Sarcomatoid carcinoma in a bladder diverticulum--a rare case.
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Carcinosarcoma↗
Biomedical subjects
J Augustine
Publications and source records attributed to J Augustine.
Evaluation of missed diagnoses for patients admitted from the emergency department.
OBJECTIVE: To define a quality assurance instrument to evaluate errors in diagnostic processes made by physicians in the emergency department (ED). METHODS: This was a retrospective clinical investigation of inpatient ED records. Over a six-year period, 5,000 medical records of admitted patients were randomly selected for evaluation. Each record was initially examined by one of five physician evaluators. If the primary ED diagnosis differed from the primary discharge diagnosis, the ED record was inspected to determine reasons for the misdiagnosis. The authors considered several aspects of the diagnostic process, including patient history, tests ordered, interpretation of clinical data, choice and performance of procedures, injury pattern recognition, reasoning, and evaluation. Records that demonstrated errors in the diagnostic process were reevaluated for the same diagnostic process errors by a sixth physician. Disagreements regarding suspected errors in the diagnostic process were settled by discussion. Finally, to determine potential medical consequences of the misdiagnosis, one individual reviewed the complete medical records of patients whose ED medical records were scored with errors by both evaluators. Interevaluator reliability was assessed using Cochran's Q-test with a selected series of medical records. RESULTS: Twenty-eight records (0.6%) were found to contain one or more errors in the diagnostic process that contributed to misdiagnosis. For these patients appropriate diagnosis was not made until one to 16 days after admission. Three patients of 18 whose records were available for detailed review may have suffered complications that resulted, in part, from the delay in diagnosis and subsequent treatment. Significant interevaluator reliability for identification of errors in the diagnostic process was obtained (p > 0.1). CONCLUSIONS: A two-tiered evaluation of ED records selected by inconsistent initial and final diagnoses can be used reliably to screen for errors in the diagnostic process made by emergency physicians (EPs). The rate of physician error contributing to a misdiagnosis is very low, suggesting that EPs are delivering quality patient care.
Diagnostic Errors↗
Studies on digoxin--14C-acetate incorporation in to digoxin and degenerative changes in the brain in rats administered digoxin.
The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin. Digoxin is a steroidal glycoside and could be synthesised by the isoprenoid pathway. The other metabolites of the isoprenoid pathway are cholesterol, dolichol and ubiquinone. We have tried to find out the extent of incorporation of 14C acetate into digoxin in rat brain. The effects of digoxin administration on the rat brain was also studied. The results show that the percentage incorporation of 14C acetate into digoxin is low but detectable. The maximum incorporation was observed for cholesterol, followed by dolichol and finally ubiquinone. The histopathological changes observed after digoxin administration were focal degeneration of the ganglion cells in the cerebrum and cerebellum. The carbohydrate components of the glycoproteins were reduced and the concentration of serotonin, dopamine, and epinephrine showed a significant increase. The role of digoxin in mediating neuronal cell death is discussed.
Acetates↗
Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders.
Two substances which are products of the isoprenoid pathway, can participate in lipid peroxidation. One is digoxin, which by inhibiting membrane Na(+)-K+ ATPase, causes increase in intracellular Ca2+ and depletion of intracellular Mg2+, both effects contributing to increase in lipid peroxidation. Ubiquinone, another products of the pathway is a powerful membrane antioxidant and its deficiency can also result in defective electron transport and generation of reactive oxygen species. In view of this and also in the light of some preliminary reports on alteration in lipid peroxidation in neuropsychiatric disorders, a study was undertaken on the following aspects in some of these disorders (primary generalised epilepsy, schizophrenia, multiple sclerosis, Parkinson's disease and CNS glioma)--1) concentration of digoxin, ubiquinone, activity of HMG CoA reductase and RBC membrane Na(+)-K+ ATPase 2) activity of enzymes involved in free radical scavenging 3) parameters of lipid peroxidation and 4) antioxidant status. The result obtained indicates an increase in the concentration of digoxin and activity of HMG CoA reductase, decrease in ubiquinone levels and in the activity of membrane Na(+)-K+ ATPase. There is increased lipid peroxidation as evidenced from the increase in the concentration of MDA, conjugated dienes, hydroperoxides and NO with decreased antioxidant protection as indicated by decrease in ubiquinone, vit E and reduced glutathione in schizophrenia, Parkinson's disease and CNS glioma. The activity of enzymes involved in free radical scavenging like SOD, catalase, glutathione peroxidase and glutathione reductase is decreased in the above diseases. However, there is no evidence of any increase in lipid peroxidation in epilepsy or MS. The role of increased operation of the isoprenoid pathway as evidenced by alteration in the concentration of digoxin and ubiquinone in the generation of free radicals and protection against them in these disorders is discussed.
Central Nervous System Neoplasms↗
Catalytic defects in mutants of class II histidyl-tRNA synthetase from Salmonella typhimurium previously linked to decreased control of histidine biosynthesis regulation.
The expression of histidine biosynthetic genes in enteric bacteria is regulated by an attenuation mechanism in which the level of histidyl-tRNA serves as a key sensor of the intracellular histidine pool. Among the early observations that led to the formation of this model for Salmonella typhimurium were the identification of mutants in the gene (hisS) encoding histidyl-tRNA synthetase. We report here the detailed biochemical characterization of five of these S. typhimurium bradytrophic mutants isolated by selection for resistance to histidine analogs, including identification of the deduced amino acid substitutions and determination of the resulting effects on the kinetics of adenylation and aminoacylation. Using the crystal structure of the closely related Escherichia coli histidyl-tRNA synthetase (HisRS) as a guide, two mutants were mapped to a highly conserved proline residue in motif 2 (P117S, P117Q), and were correlated with a fivefold decrease in the kcat for the pyrophosphate exchange reaction, as well as a tenfold increase in the Km for tRNA in the aminoacylation reaction. Another mutant substitution (A302T) mapped to a residue adjacent to the histidine binding pocket, leading to a tenfold increase in Km for histidine in the pyrophosphate exchange reaction. The remaining two mutants (S167F, N254T) substitute residues in or directly adjacent to the hinge region, which joins the insertion domain between motif 2 and motif 3 to the catalytic core, and cause the Km for tRNA to increase four- to tenfold. The kinetic analysis of these mutants establishes a direct link between critical interactions within the active site of HisRS and regulation of histidine biosynthesis, and provides further evidence for the importance of local conformational changes during the catalytic cycle.
Amino Acid Sequence↗
Emergency medicine in a managed care environment.
Managed care has changed the face of the health care system. Providers who schedule care have responded and modified their systems of delivery and provision of care. The focus has now turned to unscheduled care, such as urgent and emergency services. This market is much more difficult to control and reconstruct. This article discusses the role of emergency medicine within a managed care system and future opportunities.
Consumer Behavior↗
Design of an active fragment of a class II aminoacyl-tRNA synthetase and its significance for synthetase evolution.
Primordial aminoacyl-tRNA synthetases (aaRSs) based on the Rossman nucleotide binding fold of class I enzymes or the seven-stranded antiparallel beta-sheet fold of class II enzymes have been proposed to predate the contemporary aaRS. As part of an inquiry into class II aaRS evolution, the individual domains of the homodimeric Escherichia coli histidyl-tRNA synthetase (HisRS) were separately expressed and purified to determine their individual contributions to catalysis. A 320-residue fragment (Ncat HisRS) truncated immediately following motif 3 catalyzes both the specific aminoacylation of tRNA and pyrophosphate exchange, albeit less efficiently than the full-length enzyme. Ncat HisRS showed no mischarging of noncognate tRNAs but exhibited reduced selectivity for the C73 discriminator base, a principal aminoacylation determinant for histidine tRNAs. Size exclusion chromatography showed that Ncat HisRS is monomeric, indicating that the C-terminal domain is essential for maintaining the dimeric structure of the enzyme. The stably folded C-terminal domain (Cter HisRS) was inactive for both reactions and did not enhance the activity of Ncat HisRS when added in trans. The fusion of one or more accessory domains to a primordial catalytic domain may therefore have been a critical evolutionary step by which aminoacyl-tRNA synthetases acquired increased catalytic efficiency and substrate specificity.
Acylation↗
Molecular analysis of a compound heterozygote for hypoprothrombinemia and dysprothrombinemia (-G 7248/7249 and ARG 340 TRP).
Hypoprothrombinemia is an uncommon hereditary coagulation defect characterized by low levels of biologically active prothrombin. Automated fluorescence-based DNA sequence analysis of amplified genomic DNA was used to define prothrombin gene regions from a patient with severe functional hypoprothrombinemia and little detectable prothrombin antigen. Two changes that alter amino acid sequence were observed: a deletion of one nucleotide (-G, 7248/7249) in exon 8 of one allele, causing a frameshift at codon 249/250 that results in premature termination of translation; and a C --> T change resulting in the substitution of tryptophan (TGG) for arginine (CGG) at amino acid 340 in exon 10 of the prothrombin gene. Computer modeling of the thrombin molecule confirmed that arginine 340 is located at the surface of the thrombin molecule, which points to the aqueous solvent. As tryptophan is a highly hydrophobic amino acid, the Arg --> Trp change may be associated with instability of the thrombin molecule.
Adult↗
Early diagnosis of bone biopsies--the role of sediment cytology.
This study analyses the role of the cytological examination of the sediment of the formalin in which bone biopsy specimens are received, in the early diagnosis of bone lesions. Of the one hundred lesions studied using this technique, twenty six of thirty three malignant lesions (seventy nine percent) could be diagnosed as malignant when relevant clinical and radiological data were considered. Sixty six benign lesions yielded sparsely cellular smears with benign cell. There was one false positive for malignancy. This simple rapid diagnostic technique can be used to advantage in the early diagnosis, and treatment planning of bone lesions.
Biopsy↗
Expression of epidermal growth factor in gestational trophoblastic disease (GTD).
Gestational Trophoblastic Disease (GTD) is an abnormal condition of the placenta, the incidence of which is very high in the State of Kerala, India. The biology of the disease is vague and methods to determine the malignant potentialis limited. Placentae of normal (50) and molar pregnancy (95) including 32 patients showing persistent disease were used in this study. EGF expression was analyzed by immunohistochemistry using monoclonal antibody to EGF and quantitated using isotope labelled antibody to EGF. EGF was expressed more strongly in molar placentae in all gestational ages in comparison with normal placentae of similar gestational age, the expression being restricted mainly to first and second trimesters in normal placentae. Moles with early presenting symptoms (< 12 weeks) were at a higher risk for developing persistent disease. In conclusion, the immunohistochemical study shows high expression of EGF in early normal placentae and moles linking its role to proliferative and differentiating activity of trophoblasts. Tumors with histological diagnosis of invasive moles and choriocarcinoma showed very strong binding of EGF and thus EGF has the potential of identifying high risk lesions.
Adolescent↗
A tRNA identity switch mediated by the binding interaction between a tRNA anticodon and the accessory domain of a class II aminoacyl-tRNA synthetase.
Identity elements in tRNAs and the intracellular balance of tRNAs allow accurate selection of tRNAs by aminoacyl-tRNA synthetases. The histidyl-tRNA from Escherichia coli is distinguished by a unique G-1.C73 base pair that upon exchange with other nucleotides leads to a marked decrease in the rate of aminoacylation in vitro. G-1.C73 is also a major identity element for histidine acceptance, such that the substitution of C73 brings about mischarging by glycyl-, glutaminyl-, and leucyl-tRNA synthetases. These identity conversions mediated by the G-1.C73 base pair were exploited to isolate secondary site revertants in the histidyl-tRNA synthetase from E. coli which restore histidine identity to a histidyl-tRNA suppressor carrying U73. The revertant substitutions confer a 3-4 fold reduction in the Michaelis constant for tRNAs carrying the amber-suppressing anticodon and map to the C-terminal domain of HisRS and its interface with the catalytic core. These findings demonstrate that the histidine tRNA anticodon plays a significant role in tRNA selection in vivo and that the C-terminal domain of HisRS is in large part responsible for recognizing this trinucleotide. The kinetic parameters determined also show a small degree of anticooperativity (delta delta G = -1.24 kcal/mol) between recognition of the discriminator base and the anticodon, suggesting that the two helical domains of the tRNA are not recognized independently. We propose that these effects substantially account for the ability of small changes in tRNA binding far removed from the site of a major determinant to bring about a complete conversion of tRNA identity.
Anticodon↗
Optimal positioning for cervical immobilization.
STUDY OBJECTIVE: We hypothesized that optimal positioning of the head and neck to protect the spinal cord during cervical spine immobilization can be determined with reference to external landmarks. In this study we sought to determine the optimal position for cervical spine immobilization using magnetic resonance imaging (MRI) and to define this optimal position in a clinically reproducible fashion. METHODS: Our subjects were 19 healthy adult volunteers (11 women, 8 men). In each, we positioned the head to produce various degrees of neck flexion and extension. This positioning was followed by quantitative MRI of the cervical spine. RESULTS: The mean ratio of spinal canal and spinal cord cross-sectional areas was smallest at C6 but exceeded 2.0 at all levels from C2 to T1 (P < .05). At the C5 and C6 levels, the maximal area ratio was most consistently obtained with slight flexion (cervical-thoracic angle of 14 degrees) (P < .05). For a patient lying flat on a backboard, this corresponds to raising the occiput 2 cm. More extreme flexion or extension produced variable results. CONCLUSION: In healthy adults, a slight degree of flexion equivalent to 2 cm of occiput elevation produces a favorable increase in spinal canal/spinal cord ration at levels C5 and C6, a region of frequent unstable spine injuries.
Adult↗
Nurse management of posttransplant hypertension in liver transplant patients.
Hypertension develops soon after organ transplantation using cyclosporine- or FK506-based immunosuppression. Sustained rises in blood pressure require intervention to reduce the risk of intracranial bleeding and other cardiovascular complications. Antihypertensive treatment is complicated by reduced renal function and potential interference with absorption and/or metabolism of cyclosporine or FK506. To manage early and long-term hypertension related to immunosuppression with cyclosporine or FK506 and prednisone following orthotopic liver transplantation, a comprehensive nurse-managed hypertension clinic was developed. Blood pressure, heart rate, and antihypertensive and immunosuppressive regimens were evaluated according to a standard protocol at 1, 4, 12, 24, and 36 months after orthotopic liver transplantation. Data indicate that posttransplantation hypertension develops within the first months after orthotopic liver transplantation and persists indefinitely. If comprehensively managed by the hypertension nurse-clinician, the percentage of controlled hypertension patients can increase over time.
Blood Pressure Monitoring, Ambulatory↗
A cytological study of hepatitis B surface antigen localization using orcein staining in hepatocellular carcinoma.
Twenty patients of suspected hepatocellular carcinoma (HCC) were studied to test the hypothesis that orcein staining of cytological specimens from HCC can detect hepatitis B surface antigen (HBsAg). HBsAg status, cytological examination of fine needle aspiration cytology (FNAC) material for diagnosis by Papanicolaou and modified orcein staining for HBsAg were carried out. Observer variability and agreement on orcein positivity was assessed and analyzed using kappa statistics. HCC was diagnosed in 13 patients and 8 were HBsAg positive; 8 had orcein positivity as judged by observer 2 and 7 by observer 1. A significant kappa value of 0.837 suggested a high degree of observer agreement in the interpretation of orcein positivity. This technique is safe and quick and can supplement the histopathological diagnosis of hepatitis B virus associated HCC.
Adult↗
Elevated serum glycosaminoglycans with hypomagnesemia in patients with coronary artery disease & thrombotic stroke.
Elevated levels of serum glycosaminoglycans (GAG), associated with hypomagnesemia were observed in patients of proven CAD and thrombotic stroke in Kerala. Serum lipid profile was normal in the majority of these patients, indicating that elevated serum GAG may be an even more reliable indicator of atherosclerosis than elevated serum total cholesterol or LDL cholesterol. Autopsy samples of carotid artery and aorta which had atheroma showed significantly higher GAG when compared to samples which showed no atheroma. Serum Mg levels were significantly lower in CAD and thrombotic stroke patients as compared to controls. Mg deficiency may be one of the factors involved in the increased level of GAG.
Adult↗
Cytodiagnosis of primary malignant melanoma of the female urethra--a case report.
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Aged↗
Hypertension after liver transplantation.
Hypertension developing after liver transplantation is nearly universal and likely reflects several pathogenic mechanisms. Foremost among these are altered vascular reactivity and vasoconstriction related to CSA, and probably FK506, administration, impaired GFR and sodium excretion, and the effects of steroids. This disorder is of both theoretical and practical importance in understanding blood pressure regulation in humans. Most importantly, it poses a considerable long-term cardiovascular risk for the transplant recipient. Recognition of acquired hypertension and timely intervention are among the primary management challenges for the transplant clinician.
Animals↗
Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.
Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.
6-Ketoprostaglandin F1 alpha↗