Emergence of acute promyelocytic leukemia in a patient with granulomatosis with polyangiitis during treatment with cyclophosphamide: a rare case report.

Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease that affects multiple organs and causes inflammation, necrosis, and vasculitis in small blood vessels. Treatment for GPA involves achieving and maintaining remission. In recent studies, cyclophosphamide-based regimens have been linked to comorbidity hazards, including an increased risk of malignancies, especially hematological ones. Acute myeloid leukemia is the main hematologic malignancy that can complicate GPA. In this context, we report the case of a middle-aged woman with GPA who developed acute promyelocytic leukemia (APL) during maintenance with cyclophosphamide. She was treated with all-trans retinoic acid at 50 mg/day and arsenic trioxide at 10 mg/day, along with steroids. This case highlights the unique emergence of APL in a GPA patient during cyclophosphamide therapy. A single case has previously been reported on the development of APL in a patient with GPA while using azathioprine monotherapy for 2 years.

Estimation of Interleukin 32 and Interleukin 37 Serum Levels in Iraqi Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune condition characterized by persistent inflammation in synovial joints. Interleukine-32 (IL32) is known to have significant pro-inflammatory effects in RA, and IL37 is an anti-inflammatory cytokine that reduces the immune response and inflammation. This study aimed to investigate serum levels of IL32 and IL73 in RA patients. The sample included 50 patients (46 females and four males) with RA and 40 healthy controls. The enzyme-linked immunosorbent assay (ELISA) detected serum levels of IL32 and IL37. The disease parameters' activity was measured by the clinical disease activity index, and the Erythrocyte sedimentation rate was measured by the Westergren method. Moreover, C-Reactive protein, Rheumatoid factor, and Anti-Cyclic Citrullinated Peptide antibodies were measured using the ELISA. The results showed elevated serum levels of IL32 and IL37 in patients with RA (P<0.05). The mean duration of RA in most patients was <12 years, and the level of disease activity among the cases group was mainly moderate (70%). There was no significant difference between the mean levels of IL32 and IL37 in patients with RA. This study showed that although IL32 and IL37 played an essential role in RA pathogenesis, there was no significant correlation between serum levels of IL32 and IL37 and disease duration or activity.

Post-streptococcal scleredema an unusual rare mimicker of scleroderma: a case report.

cleredema of Buschke is a rare pathological disorder of connective tissue, which is characterized by a woody, diffuse induration of the skin, most often in the upper extremities. We report an extremely rare complication of post-streptococcal infection in a six-year-old male complaining of gradually progressing, painless skin thickening and tightness which was preceded by a one-month history of fever, cough, and tonsillitis. By reporting this case, we hope to contribute to the creation of a database for future research aimed at better understanding the incidence, pathophysiology, and management of this extremely rare complication.

New peperomin and polyketides from dichloromethane extract of Peperomia blanda Jack. (Kunth).

Much of the new research and investigation in pharmacy sciences are concerned with developing therapeutic agents, and identifying and finding new drugs with their chemical structure to treat different human diseases such as infectious diseases from natural products. Therefore, the present findings relate to isolating five new compounds the dichloromethane extract of Peperomia blanda (Jacq.) Kunth grown on Socotra Island, Yemen. two new secolignans; which have been proposed as peperomin I & J. These compounds were isolated together with the other two polyketides presented as surinone D and dindygulerione F. The chemical structures were elucidated and confirmed with nuclear magnetic resonance (NMR) and liquid chromatography-mass spectroscopy (LCMS) analysis. These compounds were first isolated and reported from this plant. These new compounds' antimicrobial activity has been evaluated, and minimum inhibitory concentration has been recorded in the range of 125-250 µg/mL. The pharmacotherapeutic spectrum of compounds was predicated using PASS software which showed potential activity.

Pulmonary Renal Syndrome: Experience from Tertiary Centre in Mumbai.

INTRODUCTION: Pulmonary Renal Syndrome (PRS), is characterized by diffuse alveolar haemorrhage (DAH) and glomerulonephritis (GN), occurring simultaneously. It has high mortality and dialysis dependence at one year, if not timely diagnosed and aggressively treated. OBJECTIVES: To study etiology and short term outcome of PRS in India. MATERIALS AND METHODS: This study included patients of PRS seen in a tertiary care center in Mumbai, by one consultant from 1997- 2013, analyzed retrospectively and from January 2014 to December 2015 collected prospectively from six medical units, intensive care unit, nephrology and respiratory units. Patients with DAH (haemoptysis, breathlessness and x-ray chest with bilateral alveolar shadows with sparing of apices) and glomerulonephritis (Proteinuria, heamaturia, hypertension with or without raised serum Creatinine) were included in the study after carefully excluding other causes of haemoptysis and breathless like tuberculosis, pulmonary oedema, pneumonia, ARDS. During prospective enrollment of patients, in all admitted patients with haemoptysis, urine examination was carried out to specifically look for proteinuria and red blood cells in urine, same was also followed in those admitted for breathlessness with chest x-ray suggestive of alveolar haemorrhage. Patients were extensively investigated for etiology and were treated with steroids and pulse cyclophosphamide (after ruling out infectious etiology). Supportive care with ventilator or dialysis was given as per usual indications. Palsmapheresis was initiated in those with serum Creatinine ≥ 5.7mg/dl. Rituximab was used in refractory cases, as per treating physicians' choice. Final outcome was death or discharge. RESULTS: There were 25 patients of PRS (13 retrospective, 12 prospective), with following etiology : Granulomatosis with polyangiitis (GPA) 7, Microscopic polyangiitis (MPO) 4, Churg Strauss Syndrome (EGPA) 1, Goodpasture's syndrome 1, lupus 5, leptospirosis 5, dengue 2. All were given steroids, 18 (72%) were given pulse Cyclophosphamide (barring those with leptospirosis and dengue), ventilator support in 14 (56%) patients (8 invasive, 6 non-invasive), haemodialysis 3, plasmapheresis 1, Rituximab 2. Seventeen (68%) patients survived, mortality was high in those requiring invasive ventilator. CONCLUSION: Most common etiology of PRS is ANCA positive vasculitis in India. With high degree of suspicion for DAH in patients presenting with haemoptysis, breathlessness and alveolar opacities in chest x-ray and carefully investigating by simple urine examination for evidence of GN, timely diagnosis of PRS can be made. With timely appropriate treatment survival is 68%. Patients with PRS due to leptospirosis or dengue have features suggestive of underlying disease (like icterus with raised bilirubin but < 200U SGOT/SGPT, subconjunctival haemorrhage, typical rash of dengue with thrombocytopenia).

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

On the affinity and specificity of quercetin for DNA.

The potential of quercetin (QUE), being a member of the whole family of structurally different flavonoids, to serve as an anti-tumor agent has been recognized, but not fully understood. The interactions between DNA and a series of the flavonoids have so far been mainly investigated using a variety of experimental techniques. Herein, the specificity of QUE for DNA is explored using sophisticated density functional theory (DFT) methods employed to generate the optimized structure of QUE in complex with adenine (A), guanine (G), thymine (T) and cytosine (C), respectively. As far as a preference of QUE is concerned, structural and energetic as well as NMR chemical shift arguments clearly indicate a highest for G and a lowest for C. This observation is further substantiated by analyzing the binding modes of QUE docked in a quadruplex receptor structure of DNA and in a duplex receptor structure of DNA. Among all possible single point mutations of the DNA quadruplex and duplex residues, several critical ones causing a conspicuous stabilizing effect on the original complexes of QUE with the DNA receptors are identified. Consequently, several fundamental standpoints shedding new light on the molecular mechanisms underlying the interactions between QUE and DNA are discussed.

A new tyrosinase inhibitor from Crinum yemense as potential treatment for hyperpigmentation.

A new pyran derivative, 6-hydroxy-2H-pyran-3-carbaldehyde, has been isolated from the methanolic extract of Crinum yemense along with the known alkaloid haemanthamine, benzoic acid and 1,1'-bis(1,1'-carboxyethyl) ether which is isolated from a natural source for the first time. Structure elucidation of these compounds based on spectroscopicevidences. The pyran derivative was found to be a tyrosinase inhibitor more potent than kojic acid.

Airway wall thickness in patients with near fatal asthma and control groups: assessment with high resolution computed tomographic scanning.

BACKGROUND: Airway wall thickening has been observed in post mortem studies of patients with asthma. Assessment of airway wall thickening by high resolution computed tomographic (HRCT) scanning has been reported in experimental studies. We have used HRCT scanning to measure airway wall thickness at the segmental and subsegmental levels in 40 patients with asthma and 14 normal controls. METHODS: The subjects were prospectively divided into four age and sex matched groups: 14 patients with a history of near fatal attack of asthma (NFA; group 1), 12 patients with moderate asthma (group 2), 13 patients with mild asthma (group 3), and 14 normal controls (group 4). All subjects were non-smokers. High resolution (1 mm collimation) CT scans of the chest were done at five different levels. RESULTS: The mean (SD) forced expiratory volume in one second (FEV1) was 68 (20)% of predicted for group 1, 73 (12)% for group 2, 102 (12)% for group 3, and 103 (12)% for group 4. The ratio of airway wall thickness to outer diameter (T/D) and the percentage wall area (WA%) defined as (wall area/total airway area) x 100 were used to compare airway wall thickness between the groups. The mean (SD) T/D and WA% were 0.27 (0.05) and 78.0 (9.2)% for group 1, 0.27 (0.05) and 78.8 (9.2)% for group 2, 0.25 (0.04) and 74.2 (7.5)% for group 3, and 0.23 (0.04) and 70.9 (8.2)% for group 4. T/D and WA% were not significantly different between groups 1 and 2. However, both groups 1 and 2 had higher T/D and WA% than either group 3 or 4 (p < 0.001) and group 3 had a higher T/D and WA% than group 4 (p < 0.03). The differences (95% CI) between the groups in WA% were 7.1% (0 to 14.4) for groups 1 and 4, 3.8% (-3.4 to 10) for groups 1 and 3, and 3.3% (-4.4 to 10) for groups 3 and 4. The differences between the groups in T/D and WA% were noted both for those with airways with a luminal diameter of > 2 mm and those with a luminal diameter of < or = 2 mm. CONCLUSIONS: All the patient groups had greater airway wall thickening than the normal subjects as assessed by HRCT scanning, but patients with more severe asthma had greater airway wall thickening than those with mild asthma. The methodology described in this study may be useful in assessing airway calibre in early intervention studies with anti-inflammatory therapy.

beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma.

Excess beta2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the beta2-adrenergic receptor (beta2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functions in vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. In preliminary studies we found significant differences in allele frequencies due to ethnic background: Caucasian, Black, Asian Gly16 = 0.61, 0.50, 0.40 and Gln27 = 0.57, 0. 73, 0.80, respectively. beta2AR genotyping was performed on DNA from Caucasians classified as nonasthmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mild/moderate asthmatics (n = 86). No polymorphism or haplotype was found to be associated with fatal/near-fatal asthma. However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulation in vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the beta2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of beta2AR polymorphisms in asthma.

Airway obstruction in asthmatic and healthy individuals: inspiratory and expiratory thin-section CT findings.

PURPOSE: To determine differences in computed tomographic (CT) findings in asthmatic and healthy individuals and to correlate the findings with severity of airway obstruction. MATERIALS AND METHODS: Thirty-nine asthmatic patients and 14 healthy subjects were prospectively evaluated with thin-section CT. Inspiratory CT scans were subjectively evaluated for presence of bronchial wall thickening, bronchial dilatation, and mosaic lung attenuation; expiratory scans were subjectively evaluated for presence of air trapping. Objective measurement of bronchoarterial-diameter ratio was performed on inspiratory scans. CT findings were compared with pulmonary function test results. RESULTS: Bronchial wall thickening, severe air trapping, and reduced bronchoarterial-diameter ratio were observed more commonly in asthmatic patients than in healthy subjects. Bronchial wall thickening was more prevalent among patients with severe airflow obstruction (10 of 12 readings [83%]) than in patients with normal airflow (15 of 40 readings [38%]) or mild obstruction (nine of 26 readings [35%]). Other subjectively determined CT findings did not correlate with pulmonary function test results. The mean bronchoarterial-diameter ratios +/- 1 standard deviation were 0.65 +/- 0.16 in healthy subjects and 0.60 +/- 0.16, 0.60 +/- 0.18, and 0.48 +/- 0.11 in patients with normal airflow and mild and severe obstruction, respectively. CONCLUSION: Thin-section CT is of limited value in distinguishing asthmatic patients with normal airflow or mild airflow obstruction from healthy subjects.

Comparison of males and females presenting with acute asthma to the emergency department.

OBJECTIVES: To determine the female:male ratio and compare the severity of asthma between female and male patients presenting with acute asthma to the authors' emergency department (ED). PATIENTS: Patients aged 15-50 years presenting with acute asthma. SETTING: Emergency department of a university-affiliated hospital. METHODS: Retrospective analysis of asthma surveillance data and medical records of all asthma-related visits to ED over 6 months (January 1992-June 1992). RESULTS: One hundred and thirty-seven patients aged 15-50 years made 196 consecutive visits to the authors' ED over 6 months. The ratio of female:male patients was 1.9 and the ratio of the number of visits made by female vs. male patients was 2.6. Initial peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1) were recorded in 94% and 49% of the visits, respectively. There was no statistically significant difference between the male and female patients in heart rate, respiratory rate or percentage of patients admitted to hospital. The mean (SD) initial FEV1 as a percentage of predicted was significantly higher in females compared to males (49% +/- 20% vs. 33% +/- 15%; P < 0.001). CONCLUSION: In the authors' institution there is a high female:male ratio among patients presenting with acute asthma, and males tend to present later or with more severe disease. These findings need to be confirmed by a prospective study looking at all the factors that may contribute to asthma patients presenting to the ED.

Spontaneous pulmonary hemorrhage after thrombolytic therapy for acute myocardial infarction.

We report a case of 63-year-old man who developed massive pulmonary hemorrhage following intravenous streptokinase for acute myocardial infarction. Pulmonary hemorrhage was diagnosed by the triad of hemoptysis, a drop in hematocrit, and a new unilateral infiltrate on chest radiograph. This diagnosis was confirmed by autopsy findings. Pulmonary hemorrhage has rarely been reported following thrombolytic therapy. We believe that pulmonary hemorrhage is a rare but a potentially life-threatening complication of thrombolytic therapy and should be considered in the differential diagnosis of pulmonary infiltrates or falling hemoglobin after thrombolytic therapy for acute myocardial infarction with no obvious site of bleeding.