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Biomedical subjects

D Lancaster

Publications and source records attributed to D Lancaster.

At least 19 recordsLinked to original sources

Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.

We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.

AIDS-Related Opportunistic Infections↗

Use of capecitabine as first-line therapy in patients with metastatic breast cancer relapsing after high-dose chemotherapy and autologous stem cell support.

High-dose chemotherapy with autologous stem cell support (HDC-ASCS) can produce high complete remission rates in patients with metastatic breast cancer (MBC). However, the majority of those so treated will relapse within 3 years. The ability of such patients to tolerate further myelosuppressive chemotherapy may be limited and the best therapy is undefined. In this retrospective study we assessed the role of capecitabine as initial therapy after relapse. Ten patients (median age = 47 years; oestrogen receptor-positive, n = 4; visceral disease, n = 6; prior anthracycline, n = 8, prior taxanes, n = 10), whose disease progressed at a median of 246 days (range 69-480) after HDC-ASCS and who were treated with capecitabine (2500 mg/m2 per day for 2 weeks of a 3-week cycle) as initial therapy for relapse, were assessed retrospectively for response and toxicity. They received a median of eight cycles (range 4-24) of capecitabine. The toxicities encountered while receiving capecitabine were: hand-foot syndrome (grade 1, n = 3; grade 2, n = 4; grade 3, n = 1); diarrhoea (grade 1, n = 1; grade 2, n = 3); nausea (n = 2) and fatigue (n = 5). Haematological toxicity was seen in only one patient. No patient required hospitalization for toxicity. Three achieved a complete remission, four a partial remission and three disease stabilization. After a median follow-up of 183 days from commencing capecitabine (range 97-540), all patients were alive and five were in remission. Five progressed after remissions that lasted between 63 and 252 days. Oral capecitabine is an active and well-tolerated agent when used alone as first-line therapy in patients who have relapsed after HDC-ASCS for MBC.

Adult↗

Field intercomparison of a novel optical sensor for formaldehyde quantification.

A one-week in situ intercomparison campaign was completed on the Rice University campus for measuring HCHO using three different techniques, including a novel optical sensor based on difference frequency generation (DFG) operating at room temperature. Two chemical derivatization methods, 2,4-dinitrophenylhydrazine (DNPH) and o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA), were deployed during the daylight hours for three- to four-hour time-integrated samples. A real-time optical sensor based on laser absorption spectroscopy was operated simultaneously, including nighttime hours. This tunable spectroscopic source based on difference frequency mixing of two fiber-amplified diode lasers in periodically poled LiNb03 (PPLN) was operated at 3.5315 micrometers (2831.64 cm 1) to access a strong HCHO ro-vibrational transition free of interferences from other species. The results showed a bias of -1.7 and -1.2 ppbv and a gross error of 2.6 and 1.5 ppbv for DNPH and PFBHA measurements, respectively, compared with DFG measurements. These results validate the DFG sensor for time-resolved measurements of HCHO in urban areas.

Atmosphere↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗