PubMed Health⌕ Search

Biomedical subjects

A M Harper

Publications and source records attributed to A M Harper.

At least 19 recordsLinked to original sources
PubMed2006

Reduced priority MELD score for hepatocellular carcinoma does not adversely impact candidate survival awaiting liver transplantation.

The liver organ allocation policy of the United Network for Organ Sharing (UNOS) is based on the model for end-stage liver disease (MELD). The policy provides additional priority for candidates with hepatocellular carcinoma (HCC) who are awaiting deceased donor liver transplantation (DDLT). However, this priority was reduced on February 27, 2003 to a MELD of 20 for stage T1 and of 24 for stage T2 HCC. The aim of this study was to determine the impact of reduced priority on HCC candidate survival while on the waiting list. The UNOS database was reviewed for all HCC candidates listed after February 27, 2002, The HCC candidates were grouped into two time periods: MELD 1 (listed between February 27, 2002, and February 26, 2003) and MELD 2 (listed between February 27, 2003 and February 26, 2004). For the two time periods, the national DDLT incidence rates for HCC patients were 1.44 versus 1.53 DDLT per person-year (p = NS) and the waiting times were similar for the two periods (138.0 +/- 196.8 vs. 129.0 +/- 133.8 days; p = NS). Furthermore, the 3-, 6- and 12-month candidate, patient survival and dropout rates were also similar nationally. Regional differences in rates of DDLT for HCC were observed during both MELD periods. Consequently, the reduced MELD score for stage T1 and T2 HCC candidates awaiting DDLT has not had an impact nationally either on their survival on the waiting list or on their ability to obtain a liver transplant within a reasonable time frame. However, regional variations point to the need for reform in how organs are allocated for HCC at the regional level.

Cadaver↗
PubMed2006

Waiting list removal rates among patients with chronic and malignant liver diseases.

Equitable liver allocation should ensure that nonelective removal rates are fairly distributed among waiting candidates. We compared removal rates for adults entered with nonmalignant (NM) (N = 9379) and hepatocellular cancer (HCC) (N = 2052) diagnoses on the Organ Procurement and Transplantation Network (OPTN) list between April 30, 2003, and December 31, 2004. Unadjusted removal rates for NM vs. HCC diagnoses were 9.4% vs. 8.7%, 13.5% vs. 16.9% and 19.1% vs. 31.8% at 90, 180 and 365 days, respectively after listing. For NM candidates, model for end-stage liver disease (MELD) score (RR = 1.16), age (RR = 1.03) and metabolic disease diagnoses (RR = 1.66) had higher risks of removal; and PSC (RR = 0.62) and alcoholic cirrhosis (RR = 0.82) had lower risks of removal. For HCC candidates, MELD score at listing (RR = 1.09), AFP (RR = 1.02), maximum tumor size (RR = 1.16) and age at listing (RR = 1.02) had increased risks of removal. The equation 1 - 0.920 exp[0.09369 (MELD at listing - 12.48) + 0.00193 (AFP - 97.4) + 0.1505 (maximum tumor size - 2.59) defined the probability of dropout for HCC candidates within 90 days of listing. We conclude that factors associated with the risk of removal for HCC are different from NM candidates, although MELD score at listing remains the most predictive for both groups. Liver transplant candidates with HCC may be prioritized using a risk score analogous to the MELD score.

Adolescent↗
PubMed2001

Application of a continuous disease severity score to the OPTN liver waiting list.

In a move to establish measurable, objective criteria for cadaveric liver allocation, the United Network for Organ Sharing OPTN will implement the Model for End Stage Liver Disease (MELD) system in early 2002 as a replacement for the current Child-Turcotte-Pugh (CTP)-based Status 2A, 2B, and 3 categories for patients waiting for a cadaver donor liver transplant. The MELD is a continuous mortality risk score based on serum creatinine, bilirubin, and INR. Although originally developed in patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure, analysis of OPTN data shows that the components of MELD (in particular, bilirubin) have a very strong correlation with mortality in liver transplant candidates. Univariate analyses showed that pretransplant mortality significantly increased when the MELD score was > 1.8. In the study cohort, 25% of the patients had a MELD score > 1.8. Multivariate analysis showed that the MELD score was an independent predictor of mortality, with a 2-unit increase multiplying the risk of mortality by a factor of 5.6. The MELD and CTP scores were correlated, but MELD scores varied widely for any given CTP score, indicating that some patients could be disadvantaged with the status-based system. The MELD score was validated in an independent dataset; concordance with 3-month mortality was 0.88. We conclude that the MELD score is a good indicator of disease severity and that implementation of this system should direct more livers to those patients in greatest need of transplantation.

Health Care Rationing↗
PubMed2001

The OPTN waiting list, 1988-2000.

More patients in the United states are waiting for organ transplants that at any time in the past and the remarkable growth of the UNOS waiting list has become a key issue for the transplant community. 1. On October 31, 2001, there were 84,277, registrations on the combined UNOS waiting list. Among these, 63% were awaiting kidney transplantation, and 22% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 2000, were of blood type O (52%), white (55%) and male (58%), and awaiting their first transplant (87%). 3. The percentage transplanted within one year of listing has been declining for most organs, although that percentage has been somewhat stable for heart and lung between 1998-2000. 4. Blood type and medical urgency have a significant impact upon the percent transplanted within one year of listing for most organ types. Patients awaiting heart, pancreas, and intestinal transplants experience the highest probability of receiving a transplant within one year. 5. Deaths per patients waiting have declined since 1988 for most patients awaiting life-saving organs and have remained relatively low for those awaiting a kidney, pancreas, or kidney-pancreas transplant. Deaths were highest for lung and heart-lung patients, but appear to be declining.

Adolescent↗
PubMed2000

The OPTN waiting list, 1988-1999.

1. On October 31, 2000, there were 77,999 registrations on the combined UNOS waiting list. Of these, 63% were awaiting kidney transplantation, and 21.5% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 1999 were of blood type O (52%), White (56%) and male (58%), and awaiting their first transplant (87%). 3. Median waiting times have increased steadily for nearly every organ since 1988, especially for liver, kidney, and lung registrants. 4. In general, the percent transplanted within one year of listing is highly influenced by blood type and medical urgency. Patients awaiting heart, pancreas, and intestinal transplants experience the highest probability of receiving a transplant within one year. 5. Since 1988, death rates per patients waiting at risk have declined for most patients awaiting life-saving organs and have remained relatively stable for those awaiting a kidney transplant. Deaths are highest among intestinal patients, but appear to be declining.

Female↗
PubMed1999

The UNOS OPTN waiting list, 1988-1998.

1. On October 31, 1999, there were 71,024 registrations on the combined UNOS waiting list. Of these, 64% were awaiting kidney transplantation and 20% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 1999 were blood type O (52%), White (59%) and male (58%), and awaiting their first transplant (85.9%). 3. Median waiting times have increased steadily for nearly every organ since 1988, especially for liver, kidney, and lung registrants. 4. Median waiting times to transplant were longest for kidney registrants (938 days). The shortest waiting times for this cohort were experienced by intestine registrants (161 days). 5. Death rates per patients waiting at risk have been declining for most patients awaiting life-saving organs and have remained relatively stable for those awaiting for a kidney transplant. Deaths for intestinal patients have risen every year since the list was created (1993), but appears to be stabilizing.

Adolescent↗
PubMed1998

The UNOS OPTN waiting list and donor registry.

1. On October 31, 1998, there were 62,994 registrants on the combined UNOS waiting list. Of these, 66% were awaiting kidney transplantation, and 18% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 1998 were blood type O (52%), White (60%) and male (58%). 3. Median waiting times (MWTs) have increased steadily for nearly every organ since 1988, especially for liver, kidney, and lung registrants. 4. For patients added to the waiting list in 1996. MWTs to transplant were longest for heart-lung registrants (742 days). The shortest waiting times for this cohort were among heart registrants (223 days). No median could be calculated for kidney registrants added in 1996. 5. Death rates per patients waiting at risk declined during 1988-1997. Death rates were higher for patients awaiting life-saving organs (liver, heart, lung, heart-lung) than for non-lifesaving organs (kidney, pancreas, kidney-pancreas). 6. There were 5,478 cadaveric and 3,820 living donors recovered in 1997, a 34% and 109% increase over those recovered in 1988. 7. Large increases were seen in the number of liver (45-84%), pancreas (14-24%), and lung (3-15%) donors between 1988-1997. 8. The number of cadaveric donors aged 50 or older has increased from 12% of all donors in 1988 to 28% of all donors in 1997. 9. The typical cadaveric donor in 1997 was a white male with ABO blood type O, between the ages of 18-34. In 1997, a typical living donor was a white female with ABO blood type O between the ages of 35-49. 10. Between 1988-1997, the percentage of minority donation increased for cadaveric donors (17-24%), and for living donors (23-27%). 11. The number of living donors who were either spouses or unrelated to the recipient increased from 4% in 1988 to 15% in 1997.

ABO Blood-Group System↗
PubMed1997

The UNOS OPTN waiting list and donor registry.

1. On October 31, 1997, there were 55,789 registrations on the combined UNOS waiting list. Of these, two-thirds were awaiting kidney transplantation, and 17% were awaiting liver transplantation. 2. More than one-half of all patients on the UNOS waiting list on October 31, 1997 had blood type O, 59% were White, 58% were male, and 54% were aged 18-49. 3. Annual additions to the UNOS kidney waiting list grew from 11,916 in 1988 to 18,253 in 1996. The largest increase in waiting list size was seen in the lung waiting list, which grew 1,482% during this time. 4. Median waiting times have increased steadily for nearly every organ since 1988, especially for liver, kidney, and lung registrants. 5. For patients added to the waiting list in 1995, MWTs to transplant were longest for heart-lung registrants (887 days); however, no median could be calculated for kidney registrants added in 1995. The shortest waiting times for this cohort were experienced by heart registrants (208 days). 6. Death rates per 1,000 patient-years at risk have declined during 1988-1996. Death rates were higher for patients awaiting life-saving organs (liver, heart, lung, heart-lung) than for non-lifesaving organs (kidney, pancreas, kidney-pancreas). 7. There were 5,417 cadaveric and 3,553 living donors recovered in 1996, a 33% and 95% increase, respectively, over those recovered in 1988. 8. The number of organs recovered per cadaveric donor increased from 3.0 in 1988 to 3.8 in 1994 and dropped to 3.6 in 1996. At the same time, the number of organs transplanted per cadaveric donor recovered increased from 2.7 to 3.2. 9. Large increases in the number of donors who were liver (45-82%), pancreas (14-23%), and lung (3-14%) donors occurred between 1988 and 1996. 10. The number of cadaveric donors aged 50 or older has increased from 12% of all donors in 1988 to 27% of all donors in 1996. 11. The typical cadaveric donor in 1996 was a White male with ABO blood type O, between the ages of 18-34. In 1996, a typical living donor was a White female with ABO blood type O between the ages of 35-49. 12. Between 1988 and 1996, the percentage of minority donations increased for cadaveric donors (17-23%), and for living donors (24-27%). 13. The number of living donors who were either spouses or unrelated to the recipient increased from 4% in 1988 to 14% in 1996.

ABO Blood-Group System↗
PubMed1996

The UNOS OPTN Waiting List and Donor Registry: 1988-1996.

1. There were 49,233 registrations on the combined UNOS waiting list as of October 31, 1996, an increase of 207% over December 31, 1988. Of these, 69% were awaiting kidney transplantation, and 14.6% were awaiting liver transplantation. 2. More than one-half of all patients on the UNOS waiting list on October 31, 1996 were blood type O, 60% were White, 58% were male, and 56% were aged 18-49. 3. Annual additions to the UNOS kidney waiting list grew from 11,909 in 1988 to 17,635 in 1995. The largest increase in waiting list size was in the lung waiting list, which grew from 126 additions in 1988 to 1,706 additions in 1995. 4. For patients registering in 1994, median waiting times to transplant were longest for kidney registrants (842 days), followed by heart-lung registrants (612 days). The shortest waiting times for this cohort were experienced by liver registrants (173 days). 5. In general, death rates per 1,000 patient years at risk have declined during 1988-1995. Death rates were higher for patients awaiting life-saving organs (liver, heart, lung, heart-lung) than for non-lifesaving organs (kidney, pancreas, kidney-pancreas). 6. There were 5,359 cadaveric and 3,215 living donors recovered in 1995, a 31% and 76% increase, respectively, over the numbers recovered in 1988. 7. The number of organs recovered per cadaveric donor increased from 2.98 in 1988 to 3.68 in 1995. At the same time, the number of organs transplanted per cadaveric donor recovered increased from 2.73 to 3.24. 8. Large increases were seen in the number of recovered donors who were liver (45-81%), pancreas (14-24%), and lung (3-17%) donors between 1988-1995. 9. The number of cadaveric donors aged 50 or older has increased 172% from 1988 (475 donors) to 1995 (1,292 donors). 10. The typical cadaveric donor in 1995 was a White male with blood type O, between the ages 18-34. In 1995, a typical living donor was a White female with blood type O, aged 35-49. 11. Between 1988-1995, the percentage of minority donation has increased for cadaveric donors (16.4-22.8%), and for living donors (24.0-27.5%). 12. The number of spouses or other unrelated living donors has increased from 4% in 1988 to 11% in 1995.

Adolescent↗
PubMed1995

The UNOS OPTN waiting list: 1988-1995.

On November 30, 1995, the combined waiting list contained 43,370 registrants, a 15.1% increase from the 37,684 registrations as of December 31, 1994. Kidney registrations accounted for the majority (70.9%) of registrations. The predominant characteristics of the registrants on the combined waiting list as of November 30, 1995 are as follows: 57.6% were male; 59.2% were White; 57% were between 18-49 years of age; 51.4% were of blood type 0; and 82% had no previous transplant. The majority of kidney registrants (68.1%) had a current PRA value of 0-19%. The number of new registrations increased 69.6% from 17,441 additions in 1988 to 29,402 in 1994. The waiting lists with the highest percentage increase in additions over this period were the lung waiting list, ranging from 125 additions in 1988 to 1,544 additions in 1994, and the liver waiting list, ranging from 2,140 additions in 1988 to 6,211 additions in 1994. Since 1992, additions to the kidney-pancreas waiting list ranged from 743 to 1,222, a 64.5% increase. Over the 1988-1992 time period, the rate of transplantation as a percentage of total waiting list registrations declined, decreasing approximately 1% per year. Meanwhile, the death rate per patient registered remained fairly stable, averaging 5.6% each year. The death rate for patients on the heart-lung waiting list decreased each year since 1989. Median waiting times increased annually for patients awaiting kidney and liver transplantation. For those registrants on the heart waiting list, median waiting times increased from 1988-1992, but decreased over the last 2 years. In contrast, lung registrants experienced decreasing median waiting times from 1988-1990, but median waiting times for lung registrants have increased since 1991. Patients awaiting heart-lung transplantation experienced the longest median waiting time in each year except 1993, when the median waiting time for kidney waiting list registrants surpassed that of heart-lung registrants. Patients awaiting liver transplantation experienced the shortest median waiting times each year except 1992. Of those patients added to the combined waiting list in 1993, patients with blood type O on the kidney, liver, heart, lung and heart-lung waiting lists had longer median waiting times than those with blood types A, B or AB. In general, patients having a previous transplant waited longer than those who had not had a previous transplant, with the exception of patients awaiting liver and pancreas transplantation. Females on the kidney, kidney-pancreas, liver, lung and heart-lung waiting lists experienced longer median waiting times than males. Median waiting times were shorter for females on the pancreas (278 vs 436 days) and heart (144 vs 240 days) waiting lists. Median waiting times were shortest for Whites registered on the kidney and lung waiting lists, for Hispanics on the liver list and for Asians on the heart and heart-lung waiting lists. Patients of ¿other¿ racial backgrounds experienced the shortest median waiting time on the kidney-pancreas waiting list. In general, pediatric patients experienced the shortest median waiting times of patients added to the waiting lists in 1993: Kidney and heart registrants less than one year of age had a median waiting time of 90 days and 47 days, respectively. Kidney-pancreas, lung and heart-lung registrants aged 1-5 years had a median waiting time of 81.5 days, 220 days, and 153 days, respectively. Conversely, older patients typically waited the longest for an organ transplant. Patients over 50 years of age experienced the longest median waiting times of patients registered on the kidney, kidney-pancreas, pancreas and heart waiting lists.

Adolescent↗
PubMed1990

Efficacy of nimodipine in cerebral ischemia or hemorrhage.

Our studies showed that in an appropriate dose, nimodipine increased local cerebral blood flow with no corresponding increase in local metabolism. Nimodipine treatment given before experimental ischemic insult, resulting from either vascular occlusion or intracranial hemorrhage or after subarachnoid hemorrhage, maintained or improved blood flow and minimized the severity of subsequent brain damage. Lack of benefit from nimodipine treatment after the insult may occur because the inexorable progression of events leading to ischemic neuronal damage, once initiated, cannot be arrested. On the other hand, pharmacokinetic factors may be important, and post-treatment efficacy may depend on administration protocols that achieve an adequate concentration in ischemic tissue sufficiently soon after an insult. Our findings are compatible with the benefit of nimodipine being due to an improvement in blood flow that reduces the severity of ischemia. However, they do not exclude the possibility that treatment may minimize the accumulation of calcium in damaged cells as a result of "cytoprotective" effects.

Animals↗
PubMed1989

A cerebral vasoconstrictive effect of some adenosine analogues. A study of adenosine analogues on local cerebral blood flow and glucose utilisation in the rat.

Local CBF (LCBF) in the rat was determined using [14C]iodoantipyrine autoradiography. Adenosine and 5'-(N-ethyl)carboxamidoadenosine in a 15-min infusion had no significant effect on LCBF, although there was a tendency to increase. N6-Cyclohexyladenosine (CHA) and 2-chloroadenosine (2-CADO) significantly decreased LCBF in a number of brain regions. Laser-Doppler experiments using CHA confirmed that CHA decreased CBF and that this change was monophasic. Further experiments involving the use of [14C]2-deoxyglucose autoradiography showed that the unexpected vascular effects of CHA and 2-CADO were not a consequence of a decreased metabolic demand. The available data do not allow us to identify the mechanism of action by which the known vasodilators CHA and 2-CADO were able to cause a vasoconstriction and a decrease in LCBF.

2-Chloroadenosine↗
PubMed1988

Effects of adenosine and its analogues on porcine basilar arteries: are only A2 receptors involved?

The aim of this study was to test the effect of adenosine and four of its analogues, 5'-(N-ethyl)carboxamidoadenosine (NECA), 2-chloroadenosine (2-CADO), L-phenylisopropyladenosine (L-PIA), and N6-cyclohexyl-adenosine (CHA), on prostaglandin (PG) F2 alpha-constricted pig basilar arteries, and from their rank order of potency determine the receptor type involved. The order of potency for the relaxation of the PGF2 alpha constriction was NECA greater than adenosine, 2-CADO greater than L-PIA greater than CHA, which is in keeping with the A2 receptor subtype. The study also investigated the effects of a known adenosine antagonist, namely, the xanthine derivative 8-phenyltheophylline, which at concentrations having no intrinsic effect (10(-8) and 10(-7) M) produced a significant shift to the right only for the NECA dose-response curve.

2-Chloroadenosine↗
PubMed1986

Nimodipine and the haemodynamic and histopathological consequences of middle cerebral artery occlusion in the rat.

The effect of the administration of nimodipine (1 microgram kg-1 min-1), initiated 5 min after occlusion of a middle cerebral artery (MCA), upon cerebral haemodynamics ([14C]iodoantipyrine autoradiography) and neuropathological outcome (volume of histologically ischaemic tissue) was investigated in anaesthetized rats. Measurements were made of the level of local CBF (LCBF) in a total of 37 neuroanatomically defined areas, either ipsilateral or contralateral to the occluded vessel, and the autoradiograms were examined using a new approach to quantitative densitometry that employed a frequency distribution analysis of the CBF in sections of the brain at different coronal planes. Both methods of analysis showed that nimodipine, administered after the ischemic event, did not modify the pattern of CBF distribution after MCA occlusion. The extent of ischaemic brain damage was determined by histological examination. There was no evidence that the extent of ischaemic damage, either in sections at eight different coronal planes or in overall volume, was significantly different in animals that received nimodipine from that observed in animals that received only the vehicle used to dissolve the drug. The lack of cerebral circulatory and neuropathological alterations when nimodipine administration is initiated after occlusion of the MCA is contrasted with the higher levels of LCBF and the reductions in the volume of ischaemic tissue that were found when nimodipine was administered before occlusion of the artery.

Animals↗
PubMed1986

Local cerebral glucose utilisation following indoleamine- and piperazine-containing 5-hydroxytryptamine agonists.

Substances with varying structural components have been shown to have 5-hydroxytryptamine (5-HT)-like properties in the CNS. In this study, putative 5-HT agonists with indoleamine moeities--lysergic acid diethylamide (LSD) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)--and with piperazine moieties--quipazine (Quip) and 6-chloro-2-(1-piperazinyl)pyrazine (6-CPP) were administered to rats. Local cerebral glucose utilisation was measured using the [14C]2-deoxyglucose autoradiographic technique. It was found that in most cerebral structures, these substances produced dose-dependent reductions in glucose utilisation. However, Quip and 6-CPP increased glucose utilisation in specific areas of the diencephalon (e.g., nucleus reuniens) and produced a biphasic effect in some but not all extrapyramidal structures (e.g., ventromedial caudate nucleus). No such increases in local cerebral glucose utilisation were measured following LSD or 5-MeODMT administration. These results indicate that although similarities exist between the effects of indoleamine- and piperazine-containing 5-HT agonists on local cerebral glucose utilisation there are also significant differences in the overall patterns of response produced.

Animals↗