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J Guy

Publications and source records attributed to J Guy.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Examination of some statistical evaluations of independence. Application to drug evaluation].

When two classes of events (E1, E2, ..., Em) on the one hand, (F1, F2, ..., Fn) on the other hand are such that the set of the m x n couples (Ei, Fj) represent all the possible issues of a common random experiment, it is often useful to know whether these two classes must be considered or not as independent of each other. In most cases, the answer to this important question is obtained through a chi 2-test and, less frequently, through various interpretations based upon the value rho of the linear correlation coefficient. A different method is also available to reach a conclusion, after estimating another coefficient mu characterizing the independence. The goal of the present lecture is to compare the possibilities, advantages and inconveniences of the three computational techniques leading to chi 2, rho and mu. Some examples of application to drugs evaluation are exposed.

Drug Evaluation↗
PubMed1994

A randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness.

OBJECTIVE: Our purpose was to assess the potential benefit of therapy with conjugated estrogens therapy on skin thickness in postmenopausal women. STUDY DESIGN: Sixty postmenopausal women were randomly allocated to receive conjugated estrogens or placebo treatment for 12 months. Neither participants nor investigators were aware of the group allocation. Skin thickness was measured by ultrasonography at baseline and after 6 to 12 months of treatment. Histologic changes were evaluated by skin biopsy at baseline and after 12 months' treatment. Quality of life and adverse events were recorded at each visit and at the end of treatment. RESULTS: Treatment with conjugated estrogens for 12 months significantly increases, at the level of the right great trochanter, the thickness of the skin (p < 0.01), as assessed by ultrasonography, and of the dermis (p < 0.05), as assessed by skin biopsy. No statistically significant difference was observed in the control population. Quality of life was reported to be improved (p < 0.05) in women treated with estrogen compared with those in the placebo group. CONCLUSION: The results may help postmenopausal women to better appraise the benefits of estrogen replacement therapy, and they provide further evidence of the potential of conjugated estrogens in preventing skin aging.

Aged↗
PubMed1994

Evaluation of anterior segment tolerance to short-term intravitreal perfluoron.

PURPOSE: A study was performed to evaluate corneal and anterior segment toxicity from short-term (24-hour) intravitreal use of perfluoro-n-octane. METHODS: Forty aphakic, vitrectomized eyes of pigmented rabbits underwent intravitreal injection of either 0.5 ml of perfluoro-n-octane (Perfluoron; Infinitech, St. Louis, MO; treated) or 0.5 ml balanced saline solution (control). Perfluoron was allowed to remain in the vitreous cavity for 24 hours. Serial measurements of corneal pachymetry and pneumotonometry were performed at 1, 4, 12, and 24 hours after injection. After 24 hours, endothelial cell morphology and barrier function were evaluated. RESULTS: No significant differences in corneal thickness or intraocular pressure were noted between the two groups at any of the time points studied, and no differences in endothelial cell density/hexagonality or endothelial cell barrier function were observed 24 hours after injection. CONCLUSIONS: In the absence of sustained corneal contact, no evidence of significant acute corneal or anterior segment toxicity was observed in response to short-term intravitreal perfluoro-n-octane in aphakic, vitrectomized rabbit eyes.

Animals↗
PubMed1994

Regulation of herpes simplex virus thymidine kinase in cells treated with a synergistic antiviral combination of alpha interferon and acyclovir.

Alpha interferon (IFN-alpha) and acyclovir (ACV) are synergistic in their anti-herpes simplex virus activities. IFN-alpha treatment reduced the herpes simplex virus thymidine kinase (TK) activity present in cells 6 h postinfection, while steady-state levels of TK mRNA remained at or above the amount in infected, untreated cells. The inhibition of TK production by IFN-alpha treatment appeared to be transient and translational, not transcriptional.

Acyclovir↗
PubMed1994

Conjugated deferoxamine reduces blood-brain barrier disruption in experimental optic neuritis.

The purpose of this paper was to investigate the role of deferoxamine (DFO) scavenging of hydroxyl radical (.OH) on disruption of the blood-brain barrier (BBB) and demyelination in experimental optic neuritis. Eighteen strain-13 guinea pigs were sensitized for experimental allergic encephalomyelitis. Nine animals received 100 mg/kg of hydroxyethyl starch-conjugated (HES) DFO by daily intraperitoneal injection commencing the day of antigenic sensitization. Nine paired litter mates received daily IP injections of HES. Serial fat-suppressed magnetic resonance imaging of the optic nerves was obtained with a T2 weighting (T2w) to evaluate demyelination and after intravascular administration of Gd-DTPA to evaluate BBB disruption. The intensity of Gd-DTPA enhancement and T2w signal of the optic nerves was quantitated 3, 7, 10 and 14 days after antigenic sensitization. Animals were then sacrificed and the optic nerves processed for light and transmission electron microscopy with ultracytochemical localization of endogenous hydrogen peroxide (H2O2) and immunogold colocalization of extravasated serum albumin. The area of the optic nerve head, intensity of toluidine blue staining, and the cellular infiltrate were digitized and quantitated. Administration of HES-DFO significantly reduced the intensity of Gd-DTPA enhancement in the optic nerves of HES-DFO-treated animals compared to paired control HES animals (p = 0.0236), with the mean difference between control and treated animals of 19.39. The difference in T2w signal was not significant (p = 0.39), with a mean difference between control and treated animals of -5.51. The intensity of toluidine blue staining of optic nerve specimens was slightly less with HES-DFO compared to untreated animals (mean pair difference 2.48), and the inflammatory infiltrate was reduced with HES-DFO compared to untreated animals (mean pair difference = 61.57); these differences were not statistically significant. In the optic nerve specimens of both groups cerium perhydroxide-derived H2O2 reaction product was evident in a predominantly perivascular and perineural distribution. Immunogold-labeled serum albumin showed extravasation at foci of perivascular inflammation in both the presence and absence of H2O2-derived reaction product. Conjugated DFO reduces disruption of the BBB, as measured by Gd-DTPA enhancement, suggesting the .OH radical generated from perivascular H2O2 may play a role in alterations of vascular permeability in experimental optic neuritis.

Animals↗
PubMed1994

Fat-suppressed MR of the orbit and cavernous sinus: comparison of fast spin-echo and conventional spin-echo.

PURPOSE: To compare T2-weighted fat-suppressed fast spin-echo imaging with fat-suppressed conventional spin-echo imaging in the detection of normal intraorbital and pericavernous anatomy and orbital disease, and to determine the efficacy of fat saturation with T2-weighted fast spin-echo imaging of the cavernous sinus. METHODS: Contrast-to-noise ratios of normal intraorbital anatomy were calculated and compared in 10 consecutive patients using fat-suppressed fast spin-echo and conventional spin-echo T2-weighted images. Contrast-to-noise ratios of common intraorbital lesions were calculated and compared using fat-suppressed fast spin-echo and fat-suppressed conventional spin-echo. Qualitative evaluation was performed and compared for normal intraorbital anatomy using both fat-suppressed fast spin-echo and fat-suppressed conventional spin-echo in 16 patients. Qualitative evaluation for the detection of normal anatomic structures of the pericavernous region was performed and compared using fast spin-echo with and without fat suppression and fat-suppressed conventional spin-echo T2-weighted images in 16 patients. Fat saturation was performed using standard commercially available chemical saturation technique. RESULTS: Reduced imaging time allowed more acquisitions for fat-suppressed fast spin-echo images, which significantly improved visibility of intraorbital and pericavernous anatomy over fat-suppressed conventional spin-echo. Anatomic visibility was also improved because of reduced motion, phase encoding, and susceptibility artifacts. There was no significant difference between contrast-to-noise ratios for fat-suppressed fast spin-echo and fat-suppressed conventional spin-echo imaging of the lateral and medial rectus muscles. Contrast-to-noise ratios of fat suppressed fast spin-echo of orbital disease was significantly greater than contrast-to-noise ratios of fat-suppressed conventional spin-echo. Detection of several normal anatomic structures of the pericavernous region was significantly improved with non-fat-suppressed fast spin-echo over fat-suppressed fast spin-echo because of significantly reduced magnetic susceptibility artifact. CONCLUSIONS: Fat-suppressed fast spin-echo is superior to fat-suppressed conventional spin-echo for T2-weighted orbital imaging. Non-fat-suppressed fast spin-echo is the preferred pulse sequence for T2-weighted imaging of the cavernous sinus because of the minimal susceptibility artifact.

Adipose Tissue↗
PubMed1994

Reversals of blood-brain barrier disruption by catalase: a serial magnetic resonance imaging study of experimental optic neuritis.

PURPOSE: To investigate serially the role of catalase detoxification of endogenous H2O2 in the disruption of the blood-brain barrier (BBB) and demyelination of experimental optic neuritis. METHODS: Serial contrast-enhanced magnetic resonance imaging (MRI) of the optic nerves (T1 weighted) and T2 weighted MRI without contrast were performed on 18 guinea pigs 3 to 14 days after sensitization with central myelin for experimental allergic encephalomyelitis. Sex and age-matched littermates were paired and sensitized with the identical antigenic emulsion. To detoxify endogenous hydrogen peroxide (H2O2), animals received daily intraperitoneal injections of polyethylene glycol (PEG)-catalase at a dose of 12,000 U/kg per day for 3 days, then 1,200 U/kg daily for the next week, commencing 3 days after antigenic sensitization. Littermates received an equal volume of preservative-free saline. The intensity of gadolinium-DTPA (Gd-DTPA) enhancement was quantitated by obtaining the value for a region of interest (ROI) of the right optic nerve and the left optic nerve. The effect of H2O2 detoxification by catalase was evaluated by differences in the intensity of Gd-DTPA enhancement and T2 weighted signal in the ROI of the right and the left optic nerves at 7, 10, and 14 days after antigenic sensitization, from the pretreatment value obtained at day 3. The effectiveness of catalase detoxification of H2O2 was assessed with quantitative ultracytochemical localization of electron-dense, H2O2-derived cerium perhydroxide in the optic nerves. RESULTS: With PEG-catalase treatment, mean differences for Gd-DTPA enhancement in the ROI at 7, 10, and 14 days after antigenic sensitization were significantly reduced from the pretreatment values obtained 3 days after antigenic sensitization compared with the comparable interval values for untreated littermates. For T2 weighted signal intensity, only the 7- and 14-day values were significantly less with PEG-catalase compared with values for littermates obtained at comparable intervals. Quantitative ultracytochemical localization of H2O2-derived cerium perhydroxide reaction product revealed significant reductions in the medium number of cerium particle counts of the optic nerve head, sheath, and myelinated retrobulbar nerve. CONCLUSIONS: PEG-catalase reduced H2O2-derived cerium perhydroxide reaction product in the optic nerve but did not eliminate it, reversed disruption of the BBB as measured by Gd-DTPA enhancement, and reduced demyelination and edema as measured by T2 weighted signal intensity, suggesting detoxification of H2O2 as a new treatment strategy for disorders of primary demyelination of the central nervous system.

Animals↗
PubMed1994

Disruption of the blood-brain barrier in experimental optic neuritis: immunocytochemical co-localization of H2O2 and extravasated serum albumin.

PURPOSE: To probe the role of endogenous hydrogen peroxide (H2O2) in the pathogenesis of disruption of the blood-brain barrier (BBB) associated with experimental allergic encephalomyelitis (EAE), an animal model for primary central nervous system demyelination. METHODS: Strain-13 guinea pigs were sensitized for EAE with central myelin in complete Freund's adjuvant. Magnetic resonance imaging with Gd-DTPA was performed twice a week for 2 weeks to assess disruption of the BBB, in vivo, by the enhancement of the optic nerves. Two weeks after antigenic sensitization, ultracytochemical localization of endogenous H2O2 was performed using the cerium perhydroxide method, with co-localization of endogenous serum albumin extravasation using gold-labeled antibodies against serum albumin. Examination of blood vessels for perivascular immunogold-labeled serum albumin and H2O2 derived reaction product began in the optic nerve head and proceeded toward the retrobulbar optic nerve until a total of 20 vessels were evaluated per animal. RESULTS: Magnetic resonance imaging revealed Gd-DTPA enhancement of the optic nerves in all animals sensitized for EAE. Optic nerve ultrastructure revealed colloidal gold-labeled antibodies against serum albumin in the perivascular and adjacent interstitial spaces of capillaries and small venules in which H2O2 derived cerium perhydroxide reaction product was also simultaneously evident. Immunogold-labeled serum albumin was predominantly confined to the intravascular compartment of the optic nerve in the absence of perivascular H2O2 and/or perivascular foci of inflammatory cells. The difference between the mean percentage of blood vessels (61.8%) with co-localization of perivascular immunogold-labeled serum albumin and cerium perhydroxide reaction product, to the mean percentage of blood vessels (9.5%) with perivascular immunogold-labeled serum albumin in the absence of cerium perhydroxide, was statistically significant (P = 0.0019). CONCLUSIONS: Endogenous H2O2, found at the foci of BBB disruption, may be one of the mediators involved in the alteration of vascular permeability in experimental optic neuritis.

Animals↗
PubMed1993

Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina: comparative studies with basic fibroblast growth factor.

The release of growth factors from ischaemic retina has been hypothesized as the central stimulus for retinal neovascularization in proliferative diabetic retinopathy. Two of the growth factors implicated are insulin-like growth factor-I and basic fibroblast growth factor. We examined the effect of insulin-like growth factor-I on in vivo neovascularization using the established angiogenic model of the rabbit cornea (n = 30), and also compared the effects of insulin-like growth factor-I and basic fibroblast growth factor using two new in vivo systems. Either supraphysiologic concentrations of each growth factor (600 micrograms) were injected intravitreally into pigmented rabbits (n = 21) or porous polyfluorotetraethylene chambers filled with an emulsion containing collagen and growth factor (500 ng) were placed on the retina surface (n = 8). Our results demonstrate that when insulin-like growth factor-I was implanted together with a slow release carrier into the pocket of the normally avascular cornea, insulin-like growth factor-I (10 micrograms/pellet) induced angiogenesis in all rabbits. This degree of angiogenesis was comparable to that previously shown for basic fibroblast growth factor. For the intravitreal studies, the fibrotic component was greater in the basic fibroblast growth factor injected eyes, whereas the vascular component was accentuated in the eyes injected with insulin-like growth factor-I. Light and electron microscopy demonstrated areas of vascular proliferation in both groups. Porous polyfluorotetraethylene chamber studies with insulin-like growth factor-I and basic fibroblast growth factor demonstrated vascular proliferation in the vicinity of the chamber similar to the intravitreal injected eyes, but to a lesser degree than the injected eyes. Our experiments overall support the angiogenic potential of both insulin-like growth factor-I and basic fibroblast growth factor and support distinct but complimentary roles for each growth factor in the pathogenesis of proliferative diabetic retinopathy.

Animals↗
PubMed1993

Use of intraosseous infusion in the pediatric trauma patient.

Intraosseous infusions (IO) are frequently used for gaining rapid vascular access in critically ill children. Few studies exist evaluating the efficacy of this procedure in the injured child. The objective of this study was to describe one pediatric institution's experience with the procedure of IO in young trauma victims. This study evaluated indications, insertion sites, complications, infused pharmacological agents, age, injury severity, and outcome. Fifteen patients received IO placement for cardiopulmonary arrest, seven for hypovolemic shock, and five for neurological compromise. Patient ages ranged from 3 months to 10 years (mean, 2.9 years). Twenty-nine IO lines were attempted in the tibia and three in the femur. Four of 32 attempts were unsuccessful. Of 32 attempts at IO placement (5 patients received multiple attempts), 15 were started in the prehospital setting and 17 in the emergency department. Multiple resuscitation medications as well as large colloid, crystalloid, and blood boluses were successfully infused. Seven of the 27 patients survived without observed IO-related complications. This study supports the use of IO infusion by prehospital as well as hospital personnel in the initial resuscitation of critically injured children. IO has a been established as a rapid, safe, and simple method of obtaining short term vascular access in both critically ill and injured children. This route deserves primary consideration as an alternate route for fluid resuscitation in pediatric trauma patients regardless of age. IO should be placed without delay when venous access is not rapidly obtainable.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion↗
PubMed1993

Role of hydrogen peroxide in experimental optic neuritis. A serial quantitative ultrastructural study.

In order to determine the role of H2O2 in demyelination of the optic nerve, serial quantitative analysis of H2O2-derived cerium perhydroxide reaction product particles was obtained by computerized digitization of electron micrographs of the myelinated retrobulbar optic nerve, unmyelinated optic nerve head, and the optic nerve sheath of guinea pigs sensitized for experimental allergic encephalomyelitis (EAE) and euthanized 3-14 days later. We found that cerium perhydroxide reaction product particles were greatest in the myelinated optic nerve 3 days after antigenic sensitization, but at this focus decreased 7-14 days after antigenic sensitization. Reaction product accumulated in the unmyelinated optic nerve head and optic nerve sheath 3-14 days after sensitization. These results in the myelinated optic nerve suggest H2O2 consumption results in peroxidation of myelin lipid as demyelination proceeds 7-14 days after antigenic sensitization. Hydrogen peroxide accumulation in the optic nerve head and the optic nerve sheath appears to provide a reservoir for diffusion of H2O2 into the retrobulbar optic nerve and adjacent perineural nerve, contributing to the frequent predilection for optic nerve involvement in EAE and perhaps in multiple sclerosis.

Animals↗
PubMed1993

Role of anti-recoverin autoantibodies in cancer-associated retinopathy.

PURPOSE: To examine the retina and test the serum of a patient with cancer-associated retinopathy syndrome who was diagnosed with small cell carcinoma of the lung and experienced unexpected visual loss. METHODS: Proteins from normal human retina were extracted, separated by one- and two-dimensional gel electrophoresis, transferred to PVDF membrane, and used for immunostaining. Antibody specificity was determined by use of solid-phase peptides in a solid-phase immunoassay. RESULTS: Histologic examination of the retina showed loss of the photoreceptor cell layer. This finding correlated with the results of clinical (loss of vision) and electrophysiologic (abnormal electroretinograph [ERG]) tests. The patient's serum antibodies specifically recognized recoverin, a protein predominantly found in retinal photoreceptor cells. The patient's serum also labeled some higher molecular weight proteins present in normal lung and other normal tissues, as well as in lung cell carcinoma cell lines. The only other tissue in which immunoreactivity against p23 could be found was the optic nerve. Our data revealed a lack of cross-reactivity between specific anti-recoverin antibodies and lung proteins. The results indicate that the patient serum contains more than one type of antibody activity. The autoantibodies were tested for fine immunospecificity by use of solid-phase peptides in a solid-phase immunoassay. Patient's antibodies reacted with a major determinant located in the recoverin sequence 62-68 (PKAYAQH) and with several minor ones. CONCLUSION: Based on the fact that the recoverin appears to be distributed in several different cell types, we suggest that this protein may be present in cancer cells and may play a role in the pathogenesis of some cancer-associated retinopathies.

Amino Acid Sequence↗
PubMed1993

[Statistical interpretations in biology using a coefficient of independence].

From tables of contingency, chi 2-test is frequently used to decide whether two classes of events may be considered as independent or not. After a preliminary choice of a confidence level, the results of this method (rejection or non-rejection of a probability law of independence admitted as our null-hypothesis) are practically very difficult to soften, despite the fact that it would be often interesting to point out some further important informations. We are however able to deduce easily, from these same tables of contingency, a coefficient mu, characterizing the independence and belonging to [0, 1]: when the unit value can be reached by mu, a complete independence appears possible but, for mu < 1, we can also specify the proportion of independence law which is hidden within the complete law of probability associated with our random sample.

Biometry↗
PubMed1993

Parainfectious optic neuritis and encephalomyelitis. A report of two cases with thalamic involvement.

Two children developed mental status alteration and bilateral profound visual loss secondary to optic neuritis. The clinical picture was consistent with parainfectious encephalomyelitis. Magnetic resonance imaging showed bilateral involvement of the thalamus in both cases. In one case the thalamic involvement was solitary and was suspected initially to represent a primary thalamic neoplasm. This was ruled out by a stereotactic biopsy of the thalamus, which showed perivascular inflammation consistent with parainfectious encephalomyelitis. The clinical and neuroimaging findings improved significantly following corticosteroid administration. Several relapses occurred upon initial attempts at corticosteroid cessation.

Child, Preschool↗
PubMed1993

Who's protected? Legal, ethical issues in employing the immunosuppressed.

There does exist a growing population of immunosuppressed people who are entering or re-entering the workforce, and their impact will be felt in the future. They present unique needs that should be addressed clearly, but the waters remain muddy. How do all remain protected and at what cost? The government has established mandates for hiring and accommodating the disabled, but how does the small employer survive the financial consequences? What happens when the 16-year-old bone-marrow transplant recipient cuts her hand on metal shelving at the hardware store where she works? Who is liable for the medical costs if the individual contracts an infection, or worse, tetanus? Is the individual's transplant considered a pre-existing condition? Will the employer's worker's compensation package cover the expense? Worse yet, what happens if this individual should die of complications from the injury? Who is responsible? Would the outcome be different if the employer knew the individual was immunosuppressed? Does the pre-existing condition influence the medical insurance coverage or costs? Can a truly safe environment be provided? At what cost to whom?

Confidentiality↗