Paediatric ventilation treatment of acute lung injury in Nordic intensive care units.

BACKGROUND: Treatment of acute respiratory distress syndrome (ARDS) in children is largely based on extrapolated knowledge obtained from adults and which varies between different hospitals. This study explores ventilation treatment strategies for children with ARDS in the Nordic countries, and compares these with international practice. METHODS: In October 2012, a questionnaire covering ventilation treatment strategies for children aged 1 month to 6 years of age with ARDS was sent to 21 large Nordic intensive care units that treat children with ARDS. Pre-terms and children with congenital conditions were excluded. RESULTS: Eighteen of the 21 (86%) targeted intensive care units responded to the questionnaire. Fifty per cent of these facilities were paediatric intensive care units. Written guidelines existed in 44% of the units. Fifty per cent of the units frequently used cuffed endotracheal tubes. Ventilation was achieved by pressure control for 89% vs. volume control for 11% of units. Bronchodilators were used by all units, whereas steroids usage was 83% and surfactant 39%. Inhaled nitric oxide and high frequency oscillation were available in 94% of the units. Neurally adjusted ventilator assist was used by 44% of the units. Extracorporeal membrane oxygenation could be started in 44% of the units. CONCLUSION: Ventilation treatment strategies for paediatric ARDS in the Nordic countries are relatively uniform and largely in accordance with international practice. The use of steroids and surfactant is more frequent than shown in other studies.

Associations of current and remitted major depressive disorder with brain atrophy: the AGES-Reykjavik Study.

BACKGROUND: To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia. METHOD: Within the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 4354 persons (mean age 76 ± 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI). RESULTS: Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = -1.25%, 95% confidence interval (CI) -2.05 to -0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = -1.62%, 95% CI -3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI -0.54 to 0.66). CONCLUSIONS: In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia.

Pleistocene genetic legacy suggests incipient species of Sebastes mentella in the Irminger Sea.

To investigate a possible speciation event within the redfish (Sebastes mentella) complex in the Irminger Sea, we examined genetics, traditional morphology, geometric morphometrics and meristics of individuals sampled throughout the Sea. Tissue samples from 1901 fish were collected in 1995 and 1996 and from 1999 to 2002, and the fish were genotyped at nine microsatellite loci, two of which were developed for this study. Individual-based genetic analyses showed that two different gene pools exist in the Irminger Sea. Although these groups overlap extensively geographically, they segregate according to depth: those above and below 550 m. This signal of genotype distinction with depth was evident in both the earlier and later sampling. Historical imprints in the genetic data indicated that the redfish in the Irminger Sea are likely to represent a case of an incipient speciation event that began in allopatry during the Pleistocene glaciations followed by secondary contact. Although hybridization was observed between groups, an analysis of traditional and geometric morphometrics and of meristic variables suggested that restricted gene flow between the currently parapatric deep- and shallow-mesopelagic incipient species may be maintained by ecological isolation mechanisms.

Neural circuit dysfunction in schizophrenia: Insights from animal models.

Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research.

Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects.

Regeneration of alveolar bone and cementum following reconstructive therapy with reinforced space providing expanded polytetrafluorethylene (ePTFE) membranes was evaluated in supraalveolar mandibular premolar periodontal defects in five beagle dogs. The surgically-created defects in contralateral jaw quadrants were randomly assigned to receive the dome-shaped membrane or serve as surgical control. Flaps were positioned to completely submerge the teeth and sutured. The dogs were sacrificed 8 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histology. Membrane treated defects in two animals became exposed and infected leaving intact quadrants in three dogs for histometric analysis. Parameters evaluated included defect height, height and area of regenerated alveolar bone, height of regenerated cementum, root resorption, and ankylosis. Mean defect height approximated 4.1 mm. Mean height (+/- s.d.) of regenerated alveolar bone amounted to 2.9 +/- 0.6 and 0.6 +/- 0.2 mm for membrane and control defects, respectively (P = 0.006). Corresponding values for bone area were 1.4 +/- 0.7 and 0.4 +/- 0.4 mm2 (P = 0.02). Cementum regeneration was observed in all teeth averaging (+/- s.d.) 1.6 +/- 0.3 mm for membrane treated and 0.1 +/- 0.1 mm for control defects (P = 0.01). Small amounts of root resorption were seen in all teeth with no significant difference between treatments. Ankylosis was noticed in three membrane treated and two control teeth. The present study provides a biologic rationale for space provision for enhanced bone and cementum regeneration in periodontal defects subject to reconstructive therapy.

Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenetic proteins.

A concept of space provision to support skeletal repair has long been used in orthopedic and oral maxillofacial reconstructive therapy. More recently, this concept has been studied and adapted to periodontal reconstructive therapy. Other studies have demonstrated that skeletal tissues represent a significant reservoir of growth factors, including bone morphogenetic proteins. Such factors have been shown to stimulate skeletal repair in preclinical models and in clinical defects. We herein review studies using the critical size supraalveolar periodontal defect model in which clinically meaningful periodontal regeneration was achieved following reconstructive surgery, including space provision by reinforced expanded polytetrafluoroethylene membranes or including surgical implantation of recombinant human bone morphogenetic protein-2. Potential mechanisms involved in observed regeneration are discussed.

Cigarette smoking negatively affects healing response following flap debridement surgery.

BACKGROUND: The purpose of the present parallel design, controlled clinical trial was to evaluate the treatment outcome following flap debridement surgery (FDS) in cigarette smokers compared to non-smokers. METHODS: After initial therapy, 57 systemically healthy subjects with moderate to advanced periodontitis who presented with one area (at least 3 teeth) where surgery was required were selected. Twenty-eight patients (mean age: 39.6 years, 20 males) were smokers (> or = 10 cigarettes/day); 29 patients (mean age: 43.9 years, 7 males) were non-smokers. Full-mouth plaque (FMP) and bleeding on probing (BOP) scores, probing depth (PD), clinical attachment level (CAL), and recession depth (RD) were assessed immediately before and 6 months following surgery. Only sites with presurgery PD > or = 4 mm were used for statistical analysis. RESULTS: Presurgery FMP and BOP were similar in smokers and non-smokers and significantly decreased postsurgery in both groups. Overall, PD reduction and CAL gain were greater, although not significantly, in non-smokers (2.4 +/- 0.9 mm and 1.6 +/- 0.7 mm, respectively) than in smokers (1.9 +/- 0.7 mm and 1.2 +/- 0.7 mm, respectively). For moderate sites (PD 4 to 6 mm), no significant differences in PD and CAL changes were found between groups. For deep sites (PD > or = 7 mm), PD reduction was 3.0 +/- 1.0 mm in smokers and 4.0 +/- 0.8 mm in non-smokers, and CAL gain amounted to 1.8 +/- 1.1 mm in smokers and 2.8 +/- 1.0 mm in non-smokers (P = 0.0477). In smokers, 16% of deep sites healed to postsurgery PD values < or = 3 mm as compared to 47% in non-smokers (P = 0.0000); 58% of deep sites in smokers showed a CAL gain > or = 2 mm, as compared to 82% in non-smokers (P = 0.0000). CONCLUSIONS: Results of the study indicated that: 1) FDS determined a statistically significant PD reduction and CAL gain in patients with moderate to advanced periodontitis; 2) smokers exhibited a trend towards less favorable healing response following FDS compared to non-smokers, both in terms of PD reduction and CAL gain; and 3) this trend reached clinical and statistical significance at sites with initial deep PD.

Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration.

This study evaluated bone and cementum regeneration following periodontal reconstructive surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2) in six beagle dogs. Surgically created mandibular supraalveolar premolar tooth defects in contralateral jaw quadrants were randomly assigned to receive rhBMP-2 or control vehicle. Clinical defect height was prepared to 5 mm. rhBMP-2 was applied with synthetic bioerodable particles and autologous blood using 20 micrograms rhBMP-2 per 100 microliters implant volume. Flaps were advanced to submerge the teeth and sutured. The dogs were sacrificed 8 weeks postsurgery. Histometric recordings included defect height, height and area of alveolar bone regeneration, height of cementum regeneration, root resorption, and ankylosis. Group means, standard deviations, and P values are shown (Student t test; n = 6). Histometric defect height for rhBMP-2 and control defects was 3.7 +/- 0.3 and 3.9 +/- 0.4 mm, respectively (P = 0.446). Height of alveolar bone regeneration amounted to 3.5 +/- 0.6 and 0.8 +/- 0.6 mm for rhBMP-2 and control defects, respectively (P = 0.000). Corresponding values for bone area were 8.4 +/- 4.5 and 0.4 +/- 0.5 mm2, respectively (P = 0.006). Cementum regeneration was observed in all experimental defects (17/17) and in 15 out of 17 controls, averaging 1.6 +/- 0.6 and 0.4 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P = 0.005). Small amounts of root resorption were seen in rhBMP-2 defects, whereas controls exhibited substantial resorption (0.2 +/- 0.1 and 1.1 +/- 0.3 mm, respectively; P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of periodontal probing using a conventional manual and an automated force-controlled electronic probe.

A total of 1,128 sites in 15 periodontal maintenance patients were examined twice, 7 to 10 days apart, to evaluate reproducibility of periodontal probing by a conventional manual and an automated force-controlled electronic probe. Probing depths (PD) and relative attachment levels (AL) were recorded to the nearest 0.5 mm with both instruments. At each visit, all sites were probed first with the conventional and then with the electronic probe. Reproducibility of PD at shallow sites (PD < or = 3 mm) by the manual probe was 59.1% for exact agreement and 98.6% within +/- 1.0 mm variation. For the electronic probe, corresponding values were 41.3% and 91.5%, respectively. Reproducibility of PD measurements at deeper sites (PD > 3 mm), was 33.0% for exact match and 96.4% within +/- 1.0 mm for the manual and, correspondingly, 31.7% and 85.9% for the electronic probe. Reproducibility of AL followed a similar pattern, but was consistently lower than for PD. Reproducibility was consistently higher for anterior than for posterior sites and, for some comparisons, higher in the maxilla than in the mandible. These differences were smaller for the manual than for the electronic probe. Time required to complete the probing was longer for the conventional probe than for the electronic instrument. Under the prevailing study conditions, the automated force-controlled electronic probe failed to offer significant advantages over the conventional manual probe.

Effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in supra-alveolar peri-implant defects in dogs.

This randomized, split-mouth design study evaluated the adjunctive effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in a critical-size, supra-alveolar, peri-implant defect model. Contralateral supra-alveolar peri-implant defects, 5 mm in height, each including two titanium implants, were surgically created in five beagle dogs. Demineralized bone matrix in autologous blood was placed over the implants in one randomly selected mandibular jaw quadrant. A space-making expanded-polytetrafluoroethylene membrane was used to provide guided bone regeneration bilaterally. Following a 16-week healing interval, tissue blocks were harvested and prepared for histometric analysis. Differences between experimental conditions (guided bone regeneration sites with and without demineralized bone) were evaluated using paired t tests (n = 4). Demineralized bone particles were discernible, with limited signs of resorption. The bone matrix particles appeared to be solidified within a dense connective tissue matrix and in close contact with the implants. Limited matrix remineralization was apparent adjacent to the alveolar crest. No statistically significant differences were found between experimental conditions for any parameter examined. Peri-implant defect height averaged 5.0 +/- 0.2 mm and 4.9 +/- 0.4 mm, vertical bone regeneration 1.5 +/- 0.9 mm and 1.1 +/- 0.4 mm, osseointegration within the extent of the defect 10.0 +/- 3.9% and 15.3 +/- 5.3%, osseointegration within the extent of regenerated bone 30.4 +/- 13.7% and 52.1 +/- 17.9%, and osseointegration within the alveolar base 68.8 +/- 13.1% and 74.4 +/- 7.1% for guided bone sites with and without demineralized bone, respectively (P > .05). The results suggest that freeze-dried demineralized bone has no adjunctive effect on guided bone regeneration in supra-alveolar peri-implant defects, that guided bone regeneration has a limited potential to enhance alveolar regeneration in this defect model, and that a 16-week healing interval appears insufficient for turnover and maturation of demineralized bone under provisions for guided bone regeneration.

Evaluating surgical, non-surgical therapy in periodontic patients.

Eleven highly susceptible periodontitis patients volunteered for a one-year prospective study of surgical and non-surgical periodontal therapy. The patients had high oral hygiene standards and had not received antimicrobial therapy within six months. This study suggests that both types of therapy are equally effective in treating recurrent lesions.

Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone.

The objective of this study was to examine alveolar ridge augmentation following implantation of recombinant human bone morphogenetic protein (rhBMP-2) with an allogeneic freeze-dried demineralized bone matrix (DBM) mixed with autologous blood. A second objective was to evaluate bone-to-implant contact in induced bone. Bilateral surgically created supraalveolar ridge defects in five young adult beagle dogs were implanted with the rhBMP-2-DBM-blood device. Transmucosal dental implants were placed at weeks 8 and 16 postsurgery The animals were euthanized 24 weeks following ridge augmentation. Healing was uneventful in all animals. Radiographic observations indicated substantial bone formation, including regions of radiolucency, at week 8. At week 16, the radiolucencies were generally resolved, and the trabecular structure of the induced bone resembled that of the adjacent residual bone. There were no remarkable differences in radiographic observations between weeks 16 and 24 after ridge augmentation. Histologic analysis revealed dense woven and lamellar induced bone. Any residual DBM appeared remineralized, at least in part. A large portion of the dental implants (approximately 70%) were housed in induced bone with evidence of limited crestal resorption. There was no significant difference in bone density between induced and residual bone, and the levels of bone-to-implant contact were similar (approximately 55%). The rhBMP-2 construct used in this study has a potential to augment alveolar ridge defects. Also, no difference in levels of osseointegration may be expected in induced and residual bone following a two-stage procedure of rhBMP-2-induced ridge augmentation and dental implant placement.

"Collagen adhesion" revisited.

Histologic studies of periodontal reconstructive therapies have repeatedly shown a zone of nondescript connective tissue adaptation, or collagen adhesion, to the root surface between the apical extension of the junctional epithelium and the coronal extension of identifiable regenerated cementum. To clarify the nature of this zone, supra-alveolar periodontal defects were created bilaterally in the mandibular premolar region in three beagle dogs, and exposed roots were instrumented to remove the cementum. Flaps were then coronally advanced and sutured. Histologic analysis after 12 weeks of healing showed instrumented root dentin not associated with junctional epithelium, new cementum, root resorption, or ankylosis in 27 of 60 root surfaces. In 10 of these specimens subsequently examined by transmission electron microscopy, collagen fibrils were generally oriented parallel to and in close proximity to the root. A mechanism of collagen attachment was, in fact, functioning at sites of collagen adhesion; these areas may validly be included in the histologic attachment level reported in studies of periodontal reconstructive therapy.

Periodontal repair in dogs: evaluation of rhBMP-2 carriers.

This study evaluated candidate carriers for recombinant human bone morphogenetic protein-2 (rhBMP-2)-driven periodontal regeneration. Previous experiments indicated the ability of rhBMP-2 in a particulate delivery system to result in substantial regeneration of bone and periodontal regeneration. In the present study, canine demineralized bone matrix (DBM), bovine deorganified crystalline bone matrix (Bio-Oss), an absorbable collagen sponge (ACS) of type I bovine collagen, poly(D,L-lactide-co-glycolide) microparticles (PLGA), and polylactic acid granules (Drilac) were tested for their ability to support rhBMP-2 (0.2 mg/mL implant volume)-driven periodontal regeneration. The implants were tested in routine critical size canine supra-alveolar periodontal defects with transgingival tooth positioning. Contralateral defects in six beagle dogs were semirandomly assigned to receive: DBM/rhBMP-2, DBM (no rhBMP-2), Bio-Oss/rhBMP-2, ACS/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2. Animals were sacrificed 8 weeks postsurgery, and block sections of the defects were processed for light microscopy. Substantial bone regeneration was observed in all defects implanted with rhBMP-2. Other measures of periodontal healing, including cementum regeneration and presence of ankylosis, were more variable between the implants. DBM and Bio-Oss performed well as carriers for rhBMP-2-driven periodontal regeneration, although other impediments to their clinical use exist. This study indicates that qualities of the carrier system, including its space-maintaining capacity can affect the ability of rhBMP-2 to regenerate both alveolar bone and periodontal attachment.

Lipophilic metronidazole derivatives and their absorption through hairless mouse skin.

Previously we have shown that the diacyl glyceryl ester of naproxen is absorbed into excised mouse skin and slowly degraded to release naproxen. In the present work we have synthesised some organic acid and fatty acid derivatives of metronidazole, and studied the in-vitro degradation in aqueous buffer solutions and serum as well as their permeation through hairless mouse skin. The derivatives were enzymatically degraded in serum to form metronidazole. Only the acetic acid and butyric acid derivatives were able to permeate hairless mouse skin intact. The fatty acid derivatives released metronidazole within the skin. The metronidazole delivery through the skin was significant when the metronidazole oleate was used. This compound could therefore be considered as a suitable pro drug for dermal applications.

Dynamics of wound healing in periodontal regenerative therapy.

Experimental animal and clinical studies have increased understanding of the biology of healing following periodontal regenerative therapy and factors that may influence the outcome. Formation of a new connective tissue attachment rather than a long junctional epithelium at the tooth-gingival flap interface is dependent upon the completion of a series of interactions among the root surface, plasma and tissue factors, and the connective tissue of the gingival flap. First, plasma proteins must adsorb to and remain in undisturbed contact with a generally noncompromised root surface. Next, adhesion of the established fibrin clot to the root surface must remain intact. Within days, a cellular and fibrous attachment will form; however, the tooth-gingival flap interface will still be vulnerable to wound-rupturing forces. Within two weeks the interface may have gained sufficient mechanical strength to offset such forces, at least in limited periodontal defects. Eventually, maturation of the fibrous attachment, including bone and cementum formation, will occur, particularly following adequate space provision by barrier membranes (guided tissue regeneration). A novel research focus involves how advances in molecular biology can translate to periodontal regenerative therapy. Bone morphogenetic proteins (BMPs) have been shown to support healing in a variety of skeletal sites. Recent research has demonstrated clinically significant alveolar bone and cementum regeneration with the use of a recombinant human BMP-2 implant. Such data suggest that growth-promoting substances, such as rhBMP-2, may significantly enhance periodontal regeneration and that use of such substances may radically recast current periodontal regenerative therapy.

Trabeculectomy and gelatin implants. A retrospective, long-term follow-up study.

In a retrospective follow-up study including 60 eyes with simple or capsular glaucoma, the results obtained by using a gelatin implant under the scleral flap during trabeculectomy were compared with those obtained without such implants. One month postoperatively the mean IOP was significantly lower in the gelatin group than in the control group (15.0 mmHg and 17.9 mmHg, respectively) (p = 0.024). At the long-term follow-up, however, the mean IOP in the two groups were very similar (13.6 mmHg and 14.8 mmHg, respectively).

Erythrocyte sedimentation rate as a tumor marker in human prostatic cancer. An analysis of prognostic factors in 300 population-based consecutive cases.

BACKGROUND: The natural history of prostatic cancer is variable. Our knowledge of prognostic factors is limited; therefore, research is needed. METHODS: The cases of 300 population-based consecutive patients with a diagnosis of cancer of the prostate were analyzed regarding different prognostic factors (but with special reference to the erythrocyte sedimentation rate [ESR]). RESULTS: After a mean observation time of 100 months, M category, ESR, grade, performance status, hemoglobin level, and T category were found to correlate with disease-specific death using multivariate analysis. The variables correlating with progression in the multivariate model were M category, ESR, T category, grade, treatment, and age. Patients treated with estrogen had a significantly lower risk (relative hazard, 0.3) of relapse. ESR was highly statistically significant (P less than 0.0001) as a prognostic factor. With the variable in linear form, a 20-mm/h higher level suggested a 29% increased risk, on average, for dying of prostatic cancer (using a best-fit multivariate model). However, the relationship was not linear. After correcting for the effect of other factors, the risk for dying of prostatic cancer was lowest when the ESR was 40-50 mm/h and highest when its values were highest. CONCLUSIONS: ESR is an indicator of increased risk of progression and death in prostatic cancer. Other prognostic factors such as M and T categories, grade, performance status, hemoglobin level, and age currently are more important when planning treatment. It is possible that the ESR reflects aspects of tumor-host relationship and that both a low and high ESR are markers for patients with receding host defence mechanism.

Polidocanol sclerotherapy for hydroceles and epididymal cysts.

A total of 87 patients with 63 hydroceles and 29 epididymal cysts underwent injection sclerotherapy with polidocanol on an outpatient basis. In the hydrocele group the cure rate after 1 treatment was 67% and the overall cure rate was 87% after a median followup of 14 months. In the group treated for epididymal cyst the corresponding cure rates were 46% and 64%, respectively, with a median followup of 12 months. A low rate of complications was observed. Of 86 evaluable patients 81 (94%) were satisfied with the procedure and the treatment results. Therefore, we recommend injection sclerotherapy with polidocanol as primary treatment for hydroceles and epididymal cysts in patients older than 40 years.