Assessment of premature atherosclerosis in systemic lupus erythematosus patients with and without nephritis.

BACKGROUND: Risk of subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE). We correlated carotid intima media thickness (CIMT) and endothelial dysfunction through flow-mediated dilation (FMD) in SLE patients with the SLE Disease Activity Index (SLEDAI). METHODS: This single-centre cross-sectional study recruited 100 consenting SLE outpatients (ACR 1997 criteria) out of which 50 had nephritis, with disease duration of ≥2 years for SLE and ≥6 months for lupus nephritis. We measured baseline laboratory levels, CIMT and FMD (after brachial BP cuff inflation up to 200 mmHg for five minutes), and calculated SLEDAI. RESULTS: Mean age was 29.88 ± 6.53 years; 95/100 were female. CIMT showed positive correlation (p = 0.037; rho = 0.209), and FMD showed inverse correlation with patient's age (p = 0.011; rho = -0.252). CIMT and FMD were more deranged in patients aged ≥25 years (p < 0.05). CIMT was not significantly different between SLE patients with and without nephritis (p > 0.05), whereas SLEDAI and FMD were more deranged in nephritis patients (p < 0.05). In patients without nephritis, FMD showed significant inverse correlation with disease duration (p = 0.043; rho = -0.288) and urine albumin (p = 0.045; rho = -0.285). In nephritis patients, the correlation between age of the patient was significantly positive with CIMT (p = 0.001; rho = 0.441) and significantly inverse with FMD (p = 0.028; rho = -0.312). CONCLUSION: SLE patients with nephritis are at a higher risk to develop arterial stiffening, leading to early end-organ damage. Early aggressive treatment may prevent endothelial dysfunction. FMD using vascular ultrasonography on the brachial artery represents a non-invasive, repeatable and useful method for the assessment of endothelial dysfunction.

Role of multidetector abdominal CT in the evaluation of abnormalities in polyarteritis nodosa.

AIM: To identify arterial and end-organ abnormalities on abdominal computed tomography (CT) in patients with polyarteritis nodosa (PAN). MATERIALS AND METHODS: A prospective study comprising 27 consecutive patients with PAN was conducted from 2007 to 2013. Departmental ethics committee approval was obtained. All patients underwent contrast-enhanced CT comprising an arterial and a portal venous phase. Images were assessed for arterial irregularity, aneurysms, stenosis, and occlusion. End-organ changes, including infarcts, haematoma, and bowel involvement, were also recorded. RESULTS: A positive CT was recorded in 15 patients including eight females. The mean age was 32 years. The most common abnormalities were aneurysms seen in 12 patients. The renal artery was the most common site of aneurysms (n=9). The hepatic (n=3), superior mesenteric (n=3) and splenic arteries (n=1) were also involved. Contour irregularity was noted in four patients involving the hepatic, splenic, and superior mesenteric arteries. Stenosis/occlusion was also noted in seven patients. The most common end-organ abnormality was infarct (n=9), followed by bowel wall thickening (n=3), and perinephric haematoma (n=2). CONCLUSION: A combination of arterial and end-organ abnormalities on abdominal CT enables an accurate diagnosis of PAN in occult cases and may obviate the need for angiography and, sometimes, biopsy.

Management of hypovitaminosis D in patients with primary hyperparathyroidism.

AIM: Epidemiological studies suggest that vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). They have higher levels of serum parathyroid hormone (PTH) and markers of bone turnover and fractures are more frequent than vitamin D-replete patients. However, there are concerns that Vitamin D repletion might exacerbate pre-existent hypercalcaemia. Therefore, we aimed to determine if vitamin D replacement improved biochemical indices of calcium metabolism without worsening underlying hypercalcaemia. SUBJECTS AND METHODS: This is a prospective, observational study based on routine clinical practice, set up in a secondary care centre. 45 consecutive patients with mild biochemical hypercalcaemia due to PHPT and hypovitaminosis D were enrolled. The mean age of the cohort was 61 years (range 25-85 years), predominately Asian (32 patients) and female (41 patients). They received 20,000 IU of oral cholecalciferol, once a week, for 3 months. Calcium, phosphate, alkaline phosphatase and PTH were measured at baseline, 4, 8 and 12 weeks following treatment. Vitamin D levels were obtained at baseline and at 12 weeks, after they completed their treatment. RESULTS: Vitamin D levels normalised at week 12 (mean ± SD, 18.8 ± 9.4 versus 76 ± 20 nmol/L, p = 0.0001) and PTH levels improved following treatment completion (21.2 ± 10 versus 16.2 ± 6 pmol/L, p = 0.026). There was no significant increase in serum calcium levels during vitamin D supplementation. CONCLUSIONS: High doses of oral cholecalciferol normalised vitamin D levels without worsening underlying hypercalcaemia in individuals with PHPT.

Antibacterial and biofilm disruptive nonribosomal lipopeptides from Streptomyces parvulus against multidrug-resistant bacterial infections.

BACKGROUND: In recent years, new drugs for the treatment of various diseases, thereby the emergence of antimicrobial resistance tremendously increased because of the increased consumption rate of various drugs. However, the irrational use of antibiotics increases the microbial resistance along with that the frequency of mortality associated with infections is higher. Broad-spectrum antibiotics were effectively against various bacteria and the unrestricted application of antibiotics lead to the emergence of drug resistance. The present study was aimed to detect the antibacterial properties of lipopeptide novel drug producing Streptomyces parvulus. METHODS: A lipopeptide-producing S. parvulus was isolated from the soil sample. The inhibitory effect of lipopeptide was detected against Gram-positive and Gram-negative bacteria. Bactericidal activity and minimum inhibitory concentration (MIC) were assayed. The IC50 value was analysed against ovarian and human melanoma cell lines. The experimental mouse model was infected withKlebsiella pneumoniae and treated with lipopeptide and bactericidal activity was determined. RESULTS: The results indicated that the antibacterial activity of lipopeptide ranges from 13 ± 1 mm to 32 ± 2 mm against Gram-positive and Gram-negative strains. The lowest MIC value was noted as 1.5 ± 0.1 µg/mL against K. pneumoniae and the highest against E. aerogenes (7.5 ± 0.2 µg/mL). The IC50 value was considerably high for the ovarian cell lines and human melanoma cell lines (426 µg/mL and 503 µg/mL). At 25 µg/mL concentration of lipopeptide, only 16.4% inhibition was observed in the ovarian cell line whereas 20.2% inhibition was achieved at this concentration in the human melanoma cell line. Lipopeptide inhibited bacterial growth and was completely inhibited at a concentration of 20 µg/mL. Lipopeptide reduced bacterial load in experimental mice compared to control (p < 0.05). CONCLUSION: Lipopeptide activity and its non-toxic nature reveal that it may serve as a lead molecule in the development of a novel drug.

Molecular docking of monkeypox (mpox) virus proteinase with FDA approved lead molecules.

BACKGROUND: Monkeypox virus (mpox) disease is caused by a double-stranded DNA virus from the Poxviridae family. The mpox virus showed structural similarity with smallpox virus disease. The recent outbreak of mpox infection in the rest of African countries causes public health issues of increased pandemic potential. Mpox virus is involved in the viral replication cycle through the biocatalytic reaction of precursor polyproteins cleavage. OBJECTIVES: The main objective of the study was to analyze the molecular interactions between mpox and FDA-approved drugs. METHODS: The primary and secondary structure of the protein was retrieved and FDA approved drug was screened using AutoDock. The best hit was analyzed and the molecular interactions were studied. Model validation analyzes the peptide, energy of hydrogen bonds, steric conflicts and bond planarity. Z-score was calculated using ProSA-web tool and the score tested the native fold from other alternative folds. RESULTS: The confidence level of the submitted amino acids was> 80 % and the maximum confidence score for a single template was 98.2 %. The generated proteinase model was subjected to analyze the distribution of atoms and the using ERRAT server. The overall quality score was 88.535 and this value represents the amino acid percentage with anticipated error value and the value falling below the rejection limit. The Z-score of this study result was within the Z-score range (-4.17) validated for native enzymes. The binding pockets of the enzyme were determined in this study and two binding pockets were predicted using the automatic online tool using the web server. The selected FDA-approved drugs were ordered based on their minimum binding energy to the proteinase. CONCLUSIONS: Molecular docking studies revealed the involvement of various hydrophobic interactions between FDA-approved drugs and amino acid residues of monkeypox virus proteinase.

Rituximab induced pulmonary fibrosis in a patient with lupus nephritis.

We describe a 26-year-old woman who was diagnosed eleven years ago with systemic lupus erythematosus and who had suffered multiple relapses. She presented with class IV lupus nephritis with thrombotic microangiopathy, for which she received three doses of rituximab along with plasmapheresis, with no response, and soon became dialysis dependent. One month after the last dose of rituximab, she presented with dyspnoea and hypoxia. A transbronchial lung biopsy revealed pulmonary fibrosis. A diagnosis of rituximab induced pulmonary fibrosis was made after excluding other causes and she was treated with intravenous methyl prednisolone with which there was marked improvement in symptoms and hypoxemia. This is the first report of rituximab induced pulmonary fibrosis in a patient with lupus nephritis.

In vitro fibrinolytic activity of an enzyme purified from Bacillus amyloliquefaciens strain KJ10 isolated from soybean paste.

A fibrinolytic protease secreting producing Bacillus amyloliquefaciens strain KJ10 was initially screened from the fermented soybean. Maximum productivity was obtained in the culture medium after 40 h incubation, 34 °C incubation temperature at pH 8.0. Fibrinolytic protease production was enhanced in the culture medium with 1% sucrose (3712 ± 52 U/mL), 1% (w/v) yeast extract (3940 ± 28 U/mL) and 0.1% MgSO4 (3687 ± 38 U/mL). Enzyme was purified up to 22.9-fold with 26%recovery after Q-Sepharose HP column chromatography. After three steps purification, enzyme activity was 1606U/mg and SDS-PAGE analysis revealed 29 kDa protein and enzyme band was detected by zymograpy. Enzyme was highly active at pH 8.0, at wide temperature ranges (40 °C - 55 °C) and was activated by Mn2+ (102 ± 3.1%) and Mg2+ (101.4 ± 2.9%) ions. The purified fibrinolytic enzyme was highly specific against N-Suc-Ala-Ala-Pro-Phe-pNA (189 mmol/min/mL) and clot lytic activity reached 28 ± 1.8% within 60 minin vitro. The purified fibrinolytic enzyme showed least erythrocytic lysis activity confirmed safety to prevent various health risks, including hemolytic anemia. Based on this study, administration of fibrinolytic enzyme from B. amyloliquefaciens strain KJ10 is safe for clinical applications.

Reducing admission hypothermia in newborns at a tertiary care NICU of northern India: A quality improvement study.

BACKGROUND: Hypothermia at admission to neonatal intensive care units (NICU) is associated with increased morbidity and mortality in newborns. A baseline study at a tertiary care hospital with all out-born babies showed admission hypothermia of 82%. OBJECTIVE: To reduce admission hypothermia (moderate) in newborns at least by 50% in next 6 months. METHODS: A quality improvement (QI) study was planned using WHO Point of Care Quality Improvement Model (POCQI), [17] using PDSA (Plan-Do-Study-Act) cycle approach from April 2018 to March 2019, and including 427 term and preterm babies. We educated the staff, reinforced the use of caps, cling wraps, warm linen, introduced Ziploc bags and ensured adequate use of transport incubator. RESULTS: After 6 months, overall admission hypothermia decreased from 82% to 45%, moderate hypothermia reduced from 46% to <10% (P < 0.001) and severe hypothermia (3%) was completely eliminated. There was also significant reduction in incidence of Intraventricular hemorrhage (13% Vs 4.7%), Late onset neonatal sepsis (38% Vs 19%) and metabolic acidosis (43% Vs 28%). We were able to sustain this improvement for the next 6 months and is ongoing. The strongest predictor of hypothermia was newborns being in the phase before QI initiative was started (OR 2.36, 95% CI 1.47, 3.23). CONCLUSION: This study is a cost effective approach in reducing admission hypothermia in NICU in a resource limited setting with all outborn babies, and further decreasing the morbidity associated with it. Hence, emphasizing the importance of maintaining euthermia, not only in delivery rooms, but also during transportation.

Spectral characterization of hydroxyapatite extracted from Black Sumatra and Fighting cock bone samples: A comparative analysis.

At present, chicken business is occupying a major portion in the market and huge amount of bone wastes are dumped into the open places lead in environmental pollution. In this analysis, natural hydroxyapatite was extracted by thermal calcination process at different temperature ranges from 700 °C, 900 °C and 1100 °C and compared its spectral characteristics. The crystalline nature, functional groups and morphological characteristics of hydroxyapatite obtained from both bone samples were studied using XRD, FTIR and SEM analysis. The crystallite size, lattice parameters, specific surface area, volume and degree of crystallinity were measured using XRD data. The mean grain size of Black Sumatra and Fighting Cock bone hydroxyapatite was 62.67 nm and 31.34 nm respectively. The FTIR spectrum showed major peaks at 634.58 cm-1 and 470.63 cm-1, 1413.82 cm-1 and 1460 cm-1 indicates the presence of carbonate group and phosphate groups in both samples. The SEM micrograph confirmed the existence of maximum pores in matrix of fighting cock bone than Black Sumatra bone sample. Thus, the comparative analysis concluded that nano-sized hydroxyapetite obtained from bone wastes of fighting cock can be utilized as a low-cost biomaterial for the production of various implant coating materials and substitute for ceramics in bones and dentistry applications.

Massive gallstone in an asymptomatic Indigenous Canadian male: Case report and literature review.

INTRODUCTION: Gallstones are present in 10-15% of North Americans, but only 20% become symptomatic. This case report describes a patient with a 7.5 cm gallstone detected incidentally while being investigated for cardiac pathology. This is the first report in the English literature of a stone this size that has remained clinically asymptomatic. This work is reported in line with the SCARE criteria. CASE REPORT: The patient was a 71-year-old Indigenous Canadian male, with atrial fibrillation. His cardiologist ordered a CT scan of his chest, which incidentally identified a large gallstone. He was referred to surgery for asymptomatic cholelithiasis. An uncomplicated laparoscopic cholecystectomy was performed. Final pathology showed a 7.5 cm gallstone with features of chronic cholecystitis. DISCUSSION: The patient's ethnicity and gallstone size placed him at increased risk for gallbladder cancer, gallstone fistulization and perforation. We reviewed the literature for asymptomatic patients who may benefit from cholecystectomy: transplant recipients and those with hemolytic disorders. Laparoscopic cholecystectomy is not currently indicated in diabetics and bariatric surgery patients. CONCLUSION: This case report shows that there are asymptomatic patients with massive gallstones. A review of their history, risk factors for malignancy and future gallstone related complications must be carefully weighed and discussed prior to deciding on surgical versus expectant management.

De novo adolescent gastric carcinoma: a first case report in Saskatchewan, Canada.

Adolescent gastric cancers are extremely rare with a reported incidence of 0.05-0.10% in North America. We present a de novo case of gastric carcinoma in a 17-year-old teenager with no concomitant family history or risk factors. His main clinical presentation included anaemia and melaena stools. Despite an extensive clinical workup that included a diagnostic laparoscopy, the tumour was deemed surgically irresectable, and he was started on a palliative chemotherapy protocol at the local paediatric oncology centre. He demised 7 months later. This is the first recorded case of an adolescent gastric cancer in Saskatchewan, Canada. This case highlights the need for an international tumour registry to document and investigate rare adolescent gastric malignancies and thereby potentiate a possible cure through the pooling of limited resources.

Identification of phytochemical components from Aerva lanata (Linn.) medicinal plants and its in-vitro inhibitory activity against drug resistant microbial pathogens and antioxidant properties.

This study aimed to determine the phytochemical components, microbial inhibitory effectiveness and antioxidant properties of Aerva lanata plant extracts. The whole plant showed various medicinal applications in folklore and traditional medicine in various parts of the world. The organic extracts such as ethanol, ethyl acetate, chloroform, acetone, water and methanol were subjected for various phytochemical analysis and confirmed for the existence of flavonoids, glycosides, terpenoids and alkaloid containing components. Alternatively, the extracts were performed for the antibacterial activities against the microbial pathogens and antioxidant properties. Results indicated that, the solvent extracts showed prominent activity against the tested strains. The MIC concentrations of plant were detected from 5 mg/ml to 40 mg/ml. The plant extract was highly effective against E. coli and E. aerogenes and the MIC was 5 mg/ml. In addition, the extracts noted promising antioxidant activities. The antioxidant activities were dose dependent manner. In conclusion, A. lanata extracts showed that significant major phytochemicals and effective antioxidant and anti-microbial properties.

Intestinal Tuberculosis: A Rare Case of Massive Gastrointestinal Bleed in a Post-Renal Transplant Recipient.

Massive rectal bleeding is an uncommon presentation of ileal tuberculosis (TB). We report an uncommon cause of anemia in a post-renal transplant patient due to massive lower gastrointestinal (LGI) bleed. The index case had a normal upper and LGI endoscopy, but the 99technetium labeled red blood cell scan showed active bleeding from terminal ileum and caecum. Microscopic examination of the resected specimen revealed tubercular granuloma with acid-fast bacilli. Intestinal TB should be a differential diagnosis for massive LGI bleed in immunosuppressed patients in developing country.

A case of parathyroid carcinoma with severe hungry bone syndrome and review of literature.

We present a 45 year old female who was initially seen by Rheumatologist with long standing knee pain affecting her mobility. She was found to be severely hypercalcaemic and exhibited features suggestive of parathyroid carcinoma (palpable neck mass, extremely high parathyroid hormone, high alkaline phosphatase, concomitant presence of renal disease and skeletal involvement). Hence she was referred for parathyroidectomy. Postoperatively she developed profound hypocalcaemia with markedly raised serum alkaline phosphatase, requiring intensive intravenous calcium and oral vitamin D supplements, consistent with the development of hungry bone syndrome (HBS). HBS is a complication of parathyroid surgery where the correction of primary hyperparathyroidism is associated with rapid bone remineralisation, causing severe and prolonged hypocalcaemia. HBS is relatively rare but has to be considered in the differential diagnosis of postoperative hypocalcaemia particularly in severe cases. In the current report, we discuss pathogenesis, clinical course and management of HBS.

Weight gain during the treatment of thyrotoxicosis using conventional thyrostatic treatment.

OBJECTIVE: Patients often lose considerable weight prior to the diagnosis of thyrotoxicosis. Regaining weight with treatment of thyrotoxicosis until hormone levels normalise is expected. This study was aimed to determine whether patients continued to put on weight once they were euthyroid. STUDY DESIGN AND METHOD: The records of 60 consecutive euthyroid patients were studied. All patients were rendered euthyroid on thyrostatic medication alone. Patients on a block and replacement regime, those who developed transient hypothyroidism on treatment or other diagnoses causing weight gain were excluded. RESULTS: The mean age of study group was 46.13 yr (21-73). Male:female ratio was 5:55. 36 (60%) patients had diagnosis of Graves' disease. On initial presentation weight was 67.75 kg (SEM 2.1) with body mass index (BMI) of 25.8. Patients took 6.7 months (mean) to become euthyroid. Mean weight when euthyroid was 71.61 kg (range 46-125). Even after becoming euthyroid, patient continued to gain weight at 3, 6, and 9 months and mean weight gain was 2.04 kg (SD 18.14) at 3 months (p=0.003). This weight gain was not related to patients' age, gender, BMI, duration or dose of treatment required to achieve euthyroidism. Diagnosis of Graves' disease and non-smoking status independently predicted weight gain. CONCLUSION: We have demonstrated that patients with thyrotoxicosis continue to gain weight for at least 6 months even after becoming euthyroid. Patients with Graves' disease were more likely to gain weight compared to others. Smokers gained least weight. Preventing this weight gain warrants further investigation.

Spectrum of IgG4-related Kidney Disease at a Tertiary Care Center.

IgG4-related kidney disease (IgG4 RKD) is increasingly reported with varied manifestations. The present study was carried out to study the spectrum of IgG4 RKD. All patients with renal manifestation associated with conditions known to be associated with IgG4-related diseases (IgG4 RDs), or renal imaging or histology suggestive of IgG4 RKD were included and evaluated further. Patients with known extrarenal IgG4RD were also screened for renal involvement. Out of 40 patients screened over a period of 15 months, IgG4 RKD was diagnosed in 8. Majority were male (87.5%) with mean age being 56 years. Disease spectrum ranged from normal renal function in one to renal failure requiring dialysis in another two patients. Significant proteinuria was uncommon (12.5%) while hematuria was not seen in any patient. Tubulointerstitial nephritis was seen in all four patients who underwent kidney biopsy. Two patients had associated glomerular lesions in the form of immune complex crescentic glomerulonephritis. The most common imaging abnormality was hypodense renal lesions seen in 2 patients. Elevated IgG4 levels had 87.5% sensitivity and 78.3% specificity for IgG4 RKD and levels did not correlate with disease severity. Of 4 patients treated with steroids, 3 showed improvement in renal function. IgG4 RKD is an uncommon disease even at a referral tertiary care center. Elevated IgG4 levels alone are neither sensitive nor specific for the diagnosis of IgG4 RKD, and a combination of clinical, imaging, serological, and histological features are required for diagnosis.

Clinicopathological Spectrum of Glomerular Diseases in Adolescents: A Single-center Experience over 4 Years.

The spectrum of biopsy-proven glomerular disease was studied from a single center in Northwestern India, among adolescents aged 13-19 years. From January 2009 to December 2012, a total of 177 patients with biopsy-proven glomerular disease were studied. The same pathologist reported all the biopsy specimens after subjecting to light, immunofluorescence, and electron microscopy. The clinical profile and laboratory findings of the patients were correlated with the histopathological spectrum of glomerular diseases. Males formed 71.19% (n = 126) and the remaining 28.81% (n = 51) were females. Lupus nephritis had a strong female predominance, whereas minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) had a male predominance. Nephrotic syndrome was the indication for biopsy in 65% of the cases. Rapidly progressive renal failure and acute nephritis were the next common indications accounting for 14% and 7%, respectively. FSGS was the most common glomerular disease in adolescents (n = 45, 25.4%). The next common were MCD and lupus nephritis each contributing 21.6% and 10.7%, respectively. Primary glomerular diseases accounted for 84.75% (n = 150) of the total. The remaining 15.25% (n = 27) were attributed to secondary glomerular diseases, of which lupus nephritis was the most common, i.e., in 70.4% patients (n = 19). FSGS was the most common histology in adolescent nephrotic participants (37%). MCD was the next common, found in 31% of nephrotic patients. Electron microscopy changed the diagnosis made by light microscopy and immunofluorescence in 5.6% cases only, and it confirmed the diagnosis in another 21.6%. Kidney biopsy in adolescents is a safe procedure. The spectrum of glomerular diseases in adolescents is different from that seen in adults and smaller children.