Racial disparities in patient survival after liver transplantation in the United States

Background. Racial disparities in healthcare span such areas as access, outcomes after procedures, and patient satisfaction. Previous work suggested that minorities experience less healthcare and worse survival rates. In adult orthotopic liver transplantation (OLT) mixed results have been reported, with some showing African-American recipients having poor survival compared to Caucasians, and others finding no such discrepancy. ^ Purpose. This study’s purpose was to analyze the most recent United Network for Organ Sharing (UNOS) data, both before and after the implementation of the Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) scoring system, to determine if minority racial groups still experience poor outcomes after OLT. ^ Methods. The UNOS dataset for 1992-2001 (Era I) and 2002-2007 (Era II) was used. Patient survival rates for each Era and for adult and pediatric recipients were analyzed with adjustment. A separate multivariate analysis was performed on African-American adult patients in Era II in order to identify unique predictors for poor patient survival. ^ Results. The overall study included 66,118 OLT recipients. The majority were Caucasian (78%), followed by Hispanics (13%) and African-Americans (9%). Hispanic and African-American adults were more likely to be female, have Hepatitis C, to be in the intensive care unit (ICU) or ventilated at time of OLT, to have a MELD score ≥23, to have a lower education level, and to have public insurance when compared to Caucasian adults (all p-values < 0.05). Hispanic and African-American pediatric recipients were more likely have public insurance and less likely to receive a living donor OLT than were Caucasian pediatric OLT recipients (p <0.05). There was no difference in the likelihood of having a PELD score ≥21 among racial groups (p >0.40). African-American adults in Era I and Era II had worse patient survival rates than both Caucasians and Hispanic (pair-wise p-values <0.05). This same disparity was seen for pediatric recipients in Era I, but not in Era II. Multivariate analysis of African-American recipients revealed no unique predictors of patient death. ^ Conclusions. African-American race is still a predictor of poor outcome after adult OLT, even after adjustment for multiple clinical, demographic, and liver disease severity variables. Although African-American and Hispanic subgroups share many characteristics previously thought to increase risk of post-OLT death, only African-American patients have poor survival rates when compared to Caucasians. ^

Intracellular chemical messengers and neuronal function: Two examples

Two distinct classes of neurons have been examined in the nervous system of Aplysia. The membrane properties of these neurons are regulated by intracellular signalling molecules in both a short-term and a long-term fashion.^ The role of the phosphatidylinositol cycle in the control of neuronal properties was studied in a class of bursting pacemaker cells, the left upper-quadrant bursting neurons (cells L2, L3, L4, and L6) of the abdominal ganglion of Aplysia. These cells display a regular burst-firing pattern that is controlled by cyclic changes of intracellular Ca$\sp{2+}$ that occur during the bursting rhythm. The characteristic bursting pattern of these neurons occurs within a range of membrane potentials ($-35$ to $-50$ mV) called the pacemaker range. Intracellular pressure injection of inositol 1,4,5-trisphosphate (IP$\sb3$) altered the bursting rhythm of the bursting cells. Injection of IP$\sb3$ induced a brief depolarization that was followed by a long-lasting (2-15 min) hyperpolarization. When cells were voltage-clamped at potentials within the pacemaker range, injection of IP$\sb3$ generally induced a biphasic response that had a total duration of 2-15 min. An initial inward shift in holding current (I$\sb{\rm in}$), which lasted 5-120 sec, was followed by a slow outward shift in holding current (I$\sb{\rm out}$). At membrane potentials more negative than $-40$ mV, I$\sb{\rm in}$ was associated with a small and relatively voltage-independent increase in membrane conductance. I$\sb{\rm in}$ was not blocked by bath application of TTX or Co$\sp{2+}$. Although I$\sb{\rm in}$ was activated by injection of IP$\sb3$, it was not blocked by iontophoretic injection of ethyleneglycol-bis-(beta-aminoethyl ether), N, N$\sp\prime$-tetraacetic acid (EGTA) sufficient to block the Ca$\sp{2+}$-activated inward tail current (I$\sb{\rm B}$).^ Long-term (lasting at least 24 hours) effects of adenylate cyclase activation were examined in a well characterized class of mechanosensory neurons in Aplysia. The injected cells were analyzed 24 hours later by two-electrode voltage-clamp techniques. We found that K$\sp+$ currents of these cells were reduced 24 hours after injection of cAMP. The currents that were reduced by cAMP were very similar to those found to be reduced 24 hours after behavioral sensitization. These results suggest that cAMP is part of the intracellular signal that induces long-term sensitization in Aplysia. (Abstract shortened with permission of author.) ^