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Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 289 records · Page 16Linked to original sources
PubMed1991

Combined modality therapy of Hodgkin's disease: 10-year results of National Cancer Institute of Canada Clinical Trials Group multicenter clinical trial.

The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin's disease. Between January 1972 and September 1976, 266 patients with stage IIIB, IVA, and IVB Hodgkin's disease from 21 cancer treatment centers across Canada were registered as eligible; 40 were found to be ineligible. Of the 226 remaining patients, only seven were followed for less than 10 years. All patients received three courses of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, which induced a complete response (CR) in 36%; an additional 42% obtained adequate disease control. Patients were randomly assigned to (1) treatment with radiation to the abdomen and mantle (group AX3, 62 patients) or (2) continue their treatment with an additional three courses of MOPP (group A, 105 patients). For the A group, a second randomization took place 3 months later (regardless of status at that time) to (1) no further treatment (AC6, 23 patients), (2) radiotherapy to the abdomen and mantle (AX6, 48 patients), or (3) maintenance chemotherapy at 3-month intervals for 1 year (AC10, 26 patients). The survival of AX3 patients was somewhat better than for the A group, but the difference was not significant (P = .0565). However, there was a significant interaction (P = .0029) between age and treatment, so that among patients less than 30 years of age, the survival of the A group was better, whereas for older patients, treatment with AX3 resulted in improved survival. Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy. The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses. These results suggest that combined modality therapy may be beneficial for some patients with Hodgkin's disease and that age must be carefully considered in interpreting the results of clinical trials in Hodgkin's disease.

Adolescent↗
PubMed1991

A phase I trial of taxol given by a 6-hour intravenous infusion.

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.

Alkaloids↗
PubMed1991

Common-sense ethics in administrative decision making. Part I, Preparatory steps.

This is Part 1 of two articles demonstrating the relevance of business ethics to nurse administrators as they confront value-laden issues such as the advantages and disadvantages of 10-12-hour scheduling patterns, understaffing, emerging registered nurse partnerships, and other administrative problems. Common-sense ethics can serve as the basis of just administrative decisions. The authors present a model of preparatory attitudes and behaviors. The steps that they propose do not guarantee success, but if implemented, they may facilitate the nurse administrator's management of diverse ethical issues.

Commerce↗
PubMed1991

Common-sense ethics in administrative decision making. Part II, Proactive steps.

This article is the second in a two-part study on common-sense ethics. In Part 1 (October 1991 JONA), the authors presented preparatory steps for the nurse administrator to consider in the management of diverse ethical issues. In Part 2, the authors delineate proactive steps to facilitate the resolution of administrative problems with economic, social, and ethical dimensions. They apply the model to the problem of the nursing shortage. Although no guarantees are assured in following the steps, decision making may be facilitated during the ethical conflict.

Decision Making, Organizational↗
PubMed1990

Structural and thermodynamic studies on the adenine.guanine mismatch in B-DNA.

The structure of the synthetic dodecamer d(CGCAAATTGGCG) has been shown by single crystal X-ray diffraction methods to be that of a B-DNA helix containing two A(anti).G(syn) base pairs. The refinement, based on data to a resolution of 2.25 A shows that the mismatch base pairs are held together by two hydrogen bonds. The syn-conformation of the guanine base of the mismatch is stabilised by hydrogen bonding to a network of solvent molecules in both the major and minor grooves. A pH-dependent ultraviolet melting study indicates that the duplex is stabilised by protonation, suggesting that the bases of the A.G mispair are present in their most common tautomeric forms and that the N(1)-atom of adenine is protonated. The structure refinement shows that there is some disorder in the sugar-phosphate backbone.

Adenine↗
PubMed1990

Influence of pH on the conformation and stability of mismatch base-pairs in DNA.

A series of self-complementary dodecanucleotide duplexes containing two symmetrically disposed mismatches have been studied by pH-dependent, ultraviolet light melting techniques. The results indicate that A.C, and C.C mismatches are strongly stabilized by protonation and that the degree of stabilization of the A.C mismatch depends greatly on the flanking bases. In one case, a duplex containing two A.C mismatches is more stable than the native sequence below pH 5.5. The G.A mismatch displays conformational flexibility, with a protonated G(syn).A(anti) base-pair occurring in certain base stacking environments but not in others. The A.A and T.C mismatches are not stabilized at low pH. These solution studies correlate well with predictions based on X-ray crystallographic data.

Base Composition↗
PubMed1990

Coliform septicemia and pulmonary disease associated with canine parvoviral enteritis: 88 cases (1987-1988).

Parvovirus infection was confirmed by fluorescent antibody staining or viral culturing in 137 (22%) of 615 necropsy accessions from dogs at the Missouri Veterinary Medical Diagnostic Laboratory from Jan 1, 1987 through Sept 30, 1988. Septicemic colibacillosis was diagnosed in 88 (90%) of the 98 canine parvovirus-positive accessions in which liver or lung was cultured bacteriologically. Pulmonary edema or alveolitis similar to that seen in the human adult respiratory distress syndrome was observed in 63 (69%) of the 91 canine parvovirus-positive accessions in which the lungs were examined histologically.

Animals↗
PubMed1990

Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level.

The biosynthesis of cachectin/TNF is largely regulated at a post-transcriptional level. Bacterial endotoxin, which strongly induces cachectin/TNF production, thus seems to elicit at least some of its effects by altering the macrophage cytoplasmic milieu. It has previously been shown that the 3'-untranslated TTATTTAT element present in numerous cytokines and proto-oncogenes is capable of repressing the translation of mRNA molecules in which it is represented. Using constructs in which the CAT coding sequence is followed by varying segments of the cachectin/TNF 3'-untranslated region, we now demonstrate that downstream sequences present in the cachectin/TNF mRNA are sufficient to mediate greater than 200-fold induction of CAT synthesis in response to activation by endotoxin. Induction of CAT activity is not attributable to a change in cytoplasmic mRNA concentration, but to a marked enhancement of translational efficiency. The response to endotoxin represents "derepression," and is conferred chiefly by the translationally repressive TTATTTAT element, acting in concert with essential flanking sequences.

Base Sequence↗
PubMed1990

Oxygen as an antibiotic. The effect of inspired oxygen on bacterial clearance.

Previous experimentation with the guinea pig skin injection model showed that altering the fraction of inspired oxygen had a significant effect on infectious necrosis. Using the same model, we performed quantitative bacterial cultures to determine the number of viable injected bacteria 24 and 48 hours after injection. Animals were randomized to receive 12%, 21%, and 45% inspired oxygen. A significant decrease in bacterial number was seen at 45% inspired oxygen between 24 and 48 hours, and a significant decrease occurred at 48 hours between 12% and 45% inspired oxygen. These results demonstrated a prominent role for oxygen in bacterial clearance and host defense.

Administration, Inhalation↗
PubMed1990

Interproximal grooving and task activity in Australia.

Interproximal grooving was recorded in 85 nineteenth century aboriginal skulls from Swanport in South Australia. One or more grooved teeth were noted in 41% of individuals, but the frequency of grooving in males was twice that in females. Distal surface grooving was noted in 93 teeth in contrast to only five instances of mesial grooving. The lesions were similar in appearance to those reported in many other populations--confined primarily to the premolar-molar region, located at the cementoenamel junction, directed horizontally, and usually clean-cut and free of caries. Stripping of animal sinews between the clenched posterior teeth has been recorded on film as a common task activity in traditional aboriginal society. In our opinion, task activity and not toothpicking was the likely cause of the observed interproximal grooving in the aboriginals.

Australia↗
PubMed1990

Concepts of occlusion: Australian evidence.

Longitudinal studies of aboriginal children over a 20-year period have drawn attention to the wide variation in morphological features of the dentition and the way in which occlusal relationships develop. This paper summarizes some important determinants of optimal occlusal development, namely, tooth size relationships within and between dentitions, the patterns of alveolar growth, and tooth migrations during the transition from primary to permanent teeth and the nature of growth changes in the dental arches. Dental occlusion constantly changes throughout life in response to changing functional requirements. Observations limited to cross-sectional material provide an incomplete, and sometimes misleading, concept of dental occlusion and masticatory function.

Adult↗
PubMed1990

Occlusal variation in Australian aboriginals.

Variation of dental occlusion around established norms has frequently been related to industrialized or modernized life habits. This tendency has been tested among samples (n = 48) of older (originally nomadic) and younger (settled and rationed) Australian Aboriginals. Although significant differences are found in incisor relation traits, tooth malalignment, and relative arch breadth, these are slight compared to some other studies of peoples undergoing one-generation dietary westernization. Reasons for this might relate to concomitantly subtle differences in diet or masticatory habits, genetic buffering, attrition gradient, tooth size, biased sampling according to tooth retention, or fluoride in water supplies.

Adult↗
PubMed1990

Shape components of the maxillary molars in Australian aboriginals.

Principal components analysis was used to quantify the variability in crown outlines of maxillary molars in Australian Aboriginals. The outlines were measured by 36 radii from the central pit to the crown periphery. The first component, responsible for over half of the total variance, was concerned with general crown size. Four remaining components were retained to indicate sources of variability resulting from contrasting degrees of development or reduction of different crown components. Shape changes from the first to third molars were identified with components representing overall size reduction, diminution of the hypocone, and metacone elements and mesiodistal compression. An anteroposterior gradient along the molar series in average scores and variances for all components resulted from the progressive reduction of distal crown elements, increasing mesiodistal compression, and greater morphological variation.

Female↗
PubMed1990

Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding.

The three-dimensional structure of a complex between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 A. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5'-AAT-3' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed.

Amidines↗
PubMed1990

Dental arch morphology in south Australian twins.

Fourth-order polynomials were used to represent dental arch morphology in 29 monozygous and 19 dizygous like-sexed twin pairs, and in 45 unrelated individuals. The polynomial coefficients provided an accurate description of dental arch morphology with the quadratic (chi 2) and quartic (chi 4) terms reflecting arch shape and the linear (chi) and cubic (chi 3) terms summarizing asymmetry. There were no significant differences between the groups in either the quadratic or quartic terms. Values of correlations between polynomial terms indicated that there was no consistent relationship between maxillary and mandibular arch shape or asymmetry. Intraclass correlations between twins suggested that genetic factors contributed to variation in maxillary arch shape and to a lesser extent to variation in mandibular arch shape but not to arch asymmetry.

Adolescent↗
PubMed1990

Analysis of anticancer drugs in biological fluids: determination of taxol with application to clinical pharmacokinetics.

Taxol, a novel antimitotic, antitumor agent is currently undergoing Phase 1 clinical trials for the treatment of various tumors. An isocratic HPLC method has been developed for the determination of taxol in human plasma and urine. The method was then applied to the clinical pharmacokinetics of taxol following 6-h intravenous (i.v.) infusions at doses of 175 and 225 mg m-2. A mobile phase of methanol-acetate buffer (0.02 M, pH 4.5) (65:35, v/v) was used to elute a C8 column with detection at 227 nm. The sample preparation involved extraction with t-butyl methyl ether followed by further clean-up of the sample by solid-phase extraction. The method was linear from 0.10-10 microM injected, with a chromatographic run time of 6 min. The results obtained from the clinical study indicate that the plasma pharmacokinetics of taxol are best characterized by a two compartment open body model. Additionally, the present study resulted in the detection of a previously unreported peak which may be a metabolite of taxol.

Alkaloids↗