Practices should determine their own strategies for identifying patients.
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England↗
Biomedical subjects
R Cooper
Publications and source records attributed to R Cooper.
Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: histopathologic features-a report from the Children's Cancer Group.
BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic syndrome that occurs in about 2-3% of all cases of neuroblastoma. The histopathologic characteristics of neuroblastoma tumors associated with this syndrome were evaluated in a series of cases and controls. PROCEDURE: Pathology slides from a total of 54 neuroblastoma tumors were reviewed blindly. They included 13 tumors associated with opsoclonus-myoclonus and 41 age- and stage-matched controls. All tumors were classified into either the favorable (FH) or unfavorable histology (UH) group according to the International Neuroblastoma Pathology Classification (the Shimada system). Grade of lymphocytic infiltration was evaluated and presence or absence of lymphoid follicles was recorded in the individual tumor tissues. RESULTS: Twelve of 13 cases with opsoclonus-myoclonus were in the FH group. Twelve of 13 cases had diffuse (found in every section prepared from the multiple portions of the primary tumor) and extensive (occupying more than 50% of a single of multiple microscopic fields with x 100 magnification) lymphocytic infiltration with lymphoid follicles. Of the 41 control cases (27 FH and 14 UH tumors), 18 had focal areas of lymphocytic infiltration and six showed lymphoid follicles, but none had diffuse or extensive infiltration in their primary tumors. CONCLUSIONS: Diffuse and extensive lymphocytic infiltration with lymphoid follicles is a characteristic histologic feature of neuroblastic tumors with opsoclonus-myoclonus. This observation suggests an immune-mediated mechanism for this rare paraneoplastic syndrome.
Adolescent↗
The role of radiation therapy in children with acute lymphoblastic leukemia kidney infiltration.
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Adolescent↗
Computer visualisation of the moving human lumbar spine.
Disorders of the spine which lead to back pain are often mechanical in origin and, despite extensive research, diagnosis of the underlying cause remains problematical, yet back pain is one of the most common rheumatological symptoms presented to the general practitioner. Diagnosis must frequently be based upon evidence gathered at the segmental level which invariably means that imaging is used in the process. In addition, surgical fixation is increasingly used when the spinal column is considered to exhibit instability. A solid model of the spine creates the possibility of visualising spine motion, of assessing the effects of loading of the spinal column in conjunction with finite element analysis to investigate the consequences of vertebral fusion, and of planning surgical intervention. Such a model could also be valuable in medical education and for demonstrating spine motion to a patient to highlight abnormalities or the effects of treatment. This paper describes a three-dimensional visualisation of the human lumbar spine which runs on a personal computer operating under the Windows environment. The user interface enables the clinician to select the viewpoint for the spine model to allow the motion to be studied from different angles. Motion data are currently acquired from fluoroscopic image sequences but the model could be used to display data from different imaging modalities when they are developed sufficiently for spine motion studies.
Computer Simulation↗
Results of follow-up of human contacts of bovine tuberculosis in cattle during 1993-7 in North Staffordshire.
The purpose of the study was to describe the results of follow up of human contacts of bovine tuberculosis. The bovine tuberculosis cases occurred on farms in North Staffordshire between 1993 and 1997. A total of 162 people were identified as having close contact with cattle diagnosed as having bovine tuberculosis, or who had drunk unpasteurized milk from a herd with bovine tuberculosis. A retrospective review of chest clinic notes was performed. One hundred and thirty-eight people attended for follow up, and Heaf test results, necessity for chest X-ray and further clinical follow-up are described. No case of human Mycobacterium bovis infection was identified. It is suggested that follow-up of human contacts is limited to those with close contact with herds who have bovine tuberculosis and cattle with visible pulmonary lesions or evidence of udder infection. Children on the farms with affected cattle should also be offered BCG in advance of the routine school's programme.
Adolescent↗
CordyMax Cs-4 improves steady-state bioenergy status in mouse liver.
OBJECTIVE: To evaluate effects of CordyMax Cs-4, a mycelial fermentation product of Cordyceps sinensis, on energy metabolism. DESIGN: An in vivo pharmacology study using 31P nuclear magnetic resonance (NMR) spectroscopy. SUBJECTS AND STUDY INTERVENTIONS: Adult male C57-BL/6 mice were given an aqueous extract of CordyMax, 200 or 400 mg/kg per day or placebo for 7 days. OUTCOME MEASUREMENTS: Using 31P-NMR spectroscopy to measure cellular triphosphates and inorganic phosphate, expressed as a ratio to a reference peak, and calculate tissue pH. RESULTS: Steady-state beta adenosine triphosphate (ATP) increased in the liver of mice that received CordyMax (200 or 400 mg/kg per day) for 7 days, by 12.3% +/- 0.8% and 18.4% +/- 0.9%, respectively, compared to placebo controls (both p < 0.001), suggesting a higher hepatic bioenergy status in CordyMax-treated animals. Hepatic inorganic phosphate (Pi) decreased by 24.5% +/- 0.9% and 17.6% +/- 1.7% in the two treatment groups, respectively, compared to placebo controls (p < 0.001). The ratio of beta-ATP:Pi increased by 47.7% +/- 1.6% and 41.4% +/- 2.4%, respectively, in the treatment groups (both p < 0.001 compared to placebo). After discontinuation of CordyMax for 7 days, beta-ATP and Pi returned towards baseline. CONCLUSION: CordyMax is effective in improving bioenergy status in the murine liver, suggesting a mechanism underlying the known clinical effectiveness of CordyMax in alleviating fatigue and improving physical endurance, especially in elderly subjects.
Adenosine Triphosphate↗
Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies.
In order to develop a preliminary core set of disease outcome measures for use in clinical trials of idiopathic inflammatory myopathies (IIM), we evaluated those measures used in previous trials, assessed the validation of published instruments and discussed these at an international consensus conference. The initial proposals were further refined by a multidisciplinary group of adult and paediatric specialists experienced in IIM using the Delphi method. The proposed preliminary core set of disease activity measures consists of five domains: physician and patient/parent global assessments of disease activity; muscle strength; physical function; serum activity of muscle enzymes; and an assessment tool to capture extra-skeletal muscle disease activity. The group recommended further development of a core set of disease damage measures for assessment of persistent changes in anatomy, pathology and function of at least 6 months' duration. The group recommended that patient-reported outcomes should include generic health-related quality of life assessments using the Medical Outcomes Study 36-item Short Form (SF-36) health survey in adult IIM patients and a validated quality of life instrument for paediatric patients. We propose the core set of outcome measures as a minimum group of assessments to include in all IIM therapeutic studies. The use of this core set should assist in standardizing outcome measurement and in optimizing therapeutic trials in myositis.
Adult↗
Prenatal nicotine affects catecholamine gene expression in newborn rat carotid body and petrosal ganglion.
Nicotine exposure modifies the expression of catecholamine and opioid neurotransmitter systems involved in attenuation of hypoxic chemosensitivity. We used in situ hybridization histochemistry to determine the effect of prenatal and early postnatal nicotine exposure on tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), preproenkephalin (PPE), and D2-dopamine receptor mRNA levels in the rat carotid body and petrosal ganglion during postnatal development. In the carotid body, nicotine increased TH mRNA expression in animals at 0 and 3 postnatal days (both, P < 0.05 vs. control) without affecting TH mRNA levels at 6 and 15 days. At 15 postnatal days, DbetaH mRNA levels were increased in the carotid body of nicotine-exposed animals. Dopamine D2-receptor mRNA levels in the carotid body increased with postnatal age but were unaffected by nicotine exposure. PPE was not expressed in the carotid body at any of the ages studied in control or treated animals. In the petrosal ganglion, nicotine increased the number of ganglion cells expressing TH mRNA in animals at 3 days (P < 0.01 vs. control). DbetaH mRNA expression was not induced nor was PPE mRNA expression increased in the petrosal ganglion in treated animals. Prenatal nicotine exposure upregulates mRNAs involved in the synthesis of two inhibitory neuromodulators, dopamine and norepinephrine, in peripheral arterial chemoreceptors, which may contribute to abnormalities in cardiorespiratory control observed in nicotine exposed animals.
Animals↗
Physiological responses to two wheelchair-racing exercise protocols.
OBJECTIVE: This study investigated the blood lactate accumulation during two wheelchair-racing protocols. During exercise, energy is required, which causes metabolism to increase and blood lactate to accumulate. Proper training can reduce the amount of blood lactate accumulation and increase tolerance to blood lactate accumulation during aerobic exercise. METHODS: Eleven male wheelchair elite track athletes with a spinal cord injury were tested to determine their blood lactate response to speed and resistance workouts. A computer-monitored wheelchair dynamometer was used during all exercise tests. The order of the test (e.g., speed or resistance workout) was randomized. Blood pressure and blood samples were taken immediately before and after completion of each exercise test. RESULTS: The difference between the blood lactate concentrations before and after testing were 8.56 +/- 4.42, and 11.67 +/- 4.69 mM for the resistance and speed tests, respectively. CONCLUSIONS: Our results showed that the blood lactate responses were significantly different for the resistance and speed workouts.
Adult↗
The safe use of syringe drivers for palliative care: an action research project.
A palliative care team in north Scotland identified serious drug errors occurring in the local health-care trust. These were connected with the use of variable rate syringe drivers (IVAC P100) to deliver pain and symptom management rather than the more suitable Graseby MS26. An action research approach was taken to effecting change. An educational workshop was set up which 23 nurses attended. Clinical support was provided and 3 months later an evaluation was carried out. Of the 13 nurses who had used an MS26, most were able to correctly follow the process of setting up the driver and had made appropriate observations, but drug calculations were a problem. Change was stated to have taken place in seven clinical areas but the degree of change was variable. Facilitators and obstacles to the change process are identified and recommendations made for the next round in the action research cycle.
Equipment Design↗
Gait dysfunction in Huntington's disease: parkinsonism and a disorder of timing. Implications for movement rehabilitation.
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Aged↗
Smoking in Maywood: the unhealthy southern migrant hypothesis among African Americans.
OBJECTIVES: This paper examines the "unhealthy Southern migrant" hypothesis with regard to cigarette smoking among African Americans. METHODS: Using data collected in 1992 from a sample of 1,518 African Americans in Maywood, Illinois, as part of the International Collaborative Study of Hypertension in Blacks, logistic regression analysis was conducted to examine and compare smoking behavior and sociodemographic characteristics of Southern and Midwestern-born respondents. RESULTS: African Americans born in the South were less likely (OR = .69, CI = 95%, 0.53, 0.90) to be smokers than those born in the Midwest, after controlling for other sociodemographic variables, prior smoking status, and age of arrival to Maywood. CONCLUSIONS: The results do not support the "unhealthy Southern migrant" hypothesis, with regard to cigarette smoking, and indicate the need to identify factors that protect Southern-born African-American migrants from smoking.
Adult↗
Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: findings of the national conference on cardiovascular disease prevention.
A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.
Cardiovascular Diseases↗
Novel antihyperglycemic terpenoid-quinones from Pycnanthus angolensis.
Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.
Africa↗
Direct reversal of DNA damage by mutant methyltransferase protein protects mice against dose-intensified chemotherapy and leads to in vivo selection of hematopoietic stem cells.
Direct reversal of O6 adducts caused by chemotherapy agents is accomplished in mammalian cells by the protein O6-methylguanine DNA methyltransferase (MGMT). Some tumors overexpress MGMT and are resistant to alkylator therapy. One future approach to treatment of these tumors may rely on concurrent pharmacological depletion of tumor MGMT with O6-benzylguanine (6-BG) and protection of sensitive tissues, such as hematopoietic stem and progenitor cells, using genetic modification with 6-BG-resistant MGMT mutants. We have used retroviral-mediated gene transfer to transduce murine hematopoietic bone marrow cells with MGMT point mutants showing resistance to 6-BG depletion in vitro. These mutants include proline to alanine and proline to lysine substitutions at the 140 position (P140A and P140K, respectively), which show 40- and 1000-fold resistance to 6-BG compared with wild-type (WT) MGMT. Lethally irradiated mice were reconstituted with murine stem cells transduced with murine stem cell virus retrovirus expressing each mutant, WT MGMT, or mock-infected cells and then treated with a combination of 30 mg/kg 6-BG and 10 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with 40 mg/kg BCNU alone. Compared with mice treated with BCNU alone, significant myeloid toxicity and death occurred in mice reconstituted with mock-infected or WT MGMT (<0.1 probability of survival) or the P140A mutant (0.13 probability of survival) MGMT cDNAs. In contrast, after an initial period of mild cytopenia, mice reconstituted with the P140K mutant (0.83 probability of survival) recovered nearly normal blood counts, even during continued treatment. Comparison of peripheral blood neutrophils after completion of 5 weekly treatments in these animals showed a direct correlation between the treatment and in vivo selection for progeny of transduced cells (pretreatment, approximately 8-12% transduced cells; no treatment, approximately 6% transduced cells; BCNU only, 51% transduced cells; 6-BG/BCNU, 93% transduced cells). To determine whether this selection occurred at the stem cell level, bone marrow from each treatment group was infused into secondary recipients. Whereas animals that received bone marrow from untreated animals reconstituted with 2% transduced cells, animals receiving marrow from 6-BG/BCNU-treated animals reconstituted with 94% transduced cells, demonstrating nearly complete selection for stem cells in the primary animals. Mice reconstituted with marrow from animals treated with BCNU only demonstrated 23% transduced cells, consistent with partial selection of stem cells in the primary mice. The levels of transduced cells also correlated with survival during a second round of intensive combination chemotherapy (probability of survival: 6-BG/BCNU, 1.0; BCNU alone, >0.70; no treatment, <0.1). These data demonstrate that mutant MGMT expressed in the bone marrow can protect mice from time- and dose-intensive chemotherapy and that the combination of 6-BG and BCNU leads to uniform selection of transduced stem cells in vivo in mice.
3T3 Cells↗
Genetic inheritance of body mass index in African-American and African families.
Numerous studies have shown recessive major gene inheritance of body mass index (BMI) in white populations; few have examined the inheritance of BMI in the African-American population where obesity is more prevalent, nor in African populations where obesity is comparatively rare. To evaluate the inheritance of obesity in two different populations of African origin, we used segregation analysis to determine the transmission of BMI in 95 African-American families and 400 Nigerian families. Probands were selected from participants in the population-based International Collaborative Study on Hypertension in Blacks. Using class D regressive models, results from the segregation analysis of the African-American data showed evidence of a major gene effect on BMI. The Nigerian results were strikingly similar, with comparable estimates for the genotype frequencies and means and strong evidence for a major effect in the transmission of BMI. The high BMI allele frequency estimate of 24% is consistent with estimates in other studies, but the mode of transmission appeared codominant, which differs from studies involving predominantly white populations. In the Nigerian analysis, however, the probability of a high BMI homozygote parent transmitting a low BMI allele to his/her offspring was significantly different from the Mendelian expectation of zero (estimated tau(BB) = 0.45), suggesting that additional complexities exist in the major gene inheritance of BMI in this population. The strong similarity of the genotype frequencies and means obtained from the African-American and Nigerian samples suggests that a common codominant major gene effect may contribute to the variation in BMI in both populations.
Alleles↗
Constituents of red yeast rice, a traditional Chinese food and medicine.
Detailed analyses were undertaken of the natural constituents of red yeast rice, a traditional Chinese medicine and food known for centuries to improve blood circulation. Preparation of red yeast rice following ancient methods by fermenting the fungal strain Monascus purpureus Went on moist and sterile rice indicated the presence of a group of metabolites belonging to the monacolin family of polyketides, together with fatty acids, and trace elements. The presence of these compounds may explain in part the cholesterol-lowering ability associated with this traditional Chinese food.
Anticholesteremic Agents↗
Large-scale mobilization and isolation of CD34+ cells from normal donors.
We describe collection and purification of peripheral blood CD34+ cells from volunteer, normal donors and allogeneic stem cell donors. A total of 98 aphereses were performed on 68 volunteer donors using peripheral venous access. The mean number of nucleated cells collected was 4.6 x 10(10) which included 1.9 x 10(8) CD34+ cells corresponding to 2.7 x 10(6) CD34+ cells/kg. The number of CD34+ cells collected did not differ between males and females but did correlate with the donor's weight and the total number of nucleated cells collected. The Nexell Isolex 300i cell separator was used to isolate CD34+ cells from 30 of the collections. A mean of 0.36% of the total cells was recovered and included 43 +/- 18% of the CD34+ cells. CD34+ cells represented 85 +/- 11% of the recovered cells. The total number of CD34+ cells recovered was not influenced by the number of nucleated cells placed on the Isolex 300i. The percentage of CD34+ cells recovered was not related to the number of CD34+ cells placed on the Isolex 300i. The purity of the final product was influenced by the number of CD34+ cells but not the total number of nucleated cells. An additional 38 CD34+ cell isolations were performed on normal allogeneic stem cell donors with similar results. These observations further support the safety and feasibility of peripheral blood CD34+ cell collection and purification.
Adult↗