Low-field Mri and arthroscopy of meniscal lesions in ten dogs with experimentally induced cranial cruciate ligament insufficiency

Little is known about the magnetic resonance imaging (MRI) appearance of canine meniscal lesions. The aim of this study is to describe the MR appearance of meniscal lesions in dogs with experimentally induced cranial cruciate ligament (CCL) deficiency. The pilot study revealed dogs weighing approximately 10 kg to be too small for meniscal evaluation on low-field MRI. In the main study, dogs weighing approximately 35 kg were used. The left CCL was transected and low-field MRI was performed regularly until 13 months post-surgery. Normal menisci were defined as grade 0. Intrameniscal lesions not reaching any surface corresponded to grade 1 if focal and to grade 2 if linear or diffuse. Grade 3 lesions consisted in linear tears penetrating a meniscal surface. Grade 4 lesions included complex signal changes or meniscal distortion. Between 2 and 13 months post-surgery, all dogs developed grade 4 lesions in the medial meniscus. Most of them corresponded to longitudinal or bucket handle tears on arthroscopy and necropsy. Two dogs showed grade 3 lesions reaching the tibial surface of the lateral meniscus on MRI but not in arthroscopy. Such tears are difficult to evaluate arthroscopically; MRI provides more accurate information about the tibial meniscal surface. Grades 1 and 2 lesions could not be differentiated from presumably normal menisci with our imaging technique. An MRI grading system better adapted to canine lesions has yet to be developed. MRI is a helpful tool for the diagnosis of complete tears in the canine meniscus, especially in larger dogs.

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.