Ulnar Variance in Scaphoid Fractures: Retrospective Analysis of 182 Cases.

BACKGROUND: Literature provides little and controversial evidence regarding the influence of ulnar variance (UV) on the incidence of scaphoid fractures. The aim of this retrospective study was to assess UV in a large number of patients with acute scaphoid fracture in comparison to a control group of the same population. METHODS: During a two year period, 182 patients with acute scaphoid fractures (fracture group) and 182 ethnicity-, gender- and age-matched patients with wrist contusions (control group) were treated in three non-university hospitals. Using standardized digital wrist radiographs, UV values were measured by means of the method of perpendiculars by two independent examiners. The UV values of the fracture group were then compared to the UV values of the control group. RESULTS: Analyses of the agreement between the two raters resulted in a good to excellent inter-item correlation of 0.89, with a high intra-class coefficient of 0.93 (95% confidence interval: 0.87-0.95). Mean (SD) UV value was -0.82 mm (1.77) in the fracture group and 0.27 mm (1.44) in the control group. Paired sample t-test showed a significant difference between the two groups (p < 0.0001). CONCLUSIONS: According to this study, patients with scaphoid fractures are significantly more likely to show a negative UV than matched patients with wrist contusions.

Thumb carpometacarpal joint denervation for primary osteoarthritis: A prospective study of 31 thumbs.

We present the results of a prospective study of 31 thumbs in 30 patients affected by primary osteoarthritis at the thumb carpometacarpal (CMC1) joint who were treated with denervation of the involved joint. For every operated hand, the Kapandji score, key-pinch strength, grip strength and pain on a visual analogue scale were evaluated preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, 6 months and 1 year. The patients' satisfaction was determined. The Kapandji score and key-pinch strength improved significantly in all patients. Grip strength improved significantly in 10 hands. Pain was reduced in all cases. Nevertheless, 6 patients were dissatisfied with the operation. Of these 6 patients, 4 had stage IV arthritis in the TMC and scaphotrapeziotrapezoid joints of the thumb. Thumb CMC denervation appears to reduce pain at 1 year with an overall improvement in key-pinch strength. However, patients with stage IV CMC arthritis were not satisfied with the outcome of the procedure.

Midterm Results of Semiconstrained Distal Radioulnar Joint Arthroplasty and Analysis of Complications.

Range of motion and stability are important outcome parameters to assess function of the distal radioulnar joint (DRUJ), in particular pronation, supination, and weight-lifting capacity. The DRUJ semiconstrained implant developed by Scheker et al is intended to reproduce all the functions of the triangular fibrocartilage complex and the DRUJ. The aim of the study was to investigate the subjective, clinical, and radiographic results in 10 patients after primary implantation of the semiconstrained DRUJ arthroplasty following DRUJ derangement and painful instability, with an average follow-up of 3 years with a special focus on the complications. Standardized preoperative and postoperative evaluation included assessment of pain by a visual analog scale, radiographic examination, range of motion measurements, lifting capacity, and grip strength. The patient-perceived function was investigated using clinical score charts. Compared with the preoperative status, range of motion showed little change, while grip strength, lifting capacity, pain score, and patient-perceived functions improved significantly. One patient developed an ulna stem loosening, while two patients had to be reoperated because of an irritation of the extensor tendons and the superficial radial nerve at the first dorsal compartment of the wrist. In this study, arthroplasty of the DRUJ using the semiconstrained DRUJ arthroplasty was found to result in satisfactory outcome. Level of evidence: Level IV.

Extending the limits of reconstructive microsurgery in elderly patients.

BACKGROUND: Population aging strongly affects the demographic development of industrialized countries. While microsurgical procedures were initially believed to be only feasible in patients of younger age because of the duration of the surgical procedure and the higher risk of vascular insufficiency due to age-related comorbidities, it has become evident that these procedures are beneficial even for patients at an advanced age. METHODS: We retrospectively investigated microsurgical procedures in a patient cohort (n = 25 with 27 free flaps) with a minimum age of 78 years with regard to patients' characteristics, flap survival, and postoperative surgical and medical complications. RESULTS: Median age was 81 years (IQR 6). Most defects were located in the head and neck region. The mean operation time was 384 min (standard deviation (SD) 131). Flap failure was observed in three cases (11%). The median length of hospital stay was 17 days (interquartile range (IQR) 8). The mean ASA score was 2.48. Patients' age and ASA group did not correlate. The mortality rate was 4%. Postoperative surgical complications were observed in 11 cases (41%), while 19 patients (70%) showed one or more medical complications. Higher ASA classes tended to show more postoperative complications. However, neither age nor operating time nor ASA status showed significant influence on the occurrence of postoperative medical or surgical complications. CONCLUSION: There is growing demand for structural and functional restoration using free tissue transfer in an aging population. If there are no alternative treatment options available promising similar structural and functional preservation, free tissue transfer is justifiably in very old patients despite a potentially increased flap failure. As such, free tissue transfer is used as a curative treatment concept aiming at a maximum of patients' independence and early ambulation. Occurrence of complications can be diminished by adequate patient selection and thorough perioperative care.

Long-term clinical outcome after epineural coaptation of digital nerves.

UNLABELLED: This study evaluates the long-term clinical outcome and complication rate after digital nerve repair in adults and aims to identify possible prognostic factors of sensory recovery. End-to-end epineural coaptation was performed under magnification. A total of 93 coapted digital nerves were clinically evaluated with a mean follow-up of 3.5 years (range 1-6 years). The mean two-point discrimination was 10.6 mm (versus 4.4 mm for the contralateral side). Cutaneous pressure threshold tested with Semmes-Weinstein monofilaments showed a mean value of 2.7 (versus 2.2 for the contralateral side). Only 2% of our patients developed painful neuromas. None of our patients recovered normal functional sensibility, however, recovery of protective sensation contributed to a high reported level of satisfaction. No correlation was observed between the sensory outcome and age, smoking, mechanism of injury, lesion to or anastomosis of a digital artery, or time of immobilization. The only identified predictor of the result was the surgeon's level of experience. This highlights the importance of adequate training and practice in the surgical repair of smaller peripheral nerves. LEVEL OF EVIDENCE: IV.

Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation.

Sensitization describes the acquired ability of the immune system to react to foreign human leukocyte antigens (HLA) by producing antibodies and developing memory cells. In the field of transplantation, recipient preformed HLA antibodies due to previous sensitization have been identified - beneath ABO incompatibility - as a major factor for acute graft rejection. Several reasons for sensitization have largely been studied, such as previous blood transfusions, pregnancies or former transplants. Recent studies indicate that the use of assist devices (e.g. ECMO) or cadaveric skin allotransplantation providing temporary coverage in burn patients may lead to additional sensitization. As vascularized composite allotransplantation (VCA) has become a rapidly advancing therapeutic option for reconstruction of complex tissue defects in burns, it seems even more important to become familiar with immunological principles and to be cautiously aware of both sources of sensitization and therapeutic concepts in burns avoiding sensitization. This may also include emergency VCAs in burn patients as potential strategy for early definitive reconstruction avoiding procedures triggering HLA antibody formation. We hereby provide an overview on current evidence in the field of pre- and peritransplant sensitization, followed by posttransplant strategies of desensitization and their potential impact on future treatments of burn patients.

Outbreak of pathogenic Escherichia coli in an outdoor-housed non-human primate colony.

BACKGROUND: Pathogenic Escherichia coli has been identified as an etiologic agent in humans causing acute diarrhea or even death but has been rarely reported in non-human primates (NHP). An outbreak of diarrhea occurred in an outdoor-housed NHP colony over a period of 2 months with an attack rate of 29%. METHODS: Bacterial culture and PCR were performed on the fecal specimens to identify enteroinvasive E. coli (EIEC) and Enterohemorrhagic E. coli (EHEC) in the NHPs. RESULTS: By random sampling of 10% of fecal samples of diarrheal cases, four cases of EIEC in rhesus macaques and two cases of EHEC in cynomolgus macaques were confirmed. CONCLUSION: This is the first time EIEC and EHEC have been reported in NHPs associated with diarrhea. The primary source of infection could not be determined.

Helicobacter pullorum outbreak in C57BL/6NTac and C3H/HeNTac barrier-maintained mice.

Helicobacter pullorum is a bacterial pathogen in humans. By using microaerobic culture techniques, H. pullorum was isolated from the feces of barrier-maintained mice and identified, on the basis of biochemical, restriction fragment length polymorphism, and 16S rRNA gene sequence analyses. This finding presents an opportunity to study H. pullorum pathogenesis in mice.

Establishing a culture of care, conscience, and responsibility: addressing the improvement of scientific discovery and animal welfare through science-based performance standards.

Science-based performance standards offer a viable means of reducing regulatory burden while ensuring that research animal welfare and high-quality research data are realized. Unlike rigid regulations, science-based performance standards evolve as new information becomes available, thereby allowing new discoveries to be implemented in a timely manner and in a way that more effectively benefits the animals and the science. The implementation of performance standards requires a well-coordinated institutional team composed of the administration, research staff, the institutional animal care and use committee, professional and technical animal care personnel, occupational health and safety staff, and physical plant staff. This animal program team is best supported in an institutional environment that reflects a culture of care, compliance, and responsibility. In such a culture, the professional judgment exercised by the team is well grounded in meeting the diverse needs of the program's customers, who include the animals, the researchers, and research stakeholders such as the public. The institutional culture of care, compliance, and responsibility fosters workplace integrity, an ethics-based decision-making paradigm, sound understanding of institutional expectations through good communication and clear lines of authority, the hiring and retention of trained and well-qualified individuals, and a system for continuous development and improvement of the program.

A novel approach for assessing the quality and effectiveness of IACUC oversight in investigator compliance.

In research facilities that are registered with the U.S. Department of Agriculture (USDA), funded by the Public Health Service, or accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, the Institutional Animal Care and Use Committee (IACUC) is charged with oversight and evaluation of animal care and use under the terms of the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals. Although the committee's oversight of investigator compliance may be evaluated annually during USDA inspections and triennially during AAALAC International site visits, routinely assessing the quality and effectiveness of the IACUC's performance is difficult. To measure the successfulness of IACUC oversight, our committee retained a management consultant to objectively design and conduct a confidential survey that could be used to determine how the IACUC could improve the process of facilitating researcher compliance with federal regulations and accreditation standards. The consultant based the content of the survey on confidential interviews with all IACUC members, the IACUC administrator, and a cross sectional representation of the key animal-user population at the facility. The survey was then distributed to the entire animal-user population. Vice-presidents, directors, principal investigators, and technicians were included in the distribution. With a response rate of 34%, the survey results indicated that the facilitation process warranted refinements. The consultant provided the IACUC with its recommendations, which were based on the discernible trending information indicated in the survey responses. The IACUC developed a specific plan of action to address the consultant's recommendations and intends to re-survey the animal-user population once the action plan has been fully implemented. In summary, the survey is an excellent way to assess the quality and effectiveness of IACUC oversight in investigator compliance by determining the level of researcher satisfaction. The evaluation, review, and follow-up process using a confidential interview and questionnaire technique can enhance the performance and effectiveness of IACUC oversight.

Goal commitment and the goal-setting process: conceptual clarification and empirical synthesis.

Goals are central to current treatments of work motivation, and goal commitment is a critical construct in understanding the relationship between goals and task performance. Despite this importance, there is confusion about the role of goal commitment and only recently has this key construct received the empirical attention it warrants. This meta-analysis, based on 83 independent samples, updates the goal commitment literature by summarizing the accumulated evidence on the antecedents and consequences of goal commitment. Using this aggregate empirical evidence, the role of goal commitment in the goal-setting process is clarified and key areas for future research are identified.

Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate markers using the adenovirus delivery method. Rate of weight loss and percentage satiety were significantly greater in the mice treated with Adleptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 +/- 2.6 ng/ml for the human gene, and 48.9 +/- 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 +/- 36.0 ng/ml). (Values are given as mean +/- standard error of the mean.) Importantly rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin in the treatment of obesity.

Protease activity in a hapten-induced model of ulcerative colitis in rats.

Inflammatory bowel disease (IBD) is a painful and debilitating condition affecting the mucosal lining of the colon and other areas of the gastrointestinal tract. IBD generally falls into two major categories: ulcerative colitis (UC) and Crohn's disease. We have utilized dinitrobenzenesulfonic acid (DNBS) to induce experimental UC in rats. Histopathologic analysis indicates that DNBS induces a condition in animals similar to human UC. Biochemical results revealed 6- to 10-fold elevated levels of serine protease activity in colon tissue from animals with UC as compared with matched controls. We also observed elevated levels of protease activity in tissue samples obtained from human patients with UC. Hence, our results demonstrate that protease activity is increased in rodent and human UC. These proteases may play a significant role in destruction of colonic tissue in IBD. Protease inhibitors that target serine proteases may be useful pharmacological agents to limit tissue destruction in IBD.

Effects of anesthesia and open-thorax surgery on coronary vascular reserve in swine.

The coronary reactive hyperemic response was examined in seven pigs under anesthetized and conscious conditions, (i.e., 5 days and 3 and 5 weeks after surgery). Tygon catheters were inserted in the descending aorta of five pigs; transonic flow probes and hydraulic occluders were placed on the left cranial descending and/or left circumflex coronary arteries. Two pigs underwent long-term implantation of similar instruments. The coronary reactive hyperemic response, expressed as repayment of flow deficit, was induced by brief complete coronary artery occlusion for 15 sec. Baseline mean arterial pressure, heart rate, and coronary blood flow were similar in the anesthetized and conscious pigs. There was also no significant difference in repayment of flow deficit between the anesthetized and conscious pigs 5 days after surgery. The repayment of flow deficit (709 +/- 144%) in conscious pigs 5 days after surgery tended to be greater, but was not statistically significant from that observed in the anesthetized pigs (510 +/- 79%). However, at 3 and 5 weeks after surgery, the reactive hyperemic flow and the repayment of flow deficit were numerically greater than those values observed in anesthetized pigs. The difference in reactive hyperemic flow between conscious and anesthetized pigs was statistically significant at week 3. The difference in repayment of flow deficit between conscious and anesthetized pigs was statistically significant at week 5. These results suggest that anesthesia, as well as recent surgery, attenuates coronary vascular reserve. The major factor in the attenuation of coronary reserve appears to be recent surgical manipulation, because repayment of flow deficit was still depressed in conscious pigs during the early phase of recovery from surgery.

Diagnosis of Helicobacter pylori infection in a colony of rhesus monkeys (Macaca mulatta).

Twenty-three young adult rhesus monkeys from China were evaluated for the presence of Helicobacter pylori. Gastric body and antral biopsy samples were tested for H. pylori by PCR analysis, culture, rapid urease testing, and histologic evaluation. Serologic testing to detect H. pylori immunoglobulin G (IgG) antibodies was performed by using a commercially available human-based enzyme-linked immunosorbent assay (ELISA) test and an ELISA test which utilized homologous H. pylori antigens and an anti-rhesus IgG conjugate. PCR analysis with H. pylori-specific 26-kDa protein primers detected H. pylori in 21 of the 23 rhesus monkeys (91%). Culture testing identified the organism in 12 of the 23 animals (52%). Rapid urease tests were positive for all animals. H. pylori was diagnosed by histological examination in 11 of 23 monkeys (48%). Of the 21 monkeys positive for H. pylori by PCR, only 3 (14%) had positive results by the commercial ELISA test, yielding a sensitivity of 14%, a specificity of 100%, and an accuracy of 22%. However, 19 of the 21 PCR-positive animals (90%) had positive results by the ELISA test with homologous rhesus H. pylori antigen and anti-monkey conjugate, with predicted index values greater than or equal to 0.7 considered positive and values between 0.5 and 0.7 considered equivocal. This test had a sensitivity of 90%, a specificity of 100%, and an accuracy of 91%. Therefore, the ELISA test with rhesus monkey origin components was more accurate for detecting infected animals than the human-based ELISA.

Findings and long-term results of subsequent operations after failed microvascular decompression for trigeminal neuralgia.

OBJECTIVE: To evaluate the indication of subsequent operations after failed microvascular decompression (MVD) for the treatment of trigeminal neuralgia, the intraoperative findings and long-term results of 16 subsequent operations are reported. METHODS: Subsequent exploration of the posterior fossa was performed for lack of pain relief (3 patients) and recurrent neuralgia (13 patients) after an average of 17 months (range, 4-62 mo). In all patients, typical arterial compression patterns at the root entry zone of the trigeminal nerve were found in the first procedure. The mean follow-up period after subsequent operation was 90 months (range, 78-104 mo). RESULTS: New arterial neurovascular conflicts were found in nine patients. After subsequent MVD procedures, seven patients were pain-free (with one recurrence after 6 mo), one had constant marked relief, and one was unchanged. Second exploration revealed no abnormalities in the other seven patients who experienced continued or recurrent pain; only careful neurolysis of the trigeminal nerve was performed in those patients. Initially, all seven patients obtained complete pain relief, but two experienced late recurrences after 64 and 68 months, respectively. Thus, subsequent operations failed in all 4 patients who had undergone prior destructive procedures but were successful in those 12 patients who had undergone only previous MVD. Two patients developed severe sequelae, and the other nine had minor complications, especially permanent (four patients) or transitory (three patients) ipsilateral trigeminal hypoesthesia. CONCLUSION: Subsequent MVD seems to have good long-term results. However, because of the significantly high incidence of complications, the indication for subsequent operations should be restricted to younger patients to avoid destructive procedures. In general, glycerol rhizolysis or radiofrequency rhizotomy may be the treatment of choice after failed MVD.

Species specificity of 2-aryl carbapenem-induced immune-mediated hemolytic anemia in primates.

L-695,256 is a novel 2-fluorenonyl carbapenem antibiotic with significant antimicrobial activity against strains of methicillin-resistant Staphylococci. This prototype compound was administered intravenously to rhesus monkeys (Macaca mulatta) at does of 50 or 200 mg/kg/day for 2 weeks to assess toxicity and found to induce a hemolytic anemia characterized by extravascular hemolysis and splenomegaly. A subsequent study in this species in which 100 mg/kg/day was administered i.v. for 4 weeks showed that all animals were direct antiglobulin test (Coombs' test) positive for IgG with 20-25% reductions in the erythron. Following 3 weeks of recovery, the erythron had returned to normal, although it took an additional 2 months for the Coombs' test to become negative. Challenge of these same animals with 0.5 million U/kg (300 mg/kg/day) of penicillin intravenously indicated no apparent cross-reactivity. Since attempts to establish a model for this immune-mediated hemolytic anemia with this drug in rats or mice were unsuccessful, a 2-week i.v. study in squirrel monkeys (Saimiri sciureus) was conducted at a dose of 200 mg/kg/day. All animals in this study remained Coombs' test negative with no changes in the erythron, suggesting an increased sensitivity to beta-lactam-induced anemia in rhesus monkeys compared to other species. Further support for this hypothesis was obtained using the cephalosporin antibiotic, cefotetan. This compound induced a high incidence of Coombs' test positive hemolytic anemia at clinically relevant doses in rhesus monkeys, despite a very low incidence of this adverse effect in patients with many years of clinical use. These data suggest that although rhesus monkeys respond in a qualitatively similar manner to humans with regard to high doses of beta-lactam antibiotics, their sensitivity may overestimate the risk of immune-mediated hemolytic anemia for clinical use.

A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge.

Protection against simian immunodeficiency virus (SIV) challenge was assessed in rhesus monkeys with a vaccine-elicited, single SIV epitope-specific cytotoxic T-lymphocyte (CTL) response in the absence of SIV-specific antibody. Strategies were first explored for eliciting an optimal SIV Gag epitope-specific CTL response. These studies were performed in rhesus monkeys expressing the major histocompatibility complex (MHC) class I gene Mamu-A*01, a haplotype associated with a predominant SIV CTL epitope mapped to residues 182 to 190 of the Gag protein (p11C). We demonstrated that a combined modality immunization strategy using a recombinant Mycobacterium bovis BCG-SIV Gag construct for priming, and peptide formulated in liposome for boosting, elicited a greater p11C-specific CTL response than did a single immunization with peptide-liposome alone. Vaccinated and control monkeys were then challenged with cell-free SIVmne by an intravenous route of inoculation. Despite a vigorous p11C-specific CTL response at the time of virus inoculation, all monkeys became infected with SIV. gag gene sequencing of the virus isolated from these monkeys demonstrated that the established viruses had no mutations in the p11C-coding region. Thus, the preexisting CTL response did not select for a viral variant that might escape T-cell immune recognition. These studies demonstrate that a potent SIV-specific CTL response can be elicited by combining live vector and peptide vaccine modalities. However, a single SIV Gag epitope-specific CTL response in the absence of SIV-specific antibody did not provide protection against a cell-free, intravenous SIV challenge.