Long-term in vivo degradation of Mg-Zn-Ca elastic stable intramedullary nails and their influence on the physis of juvenile sheep.

The use of bioresorbable magnesium (Mg)-based elastic stable intramedullary nails (ESIN) is highly promising for the treatment of pediatric long-bone fractures. Being fully resorbable, a removal surgery is not required, preventing repeated physical and psychological stress for the child. Further, the osteoconductive properties of the material support fracture healing. Nowadays, ESIN are exclusively implanted in a non-transphyseal manner to prevent growth discrepancies, although transphyseal implantation would often be required to guarantee optimized fracture stabilization. Here, we investigated the influence of trans-epiphyseally implanted Mg-Zinc (Zn)-Calcium (Ca) ESIN on the proximal tibial physis of juvenile sheep over a period of three years, until skeletal maturity was reached. We used the two alloying systems ZX10 (Mg-1Zn-0.3Ca, in wt%) and ZX00 (Mg-0.3Zn-0.4Ca, in wt%) for this study. To elaborate potential growth disturbances such as leg-length differences and axis deviations we used a combination of in vivo clinical computed tomography (cCT) and ex vivo micro CT (µCT), and also performed histology studies on the extracted bones to obtain information on the related tissue. Because there is a lack of long-term data regarding the degradation performance of magnesium-based implants, we used cCT and µCT data to evaluate the implant volume, gas volume and degradation rate of both alloying systems over a period of 148 weeks. We show that transepiphyseal implantation of Mg-Zn-Ca ESIN has no negative influence on the longitudinal bone growth in juvenile sheep, and that there is no axis deviation observed in all cases. We also illustrate that 95 % of the ESIN degraded over nearly three years, converging the time point of full resorption. We thus conclude that both, ZX10 and ZX00, constitute promising implant materials for the ESIN technique.

Successful endovascular repair of acute type B aortic dissection in undiagnosed Ehlers-Danlos syndrome type IV.

A 61-year-old man presented with an acute type B aortic dissection for which a stent-graft was introduced. He remains complication-free 4 years onwards and has since been diagnosed with Ehlers-Danlos syndrome type IV (EDS IV). His particular mutation is predicted to result in lesser levels of normal collagen and may explain his favourable outcome from endovascular intervention. Understanding the genotype-phenotype correlation may influence the choice of therapy offered to patients with EDS IV.

Cyclosporin A and therapeutic plasma exchange in the treatment of severe systemic lupus erythematosus.

Despite treatment with intensive immunosuppressive drug regimens, often the prognosis of patients suffering from systemic lupus erythematosus (SLE) is poor. Side effects such as infections and malignancies often occur. It was the aim of this trial to assess the effect of immunosuppression, in particular with cyclosporin, and the efficacy, safety, and clinical utility of intermittent treatment with therapeutic plasma exchange (TPE) in comparison to previous intensive therapy strategies using corticosteroids, azathioprine, and/or cyclophosphamide. In this prospective trial, 28 patients (24 women, 4 men, aged 36.3 +/- 11.8 years at the diagnosis of SLE) were treated for up to 10 years with drug regimens out of corticosteroids, azathioprine, and/or cyclophosphamide. Then, over a period of up to 8 years, in addition to conventional therapies, especially in active stages of the disease with extremely high concentrations of anti-DNA, anti-nuclear antibodies, and circulating immunocomplexes, TPE sessions were carried out depending on symptomatology. In addition, the patients received cyclosporin. Compared with previous treatment modalities, clinical symptoms improved more quickly and more effectively. During the study period of a mean of 5 years, corticosteroids, azathioprine, and cyclophosphamide were reduced by 40 to 100%. No severe side effects were seen. In acute stages of SLE and in forms with persistently high antibody levels, the addition of TPE sessions and cyclosporin as the basic immunosuppressive drug is mostly very effective with regard to improving clinical symptomatology.

Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene.

Ehlers-Danlos syndrome (EDS) type VIIC is a recessively inherited connective-tissue disorder, characterized by extreme skin fragility, characteristic facies, joint laxity, droopy skin, umbilical hernia, and blue sclera. Like the animal model dermatosparaxis, EDS type VIIC results from the absence of activity of procollagen I N-proteinase (pNPI), the enzyme that excises the N-propeptide of type I and type II procollagens. The pNPI enzyme is a metalloproteinase containing properdin repeats and a cysteine-rich domain with similarities to the disintegrin domain of reprolysins. We used bovine cDNA to isolate human pNPI. The human enzyme exists in two forms: a long version similar to the bovine enzyme and a short version that contains the Zn++-binding catalytic site but lacks the entire C-terminal domain in which the properdin repeats are located. We have identified the mutations that cause EDS type VIIC in the six known affected human individuals and also in one strain of dermatosparactic calf. Five of the individuals with EDS type VIIC were homozygous for a C-->T transition that results in a premature termination codon, Q225X. Four of these five patients were homozygous at three downstream polymorphic sites. The sixth patient was homozygous for a different transition that results in a premature termination codon, W795X. In the dermatosparactic calf, the mutation is a 17-bp deletion that changes the reading frame of the message. These data provide direct evidence that EDS type VIIC and dermatosparaxis result from mutations in the pNPI gene.

The deletion of six amino acids at the C-terminus of the alpha 1 (II) chain causes overmodification of type II and type XI collagen: further evidence for the association between small deletions in COL2A1 and Kniest dysplasia.

We have identified an 18 bp deletion in exon 49 of the type II procollagen gene (COL2A1) in a patient with Kniest dysplasia. The deletion is located at the very C-terminus of the helical domain and removes two of three Gly-Pro-Pro triplets at positions 1007-1012, which are thought to be involved in helix formation and stability. Morphological investigation of an iliac crest biopsy showed large inclusions in the endoplasmic reticulum of chondrocytes, reflecting impaired secretion of type II collagen. Electrophoretic analysis of collagens extracted from cartilage or synthesised by cultured chondrocytes showed that type II and also type XI procollagen molecules containing mutant alpha 1 (II) chains showed post-translational overmodification. These observations provide further evidence for the general association of Kniest dysplasia with small deletions in the helical domain of type II collagen.

Non-radioactive multiplex-SSCP analysis: detection of a new type II procollagen gene (COL2A1) mutation.

We have developed a protocol that allows fast and efficient mutation screening of the 54 exons from the type II procollagen (COL2A1) gene. The protocol is based on the multiple non-radioactive hybridization of blotted single-strand conformation polymorphism gels. Using this screening procedure we have been able to identify a new (Gly895 to Ser) mutation in the COL2A1 gene of a patient with a mild form of spondyloepiphyseal dysplasia congenita.

Autosomal dominant spondylarthropathy due to a type II procollagen gene (COL2A1) point mutation.

Osteoarthrosis represents a very common disease with heterogeneous etiology. In some pedigrees linkage of the condition with the type II collagen gene (COL2A1) has been established, but information on the underlying gene defect is still incomplete as only one mutation causing this phenotype has been identified. We analyzed the COL2A1 gene in a 27-year-old woman and her 47-year-old mother presenting with severe premature osteoarthrosis and X-ray signs compatible with mild spondyloepiphyseal dysplasia. Examination of the complete gene in both patients was done by amplification of all 54 exons, screening of the PCR products by SSCP-analysis, and subsequent sequencing. In mother and daughter a G to A transition at the 5'-end of exon 21 was detected, leading to a substitution of serine for glycine at position 274 of the triple helical domain. The mutation was not present in unaffected family members or in healthy control individuals. The autosomal dominant spondylarthropathies may represent the less severe entities of the clinical spectrum of type II collagenopathies.

Kniest and Stickler dysplasia phenotypes caused by collagen type II gene (COL2A1) defect.

Kniest and Stickler dysplasia are two chondrodysplasias characterized by specific phenotypes. No basic defect has been found in patients with Kniest dysplasia, whereas Stickler dysplasia is one of four chondrodysplasias for which mutations of type II procollagen gene (COL2A1) have been identified. We studied a 2-year-old girl presenting with manifestations of Kniest dysplasia and her mother showing a Stickler phenotype. Analysing COL2A1 in both patients, we detected the same 28 basepair deletion spanning the 3'-exon/intron boundary of exon 12 in mother and daughter. We were able to prove a somatic mosaic status for this mutation in the mother which accounts for her milder Stickler-like phenotype.

[Retinoschisis with a giant central outer layer retinal tear and concomitant detachment]. / Retinoschisis mit zentral gelegenem Aussenschichtriesenriss und Begleitamotio.

The authors report on 2 cases with a special form of senile retinoschisis with retinal detachment. In both cases, a typical retinoschisis was combined with a giant tear of the outer retinal layer and a sickle-shaped retinal detachment extending almost to the macula. In contrast to previously published cases, which were treated by a conventional scleral buckling procedure or vitrectomy with fluid air exchange, it was decided to demarcate the retinal detachment by argon laser photocoagulation. The authors consider this non-invasive procedure sufficiently safe and effective.