Radiotherapy for age related macular degeneration causes transient lens transparency changes

AIM: Evaluation of potential side effects of photon radiotherapy on the transparency of the lens. METHODS: The anterior segments of 14 phakic eyes from patients suffering from subfoveal neovascularisation as a result of age related macular degeneration (AMD) were documented by Scheimpflug photography (Topcon SL-45, Kodak Tmax 400) before the start of radiotherapy as well as 6 and 12 months afterwards. All negatives were evaluated by microdensitometry, and peak heights for distinct layers of the lens were used for statistical comparison. External beam radiotherapy (6 MeV photons) consisted of a total dose of 20 Gy, delivered as 10 fractions of 2 Gy. RESULTS: Six and 12 months following irradiation statistical comparison of the ratios in density change of lenses from irradiated versus non-irradiated fellow eyes revealed statistically significant (p相似文献   

Systolic blood pressure, not BIS, is associated with movement during laryngoscopy and intubation

OBJECTIVE: To compare bispectral index (BIS) values to hemodynamic variations, in order to evaluate adequacy of anesthesia during orotracheal intubation with muscle relaxants. METHODS: Forty-one patients ASA I-II, scheduled for elective peripheral surgery under general anesthesia with tracheal intubation were enrolled in the study. Fentanyl/thiopental followed by vecuronium were used for induction. Onset of relaxation was monitored at the orbicularis occuli (OO) muscle using train-of-four stimulation. Intubation was performed when no response at the OO was detected visually. Intubating conditions were noted. The "isolated forearm" technique was used to detect movement during laryngoscopy/intubation. BIS values, pulse rate (PR), and systolic pressure were recorded before induction, during laryngoscopy/intubation and 60 sec after intubation. RESULTS: Although intubating conditions were clinically adequate for all patients, ten out of 41 had movement of the isolated arm during laryngoscopy/intubation. BIS values were not significantly different for these patients: 67 (55-83) compared to those who had no movement: 60 (35-80), P = 0.6. During laryngoscopy, PR increased for all patients while systolic pressure increased significantly only in patients who moved: 125 (100-136) mmHg vs those who did not: 108 (67-140), P < 0.05. CONCLUSION: Systolic pressure elevations were associated with inadequate anesthesia as evaluated by the "isolated forearm" technique, during laryngoscopy/intubation. BIS values were not different between groups, suggesting that systolic blood pressure may be a better predictor of inadequate anesthesia under the circumstances described.     

Gastric Bypass in Patients with BMI <40 but >32 Without Life-threatening Co-morbidities: Preliminary Report

Background: Surgical intervention is currently indicated for patients with BMI >40 or >35 with life-threatening comorbidities. Patients with BMI 32-40 without these comorbidities not only have the increased propensity to develop them but also suffer from similar psychosocioeconomic consequences. These patients may not respond to non-surgical treatment of obesity any better than those with BMI>40. The question has been raised whether to offer them surgical intervention. Methods: A study was carried out to determine outcome of surgery on patients with BMI >32 but <40 without life-threatening comorbidities but with either psychological, economic or social impairments affecting their quality of life. The approval of our Hospital Internal Review Board was obtained. In addition to routine evaluation for surgical intervention, these patients were required to have the approval of their primary care physician, be seen pre-operatively by a psychiatrist, and have a member of the family or a very close friend present at the time of discussion of operative risks and follow-up requirements. Patients committed to at least a 5-year follow-up. They were to be self-paying patients. The transected silastic ring vertical gastric bypass with a temporary gastrostomy was used. Results: 50 patients, 49 women and one man, were entered into the study between May 1, 1999 and April 30, 2000. 50% were self-pay, and the other 50% were able to obtain coverage through their insurance companies. There were few peri-operative complica tions and no deaths. The late complications include incisional hernias, dumping and transient alopecia. Hospital stay averaged 3.7 days. Follow-up has been 18-27 months. Weight loss has been excellent. Conclusion: Preliminary results of surgical intervention extended to patients with BMI 32-40 without life-threatening comorbidities but with psychosocioeconomic ramifications are very promising. Long term follow-up and comparison with other bariatric patients are planned.     

Evidence that intermittent,excessive sugar intake causes endogenous opioid dependence

OBJECTIVE: The goal was to determine whether withdrawal from sugar can cause signs of opioid dependence. Because palatable food stimulates neural systems that are implicated in drug addiction, it was hypothesized that intermittent, excessive sugar intake might create dependency, as indicated by withdrawal signs. RESEARCH METHODS AND PROCEDURES: Male rats were food-deprived for 12 hours daily, including 4 hours in the early dark, and then offered highly palatable 25% glucose in addition to chow for the next 12 hours. Withdrawal was induced by naloxone or food deprivation. Withdrawal signs were measured by observation, ultrasonic recordings, elevated plus maze tests, and in vivo microdialysis. RESULTS: Naloxone (20 mg/kg intraperitoneally) caused somatic signs, such as teeth chattering, forepaw tremor, and head shakes. Food deprivation for 24 hours caused spontaneous withdrawal signs, such as teeth chattering. Naloxone (3 mg/kg subcutaneously) caused reduced time on the exposed arm of an elevated plus maze, where again significant teeth chattering was recorded. The plus maze anxiety effect was replicated with four control groups for comparison. Accumbens microdialysis revealed that naloxone (10 and 20 mg/kg intraperitoneally) decreased extracellular dopamine (DA), while dose-dependently increasing acetylcholine (ACh). The naloxone-induced DA/ACh imbalance was replicated with 10% sucrose and 3 mg/kg naloxone subcutaneously. DISCUSSION: Repeated, excessive intake of sugar created a state in which an opioid antagonist caused behavioral and neurochemical signs of opioid withdrawal. The indices of anxiety and DA/ACh imbalance were qualitatively similar to withdrawal from morphine or nicotine, suggesting that the rats had become sugar-dependent.     

Anti-HIV agents derived from the ent-kaurane diterpenoid linearol

Twenty-six semisynthetic ent-kaurane derivatives of linearol (1) have been investigated for their anti-HIV effects. Five compounds (4, 7, 11, 25, and 26) showed significant activity against HIV replication in H9 lymphocyte cells with EC(50) values in the range <0.1-3.11 microg/mL. With TI values of 163 and 184, compounds 4 and 25 are especially promising for further development as potential anti-HIV agents.     

Hydrolytically activated etoposide prodrugs inhibit MDR-1 function and eradicate established MDR-1 multidrug-resistant T-cell leukemia

Effective therapy of high-risk leukemia with established cytotoxic drugs may be limited by poor antitumor efficacy, systemic toxicity, and the induction of drug resistance. Here, we provide the first evidence that hydrolytically activated prodrugs may overcome these problems. For this purpose, VP16 was functionally blocked by hydrolytically cleavable carbonate linkers with unique characteristics to generate 2 novel prodrugs of VP16. First, we established a more than 3-log higher efficacy of the 2 prodrugs compared with VP16 on a panel of naturally drug-resistant tumor cell lines. Second, the prodrugs did overcome VP16-induced multidrug resistance-1 gene (MDR-1)-mediated multidrug resistance in vitro in a newly established VP16-resistant T-cell leukemia cell line MOVP-3 by functionally blocking MDR-1-mediated efflux. Third, in vivo studies showed a maximum tolerated dose of ProVP16-II (> 45mg/kg), which was at least 3-fold higher than that of VP16 (15 mg/kg). Finally, tests of ProVP16-II in a multidrug-resistant xenograft model of T-cell leukemia expressing MDR-1 indicated that only the mice treated with this prodrug revealed a complete and long-lasting regression of established, drug-resistant leukemia. In summary, the hydrolytically activated etoposide prodrugs proved effective against multidrug-resistant T-cell leukemia in vitro and in vivo and provide proof of concept for a highly promising new strategy for the treatment of MDR-1 drug-resistant malignancies.     

Polymorphism of the codon 129 of the prion protein (PrP) gene and neuropathology of cerebral ageing

We studied whether codon 129 polymorphism of the PrP gene modulates the presence of tau- and Abeta-associated lesions among 188 patients over 70 years of age without evidence of dementia. Val allele carriers, either heterozygotes or homozygotes, were more frequently affected by Abeta-associated lesions than non Val allele carriers, whereas there were no differences for tau-positive neurones. Val allele carriers also had more focal and diffuse Abeta deposits. This association was most significant in the highest Braak's stages for neurofibrillary tangles (>/=III). In this group, cases with at least one Val allele had nearly twice as many Abeta-associated lesions. The most affected areas were the entorhinal cortex, TF-TH and the superior temporal cortex, where odds ratios for focal Abeta deposits ranged from 3.5 to 4.6.