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Biomedical subjects

J Cook

Publications and source records attributed to J Cook.

At least 73 records · Page 4Linked to original sources

Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration.

OBJECTIVE: To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. METHOD: Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. RESULTS: All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. CONCLUSION: Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.

Chromatography, High Pressure Liquid↗

Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function.

The CRX (cone-rod homeobox) gene is specifically expressed in developing and mature photoreceptors and encodes an otd/Otx-like paired homeodomain protein. Mutant alleles of the CRX gene have recently been associated with autosomal dominant cone-rod dystrophy (CORD) as well as dominant Leber congenital amaurosis (LCA). Since LCA is more commonly inherited in an autosomal recessive manner, we examined a cohort of recessive LCA patients for CRX mutations. A homozygous substitution of arginine (R) at codon 90 by tryptophan (W) was identified in the CRX homeodomain of one of the probands who was nearly blind from birth. A group of 48 control individuals and 190 previously characterized CORD probands did not reveal this sequence change. The mutant CRXR90W homeodomain demonstrated decreased binding to the previously identified cis sequence elements in the rhodopsin promoter. In transient transfection experiments, the mutant protein showed significantly reduced ability to transactivate the rhodopsin promoter, as well as lower synergistic activation with the bZIP transcription factor NRL. Heterozygosity of the mutant CRX (R90W) allele was detected in both parents and in an older sibling. Ophthalmologic examination and electro-retinography revealed a subtle abnormality of cone function in both the parents. These data suggest that the R90W mutation results in a CRX protein with reduced DNA binding and transcriptional regulatory activity and that the subsequent changes in photoreceptor gene expression lead to the very early onset severe visual impairment in LCA.

Adolescent↗

Taxanes as radiosensitizers for head and neck cancer.

Combinations of paclitaxel and radiation therapy or paclitaxel with other chemotherapy agents and radiation have been tested with variable results in patient populations. To date, three phase I trials have been conducted using paclitaxel alone in combination with radiotherapy for the treatment of patients with head and neck cancer. Dose-limiting toxicity in the 1-hour infusion was mucositis, whereas in the 24-h/wk infusion, fever was the dose-limiting toxicity. In the long-term infusion (24 h/d, 7 d/wk), no dose-limiting toxicity was seen at the doses of paclitaxel given. In two of the protocols in which biopsies were obtained, a G2/M block was observed. A phase I protocol using paclitaxel in combination with fluorouracil and hydroxyurea with radiation and a phase II protocol using paclitaxel with cisplatin in operable head and neck cancers have been reported. Preliminary results suggest that paclitaxel in combination with radiotherapy is a reasonable experimental treatment that deserves further study in patients with stage III and IV squamous cell carcinomas of the head and neck.

Antineoplastic Agents, Phytogenic↗

Information Technology for postgraduate education: survey of facilities and skills in the South West Deanery.

OBJECTIVE: To determine the Information Technology (IT) infrastructure available to, and IT skills of, obstetric specialist registrars across the South West Deanery. DESIGN: Open prospective study. SETTING: NHS Hospitals in the South West Deanery. METHODS: Two separate surveys. Firstly, the computer equipment available to trainees was determined at each hospital in the deanery on site using a software programme. Secondly, IT skills of a sample of 22 specialist registrars were assessed using a checklist at a series of four workshops. MAIN OUTCOME MEASURES: Computers with sufficient specification to use CD-ROMs, to access the Internet, and to support data-, audio- and video-conferencing. The number of trainees with IT skills to use a computer-aided learning package and the Internet. RESULTS: Sixty-six percent of trainees have access to a computer with a CD-ROM drive. Sixty-six percent also have access to the Internet at their place of work. Thirteen percent have access to data-conferencing but there were no computers in the Deanery able to support audio- or video-conferencing. Twenty-five percent of trainees have no IT skills and require basic training in the use of computers. Thirty-six percent of our sample would require training to be able to use computer-based tutorials programs. Seventy-seven percent of trainees require training to be able to use the Internet without assistance. CONCLUSION: A significant minority of trainees do not have access to computers with sufficient specification to run basic tutorial programmes or access the Internet. Similarly, a large minority of trainees do not even have a basic knowledge of computer technology and IT training is required for the majority of trainees for them to reap the potential benefits which computer-based tutorials systems and the Internet can give.

Computers↗

Interclass transmission and phyletic host tracking in murine leukemia virus-related retroviruses.

Retroviruses are capable of infectious horizontal transmission between hosts, usually between individuals within a single species, although a number of probable zoonotic infections resulting from transmission between different species of placental mammals have also been reported. Despite these data, it remains unclear how often interspecies transmission events occur or whether their frequency is influenced by the evolutionary distance between host taxa. To address this problem we used PCR to amplify and characterize endogenous retroviruses related to the murine leukemia viruses. We show that members of this retroviral genus are harbored by considerably more organisms than previously thought and that phylogenetic analysis demonstrates that viruses isolated from a particular host class generally cluster together, suggesting that infectious virus horizontal transfer between vertebrate classes occurs only rarely. However, two recent instances of transmission of zoonotic infections between distantly related host organisms were identified. One, from mammals to birds, has led to a rapid adaptive radiation into other avian hosts. The other, between placental and marsupial mammals, involves viruses clustering with recently described porcine retroviruses, adding to concerns regarding the xenotransplantation of pig organs to humans.

Amino Acid Sequence↗

Low level saliva cotinine determination and its application as a biomarker for environmental tobacco smoke exposure.

1. The determination of personal exposures to environmental tobacco smoke (ETS) and respirable suspended particles (RSP) for housewives, and fixed site monitoring of their homes, have been undertaken by these authors throughout Europe, South East Asia and Australia. Median 24 h time weighted average (TWA) concentrations for ETS particles and nicotine were found to be significantly higher for housewives living in smoking households compared with those living in nonsmoking households. For Europe, median TWA concentrations of 4.1 and <0.26 microg/ml for ETS particles and 0.63 and < 0.08 microg/m3 for nicotine were found for housewives living in smoking and nonsmoking households respectively. 2. In addition to the measurement of RSP, ETS particles and nicotine, saliva cotinine concentrations were determined using a radioimmunoassay method with a limit of quantitation of 1 ng/ml. Median saliva cotinine concentrations of 1.4 and <1 ng/ml were determined for European housewives living in smoking and nonsmoking households respectively, which reflected the poor limit of quantitation of this methodology. A chromatographic method utilising tandem mass-spectrometric detection was developed and validated for the determination of both cotinine and 3-hydroxycotinine, two of the main metabolites of nicotine, with lower limits of quantitation of 0.05 and 0.10 ng/ml respectively. This method was applied to samples collected from subjects with a known ETS exposure history and median cotinine concentrations of <0.05 ng/ml for self-reported unexposed nonsmokers, 0.65 ng/ml for nonsmokers reporting some ETS exposure and 1.28 ng/ml for nonsmokers living with smokers were found. 3. In conclusion, the measurement of RSP and ETS concentrations derived from personal or fixed site monitors for housewives may provide some indication of potential exposures to dependent children. The recent development and application of a highly sensitive assay for the determination of cotinine in saliva has provided evidence to suggest that concentrations determined at sub-nanogram levels may be used as a biomarker for ETS exposure. This improved methodology, coupled with non-invasive sampling for saliva, may be of significance when considering the application of cotinine as a biomarker for ETS exposure in children.

Asia↗

[Maternal mortality and referral maternities in Morocco: how to (re)motivate professionals?].

The very high rates of maternal mortality and perinatal mortality, as well as the deficiencies and dysfunctions observed in maternity hospitals, which play the role of referential maternity wards, led the Moroccan Minister of Public Health to implement a project in order to improve the quality of care of parturient women and new-borns. This project included 8 provinces in the country. The strategy chosen was "the team approach to resolving health problems", which is a learning process which leads local teams to implement and evaluate projects they have developed themselves. This pedagogical approach, which is carried out over a period of more than a year, proved itself to be very motivating and mobilising for the professionals included, despite the obstacles that were encountered. It also contributed to creating a true team spirit. Most activities planned within these projects were carried out and many indicators improved.

Attitude of Health Personnel↗

[Natural histories of disease: a pragmatic approach to multidisciplinary research on health care seeking behavior and therapeutic itineraries].

Public health is determined by the interaction of social, cultural and biological factors. Because of this complexity, a multidisciplinary approach is needed when doing research on public health problems. Medical anthropology and epidemiology share a common interest for human behavior and health, so it is especially appropriate for these two disciplines to work together in studying health seeking behavior and the use of health systems. In order to better understand social and cultural factors associated with health seeking behavior, a suitable qualitative research method was needed for use in association with a medical and epidemiological approach in the research program "Use and perception of health systems by children and their family", carried out in Algeria, the Congo (Brazzaville), Morocco, and Togo. Three factors were considered important: coordinating the qualitative and quantitative research methods within a single time frame, involving all members of the multidisciplinary research teams in each country, and producing data accessible and useful to health care professionals and others responsible for health system performance. A case study method based on "natural histories of illness" was adopted, using home interviews of families about a recent illness episode of an under-5 child. There are several advantages to this approach: 1) analysis of illness episodes reveals the totality of the health seeking process, including therapeutic itineraries; 2) families have little difficulty in describing an illness episode in the order events occurred; 3) these accounts are easily understood by health professionals, resembling as they do a "clinical case study" approach; 4) the content is readily available in the form of common discourse for use by health program planners and administrators. The method is thus able to provide information necessary for organizing health services which meet the perceived needs of the population.

Algeria↗

[Families and children confronting health care practices in Algeria].

This paper describes results of a study on perceptions and behaviors of families concerning care of sick children, within the context of the Algerian health system as it functioned in two zones, Aïn Taya and Tigzirt, in 1991. One hundred twenty families in the two zones were interviewed at home on the health seeking process during a recent illness episode of an under-5 child. Results show families make extensive use of curative health services for children, with apparently little use of traditional medicine, and only initial use of home remedies. Access to public services is often difficult due to distance, while incompetence, long waiting times, favoritism, lack of material, and poor communication with health personnel constitute families' main complaints. Use of private physicians, in spite of costs, is considered a gain in time, and rapport and communication are better. Results of the research among these families are discussed in relation to those from a study carried out at the same time among health professionals, results which show deep dissatisfaction on their part as to the means put at their disposal and with the quality of relationships maintained with the administration on the one hand, and with the client population on the other. Improving the public health sector in Algeria will entail greater investment in the quality of peripheral services, and training of health personnel in better communication skills.

Adolescent↗

[Health care seeking behavior of children in Togo].

Epidemiological and anthropological studies were carried out in Togo on health seeking behavior for under 5 children to determine causes of dysfunctions in health services. This article reports on the main findings of the anthropological study. Anthropological literature on health seeking behavior has identified labeling and associated explanatory models of illness as important factors for making choices in the use of health services. This study, carried out among 100 families in Togo on health seeking behavior for under-five children, found little difference in the signs and symptoms of illness recalled and the health resources used. Different causal explanations similarly showed little variation in signs and symptoms of illness. The only causal explanation for illness which appeared to correspond to place of recourse was related to social causes, where traditional practitioners were more often consulted. Families explained choices more on the basis of the accessibility and quality of health services (geographical and financial accessibility, reception by health personnel, organization of services, drug availability) than on the basis of the particular signs and symptoms of the illness. Improving the organization and functioning of health services should contribute more to appropriate use of the modern health care sector than interventions targeting user populations, since the latter appear to be aware of the advantages of modern medicine, but find financial, social and organizational features of services unsatisfactory.

Adult↗

[An epidemiological study of consultations of children under 5 years of age in Brazzaville (Congo)].

In most of the large cities in developing countries, geographic accessibility to health care is not a major problem. Thus, indifference to public services and a preference for home treatment, recourse to traditional medicine or to the private sector may be related to problems in the quality of services. A cross-sectional epidemiological study of hospital visits by under-5 children was carried out in health centres and hospital out-patient services in Brazzaville (Congo). Sampling in these health facilities was done using a systematic random sample with a proportion of 25%, during 4 periods chosen according to seasonal factors. An exhaustive investigation of the entire public sector serving children was done in the study. At the same time, the same data were gathered in a sample of private facilities (doctors' and nurses' offices, traditional healers, religious healing centres), chosen as a function of their permanence and the numbers of their clientele. This article analyses services offered during 2215 visits by children, who were under 1 year of age in more than 50% of cases. In the public sector, 75% of visits were to first-line health centres. Public services show marked dysfunctions: the complexity of internal referrals, clinical examinations which are inadequate in relation to symptoms, and poor communication (explanations as to cause of illness in less than 2% of cases, and on treatments in less than 50% of cases). Communication seems well developed among private physicians and traditional healers, the latter engaging in both preventive and curative activities. Communication during well-child visits and consultations at health centres is especially disappointing, in light of the very young age of the parents (1/4 are high-school or college students). There is a two-fold risk in this situation: flight towards non-conventional medicine on the one hand, and access to private medicine based on socio-economic status on the other. It thus appears necessary to standardise procedures and acts in first line public health services and to promote training of personnel in communication skills with families (training using social science perspectives and participative pedagogical techniques).

Age Factors↗

[Contributions to the sociologic analysis of the impact of sickle cell disease on families from Northern Tunisia].

The improvement of the conditions of care and quality of life of people living with drepanocytosis now constitutes a major concern of health authorities and voluntary groups (associations of sick people and their parents). In order to examine the conditions and methods of care for children living with drepanocytosis in the Bizerte region of Northern Tunisia and to understand the problems and difficulties experienced by them and their families in their daily lives, an anthropological study was carried out in the region between January 16 and February 12, 1997. Thirty-three interviews were carried out with families of infected children. The interviews were semi-directive using a pre-established protocol (interview guide). Thirty interviews were then analysed. A multitude of information concerning various medical and psycho-social aspects of drepanocytosis in the region were revealed. The data were regrouped into the following categories: circumstances of discovering the illness; explicative model of the illness as perceived by the people interviewed; conditions and methods of care of the sick child; degree of satisfaction with the health care system; psychological profile of the children interviewed; educational level of the children interviewed; repercussions the illness has on the family; impact of the illness on household budget; suggestions and comments of the people interviewed. In light of the information collected, various actions have been proposed with the goal of improving the conditions of care and quality of life of people living with drepanocytosis in the region.

Anemia, Sickle Cell↗

The nutritional assessment of iron status.

In nutritional studies to assess the prevalence of iron deficiency, it has been common practice to define 3 stages of increasing severity: iron storage depletion as defined by low serum ferritin, mild iron deficiency without anemia based on laboratory evidence of iron deficient erythropoiesis (IDE), and overt iron deficiency anemia (IDA). While this approach provides a broad perspective of impaired iron status, the main liabilities of iron lack are associated only with the more advanced stage of IDA. Consequently, the hemoglobin determination can be used to screen for nutritionally significant iron deficiency. Having identified anemia, more specific laboratory studies are needed to establish iron lack as the cause. The traditional measurements of iron deficient erythropoiesis (IDE) such as a low transferrin saturation, elevated erythrocyte protoporphyrin, or decreased mean corpuscular volume are commonly used. The major drawback in using these parameters is that they are affected similarly in individuals with the anemia of chronic disease (ACD), a common form of anemia in low socioeconomic populations. Because iron stores are invariably absent in individuals with uncomplicated IDA, a low serum ferritin concentration below 20 micrograms/L confirms the diagnosis of IDA when anemia is present. The main limitation of the serum ferritin is that it is falsely elevated to within the normal range when IDA develops in individuals with concurrent infection or chronic inflammation. When this occurs in a clinical setting, a bone marrow examination is commonly performed to identify IDA. Recent investigations indicate that this cumbersome procedure can be avoided by measuring an important new iron-related measurement, the serum transferrin receptor (TfR). Because the synthesis of TfR is upregulated with tissue iron deficiency, IDA can be identified readily by an elevated serum TfR. Importantly, the serum TfR is normal in individuals with the ACD but becomes elevated if these individuals develop IDA. The optimal combination of laboratory measurements for detecting IDA is the hemoglobin, serum ferritin and serum TfR.

Anemia, Iron-Deficiency↗

Preparation and EPR studies of lithium phthalocyanine radical as an oxymetric probe.

The electron paramagnetic resonance (EPR) spectrum of the paramagnetic center in solid lithium phthalocyanine, LiPc, exhibits a pO2 (partial pressure of oxygen)-dependent line width. The compound is insoluble in water and is not easily biodegradable and, therefore, is a useful spin probe for quantitative in vivo oxymetry. Because EPR spectrometry is potentially a useful technique to quantitatively obtain in vivo tissue pO2, such probes can be used to obtain physiological information. In this paper, a simple experimental procedure for the preparation of LiPc using potentiostatic electrochemical methods is described. The setup was relatively inexpensive and easy to implement. A constant potential ranging from 0.05 to 0.75 V versus Ag+/AgCl(s) was used for obtaining LiPc. The EPR spectral studies were carried out using spectrometers operating at X-band and at radiofrequency (RF) at different pO2 values to characterize the spectral response of these crystals. The results indicate that, depending on the electrolysis conditions, the products contain mixtures of crystals exhibiting pO2-sensitive and pO2-insensitive line widths. Electrolysis conditions are reported whereby the pO2-sensitive LiPc crystals were the predominant product. The influence of the working surface of the electrode and the electrolysis time on the yield were also evaluated. The crystals of LiPc were also studied using a time-domain RF EPR spectrometer. In time-domain EPR, the signals that survive beyond the spectrometer dead time are mainly the narrow lines corresponding to the pO2-sensitive crystals, whereas the signals arising from the pO2-insensitive component of LiPc were found not to survive beyond the spectrometer dead time. This signal survival makes the time-domain EPR method more sensitive for pO2 measurements using LiPc because the line width becomes very narrow at very low pO2 and, concomitantly, the relaxation time T2 longer, with no modulation or power saturation artifacts that are encountered as in the continuous wave (cw) mode. Further, minimal contributions from object motion in the spectral data obtained using time-domain methods make it an advantage for in vivo applications.

Crystallization↗

Release of nociceptin-like substances from the rat spinal cord dorsal horn.

Release of nociceptin-like substances from the dorsal horn of rat spinal cords in situ was measured by the immobilized-antibody microprobe technique. Spinal cords removed from anesthetized 4-6 week-old rats were superfused with oxygenated Krebs solution at room temperature (21+/-1 degrees C). Glass microelectrodes, coated with antibodies to nociceptin, were inserted into the dorsal horn of the lumbar spinal cord (1.9 mm lateral to the midline to a depth 2.5 mm below the surface of the cord) for 15 min periods before, during and after electrical stimulation applied to the dorsal root entry zone of the same segment. There was a basal release of immunoreactive nociceptin-like substance (irNC) from the dorsal horns during the pre-stimulation period. A significant increase in irNC release was detected during the period of electrical stimulation and this increase was maintained for at least 15 min following the cessation of electrical stimulation. These results provide the first evidence on the release of irNC, albeit non-quantitative, from the in situ rat spinal cord dorsal horn and an enhanced release upon electrical stimulation.

Animals↗

Synergistic activation of CD4+ T cells by IL-16 and IL-2.

IL-16, in a CD4-dependent manner, induces high affinity IL-2R (CD25) selectively on CD4+ T cells. Based on this observation, we determined the relative effects of IL-16 on IL-2Ralpha, beta, and gamma expression on CD4+ T cells and of IL-16/IL-2 cotreatment of resting human PBMC obtained from normal individuals on CD4+ T cell proliferation and cytokine production, in vitro. IL-16 increased CD4+ T cell IL-2Ralpha and beta expression, but had no effect on expression of IL-2Rgamma. There was marked synergy of thymidine uptake and expansion of CD4+ T cell numbers in the presence of IL-16 and IL-2 or IL-16 and IL-15 compared with the responses to any of the cytokines alone. By 4 wk, IL-16/IL-2-cotreated PBMC cultures were predominantly CD4+, CD25+ CD45RO T cells. Of the cytokines measured, IL-16 treatment alone was sufficient to induce synthesis of granulocyte-macrophage CSF by 2 wk. IL-16/IL-2 cotreatment did not appear to induce selective proliferation of any Th subset, as cytokines of both Th1 (e.g., IFN-gamma) and Th2 (e.g., IL-5) types were synthesized by the expanded cell populations at 2 and 4 wk. These results suggest that IL-16 can prime CD4+ T cells for IL-2 responsiveness, and therefore may be a useful adjunct to IL-2 therapy for immune reconstitution in disease or therapeutic conditions resulting in CD4+ T cell depletion.

CD4-Positive T-Lymphocytes↗

Mohs micrographic surgery: a cost analysis.

BACKGROUND: The incidence of skin cancer is increasing significantly, and many people have declared the increase an epidemic. It was estimated that 900,000 to 1.2 million cases of nonmelanoma skin cancer occurred in the United States in 1994. With increasing pressure to deliver cost-effective medical care, physicians must understand the cost and value of the various methods to treat skin cancer. OBJECTIVE: Our purpose was to define the true cost of treating a series of skin cancers with the Mohs micrographic technique and compare our costs with calculated estimates of the costs to treat the same cancers with traditional methods of surgical excision. METHODS: A group of 400 consecutive tumors was selected. The cost of treatment in the reference group included diagnosis, Mohs micrographic surgery, reconstruction (if applicable), follow-up, and the cost to treat disease recurrence. These costs were then compared with traditional methods of surgical excision: excision with permanent section margin control, excision with frozen section margin control, and excision with frozen section margin control in an ambulatory surgical facility. For cost comparisons, it was assumed that all tumors in the comparison groups would be excised with standard surgical margins and the resultant surgical defects would be reconstructed with the simplest method possible. The costs of diagnosis, excision, pathology, reconstruction, and the cost to treat disease recurrence were then calculated and compared with the costs of treating the lesions with Mohs micrographic surgery. RESULTS: Our calculation of costs documents that Mohs micrographic surgery is similar in cost to office-based traditional surgical excision and less expensive than ambulatory surgical facility-based surgical excision. The average cost of Mohs micrographic surgery was $1243 versus $1167 for excision with permanent section margin control, $1400 for excision in the office with frozen section margin control, and $1973 for excision with frozen section margin control in an ambulatory surgical facility. Analysis based on anatomic location yielded similar results. CONCLUSION: Mohs micrographic surgery is a method of surgical excision with high intrinsic value that is cost-effective in comparison to traditional surgical excision.

Adult↗