GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis

The quality of articular cartilage engineered using a cell-polymer construct depends, in part, on the chemical composition of the biomaterial and whether that biomaterial can support the chondrocytic phenotype. Acknowledging the supportive influence of tissue-specific matrix molecules on the chondrocytic phenotype, we have combined chondroitin sulfate-A (CSA) and chitosan, a glycosaminoglycan (GAG) analog, to develop a novel biomaterial to support chondrogenesis. Chitosan is a polycationic repeating monosaccharide of beta-1,4-linked glucosamine monomers with randomly located N-acetyl glucosamine units. Chitosan may be combined with the polyanionic CSA such that ionic crosslinking results in hydrogel formation. Bovine primary articular chondrocytes, when seeded onto a thin layer of CSA-chitosan, form discrete, focal adhesions to the material and maintain many characteristics of the differentiated chondrocytic phenotype, including round morphology, limited mitosis, collagen type II, and proteoglycan production. Our findings suggest CSA-chitosan may be well suited as a carrier material for the transplant of autologous chondrocytes or as a scaffold for the tissue engineering of cartilage-like tissue.     

Suprasternal Doppler ultrasound for assessment of stroke distance

An assessment of a non-invasive technique for measurement of stroke distance was made using a portable Doppler ultrasound machine. The aim was to determine the measurement error of repeated stroke distance measurements (Within-observer variability) and to assess measurement agreement between two operators (between-observer variability). The measurement error (within-observer variability) for both operators was similar at approximately 2 cm. However, the measurements of the two operators (between-observer variability) did not agree well. Using the mean (SD) of three readings by each operator, the mean difference between the operators was -0.21 cm (1.96) giving a 95% confidence interval for the differences of -4.0 to +3.6 cm. There were significant positive and negative correlations between stroke distance and a variety of variables (age, height, weight, heart rate), but the relations were weak. The results indicate that the Doppler ultrasound technique for measurement of stroke distance would best be used to study trend changes in an individual patient, or subject, by a single operator.     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

Mycobacterial infection in an inner city children's hospital

Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition.     

Operative compared with nonoperative treatment of a thoracolumbar burst fracture without neurological deficit. A prospective,randomized study

BACKGROUND: To our knowledge, a prospective, randomized study comparing operative and nonoperative treatment of a thoracolumbar burst fracture in patients without a neurological deficit has never been performed. Our hypothesis was that operative treatment would lead to superior long-term clinical outcomes. METHODS: From 1994 to 1998, forty-seven consecutive patients (thirty-two men and fifteen women) with a stable thoracolumbar burst fracture and no neurological deficit were randomized to one of two treatment groups: operative (posterior or anterior arthrodesis and instrumentation) or nonoperative treatment (application of a body cast or orthosis). Radiographs and computed tomography scans were analyzed for sagittal alignment and canal compromise. All patients completed a questionnaire to assess any disability they may have had before the injury, and they indicated the degree of pain at the time of presentation with use of a visual analog scale. The average duration of follow-up was forty-four months (minimum, twenty-four months). After treatment, patients indicated the degree of pain with use of the visual analog scale and they completed the Roland and Morris disability questionnaire, the Oswestry back-pain questionnaire, and the Short Form-36 (SF-36) health survey. RESULTS: In the operative group (twenty-four patients), the average fracture kyphosis was 10.1 degrees at the time of admission and 13 degrees at the final follow-up evaluation. The average canal compromise was 39% on admission, and it improved to 22% at the final follow-up examination. In the nonoperative group (twenty-three patients), the average kyphosis was 11.3 degrees at the time of admission and 13.8 degrees at the final follow-up examination after treatment. The average canal compromise was 34% at the time of admission and improved to 19% at the final follow-up examination. On the basis of the numbers available, no significant difference was found between the two groups with respect to return to work. The average pain scores at the time of the latest follow-up were similar for both groups. The preinjury scores were similar for both groups; however, at the time of the final follow-up, those who were treated nonoperatively reported less disability. Final scores on the SF-36 and Oswestry questionnaires were similar for the two groups, although certain trends favored those treated without surgery. Complications were more frequent in the operative group. CONCLUSION: We found that operative treatment of patients with a stable thoracolumbar burst fracture and normal findings on the neurological examination provided no major long-term advantage compared with nonoperative treatment.     

Use of confirmatory factor analysis for the identification of new components of the metabolic syndrome: the role of plasminogen activator inhibitor-1 and Haemoglobin A1c

BACKGROUND AND AIM: This study was aimed to identify additional components of metabolic syndrome from a set of cardiovascular risk markers. METHODS AND RESULTS: The homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were assessed in a population-based sample of 902 nondiabetic adult subjects. Those biomarkers that were associated with metabolic syndrome were evaluated by multiple regression analysis, along with other traditional cardiovascular risk factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that both the established components of metabolic syndrome and the novel variables identified by the regression analysis were associated with a single underlying factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related to metabolic syndrome. CFA validated a one-factor model that included these variables. Moreover, the indices of goodness of fit were better for this expanded model than those obtained for a previously validated one-factor model that was restricted to the conventional elements of the syndrome. CONCLUSIONS: These findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. Their elevation is presumably another manifestation of the same pathophysiological mechanism that underlies the recognized traits of the syndrome.     

Glucose-6-phosphate dehydrogenase variants: reexamination of G6PD Chicago and Cornell and a new variant (G6PD Pea Ridge) resembling G6PD Chicago

Two large and unrelated families were investigated for hereditary nonspherocytic hemolytic anemia associated with deficiency of erythrocyte glucose-6-phosphate dehydrogenase (G6PD). In both families, the kinetic and electrophoretic features of the G6PD variants resembled those of G6PD Chicago. Further investigation revealed that members of one of these families previously had been characterized as having the G6PD variants Chicago and Cornell. However, it is clear that each of these terms has been applied to the same variant in this single large kindred. In the second family, we describe a newly identified variant with unique characteristics, which we have designated G6PD Pea Ridge. G6PD Pea Ridge resembles G6PD Chicago but differs in electrophoretic mobility and in a few kinetic parameters. It exhibits an unusually high Ki for NADPH and thus appears to be insensitive to product inhibition. As other cases previously considered to be the Chicago variant become more fully characterized, this probably will be shown to be a heterogeneous group of variants.