Biomedical subjects
Publications and source records attributed to P Rao.
Out of 156 cases of various gastro duodenal disorders studied H. pylori was diagnosed in 119 (76.28%) as indicated by Biopsy urease test and IgG ELISA. Biopsy urease test detected higher number of cases 119 when compared to IgG ELISA 107 cases. ELISA being a non invasive technique can be used successfully for the diagnosis of H. pylori infections.
A sensitive and rapid method was developed for angiotensin-converting enzyme (ACE) activity determination by capillary zone electrophoresis. Hippuryl-l-histidyl-l-leucine, a synthetic tripeptide, was used as the ACE-specific substrate. Capillary zone electrophoresis was employed to separate the products of the enzymatic reaction and the ACE activity was determined by quantification of hippuric acid, a result of the enzymatic reaction on the tripeptide. The capillary electrophoresis was performed in a 27 cm x 75 micrometer i.d. fused-silica capillary using 200 mM boric acid-borate buffer (pH 9.0) as a run buffer with an applied voltage of 8.1 kV at a capillary temperature of 23 degrees C. The electrophoresis was monitored at 228 nm. Each electrophoretic run requires only a nanoliter of the enzymatic reactant solution, at only 6 min, rendering a powerful tool for the ACE assay.
Cytogenetic and molecular analyses have shown that the chromosome band 12q22 is recurrently deleted in male germ cell tumors (GCTs), indicating the presence of a candidate tumor suppressor gene (TSG) in this region. To identify the TSG, we mapped the APAF1 gene, a proapoptotic mammalian homologue of ced-4, to chromosomal band 12q22, that suggested that this might be the candidate deleted gene in GCTs. We further localized the gene between the polymorphic markers D12S1671 and D12S1082 at 12q22 to determine the role of APAF1 in the pathogenesis of GCT, and we characterized its normal genomic structure and analyzed its alterations in GCTs. The APAF1 gene comprises 27 exons, with the coding region spanning 26. The region containing APAF1 was found to be deleted in GCT by fluorescence in situ hybridization analysis, but without evidence of coding sequence alterations. RT-PCR and Western blot analysis showed APAF1 gene expression at detectable levels in all GCT cell lines analyzed. An aberrant-sized APAF1 protein was seen in one cell line. This and 2 other cell lines carrying APAF1 deletions also exhibited defects in dATP-mediated caspase-3 activation. Caspase-3 activity was effectively restored by addition of recombinant caspase-9 and APAF1 proteins, and to a lesser extent by caspase-9 alone, but not by APAF1 alone. These data do not support a TSG role for APAF1, but defects in other components of the apoptotic pathway that may be related to 12q22 deletion cannot be ruled out. Genes Chromosomes Cancer 28:258-268, 2000.
Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with the development of several human malignancies. A closely related herpesvirus in the same lymphocryptovirus (LCV) genera as EBV naturally infects rhesus monkeys and provides an important animal model for studying EBV pathogenesis. We cloned the small viral capsid antigen (sVCA) homologue from the rhesus LCV and developed a peptide enzyme-linked immunosorbent assay (ELISA) to determine whether epitopes in the rhesus LCV sVCA are a reliable indicator of rhesus LCV infection. In order to define a "gold standard" for rhesus LCV infection, we also cloned the EBV-encoded small RNA 1 (EBER1) and EBER2 homologues from rhesus LCV and developed a reverse transcription (RT)-PCR assay to detect persistent LCV infection in rhesus monkey peripheral blood lymphocytes. Animals from a conventional and a hand-reared colony were studied to compare the prevalence of rhesus LCV infection in the two groups. There was a 100% correlation between the peptide ELISA and EBER RT-PCR results for rhesus LCV infection. In addition, specificity for LCV infection and exclusion of potential cross-reactivity to the rhesus rhadinovirus sVCA homologue could be demonstrated using sera from experimentally infected animals. These studies establish two novel assays for reliable diagnosis of acute and persistent rhesus LCV infections. The rhesus LCV sVCA peptide ELISA provides a sensitive and reliable assay for routine screening, and these studies of the hand-reared colony confirm the feasibility of raising rhesus LCV-naive animals.
Because of the great efficacy of multidrug therapy (MDT), it had been hoped that the widespread use of MDT would bring about a rapid decrease of the incidence of leprosy. To the present, a decrease of incidence has not been observed, possibly because of the long incubation period of the disease, and because general implementation of MDT is still recent. Other reasons, such as environmental sources of infection or the role of healthy carriers in transmitting Mycobacterium leprae, cannot be excluded. Therefore, one must seek alternative or supplementary strategies, such as chemoprophylaxis. Household contacts of leprosy patients are at greater risk of developing leprosy than is the general population. Therefore, a randomized, controlled trial of chemoprophylaxis, using a single 10 mg/kg dose of rifampicin, or a placebo, is planned in nine projects in India, among the household contacts of newly detected leprosy patients. Based upon assumptions of a protective efficacy of the chemoprophylaxis of 50%, an annual incidence of 2 per 1000 contacts, a desired power of the study of 90%, and a level of significance of 95%, 15,000 household contacts will be allocated randomly by household to each arm of the study, and followed for 5 years. Considered as household contacts will be all persons living in the same household as an index case and sharing the same kitchen. Pregnant women and infants will be excluded. To be certain that transmission of the organisms from the index case cannot occur once the prophylaxis is administered, rifampicin will be administered 2 months after diagnosis of the index case. Diagnosis of leprosy will be clinical, and confirmed independently. Although household contacts usually constitute only a small proportion of the new patients detected in a control programme, their high-risk status makes them particularly appropriate for a study of the potential effect of chemoprophylaxis. Following the trial, one could evaluate the usefulness and feasibility of using the same strategy in other population-groups, based on the number of persons necessary to treat to prevent one case.
We present a case of significant over-anticoagulation temporally associated with a bout of protracted diarrhea in a patient on warfarin therapy. Cholestyramine was utilized to interrupt the enterohepatic recycling of warfarin and for its antidiarrheal effects to prevent gastrointestinal vitamin K wasting. Cholestyramine enabled the use of very low doses of sc vitamin K1 (2 mg total) with subsequent attainment of a therapeutic International Normalized Ratio in 39 h.
OBJECTIVES: (1) To compare the intracranial computed tomography (CT) appearances of patients admitted with various causes of hypoxic ischaemic encephalopathy. Children with known documented accidental trauma were excluded. (2) To compare our results with those in the published literature. MATERIALS AND METHODS: Seventy-three patients aged between 1 day and 15 years were admitted with clinical features of brain injury and underwent cranial CT. A retrospective review of their medical records and radiology was undertaken. Clinical and radiological data were collected. RESULTS: On the basis of the combination of the presenting clinical history, progress, outcome, long term follow up and radiology, two groups of patients were identified. Forty-seven children had been the victims of non-accidental injury (NAI). No child in this group had any associated medical condition or any other medical cause for brain injury. All 47 children demonstrated hypoxic ischaemic encephalopathy and had CT signs of cerebral oedema and 'Reversal Sign'. Intracranial haemorrhage was a highly associated feature. Subdural blood was demonstrated in all 47, acute interhemispheric fissure subdural in 42, intracerebral blood in 16 and intraventricular blood in nine. The remaining 26 children were found to have an identifiable 'medical' cause for brain injury. Acute reversal was demonstrated in 21 of this group. Intracranial haemorrhage was uncommon, found in only five and all five had an underlying predisposition to bleeding. No patient in this group demonstrated subdural blood. CONCLUSION: Non-accidental injury is strongly associated with the finding on CT of intracranial blood, particularly subdural haematoma and interhemispheric fissure bleeding in the presence of hypoxic ischaemic brain injury. The outlook is extremely poor whatever the underlying cause for hypoxic ischaemic brain injury.
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OBJECTIVE(S): To measure vascular endothelial growth factor (VEGF), nitric oxide (NO) and leptin levels in individual ovarian follicles and to examine their relationships with perifollicular blood flow, follicular metabolic indices, and the developmental potential of the corresponding oocyte and embryo. DESIGN: Prospective study. SETTING: Academic, tertiary care institution. PATIENT(S): Unselected IVF patients. INTERVENTION(S): Color-pulsed Doppler analysis of perifollicular blood flow; determination of partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and pH and VEGF, leptin and NO levels in follicular fluid. MAIN OUTCOME MEASURE(S): Fertilization and day 3 embryo morphology and cleavage. RESULT(S): Fifty-five follicular fluid samples from 16 patients were studied. Mean follicular fluid levels were as follows: VEGF, 1,046+/-863.7 pg/mL (range, <63-3,332.7 pg/mL); NO3/NO2, 34.2+/-12 microM (range, 16.4-76.1 microM); and leptin, 20.1+/-12.1 ng/mL (range, 3.3-52.2 ng/mL). Vascular endothelial growth factor had a negative correlation with embryo morphology (r = -0.28, P = .01). Leptin demonstrated a negative correlation with follicular pO2 (r = -0.42, P = .005) and a positive correlation with follicular pCO2 (r = 0.36, P = .02). Follicular leptin levels correlated positively with VEGF levels (r = 0.46, P = .008) and with NO3/NO2 levels (r = 0.39, P =.006). CONCLUSION(S): Vascular endothelial growth factor, NO and leptin appear to be markers of follicular hypoxia and suboptimal embryo development. Whether fluctuations of these regulatory factors determine or reflect changes in the follicular microenvironment affecting oocyte developmental potential remains to be elucidated.
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Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptovirus (LCV) subgroup. Several potential strategies for immune evasion and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experimentally. Interest has focused on the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and replication of the episomal viral genome in latently infected cells and because EBNA1 endogenously expressed in these cells is protected from presentation to the major histocompatibility complex class-I restricted cytotoxic T-lymphocyte (CTL) response through the action of an internal glycine-alanine repeat (GAR). Given the high degree of biologic conservation among LCVs which infect humans and Old World primates, we hypothesized that strategies essential for viral persistence would be well conserved among viruses of this subgroup. We show that the rhesus LCV EBNA1 shares sequence homology with the EBV and baboon LCV EBNA1 and that the rhesus LCV EBNA1 is a functional homologue for EBV EBNA1-dependent plasmid maintenance and replication. Interestingly, all three LCVs possess a GAR domain, but the baboon and rhesus LCV EBNA1 GARs fail to inhibit antigen processing and presentation as determined by using three different in vitro CTL assays. These studies suggest that inhibition of antigen processing and presentation by the EBNA1 GAR may not be an essential mechanism for persistent infection by all LCV and that other mechanisms may be important for immune evasion during LCV infection.
The normalized peritoneal clearances of small solutes depend on the ratio of their concentration in dialysate and plasma (D/P) and the drain volume (Dv) corrected for some measure of body size such as body water (V) or body surface area (BSA). The clearance formulas (D/P) x (Dv/V) and (D/ P) x (Dv/BSA) can be used to examine why large individuals tend to be underdialyzed. Large people have low normalized drain volumes (Dv/V, Dv/BSA). It is not known whether size affects the D/P ratios. The purpose of this study was to examine the relationship between normalized peritoneal clearances (Kt/Vurea, CCr per 1.73 m2 BSA) and four size indicators (weight, height, V, BSA) in 301 patients on continuous ambulatory peritoneal dialysis (four daily exchanges with 2-L exchange volume) who underwent 613 clearance studies. Highly significant (P < 0.001) nonlinear relationships were found between Kt/Vurea and weight (r2 = 0.371), height (r2 = 0.289), BSA (r2 = 0.436), and V (r2 = 0.527); and between CCr and weight (r2 = 0.178), height (r2 = 0.115), BSA (r2 = 0.199), and V (r2 = 0.151). There were also significant negative correlations between the normalized drain volumes (Dv/V and Dv/BSA) and all four indicators of body size. Raw (not normalized) peritoneal clearances and drain volumes correlated positively with size. However, D/P(urea) or D/P(creatinine) did not vary with any size indicator except for a weak association between D/P(creatinine) and V (r = 0.089, P = 0.028). This association was not confirmed when V was used to stratify subjects into quartiles, and group differences for D/P(creatinine were tested by one-way ANOVA. This study shows that the exclusive cause of the low normalized peritoneal clearances in large subjects on continuous ambulatory peritoneal dialysis is a low normalized drain volume. No evidence was found to indicate that body size influences the D/P ratio of small solutes. The portion of the variance in normalized clearance explained by size varies by size indicator and solute (urea versus creatinine).
This article reviews the 1997 Balanced Budget Act as it pertains to Medicare reimbursement and its consequent impact on medical rehabilitation in general and on persons with stroke in particular. Following a description of the concept and practice of "consumer choice" in health care today, the author frames "choice" in the context of outcomes management wherein the person with stroke may be provided with a report card that describes what outcomes the patient might expect following a course of rehabilitation. Today more than ever, patients are beginning to require information about provider performance that is easy to understand and allows for them to make intelligent purchasing decisions. Literature is reviewed that documents better stroke outcomes in specific types of rehabilitation settings. Finally, a variety of existing consumer tools are reviewed that assist the person with stroke in making an enlightened choice for an optimal setting for stroke rehabilitation. Unfortunately, persons with stroke may not consistently be able to exercise an educated choice because the payer may independently determine placement. An extensive consumer check list of quality indicators is provided to enable the patient's family and provider to evaluate the appropriateness of placing a person with stroke in a given setting.
Normalized clearances for urea and creatinine were compared between 121 diabetic subjects (256 clearances) and 181 nondiabetic subjects (357 clearances) on continuous ambulatory peritoneal dialysis (CAPD) with four 2-L exchanges daily. Urea clearance was normalized by VWatson (Kt/Vur), while creatinine clearance was normalized by both VWatson (Kt/Vcr) and body surface area (Ccr). Height, weight, body water (V), and body surface area did not differ between the diabetic and the nondiabetic groups. Also, renal Kt/Vur, renal Kt/Vcr, renal Ccr, and peritoneal Kt/Vur did not differ between the groups. Weekly peritoneal Kt/Vcr (diabetic group 1.36 +/- 0.38, nondiabetic group 1.31 +/- 0.31, p = 0.048) and weekly peritoneal Ccr (diabetic group 47.6 +/- 11.0 L/1.73 m2, nondiabetic group 45.4 +/- 9.2 L/1.73 m2, p = 0.012) were both higher in diabetic subjects. The percentage of high/high-average transporters was higher in the diabetic group (64.9% vs 48.6% in nondiabetic group, p = 0.006). The following total (peritoneal + renal) weekly clearances were obtained: Kt/Vur, diabetic group 2.07 +/- 0.63, nondiabetic group 2.02 +/- 0.56, NS; Kt/Vcr, diabetic group 2.06 +/- 0.78, nondiabetic group 1.92 +/- 0.74, p = 0.026; Ccr, diabetic group 72.7 +/- 28.5 L/1.73 m2, nondiabetic group 67.2 +/- 26.4 L/1.73 m2, p = 0.013. Normalized total creatinine clearances are higher in diabetic subjects than nondiabetic subjects on the same CAPD schedule and with the same renal clearances of urea and creatinine and the same total Kt/Vur, because peritoneal creatinine clearances are higher in the diabetic subjects. This finding is caused by higher peritoneal transport in the diabetic subjects and is not an artifact caused by the normalization process.
PURPOSE: To evaluate ocular tolerance of methylated collagen gel injected intravitreally and into the anterior chamber. METHODS: Methylated collagen (type I/III) was tested in New Zealand white rabbits. Vitreous cavity: After pars plana vitrectomy, methylated collagen gel was injected intravitreally. The eyes were examined clinically; electroretinogram recordings were made before and after surgery. Vitreous samples were taken for immunological analysis for the presence of the injected collagen. The rabbits were sacrificed 6 months after surgery; the retina was evaluated by light microscopy. Anterior chamber: In another group of rabbits, methylated collagen gel (0.2 ml, 0.1 ml, or 0.05 ml) was injected into the anterior chamber after paracentesis. The eyes were examined with a slit lamp; intraocular pressure was measured postinjection. The rabbits were sacrificed after 4 months; the corneas were evaluated histologically. RESULTS: Vitreous cavity: The fundus view was clear for 6 months after intravitreal injection. Scotopic and photopic electroretinograms were normal in 6/7 eyes; one eye experienced a mild decrease one month postoperatively. No abnormal changes were found in the retinal histology. Anterior chamber: Some corneas were hazy and edematous around the injection site for one week. The injected collagen appeared in bundles, patches, and little pieces in the anterior chamber with precipitates on the corneal endothelium, pupillary margin, and the anterior capsule of the lens. The collagen diminished gradually, without causing permanent opacity. Histologically, the corneal endothelium in the eye which received 0.2 ml collagen showed a mild distention of the mitochondriae and vesicle formation between endothelial cells under transmission electron microscope. CONCLUSION: Methylated collagen gel was tolerated by the eye after intravitreal injection. Localized temporary clinical and mild ultrastructural corneal changes were observed after anterior chamber injection.
Endothelial receptor tyrosine kinases may play important roles in pathological vascular growth, particularly in tumours. In this study, immunohistochemistry was used to evaluate the expression of a novel endothelial receptor tyrosine kinase, Tie2/Tek, in the endothelium of vascular 'hotspots' in normal breast tissue (n = 10), benign breast lesions (n = 10) and in breast tumours (n = 123). Tie2 expression was detected in the endothelium of all breast tissues examined. However, the strongest expression of Tie-2 was seen in vascular 'hot spots' within the inflammatory infiltrate at the periphery of invasive tumours. Moreover, the proportion of Tie2-positive vessels (Tie2 counts/CD31 counts) was significantly higher in breast tumours than the proportion of Tie2-positive vessels in either normal breast tissue or benign breast lesions (P = 0.004 and 0.0001 respectively). These data are consistent with a role for Tie2 in tumour angiogenesis and demonstrate the potential use of Tie2 expression as a novel marker of the tumour vasculature.
We studied whether anuric subjects on continuous ambulatory peritoneal dialysis (CAPD) who achieve the target Kt/V urea of 2.0 weekly will also achieve the target normalized creatinine clearance (NCCr) of 60 liter/1.73 m2 weekly, and the reasons of discrepancy between the two clearances in anuric subjects, by analyzing 476 clearance studies performed in 309 CAPD patients within 12 months of the performance of a peritoneal equilibration test (PET). On the basis of the PET, peritoneal solute transport was classified as low (37 clearance studies), low-average (199 studies), high-average (186 studies) and high (54 studies). We found that weekly values of Kt/V urea in the low transport group (LTG) was 1.74 +/- 0.51, in the low-average transport group (LATG) was 1.66 +/- 0.41, in the high-average transport group (HATG) 1.68 +/- 0.41, and in the high transport group (HTG) 1.73 +/- 0.46 (NS, variance analysis). Weekly values for NCCr, liter/1.73 m2 were: LTG, 37.8 +/- 9.0; LATG, 44.0 +/- 9.2; HATG, 49.2 +/- 10.0; HTG 56.8 +/- 13.3 (P < 0.0001). The ratios of raw (not-normalized) peritoneal creatinine clearance to peritoneal urea clearance were: LTG, 0.65 +/- 0.14; LATG, 0.76 +/- 0.09; HATG, 0.84 +/- 0.09; HTG, 0.91 +/- 0.12 (P < 0.0001). Linear regression with Kt/V urea as x and NCcr as y revealed the following results: LTG, y = 19.486 + 10.500x, r = 0.591 [if x = 2.0, y = 15.004 + confidence interval (95% CI) of y 25.3 to 55.7]; LATG, y = 15.0004 + 17.482x, r = 0.774 (if x = 2.0, y = 50.0, 95% CI of y 38.4 to 61.6); HATG, y = 15.285 + 20.162x, r = 0.829 (if x = 2.0, y = 55.6, 95% CI of y 44.4 to 66.8); HTG, y = 14.945 + 24.134x, r = 0.839 (if x = 2.0, y = 63.2, 95% CI of y 48.4 to 78.1). Peritoneal solute transport type has a major effect on peritoneal creatinine clearance, but an insignificant effect on peritoneal urea clearance. Consequently, the majority of anuric patients who achieve a weekly Kt/V urea of 2.0 will have a weekly NC cr lower than 60 liter/1.73 m2 and will require a Kt/V urea much higher than 2.0 to achieve the target NCcr of 60 liter/1.73 m2 weekly. The current targets of urea and creatinine clearance are not compatible in anuric patients on CAPD.
A retrospective study was conducted in 93 patients (55 adults and 38 children) with classical focal segmental glomerulosclerosis drawn from the Toronto Glomerulonephritis Registry. The average follow-up period was 11 years, with a cumulative experience of 1,053 patient-years. Both adults and children were similar in profile at the time of entry, except that the nephrotic syndrome was more common in children (55% of adults v 76% of children; P < 0.05). During evolution of the disease, however, the percentages became very similar with 82% of adults and 89% of children developing nephrotic-range proteinuria. At the last observation point, the outcome of patients (adults v children) was complete remission, 22% versus 42%; end-stage renal disease, 42% versus 34%; chronic renal insufficiency, 13% versus 11%; and persisting abnormality, 24% versus 13%. Although there were more children than adults in complete remission, the rate was equal in the treated adults compared with the treated children (44% v 47%). Although optimal duration of steroid therapy cannot be determined by this review, treatment beyond 6 months does not appear to be beneficial. The best guide to prognosis remains complete remission, since long-term renal survival in both age groups with this event was 100%. Those without a complete remission generally progress, although even at 10 years the survival rate is 62% in adults and 58% in children.