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Biomedical subjects

M G White

Publications and source records attributed to M G White.

At least 19 recordsLinked to original sources

Magnetic resonance imaging and neuropathology findings in the goat nervous system following hyperbaric exposures.

Divers may be at risk of long-term CNS damage from non-symptomatic hyperbaric exposure. We investigated the effect of severe, controlled hyperbaric exposure on a group of healthy goats with similar histories. Thirty goats were exposed to various dive profiles over a period of 5 years, with 17 experiencing decompression sickness (DCS). Brains were scanned using magnetic resonance (MR) imaging techniques. The animals were then culled and grossly examined, with the brain and spinal cord sent for neuropathological examination. No significant correlation was found between age, years diving, DCS or exposure to pressure with MR-detectable lesions in the brain, or with neuropathological lesions in the brain or spinal cord. However, spinal scarring was noted in 3 animals that had suffered from spinal DCS.

Animals↗

State-resolved dynamics of oxygen atom recombination on polycrystalline Ag.

Rotationally resolved, velocity distributions for desorbed O2 molecules formed by O-atom recombination on the surface of a polycrystalline Ag surface are reported. Surface O atoms are generated by oxygen permeation through a 0.25-mm-thick Ag foil heated to 1020 K. Desorbing O2 molecules are probed by (2 + 1) resonant multiphoton ionization via the C 3Pig (3ssigma), v' = 2 <-- <-- X 3Sigmag-, v" = 0 transition and time-of-flight mass spectrometry. Measured velocity distributions are near Maxwell-Boltzmann and yield average translational energies which are significantly lower than the surface temperature ([Et]/2kB approximately 515 K) and essentially independent of rotational excitation. Comparison of the observed C-X (2,0) resonantly enhanced multiphoton ionization spectrum with spectral simulations suggests that the v" = 0 rotational state distribution is more consistent with the surface temperature, but spectral congestion and apparent intensity perturbations prevent a more quantitative analysis. The calculated, sticking curves show a small barrier energy barrier (approximately 10 meV) beyond which sticking decreases. These observations are consistent with low energy desorption and adsorption pathways involving a weakly bound molecular O2 precursor.

Journal Article↗

The effect of breathing hyperoxic gas during simulated submarine escape on venous gas emboli and decompression illness.

Raised internal pressure in a distressed submarine rapidly increases the risk of decompression sickness (DCS) following submarine escape. The hypothesis that breathing a hyperoxic gas during escape may reduce the risk of DCS was tested using goats. Shallow air saturation and simulated submarine escape dives were carried out either singularly or in combination (saturation, escape, or saturation followed by escape) using air or 60% / 40% oxygen (O2) / nitrogen (N2) mixture as breathing gas during the escapes. Post-surfacing, animals were observed for signs of DCI and O2 toxicity. Precordial Doppler ultrasound was used to score venous gas emboli (VGE) using the Kisman Masurel (KM) scale. Following escape from 2.5 MPa, the rate at which VGE disappeared in the hyperoxic group (n = 8) was significantly faster(p < 0.05) than the air group (n = 7). One case of pulmonary barotrauma with arterial gas embolism occurred in the air group, but no cases of DCS were observed. After saturation at 0.18 MPa followed by escape from 2.5 MPa, DCS occurred in four of 15 animals in the air group and in two of 16 animals in the hyperoxic group. The rate of disappearance of VGE was significantly faster (p < 0.01) in the hyperoxic group. O2 toxicity was not discernible in any of the animals.

Air↗

Chemokines and receptors in HIV encephalitis.

BACKGROUND: Chemokines are involved in the migration of leukocytes and have been implicated in several inflammatory diseases of the central nervous system. Some of their receptors have been proposed to mediate HIV infection. OBJECTIVE: To determine changes in chemokine and receptor expression in HIV encephalitis, and to determine whether upregulation leads to recruitment of infected monocytes across the blood-brain barrier and participates in HIV neuropathology. METHODS: Immunocytochemistry and double-label immunofluorescent laser confocal microscopy was performed with antibodies to chemokines and their receptors on brain tissues from patients who died with or without HIV encephalitis. In vivo distribution was compared with in vitro cultures of human neuroglial cells. RESULTS: The beta-chemokines monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, and RANTES were detected on brain macrophages. Their presence was associated with the histopathological signs of HIV encephalitis. The alpha-chemokines IP-10 (10 kDa inflammatory protein) and interleukin-8 were expressed by astrocytes in all tissues, including controls. Presence of the CXC-chemokine receptor (CXCR)-4 was seen on brain macrophages/microglia, neurons, and astrocytes. CC-Chemokine receptor (CCR)-5 was detected only on macrophages/microglia. CCR-3 and CCR-1 were expressed by macrophages and endothelial cells. In vitro studies examining the presence of CCR-3, CCR-5, and CXCR-4 on human brain cell cultures demonstrated abundant neuronal and microglial expression. CONCLUSIONS: Expression of a variety of chemokines and receptors was shown to be increased in HIV encephalitis brain tissues particularly in areas of neuroglial reaction. The expression pattern supported their involvement in the recruitment of inflammatory infiltrates and formation of microglial nodules. Presence of chemokine receptors on neurons may be involved in the pathogenesis of neurologic damage in AIDS patients.

AIDS Dementia Complex↗

A murine model of HIV encephalitis: xenotransplantation of HIV-infected human neuroglia into SCID mouse brain.

The degree of neuronal damage in HIV encephalitis (HIVE) and the mechanisms leading to it are not known. Post-mortem human studies provide limited information concerning pathogenesis, and there are few animal models of HIVE. We have developed a murine model of HIVE based on HIV-infected human brain tissues grafted within the host CNS milieu. HIV-infected blood-derived macrophages were cocultured with and incorporated within second trimester human fetal brain neuroglia. Mixed neuronal-glial aggregates were injected into the striatum of SCID mice where they survived for more than 6 months. Cellular proliferation and differentiation were determined by immunohistochemical staining for proliferating cell nuclear antigen and cellular markers. Synapse formation was seen by immunocytochemistry for synapsin and by electron microscopy. Virus was detected by immunohistochemical staining for HIV gp41. Based on the long-term survival of human neuroglial xenografts containing HIV infected macrophages, we believe that this model will support the study of chronic HIV-associated neurodegeneration and the testing of various CNS targeted therapeutic interventions.

AIDS Dementia Complex↗

Developmental changes in calcium current pharmacology and somatostatin inhibition in chick parasympathetic neurons.

Voltage-dependent calcium (Ca2+) currents were characterized and modulatory effects of somatostatin were measured in acutely dissociated chick ciliary ganglion neurons at embryonic stages 34, 37, and 40. This developmental time period coincides with the period of synapse formation between ciliary ganglion neurons and peripheral eye muscles. At all three developmental stages Ca2+ current could be blocked almost completely by combined application of omega-CgTX GVIA and nitrendipine. At young embryonic ages there was significant overlap in sensitivity, with approximately 75% of the current sensitive to either blocker applied independently. By stage 40, there was very little or no overlap in sensitivity, with approximately 75% of the current blocked by omega-CgTX GVIA (N-type) and 30% blocked by nitrendipine (L-type). These data are consistent with earlier findings that the pharmacology of acetylcholine release from ciliary ganglion nerve terminals changes during development from sensitivity to both dihydropyridines and omega-CgTX GVIA to selective sensitivity to omega-CgTX GVIA (Gray et al., 1992). Somatostatin reduced Ca2+ current by 50-60% at all three developmental stages. At early developmental stages somatostatin receptors coupled predominantly to the current that was sensitive to both omega-CgTX GVIA and nitrendipine. By stage 40, somatostatin primarily inhibited classically defined N-type current (selectively sensitive to omega-CgTX GVIA). Thus, somatostatin receptor coupling to Ca2+ channels persisted throughout development as Ca2+ current pharmacology changed.

Animals↗

The Norwood operation and subsequent Fontan operation in infants with complex congenital heart disease.

From April 1987 to September 1993, 60 infants underwent a Norwood operation for complex congenital heart disease including hypoplastic left heart syndrome (n = 41), ventricular septal defect and subaortic stenosis with aortic arch interruption/severe coarctation (n = 7), complex single right ventricle with subaortic stenosis (n = 8), critical aortic stenosis with endocardial fibroelastosis (n = 2), and malaligned primum atrial septal defect with coarctation (n = 2). Age at operation ranged from 1 day to 3.9 months (mean 9 days, median 3.5 days). The operative mortality (< 30 days) was 33% (20 patients). Late mortality was 17% (10 patients). Nine of the 20 (45%) operative deaths occurred during the first 2 days after the operation as a result of sudden hemodynamic instability. All four infants with premature closure of the foramen ovale had pulmonary lymphangiectasia and died of pulmonary failure. Seven operative deaths have occurred in 36 patients since 1990 (19%); in the past 2 years, no operative deaths have occurred in 22 patients. Overall, there are 30 long-term survivors (50%). Twenty-one of these 30 infants have undergone a two-stage repair with a modified Fontan operation at 7.3 to 27.6 months of age (mean 18.1 months) with no mortality. Six patients have entered a three-stage repair strategy by undergoing a hemi-Fontan procedure at 6.8 to 23.0 months (mean 8.8 months) with no mortality, and two of these patients have now had their modified Fontan operation at 23.0 to 46.7 months of age with no mortality (four are still awaiting surgery). Two patients have undergone a two-ventricle repair with a Rastelli procedure, with no mortality at 7.4 and 14.1 months of age. Early in our experience, infants undergoing the Norwood operation had a high early mortality most often related to sudden hemodynamic instability. After we instituted a protocol that adds carbon dioxide to the inspired gas during postoperative mechanical ventilation, the postoperative course became more stable and there have been no operative deaths. In summary, the operative mortality for the Norwood operation continues to improve. A subsequent Fontan operation can be performed with excellent clinical results.

Cardiac Surgical Procedures↗

Glomerular filtration rates in persons evaluated as living-related donors--are our standards too high?

We have retrospectively analyzed the glomerular filtration rate by 125-I iothalamate clearance and creatinine clearance in a group of 661 persons evaluated as potential kidney donors. The average GFR in this population is lower than that reported in previous studies and ranges from 102 +/- 15 and 114 +/- 17 ml/min for males and females age 21-30 to 84 +/- 13 and 79 +/- 15 ml/min for males and females age 51-60. Furthermore, there has been a gradual decrease in GFR in this population from 1970 to 1990 in both the entire population and in those under the age of 40. The cause of this drop is not apparent. These data can be utilized to determine the appropriateness of a potential donor for donation, and may indicate that our current standards are too high.

Adult↗

Seasonal trends in erythemal and carcinogenic ultraviolet radiation at mid-southern latitudes 1989-1991.

A network of solar carcinogenic/erythemal ultraviolet radiometers has been established in New Zealand. Daily integrated irradiances of this biologically harmful ultraviolet radiation for 1989, 1990 and 1991 are reported from radiometers located at Wellington (41 degrees S) and Christchurch (43.5 degrees S) and for 1990 and 1991 from the Auckland (37 degrees S) radiometer. Although the monitoring program has not been running sufficiently long to discern any long-term changes in levels of solar ultraviolet radiation, shorter term trends are apparent, which are attributed to a seasonal cycle in levels of ozone at midlatitudes and changes in atmospheric aerosols.

Erythema↗

Carpal tunnel syndrome with cystic bone lesions secondary to amyloidosis in chronic hemodialysis patients.

Carpal tunnel syndrome (CTS) is increasingly recognized in patients undergoing chronic hemodialysis. Although the etiology remains obscure, angioaccess-related vascular engorgement and edema, and ischemic neuropathy are two likely possibilities. Amyloidosis is a relatively rare cause of CTS and had previously been thought to occur almost exclusively in patients with multiple myeloma. We report seven patients on chronic hemodialysis who developed CTS and were shown to have amyloid deposition within the synovium. Amyloid was demonstrated by characteristic staining with Congo red on polarizing microscopy and confirmed by electron microscopy. Six patients also exhibited radiolucent carpal bone cysts which were histologically shown to be due to bone replacement by an amyloid-positive synovitis. The average age of the patient and time on dialysis were 59.1 and 7.9 years, respectively. Serum and urine immunoelectrophoresis and bone marrow aspirates showed no evidence for plasma cell dyscrasia in six patients, while one patient did manifest a monoclonal IgA spike. Autopsies in three patients and liver biopsy in another showed no other evidence for disseminated amyloid. These hemodialysis patients exhibited a unique syndrome of CTS, lytic lesions of the carpal bones, and amyloid deposition in the synovium and within the bone cysts.

Adult↗