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51.
Acyclovir suppression of frequently recurring genital herpes. Efficacy and diminishing need during successive years of treatment 总被引:3,自引:0,他引:3
S E Straus K D Croen M H Sawyer A G Freifeld J M Felser J K Dale H A Smith C Hallahan S N Lehrman 《JAMA》1988,260(15):2227-2230
Forty-seven patients with frequently recurring genital herpes participated in one or more of five sequential trials of oral suppressive therapy with 200 mg of acyclovir three times daily from four to 12 months' duration. The prolonged use of acyclovir was extremely well tolerated, and treatment efficacy was sustained through successive studies. Recurrences in eight patients with repeated treatment "failures" were more effectively suppressed with higher doses of acyclovir. All patients experienced recurrent infections after the treatments were completed; however, the mean time to recurrence following each treatment period became progressively longer, and resumption of suppressive therapy was no longer warranted for ten patients. These data indicate the efficacy and safety of chronic suppressive therapy with acyclovir and the value of interrupting prolonged treatment to assess its further need. 相似文献
52.
Phillip A. Reece Heather S. Hill R. Malcolm Green Raymond G. Morris Barry M. Dale Dusan Kotasek Robert E. Sage 《Cancer chemotherapy and pharmacology》1988,22(4):348-352
Summary The renal clearance of melphalan and the fraction unbound in plasma were determined after intravenous infusion of 5 mg/m2 over 5 min in nine patients with cancer to obtain information regarding the mechanism of renal handling of melphalan. Four of the patients underwent bone marrow transplantation and also received an IV dose of 220 mg/m2. Total melphalan clearance after the 5 mg/m2 dose ranged from 66.0 to 272 ml/min per m2; the percentage of the dose excreted unchanged in urine, from 2.5% to 92.8%; renal clearance, from 4.1 to 188 ml/min per m2; the fraction unbound in plasma, from 0.0598 to 0.460; and t1/2, from 39.4 to 84.3 min. Unbound melphalan clearance and renal clearance calculated from the unbound fraction in plasma for each patient ranged from 441 to 3356 ml/min per m2 and 15 to 961 ml/min per m2 respectively and were not related to serum albumin, serum creatinine or creatinine clearance. The percentage of the dose exctreted and melphalan renal clearance were not related to urine flow. There was evidence of active secretion of melphalan in the kidney an possible reabsorption. There were no significant paired differences in melphalan disposition between the high- and low-dose studies. Highly variable renal clearance involving active secretion may contribute in part to large interpatient differences in the total plasma clearance of melphalan in patients with cancer.This study was supported by a grant from The Queen Elizabeth Hospital Research Foundation 相似文献
53.
Band-pass response properties of rat SI neurons 总被引:6,自引:0,他引:6
Garabedian CE Jones SR Merzenich MM Dale A Moore CI 《Journal of neurophysiology》2003,90(3):1379-1391
Rats typically employ 4- to 12-Hz "whisking" movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates =40 Hz. As previously reported, vibrissa deflection evoked robust neural responses that consistently adapted to stimulus rates >/=3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0-35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (>15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5-10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior. 相似文献
54.
HIV seroincidence among patients at clinics for sexually transmitted diseases in nine cities in the United States 总被引:1,自引:0,他引:1
Weinstock H Dale M Gwinn M Satten GA Kothe D Mei J Royalty J Linley L Fridlund C Parekh B Rawal BD Busch MP Janssen RS 《Journal of acquired immune deficiency syndromes (1999)》2002,29(5):478-483
Although the numbers of newly reported diagnoses of AIDS decreased in the 1990s, it is not clear whether they reflect a decreasing number of new HIV infections. Direct measurement of HIV incidence through follow-up cohort studies is difficult and costly. We estimated HIV incidence and trends in incidence among men who have sex with men (MSM) and heterosexual men and women at clinics for sexually transmitted diseases (STDs) by using a recently developed serologic testing algorithm that requires only a single blood specimen. Cross-sectional anonymous serosurveys were conducted at 13 STD clinics in nine cities in the United States from 1991 through 1997. Before anonymous HIV testing, demographic and clinical information was abstracted. Of 129,774 specimens tested, 362 (0.28%) were from persons estimated to be recently infected. Incidence among MSM was 7.1% (95% confidence interval (CI): 4.8-10.3), 14 times higher than that among heterosexuals, which was 0.5% (CI: 0.4- 0.7). Incidence among MSM and heterosexuals remained unchanged during the time studied. Decreasing rates of new AIDS diagnoses in the 1990s do not reflect stable rates of new HIV infections among MSM and heterosexual patients attending these clinics. 相似文献
55.
Mario T. Philipp Gary P. Wormser Adriana R. Marques Susan Bittker Dale S. Martin John Nowakowski Leonard G. Dally 《Clinical and Vaccine Immunology : CVI》2005,12(9):1069-1074
C6, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C6-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C6 antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C6 negative or had a ≥4-fold decrease in C6 antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C6 negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C6 antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis. 相似文献
56.
Determination of optimal cryoprotectants and procedures for their addition and removal from human spermatozoa 总被引:9,自引:7,他引:9
The objective was to test the hypothesis that the optimal cryoprotective
agent for cryopreservation of human spermatozoa would be a solute for which
cells have the highest plasma membrane permeability, resulting in the least
amount of volume excursion during its addition and removal. To test this
hypothesis, theoretical simulations were performed using membrane
permeability coefficients to predict optimal procedures for the addition
and removal of a cryoprotectant. Simulations were performed using data from
four different cryoprotectants: (i) glycerol, (ii) dimethyl sulphoxide,
(iii) propylene glycol and (iv) ethylene glycol. Thermodynamic formulations
were applied to determine approaches for the addition and removal of 1 M
and 2 M final concentrations of cryoprotectant, allowing the spermatozoa to
maintain a cell volume within their osmotic tolerance limits. Based on
these data, ethylene glycol was predicted to be optimal for minimizing
volume excursions among the solutes evaluated. These predictions were then
experimentally tested using glycerol as the control cryoprotectant and
ethylene glycol as the experimental cryoprotectant. The results indicate
that there was a higher (P < 0.05) recovery of motile spermatozoa after
cryopreservation when using 1 M ethylene glycol than with 1 M glycerol,
supporting the hypothesis that use of the cryoprotectant for which the cell
has the highest permeability will result in higher cell survival.
相似文献
57.
CD1d-restricted invariant natural killer T cell (iNKT cells) have a limited T cell receptor (TCR) repertoire and share characteristics common to T cells and natural killer cells. While intrathymic selection facilitates the production of T cells carrying self major histocompatibility complex-restricted TCRs, natural killer cells carry an appropriate repertoire of self major histocompatibility complex-recognizing receptors to avoid self-reactivity. Here we show that chronic exposure to specific glycolipid antigen resulted in iNKT cell disappearance and thymus-dependent repopulation of iNKT cells with increased expression of inhibitory Ly-49 molecules that resulted in impaired responsiveness. Thymic selection of peripheral Ly-49-expressing iNKT cell repertoire inhibited cytokine production and other functions in vivo. These observations emphasize the acquisition of self-recognizing inhibitory receptors on NKT cells as a previously unknown mechanism of thymic tolerance after chronic antigen exposure. 相似文献
58.
Donor insemination: Dutch parents' opinions about confidentiality and donor anonymity and the emotional adjustment of their children 总被引:1,自引:4,他引:1
Brewaeys A; Golombok S; Naaktgeboren N; de Bruyn JK; van Hall EV 《Human reproduction (Oxford, England)》1997,12(7):1591-1597
Results from a comparative study investigating 38 donor insemination (DI)
Dutch families with 4-8 year old children are presented. The aims of this
study were to investigate parents' opinions on the issues of
confidentiality and donor anonymity, to assess the emotional development of
the children, and to examine in DI families the association between secrecy
with regard to the use of a donor and the emotional adjustment of the
children. The DI families were compared to families with a child conceived
by in-vitro fertilization (IVF) and to families with a naturally conceived
child. Secrecy appeared to be associated with DI and not with IVF: 74% of
the DI parents intended not to inform the child about the way in which
she/he was conceived, whereas none of the IVF parents intended to keep the
secret. Only one set of DI parents and two sets of IVF parents had actually
told the child. As to donor anonymity, a spread of opinions appeared among
DI parents; 57% preferred an anonymous donor, 31% would have liked non-
identifying information about the donor, 9% preferred the donor's identity
to be registered and 3% remained unsure. Parents' major concern was to know
more about the medical/genetic background of the donor. Mothers and fathers
in the DI families differed in their opinions concerning the issues of
confidentiality and donor anonymity: fathers, more often than mothers, were
secretive with regard to the use of a donor and husbands, more often than
their wives, were in favour of donor anonymity. With regard to the
emotional development of the children, more emotional/behavioural problems
were revealed among DI children than among children who were naturally
conceived. No association was found between secrecy and the
emotional/behavioural adjustment of the children.
相似文献
59.
Bruce R. Thorley Julie Milland Dale Christiansen Marc B. Lanteri Beth McInnes Ingrid Moeller Pierre Rivailler Branka Horvat Chantal Rabourdin-Combe Denis Gerlier Ian F. C. McKenzie Bruc. E. E. Loveland 《European journal of immunology》1997,27(3):726-734
CD46 (membrane cofactor protein) is a human cell-surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody-dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high-level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies. 相似文献
60.