An algorithm to avoid missed open-book pelvic fractures.

OBJECTIVE: In polytrauma patients, to limit the pelvic space favouring internal bleeding, the use of pelvic binders is now a standard practice. In case of external pelvic binder placement with anatomic reduction of the symphyseal and sacroiliac joints, delayed diagnosis and missed injuries could occur. The aim of this study is to document the risk of missed diagnosis, as well as to identify a possible algorithm for optimal management of traumatized patients with pelvic binders, in order to reach an early diagnosis of pelvic fractures without additional risks. CASE REPORT: We report three cases of open-book pelvic fractures that were initially missed. The external pelvic binders applied had adequately reduced the fractures. The computed tomography on arrival excluded a diastasis of the symphysis pubis. On removal of the pelvic binder and repetition of the radiological imaging, the fractures were evidenced. CONCLUSIONS: We have accordingly created an algorithm for polytrauma patients to determine when the pelvic binder should be released before radiological imaging and when repeated radiological imaging should be done. The use of this algorithm in trauma centers will help to reduce the number of missed injuries, and the number of late diagnoses as well as will increase the patient survival rates.

PET studies of 18F-memantine in healthy volunteers.

Previous studies in mice and PET investigations in a Rhesus monkey showed that the regional uptake of 18F-memantine could be blocked by pharmacological doses of memantine and (+)-MK-801. In the present study, the binding characteristics of 18F-memantine was examined in five healthy volunteers. In humans, 18F-memantine was homogeneously distributed in gray matter i.e. cortex and basal ganglia regions, as well as the cerebellum. No radioactive metabolites were detected in plasma during the time-frame of the PET studies. The uptake of 18F-memantine in receptor-rich regions such as striatum and frontal cortex could be well described by a 1-tissue compartment model. The DV" values of all gray matter regions were similar and ranged from 15 to 20 ml/ml. The white matter showed lower DV" values of 15 +/- 1.4 ml/ml. These results suggest that 18F-memantine distribution in human brain does not reflect the regional NMDA receptor concentration, and therefore, this radioligand is not suitable for the PET imaging of the NMDA receptors.

Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors.

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

Simplified quantitative determination of cerebral perfusion reserve with H2(15)O PET and acetazolamide.

The measurement of regional cerebral blood flow (rCBF) and perfusion reserve (PR) with H2(15)O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H2(15)O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PRnAA) and rCBF (PRrCBF) (PRnAA=0.843 PRrCBF + 0.092, r=-0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PRnAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling.

Evaluation of serotonergic transporters using PET and [11C](+)McN-5652: assessment of methods.

[11C](+)McN-5652 is an established positron emission tomography tracer used to assess serotonergic transporter density. Several methods have been used to analyze [11C](+)McN-5652 data; however, no evaluation of candidate methods has been published in detail yet. In this study, compartmental modeling using a one-tissue compartment model (K1, k2"), a two-tissue compartment model (K1 to k4), and a noncompartmental method that relies on a reference region devoid of specific binding sites were assessed. Because of its low density of serotonergic transporters, white matter was chosen as reference. Parameters related to transporter density were the total distribution volume DV" (= K1/k2", one tissue compartment), DVtot, (=K1/k1' (1 + k3/k4), two tissue compartments), and Rv (= k3'/k4, noncompartmental method). The DV", DVtot, and Rv values extended over a similar range and reflected the known pattern of serotonergic transporters. However, all parameters related to transporter density were markedly confounded by nonspecific binding. With regard to K1, the one-tissue compartment model yielded markedly lower values, which were, however, more stable. The minimal study duration needed to determine stable values for the distribution volume was approximately 60 minutes. The choice of the method to analyze [11C](+)McN-5652 data depends on the situation. Parametric maps of Rv are useful if no information on K1 is needed. If compartmental modeling is chosen, both the one- and the two-tissue compartment models have advantages. The one-tissue compartment model underestimates K1 but yields more robust values. The distribution volumes calculated with both models contain a similar amount of information. None of the parameters reflected serotonergic transporter density in a true quantitative manner, as all were confounded by nonspecific binding.

Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors.

Vigilance, anxiety, epileptic activity, and muscle tone can be modulated by drugs acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABAA) receptors. In vivo, BZ sites are potential targets for endogenous ligands regulating the corresponding central nervous system states. To assess the physiological relevance of BZ sites, mice were generated containing GABAA receptors devoid of BZ sites. Following targeted disruption of the gamma 2 subunit gene, 94% of the BZ sites were absent in brain of neonatal mice, while the number of GABA sites was only slightly reduced. Except for the gamma 2 subunit, the level of expression and the regional and cellular distribution of the major GABAA receptor subunits were unaltered. The single channel main conductance level and the Hill coefficient were reduced to values consistent with recombinant GABAA receptors composed of alpha and beta subunits. The GABA response was potentiated by pentobarbital but not by flunitrazepam. Diazepam was inactive behaviorally. Thus, the gamma 2 subunit is dispensable for the assembly of functional GABAA receptors but is required for normal channel conductance and the formation of BZ sites in vivo. BZ sites are not essential for embryonic development, as suggested by the normal body weight and histology of newborn mice. Postnatally, however, the reduced GABAA receptor function is associated with retarded growth, sensorimotor dysfunction, and drastically reduced life-span. The lack of postnatal GABAA receptor regulation by endogenous ligands of BZ sites might contribute to this phenotype.

Stoichiometry of a recombinant GABAA receptor deduced from mutation-induced rectification.

Ligand-gated ion channels generally display a heterooligomeric subunit structure. The present report describes an electrophysiological method that provides criteria indicating the subunit stoichiometry of a recombinant GABAA receptor composed of alpha 3, beta 2 and gamma 2 subunits. Our results exclude the stoichiometries 3 alpha 1 beta 1 gamma, 1 alpha 3 beta 1 gamma, 1 alpha 1 beta 3 gamma and suggest that the possible subunit stoichiometries for this receptor are 2 alpha 1 beta 2 gamma, 2 alpha 2 beta 1 gamma or 1 alpha 2 beta 2 gamma, of which the alpha subunit composition 2 alpha 1 beta 2 gamma may be favoured. The method is based on the quantification of the outward rectification of the GABA-evoked current induced by point mutation of charged amino acids located near the ion channel pore.

[Colostomy closure after Hartmann operation: functional results]. / Kolostomieverschluss nach Hartmannscher Operation: funktionelle Resultate.

The "Hartmann operation" for complication of acute diverticulitis or obstruction of the rectosigmoid is a safe procedure with few complications. However, it needs a second operation to reconstruct the continuity of the intestinal tract with more difficulties. The goal of our report is to show the 30-day morbidity and the late sequelae after colostomy closure with special concern to the late anorectal function. We analyzed 43 patients who underwent colostomy closure after Hartmann's procedure between 1985 and 1990. We controlled personally 35 patients after 32 months (range: 5-64 months) concerning their bowel habits, anal sphincter function (digital measure) and endoscopic anastomosis diameter. There were no deaths, but there was a 9% perioperative morbidity (1 anastomotic leak, 1 anastomotic bleeding and 2 wound infections). In the further course 2/35 patients were incontinent for gas and liquid stool. Further 3 patients lost water after coughing and had a poor sphincter rest tone. Our results demonstrates a low 30-day morbidity after reversal of Hartmann's procedure. It needs further investigation to show, if a damaged sphincter muscle or a lower rectum capacity could be responsible for these results.

[Final evaluation of the randomized multicenter study SAKK 40/81: adjuvant portal chemotherapy of curatively resected colorectal cancer]. / Endauswertung der randomisierten Multizenter-Studie SAKK 40/81: Adjuvante portale Chemotherapie beim kurativ resezierten kolorektalen Karzinom.

Between 1981 and 1987, 533 patients from 9 institutions have been entered in a randomized trial to assess the value of adjuvant portal infusion (5-Fluorouracil, Mitomycin C) compared to radical surgery alone. Analysis of 469 evaluable patients at a median follow-up of 5.8 years revealed 110 recurrences in the control and 94 recurrences in the infusion group. Estimated 5-year disease-free survival was 52% and 61% respectively (hazard ratio 1:0.75; 95% confidence interval 0.57-0.99; p = 0.046). Overall survival was 59% in the control and 69 in the infusion group (p = 0.048). Adjuvant portal infusion did not influence the occurrence of liver metastases but reduced the overall recurrence rate.

Randomized multicenter trial of adjuvant intraportal chemotherapy for colorectal cancer (SAKK 40/81). An interim report.

A prospective, randomized trial of adjuvant portal infusion of 5-fluorouracil in combination with mitomycin C was conducted on 469 patients with operable colorectal cancer. A single postoperative course of the cytotoxic agents was compared with radical surgery alone. The actuarial 5-year survival (median follow-up 48 months) was 70 +/- 3% in the chemotherapy group and 57 +/- 4% in the control group (p = 0.10). The respective figures for disease-free survival were 62 +/- 4% and 53 +/- 4% (p = 0.09). Among the 195 cases with strict adherence to the protocol for adjuvant chemotherapy there were 59 recurrences and 44 deaths in the follow-up period, whereas in the 274 with no or incomplete chemotherapy there were 120 recurrences and 99 deaths (p less than 0.05). Perioperative adjuvant chemotherapy via portal infusion proved to be feasible in a multicenter setting. Follow-up will be continued, in order to provide definitive information on survival according to randomization.