TACROLIMUS DRUG LEVEL AND RESPONSE TO TREATMENT IN IDIOPATHIC CHILDHOOD STEROID RESISTANT NEPHROTIC SYNDROME.

BACKGROUND: The management of Steroid Resistant Nephrotic Syndrome (SRNS) is an uphill task for paediatric nephrologists as immunosuppressive agents are the mainstay of treatment in these patients. Tacrolimus is used along with steroids. This study is conducted to see the relationship between the tacrolimus dose, drug level and response in the management of SRNS. METHODS: This quasi experimental study was conducted at The Children's Hospital Lahore over a period of one year. Patients with SRNS of either sex and 1-10 years of age were included and those with secondary nephrotic syndrome were excluded. Tacrolimus was given at a dose of 0.05-0.1 mg/kg/day in 2 divided doses along with steroids. The follow-up was done for six months with proteinuria monitoring and tacrolimus drug levels done two weeks after initiation of treatment. RESULTS: Out of 42 patients, 27 (64.3%) were males and 15 (35.7%) were females. The most common histological diagnosis observed was mesangio-proliferative glomerulonephritis in 30 (71.4%) patients. The tacrolimus trough level range was 0.5-15.20 ng/ml with a mean value of 4.68 ng/ml ± 2.85. Forty-one (97.6%) children showed complete response to treatment while one patient showed partial response. CONCLUSION: This study suggests that tacrolimus is an effective drug for treatment of SRNS in paediatric patients and there is no linear relationship between the drug dose, response and drug level.

COMPLICATIONS AND SAFETY OF POST PERCUTANEOUS RENAL BIOPSY IN PAEDIATRIC PATIENTS.

BACKGROUND: Renal biopsy is gold standard in diagnosis of various renal diseases. Though it is safe yet it requires adequate patient evaluation, preparation and monitoring after the procedure. METHODS: This descriptive case series was conducted in the Paediatric Nephrology Department, The Children's Hospital Lahore over a period of one year. Children aged less than 16 years were included who were suffering from renal diseases requiring renal biopsy for diagnosis. After renal biopsy patients were monitored for complications and were discharged after short stay of eight hours who got no complication during the observation period. RESULTS: Out of total 145 patients, 97 (66.1%) were males and 48 (33.9%) were females. The age range was from 0.7 years to 16 years. The duration of stay after renal biopsy was up to eight hours in 131 (90.34%) patients, while 14 (9.66%) stayed longer. Post-biopsy stay of 24 hours was observed in 8 patients and 48 hours in 5 patients. Only 1 patient stayed for 96 hours. Patients with gross haernaturia were 6 (4.1%) who were checked for perinephric hematoma formation by ultrasonography. Only one patient required blood transfusion along with fresh frozen plasma. The most common histopathological diagnosis was Mesangioproliferative with 67 (46.2%) cases, followed by Glomerulonephritis in 35 (24.1%) patients having Membranoproliferative Glomerulonephritis (MPGN) while Systemic Lupus Erythematous (SLE) nephritis was reported in 15 (10.35%) patients. CONCLUSION: Patients can be discharged after short stay post renal biopsy procedure provided done after proper screening of patients. As it not only reduces patient stay but also is cost effective.

HISTOPATHOLOGICAL PATTERNS IN PAEDIATRIC IDIOPATHIC STEROID RESISTANT NEPHROTIC SYNDROME.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a common problem but difficult to treat for pediatric nephrologists. Due to paucity of studies done in few centres in southern Pakistan regarding the histopathological aspects in paediatric patients with SRNS, this study was conducted to determine the histopathological spectrum in children with SRNS at our centre. METHODS: This descriptive study has been conducted at the Nephrology department, The Children's Hospital Lahore from February 2014 to January 2015. Based upon history, physical examination and laboratory results, all patients diagnosed as idiopathic SRNS were included in the study and renal biopsy was done to determine the underlying pathology. Histopathology reports were retrieved and data analysis done using SPSS-20.0. RESULTS: There were a total of 96 patients, 64 (66.7%) males and 32 (33.3%) females. The age range was from 0.80 to 15 years with mean age of presentation being 6.34+3.75 years. The most common histo-pathological pattern was mesangio-proliferative Glomerulonephritis found in 79 (82.3%) cases followed by Focal segmental glomerulosclerosis (FSGS) in 9 (9.4%) patients while Minimal change disease (MCD) was seen in 5 (5.2%) subjects. CONCLUSION: Mesangioproliferative glomerulonephritis is the most common histological pattern seen in children presenting with idiopathic SRNS at our centre followed by FSGS and MCD.

Rare case with megaloblastic anaemia.

A nine years old boy presented with history of pallor and anaemia since early infancy along with neural hearing loss responding to empirical multivitamin and folic acid therapy started on basis of blood complete picture showing anaemia and megaloblastic anaemia. On investigation he was diagnosed with Thiamine Responsive Megaloblastic Anaemia, a very rare condition in our settings.

Neuromuscular paralysis by a single injection of lincomycin.

A seven years old girl presented with history of sudden onset of generalized body weakness to an extent that she was not able to move any body part. On thorough history it was revealed that she was given intramuscular injection lincomycin at private clinic which lead to neuromuscular paralysis of whole body. This antibiotic is currently not being used in humans and being only used as veterinary medication.

The Evaluation of Artificial Intelligence Technology for the Differentiation of Fresh Human Blood Cells From Other Species' Blood in the Investigation of Crime Scenes.

OBJECTIVES: The current study used the deep machine learning approach to differentiate human blood specimens from cow, goat, and chicken blood stains based on cell morphology. METHODS: A total of 1,955 known Giemsa-stained digitized images were acquired from the blood of humans, cows, goats, and chickens. To train the deep learning models, the well-known VGG16, Resnet18, and Resnet34 algorithms were used. Based on the image analysis, confusion matrices were generated. RESULTS: Findings showed that the F1 score for the chicken, cow, goat, and human classes were all equal to 1.0 for each of the three algorithms. The Matthews correlation coefficient (MCC) was 1 for chickens, cows, and humans in all three algorithms, while the MCC score was 0.989 for goats by ResNet18, and it was 0.994 for both ResNet34 and VGG16 algorithms. The three algorithms showed 100% sensitivity, specificity, and positive and negative predictive values for the human, cow, and chicken cells. For the goat cells, the data showed 100% sensitivity and negative predictive values with specificity and positive predictive values ranging from 98.5% to 99.6%. CONCLUSION: These data showed the importance of deep learning as a potential tool for the differentiation of the species of origin of fresh crime scene blood stains.

Rare case of Bland White-Garland syndrome with myocardial infarction in paediatrics.

A 3.5 months old female infant presented with acute history of loose motions, fever and irritability for 5 days. The infant had history of respiratory distress since birth that exaggerated while feeding along with sweating and increased milk intake. Patient had poor weight gain. On investigations she was found to have anomalous origin of the left coronary artery from the left pulmonary artery (ALCAPA) with dilated cardiomyopathy and anterior wall myocardial infarction which is a very rare diagnosis in paediatrics and very rare condition diagnosed in our settings.

A Systematic Review of Chronic Diseases and Their Prevalence Among the Population of Northern Borders Province (NBP) in Saudi Arabia.

Estimation of the prevalence of chronic conditions is pivotal to effective healthcare planning and management. Therefore, our objective was to systemically review previous literature about the prevalence of chronic diseases among residents of Northern Borders Province (NBP) in Saudi Arabia. The electronic search has been done using scientific databases (PubMed, Ebsco, SciFinder, and Web of Science) and search engines up to September 2021. The following main key terms: chronic disease OR chronic conditions AND prevalence AND Northern Borders Province OR Northern Borders AND Saudi Arabia were applied. Other related terms with a more specific search were done with names of the main cities in the province and the most common diseases in Saudi Arabia. Duplicates were removed electronically by Endnote and manually. Extracted data were tabulated in the literature matrix. The risk of bias and quality of included studies were assessed using the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) checklist. Out of 63 observational studies that were assessed for eligibility, 21 observational studies were included to synthesize the evidence. These studies were conducted on Arar (n=16), Turaif (n=2), and Rafha (n=1), while the remaining were national studies in which NBP was one of the included regions (n=2). The most frequently studied diseases were diabetes (4 records), psychological diseases (4 records), and obesity (3 records). The most prevalent disease was gastroesophageal reflux disease (GERD), with an estimated prevalence of 61% among adults in Arar city. In conclusion, although some research is conducted about chronic diseases somewhere in NBP, further studies are needed to study chronic diseases using a representative sample of the whole NBP population.

Presentation Of Children With Masturbation.

Childhood masturbations (CM) is stimulation of genital by pre-adolescent children with accompanying symptoms including sweating, tachycardia, blushing, muscle contraction and increase rate of breathing. We are presenting case series of three patients, who presented with history of vague symptoms and ultimately diagnosed and managed as case of CM. A 2 years old girl presented with history of to and fro movements. A 3 years old girl presented with history of rubbing of inner thighs and 3 years old boy presented with history of holding and rubbing genitalia with forward bending and symptoms of increase breathing, flushing and sweating. Video recording was available with two patients, which helped in making final diagnosis. Parents were counselled and patients referred for behavioural therapy. Conclusion: In young child CM should be considered in differential diagnosis whenever history is not fully suggestive of seizures.

Evaluation of Antioxidant Activity and Histopathological Changes Occurred by the Oral Ingestion of CuO Nanoparticles in Monosodium Urate Crystal-Induced Hyperuricemic BALB/c Mice.

Nanotechnology is an intensive branch of science due to the unique features of nano range particles (1-100 nm). Their nano size results in a high surface area of absorption when orally administered. Monosodium urate crystal excessive deposition causes a commonly known inflammatory disease called gout into the synovial joints. Previously it has been observed that copper oxide nanoparticles (CuONPs) had a significant effect in reducing the serum uric acid levels in BALB/c mice as well as reducing the inflammation in the ankles of mice. This study was made to investigate the antioxidant and histopathological changes in hyperuricemic BALB/c mice upon the oral administration of copper oxide nanoparticles. Different concentrations of copper oxide nanoparticles 5, 10, and 20 ppm were given orally to gouty mice. To investigate the antioxidant activity of CuONPs, various antioxidant protocols were applied. It was noted that the nanoparticle-treated group of 20 ppm showed no significant changes in superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), and ROS values while the protein estimation values of the negative control group exhibited a significant increase (0.001). When compared to negative control, no significant effect was shown on the interpretation of histopathological changes of muscles, kidney, and liver tissues.

Antihyaluronidase and Alkaline Phosphatase (ALP) Activities of Medicinal Plants to Combat Echis carinatus Venom-Induced Toxicities.

Snakebite is one of the most neglected diseases of developing countries. Deaths due to snakebite envenoming are quite high in Pakistan, and many deaths are caused by Echis carinatus envenomation. Traditional use of medicinal plants against snakebites is a common practice in Pakistan due to countless benefits. The current study was performed with the objective to evaluate eighteen Pakistani medicinal plants inhibitory potential against hyaluronidase and alkaline phosphatase enzymes of Pakistani Echis carinatus venom. Hyaluronidase activity (0.2-1.6 mg/0.1 mL) and alkaline phosphatase activity (0.1-0.8 mg/0.1 mL) were measured in dose-dependent manner. Crude methanolic extracts of medicinal plants were used for in vitro investigation of their inhibitory activity against toxic enzymes. All active plants were fractioned using different solvents and were again analyzed for inhibitory activity of same enzymes. Results indicated all plants were able to neutralize hyaluronidase that Swertia chirayita (Roxb. ex Flem.) Karst., Terminalia arjuna Wight and Arn, Rubia cordifolia Thumb., and Matthiola incana (L.) R.Br. inhibited maximum hyaluronidase activity equivalent to standard reference (p > 0.5). Pakistani medicinal plants are dense with natural neutralizing metabolites and other active phytochemicals which could inhibit hyaluronidase activity of Pakistani Echis carinatus venom. Further advanced studies at molecular level could lead us to an alternative for envenoming of Pakistani Echis carinatus venom.

Effect of Endoxylanase and Iron Oxide Nanoparticles on Performance and Histopathological Features in Broilers.

Endoxylanase enzyme is used as poultry feed additive to degrade anti-nutritional factors like non-starch polysaccharides. Moreover, iron is one of the most important trace elements, and its deficiency can lead to various pathological conditions and stunted growth. In the current study, a combination of xylanase and iron nanoparticles is used to assess the overall effect on poultry growth. Endoxylanase enzyme was obtained from Aspergillus awamori SAIB-17 (identified on the basis of internal transcribed spacer (ITS) sequence analysis). The characterization of purified endoxylanase revealed that the Km and Vmax were 0.25 g/ml and 833.33 nkat/ml/s, respectively. Effect of pH and temperature showed that pH 4.5 and temperature 45 °C was best for enzyme activity. Iron nanoparticles were synthesized by co-precipitation of ferric chloride and ferrous chloride. Characterization of nanoparticles using X-ray diffraction (XRD) and SEM revealed that the mean diameter of synthesized iron nanoparticles was around 50 nm. These nanoparticles have no inhibitory effect on endoxylanase up to concentration of 20 ppm. Iron oxide nanoparticles along with endoxylanase were used as additives in different concentrations and were fed to the groups of broiler chicks. It was observed that the group fed with 40 nkat of endoxylanase and 15 ppm of iron nanoparticles showed 54.5% (2010 ± 103.58) more weight gain by the fifth week as compared with the control group. The iron analysis in the muscles showed no increase in iron concentration while histopathology slides showed no morphological changes in liver cells. The combination of iron oxide nanoparticles and xylanase proved to have great potential to be used in poultry feed for large-scale meat production without any toxicological effects.

Comparison of Efficacy of Tacrolimus Versus Cyclosporine in Childhood Steroid-Resistant Nephrotic Syndrome.

OBJECTIVE: To compare the efficacy of tacrolimus versus cyclosporine (Calcineurin Inhibitors) in the management of childhood steroid-resistant nephritic syndrome (SRNS). STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: Department of Paediatric Nephrology at The Children's Hospital and Institute of Child Health, Lahore, from August 2014 to September 2015. METHODOLOGY: Patients of either gender aged 1 - 12 years, with the diagnosis of mesangioproliferative glomerulonephritis (MesangioPGN), focal segmental glomerulosclerosis (FSGS) or minimal-change disease (MCD) were included. Patients were assigned into two groups, one given tacrolimus in dose of 0.1 - 0.2 mg/kg/day in two divided doses, and other given cyclosporine in dose of 150 - 200 mg/m2/day in two divided doses along with oral steroids 30 mg/m2/day in divided doses, followed by alternate day with tapering dosage. Trough drug levels were done with dose adjustment accordingly. Patients were monitored and followed for the response to treatment and adverse effects of these two calcineurin inhibitors. RESULTS: Atotal of 84 patients, 58% males and 42% females, were included in the study. The age ranged from 1.25 to 12 years. The most common histopathological diagnosis was MesangioPGN (69.04%), FSGS (21.4%), and MCD (9.52%). Complete response was seen in 80.95% and 97.6% patients treated with cyclosporine and tacrolimus, respectively. Partial response was in 19.05% patients treated with cyclosporine and 2.4% in patients with tacrolimus. The most common adverse effect with cyclosporine and tacrolimus was hypertrichosis in 80.95% and 2.38%, hypertension 16.66% and 11.9% respectively while gum hypertrophy with cyclosporine was seen in 26.19% patients. CONCLUSION: Tacrolimus was more efficacious than cyclosporine in achieving remission in childhood SRNS with insignificant adverse effects.