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Biomedical subjects

R Joshi

Publications and source records attributed to R Joshi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography.

We report a series of studies that assess the feasibility and sensitivity of imaging of herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression with [124I]-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil ([124I]-FIAU) and positron emission tomography (PET) and the ability of [124I]-FIAU-PET imaging to discriminate different levels of HSV1-tk gene expression. Studies were performed in rats bearing multiple s.c. tumors derived from W256 rat carcinoma and RG2 rat glioma cells. In the first set, we tested the sensitivity of [124I]-FIAU-PET imaging to detect low levels of HSV1-tk gene expression after retroviral-mediated gene transfer. HSV1-tk gene transduction of one of preestablished wild-type W256 tumor in each animal was accomplished by direct intratumoral injection of retroviral vector-producer cells (W256-->W256TK* tumors). Tumors produced from W256 and W256TK+ cells served as the negative and positive control in each animal. Highly specific images of [124I]-FIAU-derived radioactivity were obtained in W256TK* tumors (that were transduced in vivo) and in W256TK+ tumors but not in nontransduced wild-type W256 tumors. The level of "specific" incorporated radioactivity in transduced portions of both W256TK* and W256TK+ tumors was relatively constant between 4 and 50 h. In the second set, we tested whether [124I]-FIAU and PET imaging can measure and discriminate between different levels of HSV1-tk gene expression. Multiple s.c. tumors were produced from wild-type RG2 cells and stably transduced RG2TK cell lines that express different levels of HSV1-tk. A highly significant relationship between the level of [124I]-FIAU accumulation [% injected dose/g and incorporation constant (Ki)] and an independent measure of HSV1-tk expression (sensitivity of the transduced tumor cells to ganciclovir, IC50) was demonstrated, and the slope of this relationship was defined as a sensitivity index. We have demonstrated for the first time that highly specific noninvasive images of HSV1-tk expression in experimental animal tumors can be obtained using radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a clinical PET system. The ability to image the location (distribution) of gene expression and the level of expression over time provides new and useful information for monitoring clinical gene therapy protocols in the future.

Animals↗
PubMed1998

Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been investigated as a potent mediator of brain tumor angiogenesis and tumor growth. We evaluated the effect of VEGF expression on the pathophysiology of tumor growth in the brain. Human SK-MEL-2 melanoma cells, with minimal VEGF expression, were stably transfected with either sense or antisense mouse VEGF cDNA and used to produce intracerebral xenografts. Vascular permeability, blood volume, blood flow, and tumor fluorodeoxyglucose metabolism were assessed using tissue sampling and quantitative autoradiography. Tumor proliferation was assessed by measuring bromodeoxyuridine labeling indices. Tumor vascular density and morphological status of the blood-brain barrier were evaluated by immunohistochemistry. SK-MEL-2 cells transfected with sense VEGF (V+) expressed large amounts of mouse and human VEGF protein; V+ cells formed well-vascularized, rapidly growing tumors with minimal tumor necrosis. V+ tumors had substantial and significant increases in blood volume, blood flow, vascular permeability, and fluorodeoxyglucose metabolism compared to wild-type and/or V- (antisense VEGF) tumors. VEGF antisense transfected V- expressed no detectable VEGF protein and formed minimally vascularized tumors. V- tumors had a very low initial growth rate with central necrosis; blood volume, blood flow, vascular permeability, and glucose metabolism levels were low compared to wild-type and V+ tumors. A substantial inhibition of intracerebral tumor growth, as well as a decrease in tumor vascularity, blood flow, and vascular permeability may be achieved by down-regulation of endogenous VEGF expression in tumor tissue. VEGF-targeted antiangiogenic gene therapy could be an effective component of a combined strategy to treat VEGF-producing brain tumors.

Animals↗
PubMed1998

Labor ward workload waxes and wanes with the lunar cycle, myth or reality?

Objective: To test the validity of the statement "We are busy because it is getting close to the full moon" often heard on labor ward, by analysis of birth statistics in relation to lunar cycles.Method: Data for births from spontaneous onset labors for 12 lunar cycles from January 1 to December 31, 1994 was analyzed. Births resulting from induced labors were excluded. Birthrate for each day of the lunar cycle from new moon to full moon (ascending lunar phase) and from full moon to new moon (descending lunar phase) were analyzed using Pearson correlation coefficient. Birthrate at full moon was compared to that at new moon and that at mid ascending lunar phase was compared with that at mid descending lunar phase using t test.Results: There were 3706 spontaneous births during the study period. The average daily birthrate was 10.58 with standard deviation (SD) of 1.27. There was no statistically significant difference in the daily birthrate between the ascending and the descending lunar phases, r = -0.21. Statistical analysis showed no significant difference in the number of births at full moon as compared to that at new moon, P =.44. No difference was found on comparison of number of births during the mid ascending phase to that at the mid descending lunar phase, P =.84.Conclusion: Scientific analysis of data does not support the belief that the number of births increases as the full moon approaches, therefore it is a myth not reality.

Journal Article↗
PubMed1998

Bilirubin as an anti precipitant against copper mediated denaturation of bovine serum albumin: formation of copper-bilirubin complex.

BR forms a beautiful 1:1 greenish complex with Cu2+, having a characteristic absorption maximum at 343 nm. To our knowledge, this is the first metal complex of bilirubin in aqueous solution so far to be reported. It has also been shown that bilirubin (BR) at a concentration more than protein binding capacity has a definite role as an anti precipitant of bovine serum albumin by excess copper. At a concentration of 1 x 10(-3) moll-1 of the Cu-BR complex, the colour becomes greenish black. The rate of formation of this Cu-BR complex when BR extracts copper from copper-albumin complex as obtained in our experiment is 34.981 mol-1 s-1. The Cu-BR complex is stable at a pH ranging from 3.5 to 13.2, and also can scavenge radicals like CCl3OO., eaq- and OH.. Addition of excess copper sulfate to the solution of this complex causes a greenish black precipitate which can be re dissolved in HCl but insoluble in 99% ethanol. The complex does not give positive test in Gmelin reaction for bile pigments. The fluorescence spectrum of the complex in solution exhibits a peak at 450 nm when excited at 343 nm. The precipitated complex is insoluble in a number of solvents like ether, xylene, benzene, acetone, chloroform-methanol mixture and DMSO. These results show that BR may protect mammals from copper poisoning.

Animals↗
PubMed1998

In vivo properties of an in situ forming gel for parenteral delivery of macromolecular drugs.

PURPOSE: This study characterizes the in vivo properties of an in situ forming gel, comprising of IPC of water-soluble polymers, PMA and PEG, for sustained release of macromolecular drugs. METHODS: 40, 50, or 60% w/v formulations were injected subcutaneously in a rat model either alone, or containing model macromolecules, 3A2-ATG-psODN or REV-psODN, to (i) determine the approximate gelling and residence time of the gel at the site of injection (ii) assess the biological efficacy of the formulation using a MZ sleep time model and (iii) demonstrate specificity of the sequence and selectivity of the psODNs by measuring changes in microsomal enzyme levels and urine volumes. RESULTS: A sol to gel transition requires 15 min in vivo, and the 60% w/v IPC gel remains at the site of injection for up to 72 hr. The MZ sleep times and CYP3A2 expression due to 3A2-ATG-psODNs released from the gel are significantly different compared to that of REV-psODNs. CONCLUSIONS: The IPC solutions exhibit phase transformation in vivo. and demonstrate no evidence of toxicity. The pharmacological effects observed from the of release of 3A2-ATG-psODNs suggest that the formulation can entrap, protect, and sustain the delivery of macromolecules. .

Animals↗
PubMed1998

External hydrocephalus: a report of 16 cases from Oman.

Sixteen cases of external hydrocephalus (EH) were seen from January 1993 to June 1995. There were 13 (81 per cent) male and three female children. Fourteen (88 per cent) were under 12 months of age. Three siblings with EH were seen in one family. All, but three recovered over time without medical or surgical intervention. These three needed cerebral decongestants in the acute phase. This is the first report of EH from Oman.

Cephalometry↗
PubMed1997

Synthetic peptides corresponding to a repetitive sequence of malarial histidine rich protein bind haem and inhibit haemozoin formation in vitro.

Synthetic peptides containing a repetitive hexapeptide sequence (Ala-His-His-Ala-Ala-Asp) of malarial histidine-rich protein II were evaluated for binding with haem in vitro. The pattern of haem binding suggested that each repeat unit of this sequence provides one binding site for haem. Chloroquine inhibited the haem-peptide complex formation with preferential formation of a haem chloroquine complex. In vitro studies on haem polymerisation showed that none of the peptides could initiate haemozoin formation. However, they could inhibit haemozoin formation promoted by a malarial parasite extract, possibly by competitively binding free haem. These results indicate this hexapeptide sequence represents the haem binding site of the malarial histidine-rich protein and possibly the site of nucleation for haem polymerisation.

Amino Acid Sequence↗
PubMed1997

Hydrated Electrons in a Quaternary Microemulsion System: A Pulse Radiolysis Study

Using the technique of pulse radiolysis, hydrated electrons have been produced and studied in quaternary microemulsion (sodium lauryl sulfate (NaLS)/water/cyclohexane/1-pentanol) system. Remarkably high lifetimes ( approximately 20 &mgr;s) for hydrated electrons have been obtained. In general, these are two orders of magnitude higher than those reported earlier in reverse micelles. The water droplet sizes and location of the probes have been determined from the decay kinetics of hydrated electrons. The yields and half-lives (t 1/2 ) of the hydrated electrons vary smoothly as the water droplet sizes are changed. We believe that these studies will be useful not only in interpreting electron transfer reactions occurring in small water pockets in biological systems but also in the production of metal nanoclusters by radiation chemical method.

Journal Article↗
PubMed1997

The use of adhesive metal-ceramic restorations as an alternative to conventional crown and bridge materials.

A compromise is often necessary when choosing the most appropriate material in the construction of crowns and bridges. The most commonly used material is porcelain fused to metal since it is aesthetic and has acceptable physical characteristics to be used in the restoration of both anterior and posterior teeth. Unfortunately, to achieve a predictable and durable result extensive tooth preparation is invariably necessary. More conservative alternatives such as dentine-bonded crowns may have inferior physical characteristics and allow less predictable control over the occlusal contour. This paper describes the construction of fixed restorations which use both lost wax and refractory die techniques in their construction. This results in a restoration which has the combined advantages of both traditional porcelain fused to metal and dentine-bonded crowns and bridges.

Adhesiveness↗
PubMed1997

Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions.

The goal of this study was to evaluate the differences and define the advantages of imaging experimental brain tumors in rats with two nonmetabolized amino acids, 1-aminocyclopentane carboxylic (ACPC) acid and alpha-aminoisobutyric (AIB) acid compared with imaging with fluorodeoxyglucose (FDG) or the gallium-diethylenetriaminepentaacetic acid chelate (Ga-DTPA). 1-aminocyclopentane carboxylic acid, AIB, and FDG autoradiograms were obtained 60 minutes after intravenous injection to simulate positron emission tomography (PET) imaging, whereas the Ga-DTPA autoradiograms were obtained 5 or 10 minutes after injection to simulate gadolinium (Gd)-DTPA-enhanced magnetic resonance (MR) images. Three experimental tumors were studied (C6, RG2, and Walker 256) to provide a range of tumor types. Triple-label quantitative autoradiography was performed, and parametric images of the apparent distribution volume (Va, mL/g) for ACPC or AIB, relative glucose metabolism (R, micromol/100 g/min), vascular permeability to Ga-DTPA (K1, microL/min/g), and histology were obtained from the same tissue section. The four images were registered in an image array processor, and regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images. A comparative analysis of all measured values was performed. The location and morphologic characteristics of the tumor had an effect on the images and measurements of Va, R, and K1. Meningeal extensions of all three tumors consistently had the highest amino acid uptake (Va) and vascular permeability (K1) values, and subcortical portions of the tumors usually had the lowest values. Va and R (FDG) values generally were higher in tumor regions with high-cell density and lower in regions with low-cell density. Tumor areas identified as "impending" necrosis on morphologic criteria consistently had high R values, but little or no change in Va or K1. Tumor necrosis was seen consistently only in the larger Walker 256 tumors; low values of R and Va for AIB (less for ACPC) were measured in the necrotic-appearing regions, whereas K1 was not different from the mean tumor value. The highest correlations were observed between vascular permeability (K1 for Ga-DTPA) and Va for AIB in all three tumors; little or no correlation between vascular permeability and R was observed. The advantages of ACPC and AIB imaging were most convincingly demonstrated in C6 gliomas and in Walker 256 tumors. 1-aminocyclopentane was substantially better than FDG or Ga-DTPA for identifying tumor infiltration of adjacent brain tissue beyond the macroscopic border of the tumor; ACPC also may be useful for identifying low-grade tumors with an intact blood-brain barrier. Contrast-enhancing regions of the tumors were visualized more clearly with AIB than with FDG or Ga-DTPA; viable and necrotic-appearing tumor regions could be distinguished more readily with AIB than with FDG. [11C]-labeled ACPC and AIB are likely to have similar advantages for imaging human brain tumors with PET.

Aminoisobutyric Acids↗
PubMed1997

Administration to innovation: the evolving management challenge in primary care.

The concept of the primary health-care team involving an increasingly diverse range of health care professionals is widely recognized as central to the pursuit of a primary care-led health service in the UK. Although GPs are formally recognized as the team leaders, there is little by way of policy prescription as to how team roles and relationships should be developed, or evidence as to how their roles have in fact evolved. Thus the notion of the primary health-care team while commonly employed, is in reality lacking definition with the current contribution of practice managers to the operation of this team being poorly understood. Focusing on the career backgrounds of practice managers, their range of responsibilities, and their involvement in innovation in general practice, presents a preliminary account of a chief scientist office-funded project examining the role being played by practice managers in primary health-care innovation. More specifically, utilizing data gained from the ongoing study, contextualizes the role played by practice managers in the primary health-care team. By exploring the business environment surrounding the NHS general practice, the research seeks to understand the evolving world of the practice manager. Drawing on questionnaire data, reinforced by qualitative data from the current interview phase, describes the role played by practice managers in differing practice contexts. This facilitates a discussion of a set of ideal type general practice organizational and managerial structures. Discusses the relationships and skills required by practice managers in each of these organizational types with reference to data gathered to date in the research.

Community Health Services↗
PubMed1997

Continuous midazolam infusion as treatment of status epilepticus.

In a tertiary referral centre, midazolam infusion was tried as treatment for 20 children with status epilepticus over a period of two years. The mean age of the children was 4.07 years. Twelve children with refractory status epilepticus had received intravenous or per rectal diazepam and intravenous phenytoin/ phenobarbitone or both before midazolam was given (0.15 mg/kg bolus followed by 1-5 micrograms/kg/min infusion). Eight children required only midazolam to control the established status epilepticus. The seizures were controlled in 19 children. The mean time required for complete cessation of seizures was 0.9 hours. The mean infusion rate required was 2.0 micrograms/kg/min. All children had regained full consciousness by a mean of 5.1 hours after discontinuation of midazolam treatment. No metabolic derangement or compromise of vital functions was noted in any of the children. Midazolam infusion is thus an effective and safe therapeutic approach for the management of childhood status epilepticus.

Adolescent↗
PubMed1997

Wear now? An update on the etiology of tooth wear.

Tooth wear is an ever-increasing problem, and younger patients are particularly at risk. The problem is likely to continue as patients' demands and expectations rise and as more natural teeth are retained into old age. The etiology of tooth wear is reviewed, with emphasis on those factors that appear to be major contributors to the problem at the moment. The clinical appearance of tooth wear is also discussed. It would appear that erosive factors are a significant cause of tooth wear. The prominence of acidic damage of tooth tissue is probably a reflection of society's concern with healthy eating and appearance.

Humans↗
PubMed1996

Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy.

Noninvasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is possible with a clinical gamma camera and by single-photon emission tomography (SPECT) using 131I-labeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil (FIAU). Studies were performed in rats bearing s.c. tumors. Tumors were produced by injection of wild-type RG2 glioma or W256 mammary carcinoma cells into one flank and RG2TK+ glioma or W256TK+ mammary carcinoma cells (that had been transduced in vitro with the HSV1-tk gene) into the opposite flank. In some animals, HSV1-tk gene transduction of the pre-established wild-type tumors was accomplished in vivo by direct intratumoral injection of retroviral vector-producer cells. Imaging studies were performed 2 weeks after tumor transduction to allow time for production and spread of the retroviruses through the tumor and for sufficient growth and increase in size of the tumors to facilitate imaging. The gamma camera and SPECT images revealed highly specific localization of [131I]FIAU-derived radioactivity to areas of HSV1-tk gene expression at 24, 36, and 48 h after i.v. administration of 1.6-2.8 mCi of [131I]FIAU. Comparative analysis of quantitative autoradiographic images obtained from the same tumors confirmed that the high levels of [131I]FIAU-derived radioactivity (> 1% dose) were localized to areas of HSV1-tk gene expression demonstrated by immunohistochemical staining for HSV1-tk protein. In contrast, significantly lower levels of [131I]FIAU-derived radioactivity (< 0.01%) were observed in the surrounding nontransduced tumor tissue, contralateral wild-type tumors, and other tissues that showed no immunohistochemical staining for the HSV1-tk protein. The magnitude of FIAU accumulation in RG2TK+, W256TK+, and wild-type tumors corresponded to the in vitro ganciclovir sensitivity of the cell lines used to produce these tumors, which indicates that the magnitude of FIAU accumulation reflects the level of HSV1-tk gene expression. We suggest that "clinically relevant" levels of HSV1-tk gene expression in transfected tissue can be imaged with [131I]FIAU and a gamma camera or SPECT, and that a significant improvement in imaging sensitivity and resolution is expected with [124I]FIAU and PET.

Animals↗
PubMed1996

Circadian variation in sudden cardiac death: effects of age, sex, and initial cardiac rhythm.

STUDY OBJECTIVE: Previous studies based on data obtained from vital statistics records have demonstrated circadian variation in the occurrence of sudden cardiac death. The purpose of this study was to examine the effects of age, sex, and initial cardiac rhythm on circadian variability in sudden cardiac death. METHODS: This study employed a retrospective analysis of the records of adult patients with witnessed cardiac arrest who underwent resuscitation in an urban paramedic system during a 5-year period. RESULTS: The records of 2,250 consecutive patients with witnessed cardiac arrest were reviewed. Spectral analysis was used to decompose the data into frequency components. A circadian variation in the occurrence of sudden cardiac death was demonstrated, with a low occurrence rate between midnight and 6 AM and a 2.4-fold increase between the rate at 6 AM and the rate at noon. The same circadian pattern was noted among both men and women, among both patients aged 18 to 70 and those older than 70 years, and among patients with various initial cardiac arrest rhythms (ventricular tachycardia or fibrillation, asystole, and electromechanical dissociation). However, the outcome of resuscitation in these patients (ie, the rate of successful resuscitation and the rate of survival) did not demonstrate circadian variation. CONCLUSION: Witnessed out-of-hospital sudden cardiac death demonstrated circadian variation, and this variability was observed regardless of the patient's age, sex, or initial cardiac arrest rhythm. The outcome of resuscitation did not show circadian variability. These results suggest a common pathophysiologic mechanism leading to sudden cardiac death.

Adolescent↗
PubMed1996

Cardiac manifestations of Lyme disease: a review.

OBJECTIVE: To describe the clinical features of cardiac manifestations of Lyme disease, the most common vector-borne illness in North America, which occasionally results in cardiac involvement. DATA SOURCES: A review of the English-language clinical literature pertaining to Lyme disease and Lyme carditis indexed in MEDLINE from 1975 to 1995. DATA EXTRACTION: Studies describing diagnosis, clinical features, treatment or outcome were reviewed. DATA SYNTHESIS: Cardiac complications of Lyme disease may occur in up to 8% of patients. Cardiac manifestations occur in the early phase of the illness, at a median of 21 days from the onset of erythema migrans. Manifestations of Lyme carditis include atrioventricular block, myopericarditis, intraventricular conduction disturbances, bundle branch block and congestive heart failure. Temporary cardiac pacing may be required in up to a third of cases and complete recovery occurs in most (greater than 90%) patients. The overall prognosis of Lyme carditis is very good, although recovery may be delayed and late complications such as dilated cardiomyopathy may occur. CONCLUSION: Lyme disease is a tick-borne spirochetal infection caused by Borrelia burgdorferi. Cardiac complications of Lyme disease generally occur in the early phase and include conduction system disturbances, myopericarditis and congestive heart failure.

Anti-Bacterial Agents↗