Sphingomyelin hydrolysis and regulation of the expression of the gene for cytochrome P450.
Explore the source record for details and available documents.
Acute-Phase Reaction↗
Biomedical subjects
J Stewart
Publications and source records attributed to J Stewart.
Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast cancer.
The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1-3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.
Adult↗
The cosmetic outcome in early breast cancer treated with breast conservation.
AIMS: To measure the cosmetic outcome of breast-conserving surgery and identify the factors which influence cosmesis. METHODS: A total of 254 patients with primary breast cancer treated by wide local excision, with or without radiotherapy, were subjectively assessed for cosmesis by a six-member panel using photographic evaluation and objectively by an independent observer using specific measurement. RESULTS: Good to excellent cosmetic results were achieved in 184 (72%) patients on panel subjective assessment and 201 (79%) patients on objective assessment. Good correlation (P<0.001) and agreement were found between the panel's subjective photographic assessment and the objective assessment. The main factors found to affect cosmesis negatively were: medially located tumours; weight of specimen; re-excision procedures; radiotherapy; small breasts and longer scars. CONCLUSION: These cosmetic results, combined with a low local recurrence rate following wide local excision, validate the operative method used.
Adult↗
Transurethral needle ablation of the prostate: outcome at 1 year.
BACKGROUND: Urologists continue to search for alternatives to transurethral prostatectomy that carry a lower potential for complications. PATIENTS AND METHODS: Twenty-five patients on the public waiting list for transurethral resection of the prostate, all spontaneously voiding, underwent transurethral needle ablation of the prostate (TUNA). Eight patients had a simultaneous bladder neck incision (BNI). Follow-up with International Prostate Symptom Scores and flow rate measurement was performed at 6 weeks, 7 months, and 1 year. RESULTS: A statistically significant increase in flow rate and fall in symptom scores occurred out to 1 year after TUNA. Despite this result, six patients (24%) were not satisfied with their outcome and underwent a second endoscopic operation. CONCLUSION: In our hands, TUNA produced an unsatisfactory clinical result.
Aged↗
Functional diversity of natural IgM.
This paper proposes a method for the quantitative characterization of repertoire diversity of an unknown mixture of antibodies on the basis of its reactivity profile in the quantitative immunoblot (QIB). The QIB is calibrated by measuring the reactivity profiles of supernatants of known 'diversity' (i.e. known numbers of B cell clones). We define a quantitative 'index of variability' (IV) which decreases regularly as the diversity increases and the profiles tend towards a common 'convergence profile'. The calibration procedure is consolidated by a mathematical model based on the Poisson distribution; this theoretical model accounts correctly for the observed convergence behavior. On the basis of this calibration curve, it is possible to estimate the diversity of an unknown antibody mixture from a measure of its IV. We conclude that the functional diversity of natural serum IgM in mice can be estimated at approximately 16,000 clones.
Animals↗
Influence of apolipoprotein E genotype on neuronal damage and apoE immunoreactivity in human hippocampus following global ischemia.
Apolipoprotein E (apoE) influences the response to and outcome from brain injury possibly through alterations in neuronal repair mechanisms. This study aimed to determine alterations in neuronal and glial apoE after brain injury in patients and sought to determine whether possession of an apoE-epsilon4 allele influences the degree of apoE immunoreactivity or the degree of neuronal damage following brain injury. ApoE immunoreactivity and neuronal damage were semiquantitatively assessed in the temporal lobe of a group of controls (n = 44) and in a group of patients who had an episode of global ischemia and subsequently died (n = 58, survival ranged from 1 hour to 3 months). There was a significant degree of neuronal damage in all hippocampal sectors and in the neocortex of the global ischemia group compared with controls (p < 0.0001). Glial apoE immunoreactivity was significantly increased in hippocampal sectors (CA1, CA2, CA3/CA4, dentate fascia) in the global ischemia group compared with controls (p < 0.01). Neuronal apoE immunoreactivity was significantly increased in all hippocampal sectors (CA1, CA2, CA3/CA4, dentate fascia) and in the neocortex of the global ischemia group compared with controls (p < 0.0001). There was a significant and positive association between the degree of neuronal apoE immunoreactivity and the degree of neuronal damage in the global ischemia cases (r2 = 0.691, p < 0.001) and there was not an association in the control group. Possession of an apoE-epsilon4 allele did not influence the degree of neuronal or glial apoE immunoreactivity or the degree of neuronal damage in the global ischemia cases or the controls. The data indicate apoE is markedly increased in neurons and glia following brain injury. In this study, apoE genotype did not appear to influence neuronal damage, glial apoE or intraneuronal apoE following injury
Adolescent↗
The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage.
Cerebral amyloid angiopathy (CAA) is associated with apolipoprotein E (APOE gene, apoE protein) polymorphism: current evidence suggests that the epsilon4 allele is a risk factor for the development of CAA and the epsilon2 allele predisposes to hemorrhage. We sought to determine the relationship between the APOE epsilon2 allele and both the immunoreactivity profiles and vascular complications of CAA. We performed immunohistochemistry for amyloid beta-protein (A beta), apoE, cystatin C, and activated microglia, and examined the morphology of cortical and leptomeningeal vessels in 37 CAA-related hemorrhage (CAAH), 26 Alzheimer disease (AD) patients, and 20 controls. The extent of immunostaining of vessels for A beta, apoE, cystatin C, and perivascular activated microglia increased from controls through AD to a maximum in CAAH patients. Among cases with CAA (37 CAAH, 19 AD, and 6 controls, n = 62) vascular apoE (p < 5 x 10(-4)), cystatin C (p < 10(-4)), activated microglia (p < 10(-4)), vessels with a high ratio of wall thickness to lumen diameter (p < 0.003) as well as dilated/microaneurysmal vessels (p < 0.01) were present more frequently in patients with hemorrhage than without; however, these features were not associated with the APOE epsilon2 allele. Fibrinoid necrosis alone was associated with the APOE epsilon2 allele (p < 0.04) and we suggest that over-representation of APOE epsilon2 in CAAH may result from its association with fibrinoid necrosis.
Aged↗
Trends in hospitalization and mortality from rotavirus disease in New Zealand infants.
BACKGROUND: Rotavirus illness is associated with significant morbidity and mortality worldwide. We have examined trends in diarrheal disease in New Zealand children to determine the disease burden attributable to rotavirus and to estimate the proportion of hospitalizations preventable by vaccination. METHODS: Hospital admissions data and laboratory records for 1994 to 1996, were obtained for children 0 to 4 years at four sites (serving -60% of the New Zealand population). Rotavirus disease burden was estimated using combined admissions and laboratory data. Severity of disease was estimated in a sample of 150 hospitalizations for rotavirus diarrhea, and the proportion of vaccine-preventable admissions was extrapolated. Mortality attributed to diarrheal causes was determined from national records for 1974 to 1993. RESULTS: Between 1994 and 1996, 4436 children <5 years of age were hospitalized with diarrhea (1047/100000 children per year). Admissions associated with rotavirus were estimated at 1522 to 1535 (315 to 362/100000 annually). Infants between 6 and 17 months were most commonly affected (42% of all cases). More male children than female children were hospitalized (P < 0.001) and mean length of stay was calculated as 1.51 days (SD 2.35). Disease severity scoring revealed that 61.3 and 38.0% of admissions reviewed were severe and very severe, respectively. Deaths from diarrheal causes numbered 138 among children 0 to 4 years old for the 20-year period 1974 to 1993, with 18 deaths occurring between 1984 and 1993 (10 years). CONCLUSION: Current vaccines control severe disease, suggesting that 72% of cases reviewed would be eligible for prevention. A full cost effectiveness analysis is required to demonstrate anticipated benefits of vaccination.
Child, Preschool↗
Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia.
The most common neuropathological substrates of dementia are Alzheimer's disease, cerebrovascular disease, and dementia with Lewy bodies. A preliminary, retrospective postmortem analysis was performed of the relative burden of each pathology in 25 patients with predominantly Alzheimer's disease-type dementia. Log linear modelling was used to assess the relations between ApoE genotype, Alzheimer's disease, and cerebrovascular disease pathology scores. Sixteen of 18 cases (89%) with a Braak neuritic pathology score </=4 had, in addition, significant cerebrovascular disease, or dementia with Lewy bodies, or both. There was a significant inverse relation between cerebrovascular disease and Braak stage (p=0.015). The frequency of the ApoE-epsilon4 allele was 36.4%. No evidence was found for an association between possession of the ApoE-epsilon4 allele and any one pathological variable over another. In this series most brains from patients with dementia for which Alzheimer's disease is the predominant neuropathological substrate also harboured significant cerebrovascular disease or dementia with Lewy bodies. The data suggest that these diseases are perhaps pathogenetically distinct, yet conspire to produce the dementing phenotype.
Aged↗
Healthy housing: the role of the environmental health officer.
The relationship of health and housing has been well documented. There is less said about action that can be taken to deal with poor housing conditions. Environmental Health Officers in UK Government are key actors enforcing legislation relevant to housing conditions. Despite a century of legislative intervention in private sector housing conditions, the English House Condition Survey continues to report an excessive amount of poor conditions, and a particular decline in quality amongst the most disadvantaged in society who are increasingly accommodated in the private rented sector. This paper examines the role of poor housing in ill health and the difficulties faced in enforcing largely reactive legislative, arguing that wider changes are needed if the link between poor health and housing is to be broken.
Administrative Personnel↗
Thoughts on the interpretation of responses to drug-related stimuli.
Explore the source record for details and available documents.
Cues↗
Violence prevention: reaching adolescents with the message.
OBJECTIVE: To identify an effective medium for communicating with adolescents in a large-scale, cost-effective violence prevention program. METHODS: A set of youth violence prevention programs was established at The Stamford Hospital, a level II trauma center. The traveling version of the program was presented to middle school students in four parts: 1) a rap music video created by our violence prevention staff, 2) a facilitated discussion about dealing with anger, 3) a video of a trauma resuscitation in our emergency department, and 4) a commercial video of a teenage boy paralyzed after a gunshot wound. A written questionnaire with a five-point rating scale (1 to 5) was used to survey the audience 1 month after the program. The survey assessed the respondents' recall of each part of the program and the perceptions of the value of each part in identifying the problem of violence and reducing violent behavior. RESULTS: Of 99 respondents, the highest ratings for retention, problem identification, and impact were given to the commercial video (combined average category ranking of 11.394) and the rap music video (11.182). The trauma resuscitation video and the discussion of anger were ranked as being less effective (10.253 and 9.383, respectively). The audience seemed to comprehend the main point of the program and ranked the program, as a whole, higher than any of the parts when measured by success at problem identification and impact. CONCLUSION: Effective communication with adolescents is possible through many avenues. Children of the video age respond well to visual material. A violence prevention program should incorporate effective multimedia presentations. A variety of methods in combination proves to be most effective.
Adolescent↗
Comparison of breast cancer patient satisfaction with follow-up in primary care versus specialist care: results from a randomized controlled trial.
BACKGROUND: Routine follow-up of breast cancer patients in specialist clinics is standard practice in most countries. Follow-up involves regularly scheduled breast cancer check-ups during the disease-free period. The aims of follow-up are to detect breast cancer recurrence and to provide psychosocial support to the patient; however, little is known about patients' views on breast cancer follow-up. AIM: To assess the effect on patient satisfaction of transferring primary responsibility for follow-up of women with breast cancer in remission from hospital outpatient clinics to general practice. METHOD: Randomized controlled trial with 18 months' follow-up in which women received routine follow-up either in hospital outpatient clinics or from their own general practitioner. Two hundred and ninety-six women with breast cancer in remission receiving regular follow-up care at two district general hospitals in England were included in the study. Patient satisfaction was measured by means of a self-administered questionnaire supplied three times during the 18-month study period. RESULTS: The general practice group selected responses indicating greater satisfaction than did the hospital group on virtually every question. Furthermore, in the general practice group there was a significant increase in satisfaction over baseline; a similar significant increase in satisfaction over baseline was not found in the hospital group. CONCLUSION: Patients with breast cancer were more satisfied with follow-up in general practice than in hospital outpatient departments. When discussing follow-up with breast cancer patients, they should be provided with complete and accurate information about the goals, expectations, and limitations of the follow-up programme so that they can make an informed choice.
Ambulatory Care↗
Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders.
Loss of chromosome 7 (-7) or deletion of the long arm (7q-) are recurring chromosome abnormalities in myeloid leukemias. The association of -7/7q- with myeloid leukemia suggests that these regions contain novel tumor suppressor gene(s), whose loss of function contribute to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified, one in band q22 and another in bands q32-q35. Presently there are no data available on the molecular delineation of the distal critical region. In this study we analyzed bone marrow and blood samples from 13 patients with myeloid leukemia (de novo myelodysplastic syndrome [MDS], n = 3; de novo acute myeloid leukemia [AML], n = 9; therapy-related (t-) AML, n = 1) which, on chromosome banding analysis, exhibited deletions (n = 12) or in one case a balanced translocation involving bands 7q31-qter using fluorescence in situ hybridization (FISH). As probes we used representative clones from a contig map of yeast artificial chromosome (YAC) clones that spans chromosome bands 7q31.1-qter. In the 12 cases with loss of 7q material, we identified a commonly deleted region of approximately 4 to 5 megabasepairs in size encompassing the distal part of 7q35 and the proximal part of 7q36. Furthermore, the breakpoint of the reciprocal translocation from the patient with t-AML was localized to a 1,300-kb sized YAC clone that maps to the proximal boundary of the commonly deleted region. Interestingly, in this case both homologs of chromosome 7 were affected: one was lost (-7) and the second exhibited the t(7q35). The identification and delineation of translocation and deletion breakpoints provides the first step toward the identification of the gene(s) involved in the pathogenesis of 7q35-q36 aberrations in myeloid disorders.
Chromosome Mapping↗
Long-lasting induction of astrocytic basic fibroblast growth factor by repeated injections of amphetamine: blockade by concurrent treatment with a glutamate antagonist.
Repeated administration of stimulant drugs leads to lasting changes in their behavioral and neurochemical effects. These changes are initiated by drug actions in the somatodendritic regions of midbrain dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) and continue to develop for a period of time after termination of drug treatment. Here we show that repeated administration of amphetamine (3.0 mg/kg, i.p.; three injections, once every other day) results in sustained increases in basic fibroblast growth factor immunoreactivity (bFGF-IR) in both VTA and SNc, 200-500% over that seen in saline-treated animals. Increases were observed 24 hr, 72 hr, 1 week and 1 month after the last drug injection. Because glutamate participates in the development of sensitization to stimulant drugs, we assessed the effect of the glutamate antagonist, kynurenic acid (KYN), on amphetamine-induced bFGF-IR. Coadministration of KYN prevented the increases in bFGF-IR in both VTA and SNc assessed 1 week after the amphetamine treatment. No changes in bFGF-IR were observed in the nucleus accumbens or dorsal striatum. bFGF-IR was found to be associated with astrocytes and not with dopaminergic neurons. These findings suggest that sustained enhancement of astrocytic bFGF expression in DA somatodendritic regions is a mechanism whereby stimulant drugs exert enduring effects on midbrain DA function. We hypothesize that increased glutamatergic activity elicited by amphetamine and other stimulant drugs places excessive demands on the functioning of DA neurons recruiting regulatory and neuroprotective processes that lead to enduring changes in DA neuron functioning and connectivity.
Amphetamine↗
Winnipeg software designed to give FPs easy access to specialists' advice.
Specialists in Winnipeg have developed a method of consultation that they think may reduce their waiting lists by providing primary care physicians with computer-based advice on different conditions. This would help them assume some of the care currently provided by specialists.
Clinical Competence↗
Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes.
Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-->T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.
Aged↗