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Biomedical subjects

K Murray

Publications and source records attributed to K Murray.

At least 109 records · Page 6Linked to original sources
PubMed1993

Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible. PATIENTS AND METHODS: From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm. RESULTS: Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047). CONCLUSION: SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.

Carmustine↗
PubMed1992

A randomized trial of accelerated hyperfractionated radiation therapy and bis-chloroethyl nitrosourea for malignant glioma. A preliminary report of Radiation Therapy Oncology Group 83-02.

BACKGROUND: The third and final randomization of Radiation Therapy Oncology Group (RTOG) 83-02 was performed to identify the maximal tolerated dose and potential efficacy of accelerated hyperfractionated radiation therapy (AHRT) in 1.6 Gy twice-daily fractions for adult malignant glioma. METHODS: From December 1987 to July 1989, 304 patients with malignant glioma were stratified by age, performance status, and histologic findings and randomized to receive total AHRT doses of 48.0 or 54.4 Gy, with 80 mg/m2 of bis-chloroethyl nitrosourea (BCNU) for 3 days every 8 weeks. Distribution of other prognostic factors, including neurologic function, extent of surgery, tumor size, and sex, was comparable in each treatment arm. RESULTS: One Grade 5 radiation therapy (RT)-related toxic effect was reported (in the 54.4-Gy treatment arm), and the incidence of late Grade 3-5 RT-related toxic effects at 18 months was 1% at 48.0 Gy and 4% at 54.4 Gy. The median survival times (MST) for the 48.0 Gy and 54.4 Gy treatment arms were 11.7 and 10.8 months, respectively, comparable to the MST in prior RTOG trials with a similar proportion of patients with glioblastoma multiforme (79%). For the 123 patients who were 60 years of age or older, the MST for the 48.0 Gy and 54.4 Gy treatment arms were 8.9 and 10.4 months, respectively, and compare favorably with the MST of 6.0 months reported with standard RT and BCNU treatment used for 101 patients who were 60 years of age or older in two prior RTOG malignant glioma trials (74-01 and 79-18). Although these results differ significantly (P = 0.0015), this contrast is not significant when adjusted by performance status. CONCLUSIONS: The maximum tolerated dose of AHRT has yet to be identified, and pursuit of this information may most benefit patients with malignant glioma who are 60 years of age or older.

Carmustine↗
PubMed1992

A programme of preventive dentistry in field conditions carried out in Glasgow, Scotland.

A caries-preventive regime comprising fluoride supplementation in age-related doses, three monthly acid-phosphate-fluoride applications, fissure sealing of deciduous and first permanent molars and chair-side dental health education, had been proved cost-effective in a single health centre setting. It was therefore expanded to a community-wide project in the Greater Glasgow area. This study describes the coverage achieved by the scheme, the demographic details of the children involved, and measured the dental health benefits accrued by the participants. The children received an annual dental examination and, to assess the effects of the programme, the records of 310 subjects who had attended three annual examinations were used. The deft and defs reductions ranged from 60 to 6.5 per cent and 58.8 to 9.6 per cent respectively, and equivalent DMFT and DMFS reductions ranged from 11.1 to 0 per cent, and 33.3 to 16.7 per cent respectively. Previously, deft reductions of 63.7 to 86.2 per cent, and defs reductions of 77.6 to 92.6 per cent had been reported (Stephen et al., 1983). In contrast, the corresponding deft and defs reductions achieved in this project were only up to 16.7 and 9.6 per cent respectively. The programme was most beneficial for children who had reached the age of three years after two year's participation in the scheme. The dental health benefits accrued by those receiving the preventive programme appear to be inversely proportional to its size. Therefore it represents an important example of the reduction of a preventive agents' effectiveness when used under field conditions, as opposed to those of controlled clinical trials.

Acidulated Phosphate Fluoride↗
PubMed1992

Allogeneic marrow transplantation using T cell depletion for patients with juvenile chronic myelogenous leukemia without HLA-identical siblings.

Six children with clinical and hematologic features of juvenile chronic myelogenous leukemia (JCML) underwent bone marrow transplantation (BMT) using T cell-depleted marrow from non-HLA-matched related or closely HLA-matched unrelated donors. Patient ages ranged from 1.2 to 5 years. Four patients received cytoreductive chemotherapy prior to BMT conditioning, and four had undergone pretransplant splenectomies. The donor-recipient matching included: four transplants disparate at one HLA locus (three from unrelated donors and one from a related donor), one transplant disparate at two HLA loci, and one transplant from a one haplotype-mismatched donor. All patients were MLC reactive with their donors. Graft-versus-host disease (GVHD) prophylaxis consisted of in vitro T cell depletion with a monoclonal antibody directed against CD3, and complement in conjunction with cyclosporin A begun on day -1. Conditioning included busulfan, cytosine arabinoside, cyclophosphamide, methyl-prednisolone, and hyperfractionated total body irradiation. All patients engrafted, with median time to neutrophils greater than 500 x 10(6)/l and platelets greater than 25 x 10(9)/l of 20 and 21 days, respectively. Acute GVHD was less than or equal to grade II in all patients. Two patients died of infection (Candida, CMV) at days 74, 157. One patient relapsed at day 177, and subsequently died on day 939. Three patients are alive and disease free at 180 +, 1610 + and 2400 + days from BMT. Although intensive chemotherapy may play a role in providing transient disease control in patients with JCML, allogeneic BMT is the only curative therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1992

Localization of human immunodeficiency virus core antigen in term human placentas.

Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Osteoblastoma response to chemotherapy.

An 8-year-old boy had an osteoblastoma of the body of C2. After attempted excision, the tumor recurred rapidly and massively. The tumor shrank progressively after treatment with high-dose methotrexate, doxorubicin, and cisplatin. The patient has stopped treatment and been stable for 33 months. Surgical excision remains the treatment of choice for osteoblastoma. Chemotherapy may be useful in selected patients with a recurrent, aggressive tumor or in patients with surgically inaccessible disease.

Bone Neoplasms↗
PubMed1991

Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus.

The influence of kainic acid (KA)-induced limbic seizure activity on the expression of mRNA for nerve growth factor (NGF) in adult rat brain was studied using in situ hybridization and S1 nuclease protection techniques with RNA probes complementary to murine and rat NGF mRNA. Within hippocampus, intracerebroventricular injection of 0.5 microgram KA caused a dramatic bilateral increase in hybridization of the 35S-labeled cRNA within stratum granulosum. This increase was first evident 1 h post-KA, appeared maximal at approximately 20-fold control levels at 2-3 h post-injection, and declined to control levels by 48 h post-injection. During the period of maximal hybridization, all but the deepest cells within stratum granulosum appeared to be autoradiographically labeled. Hybridization of the NGF cRNA probe was also increased within superficial layers of piriform and entorhinal cortex and, to much lesser extent, within scattered neurons of layers II and III of neocortex in KA-treated rats. In olfactory cortical areas, hybridization was maximally elevated 15.5-24.5 h after KA injection. In contrast to these effects, KA treatment did not consistently influence the density of hybridization, or number of neurons labeled, within the dentate gyrus hilus or the hippocampus proper (CA1-CA3). In agreement with the in situ hybridization results, S1 nuclease protection assay detected KA-induced increases in hybridization within pooled dentate gyrus/CA1 samples, but not hippocampal CA3 samples. These data support the conclusion that seizure activity stimulates a transient increase in NGF expression by select populations of forebrain neurons and indicates that experimental seizure paradigms might be further exploited for analyses of the mechanisms of NGF regulation and processing in the adult brain.

Animals↗
PubMed1991

Prophylactic cranial irradiation for lung cancer patients at high risk for development of cerebral metastasis: results of a prospective randomized trial conducted by the Radiation Therapy Oncology Group.

Beginning in February 1984, 187 evaluable patients with adenocarcinoma or large cell carcinoma of the lung clinically confined to the chest were randomized to receive either conventionally fractionated thoracic irradiation alone or thoracic irradiation with concurrent, prophylactic cranial irradiation. The study population included 161 patients treated for medically or surgically inoperable primary cancers, and 26 patients undergoing adjuvant postoperative mediastinal irradiation following attempted curative resection of primary cancers found to have metastasized to hilar or mediastinal lymph nodes. Elective brain irradiation was not effective in preventing the clinical appearance of brain metastases, although the time to develop brain metastases appears to have been delayed. Eighteen of 94 patients (19%) randomized to chest irradiation alone have developed brain metastases as opposed to 8/93 patients (9%) randomized to receive prophylactic cranial irradiation (p = .10). No survival difference was observed between the treatment arms. Among the 26 patients undergoing prior resection of all gross intrathoracic disease, brain metastases were observed in 3/12 patients (25%) receiving adjuvant chest irradiation alone, compared to none of 14 receiving prophylactic cranial irradiation (p = .06). In the absence of fully reliable therapy for the primary disease, and without effective systemic therapy preventing dissemination to other, extrathoracic sites, prophylactic cranial irradiation for inoperable non-small cell lung cancer cannot be justified in routine clinical practice. Further investigation in the adjuvant, postoperative setting may be warranted.

Adenocarcinoma↗
PubMed1991

Forensic aspects of 'crack' abuse.

Two cases of paranoid psychoses resulting from 'Crack' abuse are described. In each case the content of the delusions led to violence. These cases were referred to forensic psychiatric services for assessment, without prior contact with services for drug abusers. The importance of eliciting a full drug history in assessment of violent offenders is emphasized.

Adolescent↗
PubMed1991

Seizures and the regulation of neurotrophic factor and neuropeptide gene expression in brain.

Seizure-induced plasticity, in the form of either changes in cellular morphology or changes in neurochemistry, could have a profound impact upon regional excitability in brain. There is now ample evidence that in genetically 'normal' animals, seizure activity stimulates alterations in neuronal gene expression which could lead to changes in levels of excitability and, hence, to changes in the susceptibility for further seizures. Here we describe the influence of limbic seizures upon the expression of nerve growth factor (NGF), 2 related neurotrophic factors, brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), and several neuropeptides (enkephalin, dynorphin, and neuropeptide Y) in the rat forebrain. Using 35S-labeled riboprobes and in situ hybridization methods, the effects of recurrent limbic seizures and of individual hippocampal paroxysmal discharges have been evaluated. Recurrent seizures are found to increase levels of mRNAs for NGF and BDNF and to decrease levels of mRNA for NT3 within select hippocampal neurons. Temporally distinct increases in the expression of mRNAs for NGF and BDNF are also observed across broad fields of neocortex, paleocortex (entorhinal, piriform, and cingulate cortices), and the amygdala. As little as one 20-sec paroxysmal discharge is sufficient to stimulate large changes in neurotrophic factor mRNA content of hippocampal neurons. The time courses and cellular specificities of these alterations in neurotrophic factor expression are discussed and contrasted with seizure-induced changes in neuropeptide expression. Mechanisms by which seizure-induced increases in hippocampal neuropeptide and neurotrophic factor synthesis could lead to both short- and long-term changes in regional excitability, and thereby could contribute to susceptibility for further seizure activity, are considered.

Animals↗
PubMed1991

Public knowledge of hospices: a street survey in Glasgow.

A street survey was conducted in Glasgow to find out the level of public knowledge of and attitudes to hospices generally and two local hospices. The level of knowledge was not high, though attitudes to hospices were positive. Those few respondents with unfavourable attitudes had little knowledge of hospices generally and knew little about the local hospices. The factors associated with level of knowledge and attitudes were different for the two local hospices. The media and the collection of money for hospices were the main source of knowledge.

Adolescent↗
PubMed1990

Modulation of expression of the hepatitis B virus surface antigen gene by the viral X-gene product.

Human hepatoma cells (HepG2 and HUH7) transfected with a plasmid (pHBV1004) containing the transcription units for the major surface antigen (S) mRNA and the X mRNA of hepatitis B virus (HBV) secreted surface antigen (HBsAg) into the culture medium. A frameshift mutation in the X gene carried by pHBV1004 greatly reduced HBsAg production by cells transfected with an equivalent amount of the mutant (pHBV1004-B). The mutation could be complemented by cotransfection with a plasmid (pSV2HBX) containing the X structural gene under control of the SV40 early promoter. HBsAg production by cells cotransfected with pHBV1004-B and pSV2HBX was equivalent to that in cells transfected with the parent plasmid (pHBV1004) alone. Levels of HBsAg production were directly related to the amount of S mRNA produced, showing that the X-gene product (HBxAg) can modulate expression of the S gene.

Gene Expression↗
PubMed1990

Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors.

We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.

Adolescent↗
PubMed1990

Lung cancer treated on the basis of cytologic findings: an analysis of 112 patients.

The authors studied 112 patients who received definitive radiotherapy/chemotherapy solely on the basis of positive cytologic findings in the appropriate clinical context. Eighty patients (71.4%) were treated on the basis of one or more positive sputum studies, while the remainder had at least one positive bronchial cytologic preparation. Eighty-six patients (76.3%) received radiotherapy alone; 19 received both radiotherapy and chemotherapy; only 7 were exclusively given chemotherapy. The utilization of stringent verification criteria revealed that none of our patients was falsely positive for malignancy. For those patients categorized as having malignant disease by verification criteria I-IV, there were no significant disparities between histologic and cytologic diagnoses. This study demonstrated, in a systematic fashion, that patients can be reliably and definitively treated for lung cancer on the basis of positive respiratory cytology findings without tissue corroboration.

Adult↗
PubMed1990

DNA sequence analysis of the KM19 locus linked to cystic fibrosis. Design of new oligonucleotides to remove non-specific PCR products.

The PstI polymorphism detected by probe KM19 is a highly informative marker in linkage disequilibrium with the cystic fibrosis locus and has been used extensively for prenatal diagnosis. The currently available primers used for polymerase chain reaction- (PCR-) based analysis of this locus have been shown to produce spurious amplification products. In this report, we describe the sequence of the KM19 locus and the major contaminating PCR product. We have used this information to design a more specific amplification procedure for analysis of the KM19 locus.

Base Sequence↗
PubMed1989

Genetic engineering applied to the development of vaccines.

The simplest application of the modern genetic manipulation methods to vaccine development is the expression in microbial cells of genes from pathogens that encode surface antigens capable of inducing neutralizing antibodies in the host of the pathogen involved. This procedure has been exploited successfully for development of a vaccine against hepatitis B virus (HBV) that is now widely used. Similar approaches have been directed towards formulations for immunization against several other animal and human diseases and some of these preparations are now presently in trials. Of no less importance is the impact of biotechnology in providing reagents for fundamental studies of topics such as the determination of virulence, antigenic variation, virus receptors and the immunological response to viral antigens. The core antigen of HBV is a good example of a product of genetic engineering that is a valuable diagnostic reagent, and that is finding important use in immunological studies of particular pertinence to vaccine development.

Amino Acid Sequence↗
PubMed1989

Cytofluorometric analysis of the DNA content in ovarian carcinoma and its relationship to patient survival.

Forty-one patients with epithelial malignancies of the ovary treated at the Medical College of Wisconsin Affiliated Hospitals from 1976 to 1984 had paraffin embedded tissue available for review. Of the 41 patients, 40 had adequate material to provide 50 micron sections that were evaluated with flow cytometry to determine DNA content. Tumor- and patient-related parameters were then correlated with the results of flow cytometry. Overall survival at 5 years in these patients was 43%, and relapse-free survival was 50%. Forty percent of the tumors were diploid, and 60% were aneuploid. Five-year survival for diploid patients was 74% with a relapse-free survival of 71%. Corresponding overall and relapse-free survivals for aneuploid patients were 22% and 35%, respectively. Distribution of the patients by histology, stage, and grade was equal between the diploid and aneuploid groups. All patients were treated with whole abdominal plus concomitant pelvic boost irradiation; total doses to the whole abdomen ranged from 10 Gy to 46 Gy (1000 to 4600 cGy) with the median dose being 37.5 Gy. Approximately 40% of the patients received chemotherapy, which usually consisted of a single agent (Alkeran, Burroughs Welcome, Research Triangle Park, NC). This retrospective study of patients with ovarian cancer treated with radiation therapy suggests the possibility that determinations of DNA ploidy may be useful in selecting patients whose poor prognosis dictates that a more aggressive therapy be used.

Adult↗