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Biomedical subjects

E Loh

Publications and source records attributed to E Loh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Preferences for treatment outcomes in patients with heart failure: symptoms versus survival.

BACKGROUND: Patient preferences for congestive heart failure therapy outcomes may vary depending on the goals of improving symptoms versus survival, but this has not been extensively investigated. Our objective was to analyze patient preferences for congestive heart failure therapy outcomes based on the goals of symptom versus survival improvement. METHODS AND RESULTS: This was a prospective, full-profile conjoint analysis study of individual preferences for congestive heart failure treatment outcomes. Conjoint analysis was based on ratings of 16 treatment-outcome profiles, each consisting of 4 attributes (tiredness, shortness of breath, depression, and survival) varied across 4 severity levels. Part-worths (utilities) and importance weights were calculated for each attribute to determine their relative contribution to the full-profile rating decision using standard full-profile conjoint analysis techniques. Fifty-one patients with congestive heart failure from our medical center (University of Pennsylvania Medical Center, Philadelphia, PA) and 47 age-, gender-, and race-matched control subjects were studied. Part-worths and importance weights were significantly different for shortness of breath and depression between patients and control subjects. Symptom-sensitive (n = 33) and survival-sensitive (n = 17) treatment outcome preference segments were identified within the patient group. Importance weights for symptom-sensitive versus survival-sensitive patients were as follows: tiredness 0.30+/-0.10 versus 0.16+/-0.09 (P < .01); shortness of breath 0.26+/-0.08 versus 0.21+/-0.08 (P = .07); depression 0.26+/-0.09 versus 0.19+/-0.09 (P = .01); and survival 0.18+/-0.07 versus 0.43+/-0.11 (P < .01). There were no significant predictors of which treatment outcome preference segment a patient belonged. Control subjects did not display similar preference segmentation. CONCLUSIONS: Symptomatic congestive heart-failure patients were clustered into symptom-sensitive and survival-sensitive segments in a manner suggesting that treatment outcomes of improved symptoms were of greater importance to the majority than longer survival. A full understanding of these individual preferences may have important implications for the design of therapy for heart-failure patients.

Adult↗
PubMed2000

Heart transplant center practice patterns affect access to donors and survival of patients classified as status 1 by the United Network of Organ Sharing.

OBJECTIVE: To determine the effect of adult cardiac transplant center practice patterns within a single organ procurement organization on access to donors and survival for patients listed as United Network of Organ Sharing (UNOS) status 1. METHODS: A total of 662 patients listed (January 1, 1992, through December 31, 1995) as UNOS status 1 for heart transplantation by the 4 adult cardiac transplant centers in an organ procurement organization were analyzed in a retrospective cohort study to determine differences in clinical outcomes. RESULTS: The specific center at which an individual was listed as UNOS status 1 was a significant independent predictor of receiving a transplant (odds ratios for 3 centers vs center with highest likelihood = 0.73, 0.64, 0.35, respectively; P <. 01). Only 1 center had a significantly increased mortality rate compared with the other centers (odds ratio 2.03, P <.01). CONCLUSION: Within a single regional organ procurement organization, cardiac transplant centers demonstrate significant variability in the likelihood of transplantation and survival for patients listed as UNOS status 1.

Adult↗
PubMed2000

Preferential association of syntaxin 8 with the early endosome.

Members of the syntaxin family play a fundamental role in vesicle docking and fusion of diverse transport events. We have molecularly characterized syntaxin 8, a novel member of the syntaxin family. The nucleotide sequence of cloned rat cDNA predicts a polypeptide of 236 residues with a carboxyl-terminal 18-residue hydrophobic domain that may function as a membrane anchor. Characteristic of syntaxins, syntaxin 8 also contain regions that have the potential to form coiled-coil structures. Among the known syntaxins, syntaxin 8 is most homologous to syntaxin 6 which is predominantly associated with the trans-Golgi network (TGN). The syntaxin 8 transcript is detected in all rat tissues examined by northern blot. Antibodies against recombinant syntaxin 8 recognize a 27 kDa protein that is enriched in membrane fractions containing the Golgi apparatus and the endosomal/lysosomal compartments. Syntaxin 8 in membrane extract could be incorporated into a 20S protein complex in a way that is dependent on the soluble N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein ((alpha)-SNAP), suggesting that syntaxin 8 is indeed a SNAP receptor (SNARE). Indirect immunofluorescence microscopy reveals that the majority of syntaxin 8 is localized to the early endosome marked by Rab5. This is corroborated by immunogold labeling experiments showing enrichment of syntaxin 8 in the early endosome and its co-labeling with Rab5.

Amino Acid Sequence↗
PubMed2000

Carbohydrate craving by alcohol-dependent men during sobriety: relationship to nutrition and serotonergic function.

BACKGROUND: Several studies report reduced serotonin (5HT) in alcohol-dependent subjects. Furthermore, alcohol increases 5HT in animals. Thus, alcohol dependence may be an attempt to self-medicate reduced 5HT. Relevant to this, reducing 5HT increases carbohydrate intake, and several studies report increased carbohydrate intake in alcohol-dependent subjects. Like alcohol, carbohydrate increases 5HT. We hypothesized that a subgroup of the alcohol-dependent population self-medicates reduced 5HT with alcohol and alternatively with carbohydrate when not drinking. METHODS: Three groups were recruited: a high carbohydrate craving alcohol-dependent group (n = 10), a low carbohydrate craving alcohol-dependent group (n = 11), and a nonaddicted control group (n = 12). All groups were placed on a high-carbohydrate, low-protein diet for 2 days and then a high-protein, low-carbohydrate diet for 2 days. The effects of diet on mood, alcohol craving, stress, and 5HT were measured. RESULTS: Although both alcohol-dependent groups had similar alcohol cravings at baseline, only the carbohydrate-craving alcohol-dependent group craved alcohol significantly more when under the stress of the research protocol. The carbohydrate-craving alcohol-dependent subjects presented with distinct personality disorders and were uniquely sensitive to the adverse effects of carbohydrate on mood. Diet had a unique effect on 5HT in the high carbohydrate craving alcohol-dependent group. The results of platelet 5HT uptake demonstrated that the high-protein, low-carbohydrate diet significantly increased Km values of high carbohydrate craving alcohol-dependent subjects, whereas it reduced the Km values of both non-carbohydrate-craving alcohol-dependent subjects and nonaddicted controls. CONCLUSION: Carbohydrate-craving alcohol-dependent subjects are a distinct subgroup of the alcohol-dependent population.

Adult↗
PubMed2000

Identification of multiple genital HPV types and sequence variants by consensus and nested type-specific PCR coupled with cycle sequencing.

Consensus and type-specific HPV primers were employed for PCR and cycle sequencing of genital HPVs in scrapings and colposcopically directed biopsies of the cervix from a cohort of 188 female sex workers. A total of 27 individuals tested positive for a broad spectrum of HPV types, including HPVs 6b, 16, 18, 31, 33, 34, 35, 45, 56 and 58, as well as a new HPV type, with seven individuals displaying dual infections. Good correlation between the results of individually paired samples was observed. A HPV 16 primer biotinylated at the 5' end was also used as a probe, which could successfully detect amplified products of HPV 16 but not other HPV types tested by an automated ELISA detection system. DNA sequence analysis revealed several HPV sequence variants that harbored mutations, especially in the E6 gene, many of which culminated in non-conservative amino acid substitutions in the transforming E6 oncoprotein. Such an approach of coupling PCR with cycle sequencing permits the determination of many known and even novel HPV types associated with varying degrees of risk to cervical carcinogenesis, and enables the identification of HPV sequence variants of putative biological and clinical significance, thus justifying its utility as an adjunct tool to complement cervical cytology and colposcopy. This study also emphasises the need for educational, interventional and behavioral modification to minimise HPV transmission, such as through consistent condom usage among sex workers.

Cervix Uteri↗
PubMed1999

Prognostic significance of atrial fibrillation in patients at a tertiary medical center referred for heart transplantation because of severe heart failure.

Atrial fibrillation (AF) occurs frequently in advanced heart failure. The prognostic significance of AF remains controversial. To determine the relation of AF to survival in patients with advanced heart failure, 234 consecutive patients referred for heart transplantation evaluation from January 1993 to June 1996 were studied to determine the effect of AF on event-free survival (freedom from death, heart transplantation, or placement of a left ventricular assist device). Clinical characteristics of the study population included: age, 51 +/- 17 years; maximum exercise oxygen consumption, 14.2 +/- 5.3 ml/kg/min; left ventricular ejection fraction, 24 +/- 11%; pulmonary capillary wedge pressure, 23 +/- 9 mm Hg; and ischemic etiology, 52%. Medical therapy included: diuretics (86%), angiotensin-converting enzyme inhibitors (80%), digoxin (80%), and anticoagulation therapy (72%). Mean duration of follow-up was 1.1 +/- 1.0 years. Sixty-two patients (27.4%) had AF. One-year event-free survival of the study population was 48%. No difference in event-free survival between patients with and without AF was observed. Univariate predictors of decreased event-free survival included: (1) advanced New York Heart Association class; (2) higher pulmonary capillary wedge pressure; (3) lower cardiac index; (4) lower maximum exercise oxygen consumption; (5) use of inotropic therapy; and (6) greater pulmonary artery systolic pressure. By multivariate analysis, independent predictors of decreased event-free survival included advanced New York Heart Association class (p <0.002) and higher pulmonary capillary wedge pressure (p = 0.02). Thus, AF in patients with advanced heart failure is not associated with decreased event-free survival.

Adult↗
PubMed1999

Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure.

BACKGROUND: This study was undertaken to identify gene(s) that may be associated with improved clinical outcome in patients with congestive heart failure (CHF). The adenosine monophosphate deaminase locus (AMPD1) was selected for study. We hypothesized that inheritance of the mutant AMPD1 allele is associated with increased probability of survival without cardiac transplantation in patients with CHF. METHODS AND RESULTS: AMPD1 genotype was determined in 132 patients with advanced CHF and 91 control reference subjects by use of a polymerase chain reaction-based, allele-specific oligonucleotide detection assay. In patients with CHF, those heterozygous (n=20) or homozygous (n=1) for the mutant AMPD1 allele (AMPD1 +/- or -/-, respectively) experienced a significantly longer duration of heart failure symptoms before referral for transplantation evaluation than CHF patients homozygous for the wild-type allele (AMPD1 +/+; n=111; 7.6+/-6.5 versus 3.2+/-3.6 years; P<0.001). The OR of surviving without cardiac transplantation >/=5 years after initial hospitalization for CHF symptoms was 8.6 times greater (95% CI: 3.05, 23.87) in those patients carrying >/=1 mutant AMPD1 allele than in those carrying 2 wild-type AMPD1 +/+ alleles. CONCLUSIONS: After the onset of CHF symptoms, the mutant AMPD1 allele is associated with prolonged probability of survival without cardiac transplantation. The mechanism by which the presence of the mutant AMPD1 allele may modify the clinical phenotype of heart failure remains to be determined.

AMP Deaminase↗
PubMed1999

Cardiovascular effects of inhaled nitric oxide in a canine model of cardiomyopathy.

BACKGROUND: The inhalation of nitric oxide (NO) in patients with heart failure decreases pulmonary vascular resistance (PVR) and is associated with an increase in pulmonary artery wedge pressure (PAWP). The mechanism for this effect remains unclear. METHODS: In dogs rapid-paced for 8 weeks to induce cardiac dysfunction, we performed left ventricular pressure-volume analysis of unpaced hearts in situ to determine whether during NO inhalation (80 ppm), the mechanism for the rise in PAWP is due to: 1) primary pulmonary vasodilation; 2) a direct negative inotropic effect; or 3) impairment of ventricular relaxation. RESULTS: Inhalation of NO decreased PVR by 51%+/-3.8% (257+/-25 vs 127+/-18 dynes x sec x cm(-5) [NO 80 ppm]; p < 0.001) and increased PAWP (15.4+/-2.4 vs 18.1+/-2.6 mm Hg [NO 80 ppm]; p < 0.001). Calculated systemic vascular resistance remained unchanged. Left ventricular (LV) end-diastolic pressure rose (16.4+/-1.9 vs 19.1+/-1.8 mm Hg [NO 80 ppm]; p < 0.001), as did LV end-diastolic volume (83.5+/-4.0 vs 77.0+/-3.4 mL [NO 80 ppm]; p = 0.006). LV peak +dP/dt was unchanged by NO (1,082+/-105 vs 1,142+/-111 mm Hg/sec [NO 80 ppm]; p = NS). There was a trend toward a stroke volume increase (17.4+/-1.2 vs 18.8+/-1.3 mL; p = NS), but the relaxation time constant and end-diastolic pressure-volume relation were both unchanged. CONCLUSIONS: In this canine model of cardiomyopathy, inhaled NO decreases pulmonary vascular resistance. The associated increase in left ventricular filling pressure appears to be secondary to a primary pulmonary vasodilator effect of NO without primary effects on the contractile or relaxation properties of the left ventricle.

Administration, Inhalation↗
PubMed1999

Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: impact on the delivery of local-regional radiation therapy.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. PATIENTS AND METHODS: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. RESULTS: Overall and disease-free survival rates at 18 months were 83% (+/- 4%) and 77% (+/- 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%-80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%-24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. CONCLUSION: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.

Adult↗
PubMed1999

Rituximab (anti-CD20 monoclonal antibody) therapy for progressive intermediate-grade non-Hodgkin's lymphoma after high-dose therapy and autologous peripheral stem cell transplantation.

We evaluated the response and toxicity of rituximab in the setting of progressive intermediate grade non-Hodgkin's lymphoma (NHL) after autologous peripheral stem cell transplantation (PSCT). Seven patients with a median age of 59 years (45-62), ECOG performance status 0-1, and CD20-positive diffuse large cell lymphoma with progression after PSCT were treated. All patients initially received 4-weekly infusions of rituximab (375 mg/m2). The maximum response was three CR and four PR. Median progression-free survival was 197 days (range 60-282). With a median follow-up of 204 (115-299) days, the patients' disease status is classified as two CR, one PR, and four PD. Four of five patients with ECOG performance status of 1 prior to treatment showed improvement to status 0 after treatment with rituximab. While follow-up is short, these results suggest that rituximab has significant activity in intermediate-grade non-Hodgkin's lymphoma that has relapsed after PSCT.

Antibodies, Monoclonal↗
PubMed1998

Regulation of alphaIIb beta3 function in human B lymphocytes.

We studied the function of the platelet integrin alphaIIb beta3 using a B lymphocyte model in which alphaIIb beta3 can be induced to interact with fibrinogen using phorbol myristate acetate (PMA). To determine whether a G protein-coupled receptor could also activate alphaIIb beta3 in lymphocytes, we coexpressed the human formyl peptide receptor (fPR) and alphaIIb beta3, finding that the fPR agonist formyl Met-Leu-Phe (fMLP)-stimulated lymphocyte adherence to immobilized fibrinogen and binding of soluble fibrinogen to the lymphocyte surface. The response to fMLP, but not PMA, was abrogated by pertussis toxin, indicating that the fPR was coupled to the G-protein Galphai, whereas the protein kinase C inhibitor bisindolylmaleimide I inhibited the response to both fMLP and PMA, indicating that signaling from the fPR included protein kinase C. On the other hand, the tyrosine kinase inhibitor genistein, the Syk inhibitor piceatannol, and the RhoA inhibitor C3 exoenzyme had no effect, implying that neither tyrosine phosphorylation nor the GTPase RhoA were involved. Furthermore, whereas micromolar concentrations of cytochalasin D inhibited the PMA-stimulated interaction of alphaIIb beta3 with fibrinogen, nanomolar concentrations actually induced fibrinogen binding to unstimulated cells. Our studies demonstrate that alphaIIb beta3 expressed in B lymphocytes can be activated by a physiologic agonist and outline an activating pathway that includes Galphai, protein kinase C, and the actin cytoskeleton.

B-Lymphocytes↗
PubMed1998

Desmin myopathy involving cardiac, skeletal, and vascular smooth muscle: report of a case with immunoelectron microscopy.

Desmin myopathy is a rare idiopathic disorder characterized by abnormal aggregates of desmin-type intermediate filaments, which affects cardiac and skeletal muscle, and rarely the intestinal smooth muscle. We report a 42-year-old woman with atrial fibrillation and progressive restrictive cardiomyopathy. Left ventricular biopsy, cardiac explant, and subsequent autopsy study of skeletal muscle revealed cytoplasmic granulo-filamentous inclusions that were continuous with Z-lines and were immunoreactive for desmin filaments both at the light immunohistochemical and electron microscopic level. In addition, we report the presence of characteristic inclusions within the smooth muscle of intramural coronary blood vessels. This is the first description of desmin inclusions within vascular smooth muscle, and underscores the systemic nature of this rare myopathy.

Adult↗
PubMed1998

Lipoprotein(a) levels and heart transplantation atherosclerosis.

BACKGROUND: Elevated serum lipoprotein(a) [Lp(a)] levels are associated with the development of native coronary atherosclerosis. The association between increased levels of Lp(a) and the development of accelerated cardiac allograft vasculopathy (ACAV) in patients who have undergone orthotopic heart transplantation has not been firmly established. METHODS AND RESULTS: We studied 74 consecutive heart transplant recipients with at least 1 year survival to determine the relation between Lp(a) and the presence of ACAV. Recipient and donor clinical and laboratory parameters, including mean serum Lp(a) levels, were obtained. ACAV was defined angiographically as > or =30% stenosis in one or more epicardial arteries. ACAV 1 year after heart transplantation was angiographically present in 26 (35%) patients. Mean donor age (36 +/- 13 years [ACAV (+)] vs 28 +/- 10 years, [ACAV (-)]; p = 0.004) and mean serum triglyceride levels 6 months after transplantation (286 +/- 275 mg/dl [ACAV (+)] vs 169 +/- 85 mg/dl [ACAV (-)]; p = 0.025) were univariate predictors of ACAV. No significant difference in mean serum Lp(a) levels was observed (20 +/- 19 mg/dl [ACAV (+)] vs 30 +/- 30 mg/dl [ACAV (-)]; p = NS). Donor age was the single greatest independent predictor of ACAV by multivariate logistic regression (p = 0.02). CONCLUSIONS: Lp(a) does not appear to be a risk factor for the development of ACAV 1 year after heart transplantation. Further studies are needed to define the influence of serum Lp(a) on the development of cardiovascular disease after orthotopic heart transplantation.

Adult↗
PubMed1997

N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex.

Golgi soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) GS28 and syntaxin 5 can be reciprocally coimmunoprecipitated from Golgi extracts, suggesting that they exist in a protein complex. When Golgi extract is preincubated with soluble NSF attachment proteins (alpha-SNAP) and N-ethylmaleimide-sensitive factor (NSF) under conditions that allow ATP hydrolysis by NSF, GS28 and syntaxin 5 become dissociated. GS28 and syntaxin 5 remain in a protein complex when Golgi extract is preincubated with similar amounts of alpha-SNAP and NSF under conditions that prevent ATP hydrolysis by NSF, suggesting that ATP hydrolysis by NSF is necessary for dissociating the GS28-syntaxin 5 complex. Since preincubation of Golgi extract with either alpha-SNAP or NSF alone has no effect on the GS28-syntaxin 5 complex, a concerted action of alpha-SNAP and NSF therefore mediates the dissociation of the GS28-syntaxin 5 complex. Furthermore, GS28 but not syntaxin 5 is capable of binding to immobilized alpha-SNAP when the GS28-syntaxin 5 complex is dissociated.

Animals↗