Intrahepatic gas at postmortem computed tomography: forensic experience as a potential guide for in vivo trauma imaging.

BACKGROUND: Until August 2004 there were 106 forensic cases examined with postmortem multislice computed tomography (MSCT) and magnetic resonance (MR) imaging before traditional autopsy within the Virtopsy project. Intrahepatic gas (IHG) was a frequent finding in postmortem MSCT examinations. The aim of this study was to investigate its cause and significance. METHODS: There were 84 virtopsy cases retrospectively investigated concerning the occurrence, location, and volume of IHG in postmortem MSCT imaging (1.25 mm collimation, 1.25 mm thickness). We assessed and noted the occurrence of intestinal distention, putrefaction, and systemic gas embolisms and the cause of death, possible open trauma, possible artificial respiration, and the postmortem interval. We investigated the relations between the findings using the contingency table (chi2 test) and the comparison of the postmortem intervals in both groups was performed using the t test in 79 nonputrefied corpses. RESULTS: IHG was found in 47 cases (59.5%). In five of the cases, the IHG was caused or influenced by putrefaction. Gas distribution within the liver of the remaining 42 cases was as follows: hepatic arteries in 21 cases, hepatic veins in 35 cases, and portal vein branches in 13 cases; among which combinations also occurred in 20 cases. The presence of IHG was strongly related to open trauma with systemic gas. Pulmonary barotrauma as occurring under artificial respiration or in drowning also caused IHG. Putrefaction did not seem to influence the occurrence of IHG until macroscopic signs of putrefaction were noticeable. CONCLUSIONS: IHG is a frequent finding in traumatic causes of death and requires a systemic gas embolism. Exceptions are putrefied or burned corpses. Common clinical causes such as necrotic bowel diseases appear rarely as a cause of IHG in our forensic case material.

Regional and systemic chemotherapy for primary hepatobiliary cancers and for colorectal cancer metastatic to the liver.

Hepatic arterial infusional (HAI) chemotherapy is based on the premise that primary and metastatic tumors derive their blood supply from the hepatic artery, whereas normal liver derives its blood supply from the portal vein. This approach has been extensively studied in liver-only colorectal metastasis patients, with 10 published prospective randomized clinical trials comparing fluoropyrimidine-based HAI therapy with systemic chemotherapy. Most of these studies showed a statistically significant superior response rate and improved disease-free survival with HAI chemotherapy compared with systemic fluoropyrimidine-based chemotherapy alone. More advanced chemotherapeutic regimens including biologically targeted agents have clearly impacted survival in metastatic colorectal cancer patients and are currently under investigation with HAI-based trials. In contrast, hepatobiliary tumors remain difficult to treat with overall poor response and survival with systemic chemotherapy. Few clinical trials have attempted to address the role of HAI-based therapy for these regional tumors, although encouraging response rates up to 60% have been reported. Therefore, the regional approach for hepatobiliary tumors deserves further investigation as well as randomized trials for adequate comparison to new systemic chemotherapies.

Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy.

BACKGROUND: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor. We aimed to clarify the prognostic factors in patients with advanced HCC receiving hepatic arterial infusion chemotherapy (HAIC). METHODS: Forty-four HCC patients were treated with HAIC, using low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with/without leucovorin (or isovorin). Of these 44 patients, 15 received low-dose CDDP and 5-FU, and 29 received low-dose CDDP, 5-FU, and leucovorin or isovorin. Prognostic factors were evaluated by univariate and multivariate analyses of patient and disease characteristics. RESULTS: Of all patients, 5 and 12 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, 38%). The response rate (48.3%) in the low-dose CDDP and 5-FU with leucovorin/isovorin group was significantly better than that (20%) in the low-dose CDDP and 5-FU group (P = 0.002). The 1-, 2-, 3-, and 5-year cumulative survival rates of the 44 patients were 39%, 18%, 12%, and 9%, respectively. The regimen using low-dose CDDP and 5-FU with leucovorin/isovorin tended to improve survival rates (P = 0.097). Univariate and multivariate analyses showed the same variables--the Child-Pugh score (P = 0.013, P = 0.018), alpha-fetoprotein (AFP) level (P = 0.010, P = 0.009), and therapeutic effect after HAIC (P = 0.003, P = 0.01), respectively, to be significant prognostic factors. CONCLUSIONS: Patients who had advanced HCC with favorable hepatic reserve capacity and a lower AFP level were suitable candidates for HAIC. Moreover, the regimen using low-dose CDDP and 5-FU with leucovorin/isovorin may be suitable for advanced HCC patients, because of the improvement in the response rate and survival compared with the low-dose CDDP and 5-FU regimen without leucovorin/isovorin.

Phenylalanine hydroxylation across the kidney in humans rapid communication.

UNLABELLED: Phenylalanine hydroxylation across the kidney in humans. BACKGROUND: Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist. METHODS: To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. RESULTS: In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area. CONCLUSIONS: These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.

Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age.

BACKGROUND: alpha(1)-adrenergic receptors (alpha(1)ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (alpha(1a), alpha(1b), alpha(1 d)) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human alpha(1)AR subtype expression differs with vascular bed, and (2) age influences human vascular alpha(1)AR subtype expression. METHODS AND RESULTS: Five hundred vessels from 384 patients were examined for alpha(1)AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel alpha(1)AR density is 16+/-2.3fmol/mg total protein. alpha(1a)AR predominates in arteries at mRNA (P<0.001) and protein (P<0.05) levels; all 3 subtypes are present in veins. Furthermore, alpha(1)AR mRNA subtype expression varies with vessel bed (alpha(1a) higher in splanchnic versus central arteries, P<0.05); competition analysis (selected vessels) and functional assays demonstrate alpha(1a) and alpha(1b)-mediated mammary artery contraction. Overall alpha(1)AR expression doubles with age (<55 versus > or = 65 years) in mammary artery (no change in saphenous vein), accompanied by increased alpha(1b)>alpha(1a) expression (P< = 0.001). CONCLUSIONS: Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

The innervation of rainbow trout (Oncorhynchus mykiss) liver: protein gene product 9.5 and neuronal nitric oxide synthase immunoreactivities.

We have explored the innervation of the rainbow trout (O. mykiss) liver using immunohistochemical procedures and light microscopy to detect in situ protein gene product 9.5 and neuronal nitric oxide synthase immunoreactivities (PGP-IR and NOS-IR). The results showed PGP-IR nerve fibres running with the extralobular biliary duct (EBD), hepatic artery (EHA) and portal vein (EPV) that form the hepatic hilum, as well as following the spatial distribution of the intrahepatic blood vessel and biliary channels. These nerve fibres appear as single varicose processes, thin bundles, or thick bundles depending on their diameter and location in the wall of the blood vessel or biliary duct. No PGP-IR fibres were detected in the liver parenchyma. NOS-IR nerve fibres were located only in the vessels and ducts that form the hepatic hilum (EBD, EHA, EPV); in addition, NOS-IR nerve cell bodies were found isolated or forming ganglionated plexuses in the peribiliary fibromuscular tissue of the EBD. No PGP-IR ganglionated plexuses were detected in the EBD. The location of the general (PGP-IR) and nitrergic (nNOS-IR) intrinsic nerves of the trout liver suggest a conserved evolutionary role of the nervous control of hepatic blood flow and hepatobiliary activity.

Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans.

This study used regional differences in plasma concentrations of norepinephrine and its metabolites to examine how production of the transmitter by sympathetic nerves, in particular, those innervating mesenteric organs, is integrated with metabolism by the liver and elimination by the kidneys. Higher concentrations of norepinephrine, its glycol metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol and their sulfate conjugates in portal venous than arterial plasma indicate substantial production of norepinephrine by mesenteric organs (15.5 nmol/min). Much lower concentrations of norepinephrine and its glycol metabolites in plasma leaving than entering the liver indicate their efficient hepatic removal (20 nmol/min). Higher concentrations of vanillylmandelic acid in the hepatic outflow than inflow indicate that this metabolic end product is produced largely from the norepinephrine and glycol metabolites removed by the liver. Renal elimination of vanillylmandelic acid (18-20 nmol/min), produced mainly by the liver (17 nmol/min), and of 3-methoxy-4-hydroxyphenylglycol sulfate (7-9 nmol/min), produced largely by mesenteric organs (7 nmol/min), compromised 86-91% of the total renal elimination of norepinephrine metabolites. The results show that mesenteric organs produce about one-half of the norepinephrine formed in the body. The liver removes substantial amounts of circulating norepinephrine and its glycol metabolites and converts these compounds to vanillylmandelic acid, which is then eliminated from the body by the kidneys. The sulfate conjugates are also metabolic end products eliminated by the kidneys. However, these metabolites are produced by extrahepatic tissues, in particular, mesenteric organs, which represent a significant source of sulfate-conjugated norepinephrine and 3,4-dihydroxyphenylglycol, and the main source of sulfate-conjugated 3-methoxy-4-hydroxyphenylglycol.

Efeitos do cloridrato de tetraciclina em fetos de ratas tratadas com o antibiótico (Rattus Norvegicus, raça Wistar, var. Albinus, Rodentia) / Effects of tetracyclin hydrochloride in fetus of rats treated with antibiotic (Rattus Norvegicus, raça Wistar, var. Albinus, Rodentia)

Os autores utilizaram ratas prenhas, em diversos períodos de prenhez, nas quais foi administrada, em dose única, o cloridrato de tetraciclina por via intraperitoneal. No 21§ dia da prenhez, as ratas foram submetidas a cesarianas, quando entäo foi contado o número de implantes ou reabsorçöes, e o número de fetos de cada corno uterino. Processou-se posteriormente à análise histológica de alguns fetos obtidos em diversos períodos da prenhez, para evidenciar-se a distrofia adiposa hepática; relacionando-se entäo a toxicidade da droga para fetos de ratas, em virtude da dose e do tempo de prenhez das ratas utilizadas