A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.

BACKGROUND: Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. METHODS: Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. FINDINGS: Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites. CONCLUSION: Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.

Risk factors associated with morbidity and mortality outcomes of COVID-19 patients on the 28th day of the disease course: a retrospective cohort study in Bangladesh.

Diverse risk factors intercede the outcomes of coronavirus disease 2019 (COVID-19). We conducted this retrospective cohort study with a cohort of 1016 COVID-19 patients diagnosed in May 2020 to identify the risk factors associated with morbidity and mortality outcomes. Data were collected by telephone-interview and reviewing records using a questionnaire and checklist. The study identified morbidity and mortality risk factors on the 28th day of the disease course. The majority of the patients were male (64.1%) and belonged to the age group 25-39 years (39.4%). Urban patients were higher in proportion than rural (69.3% vs. 30.7%). Major comorbidities included 35.0% diabetes mellitus (DM), 28.4% hypertension (HTN), 16.6% chronic obstructive pulmonary disease (COPD), and 7.8% coronary heart disease (CHD). The morbidity rate (not-cured) was 6.0%, and the mortality rate (non-survivor) was 2.5%. Morbidity risk factors included elderly (AOR = 2.56, 95% CI = 1.31-4.99), having comorbidity (AOR = 1.43, 95% CI = 0.83-2.47), and smokeless tobacco use (AOR = 2.17, 95% CI = 0.84-5.61). The morbidity risk was higher with COPD (RR = 2.68), chronic kidney disease (CKD) (RR = 3.33) and chronic liver disease (CLD) (RR = 3.99). Mortality risk factors included elderly (AOR = 7.56, 95% CI = 3.19-17.92), having comorbidity (AOR = 5.27, 95% CI = 1.88-14.79) and SLT use (AOR = 1.93, 95% CI = 0.50-7.46). The mortality risk was higher with COPD (RR = 7.30), DM (RR = 2.63), CHD (RR = 4.65), HTN (RR = 3.38), CKD (RR = 9.03), CLD (RR = 10.52) and malignant diseases (RR = 9.73). We must espouse programme interventions considering the morbidity and mortality risk factors to condense the aggressive outcomes of COVID-19.

Anti-inflammatory role of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) in nephroprotection.

Inflammation is one of the mechanisms involved in the acute kidney injury (AKI) caused by cisplatin (CP)-induced nephrotoxicity. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) has powerful antioxidant activity. We investigated its potential nephroprotective effects and the underlying mechanisms that may add further benefits to its clinical usefulness in a CP-induced AKI model. Male Swiss albino mice were divided randomly into four groups: control, CP (20 mg/kg intraperitoneally), tempol (100 mg/kg/day, per os) + CP, and tempol only treatments. Blood samples were collected to analyze renal function parameters. Immunoblotting and immunohistochemical analysis were used to assess the level and localization of inflammatory markers. Tempol afforded protection to animals from CP-induced elevation of inflammatory markers as indicated by reduced expression of nuclear factor-kappa B, cyclooxygenase-2, and tumor necrosis factor-α in kidney tissue. Histological findings and analysis of kidney function markers corroborated with these findings confirming a nephroprotective role for tempol. In conclusion, this study provides important evidence for the promising anti-inflammatory effects of tempol which appears to contribute significantly to its nephroprotective action.

Antimicrobial resistance and in vitro biofilm-forming ability of Enterococci spp. isolated from urinary tract infection in a tertiary care hospital in Dhaka.

The biofilm mode of life conveys a survival advantage to the microorganism associated with it. Biofilm on an indwelling urinary catheter consists of adherent microorganisms, their extra cellular products, and host components deposited on the catheter and thus biofilm on urinary catheters results in persistent infections that are resistant to antimicrobial therapy. This study was done during the period of January 2010 to December 2010. Fifty nine enterococci isolated from 1203 urine samples were speciated by conventional microbiological methods and examined for their ability to form biofilm by microtitre plate assay and antimicrobial susceptibility testing by disc diffusion method for 10 clinically relevant antibiotics respectively. Biofilm producing Enterococci were more frequently found in catheterized than in non catheterized patient (p < 0.004). Enterococcus faecium showed increased resistantance to multiple antibiotic than Enterococcus faecalis. Significant relationship was found between biofilm production with antibiotic resistance to amoxicillin, co-trimoxazole, ciprofloxacin, gentamycin, cefotaxime, and cefuroxime. This study demonstrated a high propensity among the isolates of Enterococci to form biofilm and a significant association of biofilms with multiple drug resistance.

A study of ovarian cyst in a tertiary hospital of Kathmandu valley.

Ovarian cysts are an extremely common gynecological problem. Majority of ovarian cysts are benign with few cases being malignant. This is a retrospective study of all the cases of ovarian cysts operated in a tertiary hospital (Kathmandu Medical College, KMC) from January 2006 to December 2008. In this 3 years duration, 102 cases (2.0%) were of ovarian cyst out of the total histopathological specimen processed in pathology department. The mean age of presentation was 38years. Ovarian cysts (27.5%) were more commonly seen in the age group 21- 30 years. Bilateral ovaries were involved in 19 cases (18.6%). Among these ovarian cysts, 89 cases (87.3%) were benign and 13 cases (12.7%) were malignant. The most common type of ovarian cyst was serous cystadenoma (40.2%) followed by mature cystic teratoma (15.7%). Metastasis to ovary was seen in 6.9% (7 cases). The most common metastasis was adeno carcinoma from gastro intestinal tract (4 cases). Other metastases to ovary were 2 cases from endometrioid adeno carcinoma of endometrium and 1 case from Non Hodgkin's Lymphoma of small intestine.

Allergic fungal rhinosinusitis in chronic rhinosinusitis.

BACKGROUND: Rhinosinusitis is the inflammation of nasal and paranasal sinus mucosa and is associated with mucosal alteration ranging from inflammatory thickening or gross nasal polyp formation.The main objective of this study is to determine the prevalence of allergic fungal rhino sinusitis among the patients having chronic rhino sinusitis with or without polyps who under goes functional endoscopic sinus surgery. METHODS: The patient with chronic rhinosinusitis with or without polyp who FESS were studied. Surgical specimens were sent for mycology and histopathological analysis for identification of fungus. RESULTS: Headache 41(82%) and nasal block 45(90%) were the commonest clinical presentation. Out of 50 patients, fungal elements were detected by KOH in 8(16%) of cases and histopathological examination in 11(22%) of cases. CONCLUSIONS: Allergic Fungal Rhinosinusitisis a common disorder in patients with chronic rhinosinusitis, it need different specific tests for the diagnosis, a more specific diagnostic tests are fungus culture, and IgE to fungal antigen and skin test are needed for definite diagnosis.

Effectiveness of educational interventions in improving clinical competence of residents in an internal medicine residency program in Pakistan.

INTRODUCTION: Medical education is a continuously evolving field. Training institutes and programs should have a process in place to gather continuous feedback and then make appropriate modifications in order to provide education and training effectively. Our study aimed to assess the effect of a quality improvement cycle approach in using various educational interventions within a residency. Effects were measured on the key educational outcomes of residents; medical knowledge, skills and professional attitudes using results of postgraduate examination with both written and clinical skills components. METHODOLOGY: A number of educational interventions were implemented which included changes in work hours with increased time for self-study, new educational activities including a Residents Hour, a Residents Slide Session, Grand Rounds and Journal Clubs, Clinico-pathological conferences, and a two- week postgraduate course for senior residents. Newer and improved assessment tools were also implemented, including an annual in-training mock exam based on the format of the postgraduate examination. Pass rates in postgraduate examinations (Fellow of College of Physicians and Surgeons exam and Member of Royal College of Physicians exam) were compared before and after the interventions to assess the effectiveness of the interventions. RESULTS: The first group of residents after introduction of the educational interventions completed residency training in 2001. Postgraduate exam pass rates (sometimes after two or more attempts) were 59.2% (42 of 71 graduates) before 2001 and 86.4% (38 of 44 graduates after 2001 (p = 0.002). The number of candidates passing the examinations in either their first or second attempts before 2001 was 17 of 42 (40.5%), which increased to 33 of 38 (86.8%) after 2001 (p = <0.001). CONCLUSIONS: Our study describes a number of interventions that were successful in bringing about an improvement in the performance of our residents. These can serve as a guide for postgraduate training programs, particularly those of Internal Medicine, in implementing strategies to strengthen training and enhance the performance of trainees.

Barriers in initiating insulin therapy in a South Asian Muslim community.

AIMS: Insulin therapy is often required for optimal glycaemic control. Pakistani patients display reluctance to use insulin. We aimed to determine the reasons for this and to assess impressions after initiation of insulin in our patients. METHODS: Patients with Type 2 diabetes attending Aga Khan Hospital were surveyed using a questionnaire detailing opinions on insulin use. This was a cross-sectional study of two groups, one with no experience with insulin use and the other who were insulin users. RESULTS: Three hundred and seventeen patients were interviewed, 55.8% male, mean age 53.6 years. Of 210 patients who had never used insulin, 72.9% felt insulin was a measure of last resort and 45.2% thought that tolerance developed to insulin. Only 45.7% felt insulin would reduce complications, while 24% thought that insulin use would interfere with religious obligations. Thirty-four percent thought that it was difficult or very difficult to learn insulin administration, 41% felt that they could not self-inject even if absolutely necessary and 25% stated they would not use insulin in any circumstances. There was an association of lack of education with negative image of insulin usage. Among 107 patients using insulin, 52.3% were hesitant before initiation. However, 78.5% noted an improvement in glucose control and 86% said they would recommend insulin to others. CONCLUSIONS: Reluctance to use insulin prior to initiation is high, but views improve considerably after insulin initiation. Further awareness of the benefits of insulin use needs to be highlighted and the concerns of our population addressed.

Production, characterization, in vitro and ex vivo studies of babchi oil-encapsulated nanostructured solid lipid carriers produced by a hot aqueous titration method.

An aqueous dispersion of solid fat nanoparticles of babchi oil (BOSLN) was prepared by means of the hot water titration method. Surface morphology was determined by HR-TEM which revealed a fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics and ex vivo skin permeation profile, zeta potential and particle diameter, rheological measures and droplet size distribution. Highest values for steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) were observed for formulation, BOSLN3 comprised of oil [10% v/v; BO (3.33%), CAT (6.67%)], Tween 80 (9.25% v/v), transcutol-P (28.75% v/v) and distilled water (53% v/v). These results suggest that the studied SLN might be promising vehicles for babchi oil in the management of psoriasis.

Evaluation of fine needle aspiration cytology of lymph nodes in Kathmandu Medical College, Teaching hospital.

BACKGROUND: Fine Needle Aspiration Cytology (FNAC) is a simple and rapid diagnostic technique. Because of early availability of results, simplicity, minimal trauma and complications, the aspiration cytology is now considered a valuable diagnostic aid and is part and parcel of a pathologist's repertoire. OBJECTIVES: The aim of the study was to evaluate the results of fine needle aspiration cytology (FNAC) of lymph nodes in our institution in comparison to result of histopathology. MATERIALS AND METHODS: The present study on 130 patients of lymphadenopathy was conducted in the Department of Pathology Kathmandu Medical College Teaching hospital, Kathmandu from June 2006 to May 2008 (2 years). RESULTS: In this series of FNAC cervical lymph nodes were 66 (50.76%), and axillary lymph nodes were 20 (15.38%). Male to female ratio of the patients was 1: 0.9. The age of patients ranged from 3 to 85 years. FNAC diagnosis was found to be as follows : reactive hyperplasia 54( 41.55%), tubercular lymphadenitis 36 (28 %), metastatic carcinoma 16 (12.3%), granulomatous lymphadenitis 12 ( 9.2 % ), lymphoma 8 (6%) and suppurative lymphadenitis 4(3%) . Out of 28 cases of FNAC 26 (92.85%) were consistent with histopathological diagnosis of tubercular lymphadenitis. In metastatic carcinoma to lymph nodes sensitivity and specificity of FNAC were 100% each. CONCLUSION: FNAC is useful and reliable in diagnosing neoplastic and non- neoplastic lesions of lymph nodes. It helps in planning surgery for malignant cases, where definitive operative intervention can be performed in one session.

Cysticerci in palpable nodules diagnosed on fine needle aspiration cytology.

INTRODUCTION: Cysticercosis is the larval manifestation of the cestode T. solium. It commonly presents as subcutaneous and intramuscular nodules which is often clinically misinterpreted as benign mesenchymal lesions and lymph nodes. Cysticerci in subcutaneous nodules can be diagnosed rapidly and with considerable accuracy by FNAC. This study highlights the cytomorphological features of subcutaneous cysticercosis diagnosed by FNAC. METHODS: Forty three patients with palpable nodules diagnosed as cysticercosis or suspected as cysticercosis by FNAC between August 2005 to July 2008 were included in the study. Excision biopsy was done in 12 cases where definitive evidence of parasite was not found. RESULTS: Solitary nodules were present in 36 (83%) patients and multiple nodules were present in seven (17%). In 31 cases (72.09%) definite evidence of cysticercus was found. In 12 cases (27.9%) a suggestion of parasitic inflammation was made based on other cytomorphological features which was confirmed by biopsy in eight cases. CONCLUSIONS: Human cysticercosis commonly presents as subcutaneous nodules which can be diagnosed with considerable accuracy by FNAC. Definite evidence and suggestion of parasitic inflammation on cytology obviates the need for subsequent histopathological examination.

Role of FNAC in the diagnosis of salivary gland swellings.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy and efficacy of Fine needle aspiration cytology (FNAC) in various salivary gland swellings. MATERIALS AND METHODS: This retrospective study was performed at Kathmandu Medical College Teaching Hospital (KMCTH) from January 2004- December 2006.During this period a total of 978 FNAC's were done out of which 40 FNAC's were on salivary gland swellings. Correlation was done between cytological smear slides and biopsy slides. RESULTS: In this series of FNAC, 16 cases (40%) were benign neoplasms, 5 cases (12.5%) malignant neoplasms, non-neoplastic cysts 3 cases (7.5%) and inflammatory lesions 16 cases (40%).Histopathology was available in 24 cases out of which 22 cases correlated with cytology. There were no false positive reports but false negative result was seen in 4 cases. Sensitivity and specificity were 90% and 100% respectively. CONCLUSION: FNAC is useful in the diagnosis of salivary gland swellings especially in benign conditions with a sensitivity of 90% and specificity of 100%.

Hepatocyte transplantation: a review of laboratory techniques and clinical experiences.

Orthotopic liver transplantation (OLT) is standard clinical practice for patients with severe and end-stage chronic liver disease. However, the chronic shortage of donor livers and parallel growth of the transplant waiting list mean that a substantial proportion of patients die while waiting for a donor liver. Attempts to reduce the waiting list by use of split-liver and living-related live donor techniques have had some impact, but additional approaches to management are vital if the death rate is to be significantly reduced. Extensive laboratory research work and limited clinical trials have shown that hepatocyte transplantation may be useful in bridging some patients to OLT. A major limiting factor has been the shortage of mature functioning human hepatocytes, which are currently mostly obtained from livers rejected for OLT. This review examines potential hepatocyte sources, hepatocyte isolation methods and preservation protocols that have been successfully established, along with an overview of clinical results.

Fine needle aspiration (FNA) of soft tissue tumours (STT).

OBJECTIVES: The cytological findings of 50 ST Ts were evaluated aiming to determine the role of FNA in diagnosis of STTs METHODS: Fifty patients with soft tissue tumours underwent FNA in the preoperative investigation during a one year period. The smears were stained with Papanicolaou and May-Graunvald Giemsa stains. RESULTS: Forty-four cases were reported as benign, whereas 2 were malignant. Four cases revealed insufficient material. The malignant STTs were small round cell tumour and malignant spindle cell tumour. Cytological and histological correlation could be achieved in 40 cases. The overall sensitivity and specificity were 25% and 100% respectively with overall accuracy of 80%. CONCLUSION: A reliable diagnosis of STTs can be made with FNA when supported by other clinical and other diagnostic data.

Rapid detection of helicobacter pylori by endoscopic brush cytology and comparison with histopathology.

OBJECTIVES: The main objective of this study was to assess antral brush cytology as an alternate approach for the diagnosis of H. pylori infection as compared to histopathology. METHODS: 75 cases with diagnosis of antral gastritis underwent endoscopic antral biopsy as well as antral brushing cytology was included irrespective of age and sex. Cytological slides were stained with Giemsa stain & biopsy slides were stained with H&E and Giemsa stain. Correlation was done between cytological smear slides and biopsy slides. RESULTS: Among 75 cases, H. pylori were positive in 55 (73.4%) cases of biopsy specimens while in brush cytology it was positive in 48 (64%) cases. In 45 (60%) of 75 cases, H. pylori was seen in both biopsy and brush cytology. CONCLUSION: Endoscopic brush cytology provides an accurate, inexpensive and easy technique in the rapid detection of H.pylori infection.

Size-dependent superheating in confined Pb(111) films.

Molecular dynamics simulations have been carried out to explore superheating in Pb(111) films confined in an Al(111) matrix. The size dependence of the superheating has been investigated by varying the film size and keeping the host matrix unchanged. Melting is found to initiate in the interior of the film, which suggests intrinsic homogeneous nucleation. The superheating is found to be dependent on the size of the film. Superheating up to 115 K above the bulk melting temperature is achieved. A good agreement between the theoretical calculations, experimental value and the simulated results is obtained.

A new source of hepatocytes for transplantation.

INTRODUCTION: The most effective treatment for acute or chronic liver failure is orthotopic liver transplantation. Worldwide there is a shortage of organs for transplantation. This shortage has called for research into new treatments for management of patients with liver failure. One such treatment is hepatocyte transplantation. During liver resections considerable amounts of normal liver are unavoidably resected. We aim to harvest these hepatocytes and to filter the tumor cells from them to provide a source for transplantation. MATERIALS AND METHODS: After liver resection, the largest vessel at the resected liver edge was identified and cannulated. Seglen's two-stage technique of perfusing the liver with EDTA and collagenase was performed to harvest the hepatocytes. Ep-CAM Ags are consistently present on the surface of epithelial cells and in particular in colorectal cancer cells. Therefore, MOC31 antibodies (selective Abs for Ep-CAM) attached to magnetic beads were used to target the tumor cells. These tumor cells are selectively removed using a magnet. CEA staining was then used to ensure the hepatocyte collection was tumor cell free. Five million hepatocytes were rosetted with one million HT29 CRC cells to assess the immunomagnetic filtration technique. RESULTS: The hepatocyte harvesting resulted in 864,000 viable hepatocytes to be harvested per gram of liver. Histochemical staining using CEA demonstrated 75% of the HT29 cells in the hepatocyte collection were removed after one use of magnetic beads. CONCLUSION: We have demonstrated the successful initial stages of harvesting tumor-free hepatocytes from liver resected for malignancy.

Clinical characteristics and outcomes of diabetic ketoacidosis in Pakistani adults with Type 2 diabetes mellitus.

AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Pakistani adult population with Type 2 diabetes mellitus. METHODS: We reviewed the medical records of all adult patients admitted with a diagnosis of DKA and Type 2 diabetes mellitus (DM) and followed their clinical course and outcome. Follow-up data were obtained by chart review or telephone contact where necessary. RESULTS: Fifty-seven patients fulfilled criteria for inclusion in the study. Their mean age was 48 +/- 7 years. The mean body mass index was 25.5 +/- 6.2 kg/m2. Forty-nine had a prior history of Type 2 DM but DKA was the initial presentation in 14%. Nine were on no treatment, 40 were using oral hypoglycaemic agents and eight were on insulin. A history of prior DKA was noted in eight patients. Infections were the most common precipitating factor (63%). There were 12 deaths. Follow-up after a period ranging between 12 and 43 months revealed that 30/45 patients remained on OHA without recurrence of DKA. CONCLUSION: This report highlights the need for the growing recognition of DKA occurring in adults with Type 2 DM in the South Asian population. Mortality rates are unacceptably high but the majority of survivors remain insulin independent.

Antimicrobial susceptibility testing and patterns of resistance at a tertiary care center.

Clinical microbiology laboratories are faced with the challenge of accurately detecting emerging antibiotic resistance in bacterial pathogens. In recent years, vancomycin resistant enterococci have emerged, as have penicillin resistant pneumococci and more recently, methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin. In order to detect these emerging resistant pathogens it is essential that antimicrobial susceptibility be carried out by laboratories as an integral part of therapeutic strategies. In this review, we discuss patterns of susceptibility of different antimicrobials as experienced at King Faisal Specialist Hospital and Research Centre, a tertiary care center in Riyadh.

1alpha,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2.

BACKGROUND: 1alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown to inhibit the proliferation of various cancer cells including colon, prostate, melanoma, osteosarcoma and breast cancer. METHODS: The human hepatoma cell line (HepG2) was cultured with 1,25(OH)2D3 or one of two analogues EB1089 or CB1093 for various durations. Cellular proliferation was measured by uptake of [3H]thymidine, and cell numbers were determined by trypan blue exclusion counting. RESULTS: 1,25(OH)2D3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90% after 5 days of treatment, compared to the untreated controls. Decreased proliferation was associated with an approximately 50% reduction in cell numbers at concentrations of up to 10(-10) mol/L after 5 days of treatment with 1,25(OH)2D3. Cell proliferation rapidly recovered in cultures treated with lower concentrations of 1,25(OH)2D3 (10(-10) and 10(-11) mol/L) when 1,25(OH)2D3 was removed from the cultures by placing cells in serum containing medium without 1,25(OH)2D3. When HepG2 cells were treated with 10(-8) mol/L 1,25(OH)2D3 for 5 weeks, there was still significant inhibition of proliferation, although at week 5 there was 66% inhibition compared to 93% at the end of week 1. CONCLUSIONS: 1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower concentrations. Inhibition can be maintained for at least 4 weeks, but is reversed after removal of vitamin D3.