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Biomedical subjects

H K Singh

Publications and source records attributed to H K Singh.

At least 19 recordsLinked to original sources

QSAR studies in substituted 1,2,3,4,6,7,12,12a-octa-hydropyrazino[2',1':6,1]pyrido[3,4-b]indoles--a potent class of neuroleptics.

A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.688). The best model describes a high correlation between predicted and experimental activity data (r=0.967). Statistical analysis of the equation populations indicates that hydrophobicity (as measured by pi(R), logP(o/w) and SlogP_VSA8), dipole y and structural parameters in terms of indicator variable, (In(1)) and globularity are important variables in describing the variation in the neuroleptic activity in the series.

Animals↗

A new dimension of 1H-NMR spectroscopy in assessment of liver graft dysfunction.

High-resolution 1H-NMR spectroscopy of serum and urine samples of an 11-year-old male living related orthotopic liver transplant recipient is reported. Serum glutamine increased to abnormal levels along with simultaneous abnormal excretion of urinary glutamine post-transplantation. High levels of glutamine in both blood and urine and concomitant reduced urea levels in urine were found to be evidence of impairment in urea cycle and compatible with persistently abnormal graft function. Thus glutamine levels in serum and urine, and urea in the urine as observed by 1H-NMR spectroscopy highlight their important roles in monitoring liver graft function; increased glutamine levels lead to brain damage, if untreated.

Adult↗

Photocatalysed degradation of a herbicide derivative, bromacil, in aqueous suspensions of titanium dioxide.

The photocatalysed degradation of a herbicide, 5-bromo-3-sec-butyl-6-methyl uracil (bromacil, 1) has been investigated in aqueous suspensions of titanium dioxide under a variety of conditions. The degradation was studied by monitoring the depletion in total organic carbon (TOC) content as a function of irradiation time. The degradation kinetics of the model compound was studied under different conditions such as pH, catalyst concentration, substrate concentration, different types of TiO2 and in the presence of electron acceptors such as hydrogen peroxide (H2O2) and potassium bromate (KBrO3) besides molecular oxygen. The degradation rate was found to be strongly influenced by all the above factors. Higher degradation rate was observed with Degussa P25 as compared with other photocatalysts. The addition of bromate ion has been found to enhance the degradation rate markedly. 5-Hydroxy-3-sec-butyl-6-methyl uracil (2) and diisopropyl urea (16) were identified as the degradation products by GC-MS analysis and probable pathways for the formation of the products have been proposed.

Bromates↗

Prognostic value of serum cardiac troponin I in ambulatory patients with chronic renal failure undergoing long-term hemodialysis: a two-year outcome analysis.

OBJECTIVES: We sought to evaluate the prognostic value of cardiac troponin I (cTnI) in asymptomatic, ambulatory patients with chronic renal failure treated with long-term hemodialysis. BACKGROUND: Smaller, short-term follow-up studies on this subject have given conflicting results. METHODS: A total of 126 ambulatory patients with chronic renal failure treated with long-term hemodialysis were followed for two years for all-cause mortality, cardiac mortality, all-cause hospital admissions and cardiac hospital admissions. Serum cTnI was measured before dialysis at the time of study entry. RESULTS: One hundred two patients had normal serum levels of cTnI (< or =0.03 ng/ml) and 24 patients had elevated levels (0.015 +/- 0.007 vs. 0.053 +/- 0.029 ng/ml, p < 0.0001). No significant difference in all-cause mortality (20 vs. 4 deaths), cardiac mortality (4 vs. 1 death), all-cause hospital admissions (1.74 +/- 1.72 vs. 1.25 +/- 1.19 admissions/patient) or cardiac admissions (0.52 +/- 0.89 vs. 0.33 +/- 0.76 admissions/patient) was present between the patients with normal cTnI levels and those with elevated cTnI levels. Serum cTnI was not significantly different between patients who died versus those who survived (0.022 +/- 0.019 vs. 0.022 +/- 0.021 ng/ml). Serum cTnI was not an independent predictor of all-cause mortality, cardiac mortality, all-cause admissions or cardiac admissions. Age (older) and serum albumin (lower) were independent predictors of all-cause mortality, whereas a history of myocardial infarction was an independent predictor of cardiac mortality. Serum sodium (lower) was an independent predictor of all-cause hospital admissions, whereas hypertension and previous myocardial infarction were independent predictors of cardiac admissions. The best predictors of the time to death were age (older) and serum sodium level (lower), irrespective of the serum cTnI levels. CONCLUSIONS: Cardiac troponin I has a limited role in predicting mortality and hospital admissions in asymptomatic patients with chronic renal failure treated with long-term hemodialysis.

Aged↗

Choroid plexus carcinoma presenting as an intraparenchymal mass.

A 6-year-old girl with a history of a nondisplaced skull fracture diagnosed with computerized tomography (CT) scanning 3 years previously presented with a 6-week history of headaches and decreased use of her right side. On admission CT scans, a large cystic mass was identified in the left frontal lobe region of the brain. A connection between the mass and the ventricular system was not seen on radiological examination or during surgery. Gross-total resection of the mass was achieved. The histological and immunohistochemical findings in the resected tissue confirmed a diagnosis of choroid plexus carcinoma (ChPC). This is the first reported case of a ChPC arising in an extraventricular location not associated with the choroid plexus.

Carcinoma↗

Coexistence of Fabry's disease and necrotizing and crescentic glomerulonephritis.

The coexistence of Fabry's disease, an X-linked hereditary disease, and other renal diseases, has rarely been described in the same patient. Combined Fabry's disease and pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) is hitherto unreported. We present the clinical and pathologic data of two patients with combined Fabry's disease and NCGN. Both patients presented with fevers of unknown origin and progressive renal insufficiency, however, lacked any other pathognomic signs of Fabry's disease such as acroparesthesias, dyshidrosis, and cutaneous angiokeratomas. The possible pathogenic mechanisms and causal relationship between the two disease processes are discussed.

Adult↗

Myxoid chondrosarcoma of the sphenoid sinus and chondromyxoid fibroma of the iliac bone: cytomorphologic findings of two distinct and uncommon myxoid lesions.

Myxoid chondrosarcoma (MCS) and chondromyxoid fibroma (CMF) are two uncommon myxoid cartilaginous neoplasms with distinct cytologic features, histologic patterns, and immunoprofiles. Because these neoplasms have characteristic biological behaviors and management, their correct diagnosis is crucial to avoid debilitating and unnecessary surgical procedures. We report the imprint cytology (IC) preparation findings along with the differential diagnosis in one case each of myxoid chondrosarcoma and chondromyxoid fibroma of the splenoid sinus and iliac bone, respectively. The two great mimickers for these neoplasms, chordoma and chondrosarcoma, represent difficult diagnostic challenges, especially when MCS and CMF occur in unusual locations. IC in conjunction with the clinical and radiologic findings can provide a rapid preliminary intraoperative diagnostic interpretation which can aid in planning the immediate surgical management, as well as guide specific tissue triage for key ancillary studies such as electron microscopy and cytogenetic analyses. To the best of our knowledge, there have been no cytologic reports of MCS of the sphenoid sinus and CMF of the iliac bone.

Adult↗

Idiopathic collapsing glomerulopathy in children.

Idiopathic collapsing glomerulopathy (ICG) is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis, characterized clinically by rapid progression of renal insufficiency, a male and African-American racial predominance, and pathologically by segmental glomerular collapse, visceral epithelial cell hypertrophy and hyperplasia, and the absence of endothelial tubuloreticular inclusions. Pathologically similar lesions have been reported in adult and pediatric patients with human immunodeficiency virus (HIV) infection and/or intravenous (IV) drug abuse. Most patients with ICG who have been reported in the literature are adults. Six children with ICG were retrospectively identified (two from East Carolina University, four from University of North Carolina-Chapel Hill). Clinical data and renal biopsy findings were reviewed for all patients. All six patients were male; five African-American and one Hispanic. Ages ranged from 2 to 17 years (mean 12 years). Steroid-resistant nephrotic syndrome was the presenting clinical finding. Average 24-h urine protein excretion was 6.3 g (range 3.2-15 g). Five patients were serologically negative for HIV infection (one patient not tested) and none had a history of IV drug abuse or known HIV risk factors. Progression to end-stage renal insufficiency in two patients within 1 year of biopsy required renal transplantation, and within 1 month of biopsy one patient required dialysis. We report a series of pediatric patients with ICG, an aggressive variant of focal segmental glomerulosclerosis. ICG in children is similar clinically and pathologically to this disease in adult patients.

Adolescent↗

Cytomegalovirus-induced necrotizing and crescentic glomerulonephritis in a renal transplant patient.

A 35-year-old black man with end-stage renal disease from biopsy-proven focal segmental glomerulosclerosis developed worsening function of his renal allograft 160 days after living related donor renal transplantation. Renal biopsy showed necrotizing and crescentic glomerulonephritis (NCGN) and presence of intraglomerular viral inclusions confirmed by immunocytochemical stain and in situ hybridization techniques to be cytomegaloviral in origin. Electron microscopy showed no immune complexes, and workup for other causes of NCGN was negative. The patient was treated with ganciclovir without other changes in his immunosuppressive regimen. After 8 weeks of ganciclovir therapy, a second renal transplant biopsy showed resolution of the glomerular process and disappearance of the cytomegalovirus (CMV) inclusions. The resolution of the glomerular process with treatment for CMV infection, and without other change in therapy, strongly supports a causative link between CMV and NCGN in this patient. This case represents the first report of CMV-associated NCGN in a renal transplant patient.

Adult↗

Diagnostic pitfalls in fine-needle aspiration biopsy of the mediastinum.

A retrospective review of 189 fine-needle aspiration (FNA) biopsies of the mediastinum from four university medical centers was performed. Review of Diff-Quick- and Papanicolaou-stained direct smears was performed from a series of 189 FNA biopsies along with surgical pathology correlation obtained in 42% of the cases. There were 28 (14.8%) nondiagnostic or unsatisfactory for diagnosis cases. Of the satisfactory FNA specimens with histologic correlation, 12 cases (6%) were discordant. These errors primarily involve subclassification of small-cell malignancies involving the mediastinum, including a misdiagnosis of small-cell carcinoma for lymphoma. Large-cell lesions that were problematic included the accurate diagnosis of Hodgkin's lymphoma including the separation from non-Hodgkin's lymphoma. Large-cell lymphoma with sclerosis was misinterpreted in two cases due to distortion of cells by the mesenchymal tissue and sparsely cellular smears. In two cases classification of primary germ-cell tumors and separation from metastatic carcinoma was a problem. In general, FNA of the mediastinum is an accurate procedure, but can be challenging in a minority of cases due to sparse cellularity of the lesions and accurate classification of a variety of neoplasms that occur in this region. These 12 discordant cases serve as the basis of our report.

Adult↗

Fine-needle aspiration cytomorphology of clear-cell hepatocellular carcinoma.

The clear-cell type of hepatocellular carcinoma is an uncommon variant of hepatoma that can be confused with other clear-cell malignancies. We report on 4 cases of clear-cell hepatocellular carcinoma diagnosed by computed tomography (CT)-guided fine-needle aspiration (FNA) biopsy. All 4 patients were men with a median age of 71 yr (age range 66-76 yr). Three patients presented with a solitary liver mass and no known extrahepatic primary malignancies. The fourth patient, previously diagnosed with non-A, non-B posttransfusion hepatitis, presented with an irregular firm liver and abnormal serum liver function tests. Cytologically, all cases were characterized by hypercellular smears consisting of loosely cohesive groups and individually scattered malignant cells demonstrating anisonucleosis, nuclear hyperchromasia and irregularity, prominent nucleoli, and abundant finely vacuolated to clear cytoplasm. Immunocytochemical staining in three cases revealed focal positivity of the malignant cells for cytokeratin (AE1/3) and alpha-fetoprotein in one case. Electron microscopy (EM) was performed in all cases and revealed ultrastructural features consistent with hepatocellular differentiation. The cytologic differentiation of clear-cell hepatocellular carcinoma from metastatic clear-cell malignancies of renal, ovarian, and adrenal origin, among others, is presented. In addition, EM and immunocytochemistry study of the aspirated material can aid in establishing the correct diagnosis, thereby facilitating appropriate clinical management.

Adenocarcinoma, Clear Cell↗

Significance of epithelial membrane antigen in the work-up of problematic serous effusions.

Differentiation of reactive and/or atypical mesothelial cells from malignant epithelial cells in serous effusions remains a frequent diagnostic problem. Since epithelial membrane antigen (EMA) positive malignant cells in serous effusions have been reported in almost all adenocarcinomas and most malignant mesotheliomas, immunoreactivity for EMA is felt to be less useful than other antibodies in the workup of problematic serous effusions. However, immunostaining of reactive and/or atypical benign mesothelial cells for EMA has not been well studied, with only a few series reporting either weak or negative staining for EMA. This study was undertaken to evaluate how often reactive and/or atypical appearing mesothelial cells stain positively for EMA. One hundred eighty serous effusions (115 pleural, 55 peritoneal, and 10 pericardial) from 123 females and 57 males ages 20 to 89 yr were evaluated in which an antibody panel including EMA was performed on cell blocks (141 cases), cytospins (36 cases), or both (3 cases). Of the 100 cytologically positive cases, EMA immunoreactivity was present in 97/100 (97%) cases. One EMA negative case suspicious for a metastatic renal cell carcinoma was lost to follow-up and not included in the analysis. The remaining three negative cases consisted of malignancies not expected to have EMA positive cells (small cell carcinoma, neuroblastoma, and synovial sarcoma). Therefore, EMA was positive in virtually 100% of the remaining malignant cases. In the 78 cytologically negative cases, EMA positivity was present in 3/78 (3.8%) cases. Clinical follow-up of up to 14 mo in these three cases revealed no evidence of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Unusual small bone metastases from epithelial malignancies: diagnosis by fine-needle aspiration cytology with histologic confirmation.

Although epithelial malignancies can have bone metastases, involvement of small bones is exceedingly rare, representing either first manifestation of an occult carcinoma or late disseminated disease. Small bone metastases may mimic primary skeletal diseases leading to misdiagnosis and delayed treatment. We report three cases of metastatic epithelial malignancies diagnosed by computed tomography (CT)-guided fine-needle aspiration (FNA) biopsy in two patients with lytic calcaneal lesions and a patellar lesion in a third patient; all with histologic confirmation. Case 1, a 63-year-old female, presented with heel pain. FNA and tissue biopsy of the calcaneus revealed a clear cell malignancy consistent with a renal primary. Follow-up abdominal CT scan revealed a renal lesion consistent with renal cell carcinoma. Case 2, a 37-yr-old male with squamous cell carcinoma of the esophagus, presented with foot pain. FNA and tissue biopsy of the calcaneous revealed metastatic squamous cell carcinoma. Case 3, a 52-yr-old male with a history of squamous cell carcinoma of floor of mouth, presented with knee pain and swelling. FNA and tissue biopsy of the patella revealed metastastic squamous cell carcinoma. To the best of our knowledge, this is the first complete FNA cytology report with histologic confirmation of unusual small bone metastases of the feet and patella from epithelial malignancies and shows the value of FNA cytology in establishing a correct diagnosis, and excluding primary skeletal diseases.

Adolescent↗

Bleeding jejunal leiomyoma: a new approach.

Leiomyomas represent one of the most common benign neoplasms of the small intestine. Most of these are asymptomatic and are found incidentally at surgery or autopsy; however, leiomyomas may present with prominent signs and symptoms. Bleeding is the most common clinical problem and is occasionally life-threatening. We report the case of a 90-yr-old man who presented with rectal bleeding that became massive within hours, necessitating blood transfusion. An arteriogram revealed significant hemorrhage from the jejunal branch of the superior mesenteric artery (thought to be arteriovenous malformation). Arterial embolization was performed, followed after 36 h by therapeutic laparoscopy. The area of ischemic bowel was identified, and a 4.5-cm extraluminal jejunal mass was resected. Pathological examination confirmed a tissue diagnosis of leiomyoma. Our Med-Line search revealed very few cases of jejunal leiomyoma that had presented initially as massive rectal bleeding. There were no cases of embolization followed by therapeutic laparoscopy.

Aged↗

Cytomorphology of familial hemophagocytic syndrome.

Familial hemophagocytic syndrome (FHS) is a rare, fatal disorder of childhood demonstrating failure to thrive, fever, hepatosplenomegaly (HSM), recurrent infections, pancytopenia, and histologically, the infiltration of reticuloendothelial organs by benign-appearing histiocytes demonstrating hemophagocytosis. We report two fatal cases of FHS including a 3 year-old female who underwent fine-needle aspiration (FNA) biopsy of the liver in the initial workup of the disease (case 1) and an 8 month-old boy with ascites and HSM having peritoneal fluid cytology submitted as the first specimen for morphologic examination (case 2). In case 1, the FNA cytologic findings included benign hepatocytes and scattered mature and reactive lymphocytes and histiocytes. The histiocytes demonstrated fine to coarse cytoplasmic vacuoles and erythrophagocytosis. The diagnosis was confirmed at autopsy which revealed extensive lymphohistiocytic infiltrates in various organs including the central nervous system. In case 2, the peritoneal fluid cytology specimen contained numerous atypical and degenerating mononuclear lymphoreticular cells which were dispersed as a single cell suspension admixed with infrequent mesothelial elements; hemophagocytosis was not appreciated. Subsequent liver biopsy revealed portal tracts and sinusoids infiltrated by benign but atypical histiocytes with hemophagocytosis. Bone marrow examination and then autopsy confirmed the diagnosis of FHS. A panel of immunocytochemical studies was performed in the first case which was an aid in confirming the diagnosis of FHS and ultrastructural examination of the second case revealed well-developed erythrophagocytosis. Both patients had siblings who died of FHS. Although not diagnostic, cytomorphology may suggest FHS.

Ascitic Fluid↗

Substituted thiosemicarbazides and corresponding cyclized 1,3,4-oxadiazoles and their anti-inflammatory activity.

Several 1-(4-biphenoxyacetyl)-4-substituted arylthiosemicarbazides and their corresponding cyclized 2-(4-biphenoxymethyl)-5-arylamino-1,3,4- oxadiazoles were synthesized and characterized by elemental analyses and IR, mass, and nuclear magnetic resonance spectra. All compounds were evaluated for anti-inflammatory activity by determining their ability to provide protection against carrageenin-induced edema in rat paw. The anti-inflammatory activity possessed by substituted thiosemicarbazides [100 mg/kg, intraperitoneal(ip)] ranged from 22 to 68%, whereas substituted 1,3,4-oxadiazoles (100 mg/kg, ip) provided protection of 10-76%. Hydrocortisone (10 mg/kg, ip) and oxyphenbutazone (40 mg/kg, ip), used as standard reference drugs, decreased edema in rat paw by 44.6 and 52.9%, respectively. All compounds (1 mM) possessed antiproteolytic activity that was reflected by their ability to cause in vitro inhibition of trypsin-induced hydrolysis of bovine serum albumin. This inhibition ranged between 43 and 72% for substituted thiosemicarbazides and 30 and 83% for substituted 1,3,4-oxadiazoles.

Animals↗