Double-guidewire-assisted cannulation in ERCP: novel applications

Even in experienced hands, a common problem at endoscopic retrograde cholangiopancreatography (ERCP) is difficulty in reaching a selective cannulation of the common bile duct or pancreatic duct. The success rate of biliary cannulation has improved markedly in many centers after the adoption of double-guidewire-assisted cannulation technique in cases in which the guidewire repeatedly passes into the pancreatic duct although the common bile duct is intended. Here, we describe 2 novel applications of the double-guidewire technique for difficult cannulation in ERCP. In particular, we emphasize that in addition to difficult biliary cannulation, double-guidewire technique may prove useful in difficult pancreatic cannulation. The double-guidewire technique is feasible also in cases in which the guidewire repeatedly passes into the cystic duct instead of the intended common hepatic duct and intrahepatic radicals. ERCP endoscopists should be aware of all modifications of double-guidewire technique to further increase the success rates of selective cannulations in ERCP.     

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.     

Neuropeptide Y and Y2‐receptor are involved in development of diabetic retinopathy and retinal neovascularization

BACKGROUND: Neuropeptide Y is a sympathetic neurotransmitter, a potent endothelium‐derived angiogenic factor and a vascular mitogen. We have studied the role of the functional leucine7 to proline7 polymorphism of the signal peptide region of preproneuropeptide Y (prepro‐NPY) as a genetic susceptibility factor for diabetic retinopathy. In addition, we investigated the role of the NPY Y2‐receptor as a putative mediator of angiogenic NPY signaling in the retina.

METHODS: Frequencies of proline7 (Pro7) carriers in the prepro‐NPY were determined in type 1 and type 2 diabetes patients having retinopathy, in type 2 diabetes patients without retinopathy and in healthy control subjects. The role of Y2‐receptor in hyperoxemia‐induced retinal neovascularization was investigated in Y2‐receptor knockout mice (Y2 ^?/? ) and in rats administered Y2‐receptor mRNA antisense oligonucleotide.

RESULTS: The carriers having Pro7 in the preproNPY are markedly over‐represented among type 2 diabetes patients with retinopathy compared to type 2 diabetes patients without retinopathy and to the population control. Neonatal exposure to hyperoxia resulted in development of retinal neovascularization that was prevented in Y2 ^?/? ‐mice, and significantly inhibited in rats treated with the Y2‐receptor antisense oligonucleotide.

CONCLUSIONS: NPY and Y2‐receptor play important roles in diabetic retinopathy and retinal neovascularization and are thus potential new targets for drug molecules for treatment of retinopathy.     

Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity

Despite recent advances in cancer therapy, many malignant tumors still lack effective treatment and the prognosis is very poor. Paclitaxel is a potential anticancer drug, but its use is limited by the facts that paclitaxel is a P-gp substrate and its aqueous solubility is poor. In this study, three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology was evaluated in vitro as a way of enhancing delivery of paclitaxel. Paclitaxel was incorporated both in biotinylated (BP) and non-biotinylated (LP) PEG-PLA nanoparticles by the interfacial deposition method. Small (mean size approximately 110nm), spherical and slightly negatively charged (-10mV) BP and LP nanoparticles achieving over 90% paclitaxel incorporation were obtained. The successful biotinylation of nanoparticles was confirmed in a novel streptavidin assay. BP nanoparticles were targeted in vitro to brain tumor (glioma) cells (BT4C) by three-step avidin-biotin technology using transferrin as the targeting ligand. The three-step targeting procedure increased the anti-tumoral activity of paclitaxel when compared to the commercial paclitaxel formulation Taxol((R)) and non-targeted BP and LP nanoparticles. These results indicate that the efficacy of paclitaxel against tumor cells can be increased by this three-step targeting method.     

Risk factors for poor tuberculosis treatment outcome in Finland: a cohort study

Background  

We investigated the patient- and treatment-system dependent factors affecting treatment outcome in a two-year cohort of all treated culture-verified pulmonary tuberculosis (TB) cases to establish a basis for improving outcomes.     

Sampling rate causes bias in APACHE II and SAPS II scores

OBJECTIVE: To study the effect of sampling rate of laboratory and haemodynamic data on severity scorings and predicted risk of hospital death. DESIGN: Prospective study. SETTING: Medical-surgical intensive care unit (ICU) with 23 beds in a university hospital. PATIENTS: Sixty-nine consecutive emergency admission patients. INTERVENTIONS: Blood samples were drawn from indwelling arterial lines for the laboratory tests of all variables contained in the APACHE II and SAPS II scores at 2-hourly intervals from the time of admission up to 24 h or earlier discharge or death of the patient. Haemodynamic data and temperature were collected either manually by the attending nurse once an hour or as 2-min median values automatically using a Clinical Information Management System (CIMS, Clinisoft, Datex-Ohmeda, Helsinki, Finland). Three sets of severity scores were obtained. (1) "Traditional" scores (haemodynamic data from manual records and laboratory values from tests taken at admission and subsequently on clinical basis only). (2) "CIMS" scores (haemodynamic data from 2-min median values and laboratory values prescribed on clinical indication) and (3) "High rate" scores (haemodynamic data from 2-min median values and laboratory values at 2-hourly intervals). Probability of hospital death was calculated using the SAPS II and APACHE II scores, respectively. RESULTS: Increasing the sampling rate of haemodynamic monitoring interval to 2-min from once per hour resulted in 7.8 % and 11.5 % increases (p < 0.001) in the APACHE II and SAPS II scores, respectively. The combined effect of increased sampling rate of haemodynamic and laboratory tests on the APACHE II and SAPS II scores was 14.4 % and 14.5 % compared to traditional scores (p < 0.001), respectively. The probability of hospital death increased from 0.23 and 0.21 ("traditional" SAPS II and APACHE II) to 0.31 and 0.25 ("high rate" SAPS II and APACHE II), respectively, and, because eight patients died, standardised mortality ratio (SMR) decreased from 0.53 to 0.41 (SAPS II) and from 0.60 to 0.50 (APACHE II). CONCLUSIONS: Increased sampling rate results in higher scores and lower SMR. Comparisons between hospitals using severity scores are biased due to differences in the sampling rates.     

The cochlear nerve in various forms of deafness

Operative specimens of cochlear nerve of 56 patients with profound deafness of varying origin were examined under the light microscope and the number of myelinated nerve fibers in each specimen was counted. The transverse fascicular area of each nerve was also determined. When the resulting neuron populations were evaluated with regard to the cochlear implant program the only truly unsuitable ears for artificial stimulation were found to be those with cholesteatoma involving the cochlear nerve and ears with local pathology in the internal auditory canal severe enough to cause atrophy of the cochlear nerve.     

Functional and morphological effects of styrene on the auditory system of the rat

The effect of inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600, 300 or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks). Auditory sensitivity was tested prior to and after the exposure by auditory brain stem audiometry (ABR) at frequencies of 1.0, 2.0, 4.0 and 8.0 kHz. Inner ear morphological changes were studied by light- and electron-microscopy. Exposure to 600 ppm styrene caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed that 600 ppm styrene caused a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. The inner hair cells were usually intact. Exposure to lower styrene concentrations (100 and 300 ppm) caused no unequivocal functional deficit or hair cell damage. We conclude that there appears to be a concentration threshold for styrene ototoxicity in rats (between 300 and 600 ppm).