Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.     

Carrier-mediated transport in the hepatic distribution and elimination of drugs, with special reference to the category of organic cations

Carrier-mediated transport of drugs occurs in various tissues in the body and may largely affect the rate of distribution and elimination. Saturable translocation mechanisms allowing competitive interactions have been identified in the kidneys (tubular secretion), mucosal cells in the gut (intestinal absorption and secretion), choroid plexus (removal of drug from the cerebrospinal fluid), and liver (hepatobiliary excretion). Drugs with quaternary and tertiary amine groups represent the large category of organic cations that can be transported via such mechanisms. The hepatic and to a lesser extent the intestinal cation carrier systems preferentially recognize relatively large molecular weight amphipathic compounds. In the case of multivalent cationic drugs, efficient transport only occurs if large hydrophobic ring structures provide a sufficient lipophilicity-hydrophilicity balance within the drug molecule. At least two separate carrier systems for hepatic uptake of organic cations have been identified through kinetic and photoaffinity labeling studies. In addition absorptive endocytosis may play a role that along with proton-antiport systems and membrane potential driven transport may lead to intracellular sequestration in lysosomes and mitochondria. Concentration gradients of inorganic ions may represent the driving forces for hepatic uptake and biliary excretion of drugs. Recent studies that aim to the identification of potential membrane carrier proteins indicate multiple carriers for organic anions, cations, and uncharged compounds with molecular weights around 50,000 Da. They may represent a family of closely related proteins exhibiting overlapping substrate specificity or, alternatively, an aspecific transport system that mediates translocation of various forms of drugs coupled with inorganic ions. Consequently, extensive pharmacokinetic interactions can be anticipated at the level of uptake and secretion of drugs regardless of their charge.     

Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo.

The effects of human recombinant plasminogen activator inhibitor (rPAI-1) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were studied in a rabbit model of jugular vein thrombosis. Two functionally distinct rPAI-1 preparations were used in these experiments, including latent rPAI-1 (approximately 2 units of t-PA neutralizing activity per micrograms protein) and reactivated rPAI-1 (approximately 150 units/micrograms). Simultaneous intravenous infusion over 4 h of 1.7 mg/kg of reactivated rPAI-1 (inhibitory capacity approximately 0.5 mg/kg rt-PA) with 0.5 mg/kg of rt-PA completely prevented lysis of a jugular venous thrombus, whereas an equivalent amount of latent PAI-1 did not significantly influence clot lysis. These findings demonstrate that reactivated human rPAI-1 efficiently neutralizes thrombolysis with rt-PA in vivo. Since previous studies have suggested that elevated endogenous levels of PAI-1 do not attenuate the thrombolytic potency of rt-PA in the endotoxin-treated model, we compared the stability of complexes formed by 125I-rt-PA with reactivated human rPAI-1 and with rabbit PAI-1 in vitro. Our findings indicate that both forms of PAI-1 form SDS-stable complexes following incubation with 125I-rt-PA. Thus, it seems likely that elevated levels of active PAI-1 can negate the thrombolytic effects of rt-PA in vivo and argues against the possibility that t-PA can dissociate from PAI-1 and have its activity restored in the presence of a thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)     

The imaging quality of angiodynography in the ilio-femoral tract

The imaging quality of angiodynography (Quantum; Philips) in the ilio-femoral tract was compared with uniplanar angiography. One hundred ilio-femoral tracts were investigated with both translumbar conventional angiography and angiodynography. The ilio-femoral tract was divided into five parts; proximal and distal common iliac, proximal and distal external iliac and common femoral. Stenosis was scored from 0-24, 25-49, 50-74, 75-99 and 100% and the lengths of those of 25% or more were measured in centimeters. Because the thickness of the subcutaneous fat layer decreases the depth range (normally 11.5 cm) of the 5.0 MHz transducer it was also measured in centimetres. The results showed that a significantly larger number of vessels were not seen (especially the common iliac) with an increasing thickness of the subcutaneous fat. The results based on the real-time imaging quality alone of angiodynography showed a reasonable accuracy of 83.9% when detecting stenoses graded from 0-24, 25-49, 50-74, 75-99 up to 100%. The clinically more important discrimination between a haemodynamically important stenosis of more than 50% showed a sensitivity of 88% and specificity of 98% on visual information alone. By integrating the peak velocity measurements to the results, this sensitivity rose to 95% and the specificity became 99%. The correlation in length was within a range of 1 cm in 94% and within 1-2 cm in 6% of the stenoses. In conclusion, angiodynography is a reliable technique for investigating the ilio-femoral tract.     

Hepatic transport mechanisms for bivalent organic cations. Subcellular distribution and hepato-biliary concentration gradients of some steroidal muscle relaxants

In order to characterize the hepato-biliary transport of bivalent cations in more detail, the subcellular distribution of three steroidal muscle relaxants, that differ physicochemically and kinetically, was studied by differential centrifugation of liver homogenates. Binding of the muscle relaxants to macromolecular compounds was measured in Krebs-albumin solution, in cytosolic fraction of liver homogenate and in bile, to estimate the unbound concentrations in the particular fluids. Cytosol/plasma concentration ratios increased in the order pancuronium less than Org 6368 less than vecuronium, but for all of the compounds did not exceed the value that would be attained by passive equilibration according to the membrane potential. The subcellular distribution patterns of the three substances indicated that the mitochondrial fraction is a major storage compartment in the liver. Yet Org 6368 was bound to the particulate fraction of liver homogenate to a larger extent than pancuronium and vecuronium. The high bile/cytosol concentration ratios indicate that for all of these cations an active transport system is involved in the biliary excretion process. For Org 6368 and vecuronium the bile/cytosol concentration ratios are in the same range (about 30) and substantially higher than for pancuronium (about 6). This suggests that for Org 6368 and vecuronium the transport across the canalicular membrane is more efficient than for pancuronium. The combined data indicate that the extensive binding of Org 6368 to particles within the cell is a major factor in the relative efficient hepatic uptake and the modest biliary excretion of this agent. The limited hepato-biliary transport of pancuronium appears to be due to a relatively small net transport, both at the sinusoidal land at the canalicular membrane.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Sutureless re-anastomosis by laparoscopy versus microsurgical re-anastomosis by laparotomy for sterilization reversal: a matched cohort study

BACKGROUND: Sutureless re-anastomosis per laparoscopy is an alternative for microsurgical re-anastomosis by laparotomy in the treatment of sterilized women with renewed child wish. Our aim was to compare pregnancy rates after both surgical techniques. METHODS: We performed a retrospective cohort study in which consecutive women who underwent sutureless re-anastomosis per laparoscopy were compared to women who underwent microsurgical re-anastomosis by laparotomy. Both procedures were performed in neighbouring hospitals in Northern-Brabant, The Netherlands, and women were matched for age. The primary outcome was time to ongoing pregnancy. RESULTS: Overall, we included 41 women who had sutureless re-anastomosis by laparoscopy, and 41 age-matched women who underwent microsurgical re-anastomosis by laparotomy. The number of women who conceived was 20 (15 ongoing pregnancies) in the sutureless laparoscopic group versus 26 (24 ongoing pregnancies) in the laparotomic group, a difference due to a longer follow-up period in the laparotomic group. Time to ongoing pregnancy was comparable in both groups (P=0.46), with 3 year cumulative ongoing pregnancy rates of 45 and 52% respectively. After adjustment for other prognostic factors, the fecundity rate ratio was 0.97 (95% CI 0.26-3.6), indicating a similar performance of the two techniques. CONCLUSION: The simplified stitchless laparoscopic procedure for reversal of tubal sterilization with the use of a tubal splint, clip fixation of the muscularis and fibrin glue resulted in a promising pregnancy rate, which was similar to the pregnancy rate obtained with the microsurgical re-anastomosis per laparotomy.