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Biomedical subjects

D Lancaster

Publications and source records attributed to D Lancaster.

30 records · Page 2Linked to original sources
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↗
PubMed1993

Histologic analysis of the osseointegration of endosseous implants in simulated extraction sockets with and without e-PTFE barriers. Part II: Histomorphometric findings.

This investigation constitutes a pilot study of osseous changes around hydroxylapatite-coated implants analyzed histologically nine weeks following their placement into stimulated mongrel dog extraction sites either with or without e-PTFE barriers. An image analysis system was utilized for the assessment of undecalcified sections for the following parameters: (1) crestal alveolar bone height, (2) distance to the most coronal bone in residual defects, (3) distance to the most lateral bone in residual defects, and (4) area of bone regenerated in standardized 1 mm x 3 mm portions of original defects. Two-way ANOVA demonstrated that there were significant differences among the barrier, non-barrier, and control sites for all parameters except crestal bone height (p < 0.05). When one animal which displayed premature clinical exposure of e-PTFE was excluded from the analysis, crestal change showed a significant improvement (P < 0.05) for barrier vs. non-barrier sites. Therefore, the proper application of e-PTFE barriers was usually associated with crestal bone apposition rather than resorption and a greater osseous fill of the original crestal defect when compared with sites where no barrier had been placed.

Alveolar Process↗
PubMed1992

The macroscopic, microscopic and spectrometric effects of various chemotherapeutic agents on the plasma-sprayed hydroxyapatite-coated implant surface.

The purpose of this research was to determine the nature of the residual hydroxyapatite (HA)-coated implant surface after treatment with various chemotherapeutic modalities, including: citric acid, chlorhexidine gluconate, hydrogen peroxide, tetracycline HCl, stannous fluoride, polymyxin B and a prototype plastic Cavitron tip. Implant surfaces were evaluated macroscopically, microscopically (scanning electron microscopy (SEM)) and spectrometrically (energy-dispersive spectrometry and X-ray diffraction). HA-substrate bond strength and dissolution testing was also performed for surfaces treated with a supersaturated citric acid solution. All treatments left either microscopic residues or a loss of surface roughness when viewed on SEM. A 30- to 60-s application of citric acid left a significantly greater coating thickness than all other treatments, whereas a 3-min application of citric acid removed significantly more HA than untreated controls. Significant changes in Ca/P ratios were seen with most treatments. The clinical significance of this phenomenon is not known. No treatments altered the crystallinity of the residual HA coating. A 1-min application of citric acid did not significantly alter the tensile bond strength of the coating to the substrate. The clinical significance of these findings is not known at present. However, when taken with results from previous studies, it appears that in treating the infected HA-coated implant surface, a 30- to 60-s application of citric acid (pH 1) may be beneficial in detoxifying the HA coating prior to regenerative procedures. Further in vitro and in vivo studies are necessary to evaluate the biological response to citric acid when used to detoxify the infected implant surface.

Analysis of Variance↗
PubMed1991

A preliminary evaluation of 566C80 for the treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome.

BACKGROUND: The drug 566C80 is an investigational hydroxynaphthoquinone that is active against Pneumocystis carinii in vitro and in animal models. Initial studies in humans indicate that 566C80 is safe and has adequate bioavailability after oral administration. METHODS: We conducted an open-label trial of 566C80 in 34 adults with the acquired immunodeficiency syndrome (AIDS) and untreated pneumocystis pneumonia. All the patients had a partial pressure of arterial oxygen of at least 60 mm Hg while breathing room air. They were enrolled sequentially in three cohorts taking 566C80 at different dosages, all administered orally: 750 mg three times daily for 5 days, then twice daily for 16 days; 750 mg three times daily for 21 days; and 750 mg four times daily for 21 days. RESULTS: All 34 patients survived, and 27 (79 percent) were successfully treated with 566C80 alone. The mean partial pressure of oxygen in 33 patients was 78 mm Hg at entry and 93 mm Hg after the course of 566C80 (P less than 0.001). In five patients (15 percent) the drug was discontinued because of lack of response. In four patients (12 percent), the drug was discontinued because of toxicity (fever and rash in two patients each). In two of these, treatment was considered to have succeeded because 566C80 was not discontinued because of toxicity until after day 14. Five of the successfully treated patients had rashes that resolved despite continued therapy. In nine patients, serum alanine aminotransferase levels rose above 100 U per liter. During the first three months after the completion of therapy, pneumocystis pneumonia recurred in 4 of the 27 successfully treated patients, and another 3 patients had recurrences between month 3 and month 6 of follow-up. The mean (+/- SEM) steady-state plasma levels of 566C80 were similar in the three cohorts: 16.3 +/- 2.10, 20.4 +/- 2.48, and 18.9 +/- 3.08 micrograms per milliliter in the patients taking the drug twice daily, three times daily, and four times daily, respectively. CONCLUSIONS: From these preliminary data, the investigational compound 566C80 appears to be a safe, effective, and well-tolerated therapy for P. carinii pneumonia of mild-to-moderate severity in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Immunogenicity of the intradermal route of hepatitis B vaccination with the use of recombinant hepatitis B vaccine.

In March 1987, 32 hospital employees were enrolled in a prospective trial of intradermal recombinant hepatitis B vaccination. Enrollees were given 0.1 ml of vaccine on days 1, 30, and 180. Two weeks after the third intradermal vaccination, 81%, or 26, of the enrollees showed seropositivity (greater than or equal to 10 mIU antibody/ml) for hepatitis B surface antibody. Five of six nonresponders were given a fourth intradermal vaccination. Two additional seroconversions occurred, resulting in an overall conversion rate of 90% for recipients of up to four intradermal vaccine doses. Complications of vaccination were limited primarily to the occasional persistence (less than 6 months) of hyperpigmentation at the injection site. Administration of recombinant hepatitis B vaccine by the intradermal route proved to be a safe and effective method of vaccination. Cost savings of preexposure immunization with the intradermal versus the intramuscular route of vaccination were approximately $90 per enrollee. Efficacy and safety can be maximized by employing a fourth vaccine dose and routinely documenting seroconversion after vaccination.

Antibody Formation↗
PubMed1989

Bronchopulmonary cross-colonization and infection related to mycobacterial contamination of suction valves of bronchoscopes.

Recurrent episodes of mycobacterial cross-contamination of bronchoscopy specimens were identified in a large, tertiary-care referral center. One episode was followed by active pulmonary infection due to Mycobacterium tuberculosis. Initial epidemiologic investigation implicated the flexible fiberoptic bronchoscopes. In experiments, bronchoscopes and related equipment were exposed to a saline suspension of M. fortuitum (10(5)-10(7)/mL). Bronchoscopes were readily sterilized by routine cleaning and disinfection procedures, but the spring-operated suction valves remained contaminated, even after a 30-min exposure to 2% glutaraldehyde or after passage through a commercial bronchoscope washer. These results indicate that suction valves that have been heavily contaminated with mycobacterial organisms cannot be reliably disinfected with commercially available glutaraldehyde. Suction valves have since been routinely autoclaved after each use. No additional episodes of cross-contamination or infection have occurred over 24 mo of surveillance.

Bronchoscopy↗
PubMed1989

Hypothyroidism: effect on warfarin anticoagulation.

Although our observation is not the first case of reduced PT response to oral anticoagulants associated with hypothyroidism, it is the only such interaction reported since 1963, and the first case involving warfarin therapy in a human being. We submit this case as a reminder of a potentially forgotten interaction, and to stress the importance of close monitoring in patients receiving warfarin therapy who have concomitant changes in thyroid function.

Administration, Oral↗