Emergency portacaval shunt for control of hemorrhage from a parenchymal fracture after adult-to-adult living donor liver transplantation

As more adults undergo transplantation with partial liver grafts, the unique features of these segments and their clinical significance will become apparent. A patient presented with life-threatening hemorrhage from an iatrogenic laceration to a right lobe graft 11 days after transplantation. The creation of a portacaval shunt effectively controlled the bleeding, allowing more elective replacement of the organ with another right lobe graft. The regeneration process combined with increased portal blood flow and relative outflow limitation may have set the stage for this complication. Any disruption of the liver parenchyma during transplantation should be securely repaired and followed cautiously. Portacaval shunting is an option for controlling hemorrhage from the liver in transplant recipients. The timely availability of a second organ was likely the ultimate determinant of survival for this patient.     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.     

Acute ethanol counteracts the acquisition of aversive olfactory learning in infant rats.

Rodents are particularly prone to acquire associative memories during early stages of life. Yet, very little is known about how ethanol interacts with simultaneous associative learning acquired during postabsorptive periods. We have recently observed that preweanling rats avoid lemon odor previously paired with the intraoral infusion of a sapid sweet solution, a result likely to be caused by aversive consequences inherent to this procedure. Two experiments were conducted to analyze the effects of acute ethanol upon the acquisition of this avoidance response. Fourteen-day-old Wistar rats were intragastrically administered with ethanol (0.0, 0.25, 0.5, or 1.25 g/kg) and then exposed for 5 min to a lemon-scented chamber while being intraorally infused with sucrose (12% vol/vol). Four of such pairings were conducted immediately after ethanol administration. Control pups experienced these stimuli in an unrelated fashion. On postnatal day 15 animals were tested in a 5-min, two-way odor-preference test. Pups administered with vehicle during the acquisition phase exhibited a strong aversion to the lemon odor relative to control subjects. This avoidance response was reduced in pups that received 0.5 and 1.25 g/kg doses, whereas it completely vanished in those that received 0.25 g/kg dose. In a second experiment it was observed that, 10 min after the administration, blood ethanol concentrations attained with the 0.25, 0.5, and 1.25 g/kg doses were 11, 39, and 83 mg%, respectively. These data indicate that a very low dose of ethanol is able to counteract early aversive associative learning, a result likely to be mediated by anxiolytic properties of ethanol.     

Renal and antibacterial effects induced by myotoxin I and II isolated from Bothrops jararacussu venom.

Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-exchange chromatography and reverse phase HPLC. In this work we used the isolated perfused rat kidney method to evaluate the renal effects of B. jararacussu myotoxins I (Lys49 PLA2) and II (Asp49 PLA2) and their possible blockage by indomethacin. BthTX-I (5 microg/ml) and BthTX-II (5 microg/ml) increased perfusion pressure (PP; ct120=110.28+/-3.70 mmHg; BthTX I=171.28+/-6.30*mmHg; BthTX II=175.50+/-7.20*mmHg), renal vascular resistance (RVR; ct120=5.49+/-0.54 mmHg/ml.g(-1)min(-1); BthTX I=8.62+/-0.37*mmHg/ml g(-1)min(-1); BthTX II=8.9+/-0.36*mmHg/ml g(-1)min(-1)), urinary flow (UF; ct(120)=0.14+/-0.01ml g(-1)min(-1); BthTX I=0.32+/-0.05*ml g(-1)min(-1); BthTX II=0.37+/-0.01*ml g(-1)min(-1)) and glomerular filtration rate (GFR; ct120=0.72+/-0.10 ml g(-1)min(-1); BthTX I=0.85+/-0.13*ml g(-1)min(-1); BthTX II=1.22+/-0.28*ml g(-1)min(-1)). In contrast decreased the percent of sodium tubular transport (%TNa(+); ct(120)=79,76+/-0.56; BthTX I=62.23+/-4.12*; BthTX II=70.96+/-2.93*) and percent of potassium tubular transport (%TK(+);ct120=66.80+/-3.69; BthTX I=55.76+/-5.57*; BthTX II=50.86+/-6.16*). Indomethacin antagonized the vascular, glomerular and tubular effects promoted by BthTX I and it's partially blocked the effects of BthTX II. In this work also evaluated the antibacterial effects of BthTx-I and BthTx-II against Xanthomonas axonopodis. pv. passiflorae (Gram-negative bacteria) and we observed that both PLA2 showed antibacterial activity. Also we observed that proteins Also we observed that proteins chemically modified with 4-bromophenacyl bromide (rho-BPB) decrease significantly the antibacterial effect of both PLA2. In conclusion, BthTx I and BthTX II caused renal alteration and presented activity antimicrobial. The indomethacin was able to antagonize totally the renal effects induced by BthTx I and partially the effects promoted by BthTx II, suggesting involvement of inflammatory mediators in the renal effects caused by myotoxins. In the other hand, other effects could be independently of the enzymatic activity of the BthTX II and the C-terminal domain could be involved in both effects promoted for PLA2.     

Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom.

We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon.     

Thyroid cancer susceptibility and THRA1 and BAT-40 repeats polymorphisms.

Although genetic and environmental factors have been identified in the etiology of thyroid cancer, the specific genetic implications in sporadic thyroid tumors are poorly understood but, as in other common cancers, low-penetrance susceptibility genes are believed to be crucial in the tumorigenesis processes. Here, we have carried out a case-control study to investigate whether there is an association between THRA1 CA repeat or BAT-40 A repeat polymorphisms and thyroid cancer risk. The THRA1 repeat resides in the thyroid hormone receptor-alpha1 gene, which is associated with thyroid cancer and whose expression depends on the THRA1 repeat size. We also analyzed the BAT-40 repeat that maps to chromosome 1, a region known to be involved in thyroid cancer. This repeat is located in the 3-beta-hydroxysteroid dehydrogenase gene that is associated with prostate cancer susceptibility. The THRA1 repeat was genotyped in 212 thyroid cancer patients and 141 controls of a Spanish population. From these individuals, 207 patients and 138 controls were also analyzed for the BAT-40 marker. No significant difference in the THRA1 allele distribution between patients and controls was found, although short alleles (<128 bp) might have some protective effect on thyroid cancer risk of carriers (odds ratio, 0.50; 95% confidence interval, 0.22-1.13; P = 0.094). By contrast, the BAT-40 allele distribution in patients was significantly different with respect to control (P = 0.035). Essentially, the difference were found in the genotypes involving the 111- to 115-bp allele range, which seem to be associated with a protective effect on thyroid cancer susceptibility in the studied population (odds ratio, 0.18; 95% confidence interval, 0.01-0.57; P = 0.02). Therefore, our results indicate that the BAT-40 containing region and to a less extend the thyroid hormone receptor-alpha1 gene are related to thyroid cancer susceptibility. To our knowledge, this is the first study reporting the identification of genetic factors for thyroid cancer susceptibility.     

Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-).

PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics. EXPERIMENTAL DESIGN: Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated). RESULTS: After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively. CONCLUSION: According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.     

Genotoxicity testing of the furylethylene derivative 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene in cultured human lymphocytes.

The genotoxic potential of the compound 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene (G-1) was evaluated in peripheral blood lymphocytes cultured in vitro, at concentrations ranging from 1 to 20 microg/ml. Micronuclei (MN) and sister-chromatid exchanges (SCE) were scored as biomarkers of genotoxic effects. To detect the role of metabolic enzymes on the genotoxicity of this furylethylenic derivative, cultures for MN and SCE demonstrations were treated for 3 h with and without the S9 microsomal fraction as well as for 48 h without S9. Under the conditions of the study, the test agent did not induce significant increases in the frequency of micronucleated cells, irrespective of the presence/absence of the metabolic fraction. Nevertheless, a slight/moderate increase in the SCE frequency was observed in those cultures treated without the S9 mix. In addition, cytotoxic/cytostatic effects of the G-1 compound were observed mainly in cultures without S9 fraction, as indicated by the reduction of cell proliferation measured by the cytokinesis block proliferation index (CBPI) and the proliferative rate index (PRI).     

Nasal endoscopic and CT scan alterations of the paranasal sinuses as predictors of severity in patients with cystic fibrosis

Cystic Fibrosis (CF) results from mutation in the transmembrane conductance regulator gene, responsible for controlling secretory processes. The upper airways (UA) are usually involved in the form of chronic pansinusitis.ObjectiveTo evaluate UA changes in patients with CF and to establish the correlations between sinonasal CT and endoscopic endonasal findings and disease severity.MethodCross-sectional and prospective study with 20 patients older than 5 years with CF, assessing the Shwachman-Kulczycki (S-K) score, paranasal sinus tomography (CT) (Lund-Mackay score) and nasal endoscopy (Meltzer score).ResultsCT scan alterations were observed in 94% of cases. Endoscopic alterations findings in the upper airways were found in 10 patients. Nasal polyps were found in 3 patients (15%). There was a correlation between the intensity of changes on the CT and S-K score (p = 0.0097), and between endoscopic findings and S-K score (p = 0.0318). There was a positive correlation between the presence of chronic colonization and endoscopic findings (p = 0.0325), which was not observed on the CT (p = 0.2941).ConclusionThere is an inverse correlation between the S-K clinical score and nasal endoscopy and CT findings. Therefore, patients who are clinically more severe according to the S-K score have greater UA involvement.