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Biomedical subjects

J R Davis

Publications and source records attributed to J R Davis.

At least 73 records · Page 4Linked to original sources

Dematiaceous fungi are an increasing cause of human disease.

The dematiaceous fungi appear to be an increasing cause of human disease. At The Methodist Hospital, in Houston, Texas, five cases of serious disease caused by these fungi occurred between 1987 and 1992. Cerebral abscesses with Xylohypha bantiana followed treatment for lymphoma. An infection of the lower extremity with Exophiala jeanselmei var. castellanii followed cardiac surgery. Peritoneal growth of Alternaria tenuissima was a complication of peritoneal dialysis. Cerebral abscesses with Dactylaria gallopava occurred in a liver transplantation patient. A traumatic ankle wound contaminated with dirt led to an infection with Phialophora repens. All patients except the last were immunocompromised at the time of the infection; diabetics and patients on steroids may be at particular risk.

Adult↗

Impaired processing of proopiomelanocortin in corticotroph macroadenomas.

The regulation and secretion of the ACTH precursors POMC and pro-ACTH were assessed directly using a 2-site immunoradiometric assay in six patients with pituitary macroadenomas (> or = 1.2 cm in diameter) and 27 patients with Cushing's disease due to a microadenoma. ACTH precursor levels were elevated in patients with macroadenomas (150-3690 pmol/L; normal range, < 5-40 pmol/L) and significantly higher than those in microadenoma patients (median, 29 pmol/L; range, 9-104 pmol/L; P < 0.001). Patients with macroadenomas also had increased ACTH precursor/ACTH ratios (15-181:1) compared with microadenoma patients (median, 5:1, range, 0.7-18.5:1; P < 0.001). ACTH precursors were unresponsive to high dose dexamethasone in patients with macroadenomas, whereas ACTH and cortisol responses varied. After CRH administration, ACTH precursors were unchanged, whereas cortisol increased significantly, suggesting the release of biologically active ACTH. This study clearly demonstrates reduced processing of POMC to ACTH in large pituitary tumors, a characteristic usually associated with tumors causing the ectopic ACTH syndrome, and provides evidence for differential regulation of ACTH precursors and ACTH by glucocorticoid and CRH. Variation in the clinical symptoms of patients with corticotroph macroadenomas may be attributable to differences in biological potency between the ACTH precursors and ACTH.

Adenoma↗

The human placenta expresses transcription enhancer factor-1 but there is no correlation with the expression of placental lactogen.

A transcriptional enhancer which has a consensus binding sequence for transcription enhancer factor-1 (TEF-1) has been found 3' of the hPL(3) gene. We examined whether TEF-1 is expressed by the human placenta and whether such expression is co-ordinated with that of human placental lactogen (hPL). Probing Northern blots of total RNA from first trimester and term placenta, the choriocarcinoma-derived cell line JAr and primary cultured cytotrophoblast cells with a cDNA for TEF-1 revealed transcripts of 12-13 kb and 3-4 kb. The level of TEF-1 expression was the same in first trimester as compared with term placenta and in undifferentiated JAr as compared with differentiated cytotrophoblast cells. hPL expression was tenfold higher in term compared with first trimester placenta and, whilst detectable in cytotrophoblast cells, was undetectable in JAr cells. These data show that TEF-1 is expressed by the placenta but is not co-ordinated with hPL expression.

Cell Differentiation↗

Bacterial population dynamics in three anopheline species: the impact on Plasmodium sporogonic development.

The functional role of bacteria in the midgut of adult mosquitoes is unknown. In this study, we examined the population dynamics of midgut bacteria of laboratory reared Anopheles stephensi, An. gambiae, and An. albimanus. Mosquito midguts were dissected under sterile conditions and examined for the presence of bacteria using standard microbiologic techniques. Ninety percent and 73% (n = 30) of newly emerged An. gambiae and An. stephensi, respectively, harbored bacteria. In contrast, only 17% (n = 23) of An. albimanus harbored any bacteria. The bacterial population increased 11-40-fold in the presence of a blood meal, but then decreased to pre-blood meal levels in 3-5 days. Pseudomonas cepacia, Enterobacter agglomerans, and Flavobacterium spp. were found in all three anopheline species. Midgut bacteria were acquired both transtadially and through the sugar meal. Transtadial transmission was demonstrated by successfully passaging Escherichia coli HS5 from the larval to the adult stage. However, midgut bacteria were acquired more efficiently through the sugar meal than through transtadial passage. An increase in midgut bacterial counts after mosquitoes were exposed to a bacteria/sugar suspension significantly reduced oocyst infection rates and densities in Plasmodium falciparum-infected mosquito cohorts. Since bacteria occur naturally in wild mosquitoes, it may be possible to modify anopheline vector competence using introduced or indigenous bacteria.

Animals↗

Case triage model for the practice of telepathology.

OBJECTIVE: To implement and evaluate a practice model for telepathology. METHODS: A case triage practice model was devised in which general pathologists review all cases and refer them to subspecialists only when necessary. In 1993, the Arizona-International Telemedicine Network (AITN), a high-resolution static imaging telepathology diagnostic network, linking six sites to the University of Arizona in Tucson, began testing the model. Work flow through the network was analyzed, and diagnostic concordance was assessed in 150 surgical cases by comparing the diagnoses of the referring (transmitting) pathologists with diagnoses of the consulting (receiving) telepathologists as well as by comparing the referring pathologists' diagnoses with the consensus diagnoses reached by an independent review panel. Data analysis was controlled for subspecialty case type. Telepathologists had access to the referring pathologists' preliminary diagnoses, and the review panel had access to the original glass slides and the surgical pathology reports prior to rendering their respective diagnoses. RESULTS: The triage pathologist completed the telepathology consultation without the assistance of a subspecialty pathologist in 66% of the cases. The review panel examined the original glass slides from 134 cases by light microscopy. Concordance rates of the telepathologists' or review panel's diagnoses with the referring pathologists' diagnoses were not statistically different (93.1% v 83.6%, respectively; P > 0.05). CONCLUSION: The case triage model is suitable for the practice of telepathology. It significantly reduces the need for subspecialty pathologists. Static imaging telepathology is useful and reasonably efficient for rendering diagnostic opinions in the majority of referred cases. Tissue sampling limitations imposed by static imaging occasionally resulted in diagnostic errors.

Adult↗

Comparison of sampling anopheline mosquitoes by light-trap and human-bait collections indoors at Bagamoyo, Tanzania.

The mosquito sampling efficiency of CDC miniature light-traps, relative to night-biting collections, was evaluated indoors at two sites in coastal Tanzania. We found that the total number of anophelines captured overnight by light-traps (hung beside a bednet in use) was 1.23 times the number of anophelines captured by human-bait collections. This relationship was not affected significantly by changes in the mosquito density, order of trapping method, date of sampling, or number of household occupants. Malaria sporozoite rates were twice as high among mosquitoes captured by light-trap as compared to those captured by night-biting collection. This was attributed to the tendency of light-traps to capture a larger proportion of gravid mosquitoes, which also had high sporozoite rates. The differences in sporozoites rates according to abdominal stage indicates that unfed mosquitoes captured by light-traps may define more precisely the human-biting activity and sporozoite rates as seen by night-biting collections. Our study shows that light-traps, when used in combination with night-biting collections, can be an effective and sensitive means for measuring human-biting activity and the sporozoite rate.

Animals↗

Malaria infection potential of anopheline mosquitoes sampled by light trapping indoors in coastal Tanzanian villages.

Anopheline mosquito populations were studied during 1992 in seven villages south of Bagamoyo, coastal Tanzania, prior to malaria control intervention using insecticide treated bednets. To collect mosquitoes, CDC light traps were used in ten houses per village fortnightly for 12 months. Anopheles females were identified and checked by ELISA for the presence of malaria sporozoite antigen and source of bloodmeal. An.funestus peaked in June-July after the long rains. Three members of the An.gambiae complex had different seasonality: An.arabiensis, An.gambiae and small numbers of An.merus were collected. In most villages transmission was extremely high and perennial with the entomological inoculation rate reaching three to eleven infective bites per person per night in July and persisting at around 0.1 and 1 for most of the remainder of the year. Sporozoite infection rates within the An.gambiae complex ranged from 2% to 25%, with the peaks in January and July following the two rainy periods. An.funestus showed a similar pattern. The light traps were reliable, simple to operate, and proved to be satisfactory to study the mosquito vector population.

Animals↗

X-linked lymphoproliferative disease: twenty-five years after the discovery.

The X-linked lymphoproliferative disease (XLP), one of six described X-linked immunodeficiencies, stems from a mutation at Xq25 which renders males impotent to mount an effective immune response to the ubiquitous EBV. Purtilo, who first observed this disease in 1969, established a Registry in 1980 to serve as a worldwide resource for the diagnosis, treatment, and research of this condition. Since Purtilo's death in late 1992, the Registry and research unit have not only continued to function as a worldwide consultative service, but have contributed the following. First, the number of affected boys has continued to grow; some 272 among 80 kindreds have been identified. Second, some boys (10%) who inherit the mutated XLP gene are immunologically abnormal even before evidence of EBV exposure. Third, the search for the XLP gene has been narrowed to a small region on Xq25. Its identification is near at hand; once cloned, this gene may well illustrate how the body orchestrates the complex immune response to EBV. Therein lies the justification for the quest for this gene, not only for the benefit of the few surviving boys and those to be born to female carriers, but also for defining its role in defending the body against a ubiquitous DNA virus.

Child↗

Elevated levels of adrenocorticotropin (ACTH) precursors in post-adrenalectomy Cushing's disease and their regulation by glucocorticoids.

The ACTH precursor pro-opiomelanocortin (POMC) undergoes specific endoproteolytic cleavages in the anterior pituitary gland to give ACTH-(1-39). ACTH precursors circulate in normal subjects and are high both in the ectopic ACTH syndrome and in patients with aggressive pituitary adenomas. This study examines plasma levels of ACTH precursors and ACTH in 24 patients with post-adrenalectomy Cushing's disease, in 10 of whom computed tomography showed evidence of tumor progression. ACTH precursors were higher in post-adrenalectomy Cushing's disease (median 97.5 pmol/L, range 26-647 pmol/L) than in untreated Cushing's disease (median 29 pmol/L, range 9-104 pmol/L) and normal controls (5-40 pmol/L) (P < 0.001) and were significantly higher in patients with larger tumors (median 175 pmol/L, range 52-647 pmol/L) than in the remainder (median 41 pmol/L, range 26-510 pmol/L) (P = 0.02). Surprisingly, pro-opiomelanocortin (POMC) processing to ACTH was enhanced in post-adrenalectomy patients (ratio 1 +/- 0.5) compared with Cushing's disease (5.6 +/- 0.8) and normal subjects (5.3 +/- 0.9). After hydrocortisone ACTH precursors rose in 36% of post-adrenalectomy patients (increase 15-78%) and remained within 10% of basal levels in 46%. Six patients had a rise in precursors and a fall in ACTH suggesting differential regulation of these peptides. In conclusion, whereas ACTH precursors are high in post-adrenalectomy Cushing's disease and higher levels correlate with tumor progression, processing of precursors to ACTH is enhanced.

Adolescent↗

Modification of the fungi-fluor and the genetic systems fluorescent antibody methods for detection of Pneumocystis carinii in bronchoalveolar lavage specimens.

Four hundred forty-five bronchoalveolar lavage specimens from patients with the human immunodeficiency virus were preserved in Saccomano's fixative and stained for Pneumocystis carinii cysts by a modified method with Fungi-Fluor Solution A (Polysciences, Warrington, Pa) and the Genetic Systems Pneumocystis carinii Immunofluorescence Antibody (Genetic Systems Corp, Seattle, Wash). The majority of patients had been treated for suspected P carinii pneumonia for a few days prior to collection of bronchoalveolar lavage specimens. P carinii cysts were detected in 194 (43.6%) specimens. Both stains identified P carinii in 166 (37.3%) specimens and were negative in 251 (56.4%), yielding a concordance rate of 93.7%. P carinii cysts were detected in 25 (5.6%) specimens by the Genetic Systems stain only, and in 3 (0.7%) specimens by the Fungi-Fluor stain only. The sensitivity for detecting cysts of P carinii was significantly greater with the Genetic Systems stain (P < .01).

Bronchoalveolar Lavage Fluid↗

Pathology consultation services via the Arizona-International Telemedicine Network.

The Arizona-International Telemedicine Network (AITN) links 4 cities in Arizona and two international sites in China and Mexico, into a telepathology diagnostic network. Established in 1993, the Network provides second opinions on surgical pathology and cytopathology cases. Workstations are 486 PC-based computers. Static images (1024 x 774 x 8 pixels) are grabbed with a variable resolution video camera and sent by 14,400 bit per second modems over ordinary telephone lines. Second opinions are either rendered directly by a general telepathologist or triaged to a specialist. Experience with the first 37 cases indicates a high level of success in providing useful information to referring pathologists over the Network.

Computer Communication Networks↗

Aviation medicine.

There is debate about whether pilots infected with the human immunodeficiency virus should be permitted to pilot an aircraft. Approximately three in-flight medical emergencies occur each day, with physicians, flying as passengers, responding to 85% of them. There is no evidence that tuberculosis is any more likely to be contracted on a commercial airliner than on any other public conveyance.

Aerospace Medicine↗

Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial.

BACKGROUND: Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%. PURPOSE: This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN. METHODS: Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test. RESULTS: RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible. CONCLUSIONS: A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects. IMPLICATIONS: A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible.

Administration, Intravaginal↗

Strategies for the preflight circadian shifting of Space Shuttle crews.

In June, 1990, a workshop was put together at NASA/Johnson Space Center to address difficulties the astronauts were having in adjusting their wake and sleep schedule, both immediately before and during Space Shuttle missions. The workshop members, prominent investigators in human circadian research, developed a number of strategies by which astronauts could tackle the problem of circadian adaptation within the demanding timetable of a Space Shuttle mission. The strategies included both abrupt and gradual methods, and some approaches used artificial "very bright lights" to reset the physiologic circadian pacemaker. The strategies have since been operationally implemented on Space Shuttle flights, with good success. This is a report of the problems addressed by the workshop and its recommendations.

Adaptation, Physiological↗

Laboratory methods for the conduct of experimental malaria challenge of volunteers.

Experimental malaria challenge trials of volunteers are conducted to determine whether candidate sporozoite vaccines generate protective immunity against the bites of infected mosquitoes. The absence of patent erythrocytic-stage infection and clinical sequelae suggests sterile immunity among vaccinated volunteers. Sterile immunity is validated through laboratory studies that (1) demonstrate the capacity of erythrocytes and serum obtained from each volunteer before challenge to support parasite growth in vitro; (2) confirm parasitaemia by blood culture, and (3) evaluate each volunteer's blood for surreptitious use of antimalarial agents. The bites of experimentally infected laboratory-reared anophelines must elicit a 100% attack rate among non-immunized volunteers. This report presents guidelines for the laboratory methods used to validate the clinical findings during experimental Plasmodium falciparum anti-sporozoite vaccine efficacy trials.

Adult↗

Salmonella typhi vaccine strain CVD 908 expressing the circumsporozoite protein of Plasmodium falciparum: strain construction and safety and immunogenicity in humans.

rcsp, encoding amino acids 21-398 of Plasmodium falciparum circumsporozoite protein (CSP), under control of tacP was integrated into the chromosomal delta aroC locus of attenuated delta aroC, delta aroD Salmonella typhi CVD 908. By immunoblot and ELISA, rCSP expression was greater from a multicopy plasmid than from the single chromosomal gene. CVD 908 omega (delta aroC1019::tacP-rcsp) was well tolerated by 10 volunteers who were fed two doses of 5 x 10(7) organisms 8 days apart. Seven subjects excreted the vaccine strain for 1-3 days. All subjects developed serologic responses to O and H antigens of the live vector, whereas 3 vaccinees responded to the foreign antigen: 1 developed an 80-fold rise in serum anti-sporozoite antibody, another had a 4-fold rise in antibody to a recombinant portion of CSP (residues 309-345), while a third vaccinee developed CSP-specific CD8+ cytotoxic T lymphocyte activity. This is the first report of attenuated S. typhi eliciting a human serologic or a cytotoxic T lymphocyte response to a foreign protein. Improved foreign gene expression should enhance immunogenicity.

Administration, Oral↗

Diurnal biting activity and transmission of Onchocerca volvulus (Filariata: Onchocercidae) by Simulium yahense (Diptera: Simuliidae) in Liberia.

To determine the influence of meterological factors on the diurnal biting cycle of Simulium yahense Vajime & Dunbar (a member of the Simulium damnosum Theoblad complex), we captured host-seeking females as they landed on the exposed lower legs of humans in the Harbel area of Liberia. Biting activity was greatest during the morning hours and was characterized by a unimodal harmonic curve. Although meteorological conditions had no decisive influence on the unimodal pattern of diurnal biting activity, hourly variation in the number of S. yahense captured at human bait was affected by meterological factors (i.e., the diurnal pattern of S. yahense biting activity is regulated by an internal clock, but the number of bits during any given hour is in response to meterological conditions). The transmission of Onchocerca volvulus (Leuckart) was highest during the morning hours when high transmission potentials were in phase with peak human activity and served to maintain the hyperendemicity of onchocerciasis in the Harbel area.

Animals↗