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M D Ellison

Publications and source records attributed to M D Ellison.

34 records · Page 2Linked to original sources
PubMed1993

Organ donation in the United States: 1988 through 1992.

1. In 1992, 4,521 cadaveric and 2,578 living-organ donors were recovered. This represented an 11% increase for cadaveric donors and a 41% increase in living donors over the number of donors recovered in 1988. 2. An increasing emphasis on recovering multiple organs from every donor resulted in 78% of the 1992 cadaveric donors being multiorgan donors, up from 62% in 1988. 3. The most common demographic characteristics for both cadaveric and living donors in 1992 were White, blood group O, and 19-35 years old. Cadaveric donors were more commonly male, while living donors were more often female. 4. The percentage of cadaveric donors who were White decreased every year between 1988 and 1992, while the percentage of Black, Asian, and Hispanic donors increased substantially form 1988 to 1992, though not necessarily every year. 5. There has been a substantial shift in the age distribution of cadaveric donors, with the percentage of donors who are > or = 50 increasing every year. By 1992, 21% of cadaveric donors were at least 50 years old. 6. The discard rate for recovered organs increased somewhat between 1988 and 1992 for all organ types, except for lungs. In 1992, less than 7% of each organ type was discarded. The percentage of recovered lungs discarded decreased from 12% in 1988 to 4% in 1992.

Adolescent↗
PubMed1992

Organ donation in the United States: 1988 through 1991.

1. During 1988 through 1991, the total number of cadaveric donors increased by 11% and the number of living donors increased by 25%. 2. During 1991, at least 1 kidney per donor was recovered from 94% of cadaveric donors. Livers were recovered from 70% of cadaveric donors; hearts from 47%, pancreases from 24%, lungs from 8%, and heart-lung combinations from 1%. The percentage of cadaveric donors from whom multiple organs were recovered increased by 23% between 1988 and 1991. 3. During 1988 through 1991, the largest group of cadaveric donors was White, male, age 19-35, with blood group O. During 1991, the primary cause of cadaveric-donor death was cerebrovascular. The largest group of living donors was also White and age 19-35; however, most donors were female. 4. Between 1988 and 1991, the percentage of cadaveric donors age 50-64 increased by 36% (from 11% in 1988 to 15% in 1991) and the percentage of cadaveric donors 65 years old or older increased by 200% (from 1% to 3%). 5. The percentage of White cadaveric donors declined by 4% between 1988 and 1991, while the percentage of Black donors increased by 16%. The percentage of Hispanic donors increased by 25% and that of Asian donors increased by 29%. 6. Throughout 1988 to 1991, the percentage of cadaveric hearts transplanted locally increased by 18% (from 55% to 65%). Interregional cadaveric kidney sharing also increased by 70% (from almost 10% to 17%). Local cadaveric liver transplantation increased by 80% (from 25% to 45%), resulting in a smaller percentage of livers shared interregionally. Local transplantation of cadaveric lungs increased by 173% (from 15% to 41%), reducing the lung discard/research rate by 69%, from 42% to 13%.

ABO Blood-Group System↗
PubMed1992

The UNOS OPTN (Organ Procurement and Transplantation Network) waiting list: 1988 through November 30, 1992.

Based on data from the OPTN Waiting List and the Scientific Registry between 1988 and 1992: 1. The number of registrations on the overall waiting list increased by 81% between December 31, 1988 and November 30, 1992. On November 30, 1992, there were 29,047 registrations for a transplant in the United States. Organ-specific waiting lists showing strong increases during the period were lung (1,277%), liver (262%), and heart (162%). The number of heart-lung registrants decreased during the period. 2. Overall, Whites comprised the largest percentage of waiting-list registrants, followed by Blacks and Hispanics. This frequency distribution remained relatively constant between 1988 and 1991. On the organ-specific waiting lists, the percentage of Whites ranged from 80% on the liver waiting list to 90% on the pancreas waiting list. Blacks make up about 12% of the United States population, but about 32% of the kidney waiting list, due to the high incidence of end-stage renal disease among Blacks in the United States. 3. The frequency distribution of age on the waiting lists is shifting toward a greater proportion of potential recipients age 45 or older. This trend was especially true for the liver, lung, and pancreas waiting lists. 4. The percentage of highly sensitized registrants (PRA > or = 80%) on the kidney waiting list decreased by 8% between 1988 and 1991. The percentage of registrants with PRA less than 20% increased by 11.3%, probably as a result of longer waiting times for low-PRA registrants. 5. A result of the growth of the waiting lists was an increase in the median waiting time to transplant during the period. This effect was observed on every waiting list except the heart-lung. The wait for a liver transplant was the shortest (67 days in 1991), whereas the wait for a heart-lung transplant was the longest (543 days in 1990). 6. The overall death rate remained relatively stable, but was up slightly in 1991, when 6.1% of registrants died while waiting for a transplant (compared with 5.6% in 1990). The death rate on the heart-lung waiting list fell from 23.5% in 1988 to 14.8% in 1991, probably because of fewer heart-lung registrations. In 1991, the death rates were highest on the thoracic waiting lists (11.7-14.8%), followed by liver (9.3%), kidney (3.7%), and pancreas (3.0%). 7. The percentage of patients in the most urgent medical status categories remained stable on the heart waiting list and has decreased on the liver waiting list.

ABO Blood-Group System↗
PubMed1991

Appearance of cytokine-associated central nervous system myelin damage coincides temporally with serum tumor necrosis factor induction after recombinant interleukin-2 infusion in rats.

Endogenous tumor necrosis factor (TNF) activity, assessed by L-929 fibroblast bioassay, was determined in serum samples from rats infused intravenously with recombinant interleukin-2 (rIL-2) or rIL-2 vehicle. Parallel studies of cerebral ultrastructure were conducted in additional rats, comparably infused. Rats received rIL-2 or vehicle either one time only or 3 times daily for 3 days. TNF activity was assessed at 2, 4, and 8 h after the single or final infusion. Rats employed for ultrastructural studies were sacrificed at 4 h after the single or final infusion. Every rIL-2-infused rat exhibited unusual abnormalities of axonal ultrastructure, identical to those previously described after in vitro TNF application to living spinal cord slices. Serum samples drawn during and after the development of axonal changes revealed significantly elevated circulating TNF activity. Controls exhibited neither TNF activity nor altered axons. These studies demonstrate that, following rIL-2 infusion in rats, endogenous TNF circulates at elevated levels during the development of rIL-2-related central nervous system abnormalities similar to those produced in vitro by recombinant TNF. Whether rIL-2-induced circulating TNF is causally-related to the observed myelin damage remains to be determined but merits further investigation, particularly since blood-brain barrier function has been shown to be compromised following rIL-2 infusion.

Animals↗
PubMed1990

Cerebral vasomotor responses after recombinant interleukin 2 infusion.

The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstrictor effect of hypocapnia and the endothelium-dependent vasodilator effect of acetylcholine (Ach) were examined in anesthetized rats equipped with cranial windows. Prior to the functional studies, each of six animals received an i.v. infusion of rIL-2 (6 x 10(5) IU/kg) every 8 h for 3 days. At the same time, six control animals received infusions of equivalent volumes of sterile water. Eight h after the final infusion, each animal was anesthetized and equipped with a cranial window for the observation of pial arterioles overlying the left frontoparietal cortex. Pial arteriolar diameters were measured before and after the topical application of Ach which in normal cerebral arterioles elicits the release of endothelium-dependent relaxing factor, causing vasodilation. When arteriolar diameters returned to base line, they were measured again both before and during hyperventilation-induced hypocapnia. Following functional assessments, these same pial vessels were processed for study by transmission electron microscopy to determine if any observed functional changes correlated with morphological abnormality. Results of the statistical analyses suggested that normal Ach-induced endothelium-dependent vasodilation was absent in the rIL-2-infused group. Additionally, these animals exhibited reduced reactivity to the vasoconstrictive effects of arterial hypocapnia. The control group exhibited normal responsiveness to both Ach and hyperventilation. Ultrastructural studies revealed occasional morphological alterations of both vascular smooth muscle and endothelial cells in some vessels of rIL-2-infused animals but not in controls. These data suggest that repeated systemic rIL-2 infusion results in altered vasomotor responsiveness within the cerebral microcirculation. The data also suggest that the observed vasomotor changes are not always accompanied by overt morphological alterations of either endothelial or smooth muscle cells.

Acetylcholine↗
PubMed1990

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations.

Over the past few years, we and a number of other groups have conducted laboratory experiments and clinical trials of human recombinant interleukin-2 (rIL-2) alone or in combination with autologous 'activated' lymphocytes expressing in vitro tumoricidal activity in order to define toxicity and indicate its potential efficacy in patients with high-grade glioma. Because high rIL-2 concentrations can be attained with considerably less toxicity than with a systemic approach, all of the clinical trials, to date, have chosen a direct route; injecting lymphokine and cells into tumor tissue, the cystic cavity remaining after tumor excision, and/or neural parenchyma surrounding the site of tumor excision. While the rIL-2 therapies, as they have been applied in animal glioma models and patients, are safe, cerebral edema around the site of treatment has been a consistent finding. We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity. Although none of the immunotherapies involving rIL-2 have produced cures, the fact that sustained clinical responses have been reported, suggests that such therapies may slow a recurrence of tumor at the site of treatment. Efforts to improve outcome from rIL-2--based immunotherapies for malignant glioma are continuing with manipulation of rIL-2 dosing and scheduling and also with combinations of rIL-2 and other recombinant cytokines.

Adolescent↗
PubMed1990

Differential central nervous system responses following single and multiple recombinant interleukin-2 infusions.

The effects of systemic recombinant human interleukin-2 (rIL-2) infusion on cerebrovascular permeability to an endogenous circulating macromolecule, immunoglobulin G (IgG), were assessed in rats after single and multiple rIL-2 infusions. Ultrastructural detail of the cerebral vasculature and the related brain parenchyma was also examined for rIL-2-related changes following single and multiple infusions. Animals examined 6 and 24 h after a single rIL-2 infusion exhibited moderately increased permeability to IgG that was not observed in those animals examined 6 h after 5 days of rIL-2 infusion. Alterations of cerebrovascular morphology were evident as early as 6 h after a single infusion and were accompanied by occasional axonal degeneration and demyelination. Such structural changes persisted, becoming more widespread after 5 days of rIL-2 infusion, at which time they were associated with other neuronal as well as glial alterations.

Animals↗
PubMed1989

Recovery of impaired endothelium-dependent relaxation after fluid-percussion brain injury in cats.

The effect of a moderate level of fluid-percussion brain injury on acetylcholine-induced cerebral arteriolar vasodilation was examined for 12 hours after trauma in anesthetized cats equipped with cranial windows. The cats were then perfused with aldehydes, and the pial arteries were prepared for electron microscopy. Immediately after brain injury, the normal vasodilator response to topical application of acetylcholine was converted to vasoconstriction. By 4 hours after trauma, the ability of small pial arterioles (diameters less than 100 microns) to dilate after acetylcholine application had returned to the pretrauma level and was observed to be normal at both 8 and 12 hours after trauma (p less than 0.05). The vasodilator response of large caliber arterioles (diameters greater than or equal to 100 microns) at 4, 8, and 12 hours after injury was reduced relative to the pretrauma response but was significantly improved relative to their response at 30 minutes after trauma (p less than 0.05). Moreover, the response of large vessels at 4, 8, and 12 hours in injured animals was equal to that observed in noninjured control animals assessed at 4, 8, and 12 hours after window implantation. At 12 hours after injury, the ultrastuctural characteristics of both large and small vessels resembled their preinjury state. These data suggest that the impairment of acetylcholine-induced endothelium-dependent relaxation observed in cats after fluid-percussion brain injury is not irreversible but returns to normal (small arterioles) or exhibits significant recovery (large arterioles) within 4 hours after injury.

Acetylcholine↗
PubMed1987

Blood-brain barrier dysfunction in cats following recombinant interleukin-2 infusion.

The effects of systemic human recombinant interleukin-2 (rIL-2) infusion upon blood-brain barrier status and cerebral vascular ultrastructure were examined in cats. Each of eight animals received a single bolus i.v. infusion of rIL-2 (100,000 units/kg). Six control animals were infused with rIL-2 excipient only. Following a 1-h postinfusion survival time, the brain tissue of five rIL-2 infused and three excipient infused animals was processed and examined by light microscopy and electron microscopy for evidence of altered cerebrovascular permeability to systemically circulating horseradish peroxidase. The brain tissue of three additional rIL-2 infused animals and three excipient infused animals, sacrificed 4 h postinfusion, was examined at the light microscopic and electron microscopic levels for the presence of extravasated endogenous IgG. All animals infused with rIL-2 and four of six excipient infused animals showed increased cerebrovascular permeability to the probe used. Altered blood-brain barrier permeability, when present, was recognized in multiple loci throughout the brain, being most prominent within white matter regions. Horseradish peroxidase and IgG were observed within perivascular basal laminae and within the interstices of the brain parenchyma. Numerous endothelial lesions were observed as was flooding of endothelial cytoplasm by horseradish peroxidase or IgG. Every animal studied, regardless of permeability status, showed, within the perivascular brain parenchyma, numerous disrupted neuronal and glial processes as well as expanded intercellular spaces. This study suggests that a single systemic infusion of rIL-2 profoundly alters blood-brain barrier integrity and cerebrovascular morphological integrity. The data also suggest that some of the observed cerebrovascular effects of systemic rIL-2 infusion are due to components of the vehicle for rIL-2.

Animals↗
PubMed1986

Examination of the blood-to-brain transfer of alpha-aminoisobutyric acid and horseradish peroxidase: regional alterations in blood-brain barrier function following acute hypertension.

Blood-brain barrier (BBB) alterations following acute hypertension were studied in rats, employing as tracers in each animal both horseradish peroxidase (HRP) (MW 40,000) and [14C]alpha-aminoisobutyric acid ([14C]AIB) (MW 104). Eighteen animals were subjected to acute hypertension induced by the intravenous infusion of norepinephrine bitartrate (NE) (Levophed). Five animals injected with both tracers but not infused with NE served as controls. The brain of each animal was serially sectioned with adjacent sections processed either for macroautoradiography or for light microscopic visualization of HRP reaction product via histochemical reaction with tetramethylbenzidine. Quantitative blood-to-brain transfer constants for AIB were determined in each of 14 brain regions. Qualitative comparisons were also made between the AIB and HRP blood-to-brain extravasation patterns in each group. Acute hypertension increased cerebrovascular permeability to both AIB and HRP in most animals. Topographically, the sites of the most highly elevated AIB transfer corresponded with sites of HRP extravasation. Conversely, all sites of protein passage corresponded spatially to sites of elevated AIB transfer. Brain regions commonly showing increased permeability to both tracers included the cerebral cortices, corpus callosum, and thalamus. Importantly, some brain regions showed elevated AIB transfer constants where protein extravasation was absent. These regions included the caudate-putamen, hippocampus, basal forebrain, and cerebellum. These observations suggest that following acute hypertension, alterations in BBB permeability are not limited to vascular segments allowing protein extravasation.

Acute Disease↗
PubMed1986

O2 radicals in arachidonate-induced increased blood-brain barrier permeability to proteins.

We studied the effect of topical application of arachidonate on the brain surface on blood-brain barrier permeability to either 125I-labeled human albumin or to horseradish peroxidase administered intravenously. Arachidonate was applied under a cranial window, and the concentration of albumin was measured in brain after elimination of the blood by perfusion-fixation. Permeability to 125I-labeled albumin was increased in the superficial 4 mm of the cortex but not in the deeper cortical layer 4-6 mm from the surface. This increased permeability to albumin was prevented by simultaneous topical application of superoxide dismutase (60 U/ml) and catalase (40 U/ml). Alterations in vascular permeability to horseradish peroxidase were evaluated in semiquantitative fashion, and they behaved similarly. Extravasated horseradish peroxidase was found in the wall of penetrating arterioles, and to a lesser extent in the wall of intraparenchymal vessels and capillaries, but not in the wall of pial arterioles or veins, although these latter vessels displayed focal endothelial lesions. We conclude that arachidonate increases the blood-brain barrier permeability to proteins. This increase in permeability is mediated by O2 radicals. The increased permeability occurs primarily in penetrating arterioles and not in pial arterioles or veins.

Animals↗