Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study.

AIMS: GDNF plays a crucial role in the stimulation of recovery, neuroplasticity and synaptic reorganization after spinal cord injury providing neuroprotection and neuroregeneration. Plasma GDNF levels are upregulated in cases of spina bifida owing to the intrauterine damage of the exposed spinal cord. Our aim was to compare the plasma GDNF levels in patients of spina bifida with non-spina bifida cases and assess the correlation with neurological impairment at one year of follow up. METHODS: Single centre prospective analysis of cases of spina bifida from 2020 to 2022 at presentation and after one year of follow up post-surgery. Cases with hernia and hydrocele without any other disorders were recruited into the control group. Plasma GDNF levels were assessed with immunoassay kits and compared with neurological involvement. RESULTS: 85 cases were included in the study. GDNF levels were elevated in cases compared to controls (mean 6.62 vs 1.76) with significant p value (<0.01). Same was observed for open and closed defects (mean 7.63 vs 4.86: p < 0.01). At follow up of 52 cases post-surgery cases with neurogenic bladder with abnormal urodynamic studies, sphincter involvement and motor impairment had significantly elevated baseline levels of GDNF compared with those who did not have this neurological impairment (p < 0.01). DISCUSSION: The neurotrophic factor up-regulation can reflect an endogenous attempt at neuroprotection against the biochemical and molecular cascades triggered by the spinal cord damage. This upregulation can be represented as important biochemical markers of severe spinal cord damage and can be associated with severity of spine injury in MMC patients. Our results are in keeping with these findings, that, there were increased levels of plasma GDNF levels in cases of spinal dysraphism compared to control population. Also, the type of lesion reflecting the severity whether a closed or an open dysraphism, showed significant difference in levels between them suggesting, yet again, more damage in open defect as expected. The levels were higher with involvement of bladder, sphincter and lower limb power. CONCLUSION: There is significant elevation of plasma GDNF levels in cases of spina bifida and this elevation is proportional to the degree of spinal damage and hence the neurological impairment. GDNF levels are a good predictor for assessing the severity of the lesion and thus the outcome in these cases. Additional prospective and long-term studies with a larger cohort are needed for a better understanding of neurotrophin pattern modulation in MMC.

Post-tonsillectomy Hemorrhage in Patients Receiving Ketorolac Analgesic.

Background Ketorolac, the non-steroidal anti-inflammatory drug, is thought to have less sedation as well as postoperative nausea and vomiting in comparison to opioids, but with higher risk of post-tonsillectomy hemorrhage as reported in some of the literatures. There is no consensus till date in the use of ketorolac in the management of pain following tonsil and adenoid related surgeries. Objective To find out the incidence of hemorrhage following tonsil and adenoid related surgeries in patients receiving ketorolac in postoperative period. Method This is a retrospective chart review of patients undergoing tonsil and adenoid related surgeries who had received ketorolac during April, 2013 to May, 2019 at department of ENT-HNS, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal. Post-tonsillectomy hemorrhage rate was calculated in pediatric and adult patients. Result During the study period, 103 patients (male - 50 and female - 53) received ketorolac in postoperative period. Tonsillectomy and adenotonsillectomy were performed in 71and 32 patients respectively. Forty-five patients were < 18 years whereas 58 were ≥ 18 years. Most common indication for surgery was recurrent tonsillitis (66/103) followed by adenotonsillar hypertrophy (31/103). Post-tonsillectomy hemorrhage was observed in 15 patients; among them, four out 45 were < 18 years and 11 out of 58 ≥ 18 years. All five patients out of 15, who required surgical intervention for post-tonsillectomy hemorrhage, were ≥ 18 years and were operated for recurrent tonsillitis. Rest of the patients (10/15) were managed conservatively. None of the patients required blood transfusion. Conclusion Ketorolac is not associated with increased risk of post-tonsillectomy hemorrhage in children and can safely be administered. Whereas in adults, recurrent tonsillitis being the most common indication for tonsillectomy, it should be used cautiously.

Morphological diagnosis of hematologic malignancy using feature fusion-based deep convolutional neural network.

Leukemia is a cancer of white blood cells characterized by immature lymphocytes. Due to blood cancer, many people die every year. Hence, the early detection of these blast cells is necessary for avoiding blood cancer. A novel deep convolutional neural network (CNN) 3SNet that has depth-wise convolution blocks to reduce the computation costs has been developed to aid the diagnosis of leukemia cells. The proposed method includes three inputs to the deep CNN model. These inputs are grayscale and their corresponding histogram of gradient (HOG) and local binary pattern (LBP) images. The HOG image finds the local shape, and the LBP image describes the leukaemia cell's texture pattern. The suggested model was trained and tested with images from the AML-Cytomorphology_LMU dataset. The mean average precision (MAP) for the cell with less than 100 images in the dataset was 84%, whereas for cells with more than 100 images in the dataset was 93.83%. In addition, the ROC curve area for these cells is more than 98%. This confirmed proposed model could be an adjunct tool to provide a second opinion to a doctor.

Cervical congenital infantile fibrosarcoma: a case report.

BACKGROUND: Congenital infantile fibrosarcoma is a rare mesenchymal tumor seen in children as well as adults. The congenital variety is rare and out of the reported cases only one case sited in the neck has been reported so far. Another such case is presented here who was successfully managed. CASE PRESENTATION: A 3-month-old Hindu baby boy presented with a congenital neck swelling. The apparent clinical diagnosis was lympho-venous malformation. With a remote possibility of malignancy, an excisional biopsy was done. Histopathology revealed congenital infantile fibrosarcoma. CONCLUSION: A successful excision of cervical congenital infantile fibrosarcoma has not been reported. This diagnosis should be kept as a possibility in all congenital cervical swellings. These are commonly misdiagnosed as lympho-venous malformations and histopathology is confirmatory.

Antifungal and anthelmintic activity of novel benzofuran derivatives containing thiazolo benzimidazole nucleus: an in vitro evaluation.

A novel series of thiazolo[3,2-a]benzimidazole derivatives containing benzofuran nucleus (5a-l) have been synthesized. The key intermediate, substituted benzimidazol-sulfanyl benzofuran ethanone (3a-d) was prepared by refluxing the mixture of substituted 2-acetyl benzofuran and substituted 2-mercaptobenzimidazole in acetic acid. The cyclisation of compounds (3a-d) using polyphosphoric acid furnished the corresponding 6-substituted benzofuran thiazolo[3,2-a]benzimidazoles (4a-d). Further, the cyclized compounds (4a-d) were subjected for Mannich reaction to give corresponding Mannich bases (5a-l). All newly synthesized compounds were screened for antifungal and anthelmintic activity. Amongst the tested compounds, 4b and 4d exhibited potential antifungal activity. From the anthelmintic activity data, it was found that the compounds 3a, 3b and 5i were found to be more effective against the tested earthworm Pheretima posthuma. In correlation to anthelmintic activity, the selected compounds were subjected for molecular docking studies and the compounds 3a and 5i have emerged as active anthelmintic agents with maximum binding affinity (-3.7 and -5.4 kcal/mol).

Evaluation of tumor response to intra-arterial chemoembolization of hepatocellular carcinoma: Comparison of contrast-enhanced ultrasound with multiphase computed tomography.

PURPOSE: To compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with that of multiphase computed tomography (CT) in the evaluation of tumor response to transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Fifty patients (41 men, 9 women; mean age, 53 years±12.5 [SD]) with a total of 70 HCCs (mean size, 5cm±3 [SD]) were evaluated. Post-TACE therapeutic assessment of HCC was done at 4 weeks. Patients with TACE done earlier and reporting with suspicion for recurrence were also included. Patients with hepatic masses seen on ultrasound were enrolled and subjected to CEUS, multiphase CT and magnetic resonance imaging (MRI). Hyperenhancing area at the tumor site on arterial phase of CEUS/multiphase CT/MRI was termed as residual disease (RD), the patterns of which were described on CEUS. Diagnostic accuracies of CEUS and MPCT were compared to that of MRI that was used as the reference standard. RESULTS: CEUS detected RD in 43/70 HCCs (61%). RD had a heterogeneous pattern in 22/43 HCCs (51%). Sensitivities of CEUS and multiphase CT were 94% (34/36; 95% CI: 81-99%) and 50% (18/36; 95% CI: 33-67%) respectively. Significant difference in sensitivity was found between CEUS and multiphase CT (P=0.0001). CEUS and multiphase CT had 100% specificity (95% CI: 83-100%). CONCLUSION: CEUS is a useful technique for detecting RD in HCC after TACE. For long term surveillance, CEUS should be complemented with multiphase CT/MRI for a comprehensive evaluation.

Comparison of results of graft uptake using tragal cartilage perichondrium composite graft versus temporalis fascia in patients undergoing surgery for chronic otitis media - squamous type.

BACKGROUND: To assess, analyze and compare the results of graft uptake using Tragal Cartilage-Perichondrium Composite (TCPC) graft with Temporalis Fascia (TF) graft in patients who undergoing surgery for chronic otitis media - squamous type. METHODS: Patients aged 13 years and above with diagnosis of chronic otitis media - squamous type undergoing modified radical mastoidectomy, either primary or revision surgery with grafting of tympanic membrane (TM) and patients undergoing excision of postero-superior retraction pocket (PSRP) were included in this study. Patients were divided in two groups: Group A-patients undergoing TCPC graft and Group B -patients undergoing TF graft. Graft uptake results were assessed between 8-12 weeks of surgery. RESULTS: In both Groups there were 30 patients each. In Group A successful graft uptake was seen in 27 patients (90 %) and failure of graft uptake was seen in 3 patients(10 %). In Group B successful graft uptake was seen in 28 patients (93.3 %) and failure in 2 patients (6.67 %).Out of the total 60 patients, 11 patients had PSRP. All 6 patients with PSRP in Group A had successful graft uptake and no retraction. Among the 5 patients with PSRP in Group B all patients had sucessful graft uptake, however, in 2 patients retraction of the tympanic membrane was seen similar to the preoperative findings. CONCLUSIONS: There was no statistical difference (p = 0.433) between the use of temporalis fascia or tragal cartilage perichondrium in patients undergoing surgery for chronic otitis media - squamous type.

Testicular Tumors in Undescended Testes in Children Below 5 y of Age.

OBJECTIVE: To evaluate the presentation, treatment and outcome of testicular tumors in undescended testes (UDT) in boys below 5 y of age. METHODS: Case records of boys below 5 y of age, diagnosed to have germ cell tumors (GCT) in the UDT were reviewed. RESULTS: Seven children in the age range of 05-54 mo (mean 26 mo) were included. While five of these 7 (71 %) presented with abdominal mass [one antenatally detected], 2 (29 %) were detected to have a GCT during orchiopexy. In three of these five with abdominal mass, the alpha-fetoprotein (αFP) was markedly elevated. Two of these three with elevated αFP were endodermal sinus tumors while the third was embryonal carcinoma. The 4th patient with an abdominal mass was diagnosed to have an immature teratoma (IMT) while the patient with antenatally diagnosed mass had a mature cystic teratoma (MT). Both the patients with incidentally detected mass during the orchiopexy had mature teratoma (MT). All the seven children are alive and disease free at last follow-up. CONCLUSIONS: Though rare, boys with impalpable undescended testes may develop germ cell tumors early in childhood. These can be managed with chemotherapy and resection and have a good disease free outcome.

Design, synthesis and structure--activity relationship (SAR) studies of imidazo[4,5-b]pyridine derived purine isosteres and their potential as cytotoxic agents.

Drug resistance to chemotherapeutic agents paved the way to develop novel synthetic molecules which are active on MDR cancer cell lines. Regio-isomeric imidazo[4,5-b]pyridine analogues were synthesized and evaluated for their cytotoxic activity against a range of cancer cell lines. The structure-activity relationship (SAR) studies of the imidazopyridine analogues are also described. Analogue 6b displayed strong cytotoxicity and good microsomal stability.

Inflammatory markers in patients with rheumatoid arthritis.

BACKGROUND: Autoimmune diseases such as rheumatoid arthritis (RA) are the consequence of a persistent imbalance between pro- and anti-inflammatory immune mechanisms, leading to chronic inflammation. The objective of this study was to determine whether the high sensitive C-reactive protein (hs-CRP) and cytokines are elevated in RA patients and to investigate the relationship between these markers and disease activity in RA, measured by disease activity score 28 (DAS28). METHODS: We studied 110 RA patients according to American College of Rheumatology revised criteria for RA, and 55 controls matched by age and sex. Serum levels of hs-CRP and cytokines interleukin (IL)-6, IL-10 and tumour necrosis factor-α (TNF-α) were estimated and correlated with the DAS28. Serum hs-CRP was assayed immunoturbidimetrically and cytokines were analysed by commercially available ELISA kit. RESULTS: We found that RA patients had significantly higher levels of serum hs-CRP (p<0.001), IL-6 (p<0.001), TNF-α (p<0.001), and IL-10 (p<0.01) as compared to healthy controls. hs-CRP, IL-6 and TNF-α correlated positively (p<0.001) and IL-10 correlated negatively (p<0.01) with DAS28. CONCLUSIONS: These results demonstrate that RA patients have high levels of inflammatory markers, and these levels are correlated with the DAS28. These findings suggest a possible role of these markers in the pathogenesis of RA. Moreover, these biomarkers can be used as markers of disease activity in the diagnosis and treatment of RA.

Synthesis and anticancer activity of 2-benzylidene indanones through inhibiting tubulin polymerization.

In an attempt to discover a potent and selective anticancer agent, gallic acid has been modified to benzylidene indanones as tubulin polymerization inhibitors. These compounds were evaluated against several human cancer cell lines and also evaluated for inhibition of tubulin polymerase in in vitro assays. Three of the analogues exhibited strong cytotoxicity against human cancer cell lines IC(50)=10-880 nM and also showed tubulin polymerization inhibition (IC(50)=0.62-2.04 µM). Compound 9j, the best candidate of the series was found to be non-toxic in acute oral toxicity in Swiss-albino mice up to 1000 mg/kg dose.

Premature T cell senescence in Ovx mice is inhibited by repletion of estrogen and medicarpin: a possible mechanism for alleviating bone loss.

UNLABELLED: Presently the relationship between CD28, biological marker of senescence, and ovariectomy is not well understood. We show that ovariectomy leads to CD28 loss on T cells and estrogen (E2) repletion and medicarpin (Med) inhibits this effect. We thus propose that Med/E2 prevents bone loss by delaying premature T cell senescence. INTRODUCTION: Estrogen deficiency triggers reproductive aging by accelerating the amplification of TNF-α-producing T cells, thereby leading to bone loss. To date, no study has been carried out to explain the relationship between CD4(+)CD28null T cells and ovariectomy or osteoporosis. We aim to determine the effect of Ovx on CD28 expression on T cells and effects of E2 and medicarpin (a pterocarpan phytoalexin) with proven osteoprotective effect on altered T cell responses. METHODS: Adult, female Balb/c mice were taken for the study. The groups were: sham, Ovx, Ovx + Med or E2. Treatments were given daily by oral gavage. At autopsy bone marrow and spleen were flushed out and cells labelled with antibodies for FACS analysis. Serum was collected for ELISA. RESULTS: In Ovx mice, Med/E2 at their respective osteoprotective doses resulted in thymus involution and lowered Ovx-induced increase in serum TNF-α level and its mRNA levels in the BM T cells. Med/E2 reduced BM and spleen CD4(+) T cell proliferation and prevented CD28 loss on CD4(+) T cells. Further, Med abrogated TNF-α-induced loss of CD28 expression in the BM T cells. CONCLUSIONS: To our knowledge this is the first report to determine the mechanism of CD28 loss on T cells as a result of ovariectomy. Our study demonstrates that Ovx leads to the generation of premature senescent CD4(+)CD28null T cells, an effect inhibited by E2 and Med. We propose that one of the mechanisms by which Med/E2 alleviates Ovx-induced bone loss is by delaying T cell senescence and enhancing CD28 expression.

Plexiform neurofibroma in a 16-year-old girl.

Plexiform neurofibroma is a rare, poorly defined benign tumor of the peripheral nerve sheath. It spreads out just under the skin, or deeper in the body, and occurs exclusively in patients with neurofibromatosis type I. Facial plexiform neurofibroma may produce various degrees of cosmetic and functional deformities in the head and neck region. It is a virtually pathognomonic and often disabling feature of neurofibromatosis type I. We present a case of plexiform neurofibroma in an 18-year-old female.

Impact of chronic lead exposure on selected biological markers.

Lead poisoning remains a major problem in India due to the lack of awareness of its ill effects among the clinical community. Blood lead, δ-aminolevulinic acid dehydratase (δ-ALAD) and zinc protoporphyrin (ZPP) concentrations are widely used as biomarkers for lead toxicity The present study was designed to determine the impact of chronic lead exposure on selected biological markers. A total of 250 subjects, of both sexes, ranging in age from 20 to 70 years, were recruited. On the basis of BLLs, the subjects were categorized into four groups: Group A (BLL: 0-10 µg/dl), Group B (BLL: 10-20 µg/dl). Group C (BLL: 20-30 µg/dl) and Group D (BLL: 30-40 µg/dl) having BLLs of 3.60 ± 2.71 µg/dl, 15.21 ± 2.65 µg/dl, 26.82 ± 2.53 µg/dl and 36.38 ± 2.83 µg/dl, respectively. Significant changes in biological markers due to elevated BLLs were noted. The relation of BLL and biological markers to demographic characteristics such as sex, habits, diet and substances abuse (smoking effect) were also studied in the present investigation. Males, urban population, non-vegetarians, and smokers had higher blood lead levels. δ-ALAD activity was found to be significantly lower with increased BLL (P < 0.001), while the ZPP level was significantly higher with increased BLL (P < 0.001). Further, BLL showed a negative correlation with δ-ALAD (r = -0.425, P < 0.001, N = 250) and a positive correlations with ZPP (r = 0.669, P < 0.001, N = 250). Chronic lead exposure affects the prooxidant-antioxidant equilibrium leading to cellular oxidative stress.

Peripherally inserted central venous lines versus central lines in surgical newborns--a comparison.

OBJECTIVE: To compare the insertion characteristics, utilization profile, life span and the complication rates of Central lines (CL) and Peripherally inserted central lines (PICL). METHODS: A prospective study of all CL or PICL insertions during January 2007 to September 2007 in the Neonatal Surgical Intensive Care Unit of a tertiary care center was done. The number of attempts, procedure time, duration of catheter stay, number of dressing done, complication during insertion and maintenance and cause of removal were noted and the differences analyzed statistically using Pearson chi square / t test. P value. 0.05 was considered significant. RESULTS: Ninety two neonates were included in the present study of whom 60 were PICL insertions and 32 CL insertions. The two groups were comparable in terms of age, weight and the use of total perental nutrition (TPN) through the catheters. On comparing the PICL and CL groups, the number of attempts for successful insertion (p=0.003), the time taken (p=0.005), the number of dressing changes required during the indwelling period (p=0.005) and the overall complication rates (p=0.002) were significantly less in the PICL group. The PICL could be maintained for longer periods of time (p= 0.005) and only in 11.5% of the patients it had to be removed before completion of therapy as compared to 37.5% early removals for CL (p=0.02) CONCLUSION: PICL is a safe, effective and reliable method of providing prolonged IV access in newborns. It also has the least incidence of complications during insertion and maintenance over prolonged period of time when compared to CL and should be recommended for routine use in neonatal surgical patients.

Vitamin B12 deficiency and gastric histopathology in older patients.

AIM: To compare upper gastric endoscopic and histopathologic findings in older adults in the presence and absence of B12 deficiency. METHODS: A prospective analysis of upper gastric endoscopic and gastric histopathologic findings from 30 newly identified B12-deficient patients (11 males, 19 females) and 16 controls with normal B12 status (6 males, 10 females) was performed. For all subjects, the indication for upper endoscopy and gastric biopsy were unrelated to B12 status. A single pathologist, blinded to B12 status, processed and interpreted the biopsy samples. Endoscopic and histopathologic findings were correlated with age, gender, hematocrit (Hct), MCV and B12 status. RESULTS: The B12-deficient group had significantly lower mean serum B12 levels compared to the controls (P<0.00005) while their mean Hct, MCV and serum albumin levels were similar. Iron deficiency (ferritin-based) was present in 21% of B12-deficient patients and intrinsic factor antibodies were present in 29% (5/17) of B12-deficient patients. The endoscopic findings revealed significantly different rates of gastritis and atrophy between the B12-deficient and control groups (P=0.017). B12-deficient patients had significantly less superficial gastritis (62% vs 94%) and significantly more atrophic gastritis (28% vs 0%) as compared to the controls (P=0.039). Intestinal metaplasia was similar in both groups. Helicobacter pylori infection rates were similar in the B12-deficient patients and controls (40% vs 31%). CONCLUSION: Significantly different endoscopic findings and types of gastritis could often be observed in the presence and absence of B12 deficiency. Atrophy, based on endoscopy, and atrophic gastritis, based on histopathology, suggest the presence of B12 deficiency. Gastric histopathology is not influenced by the age, gender, Hct or MCV of the patients.