Respiratory changes during initial days of acclimatization to increasing altitudes

We report a case of hearing preservation after removal of the semicircular canals and discuss the possible explanations for the mechanisms of preservation of hearing after removal of the labyrinth. We hope to promote the perspectives and possibilities of functional surgery of the inner ear and for tumors of the cerebellopontine angle.     

Introducing Critical Appraisal to studies of animal models investigating novel therapies in sepsis

OBJECTIVES: To discuss theoretical and practical aspects relating to the design of animal studies investigating the efficacy of novel therapeutic agents for the treatment of sepsis, and to make explicit the process whereby these studies can be evaluated for the purpose of designing clinical trials in humans. DATA SOURCES: Relevant articles from the pertinent literature were reviewed. STUDY SELECTION: Studies relevant to an evidence-based assessment of clinical studies on therapeutic efficacy, and studies relevant to the design of animal models of sepsis were selected. DATA EXTRACTION: Concepts relevant to an evidence-based assessment of the animal literature were extracted. DATA SYNTHESIS: Articles were reviewed and an evidence-based framework for the assessment of animal studies was developed. In this process, we discuss the steps that are necessary to assess the internal validity of an individual study and review topics relevant to the application of animal data to the design of clinical trials. CONCLUSIONS: The success of clinical trials of sepsis therapies is predicated on the generation and interpretation of sound preclinical data. In this review, we have attempted to outline an evidence-based approach to the assessment of preclinical animal studies evaluating novel therapeutic interventions in sepsis.     

Patient maintained alfentanil target-controlled infusion for analgesia during extracorporeal shock wave lithotripsy

PURPOSE: The purpose of this study was to determine whether alfentanil given by a pharmacokinetic-based target controlled infusion (TCI) system under patient control is a suitable analgesic technique for extracorporeal shock wave lithotripsy (ESWL). METHODS: The design was an open, unblinded, noncomparative, prospective study. Forty outpatients undergoing ESWL were given patient maintained alfentanil TCI. Pain, nausea and sedation were assessed every 300 shocks. Vital signs were recorded every three minutes, pulse oximetry and electrocardiography being monitored continuously. Blood alfentanil concentration was measured for comparison with the predicted value. RESULTS: Alfentanil consumption (median 1.34 mg, range 0.8-3.6) and measured levels following treatment (median 60 ng.ml-1, range 15.6-134.3) varied widely. The precision of the TCI system and the median prediction error (bias) were both 49%. The median of pain scores recorded during treatment was 4 (range 0-8). The median respiration rate was 15 bpm (range 10-23), three patients required oxygen (SaO2 < 92%) cardiovascular measurements were stable and there was no excessive sedation. The incidence of nausea was 15%. All patients were ready for hospital discharge within one hour following treatment. CONCLUSIONS: Patient maintained alfentanil TCI provides good analgesia for ESWL in the majority of patients with little sedation. Respiratory depression is uncommon but supplementary oxygen should be given prophylactically. There is considerable interindividual variation in demand for alfentanil indicating the usefulness of the patient control method. The TCI system underestimated alfentanil blood concentrations but this did not affect its clinical usefulness.     

Bilateral central acetabular fracture dislocations secondary to sustained myoclonus

This case report presents a patient with bilateral central acetabular fracture dislocations secondary to sustained myoclonus treated with delayed bilateral total hip arthroplasty. This is an unusual mechanism of injury, but is similar to other uncontrolled muscular contractions, such as electroconvulsive therapy and seizures. Because of ongoing myoclonus, the patient initially was treated nonoperatively. The patient then successfully had staged bilateral total hip arthroplasty 15 months after injury. This case exemplifies that forceful, uncontrolled muscular contraction can cause bilateral symmetric fracture dislocations. In patients with a history of seizure or myoclonic contracture with subsequent pain or loss of function, radiographs are indicated and skeletal fracture or joint dislocation must be ruled out. Secondary reconstruction can be recommended when the patient is medically stable.     

Primary leiomyosarcoma of the greater omentum: case report and review of the literature

Omental leiomyosarcomas are rare intra-abdominal tumors. This report describes a case of primary leiomyosarcoma of the greater omentum discovered on abdominal CT scan. The mass was removed via laparotomy and an omentectomy performed. At 2 years postoperatively there is no sign of tumor recurrence or metastasis.     

Imaging of the ureters on intravenous urography: does a valsalva help?

A prospective trial, comparing filling of the ureters on routine urography with ureteric filling following a valsalva manoeuvre, was performed. A significantly greater length of ureter was filled by the study patients than controls, allowing this frequently poorly imaged structure to be visualized more consistently.     

Safety and accuracy of transarticular screw fixation C1-C2 using an aiming device. An anatomic study

STUDY DESIGN: In this anatomic study, the safety and accuracy of C1-C2 transarticular screw placement was tested in a normal anatomic situation in cadaver specimens using a specially designed aiming device. OBJECTIVES: To assess the safety and accuracy of transarticular screw placement using the technique described by Magerl and a specially designed aiming device. SUMMARY OF BACKGROUND DATA: Transarticular C1-C2 screw fixation has been shown to be biomechanically superior to posterior C1-C2 wiring techniques. Several clinical series have been reported in the literature. However, no previous study assessing the accuracy or safety of this technique has been published. Structures at risk are the vertebral arteries, spinal canal, and the occiput-C1 joint. METHODS: Five frozen human cadaveric specimens were thawed and instrumented with 10 C1-C2 transarticular screws, according to the technique described by Magerl but using a specially designed aiming device described by the senior author (Jeanneret). After screw placement, the accuracy of screw positioning and the distance of the screws from the spinal canal, vertebral arteries, and atlanto-occipital joint were determined by anatomic dissection and radiographic analysis. RESULTS: The structure at greatest risk was the atlanto-occipital joint, with one screw found to be damaging the joint. Vertebral artery or spinal canal penetration was not observed in any of the specimens. Screw length averaged 45 mm and, with proper length, the screw tip was found to be located approximately 7.5 mm behind the anterior tubercle of C1 on lateral radiographs. CONCLUSIONS: This anatomic study demonstrates that C1-C2 transarticular screw fixation can be performed safely in a normal anatomic situation by surgeons who are familiar with the pertinent anatomy. The aiming device allowed safe instrumentation in all patients. In case of an irregular anatomic situation (e.g., congenital abnormalities or trauma), computed tomographic scan with sagittal reconstruction is recommended-in particular, to obtain information about the course of the vertebral artery.     

Striking changes in anxiety in Huntington's disease transgenic mice

Huntington's disease transgenic mice were tested in the elevated plus-maze test of anxiety at 6, 8, 10 and 12 weeks of age. At all ages, they showed significant and striking increases in the percentages of open arm entries and time spent on the open arms, compared with their normal littermates, indicating reduced anxiety. These increases were not secondary to a non-specific stimulant effect, since the transgenic mice made fewer closed arm entries, significantly so from 10 weeks of age. The mice were also tested in the holeboard, which provides measures of locomotor activity and directed exploration. From 8 weeks of age, the Huntington's mice were significantly less active than their normal littermates and made fewer exploratory head-dips. The increased open arm activity in the elevated plus-maze cannot therefore be secondary to increased exploration in the transgenic mice. In order to determine whether the reduced anxiety was due to differences in benzodiazepine receptor function, the mice were challenged with the benzodiazepine receptor antagonist, flumazenil. The results indicated that some of the reduced anxiety could be attributed to the presence of an endogenous anxiolytic ligand.     

Synthesis, antimalarial activity, and molecular modeling of tebuquine analogues

Tebuquine (5) is a 4-aminoquinoline that is significantly more active than amodiaquine (2) and chloroquine (1) both in vitro and in vivo. We have developed a novel more efficient synthetic route to tebuquine analogues which involves the use of a palladium-catalyzed Suzuki reaction to introduce the 4-chlorophenyl moiety into the 4-hydroxyaniline side chain. Using similar methodology, novel synthetic routes to fluorinated (7a, b) and a dehydroxylated (7c) analogue of tebuquine have also been developed. The novel analogues were subjected to testing against the chloroquine sensitive HB3 strain and the chloroquine resistant K1 strain of Plasmodium falciparum. Tebuquine was the most active compound tested against both strains of Plasmodia. Replacement of the 4-hydroxy function with either fluorine or hydrogen led to a decrease in antimalarial activity. Molecular modeling of the tebuquine analogues alongside amodiaquine and chloroquine reveals that the inter-nitrogen separation in this class of drugs ranges between 9.36 and 9.86 A in their isolated diprotonated form and between 7.52 and 10.21 A in the heme-drug complex. Further modeling studies on the interaction of 4-aminoquinolines with the proposed cellular receptor heme revealed favorable interaction energies for chloroquine, amodiaquine, and tebuquine analogues. Tebuquine, the most potent antimalarial in the series, had the most favorable interaction energy calculated in both the in vacuo and solvent-based simulation studies. Although fluorotebuquine (7a) had a similar interaction energy to tebuquine, this compound had significantly reduced potency when compared with (5). This disparity is possibly the result of the reduced cellular accumulation (CAR) of fluorotebuquine when compared with tebuquine within the parasite. Measurement of the cellular accumulation of the tebuquine analogues and seven related 4-aminoquinolines shows a significant relationship (r = 0.98) between the CAR of 4-aminoquinoline drugs and the reciprocal of drugs IC50.