Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation

OBJECTIVES: Several previous studies have shown that malignant progression in Barrett's metaplasia (BM) occurs even in patients treated with fundoplication or acid suppression therapy (AST). The aim of this study was to test the hypothesis that AST may not alter malignant progression in BM if key genes involved in DNA repair and cell cycle control, particularly p53, are defective. METHODS: Initial and follow-up biopsies from 21 patients with BM treated with AST and observed for 1-13 yr were entered in the study. All biopsies were graded for dysplasia and evaluated for p53 protein accumulation and oxidative DNA damage by immunohiostochemistry, using antibodies to p53 and to 8-hydroxydeoxyguanosine, respectively. DNA ploidy was determined using image analysis. Statistical analysis was performed using Kaplan-Meier curves, log rank test, and multivariate regression. RESULTS: Patients with p53 positive initial biopsies were more likely to have progression in dysplasia grade (p = 0.022) and DNA ploidy status (p = 0.023) than those with p53 negative biopsies. In eight patients AST resulted in significant reduction in oxidative DNA damage in the five patients with p53-negative initial biopsies, but not the three with p53 positive ones (p = 0.0007). CONCLUSIONS: We conclude that failure of AST to alter malignant progression in BM may be due, at least in part, to defects in DNA repair and cell cycle control resulting from p53 gene mutation, present before AST treatment. Although AST may be effective in preventing further DNA damage, it is unlikely to alter progression in genetically unstable cells.     

Patient-controlled epidural analgesia after major urologic surgeries. A comparison of tramadol with or without bupivacaine

The efficiency and safety of patient-controlled epidural analgesia by using tramadol alone and combined with bupivacaine were investigated for postoperative pain treatment after major urological surgeries. For PCEA: in group I (n = 17) a loading dose of 20 mg tramadol with a continuous infusion of 1 mg/ml tramadol at a rate of 8 ml/h was given. In group II (n = 17), patients received an initial loading dose of 20 ml bupivacaine 0.125% and a supplemental continuous infusion of 8 ml/h. In group III (n = 17), a loading dose of 20 mg tramadol with 20 ml bupivacaine 0.125% were given and a supplemental infusion of 1 mg/ml tramadol in 20 ml bupivacaine 0.125% combination was begun with a rate of 8 ml/h. A demand epidural bolus dose of 5 ml with a lockout time of 30 min was also used in all patients. VAS for pain intensity, vital signs, sedation scale and side effects was monitored at 0, 15, 30 min and 1, 2, 3, 4, 8, 12, and 24 h of the postoperative period. Statistical significance was determined using Kruskal-Wallis, Fisher's exact, analysis of variance for repeated measurements and Tukey tests. The hemodynamic values and sedation scales were insignificantly different (p > 0.05). The adequate analgesia was provided in all patients. However VAS values were significantly lower in group III than in groups I and II at every measurement (p < 0.05). The incidence of side effects in all three groups was low (p > 0.05). In conclusion, we suggested that a combination of tramadol with bupivacaine can provide the most effective and safe postoperative analgesia with minimal risk for side effects.     

High ligation to treat pain in varicocele

Purpose: There are limited data about the effectiveness of surgery in patients withpainful varicocele. We report a retrospectivestudy done for the follow up on all varicocelehigh ligations performed for pain to evaluatethe effectiveness of the operations.Materials and methods: The patients who were all physically active workers and who underwent high inguinal ligation of varicocelefor pain from January 1995 to January 2000,were invited for interviews. Their charts werereviewed to document patient age, grade andlocation of varicocele, duration and quality ofpain, response to conservative treatment. Allpatients who could be contacted were interviewed for resolution of pain and complications, their physical examinations were made.Results: 87 of 140 (62.1%) patients wereavailable for the follow up. Median patient agewas 26 (15 to 34) years old. The varicocele wason the left side in 82 patients and bilateralin 5. The pain was dull in 42, throbbing in 25,sharp in 6 and as a pulling sensation in 14.The longest conservative therapy given in theliterature failed in all patients. Varicocelegrades were as follows: Grade I in 17, Grade IIin 34 and Grade III in 36 patients. Highinguinal ligation was used in all patients. 72(82.8%) patients reported complete resolution, 8 (9.2%) patients reported partial response, 7(8%) patients had persistant pain.Conclusions: High inguinal ligation iseffective in the treatment of painfulvaricocele in highly selected patients.Prospective randomized studies are neededcomparing surgical and conservativetreatments.     

The relation between tooth loss and bone mass in postmenopausal osteoporotic women in Turkey: a multicenter study

 The purpose of this study was to investigate the associations of tooth loss with skeletal bone mass, years since menopause, educational level, current smoking status, dietary calcium intake, and number of pregnancies in postmenopausal osteoporotic women in Turkey. The study population consisted of 1171 postmenopausal women aged 40–86 years (mean age, 61.19 ± 7.28 years). A detailed history was obtained from all women, including relevant lifestyle parameters, risk factors, and measurements of weight and height. Women were separated into three groups according to the number of teeth remaining as group 1 (edentulous, 457 women), group 2 (10 or fewer teeth, 232 women), and group 3 (more than 10 teeth remaining, 482 women). There was no significant difference among the three groups in mean age and menopausal age (P < 0.05). Body mass index of group 1 was significantly higher than that of group 2 (P < 0.01). Educational level was significantly different between three groups: groups 1 and 2 (P < 0.001), groups 1 and 3 (P < 0.0001), and groups 2 and 3 (P < 0.001). Educational level was lowest in group 1 and highest in group 3. Despite a low ratio of cigarette smoking in general, a smoking habit was most prevalent in group 3 and least in group 2. The ratio of women receiving adequate calcium was significantly lower in group 1 than in other groups (P < 0.001); mean calcium intake was similar in all groups. The number of pregnancies was significantly higher in group 1 than in other groups (P < 0.001). Lumbar bone mineral density (BMD) of group 1 was significantly lower than that of groups 2 and 3 (P < 0.001). Although no significant difference was found between groups 1 and 3, femoral neck BMD of group 2 was less than in others, and differences between groups 1 and 2 and between groups 2 and 3 (P < 0.001) were significant. Lumbar bone mineral content (BMC) of group 1 was significantly lower than that of groups 2 and 3 (P < 0.001), and lumbar BMC in group 2 was significantly higher than in group 3 (P < 0.05). Femoral neck BMC in group 1 was significantly higher than in groups 2 and 3 (P < 0.001). In conclusion, lumbar BMD and BMC in the edentulous group were significantly lower, whereas femoral neck BMD and BMC were significantly higher in edentulous group compared with the others. Our findings indicated that improvement in lifestyle factors and nutritional strategies for the treatment and prevention of osteoporosis may have additional benefit in reducing tooth loss. Received: February 18, 2002 / Accepted: June 21, 2002 Offprint requests to: A. Gur     

Direct Formation of Nanospheres from Amphiphilic β-Cyclodextrin Inclusion Complexes

Purpose. The aim of this work was to develop and characterize a highly loaded nanoparticulate system based on amphiphilic -cyclodextrins (CDs) to facilitate the parenteral administration of poorly soluble antifungal model drugs bifonazole and clotrimazole. Methods. Inclusion complexes were characterized with spectroscopic techniques. Particle size distribution of nanospheres were determined by photon correlation spectroscopy (PCS). Nanospheres were assessed for hemolytic activity. Entrapped and released drug quantities were determined and minimum inhibitory concentration (MIC) values of drugs, amphiphilic -CDs, and drug loaded nanospheres were evaluated. Results. 1:1 inclusion complexes of model drugs with amphiphilic -CDs gave nanospheres <300 nm (polydispersity index < 0.15) by nanoprecipitation technique without using surfactants. By direct preparation from preformed inclusion complexes, loading was increased 2- to 8-fold depending on CD type and loading technique. Conventionally loaded CD nanospheres displayed immediate release whereas preloaded and highly loaded nanospheres liberated model drugs over a period of 1 h reducing the initial burst effect. MIC values of bifonazole and clotrimazole were lowered significantly when associated to amphiphilic -CD nanospheres. Conclusion. Amphiphilic -CDs form nonsurfactant, highly loaded nanospheres with lower hemolytic activity than that of natural CDs directly from inclusion complexes. They enhanced solubility and subsequently therapeutic efficacy of the model drugs.     

Reliability of the disk damage likelihood scale

PURPOSE: To report the reliability of the glaucoma disk damage likelihood scale (DDLS) in comparison to the Armaly cup/disk ratio by determining the interobserver and intraobserver agreement for optic disk stereo photographs and the interobserver agreement for in vivo patient measurements of the optic disk. DESIGN: Observational case series. METHODS: Optic disk photographs: 48 stereo pairs of optic nerve photographs were selected from patients with a spectrum of glaucomatous visual field loss. Two masked observers graded the optic disk photographs three times according to the DDLS and Armaly cup/disk ratio. Interobserver and intraobserver agreements were calculated using the test-retest method. Patient measurements: three observers performed in vivo patient measurements on 34 eyes of glaucoma clinic patients and made a single determination of the DDLS stage and Armaly cup/disk ratio, based on the indirect biomicroscopic examination. Level of interobserver agreement was tabulated. RESULTS: Optic disk photographs: interobserver and intraobserver agreement for the vertical DDLS measurement was greater than for two determinations (clinical impression and measured) of the vertical Armaly cup/disk ratio (interobserver: 85% vs 68% and 74%, respectively; intraobserver grader 1: 97% vs 89% and 80%, grader 2: 99% vs 95% and 89%, respectively). In vivo patient measurements: the interobserver agreement for the DDLS and Armaly cup/disk ratio was similar (70.1% vs 67.6%, respectively). CONCLUSIONS: For the stereo optic disk photographs, the inter- and intra-observer agreement for the DDLS is greater than the Armaly cup/disk ratio. For the in vivo patient measurements, the level of agreement for the DDLS and the Armaly cup/disk ratio is similar.     

Comparison of antiallergic drugs in an experimental model of ocular anaphylaxis

PURPOSE: To compare the efficacy of antiallergic drugs in an experimental ocular anaphylaxis model. MATERIALS AND METHODS: Fifty-two rats were divided into 8 groups. Dithiothreitol and ovalbumin (OVA) were applied to both eyes of previously OVA-inoculated rats in groups 1-5 and 7. In groups 1-5, antiallergic efficacy of the drugs (lodoxamide, sodium cromoglycate, levacobastine, cimetidine, and diclofenac sodium) instilled on the right eyes were compared with the buffer instilled on the left eyes, measuring the amount of extravasated Evans blue (EB) dye by spectrophotometric analysis. Group 6 served as a control of EB dye extravasations in nonimmunized eyes. Histopathologic examinations for anaphylaxis and controls were done in groups 7 and 8. RESULTS: Only levacobastine and lodoxamide decreased vascular permeability at a significant ratio (46%, p < 0.01 and 31%, p < 0.05, respectively). CONCLUSION: Levacobastine and lodoxamide but none of the three other drugs mentioned above were found to be effective in decreasing vascular permeability.