Comparison of sevoflurane and propofol in the maintenance of and recovery from anesthesia

OBJECTIVE: To compare the recovery of patients after anesthesia with sevoflurane or propofol during open urological surgery or lumbar column surgery of intermediate duration. PATIENTS AND METHODS: Thirty-six ASA I, II or II patients were enrolled prospectively and randomly assigned to two groups to receive either sevoflurane (n = 19) or proporol (n = 17). Anesthetic induction was accomplished with thiopental, fentanil and vecuronium. During anesthetic maintenance a mixture of 60% nitrous oxide in oxygen plus the drug under study was adjusted to keep blood pressure and/or heart rate within +/- 20% of baseline. After surgery we recorded time until eye opening, spontaneous breathing, extubation, orientation, and identification of parts of the body. Side effects were likewise recorded. In the postanesthetic recovery ward patient condition was assessed using the Aldrete scale, the Newman-Trieger test and a visual analog scale for postoperative pain. Consumption of analgesic during the first 24 h after surgery was monitored. RESULTS: No significant differences were found in demographic data; duration of anesthesia; anesthetic doses; or time until spontaneous breathing, extubation, orientation or identification of parts of the body. Only time until eye opening was shorter in the sevoflurane group than in the propofol group (6.9 +/- 3.3 vs 11.5 +/- 4.8 min; p < 0.05). No differences were recorded on scales reflecting intermediate-term recovery. Analgesic consumption and the incidence of side effects were similar in both groups. CONCLUSIONS: Sevoflurane and propofol are comparable for anesthetic maintenance in urological and neurological procedures of intermediate duration.     

Management of neurotrophic keratopathy

Neurotrophic keratopathy is a degenerative corneal disease caused by an impairment of corneal sensitivity. Lack of the sensory nerve's trophic effect is responsible for the impairment in corneal healing and for the changes on the ocular surface that lead to corneal epithelial deficit, ulcer, and perforation. The etiology and recent advances in understanding of the pathogenetic mechanisms of neurotrophic keratopathy are reviewed here. An accurate history and a clinical examination that covers the function of cranial nerves often identify the cause of the disease. Clinical features and guidelines for the differential diagnosis and treatment are presented. Specific medical and surgical treatments, selected on the basis of clinical staging of the disease, can often halt disease progression. Future developments in medical treatment, including the use of neuropeptide and growth factors, are discussed. The identification of corneal anesthesia associated with an epithelial defect allows appropriate treatment and prevention of progression to stromal lysis and perforation.     

Registration of cancer mortality data in a developing area: Chennai (Madras, India) experience

Objectives: This study was carried out to evolve a method to improve the registration of cancer mortality data in Chennai (Madras, India). Methods: Data on cancer deaths have been collected from the Vital Statistics Department (VSD) by a population-based cancer registry (PBCR) in Chennai only since 1982. The low mortality-to-incidence ratio during 1982-84 suggested under-registration of mortality data. Since 1985, the PBCR has taken special effort to ascertain the vital status of cancer cases by sending reply-paid postcards and/or making house visits. The data on all deaths occurring in Chennai, irrespective of stated cause of death in the death certificate, have been collected from the VSD since 1992. Results: Deaths that occurred in Chennai and obtained by sending reply-paid postcards and/or making house visits were registered in VSD as non-cancer causes of death; hence, these data were not collected from VSD. The sensitivity and positive predictive values of death certificates on cancer diagnosis based on 1992 and 1993 mortality data were 57 percent and 99.5 percent, respectively. Conclusion: Since the accuracy of death certificate information on cancer diagnosis is relatively low in a developing country such as in India, collecting data on all deaths will improve the mortality data registration in PBCRs.     

Induction of apoptosis using inhibitors of lysophosphatidic acid acyltransferase-beta and anti-CD20 monoclonal antibodies for treatment of human non-Hodgkin's lymphomas.

PURPOSE: Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is a transmembrane enzyme critical for the biosynthesis of phosphoglycerides whose product, phosphatidic acid, plays a key role in raf and AKT/mTor-mediated signal transduction. EXPERIMENTAL DESIGN: LPAAT-beta may be a novel target for anticancer therapy, and, thus, we examined the effects of a series of inhibitors of LPAAT-beta on multiple human non-Hodgkin's lymphoma cell lines in vitro and in vivo. RESULTS: We showed that five LPAAT-beta inhibitors at doses of 500 nmol/L routinely inhibited growth in a panel of human lymphoma cell lines in vitro by >90%, as measured by [3H]thymidine incorporation. Apoptotic effects of the LPAAT-beta inhibitors were evaluated either alone or in combination with the anti-CD20 antibody, Rituximab. The LPAAT-beta inhibitors induced caspase-mediated apoptosis at 50 to 100 nmol/L in up to 90% of non-Hodgkin's lymphoma cells. The combination of Rituximab and an LPAAT-beta inhibitor resulted in a 2-fold increase in apoptosis compared with either agent alone. To assess the combination of Rituximab and a LPAAT-beta inhibitor in vivo, groups of athymic mice bearing s.c. human Ramos lymphoma xenografts were treated with the LPAAT-beta inhibitor CT-32228 i.p. (75 mg/kg) daily for 5 d/wk x 4 weeks (total 20 doses), Rituximab i.p. (10 mg/kg) weekly x 4 weeks (4 doses total), or CT-32228 plus Rituximab combined. Treatment with either CT-32228 or Rituximab alone showed an approximate 50% xenograft growth delay; however, complete responses were only observed when the two agents were delivered together. CONCLUSIONS: These data suggest that Rituximab, combined with a LPAAT-beta inhibitor, may provide enhanced therapeutic effects through apoptotic mechanisms.     

Is there a definition of remission in late-life depression that predicts later relapse?

Remission of depressive symptoms is the goal of all antidepressant therapy. Rating scales define remission in clinical trials, but it is unclear how well these definitions predict risk of later relapse. We measured the sensitivity and specificity of a range of Montgomery-Asberg Depression Rating Scale (MADRS) cutoff scores at 3- and 6-months, wherein scores above a given cutoff would predict relapse over an 18-month period. We examined 153 elderly depressed subjects exhibiting a MADRS < or = 15 after 3 or 6 months of antidepressant therapy. Subjects who subsequently exhibited a MADRS > 15 during the 18-month study period were defined as relapsed. Receiver operating characteristic (ROC) curves were developed and area under the curve (AUC) values calculated for the sensitivity and specificity of 3- and 6-month MADRS scores to predict future relapse. The 3-month ROC had an AUC value of 0.63; the 6-month ROC had an AUC value of 0.66. There was no MADRS cutoff found that could predict likelihood of relapse with good sensitivity and specificity. A post hoc analysis where relapse rate was adjusted by controlling for medical comorbidity, disability, and social support showed no change in the ROCs or AUC values. The higher the MADRS score at 3 and 6 months, the greater the likelihood of relapse. With no clean MADRS cutoff score, the goal of antidepressant therapy should be the lowest possible degree of depressive symptomatology to minimize risk of later relapse. Definitions of remission that are better associated with longer-term outcomes are needed.     

Involvement of the Anterior Segment of the Eye in Patients with Mucopolysaccharidoses: A Review of Reported Cases and Updates on the Latest Diagnostic Instrumentation

Mucopolysaccharidoses (MPS) are a heterogeneous group of rare inherited disorders, characterized by the lack or malfunction of lysosomal enzymes necessary for glycosaminoglycan (GAGs) catabolism, and their subsequent accumulation in many tissues and organs throughout the body. An overview of the current knowledge of corneal and anterior segment manifestations in patients with MPS was provided and clinical guidelines for their diagnosis and management were furnished. The anterior segment of the eye is usually involved in every subtype of MPS, with major complications including varying degrees of corneal opacification and raised intraocular pressure (IOP) with development of glaucoma. Their recognition and management can be very useful in the diagnosis of MPS. Novel techniques are available to objectively measure the grade and extent of corneal clouding and give information about the anatomy of the anterior chamber and the structures of the angle beyond the clouded cornea. It is advisable to take advantage of this new instrumentation in order to obtain thorough information on the ocular involvement and its related anterior chamber complications for a better management of patients with MPS, both in terms of visual prognosis and therapeutic outcome.     

Clinical scale electroloading of mature dendritic cells with melanoma whole tumor cell lysate is superior to conventional lysate co-incubation in triggering robust in vitro expansion of functional antigen-specific CTL

Recent commercial approval of cancer vaccine, demonstrating statistically significant improvement in overall survival of prostate cancer patients has spurred renewed interest in active immunotherapies; specifically, strategies that lead to enhanced biological activity and robust efficacy for dendritic cell vaccines. A simple, widely used approach to generating multivalent cancer vaccines is to load tumor whole cell lysates into dendritic cells (DCs). Current DC vaccine manufacturing processes require co-incubation of tumor lysate antigens with immature DCs and their subsequent maturation. We compared electroloading of tumor cell lysates directly into mature DCs with the traditional method of lysate co-incubation with immature DCs. Electroloaded mature DCs were more potent in vitro, as judged by their ability to elicit significantly (p < 0.05) greater expansion of peptide antigen-specific CD8⁺ T cells, than either lysate-electroloaded immature DCs or lysate-co-incubated immature DCs, both of which must be subsequently matured. Expanded CD8⁺ T cells were functional as judged by their ability to produce IFN-γ upon antigen-specific re-stimulation. The electroloading technology used herein is an automated, scalable, functionally closed cGMP-compliant manufacturing technology supported by a Master File at CBER, FDA and represents an opportunity for translation of enhanced potency DC vaccines at clinical/commercial scale.