Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder.

To expand, analyze and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng's Shank3tm2Gfng model, hereafter Shank3/F, Jiang's Shank3tm1Yhj model, hereafter Shank3/J and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. This study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11.2 deletion models. We found that some but not all behaviors replicated published findings and those that did replicate, such as social behavior and overgrooming in Shank3 models, tended to be milder than reported elsewhere. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. We did not detect deficits in a cognitive procedural learning test nor did we observe perseverative behavior in these models. We did, however, find differences in exploratory patterns of Cacna1c mutant mice suggestive of a behavioral effect in a social setting. In addition, only Shank3/F showed differences in sensory-gating. Both positive and negative results from this study will be useful in identifying the most robust and replicable behavioral signatures within and across mouse models of autism. Understanding these phenotypes may shed light of which features to study when screening compounds for potential therapeutic interventions.

Role of chitinase and sormatin accumulation in the resistance of sorghum cultivars to grain mold.

Experiments were conducted to determine the association between resistance to grain mold and the accumulations of chitinase and sormatin. Eight sorghum lines were treated at 50% bloom with Fusarium thapsinum, Curvularia lunata, a mixture of the two fungi, and a water-sprayed control. At maturity, percent disease severity, seed germination rates, and kernel weight were recorded. Chitinase and sormatin content (mg/g of dry weight) were measured in seed samples taken at 30 and 50 days after treatment (DAT). Seed chitinase content was moderately affected by sorghum line (P = 0.10) and significantly affected by the developmental stage of the kernels (P = 0.05). Cultivars Sureno, 98LB650, and 98LB723 exhibited larger negative changes in chitinase content at 50 DAT over water-sprayed control treatment at 30 DAT than the susceptible cultivars Dorado, RTx2536, and RTx430. In 2000, significant negative correlations were observed for percent disease severity and chitinase content at 30 DAT, seed germination and sormatin content at 50 DAT, and between seed germination and kernel weight. There also was a significant positive correlation between germination and chitinase content at 30 DAT. No association between disease severity and changes in chitinase content at 50 DAT was observed. Sormatin content also was significantly affected by the stage of kernel development. Sorghum cultivars inoculated with fungal pathogens responded differently as indicated by the significant sorghum line x treatment interaction for sormatin content in 2000. In both years, larger increases in sormatin content over the water-sprayed control treatments were observed on moderately susceptible to susceptible cultivars such as 98LB650, 98LB723, 98LB789, RTx430, and RTx2536 than on Sureno. Except for percent disease severity and germination, there was no significant association among all of the other parameters measured in 2001. The results of this study did not clearly demonstrate a strong association between resistance to grain mold and the accumulation of sormatin and chitinase. Thus, there is the possibility that certain moderately resistant to resistant sorghum cultivars, such as Sureno, may employ other strategies to eschew or restrict fungal invasion either before or after physiological maturity.

Antifungal proteins in commercial hybrids and elite sorghums.

The antifungal proteins (AFP) in the caryopsis of commercial and elite sorghums grown in several environments were related to grain mold resistance. Previous studies revealed that improved grain mold resistance was correlated with higher levels of AFP at combine harvest maturity [50 days after anthesis (DAA)] or with better retention of AFP after physiological maturity (30 DAA). Commercial hybrids and public parental lines and hybrids were grown in College Station, TX, during 2000, 2001, and 2002. Samples of caryopses were collected at 30 and 50 DAA, and caryopsis proteins were extracted, blotted, identified with immunoassays, and quantified for two AFP (chitinase and sormatin). Sorghums varied in amounts of AFP and their ability to retain AFP after physiological maturity. The environment in 2002 was conducive for fungal deterioration of grain, and a wide range of AFP and grain molding was observed at harvest maturity. High levels of AFP and low levels of grain molding were observed in non-mold-conducive environments in 2000 and 2001. Commercial and elite sorghums with higher levels and increased retention of AFP had less grain molding in the mold-conducive environment.

The utility of polyglycolic acid mesh for abdominal access in patients with necrotizing pancreatitis.

BACKGROUND: Necrotizing pancreatitis is a poorly understood process that has been treated by a variety of surgical approaches. Despite advances in operative interventions and critical care, this disease often requires prolonged resource allocation and continues to cause substantial morbidity, with mortality rates ranging from 11% to 40%. We report on our recent series of patients with necrotizing pancreatitis and our experience with the use of an absorbable mesh in a subset of these patients to facilitate their surgical care. STUDY DESIGN: From 1985 to 1994, 40 patients with culture-proved necrotizing pancreatitis underwent operative debridement and drainage. Surgical outcomes were compared among patients who underwent a single debridement and drainage, those requiring multiple procedures, and those having placement of polyglycolic acid mesh. RESULTS: The overall hospital mortality rate was 30%. The mean length of hospital stay was 35 days. The rate of infected pancreatic necrosis was 60%, with a mortality rate of 45% in patients having infected pancreatic tissue at surgery. Patients without infected pancreatic tissue at surgery had a mortality rate of 6% (p = 0.03). Eleven patients requiring multiple operations had placement of absorbable polyglycolic acid mesh. Clinic followup was possible in five of six survivors who underwent mesh closure. Abdominal-wall hernias developed in two patients and were repaired electively, and three patients had spontaneous closure by granulation without abdominal-wall hernias. The average number of operations for debridement and drainage was 2.5 (range, 1-15). Patients with limited pancreatic necrosis required a single operative debridement and drainage, and this was associated with improved outcomes. CONCLUSIONS: Necrotizing pancreatitis remains an important challenge in surgical care. It requires prolonged hospitalization, costly resources, and causes substantial morbidity and mortality. Our patients with infected pancreatic necrosis or clinical deterioration underwent open staged necrosectomy and debridement. Those patients requiring repeat laparotomy often had placement of polyglycolic acid mesh. This provided open drainage of the abdominal cavity and simplified further care by allowing easy abdominal access for repeat drainage procedures, often performed in the intensive care unit. These patients had a high rate of fistula formation, which may be decreased by changes in wound care. Polyglycolic acid mesh is a useful adjunct in the surgical care of selected patients with necrotizing pancreatitis.

Local delivery of heparin with balloon angioplasty: results of a prospective randomized trial.

PURPOSE: To evaluate the effectiveness of local delivery of heparin via hydrogel-coated balloons in the treatment of vascular stenoses associated with hemodialysis access. MATERIALS AND METHODS: This was a randomized, prospective trial comparing treatment with hydrogel-coated balloon catheters delivered with heparin coating (n = 33) and without (n = 26). All patients were undergoing hemodialysis, and all stenoses involved the venous anastomosis of a dialysis graft or a native vein. The heparin-treated balloons were soaked in concentrated heparin and delivered in a protected manner to help prevent washout of heparin. RESULTS: The mean primary patencies were 143 days with heparin treatment and 214 days without heparin (P = .174). The mean assisted primary patencies were 165 days with heparin and 194 days without (P = .315). The mean secondary patencies were 351 days with heparin and 384 without (P = .81). CONCLUSION: In this population with this technique, the treatment outcome of venous outflow stenosis in patients with dialysis grafts is not improved with local delivery of heparin.

The management of extrahepatic portal vein aneurysms: observe or treat?

A case of a 70 year old man who was found to have an extrahepatic portal vein aneurysm during an evaluation for hematuria is reported. Extrahepatic portal vein aneurysms are rare with only twenty cases reported in the literature. Typically, patients present with hemorrhage requiring surgical exploration or the aneurysm is discovered during evaluation of another abdominal process. Management includes careful follow-up in the asymptomatic patient without underlying liver disease or portal hypertension.

Selective fecal diversion in complex open pelvic fractures from blunt trauma.

OBJECTIVE: To review the outcomes of patients with open pelvic fractures. DESIGN: Retrospective review of medical records. SETTING: Patients admitted from the injury scene or transferred within 24 hours to a level 1 trauma center. PATIENTS: Thirty-three patients sustaining blunt trauma had pelvic fractures and adjacent wounding. INTERVENTIONS: Treatment protocol that included selective fecal diversion, measures to arrest hemorrhage and prevent wound sepsis, manage associated pelvic injuries, and provide optimal orthopedic outcomes. MAIN OUTCOME MEASURES: Death and sepsis. RESULTS: Exsanguination occurred in one patient and death owing to head injuries occurred in five patients. Wound sepsis occurred in 31% of patients with colostomy and 19% without colostomy. CONCLUSIONS: Management of open pelvic fractures requires a well-coordinated group using several techniques. Selected patients with open pelvic fractures do not require fecal diversion. Incisions for orthopedic surgery should be considered when decisions are made regarding fecal diversion.

Laparotomy wound closure with absorbable polyglycolic acid mesh.

A knitted mesh of polyglycolic acid was used successfully in 59 critically ill patients to bridge abdominal wall defects and prevent evisceration after celiotomy. Polyglycolic acid knit mesh was used in 31 patients who had extraordinary visceral edema after resuscitation and the mesh was inserted to avoid excessive tension in the wound closure, 15 patients who had abdominal wall defects after adequate débridement for necrotizing fasciitis, and 13 patients who had losses of abdominal wall tissue caused by trauma or after resection of tumor. There were 14 hospital deaths among the seriously ill patients. Thirteen patients had enterocutaneous fistulas, seven of which occurred after meshes were inserted. The mesh material was strong, pliable and easily inserted in large abdominal wall defects. The polyglycolic acid knit mesh was infiltrated by granulation tissue within three weeks, including in heavily contaminated wounds. Two to three months after insertion, the material was absorbed. Hernia defects were common four to six months after the meshes were inserted and repairs were performed electively after patients had recovered from the primary problems. We conclude that absorbable polyglycolic acid knit mesh can be a useful technique for quickly achieving a secure tension-free closure of abdominal wounds.

A decision analysis of traumatic splenic injuries.

We created a decision analysis model of the nonsurgical management of traumatic splenic injuries to clarify the risk of hospital survival, overwhelming postsplenectomy infection (OPSI) deaths, and transfusion-related deaths. We reviewed 72 cases of splenic injury at our institution to identify our transfusion requirements for successful observation (0.5 units), observation failure (1.0 units), and surgical splenic management (1.6 units). Using our model and baseline probabilities determined from the literature, we compared the nonsurgical management of splenic injuries with immediate laparotomy and found an increase in hospital survival with observation, but an over two-fold increase in the risk of transfusion-related death. The OPSI deaths were not markedly different between the two strategies. Overall, we found decision analysis useful in identifying important variables such as the probability of nontherapeutic laparotomy death or missed injury, and in clarifying the risk of the nonsurgical management of splenic injuries with regard to transfusion-related deaths and OPSI deaths.

Late complications after femoral artery catheterization in children less than five years of age.

Fifty-eight children who underwent diagnostic femoral artery catheterization before 5 years of age, from 5 to 14 years before the study, were randomly selected from approximately 300 surviving patients undergoing diagnostic femoral artery catheterization at our institution during the interval. Each patient underwent vascular laboratory segmental pressure and waveform examination and arterial duplex scanning, as well as lower extremity bone length radiographs, which were considered positive if the catheterized leg was greater than or equal to 1.5 cm shorter than the opposite leg. Thirteen children who had only venous catheterization served as controls. No arterial abnormalities were present in the control patients (mean ankle/brachial index, 1.01). Arterial occlusion was present in both limbs of five patients who had bilateral diagnostic femoral artery catheterization and in 14 limbs of 51 patients who had unilateral diagnostic femoral artery catheterization. Thus arterial occlusion was present in 33% of patients (19 of 58) and in 37% of limbs (24 of 65). The mean ankle/brachial index in the catheterized limbs was 0.79. Leg growth retardation was present in four limbs (8%) of 51 children undergoing unilateral diagnostic femoral artery catheterization and in one (8%) control patient. The inverse relationship between ankle/brachial index and leg growth retardation was significant (R = 0.47, p less than 0.0005). Only one patient had symptoms of arterial occlusion (claudication), and one patient had symptoms of leg growth retardation (gait disturbance). We conclude that arterial occlusion is common after diagnostic femoral artery catheterization in children less than 5 years of age, but that excellent collateral supply prevents leg growth retardation and/or symptomatic arterial insufficiency in most children.(ABSTRACT TRUNCATED AT 250 WORDS)