Response of bone marrow stroma cells to demineralized cortical bone matrix in experimental spinal fusion in rabbits

The effect of autogeneic bone marrow (BM) cells and allogeneic demineralized bone matrix (DBM), alone or combined, as transplantation materials was studied in an experimental posterior thoracic spinal fusion model in rabbits. Transplantation of composite grafts composed of BM and DBM showed the first signs of fusion between two spinal segments after four weeks, reaching 86% after 20 weeks. Late fusion results achieved with DBM alone were similar. The capacity of BM per se to build up a spinal fusion was insignificant. Calcified tissue, documented roentgenographically, was shown to develop locally with time, and the earliest bridging of an interspace was noted after four weeks. Histologically, formation of new bone and cartilage was observed after two weeks, showing mature lamellar bone formation between thoracic segments after 20 weeks. Furthermore, increased 45Ca activity was still observed in the fused tissues after 20 weeks. Although, with grafting materials used, this model for experimental spinal fusion gave promising results, further investigations with other fusion techniques could give still better effects.     

The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.     

A method combining morphological, immunocytochemical and chromosomal examinations of the same cell in the study of lymphoproliferative diseases

6 cases of different lymphoproliferative diseases were studied with the new MAC (Morphology-Antibody-Chromosome) method in order to find out 1) if the abnormal karyotype is confined to the monoclonal cell population, 2) if there are, within this clone, also cells with a normal karyotype, and 3) if the method can help the pathologist to diagnose malignant lymphoproliferative diseases. The MAC method allows a simultaneous study in the same metaphase cell of the karyotype, surface markers, and some morphological features. In all cases in which a monoclonal cell proliferation was detected immunohistologically, the MAC examination showed a chromosomal abnormality for the same light chain as was detected in immunohistology, but not in other cells. In all but a single case, all mitotic cells belonging to the clonal cell proliferation had an abnormal karyotype. In this case with lambda clonality, 2/8 lambda-positive mitoses had a normal karyotype. However, all the normal mitoses occurred in small lymphocytes whereas the abnormal mitoses were seen in large blastic cells. In 1 case, the MAC method helped in confirming the diagnosis of malignant lymphoma (nodular small cleaved cell type). Especially in lymphomas composed of a mixed cell population, the MAC method makes it possible to find out which cell types have an abnormal karyotype and which have a normal karyotype.     

Ecological effects of hepatotoxic cyanobacteria

Many species of cyanobacteria produce hepatotoxic peptides called microcystins. Toxic cyanobacteria have caused fish, wildlife, and cattle mortality in many countries, but the distribution and fate of toxins and their ecological effects are poorly known. Toxic cyanobacteria may affect sensitive organisms and populations, but also fundamental ecological processes, e.g., primary production and microbial activity. Many studies show negative effects of cyanobacteria on zooplankton, but information on the type and quantity of toxin(s) involved is usually missing. Mussels accumulate peptide toxins but accumulation in other organisms remains to be studied. Cyanobacterial blooms often affect the littoral zones, which are important reproduction and feeding areas for fish and birds.     

Development of heterotopic ossification around the hip. A long-term follow-up of patients who underwent surgery with two different types of endoprostheses

Heterotopic ossification has been reported in many pathological situations, most important clinically as a sequel to hip arthroplasty and spinal trauma. The etiology of heterotopic ossification is yet not clear, but the disease is supposed to be connected with trauma. Heterotopic bone was found in 53% (1.2% with the severe form) of 623 patients operated on at the Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland; the operations included 849 arthroplasties. The rate of heterotopic ossification was higher after revision arthroplasty, following operation of the contralateral side, in men, and in primary coxarthrosis, and the incidence was higher with the Brunswik (metal-on-plastic) endoprosthesis than in the McKee-Farrar type (metal-on-metal). Heterotopic bone formation generally seemed to increase and to be more manifest during long-term observation.     

Identification of single amino acid substitutions in the staphylococcal nuclease protein that enhance and diminish T cell clone recognition of naturally processed peptides.

It has been inferred that residue changes that affect T cell recognition of synthetic peptides will have a similar effect in the intact protein. However, since small peptides do not require antigen processing it is possible that residue changes in synthetic peptides will not have an equivalent effect in the intact protein. Mutant proteins of staphylococcal nuclease (Nase) and 15mer synthetic peptides with corresponding substitutions were compared to determine if residue changes within an immunodominant epitope have an effect on the generation of naturally processed peptides. Five different substitutions in the synthetic peptide resulted in loss of reactivity of individual Nase-specific clones. When the same single amino acid changes were made in the intact protein, the naturally-processed peptides were also unable to stimulate the Nase-specific clones. However, two other substitutions in the synthetic peptide were stimulatory for a T cell clone even though the same changes in the intact protein were non-stimulatory. These results suggest that certain residue changes affect recognition of the naturally processed peptide but not the synthetic peptide with the same amino acid change. In addition, these results demonstrate that the effects of amino acid substitutions in synthetic peptides on T cell recognition may not always reflect the effects of these substitutions in the intact protein. Substitutions located outside Nase-specific T cell epitopes were also examined. Thirty different mutant proteins were all stimulatory. Moreover, a number of these mutants proteins were 50- to 100-fold more efficient in their stimulatory capacity than the native Nase protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin resistance is associated with circulating fibrinogen levels in nondiabetic patients receiving peritoneal dialysis.

BACKGROUND: Insulin resistance (IR) and inflammation are associated with increased risk of cardiovascular disease in the general population. Continuous glucose absorption in peritoneal dialysis (PD) may induce hyperglycemia and hyperinsulinemia. METHODS: We evaluated IR in nondiabetic patients receiving PD, and analyzed the association between IR and systemic inflammation biomarkers by performing a cross-sectional study on ambulatory dialysis. A total of 25 nondiabetic patients receiving PD and 25 healthy individuals, matched for gender, age, and body mass index (BMI), were included. The PD group was composed of 11 men and 14 women, with a mean age of 47 +/- 14 years and mean BMI of 25.5 +/- 4.7 kg/m(2). The control group was composed of 10 men and 15 women, with a mean age of 45 +/- 12 years and BMI of 24.0 +/- 2.8 kg/m(2). RESULTS: IR was evaluated by the homeostasis model assessment method (HOMA-IR). Inflammation was assessed through high-sensitivity C-reactive protein (CRP) and fibrinogen. Body composition and truncal fat were evaluated by dual energy x-ray absorptiometry. HOMA-IR was significantly higher (P < .0001) in subjects receiving PD (4.9, range: 2.3-9.3 mmol/L x muU/mL) compared with healthy subjects (1.2, range: 0.4-4.8 mmol/L x muU/mL). As expected, compared with controls, patients receiving PD had significantly higher levels of insulin (26.5 +/- 7.5 muU/mL vs 6.3 +/- 3.4 muU/mL; P < .0001), CRP (6.3, range: 0.3-61.1 mg/L vs 2.4, range: 0.6-5.9 mg/L; P = .001), and fibrinogen (379 +/- 101 mg/dL vs 268 +/- 66 mg/dL; P < .0001). However, there were no significant differences in body and truncal fat mass between the groups. A significant correlation between HOMA-IR and fibrinogen (Rho = 0.48; P = .01) was observed. However, no correlation was found between HOMA-IR and CRP. Also, no significant correlations were found between HOMA-IR and body fat mass (Rho = 0.11), and between HOMA-IR and truncal fat mass (Rho = 0.19). CONCLUSIONS: Patients receiving PD demonstrate a state of IR that is associated with high circulating levels of fibrinogen. This suggests that hyperfibrinogenemia may be involved in the pathogenesis of IR in this setting.     

A demographic survey of leg and foot ulcer patients in a defined population.

By means of a questionnaire sent to all medical units in Malm?, including primary care, homes for the elderly, and industrial health clinics, 275 patients with leg and foot ulcers were identified. With a population of 232,908 in Malm?, this corresponds to a prevalence of 0.12%, which is lower than reported by others. Since the response rate was high (88% total, Primary Care: 100%), the prevalence of 0.12% is, however, believed to be real and might be explained by the urban area investigated, with easy access to care and proximity to one somatic hospital. 50% of the patients with leg and foot ulcers were treated in Primary Care, and 30% of the leg ulcer patients were treated at the Department of Dermatology. 88% of leg and foot ulcer patients were over 75 years of age. Median age was 79.5 years, with 80 for women and 76.5 for men. In Primary Care the median age was 82. There was a predominance of women in the study population with an overall sex ratio of 3:1. A higher proportion of patients living alone was found in Primary Care. The etiology of the ulcers was considered to be "unknown" or "other" or else no statement was given in 36% of the leg ulcer- and 22% of the foot ulcer patients. This might reflect an overall uncertainty about the underlying etiological cause. Medially and laterally located leg ulcers were reported equally often, but there was also a great proportion of wholly or partially circumferential ulcers. 76% of the foot ulcers were located on the toes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clonal structural chromosome aberrations in fibrous dysplasia

Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22), add(12)(p13)/46,idem,t(3;8)(p21;q13),add(10)(q26),der(15)del(15)(q15q22)ins(15;?)(q15;?)/46,idem,-X, + 2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations.     

Direct identification of gram-positive cocci from routine blood cultures by using AccuProbe tests

Rapid and reliable identification of bacteria directly from blood cultures is important in clinical practice to guide appropriate antibiotic therapy. In this study, the performance of the AccuProbe (Gen-Probe, Inc., San Diego, Calif.) in direct identification of Staphylococcus aureus, Streptococcus pneumoniae, enterococci, and group A and B streptococci from positive blood culture bottles was evaluated by using 6-year routine clinical laboratory blood culture material from Paijat-Hame Central Hospital, Lahti, Finland. With the enterococcal and group A and B streptococcal probes, the diagnostic performance of the test was excellent at a cutoff value of 50,000 relative light units (RLU) as recommended by the manufacturer. However, with the S. aureus probe, although the specificity was very high (99.8%), the sensitivity was low (72.4%). To improve the clinical usability of the direct AccuProbe identification, optimal cutoff values for the individual AccuProbe tests were defined by using receiver-operating characteristic analysis. Consequently, cutoff values for S. aureus and S. pneumoniae tests were adjusted to 30,000 RLU and for enterococci and to 55,000 RLU for group A and B streptococci. With these adjustments, the performance of the AccuProbe tests, especially that for S. aureus, was significantly improved.