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Biomedical subjects

C White

Publications and source records attributed to C White.

At least 109 records · Page 6Linked to original sources
PubMed1998

Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study.

BACKGROUND: Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. METHODS: Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. RESULTS: In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001). CONCLUSIONS: Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.

Administration, Oral↗
PubMed1998

High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer.

PURPOSE: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). RESULTS: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery. CONCLUSION: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

Adenocarcinoma↗
PubMed1998

A prospective phase II trial of concomitant chemotherapy and radiotherapy with delayed accelerated fractionation in unresectable tumors of the head and neck.

BACKGROUND: Our study is a prospective evaluation of unresectable malignant cancers of the head and neck treated with concomitant chemotherapy and radiotherapy (RT) using delayed accelerated fractionation (concomitant boost). METHODS: Between January 1988 and March 1995, 82 patients with unresectable cancers of the head and neck were enrolled in this phase II study. Of these, 52 patients were treated and followed for a minimum of 3 years and are the subject of this analysis. All patients had T4 lesions and were stage IV according to the American Joint Committee on Staging Criteria (AJCC). Patients received RT with accelerated fractionation to a total of 70 Gy in 6 weeks using a concomitant-boost technique. Concomitant cis platin (100 mg/M2) was given on days 1 and 22 of RT. Twenty-seven patients received mitomycin-C (7.5 mg/M2) on days 1 and 22, and 1 patient received mitomycin-C on day 1. In addition, 27 patients received adjuvant chemotherapy with cis platin and vinblastine. The mean follow-up was 45 months (range, 36-72 months). The minimum follow-up for surviving patients in 3 years. RESULTS: At 3 years, the local control rate was 58%. Three-year local control rates for paranasal sinus, nasopharynx, oropharynx, and larynx/hypopharynx were 78%, 78%, 64%, and 100%, respectively. For all patients, the distant-metastasis-free survival was 56%, and the overall survival rate was 36%. Patients with oral cavity cancers experienced worse overall survival versus other sites, 0% versus 47% (p = .03). Salivary cancers also showed worse survival versus other sites, 0% versus 47%, but was not statistically significant. Severe acute complications occurred in 34% of patients. Treatment-related toxicity also resulted in the death of 2 patients. Severe late complications occurred in 7% of patients. CONCLUSIONS: Treatment of this poor prognostic group of patients with aggressive chemotherapy and RT produced surprisingly good local control and survival.

Adolescent↗
PubMed1998

Long term results of primary radiotherapy with/without neck dissection for squamous cell cancer of the base of tongue.

BACKGROUND: There are several management options for patients with squamous cell cancer of the base of tongue. We have had an interest in using primary radiotherapy with or without neck dissection, in an effort to provide optimal oncologic as well as functional outcomes. METHODS: From 1981 to 1995, 68 patients with primary squamous cell cancer of the base of tongue were managed with primary radiotherapy, with neck dissection added for those who were initially seen with palpable lymph node metastases. Ages ranged from 35 to 77 years (median age, 55 years). There were 59 men and 9 women. T Stage distribution was: T1, 17; T2, 32; T3, 17; T4, 2. Fifty-eight patients (85%) were initially seen with nodal metastases. Initial treatment generally involved external-beam radiotherapy (EBRT) to the primary site and upper neck (54 Gy) and to the low neck (50 Gy). A 192-Ir brachytherapy boost (20-30 Gy) to the base of tongue was done about 3 weeks later, at the same anesthesia used for the neck dissection. All patients had temporary tracheostomy. Follow-up ranged from 1 month to 151 months (median, 36 months). Nine patients received neoadjuvant chemotherapy as part of a larynx-preservation protocol. RESULTS: Actuarial 5- and 10-year local control is 89% and 89%, distant metastasis free survival is 91% and 76%, disease-free survival is 80% and 67%, and overall survival is 86% and 52%, respectively. Complications occurred in 16%. CONCLUSIONS: Our long term data clearly demonstrate that primary radiotherapy produces excellent oncologic outcomes.

Adult↗
PubMed1998

Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a component of the extracellular matrix of articular cartilage. Its increased presence in synovial fluid and serum has been associated with accelerated joint damage in patients with rheumatoid arthritis (RA) and osteoarthritis. To fully understand the reasons for fluctuations of COMP levels, we studied the biosynthesis of this molecule in cells derived from joint tissues. METHODS: Synovial cells were derived from synovial tissues of patients with RA, and human articular chondrocytes were prepared from normal articular cartilage. Analysis by Northern blotting was used to evaluate steady-state levels of COMP messenger RNA (mRNA), while secretion of the protein into culture media was analyzed by Western blotting. Expression of COMP in synovial tissues was studied by reverse transcriptase-polymerase chain reaction analysis and by in situ hybridization. RESULTS: COMP was synthesized and secreted by synovial cells as well as by articular chondrocytes in culture. The basal rate of synthesis was very low; however, COMP biosynthesis in both cell populations was induced very strongly by transforming growth factor beta1 (TGFbeta1). Interleukin-1beta counteracted COMP induction by TGF-beta1. COMP was not detected in culture media of skin or fetal lung fibroblasts, either in the absence or the presence of TGFbeta1. COMP mRNA was also present in fresh synovial tissue specimens obtained from patients with RA. CONCLUSION: COMP is synthesized and secreted not only by articular chondrocytes, but also by synovial fibroblasts. The demonstration of COMP expression in surgical specimens of synovial tissues suggests that the inflamed synovium may provide an additional source for the elevated levels of COMP observed in arthritis. Thus, increased COMP levels in body fluids may be indicative of active synovitis as well as of accelerated joint erosion.

Cartilage Oligomeric Matrix Protein↗
PubMed1998

Isolation and characterisation of the RAD51 and DMC1 homologs from Arabidopsis thaliana.

By using RT-PCR and degenerate oligonucleotides based on the sequence homology between the yeast RAD51 and DMC1 genes, two genes belonging to the RAD51 and DMC1 families were isolated from Arabidopsis thaliana ecotype Columbia. A RAD51 genomic DNA was also sequenced which is almost identical to its Landsberg erecta counterpart, except for a few translationally silent substitutions and for the presence of a 527-bp element downstream of the polyadenylation site. This element is repeated in the genome of Arabidopsis. Northern analyses were conducted to characterize the expression pattern of both these genes. AtRAD51 and AtDMC1 are expressed in flower buds, but also in the mitotically active cells from a suspension culture. AtRAD51, but not AtDMC1, transcript level increases after gamma irradiation of the cells. Finally, a synchronisation experiment conducted with the suspension culture indicated that not only AtRAD51 but also AtDMC1 are regulated during the cell cycle, with S-phase-specific induction. Since DMC1 genes have always been regarded as being specifically meiotic, we discuss the significance of this mitotic transcriptional regulation in Arabidopsis.

Arabidopsis↗
PubMed1998

Tissue specific and vitamin D responsive gene expression in bone.

Studies of gene expression in bone have adopted a number of molecular approaches that seek to determine those cis and trans-acting factors responsible for the development and physiological regulation of this unique tissue. The majority of studies have been performed in vitro, focussing on the expression of genes such as osteocalcin, bone sialoprotein and type I collagen which demonstrate restricted or altered expression patterns in osteoblasts. These studies have demonstrated a large number of cis and trans acting factors that modulate the tissue specific and vitamin D responsive expression of these genes. These include the response elements and regions mediating basal and vitamin D dependent transcription of these genes as well as some of the transcription factors that bind to these regions and the nucleosomal organisation of these genes within a nuclear framework. In vivo studies, including the introduction of transgenes into transgenic mice, extend these in vitro observations within a physiological context. However, in part due to limitations in each approach, these in vitro and in vivo studies are yet to accurately define all the necessary cis and trans-acting factors required for tissue specific and vitamin D responsive gene expression. Advances have been made in identifying many cis-acting regions within the flanking regions of these genes that are responsible for their restricted expression patterns, but a vector incorporating all the necessary cis-acting regions capable of directing gene expression independent of integration site has not yet been described. Similarly, trans-acting factors that determine the developmental destiny of osteoblast progenitors and the restricted expression of these genes remain elusive and, despite advances in the understanding of protein-DNA interactions at vitamin D response elements contained within these genes, further intermediary factors that interact with the transcriptional machinery to modulate vitamin D responsiveness need to be identified.

Animals↗
PubMed1998

The rights of state hospital patients: from state hospitals to their alternatives.

During the 1980s and 1990s the locus of psychiatric treatment in many states shifted from state hospitals to the psychiatric units of general hospitals. The extent to which the rights guaranteed to psychiatric inpatients by state mental health agencies will survive this "privatization" process is unclear. The authors explore this issue by providing a "status report" of patient rights, identified through a national survey. They discuss the problems of preserving these rights as an ever greater proportion of care is provided in general hospitals under the mechanism of managed care.

Deinstitutionalization↗
PubMed1998

An integrated microbial process for the bioremediation of soil contaminated with toxic metals.

Microbially catalyzed reactions, which occur in the natural sulfur cycle, have been integrated in a microbiological process to remove toxic metals from contaminated soils. Bioleaching using sulfuric acid produced by sulfur-oxidizing bacteria was followed by precipitation of the leachate metals as insoluble sulfides by sulfate-reducing bacteria. Metal contaminants including Cd, Co, Cr, Cu, Mn, Ni, and Zn were efficiently leached from an artificially contaminated soil. Mn, Ni, and Zn were the only target elements that were significantly leached from soil minerals. Pb leaching was slow and remained incomplete over a period of 180 days. Mineral components such as Fe, Ca and Mg were also leached but the eventual reduction in soil mass was only approximately 10%. An industrially contaminated soil was also efficiently leached and approximately 69% of the main toxic metals present, Cu, Ni, and Mn, were removed after 175 days. The leachate that resulted from the action of sulfur-oxidizing bacteria on contaminated soil was stripped of metals using an anaerobic bioreactor containing a mixed culture of sulfate-reducing bacteria which precipitated soluble metal species as solid metal sulfides. More than 98% of the metals were removed from solution with the exception of Mn, Ni, and Pb, where 80-90% were removed. The metal content of the resultant effluent liquor was low enough to meet European criteria for discharge into the environment.

Biodegradation, Environmental↗
PubMed1998

Using modern information technology to profile faculty activities.

Most academic medical centers (AMCs) have developed mechanisms for tracking the financing of their faculty members' research and clinical activities. However, information systems for managing and reporting financial data often do not provide fully accurate or complete pictures of the accomplishments of an institution or its faculty. Modern information technology can help AMCs integrate more extensive information about their faculties from many different sources; in particular, Web publishing technologies permit large numbers of users to have easy secure access to databases across different platforms. The authors briefly describe five faculty information systems now in use. They then describe in detail the development and implementation of one of these systems, The Johns Hopkins University School of Medicine Faculty Information System (FIS), which uses Web publishing technologies, collecting and making available information about the clinical, teaching, and research activities of faculty members.

Academic Medical Centers↗
PubMed1998

Depressed and non-depressed mothers with problematic preschoolers: attributions for child behaviours.

OBJECTIVES: This study examines the spontaneous causal attributions made by mothers about their preschool children's problem behaviour and investigates the relationship between causal attributions and maternal depression. DESIGN: Two groups of mothers were compared, a depressed and a non-depressed group, while all women included identified their preschool child as having some problem behaviours. There were 25 women in each group. METHODS: The spontaneous attributions of mothers were assessed from audiotaped interviews using an adaptation of the Leeds Attributional Coding System for the extraction and analysis of attributional statements. RESULTS: Depressed mothers made more spontaneous causal attributions about their children's problem behaviour than did the non-depressed group; and the depressed group perceived these causes as being more stable, more controllable and more personal to the child than their non-depressed counterparts. There was also evidence that depressed mothers made more internal attributions about themselves as the cause of their children's problem behaviour than non-depressed mothers. The study indicates that the personal-to-child dimension is the attributional variable most strongly associated with depression. CONCLUSIONS: This study provides evidence that depressed mothers have attributional biases when compared to non-depressed mothers. The authors suggest that their attributions may mediate coping responses and hence may influence parenting behaviour. The clinical and research implications of the findings are discussed.

Adult↗
PubMed1998

Allelic variation in the vitamin D receptor, lifestyle factors and lumbar spinal degenerative disease.

OBJECTIVE: To describe the relation between spinal degenerative disease, allelic variation in the vitamin D receptor gene, and lifestyle factors in a population-based association study. METHODS: Random population-based sample of 110 men and 172 women over 60 years of age participating in the Dubbo Osteoporosis Epidemiology Study who had spinal radiographs (performed according to a standardised approach), assessment of lifestyle factors, bone densitometry as well as blood taken for genotyping. RESULTS: Spinal degenerative disease of varying severity was common in this sample. Multivariate analysis of genetic and lifestyle factors simultaneously strengthened the statistical significance of each indicating the presence of additive gene environment interaction. Allelic variation in the vitamin D receptor gene was associated with severity of osteophytosis (adjusted OR "TT" v "tt" 0.41, 95% CI 0.17, 0.97), presence of disc narrowing (adjusted OR "TT" v "tt" 0.45, 95% CI 0.20, 0.99) and weakly with presence of osteophytosis (adjusted OR "TT" v "tt" 0.47, 95% CI 0.19, 1.16) but not with severity of disc narrowing (OR "TT" v "tt" 1.05, 95% CI 0.40, 2.72) or apophyseal arthritis (OR "TT" v "tt" 0.63, 95% CI 0.24, 1.59). Adjustment for femoral neck bone density did not change these findings suggesting that the association is not mediated through bone density. Presence and severity of spinal degenerative disease increased with age at all sites. Current smoking increased both the presence (adjusted OR 9.70, 95% CI 2.08, 45.1) and severity (adjusted OR 2.91, 95% CI 1.16, 9.03) of spinal osteophytosis with intermediate values for past smokers. Severity of osteophytosis was also independently associated with body mass index and quadriceps strength consistent with a contributory effect of physical loading. CONCLUSIONS: In this elderly sample, both genetic and lifestyle factors were associated with the presence and severity of spinal degenerative disease. There were site specific differences in associations at the spine, which may be because of misclassification of disease status or may indicate possible environmental and genetic differences in the pathophysiology of spinal degenerative disease. Further studies are required to confirm these findings in different population samples and to further explore potential aetiological mechanisms particularly gene environment interaction.

Aged↗