B lymphocytes in chronic myelogenous leukemia evaluated by fluorescence in situ hybridization.

The demonstration of the Philadelphia (Ph) chromosome in B lymphocytes from patients with chronic myelogenous leukemia (CML) has provided evidence that the disorder originates in a pluripotent progenitor cell. Divergent results, however, exist as to the degree of contribution of clonally derived cells to the B-cell compartment. To address this issue, B lymphocytes were selected from the blood of seven patients in the chronic phase of Ph-positive CML and were examined with dual-color fluoresence in situ hybridization for the presence of the Ph translocation. The purity of the B-cell preparations ranged from 88% to 97% (mean 93%). The Ph translocation was detected in 22-34% (mean, 27%) of the sorted B cells. There was no evidence that the duration of the disease affects the ratio of Ph-positive and -negative B cells. In summary, clonally derived circulating B lymphocytes were present in all patients studied but made only minor contribution to this compartment.