Biomedical subjects

S Jolly

Publications and source records attributed to S Jolly.

At least 19 recordsLinked to original sources

PubMed2006

The impact of implantable cardiac defibrillators for primary prophylaxis in the community: baseline risk and clinically meaningful benefits.

OBJECTIVE: To estimate the baseline risk of arrhythmic death required for prophylactic implantable cardiac defibrillators (ICDs) to result in clinically meaningful survival benefits in the population. BACKGROUND: While proven efficacious, the absolute survival impact of ICDs for the primary prevention of sudden cardiac death among patients with left ventricular (LV) dysfunction is highly dependent upon patient's baseline risk of arrhythmic death. METHODS: Using echocardiographic data from a random sample of patients identified from community echocardiographic laboratories, patients with moderate or severe LV dysfunction (ejection fraction < 35%) were linked to administrative databases to characterize baseline mortality risk (median follow-up duration of 4.85 years). Relative efficacy was ascertained from meta-analysis and clinical trial data. The baseline annual risk of arrhythmic death required for prophylactic ICDs to result in clinically meaningful survival benefits in the population was estimated at different ranges of relative efficacy and numbers needed to treat (NNTs) thresholds. RESULTS: LV dysfunction was a significant independent predictor of adverse outcomes. In total, 35.4% of the patients with moderate to severe LV dysfunction died during the follow-up period. Assuming a base-case relative efficacy of 66%, we estimated that the baseline risk for arrhythmic death required to exert a clinically meaningful NNT threshold of 50 in order to prevent one death (from any cause) was 3% per year or higher. CONCLUSIONS: The survival impact and cost-effectiveness of prophylactic ICDs in the population will depend upon the ability to risk-stratify and identify patients whose baseline risk for sudden cardiac death exceed 3% per year.

Death, Sudden, Cardiac↗

PubMed2004

S100A6 is a negative regulator of the induction of cardiac genes by trophic stimuli in cultured rat myocytes.

S100A6 (calcyclin), a member of the S100 family of EF-hand Ca2+ binding proteins, has been implicated in the regulation of cell growth and proliferation. We have previously shown that S100B, another member of the S100 family, is induced postinfarction and limits the hypertrophic response of surviving cardiac myocytes. We presently report that S100A6 expression is also increased in the periinfarct zone of rat heart postinfarction and in cultured neonatal rat myocytes by treatment with several trophic agents, including platelet-derived growth factor (PDGF), the alpha1-adrenergic agonist phenylephrine (PE), and angiotensin II (AII). Cotransfection of S100A6 in cultured neonatal rat cardiac myocytes inhibits induction of the cardiac fetal gene promoters skeletal alpha-actin (skACT) and beta-myosin heavy chain (beta-MHC) by PDGF, PE, AII, and the prostaglandin F2alpha (PGF2alpha), induction of the S100B promoter by PE, and induction of the alpha-MHC promoter by triiodothyronine (T3). By contrast, S100B cotransfection selectively inhibited only PE induction of skACT and beta-MHC promoters. Fluorescence microscopy demonstrated overlapping intracellular distribution of S100B and S100A6 in transfected myocytes and in postinfarct myocardium but heterodimerization of the two proteins could not be detected by co-immunoprecipitation. We conclude that S100A6 may function as a global negative modulator of differentiated cardiac gene expression comparable to its putative role in cell cycle progression of dividing cells.

Actins↗

PubMed2004

Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer.

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.

Adult↗

PubMed2003

Rare B decays into states containing a J/psi meson and a meson with s(-)s quark content.

We report a study of the B meson decays, B+ --> J/psiphiK+, B0 --> J/psiphiK(0)(S), B0 --> J/psiphi, B0 --> J/psieta, and B0 --> J/psieta' using 56 x 10(6) B(-)B events collected at the Upsilon(4S) resonance with the BABAR detector at the PEP-II e(+)e(-) asymmetric-energy storage ring. We measure the branching fractions B(B+ --> J/psiphiK+)=(4.4+/-1.4(stat)+/-0.5(syst))x 10(-5) and B(B0 --> J/psiphiK(0)(S))=(5.1+/-1.9(stat)+/-0.5(syst))x 10(-5), and set upper limits at 90% confidence level for the branching fractions B(B0 --> J/psiphi)<9.2 x 10(-6), B(B0 --> J/psieta)<2.7 x 10(-5), and B(B0 --> J/psieta')<6.3 x 10(-5).

Journal Article↗

PubMed2003

Study of the rare decays B0-->D(()+)(s)pi(-) and B0-->D(()-)(s)K+.

We report evidence for the decays B0-->D(+)(s)pi(-) and B0-->D(-)(s)K+ and the results of a search for B0-->D(*+)(s)pi(-) and B0-->D(*-)(s)K+ in a sample of 84 x 10(6) upsilon(4S) decays into BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) storage ring. We measure the branching fractions B(B0-->D(+)(s)pi(-))=[3.2+/-0.9(stat)+/-1.0(syst)] x 10(-5) and B(B0-->D(-)(s)K+)=[3.2+/-1.0(stat)+/-1.0(syst)] x 10(-5). We also set 90% C.L. limits B(B0-->D(*+)(s)pi(-))<4.1 x 10(-5) and B(B0-->D(*-)(s)K+)<2.5 x 10(-5).

Journal Article↗

PubMed2003

Measurement of the Cabibbo-Kobayashi-Maskawa matrix element V(ub) with B-->rhoenu decays.

We present a measurement of the branching fraction for the rare decays B-->rhoenu and extract a value for the magnitude of V(ub), one of the smallest elements of the Cabibbo-Kobayashi-Maskawa quark-mixing matrix. The results are given for five different calculations of form factors used to para-metrize the hadronic current in semileptonic decays. Using a sample of 55 x 10(6) BB meson pairs recorded with the BABAR detector at the PEP-II e(+)e(-) storage ring, we obtain B(B0-->rho(-)e(+)nu)=(3.29+/-0.42+/-0.47+/-0.55) x 10(-4) and |V(ub)|=(3.64+/-0.22+/-0.25(+0.39)(-0.56)) x 10(-3), where the uncertainties are statistical, systematic, and theoretical, respectively.

Journal Article↗

PubMed2003

Measurement of the B0-->J/psipi+pi- branching fraction.

We present a measurement of the branching fraction for the decay of the neutral B meson into the final state J/psipi(+)pi(-). The data set contains approximately 56 x 10(6) BB pairs produced at the Upsilon(4S) resonance and recorded with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) storage ring. The result of this analysis is B(B0-->J/psipi(+)pi(-))=(4.6+/-0.7+/-0.6) x 10(-5), where the first error is statistical and the second is systematic. In addition, we measure B(B0-->J/psirho(0))=(1.6+/-0.6+/-0.4) x 10(-5).

Journal Article↗

PubMed2003

Functional identification of epithelial and smooth muscle histamine-dependent relaxing mechanisms in the bovine trachea, but not in bronchi.

Theoretically, the overall effect of histamine on respiratory smooth muscle is the result of a subtle balance of contraction and relaxation. The aim of the study was to identify histamine type 2 (H2) and 3 (H3) receptor-dependent relaxing mechanisms in the contractile elements of the bovine tracheobronchial tree. In bronchial preparations, histamine induced very weak contractions, which were not exacerbated with the H2-antagonist cimetidine. Moreover, precontracted bronchial rings never relaxed in response to cumulative doses of histamine or amthamine (H2-agonist). In intact tracheal preparations, histamine induced strong contractions that were exacerbated by cimetidine (E(max): +17.2+/-6.6%) but not by thioperamide (H3-antagonist). Precontracted tracheal bundles did not relax in response to cumulative doses of the H3-agonist R-alpha-methylhistamine. The tracheal contractile response was higher in denuded compared to intact preparations (11.0+/-1.2 vs. 6.0+/-1.7 g). Cimetidine effect was dramatically potentiated in denuded tracheal strips (+40.0+/-11.7%). It is concluded that the weak response of bovine bronchi to histamine is due to a relative scarcity of H1 receptors on bronchial smooth muscle rather than to H2- or H3-dependent relaxation. In the bovine trachea, the smooth muscle possesses relaxing H2 but no H3 receptors. The epithelium exercises a relaxation, which is independent from H2 and H3 receptors.

Animals↗

PubMed2002

Measurements of branching fractions and CP-violating asymmetries in B0-->pi+pi-, K+pi-, K+K- decays.

We present measurements of branching fractions and CP-violating asymmetries for two-body neutral B meson decays to charged pions and kaons based on a sample of about 88x10(6) Upsilon(4S)-->BB decays. From a time-independent fit we measure the charge-averaged branching fractions B(B0-->pi+pi-)=(4.7+/-0.6+/-0.2)x10(-6), B(B0-->K+pi-)=(17.9+/-0.9+/-0.7)x10(-6), and the direct CP-violating charge asymmetry A(Kpi)=-0.102+/-0.050+/-0.016 [-0.188,-0.016], where the ranges in square brackets indicate the 90% confidence intervals. From a time-dependent fit we measure the B0-->pi+pi- CP-violating parameters S(pipi)=0.02+/-0.34+/-0.05 [-0.54,+0.58] and C(pipi)=-0.30+/-0.25+/-0.04 [-0.72,+0.12].

Journal Article↗

PubMed2002

Measurement of the CP asymmetry amplitude sin2beta with B0 mesons.

We present results on time-dependent CP asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 x 10(6) Upsilon(4S)-->B(-)B decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B(0) or B(-0) from its decay products. The amplitude of the CP asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta=0.741+/-0.067(stat)+/-0.034(syst) and |lambda|=0.948+/-0.051(stat)+/-0.030(syst). The magnitude of lambda is consistent with unity, in agreement with the standard model expectation of no direct CP violation in these modes.

Journal Article↗

PubMed2002

Measurement of the branching fraction and CP content for the decay B0-->D(+)D(-).

We report a measurement of the branching fraction of the decay B0-->D(*+)D(*-) and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4 fb (-1) collected at the Upsilon(4S) resonance during 1999-2000, we have reconstructed 38 candidate signal events in the mode B0-->D(*+)D(*-) with an estimated background of 6.2+/-0.5 events. From these events, we determine the branching fraction to be B(B0-->D(*+)D(*-))=[8.3+/-1.6(stat)+/-1.2(syst)]x10(-4). The measured CP-odd fraction of the final state is 0.22+/-0.18(stat)+/-0.03(syst).

Journal Article↗

PubMed2002

Measurement of the B(0) lifetime with partially reconstructed B(0)-->D(-)l(+)nu(l) decays.

The B(0) lifetime was measured with a sample of 23 million BB pairs collected by the BABAR detector at the PEP-II e(+)e(-) storage ring during 1999 and 2000. Events from the semileptonic decay B(0)-->D(*-)l(+)nu(l) have been selected with a partial reconstruction method in which only the charged lepton and the slow pi from the D*--->D(0)pi(-) decay are reconstructed. The result is tau(B(0)) = 1.529+/-0.012(stat)+/-0.029(syst) ps.

Journal Article↗

PubMed2002

Search for the rare decays B-->Kl(+)l(-) and B-->K(*)l(+)l(-).

We present results from a search for the flavor-changing neutral current decays B-->Kl(+)l(-) and B-->K(*)l(+)l(-), where l(+)l(-) is either an e(+)e(-) or mu(+)mu(-) pair. The data sample comprises 22.7 x 10(6) Upsilon(4S)-->B(-)B decays collected with the BABAR detector at the PEP-II B Factory. We obtain the 90% C.L. upper limits B(B-->Kl(+)l(-))<0.51 x 10(-6) and B(B-->K(*)l(+)l(-))<3.1 x 10(-6), close to standard model predictions for these branching fractions. We have also obtained limits on the lepton-family-violating decays B-->Ke+/-mu(-/+) and B-->K(*)e(+/-)mu(-/+).

Journal Article↗

PubMed2002

Measurement of B0-B-0 flavor oscillations in hadronic B0 decays.

Flavor oscillations of neutral B mesons have been studied in e+e- annihilation data collected with the BABAR detector at center-of-mass energies near the upsilon(4S) resonance. The data sample used for this purpose consists of events in which one B0 meson is reconstructed in a hadronic decay mode, while the flavor of the recoiling B0 is determined with a tagging algorithm that exploits the correlation between the flavor of the heavy quark and the charges of its decay products. From the time development of the observed mixed and unmixed final states, we determine the B0-B-0 oscillation frequency deltamd to be 0.516+/-0.016(stat)+/-0.010(syst) ps-1.

Journal Article↗

PubMed2002

Measurement of the B0-B-0 oscillation frequency with inclusive dilepton events.

The B0-B-0 oscillation frequency has been measured with a sample of 23 x 10(6) BB- pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives deltamd = 0.493+/-0.012(stat)+/-0.009(syst) ps-1.

Journal Article↗

PubMed2002

Search for T and CP violation in B0-B-0 mixing with inclusive dilepton events.

We report the results of a search for T and CP violation in B0-B-0 mixing using an inclusive dilepton sample collected by the BABAR experiment at the PEP-II B Factory. The asymmetry between l+l+ and l-l- events allows us to compare the probabilities for B-0-->B0 and B0-->B-0 oscillations and thus probe T and CP invariance. Using a sample of 23 x 10(6) BB- pairs, we measure a same-sign dilepton asymmetry of A(T/CP) = [0.5+/-1.2(stat)+/-1.4(syst)]%. For the modulus of the ratio of complex mixing parameters p and q, we obtain q/p = 0.998+/-0.006(stat)+/-0.007(syst).

Journal Article↗

PubMed2002

Measurement of B --> K*gamma branching fractions and charge asymmetries.

The branching fractions of the exclusive decays B0-->K(*0)gamma and B+-->K(*+)gamma are measured from a sample of (22.74+/-0.36)x10(6) BB decays collected with the BABAR detector at the PEP-II asymmetric e(+)e(-) collider. We find B (B0-->K(*0)gamma) = [4.23+/-0.40(stat)+/-0.22(syst)]x10(-5), B(B+-->K(*+)gamma) = [3.83+/-0.62(stat)+/-0.22(syst)]x10(-5) and constrain the CP-violating charge asymmetry to be -0.170 K(*)gamma)<0.082 at 90% C.L.

Journal Article↗

PubMed2002

[Results of rehabilitation on quality of walking and outcome in elderly patients following femoral neck fracture. Development after one year].

OBJECTIVES: To examine effects of coordinated multidisciplinary inpatient rehabilitation for older patients with hip fractures. MATERIAL AND METHOD: 187 (42 men and 147 women: mean age 80.9 +/- 8.4 years) admitted with a diagnosis of fracture neck of femur. Before fracture 183 patients were living in their own house. We examine medical state before fracture, type of fracture, type of surgery, walking performance at hospital discharge and at one year, destination at this discharge, living location and quality of life at one year. RESULTS: The length stay after intracapsular fracture and prosthesis is significatively lower (p<0.01). At discharge 28% were walking alone, 38% with stick, 17% with technical aid, 8% with human aid, 2% were bedridden and 7% were dead. After hospitalisation 7% were dead, 70% were living in their own homes, 18% were in old people's homes and 6% in another hospital. One year after fracture, 19% were dead, 65% were living in their own homes, 16% were in old people's homes. Older age, medical state before fracture and male gender was found to increase mortality risk following hip fracture (p<0.01). CONCLUSIONS: Hip fracture is a major cause of morbidity in older people and its impact, both on the individual and to society is substantial. Many people do not return to their pre-fracture life style. Coordinated multidisciplinary care of patients with fractured neck of femur seems essential.

Aged↗