Frequency of severe pulmonary hypertension complicating "isolated" atrial septal defect in infancy

Atrial septal defects (ASDs) are typically asymptomatic in infancy and early childhood, and elective defect closure is usually performed at ages of 4 to 6 years. Severe pulmonary hypertension (PH) complicating an ASD is seen in adulthood and has only occasionally been reported in small children. A retrospective study was undertaken to evaluate the incidence of severe PH complicating an isolated ASD and requiring early surgical correction. During a 10-year period (1996 to 2006), 355 pediatric patients underwent treatment for isolated ASDs either surgically or by catheter intervention at 2 tertiary referral centers. Two hundred ninety-seven patients had secundum ASDs, and 58 had primum ASDs with mild to moderate mitral regurgitation. Eight infants were found with isolated ASDs (6 with secundum ASDs and 2 with primum ASDs) associated with significant PH, accounting for 2.2% of all patients with ASDs at the centers. These 8 infants had invasively measured pulmonary artery pressures of 50% to 100% of systemic pressure. They were operated in the first year of life and had complicated postoperative courses requiring specific treatment for PH for up to 16 weeks postoperatively. The ultimate outcomes in all 8 infants were good, with persistent normalization of pulmonary pressures during midterm follow-up of up to 60 months (median 28). All other patients with ASDs had normal pulmonary pressures, and the mean age at defect closure was significantly older, at 6.2 years for secundum ASDs and 3.2 years for primum ASDs. In conclusion, ASDs were rarely associated with significant PH in infancy but then required early surgery and were associated with excellent midterm outcomes in these patients.

Evidence of a Generalized Defect of Acinar Cell Function in Shwachman-Diamond Syndrome

: Because the acinar cells of the exocrine pancreas in patients with Shwachman-Diamond syndrome (SDS) are severely depleted, we hypothesized that a similar deficiency may be present in acinar cells of the parotid gland.

The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds

We investigated the inflammatory response to, and the osteoinductive efficacies of, four polymers (collagen, Ethisorb, PLGA and Polyactive) that bore either an adsorbed (fast-release kinetics) or a calcium-phosphate-coating-incorporated (slow-release kinetics) depot of BMP-2. Titanium-plate-supported discs of each polymer (n = 6 per group) were implanted at an ectopic (subcutaneous) ossification site in rats (n = 48). Five weeks later, they were retrieved for a histomorphometric analysis of the volumes of ectopic bone and foreign-body giant cells (a gauge of inflammatory reactivity), and the degree of polymer degradation. For each polymer, the osteoinductive efficacy of BMP-2 was higher when it was incorporated into a coating than when it was directly adsorbed onto the material. This mode of BMP-2 carriage was consistently associated with an attenuation of the inflammatory response. For coated materials, the volume density of foreign-body giant cells was inversely correlated with the volume density of bone (r(2) = 0.96), and the volume density of bone was directly proportional to the surface-area density of the polymer (r(2) = 0.97). Following coating degradation, other competitive factors, such as the biocompatibility and the biodegradability of the polymer itself, came into play.

Plicated patch repair for acquired Gerbode defect involving the tricuspid valve

Gerbode's defect, a left ventricular-to-right atrial communication, with involvement of the tricuspid valve acquired after bacterial endocarditis can be challenging to repair. We report a modified technique for a shunt closure and reconstruction of the tricuspid valve using a plicated bovine pericardial patch. Combining such a repair with a left ventricular patch resulted in a complete defect closure and competent tricuspid valve without regurgitation.

Osteoindctivization of dental implants and bone- defect-filling materials

http://www.woodheadpublishing.com/en/book.aspx?bookID=1598

Clinical and radiographic evaluation of intrabony periodontal defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute

The aim of this study has been to compare the clinical and radiographic outcome of periodontal intrabony defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute application. Thirty patients diagnosed with advanced periodontits were divided into two groups: the control group (OFD), in which an open flap debridement procedure was performed and the test group (OFD+NHA), in which defects were additionally filled with nanocrystalline hydroxyapatite bone substitute material. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR) and clinical attachment level (CAL) were measured prior to, then 6 and 12months following treatment. Radiographic depth and width of defects were also evaluated. There were no differences in any clinical and radiographic parameters between the examined groups prior to treatment. After treatment, BOP, GI, PD, CAL, radiographic depth and width parameter values improved statistically significantly in both groups. The PI value did not change, but the GR value increased significantly after treatment. There were no statistical differences in evaluated parameters between OFD and OFD+NHA groups 6 and 12months after treatment. Within the limits of the study, it can be concluded that the additional use of nanocrystalline hydroxyapatite bone substitute material after open flap procedure does not improve clinical and radiographic treatment outcome.

Implant-supported single tooth restoration in the aesthetic zone: transmucosal and submerged healing provide similar outcome when simultaneous bone augmentation is needed

AIM: The aim of this study was to compare the clinical outcomes after 2 years with bone level implants placed to restore a single missing teeth that needed simultaneous augmentation and were treated with a transmucosal or submerged approach. METHODS: This study analyzed a subset of patients included in an ongoing prospective multicenter randomized clinical trial (RCT) involving12 centers where patients were to be followed-up to 5 years after loading. Of the 120 implants that were placed in the original study, and randomly assigned to submerged or non-submerged healing, 52 needed simultaneous augmentation (28 women patients and 24 men patients, between 23 and 78 years of age). Twenty-seven of them received implants with submerged healing (AuS), while in 25 patients the implants were inserted with a non-submerged protocol (AuNS). At the 2-year follow-up visit, radiographic crestal bone level changes were recorded as well as soft tissue parameters included Pocket probing depth (PPD), bleeding on probing (BoP) and clinical attachment level (CAL) at teeth adjacent to the implant site. RESULTS: After 2 years a small amount of bone resorption was found in both groups (0.37 ± 0.49 mm in the AuS group and 0.54 ± 0.76 in the AuNS group; P < 0.001). There was no statistically significant difference between AuS Group and AuNS group for PPD (2.5 vs. 2.4 mm), BOP (BOP + sites: 8.8% vs. 11.5%) and CAL (2.8 vs. 2.4 mm) at the 2-year follow-up visit. CONCLUSIONS: When a single implant is placed in the aesthetic zone in conjunction with bone augmentation for a moderate peri-implant defect, submerged and transmucosal healing determine similar outcome, hence there is no need to submerge an implant in this given clinical situation.

Hip abductor defect repair by means of a vastus lateralis muscle shift

Scarring or detachment of the hip abductors, particularly of the gluteus medius, from their insertion may lead to severe abductor weakness, recurrent dislocations, pain, and diminished quality of life. We performed a retrospective study to evaluate whether vastus lateralis shift is associated with satisfactory results and low rate of complications. Eleven adults underwent vastus lateralis shift to bridge a well-documented abductor muscles' insertion defect. Preoperative and postoperative hip functions were assessed applying the Merle d'Aubigne score, British Medical Council scale, and Visual Analog Scale. Significant postoperative improvement was noted in mean Merle d'Aubigne score, gluteus medius muscle force, and quality of life. Vastus lateralis shift represents a viable treatment option for hip abductor deficiency, significantly improving abductor strength and overall quality of life.

An unusual splice defect in the mitofusin 2 gene (MFN2) is associated with degenerative axonopathy in Tyrolean Grey cattle

Tyrolean Grey cattle represent a local breed with a population size of approximately 5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle.

Pseudomyotonia, a muscle function disorder associated with an inherited ATP2A1 (SERCA1) defect in a Dutch Improved Red and White cross-breed calf

A Dutch Improved Red and White cross-breed heifer calf was evaluated for a muscular disorder resulting in exercise induced muscle stiffness. Clinical findings included generalized exercise-induced muscle spasms with normal response to muscle percussion. Electromyography showed no myotonic discharges, thus ruling out myotonia. Whereas histological examination of muscle tissue was unremarkable, Ca(2+)-ATPase activity of sarcoplasmatic reticulum membranes (SERCA1) was markedly decreased compared to control animals. Mutation analysis revealed the presence of a missense mutation in the ATP2A1 gene encoding the SERCA1 protein (p.Arg559Cys). The present case presents similarities to human Brody's disease, but also to pseudomyotonia and congenital muscular dystonia previously described in different cattle breeds.

Inhibition of endogenous antagonists with an engineered BMP-2 variant increases BMP-2 efficacy in rat femoral defect healing

Bone morphogenetic proteins (BMP) have been used successfully by orthopedic clinicians to augment bone healing. However, these osteoinductive proteins must be applied at high concentrations to induce bone formation. The limited therapeutic efficacy may be due to the local expression of BMP antagonists such as Noggin that neutralize exogenous and endogenous BMPs. If so, inhibiting BMP antagonists may provide an attractive option to augment BMP induced bone formation. The engineered BMP-2 variant L51P is deficient in BMP receptor type I binding, but maintains its affinity for BMP receptor type II and BMP antagonists including Noggin, Chordin and Gremlin. This modification makes L51P a BMP receptor-inactive inhibitor of BMP antagonists. We implanted β-tricalcium phosphate ceramics loaded with BMP-2 and/or L51P into a critical size defect model in the rat femur to investigate whether the inhibition of BMP antagonist with L51P enhances the therapeutic efficacy of exogenous BMP-2. Our study reveals that L51P reduces the demand of exogenous BMP-2 to induce bone healing markedly, without promoting bone formation directly when applied alone.