Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo.

Numerous gene and cell therapy strategies are being developed for the treatment of neurodegenerative disorders. Many of these strategies use constitutive expression of therapeutic transgenic proteins, and although functional in animal models of disease, this method is less likely to provide adequate flexibility for delivering therapy to humans. Ligand-inducible gene expression systems may be more appropriate for these conditions, especially within the central nervous system (CNS). Mifepristone's ability to cross the blood-brain barrier makes it an especially attractive ligand for this purpose. We describe the production of a mifepristone-inducible vector system for regulated expression of transgenes within the CNS. Our inducible system used a lentivirus-based vector platform for the ex vivo production of mifepristone-inducible murine neural progenitor cells that express our transgenes of interest. These cells were processed through a series of selection steps to ensure that the cells exhibited appropriate transgene expression in a dose-dependent and temporally controlled manner with minimal background activity. Inducible cells were then transplanted into the brains of rodents, where they exhibited appropriate mifepristone-inducible expression. These studies detail a strategy for regulated expression in the CNS for use in the development of safe and efficient gene therapy for neurological disorders.

Transforming Growth Factor-ß3 Therapy Delays Postoperative Reossification and Improves Craniofacial Growth in Craniosynostotic Rabbits.

Postoperative reossification is a common clinical correlate following surgery. It has been suggested that an underexpression of transforming growth factor-ß3 (TGF-ß3) may be related to craniosynostosis and postoperative reossification. Adding TGF-ß3 may delay reossification and improve postoperative growth. The present study was designed to test this hypothesis. Thirty 10-day-old New Zealand white rabbits with hereditary coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 14), (2) suturectomy treated with bovine serum albumin (n = 8), and (3) suturectomy treated with TGF-ß3 protein (n = 8). At 10 days of age, a 3-mm × 15-mm coronal suturectomy was performed, and serial three-dimensional (3D) computed tomography (CT) scans and cephalographs were taken at 10, 25, 42, and 84 days of age. Calvaria were harvested at 84 days of age for histomorphometric analysis. Mean differences were analyzed using a group by age analysis of variance. Analysis of the 3D CT scan data revealed that sites treated with TGF-ß3 had significantly (P < .05) greater defect areas and significantly (P < .05) greater intracranial volumes through 84 days of age compared with controls. Histomorphometry showed that sites treated with TGF-ß3 had patent suturectomy sites and significantly (P < .001) less new bone in the suturectomy site compared with controls. Serial radiograph data revealed significant (P < .05) differences in craniofacial growth from 25 to 84 days in TGF-ß3-treated rabbits compared with controls. Data show that TGF-ß3 administration delayed reossification and improved craniofacial growth in this rabbit model. These findings also suggest that this molecular-based therapy may have potential clinical use.

The effects of testosterone on craniosynostotic calvarial cells: a test of the gene/environmental model of craniofacial anomalies.

INTRODUCTION: The gene-environmental interaction model for craniofacial development proposes that if a genetic predisposition for an anomaly is coupled with an environmental factor that can exacerbate this predisposition, more severe phenotypes will result. Here, we utilize cells derived from our non-syndromic rabbit model of craniosynostosis to test the hypothesis that an insult, testosterone (TP) administration (exogenous source) will alter the osteogenic activity of these cells. DESIGN: Calvarial cells from wild-type (WT) (N=13) or craniosynostotic (CS) rabbits (N=11) were stimulated with TP, an androgen receptor blocker, flutamide, and combined treatments. Proliferation and differentiation assays were conducted after 7 days. anova and t-tests were used to determine differences in stimulation and cell type. RESULTS: The CS cells had significantly greater proliferation after TP administration compared to WT. There were no appreciable changes in differentiation after TP stimulation. Flutamide administration or combined TP and flutamide administration decreased both proliferation and differentiation for both cell types similarly. CONCLUSIONS: Testosterone exposure caused an increase in cell proliferation for CS osteoblast cells. However, a therapy targeted to mitigate this response (flutamide therapy) similarly affected CS and WT cells, suggesting that the administration of flutamide or TP in the presence of flutamide decreases osteogenesis of these cells. Thus, although our data support a mechanism of gene-environmental interaction, these results would not support a therapeutic intervention based on this interaction.

Clinical outcomes of combined surgical treatment of medial epicondylitis and cubital tunnel syndrome.

Surgical results for treatment of medial epicondylitis and cubital tunnel syndrome are generally satisfactory when performed alone. However, our experience suggests a combined procedure is associated with inferior outcomes. A retrospective review was conducted of consecutive surgical cases of medial epicondylectomy/debridement and ulnar nerve decompression during a single operation at our institution from March 2008 to February 2017 using CPT codes. Thirty combined procedures were identified in 29 patients. Fourteen patients and 15 elbows returned to clinic for evaluation at average 4.3 years after surgery (8 men, 6 women, mean age 45.1 years). A Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, visual analogue pain scale (VAS), and physical examination were performed. The data was stratified by type of ulnar nerve procedure and analyzed. Three of fifteen elbows underwent in situ ulnar nerve decompression, and twelve of 15 had transposition, five subcutaneous and seven submuscular. The mean DASH score for in situ decompression was significantly higher than that of transposition (68.2 vs. 13.1). The average visual pain score for patients whom underwent in situ decompression was significantly higher than that of those with ulnar nerve transposition (8.0 vs. 1.2). All other physical exam measures demonstrated no significant difference between the two groups. In situ ulnar nerve decompression in the setting of medial epicondylectomy/debridement may be associated with inferior clinical outcomes in comparison to ulnar nerve transposition. Further studies are needed to validate the results of our study and inform management.

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice.

BACKGROUND AND PURPOSE: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. EXPERIMENTAL APPROACH: Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. KEY RESULTS: Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, galegine (50 microM-3 mM) stimulated glucose uptake. Galegine (1-300 microM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 microM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 microM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. CONCLUSIONS AND IMPLICATIONS: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

Energy supply patterns for finishing steers: Feed conversion efficiency, components of bodyweight gain and meat quality.

The objective was to determine the effect of pre-slaughter growth rate on feed efficiency, components of body growth and on the tenderness of longissimus muscle from steers reared to a common age and carcass weight. Sixty Friesian steers were group-housed and offered grass silage ad libitum and 3.5kg concentrates per animal daily for 5 months and then 5kg concentrates and 1kg grass hay for 1month before the experiment began. The animals were then weighed and in a randomised block were assigned to one of 5 groups, for slaughter at the beginning of the experiment or to be offered concentrates and hay (900 and 100g/kg total diet, respectively) to achieve target growths of: 0.72kg/day continuously for 17 weeks, 0.36kg/day for the first 8 weeks and 1.08kg/day for the final 8 weeks (low-high), 1.08kg/day for the first 8 weeks and 0.36 for the final 8 weeks (high-low) or 0.36kg/day for the first 2 weeks, 0.72kg/day during weeks 4 and 14 and 1.08kg/day for the final 2 weeks (pulse). One week was allowed for transition to the different dietary allowances within each energy supply pattern. The mean age at the beginning and end of the study was 18 and 22.5 months, respectively. After slaughter, the weight of the carcass and kidney+channel fat depot were recorded, the pistola hind quarter was dissected into fat, lean and bone and the tenderness of the m. longissimus thoracis et lumborum (LTM) muscle was measured instrumentally and using a trained taste panel after 2, 7 or 14 days ageing. The pattern of energy supply did not affect carcass weight, fat score or kidney+channel fat weight. The pistola hind quarter from animals offered the low-high energy pattern had a similar composition to the continuously-fed animals but contained more muscle than that from animals offered high-low or pulse energy patterns. After 14 days ageing, LTM from the continuously-fed animals was more tender than that from animals offered the other energy supply patterns but shear force did not differ between supply patterns. The data do not support the hypothesis that pre-slaughter growth rate increases tenderness but suggest that energy supply pattern can influence body composition of finishing cattle.

Effect of concentrate feeding pattern in a grass silage/concentrate beef finishing system on performance, selected carcass and meat quality characteristics.

Steers were offered grass silage ad libitum and 6.4 kg concentrates daily for 126 days or silage ad libitum for 35 days, followed by concentrates ad libitum (Experiment 1). Steers were offered grass silage ad libitum and 6 kg concentrates daily for 154 days, concentrates ad libitum or grass silage ad libitum for 112 days followed by concentrates ad libitum (Experiment 2). All treatments received the same total concentrate allowance. In Experiment 1, there was no difference in any measurement of meat quality. In Experiment 2, ad libitum concentrate feeding per se, decreased redness and increased shear force of muscle at 2 days post-mortem. Delaying concentrate feeding decreased fat yellowness, decreased shear force at 7 and 14 days post-mortem and increased muscle redness at 14 days post-mortem. Modifications of the beef production system examined had minor effects on beef quality which are unlikely to be of commercial significance.

Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016.

For decades, dental schools in the United States have endured a significant faculty shortage. Studies have determined that the top 2 sources of dental faculty are advanced education programs and private practice. Those who have completed both DDS and PhD training are considered prime candidates for dental faculty positions. However, there is no national database to track those trainees and no evidence to indicate that they entered academia upon graduation. The objective of this study was to assess outcomes of dental school-affiliated oral sciences PhD program enrollment, graduates, and placement between 1994 and 2016. Using the American Dental Association annual survey of advanced dental education programs not accredited by the Commission on Dental Accreditation and data obtained from 22 oral sciences PhD programs, we assessed student demographics, enrollment, graduation, and placement. Based on the data provided by program directors, the average new enrollment was 33, and graduation was 26 per year. A total of 605 graduated; 39 did not complete; and 168 were still in training. Among those 605 graduates, 211 were faculty in U.S. academic institutions, and 77 were faculty in foreign institutions. Given that vacant budgeted full-time faculty positions averaged 257 per year during this period, graduates from those oral sciences PhD programs who entered academia in the United States would have filled 9 (3.6%) vacant faculty positions per year. Therefore, PhD programs have consistently generated only a small pipeline of dental school faculty. Better mentoring to retain talent in academia is necessary. Stronger support and creative funding plans are essential to sustain the PhD program. Furthermore, the oral sciences PhD program database should be established and maintained by dental professional organizations to allow assessments of training models, trends of enrollment, graduation, and placement outcomes.

Craniofacial morphology in myostatin-deficient mice.

GDF-8 (myostatin) is a negative growth regulator of skeletal muscle, and myostatin-deficient mice are hypermuscular. Muscle size and force production are thought to influence growth of the craniofacial skeleton. To test this relationship, we compared masticatory muscle size and craniofacial dimensions in myostatin-deficient and wild-type CD-1 control mice. Myostatin-deficient mice had significantly (p < 0.01) greater body (by 18%) and masseter muscle weight (by 83%), compared with wild-type controls. Significant differences (p < 0.05) were noted for cranial vault length, maxillary length, mandibular body length, and mandibular shape index. Significant correlations were noted between masseter muscle weight and mandibular body length (r = 0.68; p < 0.01), cranial vault length (r = -0.57; p < 0.05), and the mandibular shape index (r = -0.56; p < 0.05). Masticatory hypermuscularity resulted in significantly altered craniofacial morphology, probably through altered biomechanical stress. These findings emphasize the important role that masticatory muscle function plays in the ontogeny of the cranial vault, the maxilla, and, most notably, the mandible.

Moving to a purpose built acute psychiatric unit on a general hospital site--does the new environment produce change for the better?

The environment of a hospital can have a significant impact on the experiences of patients. In March 2003 a new purpose built acute psychiatric admission unit opened on the site of Kilkenny General hospital, while the admission wards of the 2 local stand-alone psychiatric hospitals closed. We sought to compare admissions before and after the move, hypothesising that there would be lower levels of aggression, sedative prescribing and intoxicant abuse in the new unit. Details of 98 acute admissions that occurred during the first 3 months of 2002 were compared to 97 acute admissions that occurred during the first 3 months of 2004. Average daily diazepam and chlorpromazine equivalents were calculated for each patient. The Modified Overt Aggression Scale (MOAS) was used to compare levels of aggression. Compared to 2002 fewer patients left the hospital against medical advice in 2004 (OR 0.35, p = 0.027). Overall levels of aggression fell significantly (p = 0.001). Levels of benzodiazapine prescribing also fell (Mean diazepam daily dose 5.75 mg in 2002 versus 4.14 mg in 2004; p = 0.003). There were trends towards reductions in involuntary admissions, admissions of intoxicated people, patients abusing intoxicants in hospital and in antipsychotic prescribing. It is likely that the more pleasant, better designed and less stigmatising environment of the new unit together with the renewed energy and optimism of clinical staff contributed to the changes observed.

Wheatstone bridge configuration for evaluation of plasmonic energy transfer.

We propose an internal (on-chip) Wheatstone bridge configuration to evaluate the efficiency of near-field transducers (NFT) as used in heat-assisted magnetic recording (HAMR). The electric field enhancement between the transducer and the image plane is monitored by measuring the resistance of metal electrodes composing the image plane. The absorption of the enhanced electric field causes an increase in the metal temperature, and thereby, in its resistance whose variation is monitored with an internal Wheatstone bridge which is accurately balanced in the absence of the electric field.

Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial.

Combination of non-nicotine pharmacotherapies has been underexamined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP + NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP + NTX, 54.1%; BUP + PBO, 33.3%), P = 0.0210, but not at 6-month follow-up (BUP + NTX, 27.9%; BUP + PBO, 15.0%), P = 0.09. Continuous abstinence rates did not differ, P = 0.0740 (BUP + NTX, 26.2%; BUP + PBO, 13.3%). Those receiving BUP + NTX reported reduced nicotine withdrawal, P = 0.0364. The BUP + NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups.

N-terminally modified glucagon-like peptide-1(7-36) amide exhibits resistance to enzymatic degradation while maintaining its antihyperglycaemic activity in vivo.

Glucagon-like peptide-1(7-36)amide (tGLP-1) is inactivated by dipeptidyl peptidase (DPP) IV by removal of the NH(2)-terminal dipeptide His(7)-Ala(8). We examined the degradation of NH(2)-terminally modified His(7)99% of His(7)-glucitol tGLP-1 remained intact at 12 h. His(7)-glucitol tGLP-1 was similarly resistant to plasma degradation in vitro. His(7)-glucitol tGLP-1 showed greater resistance to degradation in vivo (92% intact) compared to tGLP-1 (27% intact) 10 min after i.p. administration to Wistar rats. Glucose homeostasis was examined following i.p. injection of both peptides (12 nmol/kg) together with glucose (18 mmol/kg). Plasma glucose concentrations were significantly reduced and insulin concentrations elevated following peptides administration compared with glucose alone. The area under the curve (AUC) for glucose for controls (AUC 691+/-35 mM/min) was significantly lower after administration of tGLP-1 and His(7)-glucitol tGLP-1 (36 and 49% less; AUC 440+/-40 and 353+/-31 mM/min, respectively; P<0.01). This was associated with a significantly higher AUC for insulin (98-99% greater; AUC 834+/-46 and 838+/-39 ng/ml/min, respectively; P<0.01) after tGLP-1 and His(7)-glucitol tGLP-1 administration compared to controls (421+/-30 ng/ml/min). In conclusion, His(7)-glucitol tGLP-1 resists plasma DPP IV degradation while retaining potent antihyperglycaemic and insulin-releasing activities in vivo.

N-terminal glycation of cholecystokinin-8 abolishes its insulinotropic action on clonal pancreatic B-cells.

Monoglycated cholecystokinin octapeptide (Asp(1)-glucitol CCK-8) was prepared under hyperglycaemic reducing conditions and purified by reverse phase-high performance liquid chromatography. Electrospray ionisation mass spectrometry and automated Edman degradation demonstrated that CCK-8 was glycated specifically at the amino-terminal Asp(1) residue. Effects of Asp(1)-glucitol CCK-8 and CCK-8 on insulin secretion were examined using glucose-responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10(-10) mol/l CCK-8 enhanced insulin release by 1.2-1.5-fold at 5.6-11.1 mmol/l glucose. The stimulatory effect induced by 10(-10) mol/l CCK-8 was abolished following glycation. At 5.6 mmol/l glucose, CCK-8 at concentrations ranging from 10(-11) to 10(-7) mol/l induced a significant 1.6-1.9-fold increase in insulin secretion. Insulin output in the presence of Asp(1)-glucitol CCK-8 over the concentration range 10(-11)-10(-7) mol/l was decreased by 21-35% compared with CCK-8, and its insulinotropic action was effectively abolished. Asp(1)-glucitol CCK-8 at 10(-8) mol/l also completely blocked the stimulatory effects of 10(-11)-10(-8) mol/l CCK-8. These data indicate that structural modification by glycation at the amino-terminal Asp(1) residue effectively abolishes and/or antagonises the insulinotropic activity of CCK-8.

NH2-terminally modified gastric inhibitory polypeptide exhibits amino-peptidase resistance and enhanced antihyperglycemic activity.

Gastric inhibitory polypeptide (GIP) is an important insulin-releasing hormone of the enteroinsular axis that, like glucagon-like peptide 1(7-36) amide (tGLP-1), has a functional profile of possible therapeutic value for type 2 diabetes. Both incretin hormones are rapidly inactivated in plasma by the exopeptidase dipeptidyl peptidase (DPP) IV. The present study examined the ability of NH2-terminal modification of human GIP to protect from plasma degradation and enhance insulin-releasing and antihyperglycemic activity. Degradation of GIP by incubation at 37 degrees C with purified DPP IV was clearly evident after 4 h (54% intact). After 12 h, >60% of GIP was converted to GIP(3-42), whereas >99% of NH2-terminally modified Tyr1-glucitol GIP remained intact. Tyr1-glucitol GIP was similarly resistant to serum degradation. The formation of GIP(3-42) was almost completely abolished by inhibition of plasma DPP IV with diprotin A. Effects of GIP and Tyr1-glucitol GIP were examined in Wistar rats after intraperitoneal injection of either peptide (10 nmol/kg) together with glucose (18 mmol/kg). Plasma glucose concentrations were significantly lower and insulin concentrations higher after both peptides compared with glucose alone. More importantly, individual glucose values at 15 and 30 min together with the areas under the curve (AUCs) for glucose were significantly lower after administration of Tyr1-glucitol GIP compared with GIP (AUC 255 +/- 33 vs. 368 +/- 8 mmol x l(-1) x min(-1), respectively; P < 0.01). This was associated with a significantly greater and more protracted insulin response after Tyr1-glucitol GIP than GIP (AUC 773 +/- 41 vs. 639 +/- 39 ng x ml(-1) x min(-1); P < 0.05). These data demonstrate that Tyr1-glucitol GIP displays resistance to plasma DPP IV degradation and exhibits enhanced antihyperglycemic activity and insulin-releasing action in vivo.

Glycated cholecystokinin-8 has an enhanced satiating activity and is protected against enzymatic degradation.

Monoglycated cholecystokinin octapeptide (CCK-8) (glucitol-Asp1 adduct) modified at the NH2-terminus was prepared under hyperglycemic conditions, purified by high-performance liquid chromatography, and characterized by mass spectrometry (Mr 1228.4 Da) and peptide sequencing. CCK-8 (100 nmol/kg, i.p.) significantly (P < 0.001) reduced voluntary food intake of fasted mice for up to 30 min after its administration, compared with saline-administered controls. Glycated CCK-8 reduced food intake at 30-120 min (P < 0.01 to P < 0.001) and significantly reduced feeding compared with CCK-8 from 60 to 120 min (P < 0.01). In vitro plasma degradation studies indicated that glycated CCK-8 was resistant to the normal rapid enzymatic conversion to CCK fragments. This study demonstrated that CCK-8 is a potent short-term inhibitor of food intake, and that structural modification of this peptide by amino-terminal glycation leads to enhanced satiating activity, partially due to increased resistance to serum aminopeptidase degradation.

Bidirectional crossover and late outcome after coronary angioplasty and bypass surgery: 8 to 11 year follow-up.

Between March 1978 and July 1981, 217 symptomatic patients underwent coronary angioplasty as an alternative to coronary bypass surgery. Angioplasty was successful in 143 patients (66%), unsuccessful but uncomplicated in 65 (30%) and complicated in 9 (4%) by one or more of the following criteria: Q wave myocardial infarction (2%), emergency surgery (4%) or death (0.5%). Late follow-up evaluation was obtained in 213 patients at a mean of 9 +/- 1 years. Of patients in whom angioplasty was successful, 59 (42%) of 140 required another revascularization procedure (repeat angioplasty in 26% and bypass surgery in 16%). The actuarial survival rate at 5, 9 and 10 years after successful angioplasty was 98%, 93% and 92%, respectively. Of the 65 patients with unsuccessful and uncomplicated angioplasty (usually as a result of technical factors), 58 underwent elective bypass surgery within 2 months and 56 survived. These 56 surgical patients were compared with the 140 patients with successful angioplasty. Univariate analysis of prognostic factors did not reveal significant differences between these two groups. At late follow-up study, the successful angioplasty and the successful surgical groups had similar rates of survival (93% versus 95%, p = NS) and of death or infarction, or both (11% versus 12.5%, p = NS). Repeat revascularization was required more frequently after successful angioplasty than after surgery (42% versus 18%, p less than 0.001). Crossover from angioplasty to surgery occurred slightly more often than from surgery to angioplasty (16% versus 12.5%, p = NS). The time to crossover from angioplasty to surgery occurred earlier than from surgery to angioplasty (mean 21 versus 76 months, p less than 0.001).

Directional atherectomy versus balloon angioplasty for coronary ostial and nonostial left anterior descending coronary artery lesions: results from a randomized multicenter trial. The CAVEAT-I investigators. Coronary Angioplasty Versus Excisional Atherectomy Trial.

OBJECTIVES: We hypothesized that atherectomy would be superior to balloon angioplasty for ostial and nonostial left anterior descending coronary artery lesions. BACKGROUND: Balloon angioplasty of ostial coronary artery lesions has been associated with a lower procedural success rate and a higher rate of complications and of restenosis than angioplasty of nonostial stenoses. Directional coronary atherectomy has been proposed as an alternative therapy for ostial lesions. METHODS: In the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I), 1,012 patients were randomized to undergo either procedure; 563 patients had proximal left anterior descending coronary artery lesions, of which 74 were ostial. We compared balloon angioplasty with directional atherectomy for early and 6-month results for ostial as well as nonostial proximal left anterior descending coronary artery lesions. RESULTS: Directional atherectomy led to an initially higher gain in minimal lumen diameter for ostial lesions (1.13 vs. 0.56 mm, respectively, p < 0.001) but a higher rate of adjudicated non-Q wave myocardial infarction (24% vs. 13%, respectively, p < 0.001) than balloon angioplasty and no improvement in restenosis rates (48% vs. 46%, respectively). In the nonostial proximal left anterior descending coronary artery lesions, angiographic restenosis was reduced (51% vs. 66%, p = 0.012), but this was also associated with a higher rate of periprocedural myocardial infarction (8% vs. 2%, p = 0.008 by site and 24% vs. 8%, p < 0.001 by adjudication) and no difference in the need for subsequent coronary artery bypass surgery (7.3% vs. 8.4%, respectively) or repeat percutaneous coronary intervention (24% vs. 26%, respectively). CONCLUSIONS: For ostial left anterior descending coronary artery stenoses, both procedures yielded similar rates of initial success and restenosis, but atherectomy was associated with more non-Q wave myocardial infarction. In this trial the predominant angiographic benefit (increased early gain and less angiographic restenosis) of atherectomy for the left anterior descending coronary artery was in proximal nonostial lesions. However, the tradeoffs for this angiographic advantage were more in-hospital myocardial infarctions and no decrease in clinical restenosis.

The effects of guided tissue regeneration (GTR) on modified Le Fort I osteotomy healing in rabbits.

Osteogenesis following surgery depends on the osteoblasts at the wound site. Fibrous nonunions may be the result of differential and rapid migration of fibroblasts compared to osteoblasts into the wound. The present study was designed to test this hypothesis through the use of guided tissue regeneration (GTR) in a rabbit model. Bilateral, Le Fort I osteotomies (n=20) were produced in the maxillae of 10 New Zealand White rabbits. The segments were advanced 6mm and rigidly fixed using microplates and screws. One side was covered with a resorbable collagen membrane or left uncovered. Rabbits were followed for four weeks with radiographs and the maxillae were harvested for histology. Cephalometry revealed that membrane-covered defects had significantly (P<0.01) reduced defect area (by approximately 70%) compared to uncovered defects. Histologically, membrane-covered defects showed more organized osteogenesis and less fibrous tissue than uncovered defects. Histomorphometry revealed that membrane covered defects had significantly (P<0.05) reduced defect areas (by approximately 20%) compared to uncovered defects. While findings suggest that GTR can facilitate osseous wound healing in Le Fort I osteotomies, results also caution against relying exclusively on two-dimensional radiography to assess bony wound healing in lieu of three-dimensional imaging and evaluations.

Geophysical investigation of seepage beneath an earthen dam.

A hydrogeophysical survey is performed at small earthen dam that overlies a confined aquifer. The structure of the dam has not shown evidence of anomalous seepage internally or through the foundation prior to the survey. However, the surface topography is mounded in a localized zone 150 m downstream, and groundwater discharges from this zone periodically when the reservoir storage is maximum. We use self-potential and electrical resistivity tomography surveys with seismic refraction tomography to (1) determine what underlying hydrogeologic factors, if any, have contributed to the successful long-term operation of the dam without apparent indicators of anomalous seepage through its core and foundation; and (2) investigate the hydraulic connection between the reservoir and the seepage zone to determine whether there exists a potential for this success to be undermined. Geophysical data are informed by hydraulic and geotechnical borehole data. Seismic refraction tomography is performed to determine the geometry of the phreatic surface. The hydro-stratigraphy is mapped with the resistivity data and groundwater flow patterns are determined with self-potential data. A self-potential model is constructed to represent a perpendicular profile extending out from the maximum cross-section of the dam, and self-potential data are inverted to recover the groundwater velocity field. The groundwater flow pattern through the aquifer is controlled by the bedrock topography and a preferential flow pathway exists beneath the dam. It corresponds to a sandy-gravel layer connecting the reservoir to the downstream seepage zone.