Repeatability of the Oxford Foot Model: Comparison of a team of assessors with different backgrounds and no prior experience of the Oxford Foot Model.

RESEARCH QUESTION: What is the intra- and inter-assessor error of the Oxford Foot Model (OFM) during healthy adult walking when applied by three assessors with different professional backgrounds and lower limb marker placement experience, not native to the originators of the model and with no prior clinical experience of the model? BACKGROUND: No previous OFM studies have examined the repeatability of more than two assessors with different backgrounds, and many of the studies have been conducted by the model originators METHODS: The OFM was applied to ten healthy adults on three separate occasions by three different assessors with varied professional experience and no prior involvement with the OFM (other than local training). Participants walked at self-selected speeds and intra/inter assessor error was calculated using the SEM + 95% upper confidence limit. RESULTS: Inter-assessor errors ranged from 2.2° to 5.5° whereas intra-assessor errors fell between 1.8° and 5.5°. The error difference between assessors over the same joint angle varied from 0.4° (hindfoot/tibia dorsiflexion) to 1.5° (hindfoot/tibia inversion). The percentage of error to total range of motion varied from 11% (hindfoot/tibia dorsiflexion) to 126% (forefoot/hindfoot adduction). SIGNIFICANCE: Based on commonly used recommendations, the OFM is a largely repeatable tool for measuring foot kinematics during healthy adult walking when applied by assessors with no prior OFM experience, varied experience and not native to the model originators. Intra-assessor error was lower for assessors with prior anatomical knowledge and significant lower limb marker placement experience. The proportion of inter-assessor error to movement exceeded 50% of the total range of motion for four movements, notably forefoot/hindfoot adduction (126%). As such, this movement cannot be recommended as an outcome measure. Inter- and intra-assessor error, specific to each laboratory, should be considered, along with the proportion of error to range of motion when interpreting patient data.

['Will I receive a liver transplant in time?'; chance of survival of patients on the liver transplant waiting list]. / 'Komt mijn nieuwe lever wel op tijd?'.

OBJECTIVE: To calculate the chance of receiving a liver transplant for patients on the liver transplant waiting list in the Netherlands. DESIGN: Retrospective cohort research. METHOD: Data of all patients in the Netherlands on the waiting list for liver transplantation, from the introduction of the model of end-stage liver disease score on 16th December 2006 through to 31st December 2013 were collected. Survival analysis was computed with competing risk analyses. RESULTS: A total of 851 patients were listed, of whom 236 patients with hepatocellular carcinoma, 147 patients with primary sclerosing cholangitis, 142 patients with post-alcoholic liver disease, 93 patients with metabolic liver disease, 78 with viral hepatitis and 155 patients listed for other indications. The median waiting time till transplantation was 196 days. The chance to be transplanted at two years from listing was 65% and the risk of death was 17%. Patients with metabolic liver disease had the highest chance of undergoing liver transplantation. Patients with viral hepatitis were at highest risk of death while on the list, as well as having the lowest chance of undergoing liver transplantation. CONCLUSION: Our study shows a 65% chance of getting transplanted in time after a median waiting time of 6 months in the Netherlands. Sadly, 1 in 6 patients die before liver transplantation can be performed, with the highest risk of death occurring in patients with viral hepatitis.

Stereoselective metabolism of tazofelone, an anti-inflammatory bowel disease agent, in rats and dogs and in human liver microsomes.

Incubation of (R)-tazofelone and (S)-tazofelone in rat, dog, and human liver microsomes demonstrated that the (R)-tazofelone enantiomer was more rapidly metabolized, with two diastereomeric sulfoxides as the major metabolites formed in all three species. The two diasteresomers epimerized at physiological pH, therefore total sulfoxide formation rates were measured. The formation of the total sulfoxide metabolites followed Michaelis-Menten kinetics. The K(m), Vmax, and intrinsic formation clearance (Vmax/K(m)) values were determined in rat, dog, and human liver microsomes. The intrinsic formation clearance of sulfoxide from (R)-tazofelone exceeded that of (S)-tazofelone in all three species. In vivo studies in rats and dogs dosed orally and intravenously confirmed the stereoselective metabolism of tazofelone observed in vitro. Plasma concentrations of (S)-tazofelone exceeded (R)-tazofelone in rats and dogs by a factor of 3 to 4. In rat portal plasma, both enantiomers were of approximately equal concentration after oral dosing, indicating similar absorption. The half-lives of tazofelone and total sulfoxides in rats were 3.5 and 2.8 h, respectively. In dogs, the half-lives of tazofelone and total sulfoxides were 2.2 and 5.5 h, respectively. Plasma clearance was 2.3 l/h in rats and 1.4 l/h in dogs, and the volumes of distribution were 12 and 4.5 l, respectively, in rats and dogs. Both enantiomers were highly bound to plasma proteins to a similar extent in both species.

Cytochrome P-450 complex formation by dirithromycin and other macrolides in rat and human livers.

Some macrolide antibiotics cause clinical drug interactions, resulting in altered metabolism of concomitantly administered drugs, via formation of an inactive cytochrome P-450 complex. In the present study, the formation of a cytochrome P-450 type I binding spectrum and a metabolic intermediate complex by troleandomycin and dirithromycin was assessed in liver microsomes obtained from untreated rats and phenobarbital- or dexamethasone-pretreated rats. Troleandomycin produced a type I binding spectrum and metabolic intermediate complex in microsomes from dexamethasone- and phenobarbital-pretreated rats. Dirithromycin did not produce a detectable type I binding spectrum but formed a small cytochrome P-450 metabolic intermediate complex (6% of that formed by troleandomycin) in microsomes from dexamethasone-pretreated rats only. The formation of a cytochrome P-450 type I binding spectrum and a metabolic intermediate complex by troleandomycin, erythromycin, dirithromycin, and erythromycylamine was also assessed in microsomes prepared from human livers. Troleandomycin and erythromycin formed a type I binding spectrum and a metabolic intermediate complex which were larger in microsomes from subjects on barbiturate therapy than in microsomes from subjects with no recent barbiturate exposure. Erythromycylamine did not form a detectable type I binding spectrum with any of the human microsomal samples, but a small metabolic intermediate complex was formed with microsomes from a subject on phenobarbital, phenytoin, and propranolol therapy. Dirithromycin did not form a detectable type I binding spectrum or a metabolic intermediate complex in any human liver sample. Preclinical quantitation of the human metabolic intermediate complex may be helpful in predicting the possibility of clinical drug interactions of new drug candidates.

Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats.

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.

[Idiopathic bi-auricular dilatation manifested by total cardiac failure. Apropos of a case confirmed by nuclear magnetic resonance]. / Dilatation idiopathique bi-auriculaire révélée par une insuffisance cardiaque globale. A propos d'un cas confirmé par la résonance magnétique nucléaire.

Idiopathic bilateral atrial dilatation is extremely rare. We are reporting a case in a 79 year-old patient, presenting a picture of total cardiac insufficiency. The positive diagnosis was established by bi-dimensional sonography and right angiography. Nuclear magnetic resonance confirmed the diagnosis and specified the size of the various cavities. From a rhythm standpoint, there was an atrial fibrillation without conduction disorders. The main factor of the cardiac insufficiency seems to be a low atrio-ventricular output, since the valvular insufficiency due to annular dilatation is only a secondary factor. The etiology is unknown, but a congenital origin seems most probable without excluding the possibility of an acquired structural disorder.

Trichinella isolates from polar bears in Svalbard. Freeze resistance and infectivity in rats and swine.

The author isolated Trichinella strains from five polar bears in Svalbard (the high arctic region of Norway). Based on infectivity experiments with white mice (BOM:NMR), the freeze resistance limits of the Trichinella strains are outlined. Further experiments showed that white rats (MOL:WIST) and pigs (sus scrofa domestica) are almost refractory to these Trichinella strains. The infectivity of Svalbard isolates in the above mentioned test animals was compared, in parallel experiments, with that of T. spiralis (Owen). The latter showed a very high infectivity to the same species of test animals. It is thus probable that the arctic Trichinella found in the polar bear is biologically distinct from both T. spinalis (Owen) and T. nativa ( Britov and Boev ).

[Cesium-137 in soil and vegetation from Spitsbergen and continental Norway (Suldal) 1981]. / Cesium-137 i jord og beiteplanter fra Spitsbergen og fastlands- Norge (Suldal) 1981.

Concentration of Cesium-137 in samples of soil and vegetation from Spitsbergen (Svalbard) and Suldal (Western-Norway) has been measured. The results indicate that different diets can account for the large difference (1:100), in Cesium-137 concentration in reindeer meat from Spitsbergen and mainland Norway.

[Caesium 137 in meat from reindeer and grouse from Svalbard 1980 (author's transl)]. / Cesium 137 i kjøtt fra reinsdyr og ryper på Svalbard 1980.

Concentration of Caesium 137 in meat from Spitsbergen (Svalbard) and mainland Norway reindeer has been measured. It appears that the concentration values for Spitsbergen are of the order of 1 per cent of corresponding values for the mainland. It is suggested that low precipitation rates and a different reindeer diet contributes to the low Cs 137 concentration values in Svalbard. The concentration of Cs 137 in Svalbard grouse did not exceed the detection limit of the measurements (infinity 10 pCi/kg).