Combating meningococcal disease.
A thorough knowledge of the community and its networks are essential tools for a public health nurse following up contacts of someone infected with meningococcal disease.
Communicable Disease Control↗
Biomedical subjects
J Brown
Publications and source records attributed to J Brown.
Research implications of improvements in access to the ONS Longitudinal Study.
In this article we outline significant changes in the way the ONS Longitudinal Study data are stored, accessed and analysed. The data were held previously on mainframe computers. Recent technological changes have made it possible to introduce PC-based systems without compromising confidentiality. The advantages of this new computing environment are illustrated with recent findings on geographic inequalities in health.
Adolescent↗
GR196429: a nonindolic agonist at high-affinity melatonin receptors.
N-[2-[2,3,7,8-tetrahydro-1H-furo(2,3-g)indol-1-yl]ethyl]acetamide (GR196429) is a novel, nonindolic melatonin receptor agonist. GR196429 had high affinity for human mt1 (pKi 9.9) and MT2 (pKi 9.8) receptors expressed in Chinese hamster ovary cells and for 2-[125I]-iodomelatonin binding sites in human cerebellum, guinea pig superior colliculus and hypothalamus and chicken retina and tectum (pKi 8.8-9.5). GR196429 was inactive at a wide range of other hormone and neurotransmitter receptors. In Chinese hamster ovary cells expressing human mt1 or MT2 receptors, both melatonin and GR196429 dose-dependently inhibited forskolin-stimulated cAMP accumulation. In rabbit isolated retina, GR196429 inhibited calcium-dependent [3H]-dopamine release with potency (IC50 30 pM) and maximum effect (76 +/- 5% at 1 nM) similar to those of melatonin. The response was antagonized by the melatonin receptor antagonist luzindole (1 microM). In slices of rat brain suprachiasmatic nucleus, perfusion (1 h) with GR196429 at zeitgeber time 10 phase advanced the circadian peak in neuronal activity measured on the following day, with a maximum phase advance of 2.7 +/- 0.3 h at 10 pM and an EC50 of 0.6 pM, results that indicated a melatonin-like action on the phase of the circadian clock. CNS penetration and duration of receptor occupancy was determined in an ex vivo radioligand binding assay. In membranes of guinea pig superior colliculus prepared 30 min after administration of GR196429 (s.c.), 2-[125I]-iodomelatonin binding was inhibited with an ED50 of 0.04 mg/kg. After a dose of 1 mg/kg, binding was significantly inhibited for at least 3 h. Thus GR196429 is a potent and selective agonist at high-affinity melatonin receptors, which modulates circadian rhythms in an in vitro model of the circadian clock and which readily penetrates the CNS.
Animals↗
Light-curing acrylic resin as an orthodontic baseplate material.
Heat-curing autopolymerizing (self-cure or cold-cure), thermoplastic, and light-curing acrylic resin are the most commonly used orthodontic baseplate materials. While cured acrylic resins present few problems to the patient, in the laboratory acrylic resin has to be sprayed, mixed, or packed in a fume-extraction unit because of the harmful fumes emitted by the raw inflammable chemicals. Light-curing material, on the other hand, is virtually nonflammable and has virtually no aroma. A light-cure technique for the construction of orthodontic baseplates is described. While buildup of the baseplate is slightly slower than for self-cured material, the shorter time involved in trimming and polishing means that overall construction is faster. It is easier to obtain a uniform thickness with light-cured material, and it provides superior fit. These results, however, are subject to more extensive clinical trials. The only apparent disadvantage is the fine powder produced during trimming. Even with a bench equipped with an extraction unit, it is advisable to use a face mask to prevent the inhalation of dust.
Acrylic Resins↗
Bench stepping and running in women. Changes in fitness and injury status.
BACKGROUND: The purpose of this investigation was to evaluate injury rates and changes in VO2peak in women associated with aerobic exercise (bench stepping and running). METHODS: A pretest post-test repeated measures design was used to evaluate changes in VO2peak after training for 10 weeks, 3 days per week, for 1 hour per session. Injury incidence was monitored by questionnaires throughout the training program. SETTING: All testing and training took place at Auburn University Montgomery, Montgomery, AL, USA. PARTICIPANTS: The subjects were women enrolled in university physical activity courses. The exercise groups consisted of 23 women who performed bench exercise and 15 who performed running-jogging. Eleven subjects served as non-exercising controls. INTERVENTION: The 10-week exercise training program served as the intervention. MEASURES: Subjects were both pre- and post-tested for VO2peak by open circuit calorimetry. Body composition was estimated from a 7-site skinfold equation. A daily injury log was maintained to evaluate injury status. RESULTS: A repeated measures ANOVA found similar significant improvements in VO2peak for both the bench and running groups with no change for the control group. An evaluation of the injuries graded II or higher found 0.29 injuries per 100 hrs for the bench group and 0.66 injuries per 100 hrs for the running group. When all complaints were considered (grade I to grade IV) the rates increased to 2.44 per 100 hrs for the running group and 6.09 per 100 hrs for the bench group. CONCLUSIONS: Aerobic bench exercise produced similar changes in VO2peak compared to running. The results indicated that the primary injury complaints were grade I and related to delayed onset muscle soreness (DOMS). The bench group experienced an greater incidence of grade I complaints while the running group experienced a slightly greater incidence of more serious grade II or higher injuries.
Adult↗
Longitudinal study of socio-economic differences in the incidence of stomach, colorectal and pancreatic cancers.
Using the ONS Longitudinal Study, the incidence of stomach, colorectal and pancreatic cancers from 1976-90 was examined for men and women aged 30 years and over by their housing tenure and occupational social class. Large socio-economic differences in the incidence of stomach cancer for both men and women were found. The pattern of colorectal cancer was less clear, with women in more advantaged social groups experiencing higher incidence while for men there was no significant association. Pancreatic cancer showed no association with socio-economic status. Consistent findings with each indicator strengthen the interpretation of the results. Risk factors for these cancers are known to vary by socio-economic status, and this study demonstrates the importance of continued monitoring of the distribution of cancer incidence.
Adult↗
What is this thing called "randomise"?
Explore the source record for details and available documents.
Adult↗
Comparison of thoracic radiographs with images transmitted via advanced telecommunications equipment.
OBJECTIVE: To compare thoracic radiographs of clinically normal dogs and dogs with mild clinical heartworm disease with images transmitted by a desk-top, two-way audiovisual teleconferencing system. DESIGN: Prospective, matched-set study. STUDY POPULATION: 50 thoracic radiographs from clinically normal and heartworm-infected dogs and the digitally transmitted images of those radiographs. PROCEDURE: Thoracic radiographs from 25 clinically normal dogs and 25 dogs infected with 1 to 24 heartworms were evaluated by 3 clinicians. Using classic criteria for heartworm disease, evaluations of radiographs and images transmitted digitally over 2 high-speed data-transfer telephone lines (56 kilobits/s/line) were performed. Clinicians were asked to determine whether dogs had radiographic signs of heartworm disease. RESULTS: Clinicians' ability to detect heartworm disease did not differ between interpretations of radiographs and those of transmitted images. CLINICAL IMPLICATIONS: Radiographic images transmitted via a teleconference system can be used to provide reliable diagnostic information. Thoracic radiographs can be interpreted at a remote site permitting rapid consultation and immediate advice on clinical management.
Animals↗
Colorectal cancer screening.
Explore the source record for details and available documents.
Colorectal Neoplasms↗
Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis.
BACKGROUND AND METHODS: Osteoporosis is a recognized complication of corticosteroid therapy. Whether it can be prevented is not known. We conducted a 12-month, randomized, placebo-controlled study of intermittent etidronate (400 mg per day for 14 days) followed by calcium (500 mg per day for 76 days), given for four cycles, in 141 men and women (age, 19 to 87 years) who had recently begun high-dose corticosteroid therapy. The primary outcome measure was the difference in the change in the bone density of the lumbar spine between the groups from base line to week 52. Secondary measures included changes in the bone density of the femoral neck, trochanter, and radius and the rate of new vertebral fractures. RESULTS: The mean (+/-SE) bone density of the lumbar spine and trochanter in the etidronate group increased 0.61 +/- 0.54 and 1.46 +/- 0.67 percent, respectively, as compared with decreases of 3.23 +/- 0.60 and 2.74 +/- 0.66 percent, respectively, in the placebo group. The mean differences between the groups after one year were 3.72 +/- 0.88 percentage points for the lumbar spine (P = 0.02) and 4.14 +/- 0.94 percentage points for the trochanter (P = 0.02). The changes in the femoral neck and the radius were not significantly different between the groups. There was an 85 percent reduction in the proportion of postmenopausal woman with new vertebral fractures in the etidronate group as compared with the placebo group (1 of 31 patients vs. 7 of 32 patients, P = 0.05), and the etidronate-treated postmenopausal women also had significantly fewer vertebral fractures per patient (P = 0.04). CONCLUSIONS: Intermittent etidronate therapy prevents the loss of vertebral and trochanteric bone in corticosteroid-treated patients.
Adult↗
Human papillomavirus (HPV) 16 E6 sensitizes cells to atractyloside-induced apoptosis: role of p53, ICE-like proteases and the mitochondrial permeability transition.
Infection of cervical epithelial cells with certain high risk HPV genotypes is thought to play an etiologic role in the development of cervical cancer. In particular, HPV type 16 and 18 early protein 6 (E6) is thought to contribute to epithelial transformation by binding to the tumor suppressor protein p53, targeting it for rapid proteolysis, resulting in loss of its cell cycle arrest and apoptosis-inducing activities. Recent data indicate that factors responsible for triggering apoptosis reside in the cytoplasm of cells, and not in the nucleus. In particular, the findings that mitochondria are required in certain cell-free models for induction of apoptosis and that bcl-2 is localized to mitochondria have focused attention on the role of the mitochondrial membrane permeability transition (MPT) in apoptosis. Here we present data to indicate that HPV 16 E6 expression sensitizes cells to MPT-induced apoptosis. We also report that HPV 16 E6 sensitization of cells to MPT-induced apoptosis occurs only in the presence of wildtype (wt) p53 expression. The extent of apoptosis induced by atractyloside (an inducer of the MPT) in normal, temperature-sensitive (ts) p53, and HPV-16 E6 transfected J2-3T3 cells, and the HPV expressing cervical carcinoma cell lines SiHa, Hela and CaSki was determined. C33A cells, which express mutant p53 but not HPV, were also exposed to atractyloside in the presence or absence of HPV 16 E6 expression. Dose-dependent apoptosis induced by atractyloside in normal J2-3T3 cells and cervical carcinoma cells was measured by loss of cell viability, nuclear fragmentation and DNA laddering. The sensitivity of cells to atractyloside-induced apoptosis was found to be: HPV 16 E6-J2-3T3 > CaSki > normal-J2-3T3 cells approximately ts p53-J2-3T3 approximately vector-J2-3T3 cells > Hela > SiHa > C33A approximately C33A 16 E6. Cyclosporin A (CsA), an inhibitor of the MPT, and ICE-I, a protease inhibitor, provided protection against atractyloside-induced apoptosis. These findings indicate that: 1) high risk HPV 16 E6 protein is capable of sensitizing cells to apoptosis; 2) HPV 16 E6 sensitization of cells to atractyloside-induced apoptosis occurs in a p53-dependent fashion; 3) the target of HPV 16 E6 sensitization of cells to atractyloside-induced apoptosis is the mitochondria; and 4) HPV 16 E6 sensitization of cells to atroctycoside-induced apoptosis involves an ICE-like protease-sensitive mechanism, regulating the onset of the MPT. These findings constitute the first evidence that mitochondria play a role in HPV 16 E6 modulation of apoptosis.
Animals↗
Scrapie-induced neuron loss is reduced by treatment with basic fibroblast growth factor.
Neuron loss can be a prominent feature of the pathology of transmissible spongiform encephalopathies (TSEs); recent evidence indicates that this loss occurs through apoptosis. Growth factor treatment of other neurodegenerative diseases has been shown to protect neurons destined for apoptosis, and several types of experimental retinopathy have been successfully treated with basic fibroblast growth factor (bFGF). In a murine scrapie model which develops a severe loss of photoreceptors, we administered a single intravitreal injection of bFGF four-fifths of the way through the disease process; this doubled the number of photoreceptors surviving for up to 5 weeks, i.e. to the terminal stages of the disease. This is the first time that a potential late-stage therapy for the TSEs has been demonstrated.
Animals↗
Mechanism of accountability needs to be developed for changing role of healthcare professionals.
Explore the source record for details and available documents.
Clinical Competence↗
Single-stranded RNA recognition by the bacteriophage T4 translational repressor, regA.
The T4 protein, RegA, is a translational repressor that blocks ribosome binding to multiple T4 messages by interacting with the mRNAs near their respective AUG start codons. Other than the AUG, there are no obvious similarities between the affected mRNAs. High affinity RNA ligands to RegA were isolated using SELEX (systematic evolution of ligands by exponential enrichment). The selected RNAs exhibited the consensus sequence 5'-AAAAUUGUUAUGUAA-3'. The AUG was invariant, suggesting that it is the primary effector of binding specificity. The UU immediately 5' to the AUG and the upstream poly(A) tract were highly conserved among the selected RNAs. Boundary and footprinting experiments are consistent with the consensus sequence defining the RegA-binding site. Interestingly, chemical modification and nuclease digestion data indicate that the RNA-binding site is single-stranded, as if RegA discriminates between targets based on their primary sequence, not their secondary structure. Minor variations from the consensus at positions other than the universally conserved AUG have little effect on RegA binding, but accumulation of mutations has a profound effect on the interaction. Comparison of the in vivo targets for RegA to the SELEX-generated consensus suggests a repression pattern whereby the translation of individual messages is sequentially halted until the least similarly affected message, the regA gene itself, is repressed.
Bacteriophage T4↗
Buprenorphine and naloxone interactions in methadone maintenance patients.
Buprenorphine is undergoing clinical trials for the treatment of opiate addiction. Although the abuse liability of sublingual buprenorphine is low, reports of intravenous abuse have appeared. This study describes the physiologic and subjective effects of intravenously administered buprenorphine and naloxone given alone and in combination to methadone-maintained patients (40-60 mg/day). On four separate occasions at least 1 day apart, 6 subjects were administered either 0.2 mg buprenorphine, 0.1 mg naloxone, 0.2 mg buprenorphine and 0.1 mg naloxone in combination, or placebo. One male subject quit the experiment after three sessions because of excessive opiate withdrawal. Buprenorphine produced no significant physiologic or subjective effects. Naloxone produced marked opiate withdrawal symptoms. Buprenorphine in combination with naloxone produced characteristic physiologic and subjective opiate antagonist-like symptoms and signs. The parenteral abuse potential of the buprenorphine and naloxone combination is discussed.
Adult↗
Nanoliter scale PCR with TaqMan detection.
We monitored PCR in volumes of the order of 10 nl in glass microcapillaries using a fluorescence energy transfer assay in which fluorescence increases if product is made due to template-dependent nucleolytic degradation of an internally quenched probe (TaqMan assay). This assay detected single starting template molecules in dilutions of genomic DNA. The results suggest that it may be feasible to determine the number of template molecules in a sample by counting the number of positive PCRs in a set of replicate reactions using terminally diluted sample. Since the assay system is closed and potentially automatable, it has promise for clinical applications.
Actins↗
Novel transcribed sequences neighbouring a translocation breakpoint associated with schizophrenia.
A 1.3Mb chromosome 11-specific yeast artificial chromosome (YAC) that spans a t(1;11) translocation breakpoint associated with major psychosis has been used to enrich cDNAs that are encoded within it and expressed in the human foetal brain. Database analysis of the selected fragments led to the identification of 54 clones matching alpha-tubulin, 4 fragments matching two anonymous human expressed sequence tags (ESTs) and 8 fragments giving no database matches. The clones matching alpha-tubulin led to the identification of a novel alpha-tubulin locus located approximately 250 kb proximal to the translocation breakpoint. Extensive sequence and expression analysis of this locus suggests that this is a processed pseudogene, although a long open reading frame is maintained and the possibility that an abnormally acting protein may be expressed in a highly tissue or developmental specific manner cannot be discounted. The novel cDNA fragments map up to 700 kb proximal to the translocation breakpoint and are associated with potential CpG islands. Reverse transcriptase polymerase chain reaction (RT-PCR) expression analysis and high resolution genomic mapping suggest that they may comprise up to three novel genes. No major disruption of the identified fragments could be detected in the genomic DNA of translocation carriers. The psychosis associated with this translocation may therefore be due to position effects on the transcription of these genes or an involvement of translocated chromosome 1 sequences.
Chromosomes, Artificial, Yeast↗
Photodermatitis from sunscreen.
Explore the source record for details and available documents.
Humans↗