ABSTRACT
BACKGROUND: Identifying pretreatment dietary habits that are associated with weight-loss intervention outcomes could help guide individuals' selection of weight-loss approach among competing options. A pretreatment factor that may influence weight-loss outcomes is macronutrient intake. METHODS: Overweight and obese Durham Veterans Affairs outpatients were randomised to a weight-loss intervention with a low-carbohydrate diet (n = 71) or orlistat medication therapy plus a low-fat diet (n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4-day food records. Linear mixed-effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight-loss condition. RESULTS: Participant's mean age was 53 years, baseline body mass index was 39.3 kg m(-2) and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss (P = 0.02) and less rapid weight regain (P = 0.03) in the low-carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low-fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain (P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition. CONCLUSIONS: Selection of a weight-loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1-year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss.
Subject(s)
Diet, Reducing , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Feeding Behavior , Obesity/diet therapy , Weight Loss , Adult , Anti-Obesity Agents/therapeutic use , Diet, Carbohydrate-Restricted , Diet, Fat-Restricted , Energy Intake , Female , Humans , Lactones/therapeutic use , Male , Middle Aged , Obesity/drug therapy , Orlistat , Weight GainABSTRACT
Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial RNA-binding protein code exists that allows specific protein sub-complexes to control cytoplasmic gene expression under a range of pathophysiological conditions. We show that polypyrimidine tract-binding protein (PTB) is central to one such complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF-related apoptosis inducing ligand there is a change in the repertoire of RNA-binding proteins with which PTB interacts. We show that altering the cellular levels of PTB and its binding partners, either singly or in combination, is sufficient to directly change the rates of apoptosis with increased expression of PTB, YBX1, PSF and NONO/p54(nrb) accelerating this process. Mechanistically, we show that these proteins post-transcriptionally regulate gene expression, and therefore apoptotic rates, by interacting with and stimulating the activity of RNA elements (internal ribosome entry segments) found in mRNAs that are translated during apoptosis. Taken together, our data show that PTB function is controlled by a set of co-recruited proteins and importantly provide further evidence that it is possible to dictate cell fate by modulating cytoplasmic gene expression pathways alone.
Subject(s)
Apoptosis/drug effects , Polypyrimidine Tract-Binding Protein/metabolism , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Cell Nucleus/metabolism , Cyclin T/genetics , Cyclin T/metabolism , DNA-Binding Proteins , HeLa Cells , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Humans , MCF-7 Cells , Nuclear Matrix-Associated Proteins/antagonists & inhibitors , Nuclear Matrix-Associated Proteins/genetics , Nuclear Matrix-Associated Proteins/metabolism , Octamer Transcription Factors/antagonists & inhibitors , Octamer Transcription Factors/genetics , Octamer Transcription Factors/metabolism , PTB-Associated Splicing Factor , Polypyrimidine Tract-Binding Protein/antagonists & inhibitors , Polypyrimidine Tract-Binding Protein/genetics , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Y-Box-Binding Protein 1/metabolismABSTRACT
The 5' untranslated region of the proto-oncogene c-myc contains an internal ribosome entry segment (IRES) and c-myc translation can therefore be initiated by internal ribosome entry as well as by cap-dependent mechanisms. It has been shown previously that in patients with multiple myeloma (MM) and in MM-derived cell lines there is a C to T mutation in the c-myc IRES that increases IRES activity and the corresponding synthesis of c-myc protein although it is not fully understood how this occurs. Our data show that two recently identified c-myc IRES trans-acting factors, Y-box binding protein 1 (YB-1) and polypyrimidine tract-binding protein 1 (PTB-1), bind more strongly (approximately 3.5- and 2-fold respectively) to the mutated version of the c-myc IRES and in vitro these proteins exert their effect synergistically to stimulate IRES activity of the mutant IRES 4.5-fold more than the wild-type version. Importantly, we show that there is a strong correlation between the expression of PTB-1, YB-1 and c-myc in MM-derived cell lines, suggesting that by reducing either PTB-1 or YB-1 protein levels it is possible to decrease c-myc expression and inhibit cell proliferation of MM-derived cell lines.
Subject(s)
Gene Expression Regulation, Neoplastic , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Multiple Myeloma/metabolism , Polypyrimidine Tract-Binding Protein/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Ribosomes/metabolism , Up-Regulation , Y-Box-Binding Protein 1/metabolism , Animals , Base Sequence , Cell Line, Tumor , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Humans , Mice , Molecular Sequence Data , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Mutation , NIH 3T3 Cells , Polypyrimidine Tract-Binding Protein/genetics , Protein Binding , Proto-Oncogene Mas , Proto-Oncogene Proteins c-myc/biosynthesis , Proto-Oncogene Proteins c-myc/genetics , RNA, Messenger/genetics , Ribosomes/genetics , Y-Box-Binding Protein 1/geneticsABSTRACT
Children and adolescents occasionally have back symptoms, but rarely come to a physician's office for more severe back pain. When a child or adolescent appears in the clinic with complaints of back pain, a careful detailed evaluation is appropriate. The incidence of findings in children with significant back pain is high; therefore, a detailed history, physical examination, and evaluation are needed. It is also legitimate to continue monitoring children even if no obvious cause is initially identified because often a diagnosis subsequently will be made.
Subject(s)
Back Pain/etiology , Child , Diagnosis, Differential , Discitis/diagnosis , Humans , Intervertebral Disc Displacement/diagnosis , Scheuermann Disease/diagnosis , Spinal Diseases/diagnosis , Spinal Neoplasms/diagnosis , Spondylolisthesis/diagnosis , Spondylolysis/diagnosisABSTRACT
STUDY DESIGN: A retrospective analysis of eight cases of delayed spinal infection after elective posterior or combined anterior and posterior spinal instrumentation and fusion. OBJECTIVES: These cases are reviewed to identify risk factors for delayed spinal infection after elective instrumentation and to describe the treatment of this complication. SUMMARY OF BACKGROUND DATA: Delayed spinal infection after elective spinal instrumentation and fusion is uncommon. This diagnosis is frequently difficult. METHODS: Five cases seen in the senior author's practice and three referral cases are reviewed. RESULTS: Of these eight cases, the organisms were Staphylococcus epidermidis in six cases, Propionibacterium acnes in one cases, and in the final patient, all intraoperative cultures were negative. Clinical presentations were variable; however, all patients reported back pain. Seven patients had elevated erythrocyte sedimentation rates, averaging 57 mm/hour. Only two had elevated white blood cell counts. No distant foci of infection were identified in any patient. Five-patients were found to have at least one pseudarthrosis. All patients were treated with debridement, instrumentation removal, and primary wound closure over drains followed by a minimum 6-week course of culture-directed postoperative antibiotics. At an average follow-up of 18 months, no patient has evidence of infection. CONCLUSIONS: The diagnosis of delayed infection after elective spinal instrumentation and fusion requires a high index of suspicion. These infections may have been caused by intraoperative inoculation. All patients were successfully treated with debridement, instrumentation removal, and culture-directed postoperative antibiotics.
Subject(s)
Gram-Positive Bacterial Infections/etiology , Orthopedic Fixation Devices/adverse effects , Propionibacterium acnes/isolation & purification , Spinal Fusion/adverse effects , Staphylococcal Infections/etiology , Staphylococcus epidermidis/isolation & purification , Surgical Wound Infection/etiology , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Child , Debridement , Drainage , Gram-Positive Bacterial Infections/therapy , Humans , Kyphosis/surgery , Reoperation , Retrospective Studies , Risk Factors , Scoliosis/surgery , Spinal Fusion/instrumentation , Staphylococcal Infections/therapy , Surgical Wound Infection/therapyABSTRACT
STUDY DESIGN: This was a retrospective review. Short-term outcomes were compared based on two different surgical techniques. OBJECTIVES: To determine the safety, efficacy, and cost effectiveness of two different surgical techniques of anterior and posterior spinal fusion for pediatric patients with spinal deformity. SUMMARY OF BACKGROUND DATA: Brown et al, Floman et al, and Bradford et al have reported on combined anterior and posterior spine fusions with a 1-2-week recovery period between stages. However, advances in surgical and anesthetic techniques combined with the prohibitive cost of prolonged hospitalization and theoretical advantages in pulmonary function and nutrition have led to increasing use of combined anterior and posterior spinal fusion under one anesthetic. METHODS: The authors reviewed records and radiographs of patients with pediatric spinal deformities who underwent anterior spine fusion/posterior spine fusion and instrumentation performed by the senior author (HAK) at one institution. RESULTS: Same-day sequential anterior spine fusion/posterior spine fusion resulted in less blood loss (575 +/- 275 ml; P < or = 0.0045), shorter hospital stay (8.00 +/- 2.68 days; P < or = 0.0001), and reduced hospital costs ($18,762 +/- $4,925; P < or = 0.0001). Operative time and complication rate were not affected. CONCLUSIONS: In selected patients with pediatric spinal deformity, experienced spinal surgeons can reduce blood loss, hospital stay, and costs by performing anterior and posterior spinal fusions sequentially under one anesthetic.
Subject(s)
Kyphosis/surgery , Scoliosis/surgery , Spinal Fusion/methods , Adolescent , Blood Loss, Surgical/statistics & numerical data , Child , Female , Hospital Costs , Humans , Internal Fixators , Kyphosis/epidemiology , Length of Stay/economics , Male , Postoperative Complications/epidemiology , Retrospective Studies , Scoliosis/epidemiology , Spinal Fusion/economics , Time Factors , Treatment OutcomeABSTRACT
The evaluation and management of scoliosis curves depend on careful study and curve classification. This article discusses current concepts of curve classifications and analyzes Type II curves in particular in hopes of making it easier to manage these curves from both nonoperative and operative standpoints.
Subject(s)
Braces , Scoliosis/surgery , Scoliosis/therapy , Humans , Kyphosis/surgery , Scoliosis/classificationABSTRACT
A 10-year-old girl with Williams syndrome (with characteristic facies and behavior, mental retardation, and growth disturbances) was seen with scoliosis, which, despite attempted bracing, rapidly progressed to 95 degrees and required surgical stabilization. Review of the entire literature on Williams syndrome revealed hallux valgus and little-finger clinodactyly as the most commonly mentioned orthopaedic manifestations, with only brief mention of spinal deformity. As awareness of Williams syndrome increases, spine surgeons must be aware of possible rapidly progressive scoliosis and kyphosis.
Subject(s)
Developmental Disabilities/complications , Intellectual Disability/complications , Kyphosis/complications , Scoliosis/complications , Child , Facial Expression , Female , Heart Defects, Congenital/complications , Humans , Kyphosis/surgery , Scoliosis/surgery , Spinal Fusion , Syndrome , Thoracic Vertebrae/surgeryABSTRACT
Here we present evidence that strongly suggests that the well-documented phenomenon of A-band shortening in Limulus telson muscle is activation dependent and reflects fragmentation of thick filaments at their ends. Calcium activation of detergent-skinned fiber bundles of Limulus telson muscle results in large decreases in A-band (from 5.1 to 3.3 microns) and thick filament (from 4.1 to 3.3 microns) lengths and the release of filament end fragments. In activated fibers, maintained stretched beyond overlap of thick and thin filaments, these end fragments are translocated to varying depths within the I-bands. Here they are closely associated with fine filamentous structures that also span the gap between A- and I-bands and attach to the distal one-third of the thick filaments. End-fragments are rarely, if ever, present in similarly stretched and skinned, but unstimulated fibers, although fine "gap filaments" persist. Negatively stained thick filaments, separated from skinned, calcium-activated, fiber bundles, allowed to shorten freely, are significantly shorter than those obtained from unstimulated fibers, but are identical to the latter with respect to both the surface helical array of myosin heads and diameters. Many end-fragments are present on grids containing thick filaments from activated fibers; few, if any, on those from unstimulated fibers. SDS-PAGE shows no evidence of proteolysis due to activation and demonstrates the presence of polypeptides with very high molecular weights in the preparations. We suggest that thick filament shortening is a direct result of activation in Limulus telson muscle and that it occurs largely by breakage within a defined distal region of each polar half of the filament. It is possible that at least some of the fine "gap filaments" are composed of a titin-like protein. They may move the activation-produced, fragmented ends of thick filaments to which they attach, into the I-bands by elastic recoil, in highly stretched fibers.
Subject(s)
Actin Cytoskeleton/ultrastructure , Calcium/metabolism , Muscles/ultrastructure , Protein Kinases , Sarcomeres/ultrastructure , Animals , Connectin , Horseshoe Crabs , Image Processing, Computer-Assisted , Microscopy, Electron , Muscle Contraction , Muscle Proteins/analysis , Muscles/chemistry , Muscles/physiologyABSTRACT
The ability of posterior distraction instrumentation to produce indirect reduction of retropulsed bone fragments was studied in 44 patients with thoracolumbar burst fractures. Using the Denis Classification, two predominate fracture types were identified: 13 patients had type A and 29 had type B fractures. Two others had Denis type D fractures. Spinal canal stenosis was reduced from a preoperative mean of 65% to 32.8% postoperatively. Denis type A fractures had significantly better reduction of 62.5% pre- to 19.2% postoperatively. Denis type B fractures reduced from 66.3% pre- to 38.9% postoperatively. The initial kyphotic deformity and the loss of vertebral height did not influence results of indirect decompression. Neurologic function at follow-up correlated with preoperative canal stenosis, but did not correlate with residual stenosis after instrumentation. This study demonstrated that posterior distraction instrumentation can achieve approximately 50% reduction in canal stenosis and that results will be influenced by fracture morphology.
Subject(s)
Fracture Fixation, Internal/instrumentation , Internal Fixators , Lumbar Vertebrae/surgery , Spinal Cord Compression/surgery , Spinal Fractures/surgery , Spinal Stenosis/surgery , Thoracic Vertebrae/surgery , Adult , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Paraplegia/etiology , Paraplegia/surgery , Retrospective Studies , Spinal Cord Compression/etiology , Spinal Fractures/classification , Spinal Fractures/complications , Spinal Fractures/diagnostic imaging , Spinal Stenosis/etiology , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Of 32 patients with classical Rett syndrome, radiographs of the spine could be obtained in 30; two had moved. Five (17%), ranging in age from 3.2-11.5 years, had a curve of 10 degrees or less. Twenty-five (83%) had scoliosis. The age at first diagnosis of scoliosis ranged from 4.3 to 18 years of age. The curves ranged from 10 degrees to 86 degrees at a mean age of 14.9 years. Eight of the 21 curves, 38 percent, showed progression, which was first noticed from just before 5 to after 18 years of age. Bracing was done in five of the younger girls with progressive curves at ages 8.3-10.4 years. Three required surgery, performed at ages 10.9, 16.2 and 17.3 years respectively. Physicians following these patients need to refer them for orthopedic care at the first suspicious sign of scoliosis. Orthopedic surgeons taking care of children with the Rett syndrome (RS) should be aware of the clinical unpredictability of the scoliosis in this condition.
Subject(s)
Rett Syndrome/complications , Scoliosis/etiology , Child , Child, Preschool , Female , Humans , Scoliosis/therapyABSTRACT
The selection of fusion levels in idiopathic scoliosis is an important decision. Careful analysis of curve patterns and preoperative planning will help with the fusion and in the selection of fusion levels. The goal of treatment is to achieve a stable, balanced spine and yet maintain as much flexibility in the lumbar spine as possible. This article helps establish guidelines for curve analysis and the selection of fusion levels.
Subject(s)
Scoliosis/surgery , Spinal Fusion/methods , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Radiography , Scoliosis/diagnostic imaging , Scoliosis/pathology , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/pathologyABSTRACT
Sixteen children (average age 7.4 years) with nontraumatic lesions of the clavicle were reviewed. There were six cases of neoplasms, six cases of infection, and four developmental anomalies. The patients with infections all had pain at presentation, with elevated white blood cell counts and erythrocyte sedimentation rates. Tissue biopsy was an important diagnostic tool.
Subject(s)
Bone Diseases/diagnosis , Bone Neoplasms/diagnosis , Clavicle , Adolescent , Child , Child, Preschool , Clavicle/abnormalities , Eosinophilic Granuloma/diagnosis , Female , Humans , Infant , Male , Osteomyelitis/diagnosisSubject(s)
Colonic Pseudo-Obstruction/surgery , Colostomy , Intestinal Pseudo-Obstruction/surgery , Sigmoidoscopy , Aged , Aged, 80 and over , Humans , MaleABSTRACT
This article stresses the fact that the pediatric patient who presents with back pain is very different from the adult patient with the same complaint. A child is much less likely to complain of symptoms when there is no organic cause for the complaint, and therefore his or her status should be evaluated carefully. When an immediate cause is not obvious, repeated examination should be performed because time may reveal a cause of the symptoms.
Subject(s)
Back Pain/diagnosis , Adult , Age Factors , Back Pain/diagnostic imaging , Back Pain/physiopathology , Child , Diagnosis, Differential , Humans , Lumbar Vertebrae/diagnostic imaging , Medical History Taking , Physical Examination , RadiographyABSTRACT
Richter's hernia, in which only a portion of the circumference of the intestine lies within the sac, is a common complication of femoral hernia. This case report is of 39 year old female who presented with a pneumoperitoneum and was found at laparotomy to have a right femoral Richter's hernia containing a knuckle of perforated small bowel. This is a previously unreported presentation of femoral hernia.
Subject(s)
Hernia, Femoral/complications , Pneumoperitoneum/etiology , Adult , Female , HumansABSTRACT
Atlantooccipital instability is an uncommon and usually lethal result of major trauma. Nontraumatic cases of instability at this site are rare. We report the findings in two children with Down syndrome who have striking atlantooccipital subluxation demonstrated on flexion and extension radiographs. Since there is increasing radiologic evaluation of cervical spine stability in patients with Down syndrome who wish to participate in athletic activities, the status of the atlantooccipital joint needs careful assessment, especially after cervical fusion for C1-C2 instability.
Subject(s)
Atlanto-Occipital Joint/diagnostic imaging , Down Syndrome/diagnostic imaging , Joint Dislocations/diagnostic imaging , Adolescent , Athletic Injuries/prevention & control , Atlanto-Occipital Joint/physiopathology , Child , Female , Humans , Joint Dislocations/prevention & control , Joint Dislocations/surgery , Male , Mass Screening , Radiography , Spinal FusionABSTRACT
Cross-sectional spinal canal area was measured before and after surgery in 12 patients with thoracolumbar burst fractures and canal narrowing caused by retropulsed fragments. Patients were classified into Denis type A or type B. Denis type A fractures have comminution of both end-plates of the vertebral body creating multiple smaller fractures; Denis type B fractures have comminution of the superior end-plate only with a single vertical fracture line into the inferior end-plate creating larger fragments. The degree of neurologic impairment was assessed before and after surgery using the Frankel system. There was no correlation between degree of canal narrowing and degree of neurologic impairment. The degree of spinal canal narrowing reflects the final resting position of the vertebral body fragments after trauma; during trauma, greater degrees of canal impingement may have occurred. Also, significant canal narrowing may be present without pinching of the cord or cauda equina. All patients with Denis type A fractures had near-anatomic reduction of fragments out of the spinal canal by surgery; less than half of the patients with Denis type B had good reduction. There was no correlation between reduction of retropulsed fragments and subsequent neurologic improvement. However, this should not preclude surgery as a therapeutic option: Eight of 10 patients with neurologic impairment experienced some improvement in symptoms after surgery; the other two were unchanged.
Subject(s)
Fractures, Bone/surgery , Lumbar Vertebrae/injuries , Spinal Stenosis/diagnostic imaging , Thoracic Vertebrae/injuries , Adult , Female , Fracture Fixation, Internal/instrumentation , Humans , Male , Middle Aged , Movement Disorders/etiology , Nervous System Diseases/etiology , Sensation , Spinal Fusion , Spinal Stenosis/etiology , Tomography, X-Ray ComputedABSTRACT
Back pain in children and adolescents must be regarded as a significant complaint, and the physician must be aware that minimal symptoms may be associated with major problems. This article outlines an aggressive and comprehensive diagnostic approach in order to prevent overlooking a serious problem.