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Biomedical subjects

D Lancaster

Publications and source records attributed to D Lancaster.

At least 19 recordsLinked to original sources
PubMed1999

Favorable impact of stents after emergent coronary artery bypass for failed angioplasty.

BACKGROUND: This study was undertaken to determine the impact of the use and availability of coronary stents on outcomes in patients requiring emergent coronary artery bypass graft (CABG) surgery following a failed percutaneous transluminal coronary angioplasty (PTCA). METHODS: Patients were divided into two groups based on the year of their CABG for a failed PTCA and the availability of stents: group 1, 1992 to 1994, stents not available (n = 34); and group 2, 1995 to 1997, stents available (n = 26). RESULTS: CABG patients in the group where stents were not available were more likely to have had an abrupt coronary occlusion (26 of 34 versus 3 of 26; p < 0.0001) and less likely to have had a dissection (8 of 34 versus 23 of 26; p < 0.0001) as their indication for emergent CABG. Patients in the stent era had a lower incidence of perioperative myocardial infarction (5 of 26 versus 17 of 34; p < 0.01) and a decreased mortality rate (0 of 26 versus 6 of 34; p < 0.03). In the 9 patients where stents were employed, patency of the lumen was restored in 8 patients and there was only 1 myocardial infarction. CONCLUSIONS: Stents have had a favorable impact on patients requiring an emergent CABG following a failed PTCA.

Aged↗
PubMed1998

Antiretroviral effect and safety of abacavir alone and in combination with zidovudine in HIV-infected adults. Abacavir Phase 2 Clinical Team.

OBJECTIVES: To evaluate, over 12 weeks, the antiretroviral activity and safety of abacavir, used alone and in combination with zidovudine (ZDV), as treatment for HIV-1-infected subjects who had limited or no antiretroviral treatment. DESIGN: Seventy-nine HIV-1-infected subjects, with CD4 cell counts 200-500 x 10(6)/l and <12 weeks of previous treatment with ZDV were enrolled in a multicenter study. Subjects were randomly assigned to one of four cohorts receiving abacavir monotherapy for the first 4 weeks (200, 400, or 600 mg every 8 h daily, or 300 mg every 12 h daily) and, thereafter, combination therapy of abacavir with 600 mg ZDV or ZDV placebo, administered in a double-blind manner for an additional 8 weeks. METHODS: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4+ cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities during the 12-week period and for 4 weeks post-treatment. RESULTS: Treatment with abacavir, alone or in combination with ZDV, produced marked decreases in plasma HIV-1 RNA loads and increases in CD4+ cell counts in all groups. At week 4, median plasma HIV-1 RNA loads decreased by 1.11-1.77 log10 copies/ml and median CD4+ cell counts increased by 63-111 x 10(6)/l in all groups. At week 12, median HIV-1 RNA loads decreased by 1.02-2.24 log10 copies/ml (abacavir monotherapy) and by 1.81-2.01 log10 copies/ml (abacavir-ZDV); median CD4+ cell counts increased by 79-195 x 10(6)/l (abacavir monotherapy) and by 93-142 x 10(6)/l (abacavir-ZDV). At week 12, the percentage of subjects who had plasma HIV-1 RNA levels below 400 and 40 copies/ml were 28 and 11%, respectively (abacavir monotherapy) and 69 and 22%, respectively (abacavir-ZDV). Eight subjects (10%) discontinued the study prematurely because of adverse events; nausea (n = 4) and hypersensitivity (n = 3) were the most common reasons for withdrawal. There were no deaths among the study subjects. CONCLUSIONS: In HIV-infected subjects who have received little or no prior antiretroviral therapy, treatment with abacavir alone or in combination with ZDV is well tolerated and resulted in sustained improvements in key immunologic and virologic efficacy parameters through 12 weeks.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Development of a new cartridge radioimmunoassay for determination of intracellular levels of lamivudine triphosphate in the peripheral blood mononuclear cells of human immunodeficiency virus-infected patients.

A new sensitive method for the measurement of lamivudine triphosphate (3TC-TP), the active intracellular metabolite of lamivudine in human cells in vivo, has been established. The procedure involves rapid separation of 3TC-TP by using Sep-Pak cartridges, dephosphorylation to 3TC by using acid phosphatase, and measurement by radioimmunoassay using a newly developed anti-3TC serum. The radioimmunoassay had errors of less than 21% and a cross-reactivity of less than 0.016% with a wide variety of other nucleoside analogs. The limit of quantitation of the assay for intracellular 3TC-TP was 0.195 ng/ml (0.212 pmol/10(6) cells), and a cell sample of only 4 million cells was ample for the assay. This procedure, combined with our previously developed method for measuring zidovudine (ZDV) metabolite levels, proved capable of measuring 3TC-TP, ZDV monophosphate (ZDV-MP) and ZDV triphosphate (ZDV-TP) in human immunodeficiency virus (HIV)-infected subjects treated with combination 3TC and ZDV therapy. In seven subjects, intracellular 3TC-TP levels ranged from 2.21 to 7.29 pmol/10(6) cells, while intracellular ZDV-MP and ZDV-TP levels ranged from <0. 01 to 1.76 and 0.01 to 0.07 pmol/10(6) cells, respectively. Concentrations of 3TC in plasma determined in these subjects ranged from 0.34 to 9.40 microM, which was about fivefold higher than ZDV levels in plasma of 0.04 to 1.4 microM. This is the first study to determine the intracellular levels of the active metabolites in HIV-infected subjects treated with this combination. These methods should prove very useful for in vivo pharmacodynamic studies of combination therapy.

Animals↗
PubMed1997

Factors influencing mortality after emergency coronary artery bypass grafting for failed percutaneous transluminal coronary angioplasty.

BACKGROUND: Emergency coronary artery bypass grafting after failed percutaneous transluminal coronary angioplasty is associated with increased mortality. METHODS: From 1981 through 1995, 117 patients at our institution underwent emergency coronary artery bypass grafting after failed percutaneous transluminal coronary angioplasty, with an in-hospital mortality rate of 13.6%. Univariate and multivariate analyses were used to identify the factors that influenced the risk of death. RESULTS: Univariate analysis revealed that patients who died more often were women and had chronic renal failure, lower ejection fractions, and more diffuse coronary artery disease; less often received an internal mammary artery graft or an antegrade perfusion catheter; required inotropic support in the cardiac catheterization laboratory; and experienced myocardial infarction. Multivariate analysis demonstrated that the need for inotropic support in the cardiac catheterization laboratory was the best predictor of perioperative death. CONCLUSIONS: Patients with a reduced ejection fraction in whom percutaneous transluminal coronary angioplasty fails, antegrade perfusion does not produce a response, and myocardial infarction occurs are more likely to die after coronary artery bypass grafting. The risk appears to be highest for patients who require inotropic support in the cardiac catheterization laboratory.

Analysis of Variance↗
PubMed1997

Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting.

OBJECTIVE: This prospective, randomized, clinical study was undertaken to determine whether glucose-insulin-potassium solutions would benefit patients undergoing coronary artery bypass grafting because of unstable angina. METHODS: The study group consisted of 30 patients with unstable angina who required coronary artery bypass grafting. In 15 patients, glucose-insulin-potassium solution (30% dextrose in water; K+, 80 mEq/L: regular insulin, 50 units) was given intravenously at 1 ml/kg per hour after induction of anesthesia and administration continued for 12 hours after aortic unclamping. Fifteen patients in a separate group received 5% dextrose in water intravenously at 50 ml/hr. RESULTS: Patients treated with glucose-insulin-potassium solution had higher cardiac indices (2.8 +/- 0.1 vs 2.0 +/- 1 L/min per square meter; p < 0.001), lower inotrope scores (0.06 +/- 0.01 vs 0.46 +/- 0.19; p = 0.041), and less weight gain (6.4 +/- 9 vs 11.6 +/- 1.1 pounds; p < 0.001) and had shorter times of ventilator support (8.3 +/- 0.6 vs 14.2 +/- 0.2 hours; p = 0.003). They had a significantly lower incidence of atrial fibrillation (13.3% vs 53.3%; p = 0.020) and had shorter stays in the intensive care unit (14.8 +/- 1.3 vs 31.6 +/- 5.2 hours; p = 0.002) and in the hospital (6.0 +/- 0.4 vs 8.0 +/- 0.7 days; p = 0.010). CONCLUSIONS: We conclude that glucose insulin-potassium therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting.

Adult↗
PubMed1997

Profile of non-compliance in lymphoblastic leukaemia.

A nationwide study of intracellular drug metabolite concentrations in children prescribed 6-mercaptopurine for the treatment of lymphoblastic leukaemia was carried out to assess interpatient variability at a standardised dose. Nine children (2% of the total) had completely undetectable metabolites, indicative of non-compliance. Five were adolescents, but otherwise they had no obvious distinguishing characteristics. Not taking any 6-mercaptopurine at all is uncommon, but the problem cannot be predicted. The total number of children who do not comply cannot be determined from this study, but the nine children described represent only a fraction of these.

Adolescent↗
PubMed1996

Radiocephalometric evaluation of a family with mandibulofacial dysostosis.

Persons from four generations of a family with mandibulofacial dysostosis (MFD), known as Treacher Collins (TC) Syndrome, were examined for the presence of clinical signs traditionally associated with this syndrome. In this family, 14 adults, who had been judged trait bearers by an earlier family study were included in this study. Maxillary and mandibular study models were taken of affected and unaffected family members. Panoramic cephalograms and lateral radiographs were taken. The lateral cephalograms were traced and digitized on a computer system and compared. The 117 cephalometric values of the trait bearers were compared with known standard values and nontrait bearing family members. In the trait bearing group, 81 of the 117 values and, in the nontrait bearing group, 72 of the 117 values were significantly different (p < 0.05) when comparing mean values to the accepted normal range. The interfamily comparison between trait-bearing and nontrait members revealed nine values to be significantly different. This indicates that cephalometric analysis of these patients, some of whom have minimal clinical expression of the gene, may have potential value for screening and further characterization of this condition. The results also suggest that intrafamily comparisons may be of greater value for diagnostic confirmation of TC than comparison with literature norms.

Adult↗
PubMed1995

Presence of anti-hepatitis C virus serum markers in a dental school patient population.

Hepatitis C virus (HCV) has joined the list of infections liver diseases of which the practicing dentist must be aware. This recently described RNA virus causes between 20% to 40% of reported cases of viral hepatitis in the United States. Patients with HCV show symptoms only one quarter of the time, but chronicity is maintained longer than with the other liver infections. The major mode of transmission is percutaneous, so dentists are potentially at risk to contact the virus. To assess the presence of exposure to HCV, a total of 500 dental school patients were screened for serum antibody to this virus (second-generation anti-HCV). In addition, participants were required to fill out a special screening questionnaire designed to indicate high-risk groups. Their serum was also analyzed for serum chemistries known to be associated with acute and chronic liver disease. Analysis of the 15 response questionnaires revealed statistical significance relating to questions inquiring about previous exposure to blood (transfusions, surgical procedures, etc) but little significance relating to lifestyle. In either case responses were not of practical predictive value. More than 5% of our sample patients were found to be positive reactors to anti-HCV, indicating previous HCV exposure. A significant number of those positive for anti-HCV also showed elevation of serum chemistries associated with hepatitis.

Adolescent↗
PubMed1994

Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the effectiveness of fluconazole for suppression of relapse of histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective, nonrandomized, open trial. SETTING: Multicenter at two university referral centers and in five private practices. PATIENTS: Seventy-six patients with AIDS and disseminated histoplasmosis who completed induction treatment with amphotericin B, itraconazole, or fluconazole and maintained on treatment with fluconazole to prevent relapse. INTERVENTIONS: Fluconazole was given at dosages of 100 to 400 mg per day. Patients were followed by their primary physicians, who completed questionnaires collecting information about treatment and relapse status. Blood and urine specimens were submitted periodically for Histoplasma capsulatum var. capsulatum antigen determination. MEASUREMENTS AND MAIN RESULTS: Nine of the 76 patients relapsed during fluconazole therapy and another was removed from the study because of allergic rash. Survival after initiation of therapy for histoplasmosis was 94 weeks, ranging from 74 weeks for those who received less than 1 g of amphotericin B for induction and none for maintenance therapy to 156 weeks for those who received greater than 1 g for induction and additional amphotericin B for maintenance therapy before beginning fluconazole (P < 0.02). Antigen levels fell at rates of 0.05 units/week in urine and 0.02 units/week in serum in patients who were successfully maintained in remission and increased by > or = 2 units/week in 4 of 6 patients who relapsed. CONCLUSIONS: Fluconazole > or = 200 mg daily is a reasonable choice for chronic suppressive therapy of histoplasmosis in patients who cannot take itraconazole because of drug interactions, malabsorption, or side effects.

AIDS-Related Opportunistic Infections↗
PubMed1994

Adenovirus parotitis in patients with AIDS.

Adenoviruses are well documented as opportunistic pathogens in patients with immunocompromising conditions, including human immunodeficiency virus (HIV) infection. We recently diagnosed adenovirus infection of the parotid gland in two patients with AIDS. Viral cultures and electron microscopic examinations of parotid tissue were positive in both cases. Adenovirus infection should be considered in the differential diagnosis of parotid swelling in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1993

Kinematics and thermodynamics of a folding heteropolymer.

In order to elucidate the folding dynamics of protein, we have carried out numerical simulations of a heteropolymer model of self-interacting random chains. We find that folding propensity depends strongly on sequence and that both folding and nonfolding sequences exist. Furthermore we show that folding is a two-step process: the transition from coil state to unique folded state takes place through a globule phase. In addition to the continuous coil-globule transition, there exists an abrupt transition that separates the unique folded state from the globule state and ensures the stability of the native state.

Protein Folding↗
PubMed1993

Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. METHODS: We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). RESULTS: Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

AIDS-Related Opportunistic Infections↗