Radiographic Analysis of Graft Dimensional Changes in Transcrestal Maxillary Sinus Augmentation: A Retrospective Study

Background. The maxillary sinus lift is a popular and predictable technique associated with implant-supported rehabilitation of the severely atrophic maxilla. The aim of the present retrospective study was to investigate the effectiveness of transcrestal maxillary sinus augmentation and the graft resorption pattern using different heterologous bone substitutes. Methods. A total of 75 sinus-grafting procedures were performed and 89 implants were placed in 66 patients, 24 males and 42 females, with mean age 67.9 ± 10.64 years (range 43–84 years). Nineteen subjects were smokers. The mean follow-up period was 93.33 ± 54.71 months (range 14–240 months). Clinical and radiographical evaluations were performed. Graft height and width were measured at baseline and at the latest follow-up. Results. Mesiodistal and vertical resorption averaged 9.3 ± 20.7% (standard deviation), and 5.04 ± 9.9% of the postoperative size, respectively, considering the graft as the unit. Linear regression analysis showed that graft resorption in both the vertical and the mesiodistal dimension is independent of the follow-up time. Conversely, there was a trend for greater resorption when increasing the postoperative graft size, in both vertical (p = 0.001) and horizontal (p = 0.007) dimensions. When grouping the dimensional changes by graft particle size (only small (<300 μm) particles, combination of small and medium (>500 μm)/large (>1000 μm) particles, and only medium/large particles), there was a trend for greater resorption associated with smaller particles, but it was not significant; neither in the mesiodistal nor in the vertical dimension (p = 0.17 and p = 0.25, respectively). No implant was lost during the observation period. In conclusion, the transcrestal technique for maxillary sinus augmentation documented a high level of predictability. The low clinical morbidity and the contextual dental implant positioning is clinically useful in relation to a significant reduction of the time required for implant restoration, a consistent decrease of the number of surgical phases, and a cost-effectiveness approach for the rehabilitation. The graft resorption pattern in all cases was compatible with persistent implant protection and support.     

Neocortical hyperexcitability in a genetic model of absence seizures and its reduction by levetiracetam

PURPOSE: To study the effect of the antiepileptic drug levetiracetam (LEV) on the patterns of intrinsic optical signals (IOSs) generated by slices of the somatosensory cortex obtained from 3- and 6-month-old WAG/Rij and age-matched, nonepileptic control (NEC) rats. METHODS: WAG/Rij and NEC animals were anesthetized with enfluorane and decapitated. Brains were quickly removed, and neocortical slices were cut coronally with a vibratome, transferred to a submerged tissue chamber, and superfused with oxygenated artificial cerebrospinal fluid (aCSF). Slices were illuminated with a dark-field condensor and examined with a x2.5 objective; images were processed with a real time digital video image-enhancement system. Images were acquired before (background) and during electrical stimulation with a temporal resolution of 10 images/s and were displayed in pseudocolors. Extracellular stimuli (200 micros; <4 V) were delivered through bipolar stainless steel electrodes placed in the white matter. RESULTS: IOSs recorded in NEC slices bathed in control aCSF became less intense and of reduced size with age (p < 0.05); this trend was not seen in WAG/Rij slices. Age-dependent decreases in IOS intensity and area size were also seen in NEC slices superfused with aCSF containing the convulsant 4-aminopyridine (4-AP, 5 microM); in contrast, significant increases in both parameters occurred with age in 4-AP-treated WAG/Rij slices (p < 0.05). Under any of these conditions, the IOS intensity and area size slices were larger in WAG/Rij than in NEC slices. LEV (50-500 microM) application to WAG/Rij slices caused dose-dependent IOS reductions that were evident both in control and in 4-AP-containing aCSF and were more pronounced in 6-month-old tissue. CONCLUSIONS: These data demonstrate age-dependent IOS modifications in NEC and WAG/Rij rat slices and identify a clear pattern of hyperexcitability that occurs in 6-month-old WAG/Rij neocortical tissue, an age when absence seizures occur in all animals. The ability of LEV to reduce these patterns of network hyperexcitability supports the potential use of this new antiepileptic drug in primary generalized epileptic disorders.     

Defective differentiation of regulatory FoxP3+ T cells by small-intestinal dendritic cells in patients with type 1 diabetes

OBJECTIVE

The gut environment modulates the pathogenesis of type 1 diabetes (T1D), but how it affects autoimmunity toward pancreatic β-cells, a self-tissue located outside the intestine, is still unclear. In the small intestine, lamina propria dendritic cells (LPDCs) induce peripheral differentiation of FoxP3⁺ regulatory T (Treg) cells. We tested the hypothesis that the intestinal milieu impinges on human T1D by affecting differentiation of FoxP3⁺ Treg cells.

RESEARCH DESIGN AND METHODS

We collected duodenal biopsies of 10 T1D patients, 16 healthy subjects, and 20 celiac individuals and performed a fluorescent-activated cell sorter analysis to measure percentages of various immune cell subsets, including CD4⁺ and CD8⁺ T cells, NK cells, γδ T cells, CD103⁺CD11c⁺ LPDCs, and CD4⁺CD25⁺FoxP3⁺CD127⁻ Treg cells. In parallel, we assessed the tolerogenic function (i.e., capacity to induce differentiation of FoxP3⁺ Treg cells) by LPDCs of T1D patients and control subjects.

RESULTS

Our analysis revealed a significant reduction in the percentage of intestinal CD4⁺CD25⁺FoxP3⁺CD127⁻ Treg cells in T1D patients compared with healthy subjects (P = 0.03) and celiac individuals (P = 0.003). In addition, we found that LPDCs from T1D patients completely lacked their tolerogenic function; they were unable to convert CD4⁺CD25⁻ T cells into CD4⁺CD25⁺FoxP3⁺CD127⁻ Treg cells.

CONCLUSIONS

Our data indicate that T1D patients have a reduced number of intestinal FoxP3⁺ Treg cells as a result of their defective differentiation in the gut. These findings suggest that intestinal immune regulation is not only calibrated to tolerate commensal bacteria and food components but also is instrumental in maintaining immune tolerance toward pancreatic β-cells and preventing T1D.Type 1 diabetes (T1D) is a destructive islet β-cell specific autoimmune disease resulting from a yet undefined interaction between genetic and environmental factors (1). A dramatic increase in T1D incidence was recorded in most developed countries in the past 40 years (e.g., a threefold increase in Western countries) (2,3). The steady and rapid increase in T1D incidence cannot be ascribed to genetic variations and, thus, it must be related to environmental changes. Environmental agents such as viral infections (i.e., enteroviruses and rotaviruses) (4,5), reactions to dietary antigens (i.e., cow’s milk and gluten) (6–8), and microbiota alterations (9) that act at the intestinal level have been observed in association with, or as risk factors for, the development of T1D. The observation that development of clinical diabetes in patients is preceded by intestinal alterations such as increased permeability, immune activation, and ultrastructural abnormalities of the epithelium (10–16) provides additional evidence on the crucial role of the gut environment in human T1D. Although existing evidence is suggestive of a causative link between the gut milieu and the pathogenesis of T1D, it is still unclear whether and by which mechanism(s) a dysfunction in the intestine promotes autoimmunity elsewhere (i.e., in the pancreatic β-cells) and if it does, how this process occurs.Important immune regulatory mechanisms reside in the intestinal mucosa. FoxP3⁺ regulatory T (Treg) cells, a Treg cell subset that is instrumental to controlling T1D (17), arise centrally in the thymus and peripherally in the gut (18). Specifically, lamina propria CD103⁺CD11c⁺ dendritic cells (LPDCs) are responsible for extrathymic FoxP3⁺ Treg cell development and expansion (18,19). Considering the key immune regulatory role of FoxP3⁺ Treg cells, it is clear that their defective peripheral differentiation in the gut could lead to failure of self-tolerance and autoimmune disease, particularly in tissues such as pancreatic islets and lymph nodes that are directly connected to the intestinal mucosa and gut-associated lymphoid tissue (20).Here we demonstrate that the extrathymic differentiation of FoxP3⁺ Treg cells by gut-resident CD103⁺CD11c⁺ dendritic cells (DCs) is selectively impaired in humans affected by T1D. Our findings indicate that organ-specific autoimmune diseases such as T1D could be initiated and possibly maintained by virtue of changes in peripheral FoxP3⁺ Treg cell differentiation and/or expansion in the gut.     

Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse

Healing of diabetic wounds still remains a critical medical problem. Polydeoxyribonucleotide (PDRN), a compound having a mixture of deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic or adverse effect. We studied the effects of PDRN in diabetes‐related healing defect using an incisional skin‐wound model produced on the back of female diabetic mice (db+/db+) and their normal littermates (db+/+m). Animals were treated daily for 12 days with PDRN (8 mg/kg/ip) or its vehicle (100 μL 0.9%NaCl). Mice were killed 3, 6, and 12 days after skin injury to measure vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, to assay angiogenesis and tissue remodeling through histological evaluation, and to study CD31, Angiopoietin‐1 and Transglutaminase‐II. Furthermore, we measured wound breaking strength at day 12. PDRN injection in diabetic mice resulted in an increased VEGF message (vehicle=1.0±0.2 n‐fold vs. β‐actin; PDRN=1.5±0.09 n‐fold vs. β‐actin) and protein wound content on day 6 (vehicle=0.3±0.07 pg/wound; PDRN=0.9±0.1 pg/wound). PDRN injection improved the impaired wound healing and increased the wound‐breaking strength in diabetic mice. PDRN also caused a marked increase in CD31 immunostaining and induced Transglutaminase‐II and Angiopoietin‐1 expression. Furthermore, the concomitant administration of 3,7‐dimethyl‐1‐propargilxanthine, a selective adenosine A2A receptor antagonist, abolished PDRN positive effects on healing. However, 3,7‐dimethyl‐1‐propargilxanthine alone did not affect wound healing in both diabetic mice and normal littermates. These results suggest that PDRN might be useful in wound disorders associated with diabetes.     

Effects of epidural analgesia on labor length, instrumental delivery, and neonatal short-term outcome

Purpose

We aimed to clarify whether the short-term adverse neonatal outcomes associated with epidural analgesia are due to the epidural analgesia itself or to the instrumental delivery.

Methods

A retrospective case–control study was conducted to evaluate the relationship between epidural analgesia, labor length, and perinatal outcomes. A total of 350 pregnant women at term who delivered under epidural analgesia (cases) were compared with 1400 patients without epidural analgesia (controls).

Results

Vacuum extraction (6.5 vs. 2.9 %) and cesarean section (19.9 vs. 11.1 %) were more frequently performed in the cases than controls (p < 0.001). Using a Kaplan–Meier algorithm, it was determined that the mean lengths of the 1st and 2nd stages of labor and the overall durations of labor and delivery were significantly longer in cases compared with controls. A Cox regression analysis showed that the longer labor remained even after adjustment for parity. The neonatal variables stratified by mode of delivery were not different in cases and controls, except for a slightly lower umbilical arterial pH in spontaneous delivery for the cases group. However, the Apgar scores and umbilical arterial pH were significantly lower in the neonates delivered by vacuum extraction compared with those in the neonates delivered by spontaneous delivery or cesarean section, regardless of whether epidural analgesia was performed. A multivariable analysis showed that vacuum extraction much more consistently affected the arterial pH than the analgesia itself (the β coefficients were ?0.036 for epidural analgesia vs. ?0.050 for vacuum extraction).

Conclusion

Epidural analgesia was associated with slowly progressing labor, thus resulting in an increased rate of instrumental delivery. This instrumental delivery appears to adversely affect the neonatal outcomes more strongly than the analgesia itself.     

Current concepts for rehabilitation and return to sport after knee articular cartilage repair in the athlete

Articular cartilage injury is observed with increasing frequency in both elite and amateur athletes and results from the significant acute and chronic joint stress associated with impact sports. Left untreated, articular cartilage defects can lead to chronic joint degeneration and athletic and functional disability. Treatment of articular cartilage defects in the athletic population presents a therapeutic challenge due to the high mechanical demands of athletic activity. Several articular cartilage repair techniques have been shown to successfully restore articular cartilage surfaces and allow athletes to return to high-impact sports. Postoperative rehabilitation is a critical component of the treatment process for athletic articular cartilage injury and should take into consideration the biology of the cartilage repair technique, cartilage defect characteristics, and each athlete's sport-specific demands to optimize functional outcome. Systematic, stepwise rehabilitation with criteria-based progression is recommended for an individualized rehabilitation of each athlete not only to achieve initial return to sport at the preinjury level but also to continue sports participation and reduce risk for reinjury or joint degeneration under the high mechanical demands of athletic activity.     

Exploring the link between diabetes and pancreatic cancer

Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear.

Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time–risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer.

Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes observed in several epidemiological studies indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumor. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle-age patients with new-onset diabetes may be considered.     

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 ± 23 vs 217 ± 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 ± 13 vs 187 ± 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 ± 0.2 vs 23.3 ± 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.