Radical resection of hilar bile duct carcinoma and predictors of survival

BACKGROUND: Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection. METHODS: A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone. RESULTS: The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis. CONCLUSION: This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.     

Influx and efflux transport of H1-antagonist epinastine across the blood-brain barrier.

We investigated influx and efflux transporters involved in blood-brain barrier transport of the nonsedative H1-antagonist epinastine. The basal-to-apical transport of [14C]epinastine was markedly higher than that in the opposite direction in LLC-GA5-COL150 cells stably transfected with human multidrug resistance (MDR)1 gene. The brain-to-plasma concentration ratio of [14C]epinastine in mdr1a/b(-/-) mice was 3.2 times higher than that in wild-type mice. The uptake of both [3H]mepyramine and [14C]epinastine into immortalized rat brain capillary endothelial cells (RBEC)1 showed temperature and concentration dependence. The kinetic parameters, K(m), V(max), and uptake clearance (V(max)/K(m)), of the initial uptake of [3H]mepyramine and [14C]epinastine by RBEC1 were 150 microM, 41.8 nmol/min/mg protein, and 279 microl/min/mg protein for mepyramine and 10.0 mM, 339 nmol/min/mg protein, and 33.9 microl/min/mg protein for epinastine, respectively. The uptake of [3H]mepyramine and [14C]epinastine by RBEC1 was inhibited by organic cations such as quinidine, amantadine, and verapamil, but not by other organic cations, tetraethyl ammonium, guanidine, and carnitine. Organic anions such as benzoic acid, estrone-3-sulfate, taurocholate, and neutral digoxin were not inhibitory. Furthermore, some cationic H1 antagonists (chlorpheniramine, cyproheptadine, ketotifen, and desloratadine) inhibited the [3H]mepyramine and [14C]epinastine uptake into RBEC1. In conclusion, the present study demonstrated that the combination of efficient efflux transport by P-glycoprotein and poor uptake by the influx transporter, which is identical with that responsible for the uptake of mepyramine, account for the low brain distribution of epinastine.     

Morvan Syndrome Converted from Isaacs' Syndrome after Thymectomy with Positivity for Both Anti-LGI1 and Anti-CASPR2 Antibodies

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs'' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs'' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs'' syndrome, suggesting that immunotherapy should be considered for Isaacs'' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.     

Determination of paroxetine in human saliva by reversed-phase high-performance liquid chromatography with UV detection.

A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of paroxetine in human saliva. Following liquid-liquid extraction of the drug and an internal standard (dibucaine), chromatographic separation was accomplished using a C18 analytical column with a mobile phase consisting of 0.05 mol/L sodium phosphate buffer, pH 5.0, and acetonitrile (A 30:70, v/v; B 60:40, v/v). Paroxetine and the internal standard were detected by ultraviolet absorbance at 205 nm. The average recoveries of the drug and internal standard were 92.5% and 89%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curve was linear over a concentration range of 4 ng/ml. The saliva level of paroxetine in patients with depression taking 10 to 40 mg/day of the drug was significantly correlated with the plasma level of paroxetine in each patient (r = 0.617, P < 0.004, n = 19). These data indicate that the saliva level of paroxetine could be a useful marker to predict the plasma level of the drug.     

Massive cystic lymphangiomas of a fetus

We present a fetus with progressive massive subcutaneous lymphangiomas leading to intrauterine death. A 28-year-old woman was referred to our hospital because of a precordial cystic mass of the fetus. An ultrasound revealed lymphangiomas extending from bilateral axillae to the anterior chest wall. At 18 weeks' gestation, amniocentesis was performed and the karyotype of the fetus was found to be normal 46, XY. Thereafter the lesions increased in size gradually and spread over the body. Amniotic fluid decreased, pericardial, and pleural effusion appeared, and cardiomegaly became evident. The fetus died in utero at 25 weeks' gestation. Postmortem examination revealed a male fetus surrounded with multicystic soft masses spreading over the body, and syndactyly (left third and fourth fingers) was present. Histologically, a number of irregularly dilated lymphatics extended through subcutaneous tissues to the skeletal muscles. No communications between the cysts and the thoracic or abdominal cavity existed, and no lymphatic dilations in the viscera were confirmed. As far as we know, such conditions have rarely been reported. Considering that in previous literature, a favorable prognosis of a fetus with an atypically located (lateral cervical or non-cervical) lymphangioma with a normal karyotype has been reported, our case may be included in a distinct pathological entity. When we find a lymphangioma in a fetus, careful follow-up by ultrasound is mandatory.     

Hancornia speciosa: indications of gastroprotective, healing and anti-Helicobacter pylori actions

Ethnopharmacological relevance

Mangaba (Hancornia speciosa Gomez) is a medicinal plant frequently cited in ethnopharmacological inventories of the central region of Brazil against gastrointestinal disorders such as diarrhoea, ulcer, gastritis and stomachache.

Aim of the study

The hydroalcoholic extract (HE) and infusion (BI) of Hancornia speciosa bark were investigated for their ability to prevent and heal rodent gastric ulcer.

Materials and methods

The preventive and healing action of both preparations of Hancornia speciosa were evaluated in experimental models in rodents that simulated this disease in human gastric mucosa.

Results

BI did not exert gastroprotective effect, in contrast to HE (500 mg/kg, p.o.) that decreased (p < 0.05) the severity of gastric damage induced by HCl/ethanol (52%), indomethacin/bethanechol (51%), stress (52%) or pylorus ligature experiments (54%). HE increased (p < 0.05) the pH and decreased acid output of gastric juice. This extract promoted increase of mucus amount (3.62 mg/wt. tissue vs. 5.81 mg/wt. tissue), healing action (67%) and displayed anti-Helicobacter pylori effect.

Conclusions

The antiulcer action of Hancornia speciosa resulted in increase of gastric mucus formation and antioxidant properties of polymeric proanthocyanidins present in the bark composition of this medicinal plant.     

Molecular diversity of TEX101, a marker glycoprotein for germ cells monitored with monoclonal antibodies: variety of the molecular characteristics according to subcellular localization within the mouse testis

TEX101 was characterized as a unique germ cell marker molecule using the specific monoclonal antibody (mAb), TES101. Although this mAb has strong affinity/specificity for TEX101, TES101 mAb loses its reactivity under reducing conditions. In this study, we have generated new mAbs against TEX101 to compensate for the shortcomings of the TES101 mAb using different approaches. First, we immunized mice with the antigen on a baculovirus expression system and isolated new anti-TEX101 mAbs, 6002 and 6035. Second, we raised the mAb Ts4 from spleen cells of an immunologically naive old mouse. Western blot analysis revealed that the new mAbs possess immunoreactivity under reducing/non-reducing conditions. Immunopositive staining of the mAbs against Bouin-fixed sections was observed in spermatocytes, spermatids and testicular spermatozoa, but not in other cells, similar to paraformaldehyde (PFA)-fixed frozen sections stained with TES101 as previously reported. However, whereas the mAbs 6002/6035 mainly showed immunoreactivity only in spermatocytes in PFA-fixed frozen sections, the reactivity of the mAbs to spermatids and testicular spermatozoa was clearly recovered when the PFA-fixed sections were autoclaved or treated with SDS. Peptide mapping and deglycosylation analysis indicated that the epitopes for TES101, 6002 and 6035 are located within TEX101(25-94), whereas Ts4 recognized N-linked carbohydrate moieties on TEX101 in Triton X-100-soluble mouse testicular extracts but not in the extracellular or water-soluble fractions. These results suggest strongly that the molecular association or structure of N-linked carbohydrate moieties of TEX101 varies according to its subcellular localization within the seminiferous tubules. These new mAbs will be valuable tools for further analysis of TEX101, including its function(s).