Rapid characterization of folding and binding interactions with thermolabile ligands by DSC.

Differential scanning calorimetry (DSC) is a powerful technique for measuring tight biomolecular interactions. However, many pharmaceutically relevant ligands are chemically unstable at the high temperatures used in DSC analyses. Thus, measuring binding interactions is challenging because the concentrations of ligands and thermally-converted products are constantly changing within the calorimeter cell. Using experimental data for two DNA aptamers that bind to the thermolabile ligand cocaine, we present a new global fitting analysis that yields the complete set of folding and binding parameters for the initial and final forms of the ligand from a pair of DSC experiments, while accounting for the thermal conversion. Furthermore, we show that the rate constant for thermolabile ligand conversion may be obtained with only one additional DSC dataset.

Manual ability and manual dexterity in children with cerebral palsy.

INTRODUCTION: Manual ability and performance of dexterity tasks require both gross and fine hand motions and coordination. The aim of this study was to determine the level of manual dexterity (capacity) and investigate its relationship with manual ability (performance) in children with cerebral palsy. METHOD: This study was designed as a cross-sectional study of 30 children with cerebral palsy (aged 8-15 years). In order to assess gross manual dexterity the Box and Block Test was used. Manual ability was assessed according to Manual Ability Classification System (MACS). RESULTS: A relationship between the level of manual ability impairment and performance on manual dexterity tasks was expressed. Participants at MACS level IV demonstrated slowest times and transferred the smallest number of blocks (p<0.01). This study also found that correlation between Gross Motor Function Classification Scale (GMFCS) and MACS is statistically significant (p<0.001). All hand skills were more impaired in the non-dominant hand compared to the dominant hand but there were no statistically significant difference (p=0.06). CONCLUSION: The results suggest that gross manual dexterity is a good predictor of manual abilities in children with cerebral palsy. These results provide better understanding of the relationship between manual dexterity and activity limitations and lend credibility to the use of these classification systems and assessments in order to optimize treatment planning and evaluate interventions and progress. Hippokratia 2014; 18 (4): 310-314.

[Diagnosis and treatment of Paget disease of the spinal vertebrae].

Paget disease, localized only on thoracic spine is extremly rare. It is a huge diagnostic problem and an equally big therapy challenge. Course of this disease is slow, it chronically worsens, thus demanding differentiation of various conditions, along with orthopaedic, neurological, radiographic and endocrine evaluation. Paget disease is followed by back pain, progressive weakening of legs and sphincter functions, due to pathological spine fractures and spinal stenosis. The treatment is surgical, in form of decompression and applying biphosphonates. Three patients are presented, all with worsening back pain which lasted several months. Hyperthonia and hyperreflexion of lower extremities were developed significantly. Over the course of time, neurological deficite got worse, almost to the point of spastic parapalegia. All of the patients were male, 50 to 68 years old. They had higher values of alcaline phosphatase and serum calcium than usual. In all cases, bone scintigraphy was positive where the lesion of thoracic spine existed. Biopsy suggested hyperparathyroidism, but, as it turned out, wrongly. After surgical treatment, neurological improvement was noticed on all three patients. In case of two, recidives occurred after three and five years respectively, so surgical reinterventions were made. These recidives are consequences of Paget disease progression. Aside from surgical treatment, they were treated by encrinologist. Remission of the disease lasted for seven and twelve years, respectively. Third patient had his condition recognized almost two years after first reception, and, due to big changes on vertebral body and paraplegia, posterior and anterior decompression of spinal canal and stabilization were done simultaneously. Biopsy confirmed Paget disease. During the postoperative course, nearly complete neurological improvement occured almost instantly. Only moments after hospital release, twenty four days after the operation, patient got sick in the hall. Unfortunately, he passed away due to massive lung embolism, even though he recieved adequate thromboembolic prophylaxion. Monoostotic form of Paget disease localized on vertebral body must be taken and considered seriously, especially when the patients suffer from progressive evolution of neurological deficite, followed by adequate biochemical blood and urine analysis, as well as radiographic signs of pathological fracture or invasive vertebral process. Surgical treatment can lead to significant improvement of clinical findings, but due to recidive, biphosphonate treatment is recommended.

[Chondrofibrosis of adolescent hip].

Authors present 420 hips with slipped capital epiphysis treated in the IOHB "Banjica", during the period between 1970 and 2005. Research includes the analysis of incidence, diagnostics and causes which contribute to the genesis of hip chondrofibrosis. Risk factors are shown, as well as the approach to eliminate them. 39 hips in which this complication occured were individually analyzed. Every hip was separately studied with intent to determine the cause of the condition's genesis, it's evolution, treatment and it's final functionality result. Synovia biopsy was performed in 7 cases, as well as the biopsy of the capsule, articular hyaline cartilage and subchondral bone of the femoral head, which enabled detailed description of both microscopic and macroscopic changes that follow this condition. Regardless of still hypothetical comprehension of the inception of chondrofibrosis, authors clearly state all the risky procedures during treatment that can contribute to the development of chondrofibrosis. The importance of early diagnostics and well-timed treatment are highlighted in this article, for they are crucial. Results of treated hip chondrofibrosis presented here give hope for the destiny of the ill joint, which was considered highly uncertain for a long time.

[Thoracic disc herniation causing myelopathy. Our experience using transthoracic approach].

The authors have reported six cases of thoracal discus hernia in five patients. All the patients have recently been examined in neurosurgery institutions. They had different degrees of neurological deficit, with tendency to aggravation. The same procedure has been applying: thoracotomy, large decompression of neural structures, and obligatory spondylodesis with the patient's own rib. In three cases a full recovery has been achieved, a partial recovery in other two. Complete and definitive paraplegia developed in one patient. The degree of the neurological recovery was between one and two points by Frankel scale. Better results have been obtained where symptoms were present for a short period of time, and myelopathic signs were mild. The follow up period was between 43 and 68 months. Three of the patients have been returned to their professional work. In one patient, three years after the first surgery, there has been diagnosed another discus hernia, one level below. She was treated with the same surgical technique as described, for the second time. Multilevel symptomatic thoracic disc herniations are extremely rare. Although a small series, it is clearly pointed the need to think of a discus hernia, and its early diagnostics and adequate surgical treatment. The first experience with the operative technique described, demonstrated that this procedure is good and justified.

[Idiopathic avascular necrosis of the femoral head in adolescents--diagnostics and management].

Idiopathic avascular necrosis of the femoral head still represents incompletely explained clinical entity. In the period 1978-2003. we have treated sixteen hips in ten patients with this condition in the IOHB "Banjica". Diagnosis have been founded on clinical and radiographic features, in addition to MRI findings. One patient have been operated, curretaging necrotic part of the femoral head and placing homografts instead. The other fifteen patients have been treated by the same procedure: skin traction for several months following immediate rehabilitation of the hip. The goal of treatement was reducing the pain, increasing the range of movements and preservation of the normal joint space. Evaluation of the treatement was based on unique criteria founded on Howorth-Ferguson index, clinical and radiographic features.The follow-up period was 2-7 years. The authors have stressed the following advantages of the non-operative treatement in adolescents with idiopathic avascular necrosis if the femoral head: increased range of joint movements, decreased pain and low risk rate of any complications following surgical procedures. Formed changes in the femoral head are irreversible, and they are real basic for premature arthrosis of the hip.

Combined salter innominate osteotomy with femoral shortening versus other methods of treatment for Legg-Calvé-Perthes disease.

The results of treatment of Legg-Calvé-Perthes disease in 357 patients at the Institute for Orthopaedic Surgery "Banjica," Belgrade, from January 1963 to December 1987 with > or = 10 years of follow-up are summarized. The advantages of combined Salter innominate osteotomy with femoral shortening, as a one-step operation, are emphasized. Male predominance was found in a ratio of 4.75:1, and bilateral involvement was present in 21% of the patients. Disease onset was usually between ages 4 and 7 years (mean 6.5 years). Catterall criteria for the classification of the disease were used; patients in groups I and II were treated nonsurgically and those in groups III and IV were treated surgically. Most of the surgically treated patients (64.4%) had one or more head risk factors. The most frequently used surgical procedure was a Salter innominate osteotomy with or without femoral shortening. Assessment of treatment was made by measuring the final center-edge angle and by using criteria developed by Catterall, Mose, Harrison, and Stulberg. Final functional status of the operated hips was recorded as well. The greatest final center-edge angle of 34.27 degrees was found in the patients treated with combined Salter innominate osteotomy and femoral shortening, showing improvement of 14.98 degrees. Surgical treatment, except for revascularization procedures, showed good and fair results in > 90% of patients. The range of hip motion was improved in most patients. The earliest weight-bearing allowance was found in patients who underwent Salter innominate osteotomy and femoral shortening; it averaged 3.1 months. The duration of immobilization was also the shortest in this group. The average femoral shortening was 1.38 cm (range 0.9-1.9 cm). The proposed combined Salter osteotomy with femoral shortening is recommended for the treatment of more severe cases of Legg-Calvé-Perthes disease, thus preventing establishment of early secondary hip arthrosis.