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Biomedical subjects

R Subramanian

Publications and source records attributed to R Subramanian.

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

RF microcoil design for practical NMR of mass-limited samples.

This paper addresses practical issues involved in obtaining high resolution 1H NMR spectra from samples containing less than 10 nmol. Solenoidal microcoils have been constructed to: (a) assess the effects of magnetic susceptibility mismatches at 500 MHz, (b) increase the concentration sensitivity of microcoil probes, (c) incorporate a lock channel for 2D experiments and long 1D acquisitions, and (d) assess the total amount of the sample required (with respect to the coil length) to avoid line broadening due to edge effects. Compared to previously published microcoil results, sample volumes have been increased by a factor of 20 with a concomitant decrease in the required concentration (5-20 mM). Perfluorocarbon susceptibility matching remained effective at 500 MHz, allowing acquisition of high resolution NMR spectra. A lock channel has also been successfully incorporated in microcoil probes. The limits of detection for sucrose with a 10 min acquisition time were found to be 17.8 and 34.1 pmol for the single and double resonance coils, respectively. A sample length of approximately 10 times than that of the coil was required to avoid magnetic susceptibility artifacts.

Artifacts↗
PubMed1998

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium Tc 99m 88BV59H21-2V67-66 (HumaSPECT-Tc), a totally human monoclonal antibody. Patient management benefit from a phase III multicenter study.

PURPOSE: The study contained herein was undertaken to evaluate the accuracy of radiolabeled human monoclonal antibody, 88BV59H21-2V67-66 (88BV59 or HumaSPECT-Tc), in predicting disease resectability in presurgical subjects with recurrent, metastatic, or occult colorectal carcinoma. METHODS: A total of 219 patients with disease visualized on computed tomographic scan (recurrent or metastatic disease) or with negative or equivocal computed tomographic scan and rising carcinoembryonic antigen serum levels (occult group) received technetium Tc99m-labeled 88BV59 intravenously. Planar and single photon emission computed tomograhic images were obtained 14 to 20 hours postinfusion, before surgery. The ability of computed tomographic and HumaSPECT-Tc imaging to define the extent of disease and to predict resectability was evaluated based on surgical and histopathologic results. RESULTS: In patients with recurrent or metastatic disease (170 evaluable patients), the accuracy of predicting nonresectability of disease was significantly greater (P < 0.001) for HumaSPECT-Tc than for computed tomography (60 vs 29 percent). Computed tomography understaged 41 percent of patients believed to have resectable disease compared with 27 percent for HumaSPECT-Tc (P < 0.001). In occult disease patients (29 computed tomographic and 28 HumaSPECT-Tc evaluable patients), the overall accuracy of predicting resectability/nonresectability was 6 percent for HumaSPECT-Tc compared with 24 percent from computed tomography. Administration of HumaSPECT-Tc had no effect on monoclonal antibody-based in vitro diagnostic assays. Only a single patient demonstrated an anti-antibody response (90 ng/ml) at nine weeks postinfusion. CONCLUSION: HumaSPECT-Tc was more accurate than computed tomography in determining disease resectability in patients with metastatic, recurrent, or occult cancer. The addition of HumaSPECT-Tc imaging can play a significant role in patient management decisions.

Adult↗
PubMed1998

Physician-hospital integration strategies: impact on physician involvement in hospital governance.

This study investigated the impact of three physician-hospital contractual arrangements (PHCAs)--joint ventures, management service organizations, and not-for-profit foundations--on physician involvement in hospital governance and physician-hospital relationships. Analysis of data collected from a national sample of 1,013 hospitals revealed that PHCAs generate greater physician involvement in hospital decision making and result in lower physician-hospital conflict.

Budgets↗
PubMed1998

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies.

PURPOSE: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.

Adult↗
PubMed1997

Pure versus hybrid: performance implications of Porter's generic strategies.

This article identifies the strategic types in the hospital industry based on the hospital's use of Porter's generic strategies in their pure and hybrid forms. The article also examines differences in performance of hospitals across strategic types. Results indicate that hospitals that follow a focussed cost leadership strategy, in general, have superior performance on a variety of performance measures, while hospitals that use a combination of cost leadership and differentiation perform the poorest. Implications of findings for hospital administrators are also discussed.

Cost Control↗
PubMed1997

Performance-oriented: toward a successful strategy.

Changes in the health care industry have profoundly affected hospital management and have caused severe declines in hospital profitability. In 1993, Health Care Management Review reported that the average operating profit margin, around 2% in 1984, had declined to a 0.2% loss by 1990. In the past, hospitals were buffered by entry regulations and cost reimbursement; thus, they rarely dealt with traditional market pressures. But the changed terrain means that competitive factors now underscore all strategic decisions. This study examines the strategic significance of market orientation in the health care industry. The authors identified forms of market orientation by emphasizing different components, and discovered that hospitals fell into four distinct clusters or groups. They also found a critical relationship between market orientation and performance scores on a number of criteria. Finally, the authors suggest that different forms of market orientation should be employed to target specific performance measures.

Economic Competition↗
PubMed1997

Preclinical studies of indium-111-labeled IgM: a human monoclonal antibody for infection imaging.

UNLABELLED: Indium-111-labeled plasma proteins, such as albumin, transferrin and IgG, have been proven useful to image infection. We reported previously that 111In-labeled human monoclonal antibody, IgM 16.88 (In-IgM) also would localize at the site of infection. However, the kinetics of blood clearance, distribution and infection uptake have not been investigated. We compared the kinetics of distribution and infection uptake of In-IgM 16.88 with that of in-polyclonal IgG in rats with focal infection. METHODS: Both IgM 16.88 and polyclonal IgG were labeled with 111In using a bifunctional chelating agent, LiLo. The labeling efficiency was > 95%. Focal infection was induced in rats by an intramuscular injection of E. Coli in the right thigh. In-IgM (30-40 microCi) was injected into five groups of rats (five rats/group). The rats were killed at 4, 8, 16, 24 and 36 hr. The percent injected dose (%ID) in blood, infection muscle, control muscle, liver, spleen and kidney were determined. Similar studies were performed with In-IgG. RESULTS: The In-IgM activity in blood at 4 hr postinjection was 27% which decreased to 2% by 36 hr. In contrast, the In-IgG blood activity was 40% at 4 hr and 20% at 36 hr. The infection/ muscle (I/M) ratios are higher with In-IgM at all time points postinjection compared to that of In-IgG. At 24 hr, the I/M ratio was 22 compared to 9 with In-IgG. At the same time point, the infection/ blood (I/B) ratio with In-IgM was 2.7 compared to only 0.8 with that of In-IgG. In-IgM was taken up mostly by the liver compared to diffuse abdominal uptake of IgG. CONCLUSION: These result indicate that In-IgM produces higher lesion to background ratio when compared to In-IgG and, therefore, is potentially useful to image infection in patients.

Animals↗
PubMed1996

Biodistribution of 111In-labelled IgG and IgM in experimental infection.

Both the protein used and the conjugation method are factors which may be relevant for targeting infection with 111In-labelled proteins. In this study, human immunoglobulin G (IgG), conjugated to either DTPA or LiLo, and LiLo conjugated human immunoglobulin M (IgM) were evaluated. In rats with Staphylococcus aureus calf muscle infection, biodistribution was determined 6, 24 and 48 h after the injection of 111In-DTPA-IgG, 111InLiLo-IgG or 111In-LiLo-IgM. Absolute abscess uptake of 111In-LiLo-IgG was significantly higher than that of 111In-DTPA-IgG (P < 0.05). Since blood clearance of 111In-LiLo-IgG was initially significantly slower (P < 0.01), the higher abscess uptake did not result in higher abscess-to-background ratios. 111In-LiLo-IgG accumulated to a greater extent in the liver (P < 0.001). 111In-DTPA-IgG showed higher uptake in the kidneys and bone marrow (P < 0.001 and P < 0.01, respectively). Although decreasing over time, 111In-LiLo-IgM showed reasonable abscess uptake and rapid blood clearance, resulting in higher abscess-to-background ratios compared with 111In-LiLo-IgG (P < 0.01). However, liver and spleen uptake were three- to four-fold higher than that of 111In-LiLo-IgG (P < 0.001). Compared with DTPA-conjugation, chelation with LiLo has a minor influence on abscess targeting of 111In-labelled IgG. However, differences in blood clearance and organ uptake do occur. 111In-LiLo-IgM shows high relative accumulation in abscesses as well as high liver and spleen uptake. 111In-LiLo-IgM appears promising for imaging infection outside the trunk region.

Animals↗
PubMed1995

Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

Adult↗
PubMed1995

A critical analysis of the anterior-posterior radiographic anatomy of the ankle syndesmosis.

To determine the normal anatomic radiographic land-marks of the ankle syndesmosis, standardized anterior-posterior radiographs of the right ankle were performed on 40 male and 40 female volunteers. The average tibiofibular clear space was 3.8 mm in females, 4.6 mm in males, and 4.2 mm overall. The tibiofibular overlap measured 6.0 mm in females, 9.6 mm in males, and 7.8 mm overall. Due to this variability and the gender differences, we investigated the anatomy of the syndesmosis as ratios of the potentially variable values to fixed landmarks. The ratio of the tibiofibular overlap to the fibular width averaged 54% and the ratio of the tibiofibular clear space to the fibular width averaged 30%, with no statistically significant difference due to gender. Our data show that for 90% prediction intervals, the values are: (1) tibiofibular clear space less than 5.2 mm in women and 6.5 mm in men; (2) tibiofibular overlap of greater than 2.1 mm in females and 5.7 mm in males; (3) tibiofibular overlap:fibular width ratio greater than 24%; (4) tibiofibular clear space:fibular width ratio less than 44%. Additionally, using a linear regression model, a prediction of the tibiofibular overlap can be made when using the distance (in millimeters) from the incisura fibularis to the lateral tibial (LT) border: tibiofibular overlap = 0.862 x lateral tibia - 2.62 (P = .0001). Utilization of these values will help in the determination of posttraumatic disruption of the syndesmosis and postoperative assessment of mortise reduction.

Adolescent↗
PubMed1995

The need for implementing TQM in the health care industry: an empirical investigation.

The U.S. health care industry is facing an era of increased competition, declining profits, decreed hospital utilization, and consolidation. By reviewing existing literature on the application of total quality management in the health care industry, and by surveying a hospital in which this technique has been recently applied, this paper shows that service providing organization can indeed use the same methods used by manufacturing organizations to increase quality.

Contract Services↗
PubMed1995

[Cervical lymph node metastases in unknown primary tumor. Follow-up of 58 patients].

Fifty-eight patients presenting with lymph node metastases of the head and neck were treated at the Bremen ENT Clinic from 1970 to 1988. In none of the patients could a primary tumor be detected despite extensive diagnostic procedures. The 5-year survival rate was 26.3%. During the further course of the disease, six primary tumors were detected in the following areas: nasopharynx (2 cases), soft palate, oesophagus, bronchi and kidney. Prognosis decreased with increasing tumor stages, although histological grading had no influence on prognosis. Supraclavicular localization and male sex were high risk factors. Prognosis was also not improved when ampiric irradiation also included the pharynx as a possible site of the primary tumor.

Female↗
PubMed1995

Preoperative scintigraphy and operative probe scintimetry of colorectal carcinoma using technetium-99m-88BV59.

UNLABELLED: We report a pilot study of radioimmunoscintigraphy (RIS) and operative gamma probe scintimetry (OPS) using a 99mTc-labeled anti-cytokeratin human monoclonal antibody (MAb) (99mTc-88BV59) in patients with newly diagnosed, recurrent or metastatic colorectal cancer. METHODS: Twelve presurgical patients with biopsy- or contrast radiographic-proven colorectal cancer or recurrent colorectal carcinoma were studied. After chest roentgenography and abdominopelvic CT, 99mTc-88BV59 was administered intravenously, planar and SPECT external imaging was performed 3 to 6 hr after injection and planar imaging was performed 18 to 24 hr after injection. Surgery was performed immediately after late planar imaging. OPS of a standardized list of sites to document background radiation activity and of tumor sites, resection margins and tumor beds was performed. RESULTS: The patients had 23 histologically proven tumor sites. Overall sensitivity for CT, planar RIS, SPECT, surgery and OPS was 43%, 61%, 78%, 96% and 91%, respectively. SPECT was superior to CT for imaging extrahepatic abdominal and pelvic disease. OPS detected all liver and extrahepatic abdominal tumor sites and correctly predicted histological tumor-free margins and tumor beds in all cases. OPS did not identify tumor deposits that the surgeon could neither see nor feel. No patient demonstrated human anti-human immune responsiveness 1 and 3 mo after 99mTc-88BV59 infusion. CONCLUSION: Technetium-99m-88BV59 is a safe, effective radioimmunoconjugate for colorectal cancer imaging, with superior sensitivity as compared to CT.

Aged↗
PubMed1994

Myocardial function and metabolism in pig hearts after relief from chronic partial coronary stenosis.

Metabolic behavior was compared during acute extracorporeal reperfusion after removal of a chronic 4-day partial coronary stenosis in eight pig hearts (RCS group) and during comparable extracorporeal perfusion in seven chronically prepared hearts (Sham group). Coronary stenosis in RCS hearts was induced in the left anterior descending (LAD) artery by partial inflation of a hydraulic occluder to restrict LAD peak phasic velocity by approximately 50%. Regional mechanical shortening was decreased in RCS compared with Sham hearts after 4 days of chronic coronary stenosis [diminished systolic shortening (P < 0.066) with systolic expansion (P < 0.015)] but was comparable to Sham hearts after relief from stenosis. At analogous workloads (left ventricular pressure and heart rate) during reperfusion, metabolic behavior was distinctive between groups. Specifically, compared with Sham hearts, myocardial O2 consumption was selectively increased in RCS hearts (+ 49 delta %, P < 0.026) as was fatty acid oxidation estimated from 14CO2 production from [U-14C]palmitate (+ 60 delta %, P < 0.061) and exogenous glucose utilization measured from the release of 3H2O from [5-3H]glucose (+ 517 delta %, P < 0.025). At the conclusion of the studies, triphenyltetrazolium chloride staining showed no gross evidence of macroinfarction in RCS or Sham hearts, and there was an essentially unremarkable histological survey of anterior myocardium for microscopic necrosis in either group. The level of O2 consumption and preservation of preferred fatty acid utilization indicate that metabolism remains or regains its aerobic pattern of activity in early recovery immediately after removal of chronic partial coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Characterization of thrombin receptor expression during vascular lesion formation.

Blood vessels respond to injury by initiating cell proliferation and migration that result in vascular lesion formation. To determine the roles of thrombin and the thrombin receptor in this process, we characterized thrombin receptor expression in normal and injured arteries, thrombin receptor-mediated smooth muscle cell mitogenesis, and the regulation of thrombin receptor mRNA expression in vitro. Thrombin receptor mRNA was not detected in normal rat or baboon arteries by in situ hybridization. Immunohistochemistry using an antithrombin receptor antibody (TR-R9), directed against the thrombin cleavage site of the rat aortic smooth muscle cell thrombin receptor, revealed low-level staining for thrombin receptor protein in endothelial cells and smooth muscle cells of normal arteries. In contrast, balloon catheter injury increased thrombin mRNA expression in medial smooth muscle cells within 6 hours. This increased thrombin receptor expression continued within the media and in neointimal cells throughout vascular lesion formation, predominantly in areas of active cell proliferation. In vitro, alpha-thrombin stimulates rat aortic smooth muscle cell proliferation in a concentration-dependent manner. That thrombin receptor activation is required for the mitogenic response was confirmed by demonstrating that the polyclonal antibody TR-R9 inhibits thrombin-induced cell proliferation. Thrombin receptor mRNA synthesis was induced by both basic fibroblast growth factor (maximal stimulation of 1.8-fold at 1 hour) and platelet-derived growth factor (maximal stimulation of 2.4-fold at 8 and 24 hours) in quiesced cultured rat aortic smooth muscle cells. In summary, upregulation of smooth muscle cell thrombin receptor expression occurs very early after vascular injury and continues throughout neointimal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty↗
PubMed1994

Collective bargaining practices in the health care industry: an empirical analysis.

The study described in this article focuses on the effects of collective bargaining on the health care industry. Due to the wide range of bargaining groups authorized to become unionized in the health care industry, this study concentrates on how collective bargaining affects the nurses in hospitals. The authors also surveyed a number of administrators and nurses in several hospitals in the midwestern part of the United States to secure their opinions about the effect of the union on their profession. The results of the survey are presented. Finally, the authors summarize related themes and interesting points from the literature and the surveys and provide recommendations.

Attitude of Health Personnel↗
PubMed1993

Delivery of radionuclides to pretargeted monoclonal antibodies using dihydrofolate reductase and methotrexate in an affinity system.

A novel affinity system for a two-phase delivery of radionuclides to tumor cells has been developed. In the first phase, a nontoxic bivalent monoclonal antibody conjugated to an enzyme is targeted to the tumor cells. In the second phase, a radionuclide-derivatized enzyme inhibitor, specific for the enzyme conjugated to the antibody, is administered. The model system selected for this study is the recombinant human enzyme dihydrofolate reductase (rhDHFR) and its high-affinity competitive inhibitor methotrexate (MTX). MTX was labeled with a radionuclide by covalent attachment of diethylenetriaminepentaacetic acid (DTPA) complexed with 111In. Using the gamma-carboxyl residue of MTX for the attachment of DTPA, binding of the inhibitor to rhDHFR was not affected. The inhibitory activities of nonderivatized MTX and DTPA-MTX were indistinguishable. Human K562 erythroleukemia cells were used to evaluate under in vitro conditions the DHFR-MTX affinity system for the delivery of 111In-labeled DTPA-MTX to pretargeted alpha-transferrin receptor antibody-rhDHFR conjugates (alpha-TFR-DHFR). The data demonstrate that the delivery of 111In is dose dependent and highly specific. Under saturating conditions, binding of 111In-DTPA-MTX to alpha-TFR-DHFR-treated cells was 14-fold higher than to cells treated with nonconjugated alpha-TFR antibody. Further experiments indicated that the low level of nonspecific binding of 111In-DTPA-MTX was comparable to that of 111In-DTPA, known for its complete extracellular distribution and rapid clearance through the kidneys. Based on the data of this study, antibody-conjugated rhDHFR and radionuclide-labeled DTPA-MTX complexes provide components for an alternative radioimmunotherapeutic approach that can be expected to result in improved tumor tissue ratios of both the targeting moiety and the radionuclide-labeled derivative as compared to current approaches.

Antibodies, Monoclonal↗