The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases

A series of succinyl based mercaptoketones and diastereomeric mercaptoalcohols were prepared and evaluated in vitro as inhibitors of the matrix metalloproteinases collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).     

Effects of age, system experience, and navigation technique on driving with an advanced traveler information system

This paper explores the effects of age, system experience, and navigation technique on driving, navigation performance, and safety for drivers who used TravTek, an Advanced Traveler Information System. The first two studies investigated various route guidance configurations on the road in a specially equipped instrumented vehicle with an experimenter present. The third was a naturalistic quasi-experimental field study that collected data unobtrusively from more than 1200 TravTek rental car drivers with no in-vehicle experimenter. The results suggest that with increased experience, drivers become familiar with the system and develop strategies for substantially more efficient and safer use. The results also showed that drivers over age 65 had difficulty driving and navigating concurrently. They compensated by driving slowly and more cautiously. Despite this increased caution, older drivers made more safety-related errors than did younger drivers. The results also showed that older drivers benefited substantially from a well-designed ATIS driver interface.     

Virilizing ovarian tumor of low malignant potential associated with antecedent tamoxifen use for breast cancer

OBJECTIVE: To assess the value and the associated morbidity of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic endoprosthesis insertion in the treatment of patients with Klatskin tumors. DESIGN: Retrospective study. SETTING: A tertiary referral center. PATIENTS: Fifty-five consecutive patients with Klatskin tumors diagnosed through typical cholangiographic and computed tomographic findings. INTERVENTION: Standard ERCP with endoscopic stenting technique was employed. Once the diagnosis of Klatskin tumor was confirmed on cholangiogram, endoscopic stenting was performed to bypass the stricture. Multiple stents were inserted if necessary to ensure adequate biliary drainage. MAIN OUTCOME MEASURES: The success rate of ERCP and endoscopic endoprosthesis insertion, successful drainage rate, early complications of endoscopic procedure, procedure-related mortality, and long-term outcome of endoprosthesis. RESULTS: Of the 55 patients, cholangiography was performed in 53 (96%). In the 49 patients in whom endoscopic stenting was attempted, the procedure was successful in 28 patients (57%) at the first attempt and 8 patients (16%) at the second attempt, resulting in a cumulative success rate of 73%. Only 20 of these patients had satisfactory biliary drainage, resulting in an overall successful drainage rate of 41%. Early complications, including acute cholangitis, acute pancreatitis, and postpapillotomy bleeding occurred in 14 patients (25%). Three patients (5%) died of procedure-related complications. The median patency of the first endoprosthesis inserted was 1 week (range, 0-8 wk). The 30-day mortality rate was 18%. CONCLUSIONS: In patients with Klatskin tumors, ERCP and endoscopic endoprosthesis insertion have a low successful drainage rate, are associated with high morbidity and procedure-related mortality, and have a limited effect on long-term palliation. Endoscopic retrograde cholangiopancreatography and endoscopic endoprosthesis insertion have a limited value in the management of patients with Klatskin tumors.     

Recurrent spheno-orbital meningioma

A series of 15 patients who underwent neurosurgical procedures for recurrent spheno-orbital meningioma is reported. There were 11 women and four men, with a mean age of 46 years. The mean duration between the first and second operations was 46 months. Progressive proptosis without neurological deficit was the most common symptom. All tumors were large at the time of reoperation and involved the greater and lesser wings of the sphenoid bone and the orbit. Aggressive resection in all patients resulted in no deaths and only slight morbidity, with the exception of one patient who developed blindness 24 hours after surgery due to central retinal artery occlusion. Fourteen patients were improved cosmetically and one patient, treated early in the series, had persistent proptosis due to inadequate bone removal. No attempt was made to remove tumor within the cavernous sinus in patients who were neurologically normal. Although postoperative imaging demonstrated complete gross excision of tumor in nine patients, 10 underwent conventional radiation therapy for residual tumor visualized at the time of surgery in the dura of the superior orbital fissure, the cavernous sinus, or the basal optic canal. Although this study is inconclusive and requires further long-term documentation, no recurrences have been seen to date in the follow-up period, ranging from 16 to 95 months. The following important points are discussed: 1) the failure by experienced surgeons to radically excise bone, tumor, and involved dura at the first operation; 2) the importance of early aggressive therapy, depending upon the patient's age and medical condition; 3) the almost invariable intracranial dural involvement, which at times was seen only by gadolinium-enhanced magnetic resonance imaging and not visualized on computerized tomography; 4) an illustrated stepwise surgical technique for complete resection through a small craniotomy without the need for complicated reconstruction of the orbit or temporal fossa; 5) the role of radiation therapy when removal is incomplete or deemed hazardous because of cavernous sinus involvement; and 6) the excellent cosmetic results possible with minimal morbidity and no mortality.     

Tryptophan is present in glial cells and photoreceptors in the chicken retina

Tryptophan is a large neutral amino acid which is utilized in the biosynthesis of neuroactive substances such as serotonin and melatonin. However, it has been unclear where pools of tryptophan might be localized. Using a specific antiserum against tryptophan, we demonstrate that in the chicken retina tryptophan is present in radial glial cells and photoreceptors, but not in other neuronal elements. These data suggest that serotonergic neurones are probably dependent upon the transfer of tryptophan from the glial cells in order to manufacture serotonin and other tryptophan derivatives in the brain. If glia do supply tryptophan to neurones then this process will have significant practical implications for our basic understanding of and pharmacological manipulation of serotonergic systems.     

Skeletal muscle extra-aortic counterpulsation in dogs with dilated cardiomyopathy

Skeletal muscle extra-aortic counterpulsation was performed in seven dogs with dilated cardiomyopathy. A left latissimus dorsi dynamic descending thoracic aortomyoplasty was used as the autologous counterpulsator. Pulse train stimulation in diastole was used to initiate contraction and fibre type transformation. Two of the dogs died within 48 hours of surgery. The device was successfully activated in the five remaining dogs, but in one individual it failed within 48 hours of activation. Serial echocardiographic examinations of dogs in which the device functioned successfully (n = 4) showed trends towards the decrease in the left ventricular systolic internal dimension, left ventricular diastolic internal dimension, E-point to septal separation and left atrial diameter in systole seven to 14 days following the procedure, although these changes failed to persist in the long-term. The results suggest that skeletal muscle for cardiac assistances such as extra-aortic muscle counterpulsation, might be a therapeutic option for dogs with cardiac failure due to dilated cardiomyopathy.