Extreme seasonal water-level changes and hydraulic modeling of deep, high-altitude, glacial-carved, Himalayan lakes.

Himalayan lakes represent critical water resources, culturally important waterbodies, and potential hazards. Some of these lakes experience dramatic water-level changes, responding to seasonal monsoon rains and post-monsoonal draining. To address the paucity of direct observations of hydrology in retreating mountain glacial systems, we describe a field program in a series of high altitude lakes in Sagarmatha National Park, adjacent to Ngozumba, the largest glacier in Nepal. In situ observations find extreme (>12 m) seasonal water-level changes in a 60-m deep lateral-moraine-dammed lake (lacking surface outflow), during a 16-month period, equivalent to a 5 [Formula: see text] m[Formula: see text] volume change annually. The water column thermal structure was also monitored over the same period. A hydraulic model is constructed, validated against observed water levels, and used to estimate hydraulic conductivities of the moraine soils damming the lake and improves our understanding of this complex hydrological system. Our findings indicate that lake level compared to the damming glacier surface height is the key criterion for large lake fluctuations, while lakes lying below the glacier surface, regulated by surface outflow, possess only minor seasonal water-level fluctuations. Thus, lakes adjacent to glaciers may exhibit very different filling/draining dynamics based on presence/absence of surface outflows and elevation relative to retreating glaciers, and consequently may have very different fates in the next few decades as the climate warms.

Improving deformable surface meshes through omni-directional displacements and MRFs.

Deformable surface models are often represented as triangular meshes in image segmentation applications. For a fast and easily regularized deformation onto the target object boundary, the vertices of the mesh are commonly moved along line segments (typically surface normals). However, in case of high mesh curvature, these lines may intersect with the target boundary at "non-corresponding" positions, or even not at all. Consequently, certain deformations cannot be achieved. We propose an approach that allows each vertex to move not only along a line segment, but within a surrounding sphere. We achieve globally regularized deformations via Markov Random Field optimization. We demonstrate the potential of our approach with experiments on synthetic data, as well as an evaluation on 2 x 106 coronoid processes of the mandible in Cone-Beam CTs, and 56 coccyxes (tailbones) in low-resolution CTs.

In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model.

BACKGROUND CONTEXT: Prevention of osteoporotic vertebral fractures could help at-risk individuals avoid the pain and morbidity associated with these fractures. Currently, patients with osteoporosis are treated with systemic medications to reduce fracture risk. Although effective, these therapies do not eliminate fractures and also tend to have a gradual time-dependent effect on fracture risk. The mechanism of action of the bone morphogenetic protein (BMP) family theoretically makes these molecules candidates for rapidly enhancing local bone structure. STUDY DESIGN: An in vivo study analyzing the effects of BMP-7 (osteogenic protein 1 [OP-1]) treatment on osteopenic ovine vertebral architecture and biomechanics. PURPOSE: We tested the hypothesis that local injection of OP-1 into osteopenic ovine vertebrae will improve bone mass and trabecular distribution, thereby reducing bone fragility and fracture risk. We specifically evaluated compressive biomechanics and morphology of osteopenic ovine vertebral bodies 6 months after local OP-1 treatment. STUDY DESIGN: In vivo animal study. METHODS: Skeletally mature sheep (n=24) underwent ovariectomy and were placed on low cation relative to anion diet. These interventions reduce bone density and induce skeletal fragility. After 6 months, sheep were randomly assigned to six treatment groups based on OP-1 dose (370 mg or 0 mg) and carrier with 4 animals/treatment group. Carriers A and B were poly-L-glycolic acid (PLGA) biospheres with different release kinetics (B allowing sustained BMP release); Carrier C was carboxymethylcellulose. After creating an 8-mm-diameter defect in the midvertebral body, sheep underwent intravertebral body implantation at two nonadjacent levels. Animals were euthanized 6 months after implantation and bone mineral density (BMD), biomechanics, and histomorphometry were assessed. Two-way analysis of variance was used to determine effects of OP-1 (alpha=0.05). RESULTS: An 81.9%, 333.2%, and 39.9% increase in stiffness was seen for OP-1 treated vertebra with Carriers A, B, and C respectively. Although these effects did not reach statistical significance, trends toward improvement were evident. Histology showed varied degrees of bony healing in the injection sites. Histomorphometrically, OP-1 treated vertebrae showed improvements in percent bone of up to 38% and star volume of up to 55% (with Carrier B). Improvements in whole vertebral body BMD were not detected for any treatment. CONCLUSION: In this study, local OP-1 treatment showed a positive trend in improving mechanical strength and histomorphometric parameters of osteopenic vertebra, despite the absence of consistent change in BMD. Controlled slow release of OP-1 using PLGA microspheres appeared to be the most effective method of protein delivery. In conclusion, we feel that the pilot data suggest that the use of OP-1 in the treatment of vertebral osteoporosis in an attempt to enhance bone strength merits further study.

Abnormal neuronal metabolism and storage in mucopolysaccharidosis type VI (Maroteaux-Lamy) disease.

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy disease, is an inherited disorder of glycosaminoglycan catabolism caused by deficient activity of the lysosomal hydrolase, N-acetylgalactosamine 4-sulphatase (4S). A variety of prominent visceral and skeletal defects are characteristic, but primary neurological involvement has generally been considered absent. We report here that the feline model of MPS VI exhibits abnormal lysosomal storage in occasional neurones and glia distributed throughout the cerebral cortex. Abnormal lysosomal inclusions were pleiomorphic with some resembling zebra bodies and dense core inclusions typical of other MPS diseases or the membranous storage bodies characteristic of the gangliosidoses. Pyramidal neurones were shown to contain abnormal amounts of GM2 and GM3 gangliosides by immunocytochemical staining and unesterified cholesterol by histochemical (filipin) staining. Further, Golgi staining of pyramidal neurones revealed that some possessed ectopic axon hillock neurites and meganeurites similar to those described in Tay-Sachs and other neuronal storage diseases with ganglioside storage. Some animals evaluated in this study also received allogeneic bone marrow transplants, but no significant differences in neuronal storage were noted between treated and untreated individuals. These studies demonstrate that deficiency of 4S activity can lead to metabolic abnormalities in the neurones of central nervous system in cats, and that these changes may not be readily amenable to correction by bone marrow transplantation. Given the close pathological and biochemical similarities between feline and human MPS VI, it is conceivable that children with this disease have similar neuronal involvement.

Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults.

Despite an abundance of literature describing the basic mechanisms of action of L-carnitine metabolism, there remains some uncertainty regarding the effects of oral L-carnitine supplementation on in vivo fatty acid oxidation in normal subjects under normal conditions. It is well known that L-carnitine normalizes the metabolism of long-chain fatty acids in cases of carnitine deficiency. However, it has not yet been shown that L-carnitine influences the metabolism of long-chain fatty acids in subjects without disturbances in fatty acid metabolism. Therefore, we investigated the effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation by measuring 1-[(13)C] palmitic acid oxidation in healthy subjects before and after L-carnitine supplementation (3 x 1 g/d for 10 days). We observed a significant increase in (13)CO(2) exhalation. This is the first investigation to conclusively demonstrate that oral L-carnitine supplementation results in an increase in long-chain fatty acid oxidation in vivo in subjects without L-carnitine deficiency or without prolonged fatty acid metabolism.

Histologic evaluation of the efficacy of rhBMP-2 compared with autograft bone in sheep spinal anterior interbody fusion.

STUDY DESIGN: The sheep anterior lumbar spinal fusion model was used to study the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)-collagen composite in comparison with autograft to enhance spinal interbody fusion. Comparisons were drawn from temporal radiographic and end-point biomechanical and histologic data. OBJECTIVE: To analyze histologically the ability of rhBMP-2 to achieve complete arthrodesis between vertebral bodies. SUMMARY OF BACKGROUND DATA: Studies using rhBMP for enhancement of anterior interbody fusion have used numerous endpoints. However, systematic histologic evaluation of the fusion has not been conducted. METHODS: Twelve sheep underwent single-level anterior lumbar interbody fusion performed with a cylindrical fenestrated titanium interbody fusion device (INTER FIX, Medtronic Sofamor Danek, Inc., Memphis, TN). The device was filled either with rhBMP-2-collagen (n = 6) or autogenous iliac crest bone graft (n = 6). Radiologic evaluation was carried out at 2-month intervals, and all sheep were killed 6 months after surgery. Nondestructive biomechanical testing for stiffness to flexion, extension, and lateral bending moments, un-decalcified histology, and qualitative and quantitative histologic evaluation were performed. RESULTS: Radiographs revealed a bony bridge anterior to the cage in five of six rhBMP-2-treated animals, whereas it was present only in one of five in the autogenous bone graft group. Segments treated with rhBMP-2 were 20% stiffer in flexion than autograft-treated segments at 6 months. Six of six in the rhBMP-2 group and two of six in the autograft group showed complete fusion. There was a significantly higher rate of bony continuity observed at the fenestrations of the rhBMP-2 group. Three times more number of cage fenestrations in the rhBMP-2 group demonstrated "all-bone" when compared with the autograft group (P < 0.001). Further, the scar tissue in and around the autograft-treated cages was 16-fold more (P < 0.01) than that seen for rhBMP-2-treated cages. CONCLUSIONS: The study demonstrates that rhBMP-2 can lead to earlier radiologic fusion and a more consistent increased stiffness of the segments when compared with autograft in sheep anterior lumbar interbody fusion. Furthermore, a three times higher histologic fusion rate is attainable with significantly reduced fibrous tissue around the implant when rhBMP-2 is used.

The relative efficacy of fluoxetine and manual-based self-help in the treatment of outpatients with bulimia nervosa.

A randomized, placebo-controlled study was conducted examining the singular and combined effects of fluoxetine and a self-help manual on suppressing bulimic behaviors in women with bulimia nervosa. A total of 91 adult women with bulimia nervosa were randomly assigned to one of four conditions: placebo only, fluoxetine only, placebo and a self-help manual, or fluoxetine and a self-help manual. Subjects were treated for 16 weeks. Primary outcome measures included self-reports of bulimic behaviors. Fluoxetine and a self-help manual were found to be effective in reducing the frequency of vomiting episodes and in improving the response rates for vomiting and binge-eating episodes. Furthermore, both factors were shown to be acting additively on the primary and secondary efficacy measures in this study. Results are discussed in relation to previous research and the implications for treatment of bulimia nervosa.

The diet prescription for obesity. What works?

Obesity is a chronic disease, and in most cases weight reduction is the first treatment for its concomitant conditions of hyperlipidemia, diabetes, and hypertension. Weight-reduction diets are controversial in both the popular press and among clinicians treating hyperlipidemia and obesity. Both high-carbohydrate/low-fat and higher-protein/low-carbohydrate diets will produce loss of body fat if the calorie level is low enough. But selecting effective diet prescriptions for bariatric patients requires understanding of both the science and art of nutrition. Low-calorie diets, protein-sparing modified fasts, and modified-carbohydrate diets seem to be the most effective for patient compliance, and modified-carbohydrate plans are probably necessary for maintenance of the weight loss.

Direct current electrical stimulation increases the fusion rate of spinal fusion cages.

STUDY DESIGN: A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. OBJECTIVES: To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. METHODS: Twenty-two sheep underwent lumbar discectomy and fusion at L4-L5 with an 11- x 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-microA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-microA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. RESULTS: The histologic fusion rate increased as the direct current dose increased from 0 microA to 40 microA to 100 microA (P < 0.009). Histologically, all animals in the 100-microA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P < 0.120), left lateral bending (P < 0.017), right axial rotation (P < 0.004), left axial rotation (P < 0.073), extension (P < 0.078), and flexion (P < 0.029) over nonstimulated levels. CONCLUSION: Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months.

Eating disorders and psychiatric disorders in the first-degree relatives of obese probands with binge eating disorder and obese non-binge eating disorder controls.

OBJECTIVE: The purposes of the present study were to examine the possibility of a familial tendency for binge eating disorder (BED) among the obese, to clarify the relationship between BED and other eating disorders, and to test the relationship between BED and other psychiatric disorders. METHOD: We studied 32 female BED outpatients and 23 obese females without BED. A possible history of eating disorders was assessed using the Structured Clinical Interview for DSM-III-R-Eating Disorders section administered by telephone interview. Family history information for other psychiatric disorders was collected using the Family History Research Diagnostic Criteria RESULTS: The frequency of all eating disorders and the risk for other psychiatric disorders were not significantly different between the relatives of the two groups. These results were consistent across generation and gender. DISCUSSION: This study failed to show a familial tendency for BED, or any significant familial relationship between BED and other eating disorders, and did not support the hypothesis of coaggregation of other psychiatric disorders with BED.

Effect of acute gastric dilatation on gastric myoelectic and motor activity in dogs.

OBJECTIVE: To investigate the effects of experimentally induced acute gastric dilatation on electrical and mechanical activities of the stomach in dogs. ANIMALS: 7 healthy dogs. PROCEDURE: Electrodes and strain-gauge force transducers were implanted on the serosal surface of the antrum and pylorus. Eight days later, baseline gastric electrical and contractile activities were recorded. The dogs were anesthetized and mechanically ventilated to maintain normocapnia while the stomach was distended (intragastric pressure, 30 mm Hg) for 180 minutes, using a thin compliant bag. Gastric electrical and contractile activities were recorded again on days 1 and 10 after dilatation. Recordings were analyzed to determine gastric slow-wave frequency, slow-wave dysrhythmia, propagation velocity of slow-waves, coupling of contractions to slow waves, motility index on the basis of relative contractile amplitudes, and onset of contractions after a standardized meal. RESULTS: Electrical or contractile activities were not significantly different 18 hours after acute gastric dilatation (day 1). Arrhythmias were evident before and after gastric dilatation in dogs from which food was withheld and in dogs after consumption of a meal. CONCLUSIONS: Variables for assessing gastric electrical and contractile activities were unaffected 18 hours after acute gastric dilatation. CLINICAL RELEVANCE: Analysis of results of this study indicated that altered electrical and contractile activities in dogs with short-term gastric dilatation are not likely to be secondary to the process of acute gastric dilatation.

Carnitine metabolism and its regulation in microorganisms and mammals.

In procaryotes, L-carnitine may be used as both a carbon and nitrogen source for aerobic growth, or the carbon chain may be used selectively following cleavage trimethylamine. Under anaerobic conditions and in the absence of preferred substrates, some bacteria use carnitine, via crotonobetaine, as an electron acceptor. Formation of trimethylamine and lambda-butyrobetaine (from reduction of crotonobetaine) from L-carnitine by enteric bacteria has been demonstrated in rats and humans. Carnitine is not degraded by enzymes of eukaryotic origin. In higher organisms, carnitine has specific functions in intermediary metabolism. Concentrations of carnitine and its esters in cells of eukaryotes are rigorously maintained to provide optimal function. Carnitine homeostasis in mammals is preserved by a modest rate of endogenous synthesis, absorption from dietary sources, efficient reabsorption, and mechanisms present in most tissues that establish and maintain substantial concentration gradients between intracellular and extracellular carnitine pools.

Onset of binge eating and dieting in overweight women: implications for etiology, associated features and treatment.

This study investigated differences between overweight binge eating women who reported the onset of binge eating prior to or following the onset of dieting (binged first [BF], or dieted first [DF]). Of overweight binge eating subjects enrolled in a treatment study, 38.7% indicated binge eating first, and 48.1% dieting first. The mean age of onset of binge eating differed significantly between the two groups (11.8 years vs. 25.7 years). More of the BF group (82.5%) satisfied proposed binge eating disorder (BED) criteria than did the DF group (52.0%), although short of significantly. The results suggest that: (a) the leading hypothesis concerning dieting as a cause of binge eating does not apply to a substantial number of individuals who binge eat; (b) there may be an early pattern and a late pattern in the development of binge eating among overweight individuals; and (c) the early or binge first pattern may be more likely to result in BED.

Passive drainage versus primary closure after total ear canal ablation-lateral bulla osteotomy in dogs: 59 dogs (1985-1995).

OBJECTIVE: Compare passive wound drainage to primary closure of total ear canal ablation-lateral bulla osteotomy (TECA-LBO) in dogs. STUDY DESIGN: Retrospective analysis of medical records. SAMPLE POPULATION: Fifty-nine dogs with end-stage otitis externa or neoplasia of the external and middle ear. METHODS: Medical records of dogs with TECA-LBO were reviewed. Dogs were divided into postoperative drain and primary closure groups. Statistical analyses were performed to identify differences in data for signalment, preoperative treatment, duration of hospitalization, immediate complications, and long-term complications between groups. RESULTS: No significant differences were detected in signalment, diagnosis, and duration of medical management between groups (P > .05). Duration of hospitalization was greater for dogs in the drain group (P < .05). Immediate postoperative complications occurred in 26 of 59 dogs and included ipsilateral facial palsy, incision swelling, vestibular signs, premature drain removal, and one dog died of aspiration pneumonia. Long-term (> 6 months) complications were identified in 12 of 50 dogs and included dermatitis of the medial aspect of the pinna, chronic fistula formation, and permanent facial paralysis. No association between immediate or long term complications and method of closure was identified. CONCLUSIONS: Primary closure is an acceptable alternative in dogs undergoing TECA-LBO when surgical wound dead space can be managed with meticulous hemostasis, complete debridement of devitalized tissue, and accurate apposition of tissue planes.

Clinical evaluation of tube esophagostomy in small animals.

An alternative technique for placement of tube esophagostomy in small animals is described. Tube esophagostomy was placed in 13 dogs and nine cats. The mean duration of tube placement was 23 days (range, one to 48 days). No significant complications related to the tube were noted. In each case, tube esophagostomy was tolerated and time to healing of the esophagostomy site following tube removal was less than two weeks. Tube esophagostomy is suitable for use in a nutritionally compromised small animal with a functional esophagus and gastrointestinal tract.

Effect of metoclopramide on fed-state gastric myoelectric and motor activity in dogs.

OBJECTIVE: To investigate the effects of metoclopramide, a putative gastroprokinetic agent, on dogs that had recovered from gastric dilatation-volvulus (GDV), a disorder characterized by delayed gastric emptying. ANIMALS: 6 healthy dogs and 5 dogs after treatment and recovery from GDV. PROCEDURE: Baseline recordings of gastric electrical and contractile activities were made 8 or 10 days after circumcostal gastropexy and implantation of serosal electrodes and strain-gauge force transducers. Gastric activities were recorded again the next day after treatment with the clinically recommended oral metoclopramide dose (0.3 mg/kg of body weight) administered a half hour before feeding. Recordings were analyzed to determine gastric slow-wave frequency, presence of slow-wave dysrhythmia, slow-wave propagation velocity, coupling of contractions to slow waves, a motility index based on relative contractile amplitudes, and onset of contractions after a standardized meal. RESULTS: Significant differences in gastric electrical or contractile activities were not detected after metoclopramide treatment in dogs with GDV. Compared with control dogs after metoclopramide treatment, gastric slow-wave propagation velocity was significantly (P = 0.03) faster for the dogs with GDV at postprandial minute 90. CONCLUSION: At a clinically recommended dosage, metoclopramide treatment did not change gastric myoelectric and motor activities in a way that would promote increased gastric emptying in dogs with GDV. CLINICAL RELEVANCE: Metoclopramide treatment may not benefit dogs with GDV and delayed gastric emptying.

Conditions of the thoracolumbar spine.

Neurological deficits suggesting trauma to the spinal cord in the thoracolumbar area are the most common clinical presentation of neurosurgical conditions. By far, the most common cause of thoracolumbar spinal cord dysfunction is intervertebral disc disease. Disc herniation and subsequent spinal cord compression usually requires prompt medical treatment, then referral for high detail radiographs, myelogram, and surgical decompression. Other causes of thoracolumbar spinal cord dysfunction include neoplasia, discospondylitis, fibrocartilaginous embolism, and degenerative myelopathy.