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Biomedical subjects

S P Newman

Publications and source records attributed to S P Newman.

At least 19 recordsLinked to original sources
PubMed1996

The concerted regulation of cPLA2, COX2, and lipocortin 1 expression by IL-1beta in A549 cells.

The pro-inflammatory effects of IL-1beta have been linked to the induction of the enzyme COX-2. We now show that in addition to increasing the expression of COX-2, IL-1beta concomittantly decreased the expression of lipocortin 1 on the surface of A549 cells. Furthermore, cytosolic PLA2 is concomittantly activated by phosphorylation-resulting in a stimulation of arachidonic acid and PGE2 release. All of these effects appear to be mediated via a common pathway of PLC and PKC activation. Activation of cPLA2 is inhibited by dexamethasone in a lipocortin 1-dependent mechanism. We present a novel hypothesis whereby the effects of IL-1beta are not only due to activation of enzymes necessary for generation of eicosanoids but also to an inhibition of mechanisms that regulate the supply of arachidonic acid.

Adenocarcinoma↗
PubMed1996

Cerebral magnetic resonance relaxometry in HIV infection.

A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.

AIDS Dementia Complex↗
PubMed1996

Cerebral emboli and cognitive outcome after cardiac surgery.

There have been major advancements in cardiac surgery over the past two decades, with a concomitant decrease in mortality and major morbidity. However, several recent studies have demonstrated that cardiac surgery poses significant risk for negative neurologic and neuropsychologic outcome. Although very few patients die as a result of cardiac surgery, more than two thirds of the patients demonstrate evidence of neuropsychologic dysfunction postoperatively. The mechanisms contributing to post-cardiopulmonary bypass neuropsychologic deficits are uncertain. However, two major interrelated etiologic factors, hypoperfusion and emboli, are suggested as probable culprits. It is important to define the relationship between these two putative mechanisms and postoperative neuropsychologic outcome in order to either prevent the problem or treat the effects of emboli or hypoperfusion. For example, if embolism is the cause of the deficits, increasing cerebral perfusion would deliver more emboli and increase the amount of severity of injury. Conversely, if hypoperfusion is the cause of the injury, then decreasing brain blood flow would increase the likelihood of injury. If both are important, their relative significance must be established, then one prevented and the effects of the other treated. This report discusses the methodology for detecting cerebral emboli during cardiac surgery. The incidence and severity of neuropsychologic deficits after cardiac surgery are discussed, as well as emboli in relation to composition and time of occurrence and their effect on neuropsychologic outcome.

Cardiac Surgical Procedures↗
PubMed1995

Analysis and interpretation of neuropsychologic tests in cardiac surgery.

Neuropsychologic assessment in the context of cardiac surgery is constrained by the clinical time available to see patients, and as such test selection needs to be carefully planned. Besides the time limitations, it differs from clinical neuropsychologic assessment primarily because it tends to involve at least two assessments, a comparison with performance before operation, and a limited number of tests. The analysis and design issues involved in both incidence studies and intervention studies are discussed in this article. Incidence studies customarily involve a single group assessed on at least two occasions and are designed to identify the numbers of individuals who show clear evidence of neuropsychologic changes after a cardiac operation. Intervention studies involve at least two groups where one factor (eg, surgical equipment) is varied systematically. The research on neuropsychologic deficits after cardiac operations has progressed from incidence studies, which involve a conventional definition of deficit, to intervention studies, in which specific test performance can be compared.

Cardiac Surgical Procedures↗
PubMed1995

Scintigraphic assessment of the oropharyngeal and nasal depositions of fusafungine from a pressurized inhaler and from a novel pump spray device.

The distributions of fusafungine (Locabiotal, Servier) radiolabelled with 99mTc, and delivered either orally or intranasally, have been assessed in healthy volunteers from a pressurized metered-dose aerosol inhaler (125 micrograms per dose) and from a novel mechanical pump spray device (500 micrograms per dose). More than 90% of the dose was initially deposited in the oropharynx for oral dosing (n = 8), and more than 90% in the nose for nasal dosing (n = 9), with no significant penetration of aerosol into the lungs. Although not statistically significant, the mean area of deposition, measured in terms of gamma camera picture elements (pixels), was greater with the pump spray for both oral and nasal dosing. The area of deposition with the nasal pump spray extended into the turbinates in six of nine subjects, compared with only three of nine subjects for the pressurized aerosol. The data suggest that the distribution patterns of pump sprays and pressurized aerosols of fusafungine in the oropharynx and in the nasal passages are similar, and that the former can be substituted for the latter with little change in drug delivery.

Administration, Inhalation↗
PubMed1995

Differences in aerodynamic particle size distributions of innovator and generic beclomethasone dipropionate aerosols used with and without a large volume spacer.

BACKGROUND: The equivalence of generic beclomethasone dipropionate (BDP) formulations with their innovator counterpart must be demonstrated if generic formulations are to be used. This study has examined the aerodynamic particle size distributions of both innovator and generic formulations of BDP and the effect of a large volume spacer (Volumatic) on these distributions. METHODS: Aerosol clouds of three formulations of BDP delivering 250 micrograms per metered dose were characterised using a high precision multistage liquid impinger, and the amount of drug in different particle size bands was determined by spectrophotometric assay. RESULTS: The mean (SD) respirable fractions of Becloforte, Beclazone, and Filair without the spacer (n = 10) were 24.1 (2.1)%, 23.1 (2.7)%, and 23.0 (2.1)% respectively; however, the ratio of deposition on stage 4 of the impinger to that on stage 3 was lower for Beclazone and for Filair than for Becloforte, implying a smaller proportion of fine particles for the generic products. When the three products delivered via the Volumatic spacer device were compared, the respirable fraction for Becloforte (n = 10) was 25.0 (4.0)%, but those of Beclazone (n = 10) and Filair (n = 11) were 16.0 (1.9)% and 14.6 (3.4)%. Repeat testing (n = 5) at a later date showed higher mean respirable fractions for all three products, but a trend towards the highest respirable fraction for Becloforte, and the same rank order for the other two products. CONCLUSIONS: These in vitro findings suggest that the particle size distributions of the two generic formulations of BDP are not equivalent to that of the innovator product. Some differences in particle size distributions might not have been detected by a twin impinger. Clinical testing would be required to assess the therapeutic equivalence of innovator and generic corticosteroid products used with or without spacer devices.

Aerosols↗
PubMed1995

Toxoplasmosis and primary central nervous system lymphoma in HIV infection: diagnosis with MR spectroscopy.

PURPOSE: To differentiate intracranial lymphoma from Toxoplasma gondii lesions in patients infected with the human immunodeficiency virus, by means of localized spin-echo proton magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Twenty-seven lesions were studied (18 T gondii lesions, nine lymphoma lesions) at 1.5 T. Spectra were acquired at an echo time of 135 msec from voxels centered on the lesions. Both visual analysis and spectral fitting were used to obtain metabolite ratios for choline (Cho), creatine (Cr), N-acetyl (NA), lactate, and lipids. RESULTS: Three spectral categories were seen. One had large lipid peaks with suppression of other metabolites. Another had an elevated Cho/Cr ratio with relatively diminished NA. The third had features of the other two. Examples of each spectrum type were acquired from both T gondii and lymphoma lesions. Neither method of analysis allowed differentiation between lesion types. MR spectroscopy showed an overlap of spectra. CONCLUSION: The authors conclude that toxoplasmosis and lymphoma cannot be differentiated with spin-echo proton MR spectroscopy at 135 msec.

AIDS-Related Opportunistic Infections↗
PubMed1995

Factors associated with mood and mood disorders in SLE.

This study examines the relative contribution of factors associated with anxious and depressed mood, and clinical anxiety and depression in SLE. Eighty sequentially consenting patients attending a rheumatology outpatient clinic were assessed on measures of anxiety and depression; disease activity; presence of autoantibodies; neuropsychological performance; and psychological and social factors. Mood and mood disorders were found to be unrelated to measures of disease activity but were found to be associated with psychological and social factors. These findings emphasise the importance of psychosocial factors in attempts to understand mood and psychological distress in SLE.

Adolescent↗
PubMed1994

Dexamethasone suppression of IL-1 beta-induced cyclooxygenase 2 expression is not mediated by lipocortin-1 in A549 cells.

A549 cells grown under serum free conditions do not express cyclooxygenase 2 (cox 2). However, addition of IL-1 beta results in the induction of cox 2 in a time and dose dependent manner; actinomycin D completely blocks this induction. Dexamethasone completely suppressed the induction of cox 2 only if present during the first 3.5h of IL-1 beta treatment but not if added after 3.5h. Treatment with a neutralising monoclonal antibody (1A, Biogen) specific to lipocortin-1 failed to reverse this inhibition by dexamethasone. However, using this same antibody we were able to reverse completely the effects of dexamethasone on the suppression of PGE2 release. These observations support the idea that glucocorticoids directly regulate cox 2 expression at the transcriptional level and this phenomenon is not mediated by lipocortin-1.

Annexins↗
PubMed1994

The distribution of an intranasal insulin formulation in healthy volunteers: effect of different administration techniques.

The initial deposition pattern in the nasal passages and subsequent clearance of an insulin formulation labelled with 99mTc-human serum albumin have been determined in 12 healthy male volunteers. Four different administration modes from a novel aqueous spray device were compared, involving delivered volumes of 80-160 microL, and with either gentle or vigorous inhalation while firing the device. The entire dose was deposited in the nasal cavity, and no significant radioactivity was deposited in the lungs. A mean 25-33% of the radiolabel remained in the nose after 4 h. A significantly smaller area of the nasal mucosa was covered by the smallest (80 microL) bolus, but subsequent clearance rates did not vary significantly with mode of administration. Blood glucose levels fell after administration of the insulin formulation, but no serious episodes of hypoglycaemia occurred.

Absorption↗
PubMed1994

Cerebrospinal fluid-intracranial volume ratio measurements in patients with HIV infection: CLASS image analysis technique.

PURPOSE: To prospectively study the cerebrospinal fluid volume-total intracranial volume ratio (CSF/ICV) in human immunodeficiency virus (HIV)-infected patients at various stages of disease. MATERIALS AND METHODS: A total of 258 volume measurements were obtained with use of a 1.5-T magnetic resonance (MR) imager and the cluster localized automated spherical segmentation technique (which reduces two-dimensional pixel data from dual spin-echo MR images to a one-dimensional histogram) in 69 control subjects and 189 HIV-infected patients. RESULTS: The CSF/ICV was statistically significantly increased in patients with late-stage (Centers for Disease Control and Prevention group IV) acquired immunodeficiency syndrome (AIDS) (0.16 +/- 0.05 [standard deviation]) compared with seronegative control subjects (0.12 +/- 0.03) and patients without symptoms (0.13 +/- 0.03). CONCLUSION: No substantial change in CSF/ICV occurs until development of late-stage AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects.

We wanted to evaluate whether lung deposition of budesonide and terbutaline sulphate differs, and to determine lung deposition of budesonide inhaled at different peak inspiratory flows, through Turbuhaler. Lung deposition of budesonide, a lipophilic substance, and of terbutaline sulphate, a hydrophilic substance, was therefore compared, after administration via an inspiratory flow-driven, multi-dose, powder inhaler (Turbuhaler, Astra Draco AB) to 10 healthy volunteers. The radionuclide 99mTc was used to label drug particles, and radioactivity, indicating drug deposition, was measured using a gamma camera. Budesonide was inhaled at a normal flow of 58 l.min-1 and at a slow flow of 36 l-min-1. At the faster flow, a mean +/- SD 27.7 +/- 9.5% of the metered dose was deposited in the lung and at the slower flow 14.8 +/- 3.3% was deposited (p < 0.001). Mean lung deposition of terbutaline sulphate inhaled at 57 l.min-1 was 27.0 +/- 7.7%. We conclude that inspiratory flow has an important effect on lung deposition, but water solubility appears to have no effect.

Administration, Inhalation↗
PubMed1994

Efficient drug delivery to the lungs from a continuously operated open-vent nebulizer and low pressure compressor system.

A comparison of aerosol delivery has been made between two open-vent Pari jet nebulizers. Intermittent and continuous delivery were compared for one of the nebulizers. Ten healthy volunteers inhaled 99mTc-labelled diethylenetriamine penta-acetic acid (DTPA) aerosols on three occasions. The Pari LC device was operated both intermittently (by a manual interrupter that generated aerosol only in synchrony with inhalation) and continuously. The Pari LL nebulizer was operated only in the intermittent mode. A system of inspiratory and expiratory valves was fitted to each nebulizer in order to direct airflow. Both nebulizers were powered by Pari Boy compressors. The mean (SD) whole lung deposition for the LL nebulizer was 11.1 (4.0)% of the nominal dose, compared to 15.3 (12.8)% and 12.8 (7.9)% for the LC used with intermittent and continuous operation, respectively. These differences were not statistically significant. Regional deposition patterns within the lungs were similar for the three nebulizer systems. These data show that efficient nebulizer systems using relatively low power compressors are possible, and suggest that continuously operated open-vent nebulizers may be designed to give lung deposition comparable to that achieved by nebulizers fitted with manual interrupters.

Administration, Inhalation↗
PubMed1993

Lung deposition from four nebulizers.

The total and regional deposition of aerosol has been compared using four nebulizers; the Pari Boy 37.80, Pari IS-2, RespirGard II and Penta-Sonic. The aerosol was radiolabelled with [99Tcm]DTPA, administered to ten healthy subjects and the distributions monitored by gamma scintigraphy. Median lung aerosol depositions expressed as percentages of the doses initially loaded into the nebulizers were: Pari IS-2 19%, Pari Boy 37.80 13%, RespirGard II 9% and Penta-Sonic 2%. The ratios of the peripheral to central lung deposition, however, were greater with the RespirGard II and Penta-Sonic nebulizers. The choice of the most appropriate nebulizer depends on the pharmaceutical being administered, since aerosol must be delivered to the required site in sufficient quantity, whilst minimizing the incidence of local or systemic side-effects.

Administration, Inhalation↗