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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 91 records · Page 5Linked to original sources
PubMed2000

The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial.

C-Reactive protein and homocysteine are independent risk factors for the development of cardiovascular disease. This study compared the effects of hormone replacement therapy (HRT) and raloxifene on serum C-reactive protein and homocysteine levels as markers of cardiovascular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, placebo-controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo for 6 months. C-Reactive protein and homocysteine were measured in baseline and 6-month serum samples. HRT increased C-reactive protein levels by 84% (P<0.001), whereas raloxifene (60 and 120 mg/day) had no significant effect (-6% and -4%;, respectively; P>0.2). Raloxifene (60 and 120 mg/day) significantly lowered serum levels ofhomocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained with HRT. We conclude that HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women. Whereas cardiovascular risk predicted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.

Aged↗
PubMed2000

Impact of a nurse-managed heart failure clinic: a pilot study.

BACKGROUND: One approach to optimize clinical and economic management of congestive heart failure is the use of multidisciplinary outpatient clinics in which advanced practice nurses coordinate care. One such clinic was developed in 1995 at a southeastern university hospital to enhance management of patients with chronic congestive heart failure. OBJECTIVES: To evaluate the effects of a multidisciplinary outpatient heart failure clinic on the clinical and economic management of patients with congestive heart failure. METHODS: Data on hospital readmissions, emergency department visits, length of stay, charges, and reimbursement from the 6 months before 15 patients joined a heart failure clinic were compared with data from the 6 months after the patients joined the clinic. RESULTS: The patients had a total of 38 hospital admissions (151 hospital days) in the 6 months before joining the clinic and 19 admissions (72 hospital days) in the 6 months afterward. The mean length of stay decreased from 4.3 days in the 6 months before joining to 3.8 days in the 6 months afterward, and the number of emergency department visits also decreased, although neither decrease was statistically significant. Mean inpatient hospital charges decreased from $10,624 per patient admission to $5893. Reimbursements were $7751 (73% collection rate) and $5138 (87% collection rate), respectively. CONCLUSIONS: Patients seemed to benefit from participation in the heart failure clinic. If a healthcare provider is available to manage early signs and symptoms of worsening heart failure, hospital readmissions may be decreased and patients' outcomes may be improved.

Adult↗
PubMed1999

Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase.

Receptor tyrosine kinases regulate cell behavior by activating specific signal transduction cascades. Epidermal growth factor (EGF) receptor tyrosine kinases include ErbB1, ErbB2, ErbB3 and ErbB4. ErbB4 is a tyrosine kinase receptor that binds neuregulins (NRG) and several other EGF family members. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis identified two isoforms of ErbB4 that differed in their cytoplasmic domain sequences. Specifically, RT-PCR using primers flanking the putative phosphatidyl inositol 3-kinase (PI3-K) binding site of ErbB4 generated two specific bands when human and mouse heart and kidney tissues were analysed. Cloning and sequencing of these RT-PCR products revealed that one of the ErbB4 isoforms (ErbB4 CYT-2) lacked a 16 amino acid sequence including a putative PI3-K binding site, that was present in the other isoform (ErbB4 CYT-1). RT-PCR analysis of mouse tissues suggested that the expression of ErbB4 CYT-1 and ErbB4 CYT-2 was tissue-specific. Heart, breast and abdominal aorta expressed predominantly ErbB4 CYT-1 whereas neural tissues and kidney expressed predominantly ErbB4 CYT-2. To ascertain whether the absence of the putative PI3-K binding site in ErbB4 CYT-2 also resulted in the loss of PI3-K activity, NIH3T3 cell lines overexpressing ErbB4 CYT-1 or ErbB4 CYT-2 were produced. NRG-1 bound to and stimulated equivalent tyrosine phosphorylation of both isoforms. However, unlike ErbB4 CYT-1, the ErbB4 CYT-2 isoform was unable to bind the p85 subunit of PI3-K and to stimulate PI3-K activity in these cells. Furthermore, tyrosine phosphorylation of p85 or association of PI3-K activity with phosphotyrosine was not induced in NRG-1 treated cells expressing ErbB4 CYT-2, indicating that this isoform was incapable of activating PI3-K even indirectly. It was concluded that a novel naturally occurring ErbB4 isoform exists with a deletion of the cytoplasmic domain sequence required for the activation of the PI3-K intracellular signal transduction pathway and that this is the only PI3-K binding site in ErbB4.

Amino Acid Sequence↗
PubMed1999

The impact of potent antiretroviral therapy on the characteristics of hospitalized patients with HIV infection.

OBJECTIVE: Despite advances in antiretroviral treatment, a large number of HIV-infected patients still require hospitalization. This study describes the characteristics of HIV patients requiring hospitalization before and after the advent of potent antiretroviral therapies. METHODS: Information was collected on all HIV-positive patients admitted to the New York Hospital-Cornell Medical Center in New York City. Data was collected from 1 January through 30 June 1995, and during the same 6-month interval in 1997. RESULTS: In each time period over 1500 outpatients were receiving treatment for HIV infection. There was a significant decrease in the incidence of admission [60.4 per 100 patient-years (PY) in 1995, 28.8 per 100 PY in 1997], and length of stay (10 versus 8 days). The median CD4 cell count of all HIV-infected patients admitted to the hospital doubled: 37 x 10(6)/l in 1995 versus 80 x 10(6)/l in 1997. However, there was no significant change in the median CD4 cell count of patients diagnosed with opportunistic infections. The incidence of the most common diagnosis (bacterial pneumonia, 8.0 per 100 PY in 1995 versus 3.6 per 100 PY in 1997) and the most common opportunistic infection (Pneumocystis carinii pneumonia 7.6 per 100 PY in 1995 versus 2.4 per 100 PY in 1997) decreased significantly. CONCLUSIONS: Since the introduction of potent antiretroviral therapy, a significant decrease in the incidence of hospital admission and opportunistic infections has occurred. There has been a doubling of the median CD4 cell count of inpatients. There has been no significant change in the median CD4 cell count at which patients present with opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1999

Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group.

OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United States and Canada. PATIENTS: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p24 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Pressure measurements during injection of corticosteroids: in vivo studies.

Intralesional injection of corticosteroids is an effective treatment for capillary hemangiomas. Complications include embolisation of corticosteroid particles into the ocular circulation resulting in permanent loss of vision. This research is aimed at developing an injection cannula and monitoring system to prevent such inadvertent embolisation. A cannula has been designed to simultaneously estimate the pressure at its tip and the flow rate during injection. The estimation technique has previously been validated using an in vitro model. In this study, the cannula was tested in vivo with canine liver at injection flow rates of 2.5 to 21 ml min-1. The pressure generated in the tissue during injection was calculated using the technique developed. This was compared with direct in situ pressure measurements made with a coaxial outer cannula. The mean calculated pressure was seen to be linearly related to the mean measured pressure with a slope of 0.97, correlation coefficient of 0.99 and standard error of 2.74 mmHg. Similar trends were observed between the maximum calculated and maximum measured injection pressure: slope = 1.0, r = 0.99 and standard error = 5.54 mmHg. The estimation of the mean and maximum pressure from the cannula and monitoring system was accurate in canine liver. High pressures close to 250 mmHg were generated in tissues during injection.

Animals↗
PubMed1999

Lack of evidence for an immunosuppressive role for MUC1.

The in vitro anti-proliferative properties of various supernatants from MUC1-expressing cell lines and of purified preparations of MUC1 were evaluated. We have observed that supernatants from the MUC1-and MUC3-positive cell line T47D, but not from the MUC1- and MUC4-positive cell line MCF7, were able to inhibit proliferation of cells from various haematopoietic cell lines. Although the activity of T47D supernatants could be abrogated by immunodepletion of MUC1, immunopurified MUC1 from T47D was unable to inhibit cell proliferation. Significantly, supernatants from mouse 3T3 cells transfected with a secreted form of MUC1 or from BHK-21 cells infected with a recombinant vaccinia virus coding for the secreted form of MUC1, as well as preparations of purified MUC1 from bile or urine, were likewise unable to inhibit T cell proliferation. Surprisingly, a crude mixture of bile mucins had a suppressive effect on T cell growth. Our results suggest that other molecules, such as amino sugars or other mucins, which can associate with MUC1, are likely to be responsible for the observed anti-proliferative effects of T47D cells.

3T3 Cells↗
PubMed1999

Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity.

Tumor vascularization is accompanied by the migration of stromal cells, including endothelial cells, smooth muscle cells, and fibroblasts, into the tumor. The biological contributions of stromal cells to tumor vascularization have not been well-defined, partly due to the difficulty of culturing stromal cells in the presence of large numbers of fast-growing tumor cells. To address this problem, a strategy was devised to kill tumor cells but not stromal cells. Advantage was taken of the observation that diphtheria toxin (DT) kills human but not rodent cells. Human melanoma (MMAN) tumor cells were injected subcutaneously into nude mice. The tumors were excised, homogenized, and treated with 50 ng/ml DT for 24 hours. Elimination of melanoma cells by DT treatment was demonstrated by lack of detectable levels of microphthalmia, a transcription factor that is a marker for melanoma cells. The murine stromal cells were viable and found to be mostly smooth muscle cells. These cells constituted about 1.5% of the MMAN tumor. RNase protection assays using a specific murine vascular endothelial growth factor probe confirmed the murine origin of the stromal cells. This method allows rapid isolation of stromal cells and should facilitate biochemical and genetic analysis of tumor-stromal interactions.

Actins↗
PubMed1999

Innate antibody catalysis.

Catalysis by antibodies is often assumed to require immunization with artificial haptens, which are proposed to stimulate adaptive immune processes and enable the development of catalytic sites with the ability to bind the transition state. Contrary to this assumption, we describe here a serine protease-like catalytic triad in an antibody light chain raised by immunization with vasoactive intestinal peptide (VIP), the structure and function of which is inherited via a germline V(L) gene. The serine protease mechanism was evident from loss of the catalytic activity by site directed mutagenesis at a framework region residue Asp1 (present study) and at two complementarity determining region residues Ser27a and His 93 (Gao, Q-S., Sun, M., Rees, A., Paul, S., 1995. Site-directed mutagenesis of proteolytic antibody light chain. J. Mol. Biol. 253, 658-664). All three catalytic residues (Ser27a, His93, Asp1) are also present in the germline counterpart of the mature V(L) gene, but the mature and germline sequences differ by four amino acids remote from the catalytic site. Reversion mutations were introduced at these amino acids in the mature light chain (His27 d:Asp, Thr28e:Ser, Ile34:Asn, Gln96:Trp; Kabat numbering, germline encoded residues shown second), generating the germline configuration of the protein. The germline light chain expressed peptidase activity, determined by assaying the cleavage of VIP and a synthetic protease substrate, Pro-Phe-Arg-Methylcoumarinamide. Differences between the kinetic constants for the mature and germline light chains were marginal. Diisopropylfluorophosphate, a serine protease inhibitor, blocked the peptidase activity of the germline light chain, suggesting the presence of the catalytic triad in a functional state. Like the mature light chain, the germline protein preferentially cleaves peptide bonds on the C-terminal side of basic residues. We conclude that the catalytic activity of certain antibodies is an innate function, originating over the course of phylogenetic evolution of the V(L) genes, as opposed to somatic processes.

Amino Acid Sequence↗
PubMed1999

Trends in compliance with the guidelines for preventing the transmission of Mycobacterium tuberculosis among New Jersey hospitals, 1989 to 1996.

OBJECTIVE: To determine trends in compliance with the guidelines for preventing the transmission of Mycobacterium tuberculosis in healthcare facilities among New Jersey hospitals from 1989 through 1996. DESIGN: A voluntary questionnaire was sent to all 96 New Jersey hospitals in 1992. The 53 that responded were resurveyed in 1996. RESULTS: Of the 96 hospitals surveyed in 1992, 53 (55%) returned a completed questionnaire; 33 (64%) were community, nonteaching hospitals. In 1991, patients with tuberculosis (TB) were admitted at 38 (72%) of 53 hospitals, and from 1989 through 1991, patients with multidrug-resistant (MDR) TB were admitted at 15 (29%) of 52 hospitals. Twenty-nine (57%) of 51 reported having rooms meeting the Centers for Disease Control and Prevention (CDC) criteria for acid-fast bacilli (AFB) isolation. A nonfitted surgical mask was used as a respiratory protective device by healthcare workers (HCWs) at 28 (55%) of 51 hospitals. Attending physicians were included in tuberculin skin-testing (TST) programs at 5 (11%) of 45 hospitals. In the 1996 resurvey, 48 (94%) of 53 surveyed hospitals returned a completed questionnaire; 34 (81%) of 42 had TB patient admissions, and 4 (9%) of 43 had MDR TB patient admissions in 1996. Forty-five (96%) of 47 reported having rooms that met CDC criteria for AFB isolation. N95 respiratory devices were used by HCWs at 45 (94%) of 48 hospitals. Attending physicians were included in the TST programs at 22 (54%) of 41 hospitals. CONCLUSION: New Jersey hospitals have made improvements in availability of AFB isolation rooms, use of proper respiratory protective devices, and expansion of TST programs for HCWs from 1989 through 1996.

Cross Infection↗
PubMed1999

Tuberculosis in hemodialysis patients in New Jersey: a statewide study.

OBJECTIVE: To study the incidence of tuberculosis (TB), tuberculin skin testing (TST) practices, and infection control practices at outpatient hemodialysis centers. DESIGN: Mail surveys performed in December 1994 and 1995. MAIN OUTCOME MEASURES: The numbers of patients with incident active TB during 1994 and 1995, TST policies during 1994, and TB infection control policies in 1994. SETTING: All outpatient dialysis centers in New Jersey. PATIENTS OR PARTICIPANTS: Healthcare workers and patients in dialysis centers in New Jersey. RESULTS: Of 47 centers, 41 provided information on TST and TB infection control policies and practices. TSTs were performed on newly hired healthcare workers at all 41 centers and on established workers at 39 centers. In contrast, only 1 center reported performing TSTs on hemodialysis patients; 5 other centers reported screening of patients for TB using chest radiographs. Active TB was reported in 3 of 4,550 chronic hemodialysis patients in 1994 (rate, 66/100,000 patient-years) and in 4 of 4,831 patients in 1995 (rate, 83/100,000 patient-years). Both rates were several times higher than the rate in the New Jersey general population during this period (10.7-10.8/100,000). CONCLUSION: Although based on small numbers of patients with TB, we found a relatively high incidence of TB among hemodialysis patients in New Jersey. Most centers reported performing TSTs on workers but not on patients. These results suggest the need for improved TB screening and infection control precautions at outpatient dialysis centers.

Allied Health Personnel↗
PubMed1999

Developing practice protocols for advanced practice nursing.

In most states, the role of an advanced practice nurse is dependent on practice protocols that provide an organized method for analyzing and managing a disease or major symptom. They are also used to control the process of medical care and to specify steps in the delivery of that care. Creating appropriate practice protocols is one of the most important precursors to implementing the advanced practice role, because they virtually drive the clinician's ability to treat or manage clinical situations or disease states. This article outlines the steps involved in developing practice protocols and discusses the content that should be included in a protocol, providing an example of narrative and algorithm format protocols. Pros and cons, as well as legal issues related to practice protocols, are also presented.

Algorithms↗