Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model.Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 microg VEGF, carrier alone or autograft. After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow. We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.     

Effects of pneumatic dilation and myotomy on esophageal function and morphology in patients with achalasia

Only two treatment modalities-pneumatic dilation and Heller myotomy-promise long-term relief from dysphagia and regurgitation in patients with achalasia. The objective of this study was to determine whether both options differ in their effects on esophageal function, morphology, and improvement in symptoms. Eighty-nine patients diagnosed with achalasia between January 1980 and December 2002 at a single center were enrolled in this study. Sixty-four patients underwent pneumatic dilation and 25 Heller myotomy in combination with an anterior semifundoplication (Dor procedure). Clinical evaluation (Eckardt-Score), esophageal manometry, and barium swallow were performed before and within 6 months after treatment. Our data shows that Heller myotomy reduces the LES resting pressure more markedly (7.9 [3.7-16.9] mm Hg) than pneumatic dilation (14.5 [2.7-36.0] mm Hg) (P < 0.0001) with similar pressures at diagnosis in both groups. Morphologic changes, assessed by the diameter of the esophageal corpus, were also more pronounced after surgical therapy (P > 0.05). Both options will lead to an immediate and significant improvement in symptoms, although the two treatment modalities did not differ in their subjective results. As only objective findings, such as those obtained by manometry and the timed barium swallow, have proven relevance for the assessment of long-term results, surgical therapy is the superior and more effective treatment option in patients with achalasia.     

Heller myotomy for failed pneumatic dilation in achalasia: how effective is it?

OBJECTIVES: This long-term prospective study describes the effect of myotomy in patients who fail to respond to repeated pneumatic dilations and compares their clinical course with that of patients responding to dilation therapy. METHODS: Nineteen consecutive patients who had never reached a clinical remission after repeated pneumatic dilation underwent myotomy. Their clinical course was compared with that of patients who had reached a clinical remission after a single (n = 34) or multiple (n = 14) pneumatic dilation(s). Symptoms were graded with a previously described symptom score ranging from 0 to 12. Remission was defined as a score of 3 or less persisting for at least 6 months. Duration of remission was summarized using Kaplan Meier survival curves. Association between baseline factors and the need for surgery was evaluated using logistic regression. RESULTS: Complete follow-up was obtained for 98.5% of the patients. The median duration of follow-up was similar in patients treated by myotomy (10.0 years), in patients reaching a clinical remission after a single dilation (10.6 years), but differed in patients undergoing repeated dilations (6.9 years). The 10-year remission rate was 77% (95% CI 53-100%) in patients undergoing myotomy, 72% (95% CI: 56-87%) in patients "successfully" treated with a single pneumatic dilation and 45% (95% CI: 16-73%) in patients undergoing several dilations. Among all baseline factors investigated, young age was associated with an increased need of surgery. CONCLUSIONS: Myotomy is an effective treatment modality in patients with achalasia who have failed to respond to pneumatic dilation. Young patients may benefit from primary surgical therapy.     

Long-term results for Heller-myotomy with anterior semifundoplication in achalasia

INTRODUCTION: The positive success rate of cardiomyotomy in the treatment of achalasia has recently - especially in young patients - resulted in a primary operative treatment concept. Few studies of long-term effects of myotomy concerning the removal of dysphagia and the development of gastroesophageal reflux have been submitted. PATIENTS AND METHODS: In the period between September 1985 and March 2003, an open, transabdominal Heller-myotomy combined with a Dor-semifundoplication was carried out in 93 patients with achalasia. 77 patients were followed for more than 6 months postoperatively (median follow-up: 70 months). The procedure was prospectively observed, and patients were questioned concerning their clinical symptoms by means of structured interviews. X-ray examinations of the esophagus were pre- and postoperatively available of 47 patients, manometrical findings before and after myotomy of 26 patients. RESULTS: The pre-operatively existing symptoms dysphagia, regurgitation, retrosternal pain and weight-loss could be improved by myotomy in 97 % of the patients with good to excellent long-term results. Post-operatively, a significant reduction of the median maximum diameter of the esophagus of 50 mm to 30 mm was evident (p < 0.001), whereas the diameter of the cardia increased from 3 mm to 10 mm (p < 0.001). The pre-operative resting pressure of the lower esophageal sphincter (LES) of 29.3 mmHg was reduced to 7.9 mmHg (p < 0.001). Patients suffering from reflux esophagitis showed a significant lower resting pressure of the LES (4 mmHg) in comparison with patients without reflux esophagitis (8.5 mmHg) after myotomy (p=0.045). The clinical long-term results of patients with preceding pneumatic dilation did not differ significantly from those with primary myotomy. CONCLUSION: Conventional Heller-myotomy with anterior semifundoplication can in the long run remove the symptoms existent in achalasia with high efficiency. If the decrease of the post-operative resting pressure of the LES is too intense (< 5 mmHg), a possible gastroesophageal reflux has to be taken into account. The results of open cardiomyotomy have to be regarded as standard for assessing the minimal-invasive procedure.     

Shape changes in prefrontal, but not parieto-occipital regions: brains of schizophrenic patients come closer to a circle in coronal and sagittal view

There is some evidence for prefrontal (PF) lobe changes in schizophrenia while the parieto-occipital (PO) region seems to be unaffected. This magnetic resonance imaging (MRI) study was performed to examine shape differences as part of the spectrum of structural abnormalities in schizophrenia. The measurements were done on families affected with schizophrenia to identify the influence of genetic and environmental factors on these changes. The sample under study consisted of 164 subjects including 45 family members (FM) suffering from schizophrenia, 27 FM with other psychiatric disorders and 51 FM without psychiatric disorders based on ICD-10 criteria. In addition, 41 nonpsychiatric control subjects were included in the study. On defined planes at the corpus callosum boundary of the PF and the PO, brain width, height and length were measured on coronal slices. Ratios of these linear measurements were also calculated based on the idea that a plane can be approximated by a circle if the concerning ratio comes close to 1. It was hypothesized that these relative brain shape parameters, especially the PF ratio width/height, would show differences between schizophrenic patients and control subjects. For all members from families with schizophrenia compared with control subjects, there were significant differences in the PF, but not in the PO region. PF height was increased. PF ratios of width/height and height/(2 x length) were closer to 1 in affected families than in control subjects. The results can be interpreted as an indication for PF brain shape changes in subjects with a disposition for schizophrenia. On coronal and sagittal planes situated at the corpus callosum, their PF could be approximated by a circle better than in control subjects. As the frontal lobe takes shape late in brain development, underlying genetic mechanisms may be dysregulated in schizophrenic patients and subjects at risk to develop the disorder.