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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 235 records · Page 13Linked to original sources
PubMed1997

Physician rewards for different kinds of service: the RBRVS versus the CPR system.

The resource-based relative value scale (RBRVS) was introduced in 1992 by Medicare for payments to physicians. This replaced the previous system based on the physician's customary, prevailing, and reasonable (CPR) charges. This paper analyzes the RBRVS from two perspectives: (1) the economic logic of the system and (2) how it functions differently from the CPR system in practice. As a social pricing system, it can make sense under certain conditions. However, when we provided a test for a New York plastic surgeon of the alleged underpricing of evaluative relative to procedural services under CPR, we found evidence to the contrary.

Fees, Medical↗
PubMed1997

Polymorphic N-acetyltransferase (NAT2) genotyping of Emiratis.

Polymorphic N-acetyltransferase (NAT2) genotypes were determined in 106 unrelated Emiratis by PCR-RFLP analysis to obtain estimates of allele frequencies. Thirteen different genotypes were found, four associated with the rapid acetylator phenotype and nine with the slow acetylator phenotype. Among 67 phenotypically slow acetylators, there was 100% concordance between phenotype and genotype. Among 39 phenotypically rapid acetylators, 37 possessed at least one wild type allele; a 95% concordance with genotype. Seven different NAT2 alleles associated with slow acetylation were found. The commonest was a NAT2*5 type (C481T) allele which occurred with a frequency of 0.53, a significantly higher frequency than has been reported for other ethnic groups. A second slow allele, a NAT2*6 type (G590A), occurred with a frequency of 0.21. The most common genotypes found were NAT2*5/*5 homozygotes, NAT2*5/*6 heterozygotes and NAT2*4/*5 heterozygotes with frequencies of 0.25, 0.25 and 0.22 respectively. The high overall prevalence of alleles associated with slow acetylation (173/212; 81.6%) among Emiratis is consistent with previously reported high frequency of the slow acetylator phenotype in Arabs. Two apparently new slow alleles were identified but have not yet been fully characterized. One appears to be a NAT2*5 variant allele. The other uncharacterized allele appears likely to contain an entirely new mutation associated with slow acetylation.

Alleles↗
PubMed1997

Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr.

The vpr gene product of human immunodeficiency virus type 1 (HIV-1) is a virion-associated protein that is essential for efficient viral replication in monocytes/macrophages. Vpr is primarily localized in the nucleus when expressed in the absence of other viral proteins. Vpr is packaged efficiently into viral particles through interactions with the p6 domain of the Gag precursor polyprotein p55gag. We developed a panel of expression vectors encoding Vpr molecules mutated in the amino-terminal helical domain, leucine-isoleucine (LR) domain, and carboxy-terminal domain to map the different functional domains and to define the interrelationships between virion incorporation, nuclear localization, cell cycle arrest, and differentiation functions of Vpr. We observed that substitution mutations in the N-terminal domain of Vpr impaired both nuclear localization and virion packaging, suggesting that the helical structure may play a vital role in modulating both of these biological properties. The LR domain was found to be involved in the nuclear localization of Vpr. In contrast, cell cycle arrest appears to be largely controlled by the C-terminal domain of Vpr. The LR and C-terminal domains do not appear to be essential for virion incorporation of Vpr. Interestingly, we found that two Vpr mutants harboring single amino acid substitutions (A30L and G75A) retained the ability to translocate to the nucleus but were impaired in the cell cycle arrest function. In contrast, mutation of Leu68 to Ser resulted in a protein that localizes in the cytoplasm while retaining the ability to arrest host cell proliferation. We speculate that the nuclear localization and cell cycle arrest functions of Vpr are not interrelated and that these functions are mediated by separable putative functional domains of Vpr.

Amino Acid Sequence↗
PubMed1997

Chest teleradiology in a teaching hospital emergency practice.

OBJECTIVE: New standards for hospital accreditation and health care reimbursement may require that faculty subspecialists be more available after regular working hours to supervise residents in academic radiology departments. We designed a receiver operating characteristic study to determine whether a thoracic radiologist who evaluated computed radiography (CR) images of the chest at a home-based teleradiology workstation could add significant value to a junior resident's interpretations of films within the hospital for acutely ill patients. SUBJECTS AND METHODS: Using a hybrid cassette, we obtained analog chest films and CR images simultaneously for each of 252 acutely ill patients in the emergency department and in an intensive care unit. Interpretations of the analog films by three first-year residents were analyzed for 11 parameters deemed critical for patient management. Likewise, CR images of the same chest studies were viewed on a home teleradiology workstation by a faculty thoracic radiologist who analyzed the images for these 11 interpretive parameters. All interpretations by radiology residents and by the home-based thoracic radiologist were then compared with the interpretations of a consensus panel consisting of another thoracic radiologist and a full-time emergency department radiologist. RESULTS: Analysis of the pooled results from the three junior residents as a group failed to show significant differences between their interpretations of chest films and the interpretations of CR images by a thoracic radiologist at a home workstation. However, we observed significant differences for several image interpretation parameters between individual residents and the home-based radiology subspecialist. CONCLUSION: The data confirm that significant value can be added to the interpretations of chest films by individual junior residents when a home-based thoracic radiologist uses teleradiology to provide expert interpretations. Accordingly, it is reasonable to infer that on-line supervision by faculty subspecialists via teleradiology could be used to complement the scheduled visits that are being made now by individual faculty members of our institution to interpret films periodically with a radiology resident during overnight and weekend periods.

Emergency Service, Hospital↗
PubMed1997

Cerebral venography: comparison of CT and MR projection venography.

OBJECTIVE: The purpose of the study was to show equivalence or superiority of CT venography compared with the existing test of choice--MR venography--in the evaluation of dural sinus thrombosis and in the identification of cerebral veins and dural sinuses. MATERIALS AND METHODS: Twenty-four patients underwent both CT and MR venography of the intracranial venous circulation. Seventeen patients were examined for suspected dural sinus thrombosis. Four patients underwent projection venography to assess tumor invasion of a major dural sinus. The remaining three patients were examined for cavernous sinus thrombosis, arteriovenous malformation, and an elevated jugular bulb. Without knowledge of the patients' case histories, two radiologists evaluated each CT venogram and MR venogram. The radiologists then arrived at a consensus regarding the absence or presence of dural sinus thrombosis. Later, the radiologists conducted a second interpretation with knowledge of the patients' clinical histories during which time MR and CT venograms were compared with regard to the advantages and disadvantages of each imaging technique. In addition, the venograms were assessed for the presence of 12 different venous structure. Projection venograms were displayed using a maximum-intensity-projection (MIP) algorithm, and the individual source images were also evaluated. The CT venograms were also displayed using shell-MIP and integral display algorithms. RESULTS: Using MR venography, the two radiologists diagnosed dural sinus thrombosis in eight of the 17 patients with suspected dural sinus thrombosis. In these eight patients, the diagnosis was also made with CT venography. The diagnosis was confirmed by follow-up CT in four patients and by follow-up MR imaging in two patients. The MIP algorithm did not allow direct visualization of thrombus by either the CT or the MR imaging technique; however, the CT integral display algorithm enabled direct visualization of thrombus on the three-dimensional projection venograms. The systematic comparison of imaging techniques showed that CT venography reliably reveals all cerebral veins and sinuses when they are seen with MR venography. In addition, CT venography more frequently visualizes sinuses or smaller cerebral veins with low flow as compared with MR venography. CONCLUSION: Cerebral CT venography is superior to MR venography in the identification of cerebral veins and dural sinuses and is at least equivalent in the diagnosis of dural sinus thrombosis. CT venography is a viable alternative to MR venography in the examination of patients with suspected dural sinus thrombosis.

Adult↗
PubMed1997

Neurokinin receptor inhibitors: fermentation, isolation, physico-chemical properties, structure and biological activity.

Seven neurokinin (NK) receptor inhibitors SCH 60059 (1), SCH 60065 (2), SCH 64879 (3), SCH 60061 (4), SCH 60063 (5), SCH 60057 (7), and SCH 64878 (9) and two uncharacterized components 6 and 8, were isolated from the fermentation broth of a fungus taxonomically classified as an Acremonium sp. These compounds were isolated from the fermentation broth by ethyl acetate extraction. Purification and separation of the individual compounds were achieved by NK1 and NK2 assay-guided fractionation using gel filtration, reverse phase chromatography and HPLC. The NK active compounds were identified to be a family of polyhydroxy isoprenoid derivatives, including glycosylated members, by spectroscopic and degradation studies. Compounds 1 approximately 5 and 7 contain nine isoprene units connected in head to tail fashion and compound 9 contains fifteen isoprene units connected in a similar manner. All these compounds showed dual inhibition in NK1 and NK2 assays with IC50 values ranging from 2.5 approximately 11 microM in the NK1 assay and 6.8 approximately 16 microM in the NK2 assay.

Acremonium↗
PubMed1997

Carotid artery stenosis: optimization of CT angiography with a combination of shaded surface display and source images.

PURPOSE: To evaluate the accuracy of CT angiography of occlusive disease of the carotid arteries using three-dimensional surface-rendered images alone and in conjunction with display of axial source images. METHODS: Forty-eight symptomatic patients had conventional angiography followed by CT angiography within 24 hours. Images of 96 carotid arteries were acquired using contrast-enhanced spiral CT. Image postprocessing was performed on a free-standing workstation to produce 3-D shaded surface display (SSD) images. Two readers independently evaluated the CT angiographic (SSD) images and then reevaluated each case while simultaneously reviewing the SSD and axial source images. Digital subtraction angiograms were evaluated in a separate session and eventually compared with CT angiograms. All evaluations were performed under blinded conditions to control for reader bias. RESULTS: SSD images alone underestimated stenosis relative to angiograms whereas combined SSD and axial images did not. CONCLUSION: SSD angiograms in conjunction with the source images are better than SSD images alone in estimating the degree of stenosis in carotid artery disease.

Adult↗
PubMed1997

Gastric Crohn's disease complicated by adenocarcinoma of the stomach: case report and review of the literature.

Patients with Crohn's disease are at increased risk for developing adenocarcinoma of the small bowel and colon. Although several cases of gastric malignancy have been reported in patients with Crohn's disease, the association remains controversial, particularly because most patients have not had gastric Crohn's involvement. We report a patient with long-standing Crohn's disease, with gastric involvement, who developed adenocarcinoma of the gastric outlet. We discuss the association and include a review of the literature.

Adenocarcinoma↗
PubMed1997

Interleukin-1 response to arterial antigen, lipopolysaccharide, and oxidized low density lipoprotein in ischemic heart disease.

UNLABELLED: Monocytes responding to oxidized low density lipoprotein (LDL) or other antigens may initiate atherogenesis through production of interleukin-1 (IL-1) and additional cytokines. Interleukin-1 is chemotactic for circulating leukocytes, can stimulate growth of fibroblasts or smooth muscle cells, and causes activation of T- and B-lymphocytes. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 42 patients with angiographically verified ischemic heart disease (IHD) and 35 age-matched control subjects without a history of cardiac disease. Rates of proliferation and production of IL-1 beta were measured after peripheral blood mononuclear cells were cultured for 7 days in the presence of mitogens, arterial antigen, lipopolysaccharide, or native and oxidized forms of LDL. RESULTS: In patients with IHD, proliferation in response to arterial antigen was either diminished or unchanged from control values. Peripheral blood mononuclear cells from IHD and control patients had similar levels of proliferation after treatment with different mitogens. Levels of IL-1 beta, produced after stimulation with arterial antigen or lipopolysaccharide, also did not differ for PBMCs obtained from control and IHD patients. For patients with either a stable angina pattern or no history of cardiac disease, PBMC cultured in the presence of native and oxidized forms of LDL released similar amounts of IL-1 beta. In contrast, PBMCs from 4 patients with unstable angina had increased levels of IL-1 beta after culture in the presence of oxidized LDL (group means +/- standard deviation of 1.63 +/- 1.08 pg/mL for 17 control patients, 0.96 +/- 0.23 pg/mL for 4 cases with stable angina, and 4.02 +/- 5.91 pg/mL, for 19 cases with unstable angina). These values reflect a greater than 5-fold increase in variability for IL-1 beta produced on exposure to oxidized LDL for patients with unstable angina relative to control patients. CONCLUSIONS: Effects of in vitro stimulation with mitogens or lipopolysaccharide are similar for PBMC obtained from normal or IHD patients. The response to arterial antigen is also not increased in cells from patients with IHD. However, PBMCs obtained from a subset of patients with unstable angina produce greater levels of IL-1 beta after treatment with oxidized, but not native, LDL.

Adult↗
PubMed1996

Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin.

Based on preliminary but variable results with direct DNA transfer into wounds, we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin to determine whether overexpression of TGF-beta1 at the site of skin incisions would result in a significant improvement in repair. Optimization of the method with viral promoter-luciferase reporter constructs indicated that expression of luciferase activity persisted up to 5 d and was promoter, pressure, and site dependent (ventral > dorsal). Using cytomegalovirus (CMV)-driven human alpha1-antitrypsin, transgene expression was immunolocalized within keratinocytes of the stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11-21 d in both normal and diabetic rats transfected with TGF-beta1 expression vectors at surgery. Native murine TGF-beta1 under an SV40 promoter produced positive effects, while wound strengthening was more pronounced in diabetic animals using a CMV-driven construct. Transfection of rat skin with constitutively active, mutant porcine TGF-beta1 under the control of the CMV and Moloney murine leukemia virus promoters significantly increased tensile strength up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more effective. Particle-mediated gene delivery can be used to deliver viral promoter-cytokine expression constructs into rat skin in a safe, efficient, and reproducible fashion. The extent of wound repair, as evidenced by enhanced tensile strength, can be markedly improved in tissues transfected with TGF-beta1 expression constructs.

Animals↗
PubMed1996

Cytotoxicity and DNA damage associated with pyrazoloacridine in MCF-7 breast cancer cells.

We examined the effects of pyrazoloacridine (PZA), an investigational anticancer agent in clinical trials, on cytotoxicity, DNA synthesis, and DNA damage in MCF-7 human breast carcinoma cells. With PZA concentrations ranging from 0.5 to 50 microM for durations of 3-72 hr, cytotoxicity increased in proportion to the total PZA exposure (concentration x time). Inhibition of DNA and RNA syntheses increased with increasing PZA concentration x time (microM.hr). A 24-hr exposure to 1 and 10 microM PZA reduced DNA synthesis to 62 and 5% of control, respectively, decreased the proportion of cells in S phase with accumulation of cells in G2 + M phase, and inhibited cell growth at 72 hr by 68 and 100%. Newly synthesized DNA was more susceptible to damage during PZA exposure, with subsequent induction of parental DNA damage. Significant damage to newly synthesized DNA as monitored by alkaline elution was evident after a 3-hr exposure to > or = 5 microM PZA. Longer PZA exposures (> or = 10 microM for 16 hr) were required to elicit damage to parental DNA. Induction of single-strand breaks in parental DNA correlated closely with induction of double-strand breaks and detachment of cells from the monolayer. PZA-mediated DNA fragmentation was not accompanied by the generation of oligonucleosomal laddering in MCF-7 cells, but induction of very high molecular weight DNA fragmentation (0.5 to 1 Mb) was detected by pulsed-field gel electrophoresis. In vitro binding of PZA to linear duplex DNA (1 kb DNA ladder) and closed, circular plasmid DNA was demonstrated by a shift in migration during agarose electrophoresis. PZA interfered with topoisomerase I- and II-mediated relaxation of plasmid DNA in a cell-free system, but the cytotoxic effects of PZA did not appear to involve a direct interaction with topoisomerase I or II (stabilization of the topoisomerase I- or II-DNA cleavable complex). PZA-mediated cytotoxicity correlated strongly with inhibition of DNA and RNA syntheses, and damage to both nascent and parental DNA. Neither the cytotoxicity of PZA nor induction of double-stranded DNA fragmentation was prevented by aphidicolin, indicating that PZA-mediated lethality occurred in the absence of DNA replication. Since free radical formation was not detected, induction of nascent and parental DNA damage appeared to be a consequence of the avid binding of PZA to DNA, presumably by interfering with the access of replication, repair, and transcription enzyme complexes.

Acridines↗
PubMed1996

Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America.

The silver-haired bat variant of rabies virus (SHBRV) has been identified as the etiological agent of a number of recent human rabies cases in the United States that are unusual in not having been associated with any known history of conventional exposure. Comparison of the different biological and biochemical properties of isolates of this virus with those of a coyote street rabies virus (COSRV) revealed that there are unique features associated with SHBRV. In vitro studies showed that, while the susceptibility of neuroblastoma cells to infection by both viruses was similar, the infectivity of SHBRV was much higher than that of COSRV in fibroblasts (BHK-21) and epithelial cells (MA-104), particularly when these cells were kept at 34 degrees C. At this temperature, low pH-dependent fusion and cell-to-cell spread of virus is seen in BHK-21 cells infected with SHBRV but not with COSRV. It appears that SHBRV may possess an unique cellular tropism and the ability to replicate at lower temperature, allowing a more effective local replication in the dermis. This hypothesis is supported by in vivo results which showed that while SHBRV is less neurovirulent than COSRV when administered via the intramuscular or intranasal routes, both viruses are equally neuroinvasive if injected intracranially or intradermally. Consistent with the above findings, the amino acid sequences of the glycoproteins of SHBRV and COSRV were found to have substantial differences, particularly in the region that contains the putative toxic loop, which are reflected in marked differences in their antigenic composition. Nevertheless, an experimental rabies vaccine based on the Pittman Moore vaccine strain protected mice equally well from lethal doses of SHBRV and COSRV, suggesting that currently used vaccines should be effective in the postexposure prophylaxis of rabies due to SHBRV.

Animals↗
PubMed1996

Preparation and structure-activity relationship of novel P1/P1'-substituted cyclic urea-based human immunodeficiency virus type-1 protease inhibitors.

A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

Azepines↗
PubMed1996

Cholesterol 7alpha-hydroxylase activities from human and rat liver are modulated in vitro posttranslationally by phosphorylation/dephosphorylation.

Purified cholesterol 7alpha-hydroxylases (C7alphaH) from human and rat liver microsomes, and from transformed Escherichia coli expression systems, were incubated with 0.3 mmol/L [gamma-32P] adenosine triphosphate (ATP) in the presence and absence of bacterial alkaline phosphatase (AP) or rabbit muscle adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. The amounts of 32P incorporation after separation of human and rat C7alphaH proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were related to C7alphaH catalytic activities (determined by a radioisotope incorporation method) and enzyme protein mass (determined by Western blotting and laser densitometry). Both human and rat C7alphaH activities significantly decreased after dephosphorylation by AP (-57% - -72%) and increased up to twofold with phosphorylation by rabbit muscle cAMP-dependent protein kinase. The increases in C7alphaH activities were proportional to the amounts of cAMP-dependent protein kinase used, and were coupled to 32P incorporation into the purified enzymes. Both the activation of C7alphaH and the amounts of 32P incorporation were time-dependent and reached a maximum after 1 hour of incubation with 5 U of cAMP-dependent protein kinase. In a second set of experiments, purified human and rat liver C7alphaH were dephosphorylated by 30-minute incubation with AP, followed by inactivation of the phosphatase by the inhibitor NaF, and rephosphorylation of C7alphaH by 30-minute incubation with rabbit muscle cAMP-dependent protein kinase or bovine heart cAMP-independent protein kinase. Rephosphorylation of the dephosphorylated C7alphaH proteins by cAMP-dependent protein kinase increased C7alphaH catalytic activities up to fourfold, and the stimulation in catalytic activities paralleled the increases in 32P incorporation into the purified enzymes. Bovine heart protein kinase was as potent as rabbit muscle cAMP-dependent protein kinase in stimulating catalytic activity and 32P incorporation into the human C7alphaH protein. Because the protein mass of these purified enzymes did not change, the short-term regulation or catalytic efficiency of C7alphaH (activity per protein mass unit) is modulated, in vitro, posttranslationally by a phosphorylation/dephosphorylation mechanism in both the human and the rat enzymes.

Adenosine Triphosphate↗