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Biomedical subjects

K Carroll

Publications and source records attributed to K Carroll.

At least 19 recordsLinked to original sources

Electrically tunable Bragg gratings in single-mode polymer optical fiber.

We present what is to our knowledge the first demonstration of a tunable fiber Bragg grating device in polymer optical fiber that utilizes a thin-film resistive heater deposited on the surface of the fiber. The polymer fiber was coated via photochemical deposition of a Pd/Cu metallic layer with a procedure induced by vacuum-ultraviolet radiation at room temperature. The resulting device, when wavelength tuned via joule heating, underwent a wavelength shift of 2 nm for a moderate input power of 160 mW, a wavelength to input power coefficient of -13.4 pm/mW, and a time constant of 1.7 s(-1).

Journal Article↗

Outbreak of influenza A (H3N2) in a highly-vaccinated religious community: a retrospective cohort study.

An outbreak of influenza occurred at the end of the 2001-2 winter season in a highly-vaccinated, semi-enclosed, religious community. On the basis of retrospective self reporting, 43% met the case definition (151/350) and 81% (25/31) of throat swabs from cases were polymerase chain reaction (PCR) -positive for influenza A (H3N2). The risk of developing influenza in people aged 65 or more was lower than that of children aged 2 years and under (odds ratio 0.1, 95% confidence interval 0.02 to 0.38). The risk of developing symptoms of influenza was not significantly different between people who had been vaccinated in the United Kingdom and those who had not been vaccinated (OR 1.14, CI 0.41 to 3.14). Chronic disease was an independent risk factor for developing symptoms of influenza (OR 1.9, CI 1 to 3.63). Timing of the outbreak, the age structure and mode of communal living may have influenced the efficacy of the influenza vaccine, which was well matched to circulating strains at the time of the outbreak. It is important to consider the diagnosis of influenza even in a highly-vaccinated community.

Adolescent↗

Measuring fast neutrons in Hiroshima at distances relevant to atomic-bomb survivors.

Data from the survivors of the atomic bombs serve as the major basis for risk calculations of radiation-induced cancer in humans. A controversy has existed for almost two decades, however, concerning the possibility that neutron doses in Hiroshima may have been much larger than estimated. This controversy was based on measurements of radioisotopes activated by thermal neutrons that suggested much higher fluences at larger distances than expected. For fast neutrons, which contributed almost all the neutron dose, clear measurement validation has so far proved impossible at the large distances (900 to 1,500 m) most relevant to survivor locations. Here, the first results are reported for the detection of 63Ni produced predominantly by fast neutrons (above about 1 MeV) in copper samples from Hiroshima. This breakthrough was made possible by the development of chemical extraction methods and major improvements in the sensitivity of accelerator mass spectrometry for detection of 63Ni atoms (refs 8-11). When results are compared with 63Ni activation predicted by neutron doses for Hiroshima survivors, good agreement is observed at the distances most relevant to survivor data. These findings provide, for the first time, clear measurement validation of the neutron doses to survivors in Hiroshima.

Copper↗

ERK1/2 mediates PDGF-BB stimulated vascular smooth muscle cell proliferation and migration on laminin-5.

During restenosis following arterial injury, vascular smooth muscle cells (VSMCs) form a neointimal layer in arteries by changing from a differentiated, contractile phenotype to a dedifferentiated, migratory, and proliferative phenotype. Several growth factors, cytokines, and extracellular matrix components released following injury have been implicated in these phenotypic changes. We have recently detected the expression of laminin-5, an ECM protein found predominantly in epithelial tissues, in the arterial vasculature. Here we report that ln-5 expression by VSMC is upregulated by platelet-derived growth factor (PDGF-BB), epidermal growth factor, basic fibroblast growth factor, and transforming growth factor-beta1. Adhesion to ln-5 specifically enhances PDGF-BB-stimulated VSMC proliferation and migration. PD98059, a specific inhibitor of the ERK1/2 members of the Mitogen Activated Protein kinase family, increases both VSMC adhesion to ln-5 and blocks PDGF-BB-stimulated VSMC migration on ln-5. These results suggest that adhesion to ln-5 mediates a PDGF-BB-stimulated VSMC response to vascular injury via an ERK1/2 signaling pathway.

Animals↗

Toxicity of 17alpha-ethinylestradiol and bisphenol A to the freshwater Cnidarian Hydra vulgaris.

Estrogens and estrogen mimics that enter the environment are known to present a serious threat to the development and reproduction of vertebrates by disrupting their normal endocrine function. There is also concern that such chemicals may be damaging to invertebrates. In this study, Hydra vulgaris, a member of the Cnidaria, an evolutionarily primitive group of invertebrates present before the divergence of the protostomes and deuterostomes, was exposed to the synthetic estrogen 17alpha-ethinylestradiol (EE2) and bisphenol A (BPA), both of which are known to be estrogenic in fish. Effects on polyp survival, structure, and regeneration (and sexual reproduction for EE2) were examined and mortality was recorded at high concentrations, with 96-h LC(50)s of 3.8 mg/L and 6.9 mg/L for EE2 and BPA, respectively. The structure and physiology of polyps was adversely affected at concentrations greater than 58 microg/L EE2 and 42 microg/L BPA. There was a concentration-related inhibition of regeneration above 150 microg/L EE2 and 460 microg/L BPA. Sexual reproduction was only impaired at 500 microg/L EE2. These results clearly suggest that the signaling processes necessary for the control and regulation of cell movement and differentiation during normal development, regeneration, and sexual reproduction in H. vulgaris are not disrupted by estrogenic pollutants at low environmentally relevant concentrations.

Animals↗

A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6.

OBJECTIVES: To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer. METHODS: This randomised, double-blind study was conducted in the Nordic countries as part of the 'Casodex' Early Prostate Cancer programme. Patients received bicalutamide 150 mg (n=607) or placebo (n=611) in addition to standard care. RESULTS: More than 80% of patients had not received therapy of primary curative intent. Median follow-up in both groups was 3 years. Median exposure to study treatment in the bicalutamide and standard care alone groups was 2.5 and 2.3 years, respectively. Bicalutamide reduced the risk of objective disease progression by 57% compared with standard care alone (HR 0.43; 95% CI 0.34, 0.55; p<<0.0001). Survival data were immature (11.4% deaths) with no difference between the two treatment groups. CONCLUSIONS: Bicalutamide 150 mg as immediate therapy, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with early prostate cancer. The trial is ongoing to assess whether the reduction in risk of objective progression translates into an overall survival benefit.

Aged↗

Differences in the use of health services among people with and without epilepsy in the United Kingdom: socio-economic and disease-specific determinants.

We aim to examine the socio-economic, demographic and disease-specific determinants in the use of health services by patients with epilepsy, compared to people without epilepsy. We used data from the fourth national survey of morbidity in general practice, carried out in 1991-1992. Overall mean annual number of consultations with general practitioners, home visits and referrals to secondary care per person were calculated for people with epilepsy, stratified by age, sex and socio-economic status. The proportion of patients consulting for certain diseases or disease groups were also calculated for patients with epilepsy. Results were compared to these in people without epilepsy, and rate ratios were calculated. Patients with epilepsy consulted twice as often, required three to four times more home visits, and were referred to secondary care three times more often than people without epilepsy, irrespective of age, sex and social class. Among patients with epilepsy, consultation rates and home visits were higher in females, older people and people from the manual social classes. A higher proportion of patients with epilepsy consulted for neoplasms, haematological and mental health disorders, dementia, stroke and gastrointestinal bleeding. Older age and low social class were less strongly associated with health service utilisation than in people without epilepsy, indicating that people with epilepsy lose much of the protective effect of young age and high social class on health. Factors contributing to the higher utilisation of health services in people with epilepsy need to be studied further and their effects taken into account in the organisation of health services for people with epilepsy.

Adolescent↗

Chronic exposure to 17 alpha-ethinylestradiol and bisphenol A-effects on development and reproduction in the freshwater invertebrate Chironomus riparius (Diptera: Chironomidae).

The effect of 17 alpha-ethinylestradiol (EE) and bisphenol A (BPA) on development and reproduction in Chironomus riparius was determined over two generations in chronic sediment exposure assays. A number of response criteria were examined in order to identify any chemical-related effects including median emergence times (EmT50), the number and sex ratio of emerged adults, egg production and egg viability. The results showed that emergence time and percentage adult emergence were affected by EE and BPA exposure. These effects were primarily associated with the second generation of test animals, most notably in the BPA study, where the emergence of male and female adults was significantly (P<0.05) delayed at concentrations ranging from 78 ng/l to 0.75 mg/l. At very low concentrations (1 ng/l) of EE, both the first and second generation of adults emerged significantly earlier than control animals. No effect on the percentage emergence of first generation adults was evident with either chemical or in the second generation with BPA. The number of egg-ropes produced by the first generation females varied between treatments but no dose-response pattern was evident. Although certain responses were significantly affected, results in general do not suggest that the criteria examined, although validated as indicators of general sediment toxicity, could be used to detect the oestrogenic effects of EE and BPA on C. riparius.

Animals↗

Survival and precopulatory behaviour of Gammarus pulex (L.) exposed to two xenoestrogens.

The effects of the xenoestrogens ethinylestradiol (EE) and bisphenol A (BPA) on the survival and reproductive behaviour of the amphipod Gammarus pulex were determined in a series of bioassays. Acute toxicity of the test chemicals was determined under static conditions, revealing 10 d median lethal concentrations (LC50s) of 0.84 and 1.49 mg/L for EE and BPA, respectively. Several aspects of the reproductive behaviour including the ability of males and females to detect each other, form precopulatory guarding pairs and to continue the guarding behaviour, were examined during a 24 h exposure period over a wide range of concentrations. However, reproductive behaviour was only disrupted at relatively high concentrations where it would be unrealistic to attribute the effects to an endocrine mediated process. Consequently, changes in precopulatory guarding resulting from acute exposure. do not seem to be suitable for detecting the presence in water of xenoestrogens known to cause endocrine disruption in vertebrates.

Animals↗

Adaptive prosthetics for the lower extremity.

The potential for lifestyle recovery is tremendous for most lower extremity amputees. The amazing and ever-expanding array of adaptive prosthetics can help make the devastating loss of amputation more bearable for patients, their families, and their health care team. The new amputee, in a state of shock and grief, does not know what his or her prosthetic options are. It is crucial that the surgeon is knowledgeable about what the patient can have and what the patient needs to ask for. Dana Bowman stated: Ideally, the new amputee should say to their doctor, "I'd like my leg to be lightweight, flexible, durable, comfortable. I want to do sports or I want to ride bikes with my kids." Whatever it is they like to do. I was told I would never be able to wear two dynamic feet and that my sky diving days were over. I said, "Well how do you know? Can't I try?" It took years to find out what I could have and then to find people to help me get it. The prosthetic prescription the physician writes is the patient's gateway to the kind of prosthetics that will enable him or her to pursue the activities of their life. Often, new amputees end up with the bare minimum prosthesis, which can cause problems with comfort and mobility. A poorly designed or badly fitting prosthesis is as disabling as the actual amputation. When the surgeon can help the amputee and his or her family understand what kind of prosthetic choices are available, it establishes an optimistic outlook that is highly beneficial to the entire recovery process physically and mentally. "When I lost my leg, if someone would have told me that I could at least try to run again, that would have meant a lot," said Brian Frasure. "Getting that positive mental attitude is every bit as important as having good medical and prosthetic care." By asking probing questions about the patient's preamputation lifestyle and postamputation goals, the physician can write a prescription for truly adaptive prosthetics. The surgeon should consider the economic benefits of asking for a waterproof leg for an older adult that he or she can use for more stability in the shower and that can go a long way toward preventing fracture and other injuries. There are economic considerations for a younger amputee, asking for an energy-storing foot or an adjustable ankle so that he or she can be more active and independent and probably avoid the health risks associated with depression, inactivity, or obesity. If all patients received a contoured, flexible, dynamic socket from the beginning, years of medical problems and treatment for injury to the residual limb could be avoided. The initial prosthetic prescription is probably the best opportunity the patient ever will have to get the adaptive prosthetics that can meet his or her needs best. It also establishes a precedent with the payer for quality prosthetic care and begins educating all payers about what prosthetic patients can and should have. Insurance companies may resist the idea of a second prosthesis or of specialized components that increase the cost of the initial prosthesis. Physicians, patients, and the multidisciplinary team can work together, however, to pursue the most complete prosthetic coverage possible. For the prosthetic user, it is the difference between being restored to a full and active life or sitting back and becoming a spectator.

Adult↗

Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non-steroidal antiandrogens, bicalutamide ('Casodex'), flutamide and nilutamide, only bicalutamide has been compared with castration in large, controlled, randomised, Phase III trials in M1 patients. A post-hoc analysis of these studies indicated that bicalutamide 150 mg/day monotherapy may be of benefit to M1 patients with a prostate specific antigen (PSA) level </=400 ng/ml. Significant advantages for M1 patients treated with bicalutamide were observed in subjective response rate, maintenance of sexual interest and physical capacity. Patients with a higher disease burden (PSA >400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203.

Journal Article↗

Differential expression of Rab3 isoforms in high- and low-secreting mast cell lines.

The expression of several isoforms of the small-molecular-weight Rab3 GTP-binding proteins is a characteristic feature of all cell types undergoing regulated exocytosis, in which Rab3 proteins are considered to regulate the assembly/disassembly of a fusion complex between granule and plasma membrane in a positive and negative manner through interaction with effector proteins. The pattern of Rab3 protein expression may, therefore, provide a subtle means of regulating exocytosis. To investigate the relationship between Rab3 expression and secretory activity, we assessed the differential expression of individual Rab3 proteins in high- and low-secreting clones of the rat basophilic (RBL) cell line. mRNAs for Rab3 isoforms (a-d) were analyzed by constructing cDNA libraries of high- and low-secreting RBL clones. The relative abundance of mRNAs for Rab3 isoforms was initially determined from the clonal frequency of corresponding cDNA clones. RT-PCR using isoform-specific primers was successfully applied to the quantitation of Rab3a mRNA. The presence of individual Rab3 proteins was revealed by SDS-PAGE and immunoblotting, and also by in situ immunofluorescence confocal microscopy. We present evidence that Rab3a and Rab3c are expressed at high levels in the low-secreting variant, while Rab3d is predominant in the high secretor. Levels of the Rab3 effector proteins, Rabphilin and Noc2, are similar in both RBL cell lines. Subcellular fractionation of unstimulated high and low secretor RBL clones revealed that in both cell types Rab3a has a cytoplasmic location while Rab3d is present in a membrane/organelle fraction containing secretory vesicles. Differences in the pattern of expression of Rab3 isoforms in the two RBL cell lines and their localisation may influence the secretory potential. Furthermore, the presence of Rab3 and effector proteins indicates that the mechanism for regulated exocytosis in cells of mast cells/basophil lineage appears similar to that in pre-synaptic vesicles and pancreatic beta-cells.

Adaptor Proteins, Signal Transducing↗

Trends in the prevalence and management of atrial fibrillation in general practice in England and Wales, 1994-1998: analysis of data from the general practice research database.

OBJECTIVE: To determine the prevalence of atrial fibrillation in England and Wales, and examine trends in its treatment with warfarin and aspirin between 1994 and 1998. DESIGN: Analysis of data from the general practice research database. SETTING: England and Wales. PATIENTS: 1.4 million patients registered with 211 general practices. MAIN OUTCOME MEASURES: Age and sex specific prevalence rates of atrial fibrillation; percentage of patients with atrial fibrillation treated with oral anticoagulants or aspirin. RESULTS: The prevalence of atrial fibrillation in 1998 was 12.1/1000 in men and 12.7/1000 in women. Prevalence increased from less than 1/1000 in under 35 year olds to over 100/1000 in those aged 85 years and over. There was a 22% increase in the age standardised prevalence of atrial fibrillation in men and a 14% increase in women between 1994 and 1998. The percentage of patients prescribed oral anticoagulants increased from 20% to 34% in men and from 17% to 25% in women. The percentage of men with atrial fibrillation prescribed aspirin increased from 26% to 36%, and the percentage of women increased from 24% to 36%. Applying the age and sex specific prevalence and treatment rates to the population gives an estimate of around 650 000 cases of atrial fibrillation in England and Wales. The greatest number of cases occurs in the 75-84 year old age group. CONCLUSIONS: The number of patients in the community with identified atrial fibrillation is increasing. There has also been a pronounced increase in the percentage of patients with atrial fibrillation prescribed oral anticoagulants or aspirin.

Administration, Oral↗

Invasive serotype a Haemophilus influenzae infections with a virulence genotype resembling Haemophilus influenzae type b: emerging pathogen in the vaccine era?

OBJECTIVE: Haemophilus influenzae type b causes severe disease in nonimmune infants and young children; other serotypes are uncommon pathogens and thought to have low virulence. Some have hypothesized that with the virtual elimination of H influenzae type b, other serotypes might acquire virulence traits and emerge as important pathogens of children. We describe the clinical, epidemiologic, and molecular biologic features of 5 cases of severe disease attributable to Haemophilus influenzae type a. METHODS: After observing 4 cases of invasive disease caused by H influenzae type a, we reviewed microbiology records at 3 reference laboratories that perform all serotyping in Utah and surveillance databases. Strains of H influenzae type a and control strains were examined by Southern blotting with the use of the cap probe pUO38 and by pulsed-field gel electrophoresis. The putative virulence mutation, the IS1016-bexA deletion, was detected by polymerase chain reaction amplification and sequencing. RESULTS: During a 10-month period, we observed 5 children with severe invasive disease caused by H influenzae type a. No isolates of H influenzae type a had been submitted to the reference laboratories between 1992 and 1998. The median age of patients was 12 months (range: 6-48 months). Four of 5 had meningitis and bacteremia; 1 had purpura fulminans. Three isolates, representing 1 of 2 pulsed-field gel electrophoresis patterns, contained the IS1016-bexA deletion and were associated with particularly severe disease. CONCLUSIONS: We describe an unusual cluster of severe disease caused by H influenzae type a that resembles the clinical and epidemiologic features of H influenzae type b disease. Our data support the hypothesis that the IS1016-bexA deletion may identify more virulent strains of H influenzae. Haemophilus influenzae, epidemiology, virulence, serotyping, pathogenicity.

Base Sequence↗