A comparative study of resource use and costs of renal, liver and heart transplantation

Organ transplantations are among the most expensive surgical treatments performed today, but estimates of the costs of organ transplantations vary widely between settings. The aim of this study is to estimate the costs of renal, liver and heart transplantation in a university hospital, adopting a similar costing methodology for all the three kinds of transplantation. Resource use data were collected from 803 patients transplanted between January 1995 and August 2001. Data about the time physicians and other hospital employees spent per transplantation were based on interviews. All costs from pretransplantation screening up to 3 years post-transplantation were taken into account and divided into costs of patient care and programme-related costs. Mean cost of renal transplantation varied from 70,723 Euros for cadaveric donor transplantations to 76,577 Euros for living donor transplantations. Mean costs of liver transplantation were 141,510 Euros and the mean costs of heart transplantation were 17, 828 Euros. Direct costs of patient care contributed to 79%, 87% and 92% of the costs of renal, liver and heart transplantation respectively. Inpatient hospital days were the largest contributor to the costs of patient care. The mean number of inpatient hospital days from pretransplantation screening to 3 years post-transplantation varied from 46 days for renal transplantation from a living donor to 58 days for renal transplantation from cadaveric donors, 83 days for heart transplantation and 108 days for liver transplantation. In conclusion, costs of liver and heart transplantation were approximately 2.0 and 2.5 times higher than the cost of renal transplantation. Length of inpatient hospital stay for transplantation did not change substantially over time between 1995 and 2001.     

Stage I pure bronchioloalveolar carcinoma: recurrences, survival and comparison with adenocarcinoma of the lung.

OBJECTIVE: Bronchioloalveolar carcinoma (BAC) is considered a subtype of adenocarcinoma of the lung, without pleural, stromal or vascular invasion (World Health Organization (WHO) classification). Previous reports had demonstrated a better prognosis following surgery for patients affected by early stage BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse differences between stage I peripheral nodular BAC and stage I peripheral adenocarcinoma of the lung, METHODS: From January 1, 1993 to December 31, 1999, 1158 patients were submitted to surgical resection for NSCLC. Out of them, 28 patients (2.4%) resulted affected by stage I peripheral pure BAC and 80 (6.9%) by stage I peripheral adenocarcinoma. We made a comparison between these two groups. RESULTS: The percentage of females in BAC patients was similar to that registered in adenocarcinoma patients (21.4 vs. 17.5%). No differences were detected between smokers in BAC and adenocarcinoma patients (P=0.331). The upper lobes were the most common sites of the primary tumour in both tumour subtypes (71.4 vs. 67.5%). Relapse of disease was less frequent in BAC than in adenocarcinoma patients (14.2 vs. 33.7%); recurrent disease developed intrathoracic with higher frequency in BAC patients (75 vs. 33.3%). Both 5-year disease-free and long-term survival were significantly higher in patients affected by BAC (81 vs. 51% and 86 vs. 71%, respectively) (P<0.05); when analysis is performed by dividing stage IA from IB tumours, BAC patients resulted to have higher DFS (stage IA, 93 vs. 58% - P=0.044; stage IB, 61 vs. 32.5%) and higher long-term survival (stage IA, 92 vs. 79%; stage IB, 75 vs. 56%). CONCLUSION: Patients with stage I pure BAC have significantly longer disease-free and overall survival than those with similar stage adenocarcinoma. Even if classified as subtype of adenocarcinoma, BAC is characterised by clinical behaviour less aggressive than similar stage adenocarcinoma.     

Regulation of proopiomelanocortin gene expression by endogenous ligands of the GABAA receptor complex as evaluated by in situ hybridization in the rat pars intermedia

The neurotransmitter gamma-aminobutyric acid (GABA) exerts a tonic inhibitory influence on proopiomelanocortin (POMC) neurons in the hypothalamus as well as on the melanotrope cells of the intermediate lobe (IL) of the pituitary gland. Moreover, the activation of the GABA_A receptor complex by different ligands has been shown to exert a negative influence on the POMC gene expression at the hypothalamic level. In order to elucidate the in vivo regulation of the POMC mRNA levels in the intermediate lobe of the pituitary by endogenous ligands of the GABA_A receptor complex, we have studied the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injections of octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI). The possible involvement of neurosteroids in the action of ODN on melanotropic cells was evaluated following inhibition of two enzymes involved in the biosynthesis of neurosteroids known as activators of G3BA_A receptor complex: trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD), and MK-906, an inhibitor of 5-reductase. The i.v. injection of ODN produced a dose-dependent inhibition of POMC gene expression in the IL. The i.c.v. injection of ODN also depressed POMC mRNA. These effects were completely reversed by the concomitant administration of the GABA_A antagonist picrotoxin. Similar results were obtained in POMC neurons in the arcuate nucleus (AN) of the hypothalamus. Trilostane administration induced an increase in POMC mRNA and also prevented the inhibitory influence of ODN. The neurosteroid pregnenolone-sulfate, a negative modulator of the GABA_A receptor, also stimulated POMC gene expression. On the other hand, MK-906 produced a decrease in mRNA levels and could not reverse the effect of ODN. The results indicate that activation of the GABA_A receptor complex by the endogenous benzodiazepine receptor ligand ODN can induce a negative regulation of POMC gene expression in the IL of the pituitary and neurons in the AN. The present results do not provide clear evidence that neurosteroids are involved in the action of ODN on POMC gene expression in the IL. ©1997 Elsevier Science B.V. All rights reserved     

Hepatocellular Carcinoma: Comparison of Clinical Features among Ethnic Groups in an Area of Low Prevalence

We retrospectively surveyed the clinical features of 73 cases of hepatocellular carcinoma at two hospitals over a 12-yr period. The population was heterogeneous, with 39% representing immigrants from regions of high hepatitis B and hepatocellular carcinoma prevalence. The yearly incidence of cases was constant over the 12 yr. Patient data were analyzed by grouping into three broad categories based on origin from known high, medium, or low prevalence hepatocellular carcinoma zones. In this fashion, differences in clinical presentation were observed. Asians (N = 12) were younger, invariably presented with pain; 82% had markers of hepatitis B and did not have features of chronic liver disease. In contrast, Westerners (N = 45) were older by more than a decade. One-quarter were HBV positive and almost two-thirds were alcoholic. The clinical presentation of this group was more varied, over one-third presenting with features of decompensated liver disease or variceal bleeds. Mediterranean patients (N = 16) had features intermediary between the two other groups. A logistic regression model clinically separated patients with hepatitis B-related hepatocellular carcinoma from those with alcohol-related hepatocellular carcinoma, suggesting different ongoing pathogenetic influences.     

Developmental changes in nerve growth factor (NGF) binding and NGF receptor proteins trkA and p75 in the facial nerve

This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75) and high-affinity (trkA) receptors in the facial nerve and geniculate ganglion (GG) of developing quail embryos (E-3 to E-14). We used ¹²⁵I-labeled NGF (¹²⁵I-NGF) to study binding dynamics in a temporal series of isolated primordia and an autoradiographic series of staged specimens to characterize the occurrence and distribution of NGF receptors in this cranial nerve and its ganglion. In addition, expression of trkA and p75 protein-like immunoreactivity in the facial nerve and GG was studied by Western blot, in order to distinguish between high- and low-affinity NGF receptors respectively. The quantitative study of binding show that isolated facial primordia ranging from E-3 to E-14 exhibit different levels of specific binding. High initial binding levels were observed on E-3 specimens, then an initial decrease on day 4 (E-4) followed by a steady increase from days E-4 to E-7. Maximum ¹²⁵I-NGF binding was achieved on E-7, followed by a steady decline in binding on days 8 (E-8) and 9 (E-9), reaching near background levels on day 10 (E-10) of development and until the oldest stage assayed (E-14). Most of the cells bearing NGF receptors appeared to be nonneuronal crest-derived cells, but some placode-derived neurons and motor fibers of the VIIth cranial nerve transiently expressed the ability to bind ¹²⁵I-NGF. The temporal pattern of p75 expression matches the pattern of quantitative binding of NGF, while the trkA expression is restricted to a few stages mainly E7 and E9, implying that most of the binding detected is via low-affinity receptors, except for a proportion of high-affinity receptors present at stages of maximum binding. This temporal pattern of NGF binding sites suggests that cells within the VIIth cranial nerve are responsive to and/or dependent upon NGF in vivo, so NGF may play a biological role during normal development of the facial nerve. In view of the developmental events that parallel the occurrence and type of NGF binding sites, we suggest that this role may be to modulate from earlier chemotaxis and cell proliferation to much later events, such as neuronal differentiation and neuron-glia interactions. The significance of these findings in regeneration during adult life remain to be investigated.