Exchange nailing for nonunion of diaphyseal fractures of the tibia: our results and an analysis of the risk factors for failure.

AIMS: The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures. PATIENTS AND METHODS: A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 months). The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union. RESULTS: Multiple causes for the primary nonunion were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients were lost to follow-up. Further surgical procedures were required in 35 (36%) nonunions. Other fixation modalities were required in five fractures. A single nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11 out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up to five repeated exchange nailings, with or without bone grafting, ultimately achieved union in 89 (93%) fractures. The median time to union after exchange nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm or more (p = 0.04) and infection (p < 0.001), were predictive for failure of exchange nailing Multiple regression analysis found that infection was the strongest predictor of failure (p < 0.001). CONCLUSION: Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. However, in the presence of severe infection with a highly resistant organism, or extensive sclerosis of the bone, other fixation modalities, such as Ilizarov treatment, should be considered. TAKE HOME MESSAGE: Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion.

Exchange nailing for femoral diaphyseal fracture non-unions: Risk factors for failure.

The aim of this study was to identify risk factors for failure of exchange nailing for femoral diaphyseal fracture non-unions. The study cohort comprised 40 patients with femoral diaphyseal non-unions treated by exchange nailing, of which six were open injuries. The median time to exchange nailing from primary fixation was 8.4 months. The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Multiple causes for non-union were found in 16 (40%) cases, with infection present in 12 (30.0%) patients. Further surgical procedures were required in nine (22.5%) cases, one of whom (2.5%) required the use of another fixation modality to achieve union. Union was ultimately achieved with exchange nailing in 34/37 (91.9%) patients. The median time to union after the exchange nailing was 9.4 months. Cigarette smoking and infection were risk factors for failure of exchange nailing. Multivariate analysis found infection to be the strongest predictor of exchange failure (p<0.05). Exchange nailing is an effective treatment for aseptic femoral diaphyseal fracture non-union. However, 50% of patients undergoing exchange nailing in the presence of infection required at least one further procedure. It is important to counsel patients of this so that they can plan for it and do not consider that the first exchange operation has failed.

Disseminating results: community response and input on Kisumu breastfeeding study.

Communicating findings to study participants and their communities is a practice that often gets overlooked or receives low prioritization by research investigators, but is crucially important. The purpose of this study was to describe the process and community response to the dissemination of results from the Kisumu Breastfeeding Study (KiBS), specifically in terms of (1) community research knowledge and expectations and (2) impressions of result dissemination efforts. A qualitative evaluation was completed for 10 result dissemination events using focus group discussions (FGDs) (n = 10; total number of participants = 98). An inductive, thematic qualitative data analysis was completed in NVivo 8.0. Overall, FGD participants expressed great appreciation for being given information on the study results. Participants had a good understanding of what research entails and had specific expectations for the process, including that the community receive information about the study, not only at the end of the study but also at regular intervals throughout the study's conduct. They also wanted to receive the communications from a credible source, the principal investigator preferably. Other expectations centered on better community and research interactions and development and the use of community collaborators. Impressions of KiBS result dissemination events were positive, but suggestions for the future included having the event in a larger area, inviting more people, having more written materials, and putting the information in an entertaining format such as skits or movies. Sharing study findings with local community members is essential and beneficial to the researchers' long-term engagement with communities and importantly, the successful implementation of study findings when appropriate. It is imperative that dissemination of results be embedded as an integral part of research project planning and development.

Effect of particle size and density on the die fill of powders.

The flow behaviour of powders during the process of die fill was examined. Gravity and suction fill experiments were carried out using a model shoe-die system. Five grades of microcrystalline cellulose were studied to identify the effect of particle size and density on flow. Flowability was quantified using the concept of critical velocity. Under gravity fill, the critical velocity was one order of magnitude higher for powders with large particle size compared to smaller particles. Under suction fill conditions, the critical velocity increased significantly compared to gravity fill, showed no consistent relationship with particle size, and the powders performed more similar to one another. Using high speed video, the gravity and suction fill mechanisms were discussed in the context of air flow and pressure build-up. The effect of shoe velocity, suction velocity and height of the powder in the shoe was explored in more detail. It was shown that one can identify individual contributions from material properties and process parameters to the flow behaviour during die fill; however, the flow performance depends on the inter-relationships between powder characteristics and process parameters. The die fill mechanisms described can be used to assist the optimisation of powder formulation and process design.

In vivo models of bone repair.

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature. We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario. Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%. It is vital to know the limitations and success of each model when considering its application.

Field evaluation of five rapid diagnostic tests for screening of HIV-1 infections in rural Rakai, Uganda.

The performance characteristics of HIV rapid diagnostic tests (RDTs) vary by test and by population. We assessed five commercial RDTs in Uganda where all but one RDT (Determine; Abbott Laboratories, Germany) performed close to manufacturer's expectations. Determine had low specificity (85.2%, positive predictive value 67.3%) due to false-positive results with weak-positive bands. Properly trained staff, good quality control programmes and validation of RDTs with laboratories having confirmatory testing capacity may be warranted to assure accuracy in each setting.

Performance of two commercial immunochromatographic assays for rapid detection of antibodies specific to human immunodeficiency virus types 1 and 2 in serum and urine samples in a rural community-based research setting (Rakai, Uganda).

Rapid detection of human immunodeficiency virus (HIV) antibodies is of great importance in developing and developed countries to diagnose HIV infections quickly and at low cost. In this study, two new immunochromatographic rapid tests for the detection of HIV antibodies (Aware HIV-1/2 BSP and Aware HIV-1/2 U; Calypte Biomedical Corporation) were evaluated in rural Africa to determine the tests' performance and comparability to commercially available conventional enzyme immunoassay (EIA) and Western blot (WB) tests. This prospective study was conducted from March 2005 through May 2005 using serum and urine from respondents in the Rakai Community Cohort Survey. Nine hundred sixty-three serum samples were tested with the Aware blood rapid assay (Aware-BSP) and compared to two independent EIAs for HIV plus confirmatory Calypte WB for any positive EIAs. The sensitivity of Aware-BSP was 98.2%, and the specificity was 99.8%. Nine hundred forty-two urine samples were run using the Aware urine assay (Aware-U) and linked to blood sample results for analysis. The sensitivity of Aware-U was 88.7% and specificity was 99.9% compared to blood EIAs confirmed by WB analysis. These results support the adoption of the Aware-BSP rapid test as an alternative to EIA and WB assays for the diagnosis of HIV in resource-limited settings. However, the low sensitivity of the Aware-U assay with its potential for falsely negative HIV results makes the urine assay less satisfactory.

Merkel cell carcinoma in South East Scotland, 1993-2003.

BACKGROUND AND AIMS: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. The aims of this study were to look at the incidence and distribution of MCC in a predominantly skin type I Caucasian population, review overall management of the disease and assess patient outcomes. METHODS: Cases were identified through the regional pathology database. Twenty patients were diagnosed with MCC over a 10-year period (1993-2003) and managed at the Regional Plastic Surgery Unit at St John's Hospital, Livingston. RESULTS: The disease incidence was found to be 0.133 per 100,000 per annum. All patients were Caucasian, seven males and 13 females (1:1.9 ratio). The mean age at presentation was 77 years (range 58-93 years). The majority of lesions were found to be stage IA (80%), located in the head and neck region. There were two cases (10%) with stage II disease and two (10%) with stage III disease (both with liver metastases) at the time of diagnosis. All patients were managed operatively. Seventeen of the 20 had wide local excisions; of the remaining three, two were only suitable for debulking procedures and one patient (stage II) had only a diagnostic biopsy, refusing intervention thereafter. One patient received adjuvant chemoradiotherapy. CONCLUSION: Surgery remains the mainstay of treatment but adjuvant therapy, in particular chemotherapy, is problematic in a frail, elderly population.

A prothrombin gene mutation is significantly associated with venous thrombosis.

This case-control study examined the prevalence of a prothrombin gene mutation in the 3'-untranslated region (UTR) first reported by Poort et al in Dutch subjects with a history of venous thrombosis and in matched control subjects without a history of thrombosis. We tested the hypothesis that the presence of the 3'UTR prothrombin mutation would convey a higher risk of venous or arterial thrombosis and therefore would be found in a higher-than-normal percentage of subjects with a history of thrombosis. Our study included 100 subjects: 50 with a history of thrombosis (21 with venous thrombosis and 29 with arterial thrombosis, who had been recruited from an anticoagulation clinic) and 50 control subjects without a history of thrombosis. DNA from these subjects was analyzed by polymerase chain reaction and agarose gel electrophoresis. We found a statistically significant increase in the prevalence of the 3'UTR mutation in subjects with a history of venous thrombosis compared with subjects without thrombosis. The prevalence of the 3'UTR prothrombin mutation was 19% (4/21;3 heterozygous and 1 homozygous) in subjects with a history of venous thrombosis, 0% (0/29) in subjects with a history of arterial thrombosis, and 2% (1/50) in control subjects (P < .0245, by Fisher's exact test for comparison of subjects with versus those without a history of venous thrombosis). The G-->A mutation at nucleotide 20,210 in the 3'UTR was confirmed by direct DNA sequencing. The similar increased prevalence of the 3'UTR mutation in subjects with venous thrombosis in our population and in the Dutch population studied by Poort et al suggests that this mutation is an important risk factor for venous thrombosis in the general white population.

Modification of the fatty acid composition of Escherichia coli by coexpression of a plant acyl-acyl carrier protein desaturase and ferredoxin.

Expression of a plant delta 6-palmitoyl (16:0)-acyl carrier protein desaturase in Escherichia coli resulted in the accumulation of the novel monounsaturated fatty acids delta 6-hexadecenoic acid (16:1 delta 6) and delta 8-octadecenoic acid. Amounts of 16:1 delta 6 accumulated by E. coli were increased more than twofold by the expression of a plant ferredoxin together with the delta 6-16:0-acyl carrier protein desaturase.

Parallel effects of arachidonic acid on insulin secretion, calmodulin-dependent protein kinase activity and protein kinase C activity in pancreatic islets.

A potential role of arachidonic acid in the modulation of insulin secretion was investigated by measuring its effects on calmodulin-dependent protein kinase and protein kinase C in islet subcellular fractions. The results were interpreted in the light of arachidonic acid effects on insulin secretion from intact islets. Arachidonic acid could replace phosphatidylserine in activation of cytosolic protein kinase C (K0.5 of 10 microM) and maximum activation was observed at 50 microM arachidonate. Arachidonic acid did not affect the Ca2+ requirement of the phosphatidylserine-stimulated activity. Arachidonic acid (200 microM) inhibited (greater than 90%) calmodulin-dependent protein kinase activity (K0.5 = 50-100 microM) but modestly increased basal phosphorylation activity (no added calcium or calmodulin). Arachidonic acid inhibited glucose-sensitive insulin secretion from islets (K0.5 = 24 microM) measured in static secretion assays. Maximum inhibition (approximately 70%) was achieved at 50-100 microM arachidonic acid. Basal insulin secretion (3 mM glucose) was modestly stimulated by 100 microM arachidonic acid but in a non-saturable manner. In perifusion secretion studies, arachidonic acid (20 microM) had no effect on the first phase of glucose-induced secretion but nearly completely suppressed second phase secretion. At basal glucose (4 mM), arachidonic acid induced a modest but reproducible biphasic insulin secretion response which mimicked glucose-sensitive secretion. However, phosphorylation of an 80 kD protein substrate of protein kinase C was not increased when intact islets were incubated with arachidonic acid, suggesting that the small increases in insulin secretion seen with arachidonic acid were not mediated by protein kinase C. These data suggest that arachidonic acid generated by exposure of islets to glucose may influence insulin secretion by inhibiting the activity of calmodulin-dependent protein kinase but probably has little effect on protein kinase C activity.

Detection by a human monoclonal antibody of a glycoprotein associated with malignant proliferation of mammary epithelial cells.

A tumour-associated antigen (TAA.62) with an apparent mol. wt. of 62 kd, identified by a human monoclonal antibody (IgG2, kappa-light chain), was found to be expressed at elevated levels in the cytoplasmic compartment of malignant as compared with normal mammary epithelial cells in both tissues and cultured cells. Increased levels of cytoplasmic expression of the antigen were also observed in malignant cells of cervix, colon, kidney, lung, and stomach. The patterns of expression of TAA.62 in cultured cells mirrored those of tissues and the antigen was expressed at elevated levels in the established breast cancer lines or oncogenically transformed mammary carcinoma cell line (tumourigenic) compared with the immortalised mammary epithelial cell line (non-tumourigenic). Aliquots of TAA.62 were purified to homogeneity from the conditioned-medium of malignant and immortalised breast cells by immunoaffinity chromatography using immobilised anti-TAA.62 antibody, and gel filtration. Both preparations of TAA.62 yielded a single band with an apparent molecular weight of 62 kd under reducing condition on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and both were identical in terms of size and immunoreactivity to anti-TAA.62 antibody. However, TAA.62(T) isolated from tumourigenic cell lines itself interacted with a cell surface molecule having an apparent molecular weight of 160 kd on both the malignant and immortalised cells: TAA.62(I) isolated from immortalized cell lines, showed no comparable interaction. Scatchard analysis of the concentration-dependent binding of TAA.62(T) to 160 kd-receptor molecule revealed a 2.6 x 10(4) binding sites per cell. The association constant of such binding was determined to be approximately 16.6 nM. Finally, addition of anti-TAA.62 antibody to culture medium resulted in the inhibition of proliferation of the malignant cells, but showed no effect on the normal cells. The results suggest that TAA.62 may interact as a ligand with its 160 kd cell surface receptor with a possible growth related function.