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G Ray

Publications and source records attributed to G Ray.

At least 19 recordsLinked to original sources
PubMed2001

Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases.

BACKGROUND: In 1998, the US Centers for Disease Control and Prevention was notified of three patients who developed severe illnesses days after yellow fever vaccination. A similar case occurred in 1996. All four patients were more than 63 years old. METHODS: Vaccine strains of yellow fever virus, isolated from the plasma of two patients and the cerebrospinal fluid of one, were characterised by genomic sequencing. Clinical samples were subjected to neutralisation assays, and an immunohistochemical analysis was done on one sample of liver obtained at biopsy. FINDINGS: The clinical presentations were characterised by fever, myalgia, headache, and confusion, followed by severe multisystemic illnesses. Three patients died. Vaccine-related variants of yellow fever virus were found in plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samples of two vaccinees showed antibody responses of at least 1:10240. Immunohistochemical assay of liver tissue showed yellow fever antigen in the Kuppfer cells of the liver sample. INTERPRETATION: The clinical features, their temporal association with vaccination, recovery of vaccine-related virus, antibody responses, and immunohistochemical assay collectively suggest a possible causal relation between the illnesses and yellow fever vaccination. Yellow fever remains an important cause of illness and death in South America and Africa; hence, vaccination should be maintained until the frequency of these events is quantified.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Role of lipids, lipoproteins and vitamins in women with breast cancer.

OBJECTIVES: Improper balance between the production of reactive oxygen metabolites (ROMs), and antioxidative defense system have been defined as oxidative stress in various pathologic conditions. Lipids, lipoproteins and antioxidative vitamins have been associated with the risk of breast cancer. The present case-control study was conducted to investigate the status of antioxidative vitamins (A, C and E), lipids (total cholesterol; TC and triglycerides; TG), lipoproteins (high-density lipoprotein cholesterol; HDL-C and low-density lipoprotein cholesterol; LDL-C) and retinol-binding protein (RBP) in breast cancer patients. The aim of the study was to find out oxidative stress in breast cancer. DESIGN AND METHODS: Plasma lipids, lipoproteins and vitamins were estimated in 54 untreated breast cancer patients of different clinical stages and in 42 age- and sex-matched controls. RESULTS: Plasma TC (p < 0.05), and LDL-C and TG (p < 0.01) were found to be significantly elevated among breast cancer patients as compared to the controls. On the other hand, plasma HDL-C concentration (p < 0.001) and vitamin C and E (p < 0.01) were observed significantly decreased in breast cancer patients than in the controls. The maximum changes in plasma TC, and vitamin C and E concentrations were observed in breast cancer patients with stage IV when compared with controls. CONCLUSION: The study suggests that higher levels of TC and TG may play important role in carcinogenesis. Furthermore, the elevated plasma LDL-C concentration, which is more susceptible to oxidation, may result in higher lipid peroxidation in breast cancer patients. However, decreased concentrations of HDL-C and vitamin C and E are not likely to be sufficient enough to counter higher ROMs production reported earlier in breast cancer patients that may cause oxidative stress leading to cellular and molecular damage thereby resulting in cell proliferation and malignant conversions.

Adult↗
PubMed2001

Randomized controlled trial of intrasphincteric botulinum toxin A injection versus balloon dilatation in treatment of achalasia cardia.

As the few randomized controlled trials available in the literature comparing botulinum toxin (BT) injection with established endoscopic treatment of achalasia cardia, i.e. pneumatic dilatation, showed conflicting results, we conducted a prospective randomized trial. Seventeen consecutive patients with achalasia cardia diagnosed during a period between December 1997 and February 2000 were randomized into two treatment groups [pneumatic dilatation by Rigiflex dilator (n=10), BT injection by sclerotherapy needle into four quadrants of lower esophageal sphincter (LES) (n=7) 80 units in five cases, 60 units in two cases] after dysphagia grading, endoscopy, barium esophagogram, and manometry, all of which were repeated 1 week after treatment. Patients were followed up clinically for 35.2+/-14 weeks. Chi-squares, Wilcoxon rank-sum test, Kaplan-Meier method and log-rank tests were used for statistical analysis. After 1 week, 6/7 (86%) BT-treated vs. 8/10 (80%) dilatation-treated patients improved (P=NS). There was no difference in LES pressure and maximum esophageal diameter in the barium esophagogram in the two groups before therapy. Both therapies resulted in significant reduction in LES pressure. The cumulative dysphagia-free state using the Kaplan-Meier method decreased progressively in BT-treated compared with dilatation-treated patients (P=0.027). Two patients with tortuous megaesophagus, one of whom had failed dilatation complicated by perforation previously, improved after BT. One other patient in whom pneumatic dilatation had previously failed improved in a similar manner. BT is as good as pneumatic dilatation in achieving an initial improvement in dysphagia of achalasia cardia. It is also effective in patients with tortuous megaesophagus and previous failed pneumatic dilatation. However, dysphagia often recurs during 1-year follow up.

Adult↗
PubMed2000

Lipid peroxidation, free radical production and antioxidant status in breast cancer.

Reactive oxygen metabolites (ROMs), including superoxide anion (O2*-), hydrogen peroxide (H2O2) and hydroxyl radical (*OH), play an important role in carcinogenesis. There are some primary antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) which protect against cellular and molecular damage caused by the ROMs. We conducted the present study to determine the rate of O2*- and H2O2 production, and concentration of malondialdehyde (MDA), as an index of lipid peroxidation, along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients. Forty-two age- and sex-matched patients with minor surgical problems, who had no history of any neoplastic or breast disorders, were taken as controls. The rate of O2*- production was significantly higher (p < 0.001) in BC patients than controls, irrespective of clinical stages and menopausal status. Similarly, H2O2 production was significantly higher in BC patients, especially in stage III and postmenopausal groups, as compared to the respective controls. MDA concentration was also observed significantly elevated in stage II (p < 0.001), stage III (p < 0.01), postmenopausal (p < 0.005), and premenopausal (p < 0.02) group as compared to their corresponding controls. SOD and GPx activities were found significantly raised in all the groups (p < 0.001), except the GPx activity was found a smaller alteration in stage IV (p < 0.02). On the contrary, CAT activity was found significantly depressed in all the study groups. The maximum depression was observed in stage II (-61.8%). Lower CAT activity in our study may be the effect of higher production of ROMs, particularly O2*- and *OH. SOD and GPx, however, were less effected by these higher ROMs production. The results of our study have shown a higher ROMs production and decreased CAT activity, which support the oxidative stress hypothesis in carcinogenesis. The relatively higher SOD and GPx may be due to the response of increased ROMs production in the blood. However, the higher SOD and GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the most dangerous *OH radical followed by MDA. Therefore, administration of CAT may be helpful in the management of BC patients. However, further elaborate clinical studies are required to evaluate the role of such antioxidant enzymes in BC management.

Adult↗
PubMed2000

Alterations in antioxidant status during neonatal sepsis.

Septicaemia is a major threat to survival during the early stages of life. There are several reports that suggest that reactive oxygen species (ROs) play a role in a wide variety of diseases. We estimated the activity of xanthine oxidase (XO), malondialdehyde (MDA) content, creatine phosphokinase (CPK) activity, activities of key enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (PO), and non-enzymatic antioxidants, viz. uric acid (UA) and albumin (ALB), in 30 neonates with sepsis and 20 age-matched controls. The babies were categorized as preterm/term, early onset/late onset, and shock/without shock, as per clinical and laboratory investigations. The study was carried out to evaluate the status of antioxidant enzymes and non-enzymatic antioxidants with a view to suggesting the introduction of antioxidant therapy in neonatal sepsis. The activities of serum XO, CPK, SOD and GPx, and the content of MDA were found to be significantly elevated in the neonates with sepsis when compared with controls. Conversely, the activity of PO and the levels of UA and ALB were decreased. The septic, full-term neonates registered significantly higher CPK activity (70%) than the preterm septic neonates. However, infants with late-onset and shock sepsis had a significant decrease in CPK activity (p < 0.05) compared with their corresponding sub-groups. Likewise, UA levels were found to be 28% depressed (p < 0.05) in the babies with late-onset sepsis and 51% increased (p < 0.001) in babies with shock compared with their respective sub-groups. Neonates with septic shock also registered a significant elevation in GPx activity (28%) compared with those without shock. This study suggests increased production of ROs in neonates with sepsis, as evidenced by the positive regulation of XO, SOD and GPx activity. The elevation of antioxidant enzymes, however, was not so effective as to protect from cellular damage and thereby result in higher MDA production. It is evident that antioxidant therapy might be useful in the management of neonates with sepsis but further detailed clinico-biochemical investigations are required to define effective antioxidant therapy.

Antioxidants↗
PubMed2000

Evaluation of free radical status in CSF in childhood meningitis.

The study was undertaken to investigate the possible role of free radicals and antioxidants in childhood meningitis. Sixty children suffering from acute bacterial meningitis (ABM) or tuberculous meningitis (TBM) according to their clinical and laboratory findings were enrolled in the study. The production of superoxide anions (O2.-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) and the activities of xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were monitored in the study groups and findings compared with those in 20 age-matched controls. Children with ABM and TBM who died registered significant increases in the production of O2.- and MDA and in the activities of SOD and CPK compared with survivors. The rate of production of oxidants and MDA and the activities of XO, SOD and CPK were of a much higher magnitude in deceased ABM and in ABM survivors than in fatal TBM and survivors, respectively. The abnormalities in most of the biochemical parameters investigated were more marked in the children with ABM than in TBM and controls (p < 0.001). Increased MDA production and creatine phosphokinase (CPK) activity of different magnitudes in the two study groups suggest varying degrees of tissue damage. The alterations observed in 20 children who died (14 from ABM, 6 from TBM) revealed elevated levels of oxidants, antioxidants and toxicity markers, particularly in ABM patients, which suggests the possibility that natural or synthetic antioxidants might prevent disease progression and tissue damage in childhood meningitis.

Antioxidants↗
PubMed1999

Status of antioxidants and other biochemical abnormalities in children with dengue fever.

During an outbreak of dengue fever in 1996, 66 children between 45 days and 12 years of age with dengue fever and 25 healthy controls were studied for antioxidants and other biochemical abnormalities. As per World Health Organization (WHO) criteria, 14 children were classified as having classical dengue (DEN), 42 with dengue haemorrhagic fever (DHF), and 10 (including three who died) as having dengue shock syndrome (DSS). Superoxide dismutase (SOD), glutathione peroxidase (GPX), and albumin (ALB), the three main antioxidants studied, were found to be abnormal in 96, 94, and 40 per cent of the cases respectively. The levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CPK), total protein (TP), total cholesterol (CHO), and triglycerides (TGL) were abnormal in 79, 50, 30, 93, and 67 per cent of the cases respectively. Among the different groups of dengue the abnormalities were more marked in children with DSS than in those with DEN and DHF, especially with respect to ALB, TP, TGL, AST, ALT, and CPK (p < 0.005). This preliminary report of dengue confirms the assumption of free radical generation and alteration in antioxidant status during acute illness. However, to understand their complex interaction in disease progression and therapeutic utility, further studies are required.

Antioxidants↗
PubMed1999

Status of lipid peroxidation and antioxidant enzymes in hypoxic ischemic encephalopathy.

OBJECTIVE: To compare the activities of key antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase] and the level of malonyl dialdehyde (MDA) in neonates with hypoxic ischemic encephalopathy (HIE) and controls. DESIGN: Prospective cross sectional study. SETTING: Tertiary care level II neonatal unit of teaching hospital. METHODS: Fifteen term new borns with HIE were registered for the study whereas normal term appropriate for gestational age babies were enrolled as controls. Clinical features were recorded. Activities of SOD, GPx, catalase and the content of MDA were estimated at 24 hours of age. The results obtained were statistically analyzed. RESULTS: Activities of SOD and Catalase and the level of MDA were significantly higher in cases as compared to the controls. There was however no significant alternation in the activity of GPx levels in both the groups. CONCLUSION: The increased activities of antioxidant enzymes are unable to counteract the excessively generated oxidants in vivo, as is evident from the increased MDA levels. Hence, oxygen free radicals may play a significant role in the pathogenesis of HIE.

Case-Control Studies↗
PubMed1998

Effect of shipment, storage, anticoagulant, and cell separation on lymphocyte proliferation assays for human immunodeficiency virus-infected patients.

Lymphocyte proliferation assays (LPA), which can provide important information regarding the immune reconstitution of human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral therapy, frequently involve shipment of specimens to central laboratories. In this study, we examine the effect of stimulant, anticoagulant, cell separation, storage, and transportation on LPA results. LPA responses of whole blood and separated peripheral blood mononuclear cells (PBMC) to different stimulants (cytomegalovirus, varicella-zoster virus, candida and tetanus toxoid antigens, and phytohemagglutinin) were measured using fresh specimens shipped overnight and frozen specimens collected in heparin, acid citrate dextrose (ACD), and citrate cell preparation tubes (CPT) from 12 HIV-infected patients and uninfected controls. Odds ratios for positive LPA responses were significantly higher in separated PBMC than in whole blood from ACD- and heparin-anticoagulated samples obtained from HIV-infected patients and from ACD-anticoagulated samples from uninfected controls. On separated PBMC, positive responses were significantly more frequent in fresh samples compared with overnight transportation for all antigens and compared with cryopreservation for the candida and tetanus antigens. In addition, viral antigen LPA responses were better preserved in frozen PBMC compared with specimens shipped overnight. CPT tubes yielded significantly more positive LPA results for all antigens, irrespective of the HIV patient status compared with ACD, but only for the candida and tetanus antigens and only in HIV-negative controls compared with heparin. Although HIV-infected patients had a significantly lower number of positive antigen-driven LPA responses compared with uninfected controls, most of the specimen processing variables had similar effects on HIV-positive and -negative samples. We conclude that LPA should be performed on site, whenever feasible, by using separated PBMC from fresh blood samples collected in either heparin or ACD. However, if on-site testing is not available, optimal transportation conditions should be established for specific antigens.

Adult↗
PubMed1995

Inversion of (R)- to (S)-ketoprofen in eight animal species.

The (R)-enantiomer of the NSAID ketoprofen was administered orally at 20 mg/kg to a series of 8 animal species. In all species, a highly significant degree of inversion occurred after 1 h which varied from 27% (gerbil) to 73% (dog) and persisted or increased in plasma samples obtained 3 h after drug administration. Although the (R)-enantiomer was inactive as an inhibitor of cyclooxygenase, the analgesic effects of that isomer was almost the same as the (S)-isomer in animal analgesic assays, following oral administration of the drugs to mice and rats. Taken together, the present results suggest that (R)-ketoprofen administered alone functioned primarily as a prodrug for (S)-ketoprofen under the experimental conditions of this study.

Administration, Oral↗
PubMed1994

Evaluation of left ventricular function based on simulated systolic flow dynamics computed from regional wall motion.

Left ventricular (LV) chamber flow is undoubtedly influenced by the time-dependent regional motion of the LV wall. In an attempt to obtain diagnostic parameters based on LV chamber flow, we computed the LV chamber, two-dimensional systolic velocity and pressure distribution for two right anterior oblique (RAO) ventriculograms: one normal, one with ischemic coronary artery disease, and several simulations with prescribed abnormal wall motion. The flow fields are obtained by solving the discretized two-dimensional Navier-Stokes equations for viscous, incompressible unsteady flow using the finite analytic method. These solutions were used as a basis for two LV assessment parameters: (1) local pressure gradient near the LV wall, and (2) the central ejection region (CER), defined as the region of flow domain in which the obtained velocity field vectors are aligned +/- 5 degrees from the LV long axis. A CER coefficient, R, derived from the location and orientation of the CER within the LV cavity, is defined such that R = 0 for a heart which produces no CER, and R = 1 for a heart whose contraction is perfectly even along the entire RAO LV outline. The computed local pressure gradients in the ischemic heart near the apical wall region were reduced compared with those computed in the normal heart. An observable decrease in magnitude of the pressure gradients in the apical region for increasing severity of abnormal wall motion was also indicated. However, the prescribed abnormal wall motion simulations generated reduced pressure gradients in regions of abnormal wall motion and normal regions as well. Therefore, the local wall pressure gradient may not be suitable for localization of coronary occlusion but for presence of disease only. The time-averaged CER coefficient was 0.709 for the normal heart and 0.453 for the diseased heart. The CER shifted toward the region of LV wall which exhibits the abnormal motion, and the CER coefficient decreased with increasing severity of abnormal wall motion. The CER coefficient provides a qualitative and quantitative measure of global function that regional wall motion analysis cannot provide, and is a parameter which is sensitive to regional and temporal abnormalities and the resulting compensatory actions which cannot be detected by global parameters.

Blood Flow Velocity↗
PubMed1993

Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex.

OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. DESIGN: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. SETTING: Outpatient clinics of 12 AIDS Clinical Trials Units. PATIENTS: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). INTERVENTION: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. MEASUREMENTS: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

AIDS-Related Complex↗
PubMed1992

Consolidation hemibody radiotherapy following induction combination chemotherapy in high-tumor-burden multiple myeloma.

PURPOSE: Curative therapy for multiple myeloma continues to be an elusive goal. This report discusses the Northern California Oncology Group (NCOG) phase I and II trial in high-tumor-burden disease that used a strategy that consisted of induction chemotherapy (vincristine, melphalan, cyclophosphamide, and prednisone [VMCP]) for eight cycles followed by sequential hemibody radiation therapy (RT) and subsequent chemotherapy for an additional eight cycles. PATIENTS AND METHODS: Seventy-two previously untreated stage III myeloma patients were entered onto the study. Sixty-nine received induction chemotherapy, 40 received induction chemotherapy and hemibody RT, and 23 received induction chemotherapy, hemibody RT, and consolidative chemotherapy. RESULTS: Twenty-two complete responses (CRs) were obtained by induction chemotherapy, with four additional CRs after RT and consolidative chemotherapy. Nineteen patients developed grade 4 hematologic toxicity primarily after upper hemibody RT. Eight of these developed long-standing neutropenia or thrombocytopenia. Median survival of the group was 134 weeks, which was not significantly different from other approaches. CONCLUSIONS: Hemibody RT can be combined with chemotherapy as induction therapy and can be safely administered in a community setting. However, as administered here no survival advantage was demonstrated.

Adult↗
PubMed1989

Stiffness and strain energy criteria to evaluate the threshold of injury to an intervertebral joint.

This study is focused to evaluate the threshold of injury to an intervertebral joint based on its mechanical response. The load-deflection behavior of the intervertebral joint indicated non-linear and sigmoidal characteristics with continuously changing stiffness (a measure of the ability to withstand external force). The load corresponding to the point of zero stiffness was identified, according to the classical theories of mechanics, as the maximum load carrying capacity. Further, the initiation of trauma was defined to occur at the point on the load-deflection curve at which the stiffness begins to decrease for the first time. The load, stiffness and energy absorbing capabilities of normal and degenerated intervertebral joints at the initiation of trauma was determined. Axial compressive load experiments were conducted on nine intervertebral joints of fresh human male cadavers and the resulting load-deflection responses were transformed into stiffness-deflection responses using the derivative principle. Energy characteristics were also derived. Load, stiffness and energy at the initiation of trauma were found to be 9.0 kN, 2850 N mm-1, and 10.2 J for normal and 4.4 kN, 1642 N mm-1, and 5.8 J for degenerated segments, respectively. The load and energy values at failure were 11.0 kN, and 18.0 J for normal and 5.3 kN and 5.7 J for degenerated intervertebral joints, respectively.

Biomechanical Phenomena↗
PubMed1988

Microtrauma in the lumbar spine: a cause of low back pain.

Excessive mechanical stress on the intervertebral disc may be one of the causes of low back pain. Most studies testing this thesis, however, have been based on quantification of the mechanical response of functional units at failure. Typically, radiography is used to demonstrate trauma to the vertebral body at the failure load. The description of failure and radiographic demonstration of damage are meaningful in specifying the tolerance limits of the structure. It is important, however, to understand the sequence underlying the initiation of injury, which may occur at subfailure physiological loads. In this study, we identified the initiation of injury to the lumbar spine by subjecting functional units to axial compressive loads using the mechanical response as a basis. Because conventional radiography failed to detect trauma at this level, advanced sectioning techniques were used. The initiation of injury (microtrauma) is defined as the point on the load-deflection curve where the structure exhibits a decreasing level of resistance for the first time before reaching its ultimate load-carrying capacity. The load deflection curve on this basis was classified into the ambient or preload phase, physiological loading phase, traumatic phase, and post-traumatic phase. Structures loaded to the end of the physiological loading phase did not exhibit any yielding or microtrauma. Injury in the form of microfractures of the endplate not detected on radiography, however, was observed under cryomicrotomy for structures loaded into the traumatic loading phase.

Adult↗