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Biomedical subjects

T E Davis

Publications and source records attributed to T E Davis.

At least 19 recordsLinked to original sources

Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882).

To investigate the effect of adding tamoxifen to megestrol in the hormonal therapy for advanced endometrial cancer, 66 patients were entered in this study. Initially, 41 patients were randomized to either the standard progestin therapy of megestrol or to the combination of megestrol and tamoxifen between October 1982 and October 1984. The megestrol arm was terminated because of poor accrual and 25 patients were directly assigned to the combination arm. Among the 20 eligible cases on the megestrol arm, the response rate of 20% consisted of I complete response and 3 partial responses. The response rate on the megestrol plus tamoxifen arm was 19% with 1 (2%) complete response and 7 (17%) partial responses among 42 eligible cases. The median survival times were 12.0 months and 8.6 months, respectively. Only mild and moderate toxicities were observed on megestrol compared with more toxic complications observed on the combination of megestrol and tamoxifen, including a life-threatening case of pulmonary embolism. Although we could not carry out a comparative evaluation as intended, we conclude that the combination of megestrol and tamoxifen offers no clinical advantage over megestrol alone in the treatment of advanced endometrial carcinoma.

Aged↗

Clearance of fungal burden during treatment of disseminated histoplasmosis with liposomal amphotericin B versus itraconazole.

Animal studies have shown that fungal burden correlates with survival during treatment with new antifungal therapies for histoplasmosis. The purpose of this report is to compare the clearance of fungal burden in patients with histoplasmosis treated with liposomal amphotericin B versus itraconazole. In two separate closed clinical trials that evaluated the efficacy of liposomal amphotericin B and itraconazole treatment of disseminated histoplasmosis in patients with AIDS, blood was cultured for fungus and blood and urine were tested for Histoplasma antigen. The clinical response rates were similar; 86% with liposomal amphotericin B (n = 51) versus 85% with itraconazole (n = 59). Of the patients with positive blood cultures at enrollment, after 2 weeks of therapy cultures were negative in over 85% of the liposomal amphotericin B group versus 53% of the itraconazole group (P = 0.0008). Furthermore, after 2 weeks, median antigen levels in serum fell by 1.6 U in the liposomal amphotericin B group versus 0.1 U in the itraconazole group (P = 0.02), and those in urine fell by 2.1 U in the liposomal amphotericin B group and 0.2 U in the itraconazole group (P = 0.0005). The more rapid clearance of fungemia supports the use of liposomal amphotericin B rather than itraconazole for initial treatment of moderately severe or severe histoplasmosis.

AIDS-Related Opportunistic Infections↗

Evaluation of BACTEC MYCO/F Lytic medium for recovery of mycobacteria, fungi, and bacteria from blood.

MYCO/F Lytic medium (MFL), a liquid medium developed for use with the BACTEC 9240 blood culture system, was compared to the Isolator system (IS) for the recovery of fungi and to the BACTEC 13A medium for the recovery of mycobacteria. Recovery of bacteria was compared to routine BACTEC Plus Aerobic/F (AF) blood cultures. Microbial growth was detected in 203 (17%) of 1,166 blood cultures. Fifty-seven specimens were positive for fungi: 35 were positive with both IS and MFL; six were positive with IS only (three Candida albicans, one Histoplasma capsulatum, one Candida glabrata, and one Fusarium species isolate); three were positive with AF only (two C. albicans and one Candida parapsilosis isolate); and 13 were positive with MFL only (five C. glabrata, three C. albicans, two Candida krusei, two Candida tropicalis, and one C. parapsilosis isolate; P > 0.05 versus IS). Eighteen of 19 blood cultures positive for H. capsulatum grew in both IS and MFL, although the time to detection for MFL was greater. The mean time to detection for all fungi was 8.15 days for IS and 12.07 days for MFL. Seven hundred forty specimens were also cultured for mycobacteria with MFL and 13A. Forty-four grew mycobacteria; 38 were positive with both 13A and MFL; and 16 were positive with MFL only. Mycobacterium avium was recovered from 41 specimens; 36 were positive for both systems and 5 were positive for MFL alone. MFL was also compared to the AF bottle for the same 740 specimens. MFL and AF both detected 34 of the 40 clinically significant bacteria, while IS detected only 15 of 40. In summary, MFL is an excellent medium for the recovery of fungi, mycobacteria, and bacteria; however, the time to detection of H. capsulatum is increased.

Bacteremia↗

Evaluation of the Affirm Ambient Temperature Transport System for the detection and identification of Trichomonas vaginalis, Gardnerella vaginalis, and Candida species from vaginal fluid specimens.

The objective of this study was to measure the performance of the Affirm Ambient Temperature Transport System (ATTS) over time and to estimate the length of time the system can preserve a vaginal specimen containing the three common organisms causing vaginitis: Trichomonas vaginalis, Candida species, and Gardnerella vaginalis (one of the causative agents of bacterial vaginosis). Women with symptoms of vaginitis presenting to one of three clinical centers were evaluated over a 4- to 8-week period. Four simultaneously obtained swabs were collected and tested by the Affirm VPIII assay at time zero with and without a preservative reagent, at 24 h with reagent, and at either 48 or 72 h with reagent. For each of the three organisms, Trichomonas, Gardnerella, and Candida, positivity at each time point was evaluated and compared to that at reference time zero with and without the ATTS. A total of 940 specimens were obtained from the three clinical sites. Eight hundred three were positive for one or more of the three organisms. Gardnerella had the highest overall positive rate (62%), followed by Candida with 18% and Trichomonas at 9%. The percent sensitivity versus control for Trichomonas ranged from 100% at time zero with and without reagent to 91% by 72 h. Gardnerella and Candida sensitivity remained at 100% for each time period. The Affirm VPIII ATTS system performed within 10% of the control swab (no transport reagent) at all four time points (0, 24, 48, and 72 h) for Trichomonas, Gardnerella, and Candida.

Animals↗

Diet restriction in rat toxicity studies: automated gravimetric dispensing equipment for allocating daily rations of powdered rodent diet into pouches and 7-day feeders.

Survival of ad libitum-fed rats has declined in the 2-year carcinogenicity bioassay. Restriction of the number of calories, without compromise of the overall nutrition offered to animals including rats, results in increased lifespan of animals. Diet restriction in rats is best achieved through offering of rations of feed daily instead of weekly, as is routinely done in ad libitum studies. The objective of this project was to develop an accurate and precise method of dispensing daily rations of feed. A gravimetric vibratory-type dispenser was used to dispense target weights of 15 and 20 g of powdered certified rodent diet into either labeled pouches or seven-well carousel feeders. The tolerance of the dispenser was the target weight +/- 3%. The amount of food offered to the diet-restricted rats was approximately 25% lower than that consumed by rats offered diet ad libitum. After 2 years, male rats offered 20 g and female rats offered 15 g of powdered rodent diet daily had remarkably lower body weights than did animals offered the diet ad libitum. Generally, the rats ate the entire ration of food offered to them each day. Survival of the diet-restricted rats was 70% to 82% at the end of a 2-year study. This investigation demonstrates that modest reduction of food intake, resulting in increased survival of Sprague Dawley rats in 2-year carcinogenicity bioassays, can be achieved reliably and efficiently through use of an accurate and precise automated method of dispensing powdered diet for use in multiple rat studies. In addition, this method of food dispensing provides a practical way to administer test compound in the diet under the conditions of diet restriction.

Animal Feed↗

Disseminated infection due to rapidly growing mycobacteria in immunocompetent hosts presenting with chronic lymphadenopathy: a previously unrecognized clinical entity.

Disseminated infection due to rapidly growing mycobacteria is uncommon and occurs mostly in immunocompromised patients. We report 16 cases of such infection with an unusual presentation seen at Srinagarind Hospital, a university hospital in northeastern Thailand. The clinical features were different from those in previous reports. All of the patients presented with chronic bilateral cervical lymphadenopathy. Twelve had mycobacterial involvement of other organs (sinuses, 6 patients; lungs, 4; liver, 4; spleen, 3; skin, 3; bone and joint, 2; and tonsils, 2). An interesting occurrence in 11 patients was 14 episodes of reactive skin manifestations (Sweet's syndrome, 9; generalized pustulosis and erythema nodosum, 2 each; and pustular psoriasis, 1). No identifiable predisposing factors, including human immunodeficiency disease, were found in these patients. However, 8 patients had 11 episodes of prior infection or coinfection with other opportunistic pathogens (salmonellosis, 4; penicilliosis, 3; pulmonary tuberculosis, 2; and melioidosis and cryptococcosis, 1 each). These findings suggest that cell-mediated immunity is defective in these patients.

Adult↗

Phase II pilot study of combined chemohormonal therapy with doxorubicin and estramustine in metastatic prostate cancer.

Twenty-nine patients with progressive hormone-refractory metastatic adenocarcinoma of the prostate were treated with daily estramustine phosphate at 10 mg/kg, and I.V. doxorubicin 50 mg/m2 every 3 weeks. Twenty-six patients were evaluable. Four of seven patients with nonosseous measurable disease had partial responses lasting 3 to 10 months. Eleven of 19 patients with osseous metastases had stable disease or improvement on bone scan, 6 of these for 7 months or longer. Median time to progression was 20 weeks, and the median survival was 43 weeks.

Adenocarcinoma↗

Data elements for emergency department systems, release 1.0 (DEEDS): a summary report. DEEDS Writing Committee.

Variations in the way that data are entered in ED record systems impede the use of ED records for direct patient care and deter their reuse for many other legitimate purposes. To foster more uniform ED data, the Centers for Disease Control and Prevention's (CDC) National Center for Injury Prevention and Control is coordinating a public-private partnership that has developed recommended specifications for many observations, actions, instructions, conclusions, and identifiers that are entered in ED records. The partnership's initial product. Data Elements for Emergency Department Systems, Release 1.0 (DEEDS), is intended for use by individuals and organizations responsible for ED record systems. If the recommended specifications are widely adopted, then problems--such as data incompatibility and high costs of collecting, linking, and using data--can be substantially reduced. The collaborative effort that led to DEEDS, Release 1.0 sets a precedent for future review and revision of the initial recommendations.

Emergency Service, Hospital↗

Data elements for emergency department systems, release 1.0 (DEEDS): a summary report. DEEDS Writing Committee.

Variations in the way that data are entered in emergency department record systems impede the use of ED records for direct patient care and deter their reuse for many other legitimate purposes. To foster more uniform ED data, the Centers for Disease Control and Prevention's National Center for Injury Prevention and Control is coordinating a public-private partnership that has developed recommended specifications for many observations, actions, instructions, conclusions, and identifiers that are entered in ED records. The partnership's initial product, Data Elements for Emergency Department Systems, Release 1.0 (DEEDS), is intended for use by individuals and organizations responsible for ED record systems. If the recommended specifications are widely adopted, then problems--such as data incompatibility and high costs of collecting, linking, and using data--can be substantially reduced. The collaborative effort that led to DEEDS, Release 1.0 sets a precedent for future review and revision of the initial recommendations.

Emergency Service, Hospital↗

Comparison of BACTEC plus Aerobic/F, Anaerobic/F, Peds Plus/F, and Lytic/F media with and without fastidious organism supplement to conventional methods for culture of sterile body fluids.

We compared the BACTEC 9240 continuous-read instrument using Peds Plus/F, Lytic/F, Aerobic/F, and Anaerobic/F media (Becton Dickinson Diagnostic Instrument Systems, Sparks, MD) with and without fastidious organism supplement to conventional centrifugation preparation and plating for the recovery and speed of detection of microorganisms. A total of 908 sterile body fluid specimens were collected and processed, yielding 116 (13%) positive cultures. Of the 80 isolates considered clinically significant, 48 (60%) were recovered by both the BACTEC system and conventional culture, whereas 32 (40%) were recovered by BACTEC only. No clinically significant isolates were recovered only by conventional culture methods. The time to detection for isolates recovered from both sets was faster for BACTEC. It was found that BACTEC, with or without the addition of fastidious organisms supplement, exhibited improved sensitivity for the recovery of microorganisms.

Bacteria, Anaerobic↗

Surfactant protein A (SP-A) mediates attachment of Mycobacterium tuberculosis to murine alveolar macrophages.

Attachment of Mycobacterium tuberculosis organisms to alveolar macrophages (AMs) is an essential early event in primary pulmonary tuberculosis. Surfactant protein A (SP-A) is a nonimmune opsonin present in the alveolar spaces that binds carbohydrate residues such as mannose. It was hypothesized that SP-A attaches to M. tuberculosis and serves as a ligand between M. tuberculosis and AMs. [125I]SP-A was found to bind to M. tuberculosis in a time- and [Ca2+]-dependent manner with a Kd of 1.9 x 10(-9) M and an apparent number of 6.3 x 10(2) SP-A binding sites/organism. Further, deglycosylated SP-A had minimal binding to M. tuberculosis, indicating that sugar moieties are important in this interaction. SP-A specifically binds to a 60-kD cell-wall protein from M. tuberculosis. SP-A-mediated attachment of 51Cr-labeled M. tuberculosis organisms to AMs is dependent on time, SP-A concentration, and Ca2+. M. tuberculosis attachment to murine AMs in the absence of SP-A was 12.8 +/- 0.9%; however, in the presence of 5 microg/ml SP-A the attachment increased to 38.6 +/- 2.9% (P < 0.001). SP-A-mediated attachment was significantly decreased from 38.6 +/- 2.9% to 18.7 +/- 3.3% (P < 0.05) in the presence of antihuman SP-A antibodies. When the attachment assay was repeated in the presence of alpha-methylene-D-mannosepyranosidase (mannosyl-BSA) and type V collagen, SP-A-mediated attachment decreased from 38.6 +/- 2.9% to 16.6 +/- 1.5% (P < 0.001) and 19.1 +/- 1.4% (P < 0.05), respectively. Further, deglycosylated SP-A had only a minimal effect on M. tuberculosis attachment to AMs. These data indicate that SP-A can mediate M. tuberculosis attachment to AMs, and suggest possible underlying mechanisms for this.

Animals↗

Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen.

BACKGROUND: Tamoxifen and aminoglutethimide are two hormone therapies reported to be effective palliative approaches for patients with metastatic breast cancer. The current trial was designed to evaluate their relative therapeutic effectiveness. METHODS: Two hundred forty-nine postmenopausal women with advanced breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG) Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen with crossover to alternate therapy if disease progressed. Adrenalectomy was dropped as a treatment after 2 years because of low patient accrual. RESULTS: There were 216 evaluable patients entered in the study with 108 initially randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One institution had a response rate of 60% with aminoglutethimide and only 4% with tamoxifen, whereas all of the other institutions combined had a response rate of 41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable patients crossed over to the other drug (44 to aminoglutethimide and 43 to tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to tamoxifen, with stable disease in 36% of both groups. The overall survival rates were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was not life-threatening. Glucocorticoid support with either dexamethasone or hydrocortisone was acceptable. CONCLUSIONS: Both aminoglutethimide and tamoxifen produced responses in postmenopausal patients with breast cancer, and a significant number of crossover responses were observed. Of interest in this randomized study was the observation that one institution had a markedly different response rate on induction, reinforcing the need for multi-institution trials in Phase III studies.

Adrenalectomy↗

A prospective, in vivo study of the relationship between blood flow hemodynamics and atherosclerosis in a hyperlipidemic swine model.

PURPOSE: This is the first prospective evaluation of the relationship between shear stress and atherosclerotic plaque formation in a pulsatile, in vivo model. METHODS: A 50% aortic stenosis was created in six Yucatan micropigs by placing a suture line across the left half of the aorta. A specially modified 20 MHz Doppler ultrasound probe mounted at a 45 degree angle on a micromanipulator was used to measure blood flow velocity along the lateral aspects of the aorta. Shear stress at these locations was calculated with linear regression. The pigs were then fed a specially formulated hyperlipidemic diet for 7 months, after which their aortas were harvested. Plaque thickness was measured and correlated with mean, maximum, and minimum shear stress at each site and side on or away from the aortic plication and distance from the level of the aortic plication with general linear modeling. RESULTS: Plaque thickness was negatively correlated with the mean shear stress during the cardiac cycle (correlation coefficient -0.3972 p = 0.0164) and with the maximum shear stress during the cardiac cycle (correlation coefficient -0.4581 p = 0.0050). Plaque thickness was correlated with a multivariate model of mean shear stress, maximum shear stress, and their interactive effects with other parameters in the model with a correlation coefficient of 0.6733, (p = 0.0048). CONCLUSIONS: This is the first prospective, in vivo study with a pulsatile, hyperlipidemic model, which clearly demonstrates that low shear stress is associated with plaque formation.

Animals↗

Comparison of BACTEC Plus 26 and 27 media with and without fastidious organism supplement with conventional methods for culture of sterile body fluids.

We compared the BACTEC Plus 26/27 culture system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) with and without fastidious organism supplement with conventional centrifugation preparation and plating for the recovery and speed of detection of microorganisms. A total of 1,101 sterile body fluid specimens were collected and processed at five hospital laboratories, yielding 234 (21%) positive cultures. Of the 176 isolates considered clinically significant, 133 (76%) were recovered by both the BACTEC system and conventional culture, while 28 (16% [P < 0.005]) were recovered by BACTEC only and 11 (6%) were recovered by conventional culture alone. There were no statistically significant differences in the speed of detection of microbial growth. It was found that BACTEC, with or without the addition of fastidious organism supplement, exhibited improved sensitivity for the recovery of microorganisms, including fastidious bacteria.

Bacteria↗

Use of chemiluminescent DNA probes in the rapid detection of oxacillin resistance in clinically isolated strains of Staphylococcus aureus.

Chemiluminescent DNA probes (AccuProbe, species specific; and FlashTrack, bacterial generic) were used to determine oxacillin resistance in Staphylococcus aureus. Ribosomal RNA was measured at designated intervals in the presence and absence of antibiotic. A total of 48 (AccuProbe assay) and 24 (FlashTrack) S. aureus isolates with known oxacillin susceptibility patterns were inoculated into Bactec 6A bottles both with and without 4 micrograms/ml oxacillin and incubated at 35 degrees C for 4 h. Aliquots were removed at 0 and 4 h, and pellets of bacteria were obtained via selective centrifugation. Probe assay counts (relative light units, RLUs) were performed. Of 21 oxacillin-resistant S. aureus (ORSA) strains, 20 showed a > 5-fold RLU increase during the incubation period (Accu-Probe assay): 25 of 27 oxacillin-susceptible strains demonstrated a < or = 4-fold increase. AccuProbe test sensitivity and specificity were 95% and 92%, respectively. With the generic FlashTrack probe assay, all nine ORSA isolates showed a > or = 4- to 10-fold increase in RLUs, and all 15 oxacillin-susceptible strains showed a < or = 4-fold increase in RLUs during the 4-h incubation. The FlashTrack test sensitivity and specificity were both 100%. Probe assays were completed within 5 h. This study suggests that rapid and reliable determination of oxacillin resistance in S. aureus clinical isolates can be accomplished using commercially available DNA probes.

Bacteriological Techniques↗