Replacement of the N alpha-blocking group in the formyl-methionyl tripeptide chemoattractant: an insight into the mode of binding at the receptor on rabbit neutrophils

The tripeptide N alpha-carbamoyl-L-methionyl-L-leucyl-L-phenylalanine methyl ester has been synthesized in solution by classical methods and fully characterized. This compound, prepared in order to obtain a deeper insight into the mode of binding at the formyl peptide chemotactic receptor, has been tested for its ability to induce granule enzyme secretion from rabbit peritoneal neutrophils and found to be a complete agonist. These results confirm the hypothesis that a proton on the N alpha-blocking group of the tripeptide forms a hydrogen bond with an acceptor in the binding site.     

Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.     

Success rate and duration of orthodontic treatment for adult patients with palatally impacted maxillary canines.

This study was undertaken to examine the success rate and the length of orthodontic treatment of impacted maxillary canines in adult patients. A sample of 19 adults (mean age, 28.8 +/- 8.6 years; range, 20-47 years), who had been treated for a total of 23 impacted maxillary canines, was compared with a younger control group (mean age, 13.7 +/- 1.3 years; range, 12-16 years). The control subjects were chosen for a similar degree of impaction difficulty by carefully matching the positions of the impacted canines in the 3 planes of space. The success rate among the adults was 69.5% compared with 100% among the younger controls. The lower success rate was due to 5 canines that had failed to erupt and 2 canines that had been partially extruded but could not be aligned in the arch. The duration of treating the overall malocclusion of the adults and young subjects did not materially differ. However, the adults showed significant increases in the duration and number of treatment visits required for resolving the canine impaction, in both the simpler and the more difficult cases. When further divided by age, all the failed canines were found in the older (over 30) adult subgroup. It was concluded that the prognosis for successful orthodontic resolution of an impacted canine in an adult is lower than that in a younger patient and that the prognosis worsens with age. Furthermore, when such treatment is undertaken, its successful completion should be expected to take considerably longer.     

Bacterial hydrogen peroxide contributes to cerebral hyperemia during early stages of experimental pneumococcal meningitis.

Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci -- in particular, Streptococcus pneumoniae, the most frequent pathogen in bacterial meningitis -- release hydrogen peroxide (H(2)O(2)) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H(2)O(2) production on regional cerebral blood flow (rCBF) and intracranial pressure (ICP). Compared to wild-type D39 pneumococci, the increase of rCBF was diminished in meningitis induced by the H(2)O(2) defective SpxB(-) mutant (maximum increase, 135% +/- 17% versus 217% +/- 23% of the individual baseline; P<0.01) or after treatment of D39-induced meningitis with H(2)O(2)-degrading catalase or with tetraethylammonium (TEA), a blocker of calcium-sensitive potassium channels, which mediate H(2)O(2)-induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB(-), supporting the predominant role of bacterial H(2)O(2). We conclude that in addition to host-sided mediators, bacterial-derived H(2)O(2) acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis.     

Current practice patterns in pancreatic surgery: Results of a multi-institutional analysis of seven large surgical departments in germany with 1454 pancreatic head resections, 1999 to 2004 (german advanced surgical treatment study group)

Despite decreasing mortality rates, morbidity is still high after pancreatic head resection. Comparative data in the United States and Europe show a relationship between hospital volume and mortality. Treatment strategies vary frequently, partially because of the lack of evidence-based data. We performed a multi-institutional analysis in Germany evaluating current numbers, indications, techniques, and complication rates of pancreatic head resection. Questionnaires were completed by seven high-volume surgical departments regarding quantitative and qualitative aspects of pancreatic head resections in the period from 1999 to 2004 (five prospective and two retrospective institutional databases). A total of 1454 pancreatic head resections (944 for malignancy) were reported. Mean annual hospital volume ranged from 14 to 52 (10 to 43 in malignancy). Mortality was between 1.1% and 4.8%, morbidity was between 24% and 46%, and pancreatic leakage was between 9% and 20%. In malignant disease, all centers perform standard lymphadenectomy and regard arterial infiltration as a contraindication for resection. However, the rate of portal vein resection varied from 0% to 28%. No consensus is seen on the type of surgery for malignancy and chronic pancreatitis. After resection for pancreatic cancer less than one fourth of the patients receive adjuvant therapy. The results of our analysis in Germany confirm that pancreatic head resection can be performed with low mortality in specialized units. Variations in indications, operative technique, and perioperative care may demonstrate the lack of evidence-based data and/or personal and institutional experience. The low number of patients receiving adjuvant therapy after resection of pancreatic cancer suggests that more efforts must be made to establish novel adjuvant therapies under randomized study conditions. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

New insights into the pathophysiology of flail segment: the implications of anterior serratus muscle in parietal failure.

OBJECTIVE: The wisdom of surgery facing multiple and multi-focal ribs fractures (flail segment) remains controversial. By the present retrospective study, we sought to determine the advisability of surgery as well as the anatomical and biomechanical features of flail segment leading to secondary dislocation. METHOD: From 1970 to 2000, 127 patients underwent flail segment osteosynthesis. Clinical charts, operative reports and imaging data were reviewed retrospectively. Rib osteosynthesis was carried out with Judet staple and Kirschner wires until 1980, since then it has been undertaken with sliding-staples-struts. Postoperative chest X-ray was carried out to classify the flail segments into anterolateral and posterolateral types according to the location of anterior and posterior rib fractures. Each type was then divided into three subgroups of primary parietal, secondary parietal and retreat indications that were inferred retrospectively from final indications of rib osteosynthesis. RESULTS: The mean age of patients (ranging in age from 20 to 84 years) was 56+/-14.4 years with a male predominance (108/19). Seventy percent of flail segments was considered as posterolateral. The mean number of rib fractures per patient was 6+/-0.35. Rib osteosynthesis was undertaken with sliding-staples-struts in 70% of patients. The overall hospital mortality was 16%; it was subsequently reduced to 8% since sliding-staples-struts were used. The mean duration of ventilation was reduced from 5.8+/-0.76 days to 2.98+/-0.83 days with sliding-staples-struts. Seventy-seven percent of patients with posterolateral flail segment and primary parietal indication were extubated within the first 48 h postoperatively, whereas 46% of patients from other subgroups required ventilation for more than 5 days. Similarly, 83% of patients of the former subgroup returned to full previous level of activity compared with a rate of 52% for the latter subgroups. The flail segments were dislocated superoposteriorly for both anterolateral and posterolateral types, evoking the action of anterior serratus muscle. CONCLUSIONS: The anterolateral and posterolateral flail segments are rendered susceptible to secondary dislocation through a complex set of factors, of which the action of anterior serratus muscle is obvious. Restoration of parietal mechanics by early surgical reduction/fixation is a reliable therapeutic option in selected patients and offers encouraging results.