Randomized prospective trial comparing the native prothrombin antigen with the prothrombin time for monitoring oral anticoagulant therapy

The dosage of the anticoagulant warfarin sodium is based upon the prolongation of the prothrombin time into an optimal therapeutic range. We have developed a new assay for the native prothrombin antigen that measures the fully gamma-carboxylated prothrombin using a radioimmunoassay. Based on preliminary data that indicated that the native prothrombin antigen predicted both bleeding and thrombotic complications more accurately than the prothrombin time in patients anticoagulated with warfarin sodium, we have performed a randomized prospective trial comparing the complication rate in warfarin-treated patients monitored with the native prothrombin antigen or the prothrombin time. Patients with indications for anticoagulation were randomized to be monitored by the native prothrombin antigen (therapeutic range, 12 to 24 micrograms/mL) or the prothrombin time index (therapeutic range, 1.5 to 2.0). Of the prothrombin time group (N = 80), seven (8.8%) had bleeding or thrombotic complications, with a complication rate of 9.5%/patient-year. In the native prothrombin antigen group (N = 76), one subject (1.3%) had a bleeding complication. The complication rate per patient-year was 1.5%. These results indicate an 85% reduction in the complication rate of the native prothrombin antigen group compared with the complication rate of the prothrombin time group. This difference is statistically significant by the Fisher exact test (P = .037) and by Kaplan Meier survival analysis (P = .040). This study suggests that the use of the native prothrombin antigen assay has the potential to decrease the complications associated with anticoagulation therapy with warfarin sodium.     

Critical factors affecting quality of life of adult patients with anorectal malformations or Hirschsprung's disease

OBJECTIVES: The first objective was to compare the quality of life of adult patients with anorectal malformations (ARM) or Hirschsprung's disease (HD) and to compare both groups with healthy people. And the second objective was to examine the factors that affect the quality of life of patients with ARM or HD, using a theoretical model in which patients' background characteristics explain quality of life via mediating disease-specific functioning and psychosocial functioning. METHODS: Three hundred and forty-one patients completed a questionnaire, which assessed sociodemographic characteristics, disease-specific and psychosocial functioning, and quality of life. Clinical factors were extracted from the medical records. RESULTS: Patients with ARM or Hirschsprung's disease did not differ in their quality of life. Compared to healthy people, both patient groups reported more limitations in their "overall" physical quality of life, but only patients with ARM reported impaired quality of life on several specific domains (e.g., physical role-functioning, pain). The model was largely accepted. Most striking were the strong effects of the psychosocial functioning factors in contrast to weak effects of the disease-specific "constipation" and "fecal continence" factors. CONCLUSIONS: The quality of life of patients with ARM or Hirschsprung's disease was found to be comparable. Compared to healthy people, both patient groups encountered "overall" physical health problems, but only patients with ARM reported additional pain and limitations in role functioning due to physical problems. It appeared that psychosocial functioning had the most important effect on the quality of life of patients with ARM or Hirschsprung's disease, while fecal incontinence and constipation had almost no effect on their quality of life.     

Comparison of the Utrecht Scale for Evaluation of Rehabilitation-Participation With the ICF Measure of Participation and Activities Screener and the WHO Disability Assessment Schedule II in Persons With Spinal Cord Injury

Objective

To validate the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) in persons with spinal cord injury (SCI) using 2 International Classification of Functioning, Disability and Health (ICF)-based instruments: the ICF Measure of Participation and Activities-Screener (IMPACT-S) and the World Health Organization Disability Assessment Schedule II (WHODAS II).

Design

Validation study. Score distributions, internal consistency, and concurrent and discriminant validity were evaluated.

Setting

The community.

Participants

Convenience sample of persons (N=157) with long-term SCI living in The Netherlands.

Interventions

Not applicable.

Main Outcome Measures

USER-Participation, IMPACT-S, and WHODAS II.

Results

No instruments showed floor effects, and 3 out of 6 WHODAS II domains showed ceiling effects. Most scores showed adequate internal consistency (α≥.70), except for the USER-Participation frequency scale (.51) and 2 WHODAS II domains (.58–.60). Spearman correlation coefficients between the segregate USER-Participation scales were <.60 (range, .39–.46), showing that they cover separate aspects of participation. Concurrent validity of the USER-Participation was shown because >75% (83.3%) of the 24 hypotheses (Spearman correlation coefficients above or below .60) with the other measurement instruments were confirmed. Concurrent validity between the IMPACT-S and WHODAS II was not shown (53.8% of 13 hypotheses confirmed). All scores except 4 WHODAS II domains showed significant differences in participation between persons with paraplegia and tetraplegia.

Conclusions

The USER-Participation showed generally satisfactory psychometric properties in Dutch persons with long-term SCI living in the community. The IMPACT-S showed the best psychometric properties, and the WHODAS II showed less favorable results. Future research on the USER-Participation should focus on validation in other languages and different diagnostic groups.     

The influence of the CO2 pneumoperitoneum on a rat model of intestinal anastomosis healing

Background

The CO₂ pneumoperitoneum, which is used for laparoscopic surgery, causes local and systemic effects in patients. Concern arises about what the pressurized anoxic environment of the CO₂ pneumoperitoneum has on intestinal healing. Earlier experimental work showed a negative correlation between intestinal healing and the applied intra-abdominal pressure. To further elucidate this, we developed a rat model, in which enterotomy healing can be compared after open or laparoscopic surgery. Possible mechanisms of injury, such as impaired neoangiogenesis or injury through hypoxia-induced pathways were studied.

Methods

A new experimental mechanically ventilated rat model was developed. An enterotomy was made and closed via laparotomy (group I) or laparoscopy under CO₂ pressures of 5?mmHg (group II) or 10?mmHg (group III). Intestinal healing was tested in vivo after 1?week by bursting-pressure analysis. The effect of the operative procedure on neoangiogenesis was tested by counting factor VIII positive vessels in biopsies of the perianastomotic granulation tissue after 1?week. Intestinal anoxia was tested by quantifying HIF-1α protein levels in intestinal biopsies, taken before the enterotomy closure.

Results

The bursting pressures were significantly lower after laparoscopic surgery at 10?mmHg CO₂ pneumoperitoneum (group III) compared with rats that had undergone open surgery (group I) or laparoscopic surgery at 5?mmHg CO₂ pneumoperitoneum (group II). There was no significant quantitative difference between the three groups in the neoangiogenesis nor was there a difference in the amount of HIF-1α measured in the intestinal biopsies.

Conclusions

We developed a surgical model that is well fitted to study the effects of pneumoperitoneum on intestinal healing. With this model, we found further evidence of CO₂ pressure-dependant hampered intestinal healing. These differences could not be explained by difference in neoangiogenesis nor local upregulation of hypoxic factors.     

Laparoscopic treatment of gastric and duodenal perforation in children after blunt abdominal trauma

Minimal invasive surgery has not yet gained wide acceptation for the care of patients that sustained an abdominal trauma. We describe the complete laparoscopic surgical treatment of two patients after a single blunt abdominal trauma. One patient sustained a handle bar injury and presented with a gastric perforation. The other sustained a duodenal rupture by falling on a sharp edge of a table. The patients were assessed and treated laparoscopically. The perforations were identified and closed. Both patients had an uneventful postoperative recovery. Therapeutic laparoscopic treatment of patients with upper gastrointestinal perforation is feasible. We would recommend this approach to experienced laparoscopic surgeons in hemodynamically stable patients.     

Chimeric vitronectin:insulin-like growth factor proteins enhance cell growth and migration through co-activation of receptors

Complexes comprised of IGF-I, IGF-binding proteins and the ECM protein vitronectin (VN) stimulate cell migration and growth and can replace the requirement for serum for the ex vivo expansion of cells, as well as promote wound healing in vivo. Moreover, the activity of the complexes is dependent on co-activation of the IGF-I receptor and VN-binding integrins. In view of this we sought to develop chimeric proteins able to recapitulate the action of the multiprotein complex within a single molecular species. We report here the production of two recombinant chimeric proteins, incorporating domains of VN linked to IGF-I, which mimic the functions of the complex. Further, the activity of the chimeric proteins is dependent on co-activation of the IGF-I- and VN-binding cell surface receptors. Clearly the use of chimeras that mimic the activity of growth factor:ECM complexes, such as these, offer manufacturing advantages that ultimately will facilitate translation to cost-effective therapies.