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Biomedical subjects

C A Davis

Publications and source records attributed to C A Davis.

At least 55 records · Page 3Linked to original sources

Repopulation of mouse jejunal crypt cells.

The regenerative response to radiation of mouse jejunal crypt cells was investigated using a three fraction experiment. The time between the second and third fraction was varied between 5 and 60 h, and the dose in each of the three fractions was different. The data show that the onset of regeneration is within 14 h of the first dose and possibly earlier. The doubling time of the clonogenic cells during repopulation is estimated to be between 5 and 10 h, with the most likely value approximately 6 to 7 h. The data also show that the time course of repopulation in an acutely responding tissue depended in a complex way on the fractionation scheme. The implications of this for radiotherapy are that simple formulas are unlikely to be accurate predictors of acute effects in altered fractionation schemes. Detailed mathematical modelling of the data is undertaken using a model which consists of a single dose survival curve, a part to incorporate the regenerative response and a part to accommodate the delayed onset of regeneration. The model is shown to give a good, although not perfect, fit to the data. A mathematical derivation is given of the expected number of crypts following the 3 dose radiation schedule. This derivation takes into account the fact that any crypt could be denuded of cells prior to the final dose and hence not repopulate, and thus the formula given is necessarily more complex than previous formulas which were based on simpler models.

Animals↗

Black walnut (Juglans nigra) toxicosis: a model for equine laminitis.

Twelve light horse geldings developed laminitis within 8 to 12 h of being dosed by nasogastric tube with an aqueous extract of black walnut (Juglans nigra). Four of the 12 horses developed the severe signs of grade 3 laminitis (lame at a walk, refused to lift feet). Laminitis was accompanied by mild depression and limb oedema. There was no evidence of shock or colic. The horses developed neutropenia by 4 h after dosing with the extract, which shifted to a relative neutrophilia by 8 to 12 h. Minimal increases in plasma epinephrine and cortisol concentrations were suggested in severely affected horses. Severe laminitis was characterized by necrosis of dermal tips of dorsal primary epidermal laminae. A proliferative epithelial response in these laminae was distinguished by numerous mitotic figures and clusters of epithelial cells. This evidence suggests that black walnut toxicosis is not only a consistent clinical model, but is also a reliable clinico-pathological and pathological model for study of the pathogenesis and treatment of laminitis.

Animals↗

Comparison of length of stay after hernia repair in two Victorian hospitals. Standards Sub-committee of the Victorian State Committee of the Royal Australasian College of Surgeons.

The objective of this study was to ascertain factors which determine the length of stay in relation to adult patients admitted for hernia surgery in two different hospitals. It was conducted prospectively on a total of 141 patients, 82 in a central hospital and 59 in a district hospital. There were no significant differences with regard to age, sex, type of hernia, pre-existing disease and postoperative complications. There was a significant difference between the average length of stay in the two hospitals (6.7 days in the central hospital and 3.9 days in the district hospital). There was a longer pre-operative stay in the central hospital through administrative problems, availability of operating time and admission for pre-operative investigations. In the postoperative period there was a significant difference between the day of operation and the time the surgeon stated that the patient could be discharged (i.e. the surgically advised discharge (SAD) date). This period was 4 days at the central hospital, as against 2 days at the district hospital. Once the SAD date was determined, there was no difference between the two hospitals with regard to placement. Consideration should be given to improving admission practices, including patient 'work-up' in the preadmission phase and to shortening the postoperative stay after hernia surgery.

Adolescent↗

Salivary-agglutinin-mediated adherence of Streptococcus mutans to early plaque bacteria.

Interspecies binding is important in the colonization of the oral cavity by bacteria. Streptococcus mutans can adhere to other plaque bacteria, such as Streptococcus sanguis and Actinomyces viscosus, and this adherence is enhanced by saliva. The salivary and bacterial molecules that mediate this interaction were investigated. Salivary agglutinin, a mucinlike glycoprotein known to mediate the aggregation of many oral streptococci in vitro, was found to mediate the adherence of S. mutans to S. sanguis or A. viscosus. Adherence of S. mutans to saliva- or agglutinin-coated S. sanguis and A. viscosus was inhibited by antibodies to the bacterial agglutinin receptor. Expression of the S. sanguis receptor (SSP-5) gene in Enterococcus faecalis increased adhesion of this organism to saliva- or agglutinin-coated S. sanguis and A. viscosus. This interaction could be inhibited by antibodies to the agglutinin receptor. The results suggest that salivary agglutinin can promote adherence of S. mutans to S. sanguis and A. viscosus through interactions with the agglutinin receptor on S. mutans.

Agglutinins↗

The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer.

The importance of the interval between methotrexate (MTX) and fluorouracil (5-FU) was studied in 168 patients with previously untreated, measurable, advanced colorectal cancer. They were randomized to receive MTX 200 mg/m2, followed by 5-FU 600 mg/m2 either 24 hours (arm A) or 1 hour (arm B) after MTX. All patients received leucovorin (LV) 24 hours after MTX, 10 mg/m2 orally every 6 hours for six doses. The regimen was repeated every 2 weeks, with 5-FU escalation as tolerated. Arm A was significantly better than arm B with respect to overall response rate (29% v 14.5%, P = .026), time to progression (TTP; median, 9.9 months v 5.9 months, P = .009), and survival (median, 15.3 months v 11.4 months, P = .003). Significant differences between arms were not found in response rate, median TTP, or median survival for the subgroup of patients with rectal primaries who comprised 20% of the patients in each arm. Significant factors prognostic for survival were performance status and number of metastases, as well as treatment. Age did not influence survival. Toxicity was similar in both arms and was primarily gastrointestinal. More mucositis was seen in arm A. There were four toxic deaths secondary to neutropenia and infection (one from arm A and three from arm B) and three other deaths (two from arm A and one from arm B) that were possibly drug-related. The combination of MTX with LV rescue and 5-FU is an active regimen in advanced colorectal cancer; its efficacy is increased in colon, but not rectal cancer, when the interval between MTX and 5-FU is long (24 hours) rather than short (1 hour).

Aged↗

Examining pattern formation in mouse, chicken and frog embryos with an En-specific antiserum.

We have raised an antiserum, designated alpha Enhb-1, to a portion of the mouse En-2 protein containing the homeodomain. The antiserum detects both the En-1 and En-2 proteins in mouse, chick and Xenopus embryos by Western blot analysis. Using whole-mount immunohistochemistry, combined in some cases with scanning electron microscopy, we have examined the distribution of the proteins in the early embryos of these species. The major features of expression were similar. The initial production of En protein occurred, just before or during the formation of the first somites, in a band of the anterior neural plate in the prospective mid/hindbrain region. Later in development En-1 protein accumulated in the ventral ectoderm of the developing mouse and chick limb buds, indicating that a dorsal-ventral polarity is present as soon as any limb bud swelling is apparent and that, at least in the mouse, this polarity is established independently of the apical ectodermal ridge. In all three species, alpha Enhb-1 bound to a subset of ventro-lateral differentiating neurons in the spinal cord and hindbrain and their pattern of birth in the mouse reflected the division of the hindbrain into rhombomeres. En-1 protein also accumulated in a lateral stripe of dermatome in the mouse and chick, indicating a dorsal-ventral subdivision of this tissue. The results show that En expression is a good marker for pattern formation in a variety of tissues and will be useful in experimental studies designed to characterize further these processes.

Animals↗

The effect of calmodulin inhibitors with bleomycin on the treatment of patients with high grade gliomas.

Glioblastoma multiforme is a fatal malignancy of the central nervous system, demanding new methods of treatment. The combination of a calmodulin antagonist with bleomycin has shown synergistic activity in several preclinical models and has been evaluated in a Phase I clinical trial. Since phenothiazines reach high concentrations in the central nervous system, and bleomycin has been reported to have antitumoral activity as well, we studied this combination in a Phase II clinical trial. In addition, we purified calmodulin from normal brain and malignant gliomas to determine its biochemical and pharmacological characteristics. Seventeen patients were entered onto this study and all were evaluable. There were no partial or complete responses. There was one case of fatal pulmonary toxicity in a patient showing an objective tumor response. Otherwise, the treatment was well tolerated. Calmodulin purified from the normal brain and gliomas of patients undergoing resection was identical to each other and to calmodulin prepared from rat cerebrum and glioma. These characteristics included elution from a TSK phenyl high pressure liquid chromatography column, migration on 16% sodium dodecyl sulfate gels, amino acid composition, and inhibition by drugs. Therefore, the failure of this combination therapy was not due to a difference in human glioma calmodulin as compared to previously reported studies with calmodulin from murine sources.

Adult↗

Cardiovascular effects of intracoronary atrial natriuretic peptide administration in man.

An intracoronary drug infusion protocol was employed to assess the hemodynamic effects of synthetic atrial natriuretic peptide in normal subjects and to evaluate its actions on epicardial coronary artery dimensions. Increasing concentrations of synthetic atrial natriuretic peptide (1.75 to 84 micrograms/min) were infused at a constant rate directly into the left coronary artery in eight patients with normal left ventricular function and left coronary artery angiograms. Steady-state hemodynamic parameters and high-fidelity left ventricular pressure were recorded at each dose and indexes of left ventricular contractile and diastolic function were calculated. Coronary angiograms obtained at baseline and the highest dose of atrial natriuretic peptide were compared by quantitative image analysis techniques. At the highest dose administered, atrial natriuretic peptide decreased mean pulmonary artery pressure (-36%, p less than 0.01), pulmonary capillary wedge pressure (-80%, p less than 0.01), left ventricular end-diastolic pressure (-58%, p less than 0.01), left ventricular end-systolic pressure (-11%, p less than 0.01), mean arterial pressure (-8%, p less than 0.05), and pulmonary vascular resistance (-18%, p less than 0.05). Cardiac output and systemic vascular resistance were unchanged, and heart rate and peak positive dP/dt increased. Peak negative dP/dt and the time constant of early diastolic relaxation calculated by the logarithmic method both fell at the highest dose of atrial natriuretic peptide, although the time constants calculated by other less load-sensitive methods were unchanged. Doses of intracoronary atrial peptide that did not alter left ventricular load had no effect on indexes of left ventricular systolic or diastolic function despite a presumably high intramyocardial concentration of the agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Compliance of left atrium with and without left atrium appendage.

Compliance of the left atrial chamber was estimated with and without the appendage intact in six isolated canine left atria. Pressure-volume determinations were measured over a range of 5-30 mmHg for the whole left atrium and were repeated with the appendage excluded. The slope of the pressure vs. normalized volume data for the left atrium without the appendage (10.45 +/- 0.87) was significantly greater (P less than 0.01) than with the appendage intact (4.10 +/- 0.72). These data suggest that the left atrial appendage is more compliant than the remaining left atrium. Assuming that this relationship remains in vivo, the left atrial appendage may play an augmented role in maintaining hemodynamic function when filling pressures are elevated.

Animals↗

In vivo biological response to recombinant interferon-gamma during a phase I dose-response trial in patients with metastatic melanoma.

Interferon-gamma (IFN gamma), as produced by recombinant DNA technology, has shown a wide range of immunomodulatory activity in vitro and in vivo. Clinical studies have attempted to establish a dose-response relationship to define optimal dosage ranges for induction of effector cell function and host response in patients with cancer. We conducted a randomized trial to test the in vivo biologic activity of five daily dosages ranging from 3 to 3,000 micrograms/m2, administered by daily 2-hour bolus injection or by continuous infusion for 14 days. We demonstrate comparable immunobiologic effects of recombinant IFN gamma (rIFN gamma; Biogen, Inc, Cambridge, MA) administered by these two schedules at the various dosages tested, and have defined a relationship of dose to biologic response over this 3-log10 dose range. Oligo 2'5' adenylate synthetase (2'5'As) induction, natural-killer (NK) cell activity, and T-cell subset distribution (heightened T helper/suppressor ratio) showed the most consistent treatment-associated changes and the greatest immunobiologic effects at dosages of 300 to 1,000 micrograms/m2. Mononuclear cell DR and DQ antigen expression showed no consistent dose-related treatment effect. The relevance of the phenotypic, functional, and enzymologic effects observed in this trial to any clinical antitumor effects of IFN gamma in cancer therapy must now be established.

2',5'-Oligoadenylate Synthetase↗

Effects of thyroid hormones on serum and cutaneous fatty acid concentrations in dogs.

The effects of thyroid hormones on the serum and cutaneous fatty acid concentration profiles of dogs were evaluated. Thyroidectomized dogs had significant (P less than 0.05) increases in serum oleic acid and linoleic acid concentrations, and decreases in concentration of dihomo-gamma-linolenic acid, arachidonic acid, and other elongation products of fatty acid metabolism. These changes were reversed in response to thyroid hormone replacement. Similar changes were found in cutaneous fatty acid concentration profiles. Thus, in dogs, thyroid hormones may be involved in the regulation of fatty acid delta-6-desaturase activity.

Animals↗

Distribution and sequence homogeneity of an abundant satellite DNA in the beetle, Tenebrio molitor.

The mealworm beetle, Tenebrio molitor, contains an unusually abundant and homogeneous satellite DNA which constitutes up to 60% of its genome. The satellite DNA is shown to be present in all of the chromosomes by in situ hybridization. 18 dimers of the repeat unit were cloned and sequenced. The consensus sequence is 142 nt long and lacks any internal repeat structure. Monomers of the sequence are very similar, showing on average a 2% divergence from the calculated consensus. Variant nucleotides are scattered randomly throughout the sequence although some variants are more common than others. Neighboring repeat units are no more alike than randomly chosen ones. The results suggest that some mechanism, perhaps gene conversion, is acting to maintain the homogeneity of the satellite DNA despite its abundance and distribution on all of the chromosomes.

Animals↗

Percutaneous aortic balloon valvuloplasty in octogenarians: morbidity and mortality.

STUDY OBJECTIVE: To examine the morbidity, mortality, and hospital course of an elderly patient sample (mean age, 86 years; 95% CI, 84 to 87) having percutaneous aortic balloon valvuloplasty. DESIGN: Retrospective consecutive case series before and after balloon valvuloplasty. SETTING: Tertiary care referral hospital. PATIENTS: Consecutive sample of 26 patients aged 80 years or older with symptomatic aortic stenosis referred for balloon valvuloplasty from July 1987 to July 1988. MEASUREMENTS AND MAIN RESULTS: Percutaneous aortic balloon valvuloplasty reduced the transvalvular gradient from 59 (95% CI, 51 to 67) to 31 mm Hg (95% CI, 26 to 35; P less than 0.0001) and increased aortic valve area from 0.45 (95% CI, 0.38 to 0.51) to 0.67 cm2 (95% CI, 0.58 to 0.76; P less than 0.0001). The mean length of hospital stay for the entire study population was 11.2 days (95% CI, 7.3 to 15.2) at a total hospital charge per patient of $29,600 (95% CI, 21,050 to 38,150). For patients having procedural complications (11 complications in 8 patients), surgical procedures, or cardiogenic shock, the mean hospital stay increased to 16.2 days (95% CI, 6.2 to 26.2; P less than 0.05) and the hospital charge increased to $44,400 (95% CI, 24,280 to 64,520; P less than 0.01). Two patients who presented with cardiogenic shock died, and 1 patient had an aortic valve replacement before discharge. Four patients were recently discharged (less than 1 month) and follow-up was obtained in the remaining 19 patients at 6.1 months (95% CI, 4.1 to 8.1). Five more patients, including the remaining patient who presented with cardiogenic shock, died after discharge for an overall mortality of 32%. Twelve of the remaining fourteen patients had fewer symptoms and improved an average of 1.1 New York Heart Association classes (95% CI, 0.7 to 1.4; P less than 0.0001). CONCLUSIONS: Percutaneous aortic balloon valvuloplasty in patients 80 years and older improves hemodynamics and symptoms of heart failure during short-term follow-up in most patients, but overall mortality is high in this elderly patient population. Hospital charges and length of stay were much higher in patients with complications or coexisting medical illnesses. Valvuloplasty is a reasonable alternative treatment for patients with aortic stenosis who require palliative treatment of symptoms and have high surgical risk.

Aged↗

Hemodynamic and electrocardiographic effects of ioversol during cardiac angiography. Comparison with iopamidol and diatrizoate.

We studied the hemodynamic and electrocardiographic responses to left ventriculography and coronary arteriography with three angiographic contrast agents. Two were nonionic agents (ioversol 32% iodine, 60 patients, and iopamidol 37% iodine, 30 patients). The third was a conventional ionic agent (diatrizoate 37% iodine, 30 patients). Cardiovascular hemodynamics and the electrocardiogram were recorded for 5 minutes after left ventricular injection and for 2 minutes after coronary injections. Following left ventriculography, diatrizoate caused a greater increase in cardiac output, left ventricular end diastolic pressure, and corrected QT interval while causing a greater decrease in arterial pressure than did either ioversol or iopamidol, which were indistinguishable from each other. Following left coronary arteriography, diatrizoate caused a significant decrease in heart rate, prolongation of the corrected QT interval, and increase in T wave amplitude. In contrast, neither ioversol nor iopamidol caused significant changes in any electrocardiographic parameters. Adverse reactions were more common with diatrizoate than with either ioversol or iopamidol. There were no recognizable differences in angiographic image quality among the three agents. We conclude that the angiographic performance of ioversol is equivalent to that of iopamidol and that both cause less hemodynamic and electrocardiographic disturbance than diatrizoate.

Blood Pressure↗

Saliva-mediated aggregation of Enterococcus faecalis transformed with a Streptococcus sanguis gene encoding the SSP-5 surface antigen.

The interaction of a high-molecular-weight salivary glycoprotein (agglutinin) with Streptococcus sanguis M5 leads to the formation of bacterial aggregates. We have previously shown that the SSP-5 surface antigen from S. sanguis M5 binds the salivary agglutinin and therefore may be involved in the aggregation process. Here we report the transformation of a nonaggregating Enterococcus faecalis strain with the SSP-5 gene and show that the protein is expressed on the cell surface and confers an aggregation-positive phenotype. E. faecalis S161 protoplasts were transformed with pAM401 EB-5, a shuttle vector containing the S. sanguis SSP-5 gene, resulting in the isolation of E. faecalis S161EB-5. Crude cell extracts from this transformant and from S. sanguis M5 were analyzed by Western blotting. Extracts from S. sanguis M5 possessed peptides of 190 and 205 kilodaltons that reacted strongly with polyclonal antibodies against the recombinant SSP-5 antigen. E. faecalis S161EB-5 contained only the 190-kilodalton immunoreactive protein, suggesting that the antigen may be processed differently in E. faecalis S161EB-5. The parent strain, E. faecalis S161, did not react with this antibody preparation. Immunogold labeling of intact E. faecalis S161EB-5 and S. sanguis M5 with anti-SSP-5 immunoglobulin G showed that both organisms expressed similar levels of the antigen. Both organisms formed visible aggregates upon incubation with salivary agglutinin. These results suggest that the SSP-5 antigen may mediate both the binding of agglutinin to S. sanguis M5 and the subsequent formation of bacterial aggregates.

Agglutinins↗

Comparison of the gastrointestinal syndrome after total-body or total-abdominal irradiation.

In pathogen-free mice, but not standard conventionally housed laboratory rodents, two distinctly different modes of early radiation lethality can be identified by modifying the irradiation technique (total-body versus abdominal irradiation) or by therapeutic intervention such as rescue of total-body-irradiated mice with syngeneic bone marrow or spleen. While damage to the gastrointestinal tract is usually designated as the predominant cause of death occurring within 10 days of radiation exposure, it was demonstrated that damage to the hematopoietic/lymphopoietic system can result in animal lethality over the same period as the gastrointestinal syndrome and that this target cell population is more radiation-sensitive than the gastrointestinal epithelium.

Abdomen↗

Use of focus groups to explore consumers' preferences for content and graphic design of nutrition publications.

The purpose of this research was to determine consumers' preferences for the content and design of nutrition print materials through the use of focus group interviews. Thirty-seven non-pregnant, non-nursing female consumers 20 to 50 years of age attended one of six focus group interviews. Existing nutrition print materials were used to stimulate discussion on content and graphic design features of the materials. Content features discussed included glossaries, quizzes, diet evaluation checklists, diet monitoring forms, and "factual" vs. "how to " information. Graphic design features discussed included color, format, size, organization, and general appearance. Participants were asked to discuss the personal impressions and practical considerations that formed the basis of their opinions regarding each feature and to elaborate on how the existing materials might be improved to meet their particular needs. Features that drew the most positive reactions were bright food colors, organizational cues, clear information and explanations, features that help personalize the issue being addressed, and "how to" information.

Adult↗