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Biomedical subjects

M Ross

Publications and source records attributed to M Ross.

At least 19 recordsLinked to original sources
PubMed2006

A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy.

The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P<0.0001). The median overall survival for the immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a difference that is not statistically significant. Immediate high-dose chemotherapy and radiation therapy as consolidation offers a clinically and statistically significant improvement in EFS compared with radiation therapy alone following induction chemotherapy for women with metastatic breast cancer confined to the bones.

Adult↗
PubMed2005

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Amyotrophic Lateral Sclerosis↗
PubMed2004

A clinical trial of creatine in ALS.

BACKGROUND: Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons. METHODS: The authors conducted a randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS. The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles, with secondary outcomes including grip strength, ALS Functional Rating Scale-Revised, and motor unit number estimates. Patients were treated for 6 months, and evaluated monthly. RESULTS: Creatine was tolerated well, but no benefit of creatine could be demonstrated in any outcome measure. CI analysis showed that the study, although powered to detect a 50% or greater change in rate of decline of muscle strength, actually made an effect size of greater than 23% unlikely. It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability, and may be a useful outcome measure in future clinical trials. CONCLUSION: Any beneficial effect of creatine at 5 g per day in ALS must be small. Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS. In addition, motor unit number estimation may be a useful outcome measure for future clinical trials in ALS.

Adolescent↗
PubMed2004

Achievement of ultralow emittance beam in the accelerator test facility damping ring.

For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.

Journal Article↗
PubMed2003

Induction of 5alpha-reductase type II mRNA transcription in primary cultured prostate epithelial cells by a soluble factor produced by primary cultured prostate fibroblast cells.

The role of DHT in the development of BPH has resulted in the formulation of several drugs, which have been designed to inhibit the formation of DHT by the 5alpha-reductase enzymes (5alpha-reductase type I (5alpha-RI) & 5alpha-reductase type II (5alpha-RII)). Although the function of these enzymes is well understood, the biochemical stimulus for initiation of 5alpha-RI and II gene expression has not been described. Study of a co-culture model indicated the presence of a diffusible factor secreted by prostatic fibroblast cells, which is responsible for the transcription of 5alpha-II mRNA in primary prostatic epithelial cells. In this study, we describe the partial characterisation of a fibroblast-secreted, soluble factor which we believe induces the transcription of 5alpha-RII mRNA in long-term primary cultures of prostate epithelial cells which can no longer transcribe 5alpha-RII mRNA.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

A phase I trial of immunotherapy with intratumoral adenovirus-interferon-gamma (TG1041) in patients with malignant melanoma.

AIMS: Interferon-gamma (IFN-gamma) has been shown to upregulate MHC class I and II expression, and to promote generation of specific antitumor immune responses. We hypothesized that intratumoral administration of an IFN-gamma gene transfer vector facilitates its enhanced local production and may activate effector cells locally. We conducted a phase I dose-escalation study of a replication-deficient adenovirus-interferon-gamma construct (TG1041) to determine safety and tolerability of intratumoral administration, in advanced or locally recurrent melanoma. METHODS: Patients were enrolled at four successive dose levels: 10(7) infectious units (iu) (n=3), 10(8) iu (n=3), 10(9) iu (n=3), and 10(10) iu (n=2) per injection per week for 3 weeks. TG1041 was injected in the same tumor nodule weekly in each patient. Safety, toxicity, local and distant tumor responses and biologic correlates were evaluated. RESULTS: A total of 11 patients were enrolled and received the planned three injections per cycle. One patient with stable disease received a second cycle of treatment. A maximum tolerated dose was not reached in this study. No grade 4 toxicities were observed. Two grade 3 toxicities, fever and deep venous thrombosis were observed in one patient. The most frequently reported toxicities were grade 1 pain and redness at the injected site (n=8), and grade 1 fatigue (n=5) patients. Clinical changes observed at the local injected tumor site included erythema (n=5), a minor decrease in size of the injected lesion (n=5) and significant central necrosis by histopathology (n=1). Systemic effects included stable disease in one patient. Correlative studies did not reveal evidence of immunologic activity. CONCLUSION: Weekly intratumoral administration of TG1041 appears to be safe and well tolerated in patients with advanced melanoma.

Adenoviridae↗
PubMed2003

MUC1 expression, splice variant and short form transcription (MUC1/Z, MUC1/Y) in prostate cell lines and tissue.

OBJECTIVE: To detect the expression and transcription pattern of MUC1 in benign and malignant disease, and in two widely studied cell lines, and to investigate the glycosylation of MUC-1 in bone metastasis of prostate cancer, as mucins have been implicated in the progression and behaviour of several cancers. MATERIALS AND METHODS: RNA extracted from cell lines (DU145 and PC3), five samples of BPH and five samples of prostate cancer was reverse transcribed before amplification of MUC1-specific sequences by polymerase chain reaction. Paraffin-embedded sections were stained for glycosylated MUC1 and MUC1 core epitopes by HMFG1 and B27.29 antibodies, respectively. Steroid-treated cell lines were analysed by fluorescence-activated cell sorting, using the same antibodies. RESULTS: MUC1, in an under-glycosylated form, was widely expressed in the prostate and in metastatic lesions. MUC1/Z and MUC1/Y RNA were differentially expressed in BPH and prostate cancer, with no detectable expression of splice variant mRNA. This is in contrast to prostate cancer cell line cells (PC3 and DU145), which express splice variant mRNA. CONCLUSIONS: BPH, prostate cancer and metastatic prostate cancer all express high levels of under-glycosylated MUC1. This may explain the inability of previous studies to detect MUC1 in prostate tissue, as the antibody used was specific for a carbohydrate epitope which is not expressed on the under-glycosylated MUC1.

Bone Neoplasms↗
PubMed2002

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗
PubMed2001

Current management of ALS: comparison of the ALS CARE Database and the AAN Practice Parameter. The American Academy of Neurology.

BACKGROUND: The American Academy of Neurology (AAN) ALS Practice Parameter was published in April 1999. The ALS CARE Database has been collecting data on the management of patients with ALS in North America since 1996. OBJECTIVE: To compare the management of patients with ALS in North America as recorded in the ALS CARE Database with the recommendations of the AAN ALS Practice Parameter. METHODS: Data were analyzed from 2018 patients at enrollment and from 373 of these patients who died between enrollment and May 1999. RESULTS: Eighty-two percent of the enrolled patients reported that they had been given enough information about ALS. Only 54% of patients with drooling were receiving medication for this problem. Only 41% of those who reported being depressed most of the time were receiving antidepressant medications. Only 28% of those with dyspnea and only 9.2% of those with a forced vital capacity <40% predicted were receiving noninvasive positive pressure ventilator support. Only 30% of those with moderate to severe dysphagia had a gastrostomy tube. Half of the patients who died did so at home, but only 47% of them received residential hospice services. Although 89% of patients who died were recorded as having done so peacefully, 17% were reported to have had breathing difficulties (i.e., respiratory distress), 8% anxiety, 3.3% pain, and 2.5% choking. Advance directives were in place for 90% of the patients who died, and in 97% of cases these directives were followed. CONCLUSIONS: These findings indicate that in the 3-year period prior to the publication of the AAN Practice Parameter, many but not all patients received the care that is recommended in that parameter; there were deficiencies, particularly in the key areas of gastrostomy and noninvasive positive pressure ventilation.

Amyotrophic Lateral Sclerosis↗
PubMed2001

High-pressure melting curves of argon, krypton, and xenon: deviation from corresponding states theory.

The melting curves of argon, krypton, and xenon were measured in a laser heated diamond-anvil cell to pressures of nearly 80 GPa reaching melting temperatures around 3300 K. For the three gases, we observed a considerable decrease in the melting slopes (dT/dP) from the predictions based on corresponding states scaling starting near 40, 30, and 20 GPa, respectively. The melting anomaly can be understood in terms of a model in which hcp stacking faults act as solutes in a binary system.

Journal Article↗
PubMed2001

A novel poly(A)-binding protein gene (PABPC5) maps to an X-specific subinterval in the Xq21.3/Yp11.2 homology block of the human sex chromosomes.

The gene-poor human-specific Xq21.3/Yp11.2 block of homology exhibits 99% nucleotide identity, with the exception of an internal X-specific region containing the marker DXS214. This paper describes the characterization of a novel gene (PABPC5) from this X-specific subinterval that belongs to the poly(A)-binding protein gene family. The genomic structure of PABPC5 covers 4061 bp of an uninterrupted open reading frame (ORF) and a 5'UTR spanning across two exons and associated with a CpG island; the potential 382-amino-acid protein contains four RNA recognition motif domains. PABPC5 has 73% nucleotide identity with PABPC4 over 1801 bp of the ORF. At the protein level, 60% identity and 75% similarity are obtained in the comparison with human PABPC4, as well as human, mouse, and Xenopus PABPC1. RT-PCR indicates that PABPC5 is expressed in fetal brain and in a range of adult tissues. Conservation of the PABPC5 ORF and genomic structure is shown in primates and rodents. The close proximity of this gene to translocation breakpoints associated with premature ovarian failure makes it a potential candidate for this condition.

Amino Acid Sequence↗
PubMed2001

Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis.

BACKGROUND: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. METHODS: Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations. RESULTS: Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin. CONCLUSION: These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.

Acetates↗
PubMed2001

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Animals↗
PubMed2001

Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor-positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.

Adult↗
PubMed2001

Sequence analysis and transcript identification within 1.5 MB of DNA deleted together with the NDP and MAO genes in atypical Norrie disease patients presenting with a profound phenotype.

Mutations at the Norrie disease gene locus, NDP, manifest in a broad range of defects. These range from a relatively mild, late-onset, exudative vitreoretinopathy to congenital blindness and sensorineural deafness combined, in some cases, with mental retardation. In addition, extensive deletions involving the NDP locus, located at Xp11.3, the adjacent monoamine oxidadase genes MAOA and MAOB, and additional material, result in a more severe pattern of symptoms. The phenotypes include all or some of the following; mental retardation, involuntary movements, hypertensive crises and hypogonadism. We extended an existing YAC contig to embrace the boundaries of three of the largest deletions and converted this into four PAC contigs. Computer analysis and experimental data have resulted in the identification of several putative loci, including a phosphatase inhibitor 2-like gene (dJ154.1) and a 250-bp sequence which resembles a homeobox domain (dA113.3), 1.2 Mb and 400 kb respectively from the MAO/NDP cluster. The pattern of expression of dJ154.1 suggests that it may represent an important factor contributing to the complex phenotypes of these deletion patients. Hum Mutat 17:523, 2001.

Blindness↗
PubMed2001

Prevalence of asthma and other allergic diseases in an adolescent population: association with gender and race.

OBJECTIVES: To estimate the prevalence and severity of asthma in an adolescent population by sex and race. METHODS: Cross-sectional, population-based survey of school children. SETTING: Midwestern city experiencing damage from the 1993 Mississippi River flood. PARTICIPANTS: 2,693 children attending grades 7 to 12. MEASUREMENTS: Questions from the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: Two thousand six hundred ninety-three children were surveyed, for a response rate of 90%. In this population, 16.4% reported having ever been diagnosed with asthma; 25% reported wheezing in the last 12 months; 32% reported symptoms of rhinitis in the last 12 months; and 22% reported ever having hay fever. The prevalence rate for current asthma was 12.6%. Female students had significantly greater prevalence rates for current asthma (16.4% vs 9.0%, OR = 1.85); ever-diagnosed asthma (18.5% vs 14.3%, OR = 1.36); wheezing > or = 4 times in the last 12 months (12.0% vs 5.6%, OR = 1.95); current rhinitis (38.7% vs 25.4%, OR = 1.73); and hay fever (26.4% vs 18.4%, OR = 1.57). All associations with sex remained significant, except ever-diagnosed asthma, after controlling for other known risk factors in logistic regression. African-Americans had higher prevalence rates than other races with differences reaching statistical significance for ever-diagnosed asthma and current asthma; however, these relationships did not remain significant after controlling for other known risk factors in logistic regression. CONCLUSIONS: Our prevalence rates were similar to those reported by other studies that used the ISAAC questionnaire. Female students reported significantly more asthma, wheezing, rhinitis, and hay fever than male students. Female students also reported more severe symptoms and a greater number of emergency room and hospital admissions.

Adolescent↗