Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection

BACKGROUND: Diabetic foot infections cause substantial morbidity and mortality. Neutrophil superoxide generation, a crucial part of neutrophil bactericidal activity, is impaired in diabetes. Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil function. We assessed G-CSF as adjuvant therapy for the treatment of severe foot infections in diabetic patients. METHODS: 40 diabetic patients with foot infections were enrolled in a double-blind placebo-controlled study. On admission, patients were randomly assigned G-CSF (filgrastim) therapy (n = 20) or placebo (n = 20) for 7 days. Both groups received similar antibiotic and insulin treatment. Neutrophils from the peripheral blood of these participants and from healthy controls were stimulated with opsonised zymosan, and superoxide production was measured by a spectrophotometric assay (reduction of ferricytochrome C). FINDINGS: G-CSF therapy was associated with earlier eradication of pathogens from the infected ulcer (median 4 [range 2-10] vs 8 [2-79] days in the placebo group; p = 0.02), quicker resolution of cellulitis (7 [5-20] vs 12 [5-93] days; p = 0.03), shorter hospital stay (10 [7-31] vs 17.5 [9-100] days; p = 0.02), and a shorter duration of intravenous antibiotic treatment (8.5 [5-30] vs 14.5 [8-63] days; p = 0.02). No G-CSF-treated patient needed surgery, whereas two placebo recipients underwent to amputation and two had extensive debridement under anaesthesia. After 7 days' treatment, neutrophil superoxide production was significantly higher in the G-CSF group than in the placebo group (16.1 [4.2-24.2] vs 7.3 [2.1-11.5] nmol per 10(6) neutrophils in 30 min; p < 0.0001). G-CSF therapy was generally well tolerated. INTERPRETATION: G-CSF treatment was associated with improved clinical outcome of foot infection in diabetic patients. This improvement may be related to an increase in neutrophil superoxide production.     

Failure of intraoperatively customized non-porous femoral components inserted without cement in total hip arthroplasty

Seventy-four primary total hip arthroplasties were performed in sixty-eight patients between August 1990 and September 1991. Clinical assessments were made with use of the Harris hip score and, specifically, the pain component of that score. The preoperative radiographs were digitally quantified for calculation of the so-called canal-to-calcar ratio and the so-called cortical index. The postoperative radiographs were evaluated for the percentage of the cross-sectional area of the femoral canal that was occupied by the prosthesis; subsidence of the prosthesis; and adaptive osseous changes, including hypertrophic cortical remodeling, osteolysis, formation of sclerotic radiolucent lines around the prosthesis, and formation of a pedestal at the tip of the prosthesis. The indication for the arthroplasty was osteoarthrosis in fifty hips (68 per cent), avascular necrosis in fourteen (19 per cent), congenital dysplasia in six (8 per cent), and another diagnosis in four (5 per cent). The average duration of follow-up was thirty-one months (range, eleven to forty-six months). The average Harris hip score (and standard deviation) was 75 +/- 16.8 points (range, 29 to 100 points), and the average score for the pain component was 37 +/- 7.5 points (range, 0 to 44 points). The average canal-to-calcar ratio of the hips was 0.44 (range, 0.32 to 0.74), and the average cortical index was 0.54 (range, 0.33 to 0.66). The average subsidence of the component was 0.6 centimeter (range, 0.0 to 2.3 centimeters). The average fill of the canal was 100 per cent proximally, 97 per cent at the middle of the stem, and 92 per cent distally as measured on the anteroposterior radiographs made immediately postoperatively and 100, 95, and 90 per cent, respectively, as measured on the lateral radiographs. A failure occurred in twenty-one hips (28 per cent) in twenty-one patients, with an average time to failure of 21 +/- 13 months (range, one to forty-four months). The Kaplan-Meier survival estimate (and standard error) for this population was 0.45 +/- 0.11 (confidence interval, 0.67 to 0.23) at forty-four months. The average subsidence of the components that failed was 0.7 centimeter (range, 0.1 to 2.3 centimeters). There was no significant relationship between failure of the component and the age or sex of the patient, the diagnosis, or the side of the operation. Postoperative severity of pain (p = 0.09) or subsidence (p = 0.08) alone did not reach significance for predicting outcome. The Harris hip score alone (p = 0.05), the Harris hip score in combination with subsidence of the femoral component (p = 0.01), and the pain component of the Harris hip score in combination with subsidence of the femoral component (p = 0.01) were all significant for predicting outcome. No other measured radiographic variable was predictive of failure. Despite optimization of the fit of the component within the femoral canal and the percentage of the cross-sectional area of the femoral canal occupied by the component, the clinical results indicated a high rate of failure. Thus, these criteria are not the only requisites for stabilization of these femoral components without cement. On the basis of these data, we have discontinued the use of these intraoperatively customized, non-porous, smooth femoral prosthesis.     

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-microliter infusion containing 5.0 microgram of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean +/- SEM number of conditioned responses (CRs) during retention test session was 16.47 +/- 1.78 in the vehicle group and 9.93 +/- 1.59 in the AP5 group; P < 0.05). Post-training infusion of AP5 did not affect retention (mean +/- SEM number of conditioned responses during retention test session was 18.46 +/- 1.94 in the vehicle group and 20.42 +/- 2.38 in the AP5 group; P > 0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.     

Study of glomeruli in the frog olfactory bulb using a fluorescent potential-sensitive dye

Localized irradiation of the skin and subcutaneous tissues with large single doses of gamma rays can induce immediate effects characterized by erythema, desquamation, and necrosis. Correlations between the evolution of the lesions and dosimetry studies have to be established by biophysical methods. NMR studies of the effects of an irradiated Fricke solution might be a means of controlling the delivered irradiation doses. After exposition to ionizing radiations, ferrous ions are transformed into ferric ions. Both are paramagnetic ions, and proton spin-lattice relaxation is accelerated depending on the oxidation reaction. In this study, solution of ammonium ferrous sulfate in an acid environment was incorporated into a gelling substance made with agarose, so that T1 weighted image contrast could be used to detect ferric ion formation. Experiments with 192Ir and 60Co gamma rays with doses in the 0 to 100 Gy range were conducted with Fe2+ concentrations of 0.5, 1, 1.5, and 2 mM in a gelling substance containing 4% agarose. A relationship was established between the amount of Fe3+ created and the spin-lattice proton relaxation rate, which led to a straightforward dose-effect relation. The use of such high doses allowed us to reproduce realistic conditions of accidental overexposure. A linear relationship was obtained between the doses absorbed and the NMR parameters measured (T1 and relative image intensity).     

A novel locus (RP24) for X-linked retinitis pigmentosa maps to Xq26-27

Two genetic loci, RP2 and RP3, for X-linked retinitis pigmentosa (XLRP) have been localized to Xp11.3-11.23 and Xp21.1, respectively. RP3 appears to account for 70% of XLRP families; however, mutations in the RPGR gene (isolated from the RP3 region) are identified in only 20% of affected families. Close location of XLRP loci at Xp and a lack of unambiguous clinical criteria do not permit assignment of genetic subtype in a majority of XLRP families; nonetheless, in some pedigrees, both RP2 and RP3 could be excluded as the causative locus. We report the mapping of a novel locus, RP24, by haplotype and linkage analysis of a single XLRP pedigree. The RP24 locus was identified at Xq26-27 by genotyping 52 microsatellite markers spanning the entire X chromosome. A maximum LOD score of 4.21 was obtained with DXS8106. Haplotype analysis assigned RP24 within a 23-cM region between the DXS8094 (proximal) and DXS8043 (distal) markers. Other chromosomal regions and known XLRP loci were excluded by obligate recombination events between markers in those regions and the disease locus. Hemizygotes from the RP24 family have early onset of rod photoreceptor dysfunction; cone receptor function is normal at first, but there is progressive loss. Patients at advanced stages show little or no detectable rod or cone function and have clinical hallmarks of typical RP. Mapping of the RP24 locus expands our understanding of the genetic heterogeneity in XLRP and will assist in development of better tools for diagnosis.     

The new-generation laser surgical apparatus Doktor in the combined treatment of stomatological disease in an outpatient setting

Presents the design, technological characteristics (wavelength 10.6 mu cm, power up to 7 W, permanent mode) of a new-generation surgical laser Doktor and its use in the treatment of dental and maxillofacial diseases (diseases of the periodontium and buccal mucosa, pericoronitis, trophic ulcers, retention cysts, furuncles and carbuncles of the skin of the neck and face, odontogenic inflammatory processes, injuries, tumors) and in reconstructive, plastic, and cosmetologic surgery.     

The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants

The clinical, haematological and cytogenetic data for 20 patients with an acquired abnormality of 11q23 and 10p have been reviewed at this workshop. Patients predominantly presented with de novo AML M5a and the most common cytogenetic finding was an inversion of part of the long arm of chromosome 11 followed by a translocation between 11q and 10p. Band p12 represented the most common breakpoint on chromosome 10. The t(10;11) subgroup defined a subset of younger 11q23 patients, the majority of whom achieve a first complete remission despite the differing treatment regimens.