Search PubMed⌕ Search

Biomedical subjects

L Gray

Publications and source records attributed to L Gray.

At least 91 records · Page 5Linked to original sources

Antibodies to tumor necrosis factor-alpha: use as adjunctive therapy in established group B streptococcal disease in newborn rats.

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis. Adjunctive therapies are being sought to improve the outcome. Because increased blood levels of tumor necrosis factor (TNF)-alpha may play a role in the development of sepsis and an adverse outcome thereof, we evaluated the potential use of antibodies against TNF-alpha as adjunctive therapy of GBS sepsis. Using a neonatal rat model of GBS sepsis, we measured serum levels of TNF-alpha. Levels of TNF-alpha were significantly increased beginning 12 h after GBS inoculation and remained significantly increased at 30-36 h. We then examined the use of adjunctive therapy with antibody to TNF-alpha in animals with established GBS sepsis using polyclonal rabbit antirecombinant mouse TNF-alpha antiserum. Twelve hours after GBS inoculation, animals received a single dose of antibody to TNF-alpha or normal rabbit serum, and penicillin therapy (twice a day for 3 d) was begun. Animals receiving penicillin and antibody to TNF-alpha had a survival rate of 52% (13 of 25) versus 29% (7 of 24) for animals receiving penicillin and normal rabbit serum. Thus, the use of antibodies directed against TNF-alpha may have a role as adjunctive therapy of established GBS sepsis in the newborn infant.

Animals↗

The CERAD experience, Part VIII: Neuroimaging-neuropathology correlates of temporal lobe changes in Alzheimer's disease.

We compared premortem neuroimaging findings with neuropathologic evidence of temporal lobe atrophy in 20 patients with Alzheimer's disease (AD) confirmed by autopsy. There were significant correlations between temporal horn enlargement observed by neuroimaging and hippocampal atrophy at autopsy, and between the overall cerebral atrophy severity on neuroimaging and scores on the Mini-Mental State Examination. This report confirms previous studies correlating temporal lobe atrophy on neuroimaging with a clinical diagnosis of AD, although more precise neuroimaging techniques are needed for use in multicenter studies of AD.

Alzheimer Disease↗

Neuro-Behçet's disease: factors hampering proper diagnosis.

We reviewed the clinical course of nine patients with neuro-Behçet's disease to assess difficulties in making this diagnosis. Factors delaying proper diagnosis included lack of accurate history and physical examination, lack of recognition of an underlying systemic syndrome and its relationship to the neurologic symptoms, presence of intermittently normal CSF studies, and use of noncontrasted neuroimaging techniques.

Adolescent↗

Vascular malformations presenting as spinal cord neoplasms: case report.

Three cases of adult patients with subacute courses of progressive caudal spinal cord disease are presented. Computed tomography, magnetic resonance imaging, and myelographic studies were interpreted preoperatively as representing a spinal cord neoplasm in each case. No evidence of enlarged or abnormal surface vessels was observed by neuroimaging or intraoperatively. Biopsy specimens from each spinal cord lesion showed the typical histopathological features of a spinal vascular malformation. We conclude that vascular malformations of the caudal spinal cord can appear as isolated intramedullary lesions with apparently normal surface vessels and that these lesions may be difficult to distinguish from spinal cord neoplasms.

Aged↗

Designing a funding system for rehabilitation services. Part 1: Rationale and recent developments.

Part 1 of this paper presents a critical review of several aspects of risk-sharing in rehabilitation that need to be taken into account in designing a funding system. It argues the case for the development of a new rehabilitation payment system separate from both the acute care casemix system and funding arrangements for long-term residential care. The paper then outlines a number of recent developments in the United States and in Australia that draw attention to the need for such a separate system, and details the current provisions for funding rehabilitation in Victoria. An analysis of existing rehabilitation classification systems is given to set the scene for proposing further developments, which are taken up in part 2 of the paper (to be published in the next issue of Australian Health Review).

Australia↗

Regulation of fibrin deposition by malignant mesothelioma.

Malignant mesothelioma (MM) is a locally aggressive tumor that spreads by poorly understood mechanisms. Because neoplastic spread has been linked to altered fibrin turnover, we used immunohistochemistry of nine MM and three fibrous tumors of the pleura to confirm in vivo fibrin deposition and expression of selected coagulation and fibrinolytic reactants in MM. Tumor-associated fibrin was readily detectable at site of tissue invasion. Little fibrin was distributed within the tumor, but tissue factor and tissue factor pathway inhibitor, urokinase, urokinase receptor, and plasminogen activator inhibitors 1 and 2 were all detected in either epithelioid or sarcomatous areas of MM. We used the MS-1 human pleural mesothelioma cell line to determine how expression of these reactants is regulated. Fibrinolytic activity of MS-1 is mainly due to urokinase and is responsive to cytokine stimulation. Functional extrinsic activation and prothrombinase complexes assemble at the cell surface. MM express procoagulants as well as fibrinolytic reactants in vivo and in vitro that promote local fibrin formation and remodeling. Fibrin deposition occurs primarily at areas of tissue invasion and could promote local extension of this neoplasm. Sparsity of fibrin within the central portions of the tumor stroma suggests that local resorption of transitional fibrin occurs at sites of established MM.

Blood Coagulation↗

Brain computerized tomography after hyperbaric oxygen therapy for carbon monoxide poisoning.

The role of brain computerized tomography (CT) imaging in predicting clinical outcome was investigated in patients receiving hyperbaric oxygen therapy for serious carbon monoxide (CO) poisoning. From a series of 48 consecutive patients suffering loss of consciousness from CO exposures, the records of 40 selected patients were evaluated to determine how their CT findings correlated with clinical outcome. A neuroradiologist blinded to patient outcome confirmed the radiographic findings. CT abnormalities consisted of globus pallidus hypodensities (nine patients), subcortical white matter hypodensities (four), cerebral cortical lesions (one), cerebral edema (one), hippocampal lesions (one), and complete loss of gray-white differentiation (one). Of the patients with globus pallidus lesions, 44% manifested incomplete recovery, whereas white matter lesions reflected a 74% incidence of morbidity. Age, duration of CO exposure, and interval between CO exposure and treatment did not significantly relate to clinical outcome. The blood carboxyhemoglobin levels correlated with clinical prognosis (P < 0.05) and, importantly, CT results significantly predicted clinical outcome (P < 0.05). A normal scan correlated highly with a complete recovery, whereas an abnormal scan predicted incomplete recovery or death, despite prior HBO therapy. The current study establishes prognostic validity for brain CT imaging for evaluating clinical outcome after HBO therapy for CO poisoning.

Adolescent↗

Neuronal migration disorders: positron emission tomography correlations.

We analyzed the interictal [18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) findings of 17 epileptic patients with neuronal migration disorders (NMDs). Fifteen patients had abnormal PET findings, i.e., focal hypometabolism in 9 patients and displaced metabolic activity of normal gray matter in 6. All 15 patients had magnetic resonance imaging (MRI) abnormalities; however, PET abnormality assisted in the identification of NMDs on MRI in 3 patients. Two patients with negative MRI also had negative PET studies. PET hypometabolism appeared to correlate with severity of neuronal dysgenesis or temporal lobe involvement, or both. Displaced metabolic activity of gray matter is regarded as a unique interictal [18F]fluoro-2-deoxy-D-glucose-PET finding in NMD. This study demonstrates variable metabolic patterns in NMD and that PET may be a useful complement to MRI in the evaluation of NMD.

Adult↗

The effect of an intensive care unit sound environment on the development of habituation in healthy avian neonates.

There is increasing concern that environmental stimuli in the Neonatal Intensive Care Unit (NICU) may be detrimental to the preterm infants hospitalized there. Separately, there is longstanding recognition that preterm infants at 40 weeks postconceptional age habituate less reliably than full-term infants. This study uses a relevant animal model to test whether exposure to NICU sounds, as a single departure from normal neonatal experience, can alter habituation. Chicks were incubated, hatched, and reared in either a quiet or a NICU-sound environment. Habituation was measured by the length of time that chicks delay their ongoing peeping upon hearing a white noise stimulus. NICU-sound-reared 4-day-olds failed to habituate, showing as much responsiveness at the end of repeated stimulation as at the beginning. This is, to our knowledge, the first demonstration that atypical sound exposure alone can alter this fundamental aspect of neurosensory competence in an otherwise healty neonate.

Aging↗

Binaural processing after corrected congenital unilateral conductive hearing loss.

Binaural processing was measured in a series of tests in patients before and after surgery to correct congenital unilateral conductive hearing losses. Data are presented from 19 patients between the ages of 6 and 33 years that had an abnormal external and/or middle ear on one side but normal hearing in the other ear. Surgery improved thresholds an average of 36 dB HL (from 56 to 20 dB HL). Patients were tested pre- and postoperatively for interaural temporal difference limens, alternate and simultaneous loudness balances, sound localization, binaural detection thresholds, and speech perception in noise. There was statistically significant improvement after surgery in all tests, and the amount of improvement varied along a continuum that appears to be related to the simplicity of the task. For example, most postoperative patients had normal or near-normal performance in a test of interaural temporal difference limens, while almost all had difficulty localizing sounds. Neither binaural performance (before or after surgery) nor the improvement in performance was correlated with age, pure-tone thresholds, or asymmetry. Limited available data show no significant changes in performance from four weeks to over 24 weeks after surgery. In conclusion, binaural ability following corrective surgery exists in varying degrees in these tasks, suggesting different effects of abnormal early experience on different aspects of binaural hearing.

Adolescent↗

Primary access surgery for long-term haemodialysis.

This paper assessed the efficacy of arterio-venous fistulae, vein grafts, and synthetic grafts for long-term haemodialysis. Over a selected 10 year period, 486 primary access sites were established and 182 revisions were necessary. Access procedures were assessed for primary survival, the success or otherwise of revision surgery, and long-term efficacy for haemodialysis. Significant differences were shown for long-term survival of fistulae over vein grafts and synthetic grafts. Successful revision surgery favoured fistulae over synthetic grafts. Arterio-venous fistulae offered the best prospect for effective long-term dialysis. Revision surgery with continued dialysis using the primary-access site was largely unsuccessful, secondary access reconstruction being required in 78.2% of all failures.

Adolescent↗

A discharge planning patient information system.

A computerised patient information system aimed at improving the administration of discharge planning of patients with complex care requirements is described. The system was developed in two major acute general hospitals and has been operational since 1988. The system also transparently records key information about bed utilisation by patients awaiting a variety of discharge outcomes, including rehabilitation and permanent residential care. The extent of bed utilisation by patients awaiting residential care as measured by this system was compared with the results obtained by the conventional method of measuring this phenomenon in Australia--Nursing Home Type bed-days. The Nursing Home Type approach underestimated bed utilisation by this group of patients by 50 per cent, and failed to identify more than 60 per cent of the patients who were recommended for permanent residential care.

Aged↗

Cerebral imaging of decompression injury patients with 18-F-2-fluoro-2-deoxyglucose positron emission tomography.

The objective assessment of the extent of cerebral insult and the effects of therapy in decompression injury patients has proven to be difficult by most imaging modalities. In this pilot study we evaluated the ability of 18-F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) to identify metabolic brain abnormalities in decompression injury patients. Twenty-two patients who were evaluated at our institution for decompression accidents were evaluated with FDG-PET. Four of the 22 patients had no neurologic symptoms and no neurologic findings on clinical exam at the time of the FDG-PET study. No statistically significant correlations were found between the presence of symptoms and the demonstration of abnormalities on the PET study and no statistically significant correlation was found between the location of the decompression injury and the demonstration of abnormalities on the PET study. We conclude that FDG-PET imaging of the brain cannot reliably identify cerebral abnormalities in patients with decompression injuries and would be of limited benefit for monitoring therapy in patients with decompression illness.

Adult↗

Characterization of adenylate cyclase toxin from a mutant of Bordetella pertussis defective in the activator gene, cyaC.

Bordetella pertussis adenylate cyclase (AC) toxin has the abilities to 1) enter target cells where it catalyzes cyclic AMP production and 2) lyse sheep erythrocytes, and these abilities require post-translational modification by the product of an accessory gene cyaC (Barry, E. M., Weiss, A. A., Ehrmann, E. E., Gray, M. C., Hewlett, E. L., and Goodwin, M. St. M. (1991) J. Bacteriol. 173, 720-726). In the present study, AC toxin has been purified from an organism with a mutation in cyaC, BPDE386, and evaluated for its physical and functional properties in order to determine the basis for its lack of toxin and hemolytic activities. AC toxin from BPDE386 is indistinguishable from wild-type toxin in enzymatic activity, migration on SDS-polyacrylamide gel electrophoresis, ability to bind calcium, and calcium-dependent conformational change. Although unable to elicit cAMP accumulation, AC toxin from BPDE386 exhibits binding to the surface of Jurkat cells which is comparable to that of wild-type toxin. This target cell interaction is qualitatively different, however, in that 99% of the mutant toxin remains sensitive to trypsin, whereas approximately 20% of cell-associated wild-type toxin enters a trypsin-resistant compartment. To evaluate the ability of this mutant AC toxin to function at its intracellular site of action, the cAMP-stimulated L-type calcium current in frog atrial myocytes was used. Extracellular addition of wild-type toxin results in cAMP-dependent events that include activation of calcium channels and enhancement of calcium current. In contrast, there is no response to externally applied toxin from BPDE386. When injected into the cell interior, however, the AC toxin from BPDE386 is able to produce increases in the calcium current comparable to those observed with wild-type toxin. Although AC toxin from BPDE386 is unaffected in its enzymatic activity, calcium binding, and calcium-dependent conformational change, the mutation in cyaC does result in a toxin which is able to bind to target cells but unable to elicit cAMP accumulation. In that AC toxin from BPDE386 is able to function normally when injected artificially to an intracellular site, we conclude that the disruption of cyaC produces a defect in insertion and transmembrane delivery of the catalytic domain.

Adenylate Cyclase Toxin↗