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Biomedical subjects

D F Wilson

Publications and source records attributed to D F Wilson.

At least 19 recordsLinked to original sources
PubMed1998

Effect of hemorrhagic hypotension on hydroxyl radicals in cat brain.

This study investigated the relationships between blood pressure, cortical oxygen pressure and hydroxyl radicals in the brain of adult cats during hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the cortex was measured optically by the oxygen dependent quenching of phosphorescence and hydroxyl radicals by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control) to 90 +/- 1 Torr, 70 +/- 3 Torr and 50 +/- 3 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. Cortical oxygen pressure progressively decreased with decrease in MAP, decreasing from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and 22 +/- 2 Torr, respectively. The level of hydroxyl radical increased by 20-25% following first 15 min of bleeding and stay on this level during the remaining period of hypotension. Maximal increase (by 78%) in level of hydroxyl radicals was observed after 15 min of retransfusion. The present study demonstrated that during hypotension and retransfusion there was an increase in the level of hydroxyl radicals in striatum. These can be important mediators of postischemic injury to the striatum.

Animals↗
PubMed1998

Oxygen distributions within R3230Ac tumors growing in dorsal flap window chambers in rats.

R3230Ac mammary tumors were grown in transparent window chambers implanted into the dorsal skin flap of 250 g Fischer 344 rats (see Dewhirst et al, 1992). The oxygen pressure distributions in the tumor and host tissue were measured by the oxygen dependent quenching of phosphorescence (see Vinogradov et al, 1996) after injection of Oxyphor R2 (7 mg, 0.3 ml) into the tail vein. The oxygen pressure maps show the R3230Ac tumors to be hypoxic relative to the surrounding tissue. The excitation spectrum for the phosphor has peaks at 419 nm (blue light) and at 524 nm (green light), and the emitted phosphorescence spectrum and lifetime are independent of the wavelength at which the phosphor is excited. The absorption by tissue is much greater for blue light than green light, due to intrinsic chromophores such as cytochromes, hemoglobin, myoglobin etc. Thus, blue excitation measures the oxygen pressures in a much thinner, superficial, surface layer (< 50 microns) than does green excitation, allowing "optical sectioning" of tissue oxygenation. The tissue can be further optically sectioned by making measurements from both sides of the window. Viewed from the tumor side, the superficial layers (blue excitation) of these tumors were hypoxic whereas the host tissue was well oxygenated. The oxygen pressures in the growing edge of the tumors are lower than those in the central core of the tumor, and much lower than those of the host tissue. This result is in agreement with the micro-oxygen electrode measurements of perivascular oxygen pressures reported by Dewhirst and coworkers (1992).

Animals↗
PubMed1998

Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets.

The present study tested the hypothesis that the increase in extracellular striatal dopamine during hypoxia is least partly associated with activation of N-methyl-D-aspartate (NMDA) and/or non-NMDA excitatory amino acid receptors. Studies were performed in anesthetized and mechanically ventilated 2-3 days old piglets. Hypoxic insult was induced by decreasing the oxygen fraction in inspired gas (FiO2) from 22 to 7% for 1 h, followed by 1 h reoxygenation at 22%. Cortical oxygen pressure was measured optically by oxygen dependent quenching of phosphorescence, and extracellular striatal dopamine was measured using in vivo microdialysis. The microdialysis probes were perfused with Ringer solution +/- 50 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 50 microM 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). One hour of hypoxia decreased the cortical oxygen pressure from 46 +/- 3 Torr to 10 +/- 1.8 Torr. In striatum perfused with Ringer, statistically significant increase in extracellular dopamine, to 1050 +/- 310% of control, was observed after 20 min of hypoxia. By 40 min of hypoxia the extracellular level of dopamine increased to 4730 +/- 900% of control; by the end of the hypoxic period the values increased to 18,451 +/- 1670% of control. The presence of MK-801 in the perfusate significantly decreased the levels of extracellular dopamine during hypoxia. At 20, 40 and 60 min of hypoxia extracellular level of dopamine increased to 278 +/- 94% of control, 1530 +/- 339% of control and 14,709 +/- 1095 of control, respectively. The presence of NBQX caused a statistically significant decrease, by about 30%, in the extracellular dopamine compared to control, only at the end of the hypoxic period. It can be concluded that in striatum of newborn piglets, the excitatory NMDA receptors but not the non-NMDA receptors may be modulating the changes in extracellular levels of dopamine. The NMDA receptor antagonist, MK-801, may exert part of its reported neuroprotective effect to hypoxic stress in striatum by decreasing the levels of extracellular dopamine.

Animals↗
PubMed1998

Bone cement reconstruction of the ossicular chain: a preliminary report.

OBJECTIVE: To determine the feasibility and efficacy of using a bone cement, Oto-Cem, to reconstruct the ossicular chain. STUDY DESIGN: Prospective clinical trial on nine consecutively chosen adult patients with ossicular chain defects. PATIENTS AND SETTING: Nine patients with ossicular chain defects involving the long process of the incus were treated at the Carolina Ear and Hearing Clinic. The ossicular chain was reconstructed using bone cement by itself or in conjunction with a stapes prosthesis. MAIN OUTCOME MEASURES: Preoperative audiograms were compared with audiograms 3, 6, and 12 months after reconstruction. RESULTS: There was a mean pure-tone average (PTA) improvement of 15 dB in patients undergoing incus to stapes suprastructure reconstruction with the bone cement. The incus to mobile footplate reconstruction (using a stapes prosthesis attached to the newly reconstructed incus) resulted in a 34-dB PTA postoperative improvement. Two of the three patients with incus to oval window repairs experienced a 10-dB improvement in PTA. One of the three patients experienced a loss in speech discrimination and a 2-dB loss in PTA. CONCLUSIONS: Despite the limited number of patients, this preliminary study demonstrates the effectiveness of Oto-Cem in reconstructing a foreshortened incus. There was a substantial hearing improvement in all but one patient in the incus to stapes or the incus to footplate categories.

Auditory Threshold↗
PubMed1997

Tamoxifen induces hypoxia in MCF-7 xenografts.

Tamoxifen is widely used as an adjunct therapy for breast cancer. We hypothesized that hypoxia develops in tumors as a result of tamoxifen treatment because tamoxifen has been reported to be antiangiogenic and thrombogenic. MCF-7 breast tumors were grown under estrogenic stimulation in 4-6-week-old CD-1 nu/nu female mice. When the tumors were approximately 5 mm in diameter, 17beta-estradiol pellets were replaced with either placebo or tamoxifen-containing pellets. Two days later, tissue oxygenation was measured using immunohistochemical detection of binding of the 2-nitroimidazole EF5. Intravascular oxygen partial pressures were measured noninvasively by oxygen-dependent quenching of phosphorescence of an injected dye that is excited by light pulses. Tamoxifen treatment increased hypoxia in the tumors, as measured by EF5 binding (P = 0.01 by Mann-Whitney test). This observation was not dependent on the presence of tamoxifen-induced necrosis. Intravascular oxygen partial pressures were lower in tumors relative to surrounding normal tissue in tamoxifen-treated tumors as compared to placebo-treated tumors. In vitro, tamoxifen did not modify the oxygen-dependent metabolism of EF5, indicating that the increased EF5 binding in tamoxifen-treated tumors reflects a physiological decrease in tissue oxygenation. The clinical significance of these observations is discussed in the context of the sequencing of tamoxifen with other therapies, and in light of recent data suggesting that hypoxia may be associated with genetic changes resulting in a more aggressive tumor phenotype.

Animals↗
PubMed1997

Adenosine depresses transmitter release but is not the basis for 'tetanic fade' at the neuromuscular junction of the rat.

It has been suggested that during repetitive neural stimulation adenosine accumulates at the neuromuscular junction and the resulting negative feedback action of adenosine is the major basis for tetanic fade (decline in action of adenosine during repetitive stimulation) This hypothesis was examined at the rat neuromuscular junction by examining the effects of blocking adenosine A1-receptors. Intracellular recording techniques were used to monitor end-plate potentials and miniature end-plate potentials. The data suggest that while adenosine serves a role in depressing transmitter release, adenosine accumulation during brief periods of stimulation is minimal and adenosine is not the cause for tetanic fade.

Adenosine↗
PubMed1997

Response of cortical oxygen and striatal extracellular dopamine to metabolic acidosis in newborn piglets.

This study determined the relationships of metabolic acidosis, cortical oxygen pressure, and striatal extracellular dopamine in the brain of newborn piglets. After a baseline period of 120 minutes, a 0.6 N HCl solution was infused intravenously to decrease the blood pH to about 7.0-7.05. The metabolic acidosis was then corrected by injecting sodium bicarbonate and measurements were continued for one hour. The results show that decreased blood pH to about 7.2-7.15 does not cause a statistically significant change in mean blood pressure, cortical oxygen pressure or striatal extracellular dopamine. Further decrease in pH caused significant decrease in both blood pressure and cortical oxygen pressure. By the end of the period of acidosis the cortical oxygen pressure decreased from the control value of 43 +/- 4 Torr to 22 +/- 8 Torr. Changes in the extracellular level of striatal dopamine were parallel to changes in cortical oxygen pressure. The extracellular dopamine increased to 1270% of the control on the end of HCl injection. Infusion of bicarbonate to correct the acidosis resulted in an increase of cortical oxygen and progressive decline of dopamine in the extracellular medium. It is suggested that the level of extracellular dopamine in the striatum of newborn piglets was not directly affected by decrease in pH but was dependent on changes in tissue oxygen pressure during metabolic acidosis.

Acidosis↗
PubMed1997

Oxygen distribution in the vasculature of mouse tissue in vivo measured using a near infra red phosphor.

Oxygen dependent quenching of phosphorescence has been used to measure the oxygenation of tissue in mice, including the differences between normal tissue and that of a murine tumor. Approximately 0.3 mg of the phosphorescence oxygen probe, Green 2W, was injected into the tail vein of tumor bearing mice. The mice were immobilized using an anesthetic cocktail and illuminated with flashes (< 4 microseconds t1/2) of light of 636 +/- 15 nm. The emitted phosphorescence (790 nm max.) was measured using an imaging phosphorimeter with an intensified CCD camera, an instrument which provides two dimensional digital maps of oxygen pressure. Both the illumination light and the phosphorescence were in the near infra red region of the spectrum, where skin and tissue have little absorption. The light can therefore readily pass through the skin and centimeter thickness of tissue. Mice are sufficiently small that the oxygen pressure maps could be obtained by illuminating from either the same or the opposite side as the camera (and tumor). The tumors were observed as regions with oxygen pressures substantially below those of the surrounding normal tissue. Thus, it is possible to non-invasively detect these tumors and to monitor their internal oxygen pressure in real time and through cm of tissue.

Animals↗
PubMed1997

Activation of tyrosine hydroxylase in striatum of newborn piglets in response to hypocapnic ischemia and recovery.

The present study describes the effect of hypocapnic ischemia caused by hyperventilation on striatal levels of dopamine, DOPAC, HVA and activity of tyrosine hydroxylase in striatal synaptosomes isolated from the brain of newborn piglets. Hyperventilation did not result in statistically significant changes in the striatal level of dopamine and its major metabolites; however, it was observed that after 20 min of recovery the levels of striatal tissue dopamine, DOPAC and HVA increase by 195%, 110% and 205%, respectively. The level of DOPA (3,4-dihydroxyphenylalanine), which was used as an index of tyrosine hydroxylase activity, also increased after recovery. The rate of dopamine synthesis was 32 pmoles/mg protein/10 min in control piglets and after recovery this increased to 132 pmoles/mg protein/10 min. Measurement of the tyrosine hydroxylase activity in Triton X-100 treated synaptosomes showed that, after 20 min of recovery, there was an increase in Vmax with no change in K(m) for pteridine cofactor, compared to control. This is consistent with the enzyme having been covalently modified (activated) during tissue ischemia caused by hyperventilation and remaining activated well into the recovery period. We postulate that ischemia can induce long lasting alterations in dopamine synthesis, which may play some role in mediation of hypoxic cell injury in immature brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Intravascular oxygen distribution in subcutaneous 9L tumors and radiation sensitivity.

Phosphorescence quenching was evaluated as a technique for measuring PO2 in tumors and for determining the effect of increased PO2 on sensitivity of the tumors to radiation. Suspensions of cultured 9L cells or small pieces of solid tumors from 9L cells were injected subcutaneously on the hindquarter of rats, and tumors were grown to between 0.2 and 1.0 cm in diameter. Oxygen-dependent quenching of the phosphorescence of intravenously injected Pd-meso-tetra-(4-carboxyphenyl) porphine was used to image the in vivo distribution of PO2 in the vasculature of small tumors and surrounding tissue. Maps (512 x 480 pixels) of tissue oxygen distribution showed that the PO2 within 9L tumors was low (2-12 Torr) relative to the surrounding muscle tissue (20-40 Torr). When the rats were given 100% oxygen or carbogen (95% O2-5% CO2) to breathe, the PO2 in the tumors increased significantly. This increase was variable among tumors and was greater with carbogen compared with 100% oxygen. Based on irradiation and regrowth studies, carbogen breathing increased the sensitivity of the tumors to radiation. This is consistent with the measured increase in PO2 in the tumor vasculature. It is concluded that phosphorescence quenching can be used for noninvasive determination of the oxygenation of tumors. This method for oxygen measurements has great potential for clinical application in tumor identification and therapy.

Administration, Inhalation↗
PubMed1997

Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher.

The molecular defect in some patients with X-linked mixed deafness with perilymphatic gusher at stapes surgery (DFN3) was recently attributed to mutations in the POU3F4 gene. In this manuscript we describe the molecular analysis of the POU3F4 gene in 5 patients with clinical and radiographic evidence of DFN3. Novel mutations were found in 2 of the 5 patients analyzed, while 3 had an entirely normal protein coding sequence. The fact that 3 of the 5 patients with clinical histories and radiographic abnormalities characteristic of X-linked mixed deafness with perilymphatic gusher displayed normal POU3F4 gene sequences supports the possibility that not all patients with the characteristic phenotype have involvement of the POU3F4 gene.

Base Sequence↗
PubMed1997

Endolymphatic sac obliteration for large vestibular aqueduct syndrome.

The objective of this study was to investigate the effects of endolymphatic sac obliteration for stabilization of progressive hearing loss in patients with the large vestibular aqueduct syndrome. This was a retrospective case review conducted at a private neurootologic office in a metropolitan area. Seven ears in six patients were subjected to surgery for obliteration of the endolymphatic sac in an effort to stabilize progressive hearing loss associated with the large vestibular aqueduct syndrome. The study population was composed of four boys and two girls 4-17 years of age. The large vestibular aqueduct was unilateral in two patients and bilateral in four patients. All seven ears demonstrated progressive sensorineural hearing loss preoperatively. Surgical tissue obliteration was performed via a transmastoid approach in seven ears. The main outcome measure was comparison of pre- and postoperative hearing levels and stability. Magnetic resonance imaging also was performed in all cases at least 6 months postoperatively to determine patency of the endolymphatic sac and vestibular aqueduct. Six of seven ears maintained stable hearing during the follow-up period, which ranged from 6 months to 6 years (mean 3.2 years). One patient showed continued progression of hearing loss postoperatively. All seven ears demonstrated continued obliteration on postoperative imaging studies. Surgical obliteration of the endolymphatic sac may stabilize hearing in patients with the large vestibular aqueduct syndrome and progressive hearing loss. These results support the theory of pressure or fluid reflux into the labyrinth as a cause of progressive hearing loss in these patients.

Adolescent↗
PubMed1997

Extended porphyrins. New IR phosphors for oxygen measurements.

Tetrabenzoporphyrins (TBP) of Zn, Pd, Lu, Y, Sn and Pb show strong absorption bands in the near IR region of the spectrum. Phosphorescence in dimethylformamide (DMF) solutions at room temperature was measured for Pd and Lu complexes giving quantum yields of 7.9% and 3.5% and lifetimes of 250 microseconds and 870 microseconds, respectively. Pd meso-tetraphenyltetrabenzoporphyrin 1 (PdPh4TBP) shows a red shift of the absorption Q-band to 628 nm. 1 reacted with ClSO3H and obtained chlorosulfonato derivative 2 was converted to a set of water soluble chromophores: Pd meso-tetra(sulfophenyl)tetrabenzoporphyrin (Pd Ph4(SO3Na)4TBP) 3, corresponding sulfonamide (Pd Ph4(PEG)4TBP) 4 with aminopolyethyleneglycol (Av.M.W. 5,000) and sulfonamide derivatives of glucoseamine (Pd Ph4(glucoseamine)4TBP) 5 and aminophenylacetic acid (Pd Ph4(phenac)4TBP) 6. Electronic absorption and phosphorescence spectra of 1 and some of its derivatives were recorded and phosphorescence quantum yields and lifetimes were measured for deoxygenated solutions. The oxygen quenching constants were measured for the water soluble complexes 3 and 4 and found to be suitable for oxygen measurements in vivo. Tetranaphthaloporphyrin (TNP) complexes of Pd and Lu as well as Pd meso-tetraphenyltetranaphthaloporphyrin (PdPh4TNP) were synthesized and their absorption and emission properties were examined.

Animals↗