Effect of organism environment upon bacteriostatic and mechanical properties of palacos R cement with antibiotic--second part]

The results of bacteriological tests of Palacos R cement with antibiotic 4 days, 7 days, 2 weeks, 3 weeks and 4 weeks after implantation in rabbit organism have been presented in this work. The results of tests of mechanical characteristics of cement with and without antibiotic samples after being kept in physiological saline for 3 to 6 weeks have also been discussed. Bacteriological tests prove that antibiotic (III generation cephalosporin) added to surgical cement retain its bacteriostatic properties. When tested on rabbits cement plus antibiotic retains its bacteriostatic properties after 4 weeks period. It has state, that by reason of prolonged time of activity antibiotic into surgical cement, it is necessary to investigate the mechanical characteristics of cement conditioned in physiological saline for 3 months at least.     

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study

BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.     

Efficacy and Toxicity of NN′N″N‴-tetra(2,3,4-trihydroxybenzoyl)-spermine for Decorporation of 239Pu from Mice

Summary

Male SAS/4 mice were injected i.v. with 6·6 kBq ²³⁹Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 μmol kg^?1 or repeated (three or four) daily injections of 30 μmol kg^?1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DPTA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 μmol kg^?1 or at 2–13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 μmol kg^?1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 μmol kg^?1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.     

Bromodeoxyuridine Labeling Index as an Indicator of Early Tumor Response to Preoperative Radiotherapy in Patients with Rectal Cancer

Purpose Assessment of tumor proliferation rate using Bromodeoxyuridine labeling index (BrdUrdLI) as a possible predictor of rectal cancer response to preoperative radiotherapy (RT). Methods and material Ninety-two patients were qualified either to short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I), or to short RT and 4–5 weeks interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. The samples were incubated with BrdUrd for 1 h at 37°C, and the BrdUrdLI was calculated as a percentage of BrdUrd-labeled cells. Results Thirty-eight patients were treated according to schedule I and 54 patients according to schedule II. Mean BrdUrdLI before RT was 8.5% and its value did not differ between the patients in the two compared groups. After RT tumors showed statistically significant growth inhibition (reduction of BrdUrdLI). As the pretreatment BrdUrd LI was not predictive for early clinical and pathologic tumor response, prognostic role of the ratio of BrdUrdLI after to BrdUrdLI before RT was considered. The ratios were calculated separately for fast (BrdUrd LI > 8.5%) and slowly (BrdUrd LI ≤ 8.5%) proliferating tumors and correlated with overall treatment time (OTT, i.e., time from the first day of RT to surgery). One month after RT, accelerated proliferation was observed only in slowly proliferating tumors. Conclusions Pretreatment BrdUrdLI was not predictive for early clinical and pathologic tumor response. The ratio after/before RT BrdUrdLI was correlated to inhibition of proliferation in responsive tumors. The paper was presented at ECCO 13, October 30 to November 03, 2005 in Paris, France     

Survival Analysis and Clinicopathological Factors Associated With False-Negative Sentinel Lymph Node Biopsy Findings in Patients with Cutaneous Melanoma

Background We analyzed the outcomes and factors associated with false-negative (FN) results of sentinel lymph node (SLN) biopsy findings in patients with cutaneous melanoma. SLN biopsy failure rate was defined as nodal recurrence in the biopsied regional basin without previous local or in-transit recurrence.Methods Between April 1997 and December 2004, a total of 1207 patients with cutaneous melanoma with a median Breslow thickness of 2.4 mm underwent SLN biopsy by preoperative and intraoperative lymphoscintigraphy combined with dye injection. In 228 cases, we found positive SLNs; of these, 220 underwent completion lymph node dissection (CLND). Median follow-up was 3 years.Results The SLN biopsy failure rate was 5.8% (57 of 979 SLN negative). Median time to occurrence of FN relapse after SLN biopsy was 16 months (range, 3–74 months). The FN SLN biopsy results correlated with primary tumor thickness >4 mm (P = .0012), primary tumor ulceration (P = .0002), primary tumor level of invasion Clark stage IV/V (P = .0005), and nodular melanoma histological type (P = .0375). Five-year overall survival, calculated from the date of primary tumor excision, in the FN group was 53.7%, which was not statistically significantly worse than the CLND group (56.8%; P = .9). The FN group was characterized by a higher ratio of two or more metastatic nodes and extracapsular involvement of lymph nodes after LND compared with the CLND group (P < .0001 and P < .0001, respectively). Additional detailed pathological review of FN SLN revealed metastatic disease in 14 patients, which decreased the SLN biopsy failure rate to 4.4% (43 of 979).Conclusions Survival of patients with FN results of SLN biopsy does not differ statistically significantly from that of patients undergoing CLND, although it is slightly lower. The SLN biopsy failure rate is approximately 5.0% in long-term follow-up and is associated mainly with the same factors that indicate a poor prognosis in primary melanoma.Preliminary results of this study were presented as an oral presentation during the Melanoma Session on the 59th Annual Cancer Symposium of the Society of Surgical Oncology, San Diego, CA, March 23–25, 2006.     

Elevated concentrations of kynurenic acid, a tryptophan derivative, in dense nuclear cataracts

PURPOSE: Kynurenines and their glycoside derivatives in the ocular lens absorb ultraviolet radiation and thus possibly help protect the retina from ultraviolet light. The current study analysed kynurenine aminotransferase I (KAT I) activity and kynurenic acid (KYNA) concentrations in human senile cataractous lenses and in experimentally induced cataracts in diabetic rats treated with streptozotocin (STZ). METHODS: KYNA levels and KAT I activity were investigated with HPLC and detected fluorimetrically in the nuclei of 91 human cataractous lenses collected during planned extracapsular extraction. The lenses were classified on the Lens Opacity Classification System III scale and compared with clear lenses regarding KYNA concentrations. Cataractous lenses from STZ-treated rats were compared with control lenses. RESULTS: KYNA concentration was 0.95 +/- 0.22 in human NC0 (nuclear color) control lenses, 0.8 +/- 0.72 in NC1, 1.18 +/- 0.88 in NC2, 1.31 +/- 0.70 in NC3, 1.78 +/- 0.92 in NC4, 8.80 +/- 8.28 (p < 0.05 vs. NC0) in NC5, and 14.0 +/- 11.1 (p < 0.05 vs. NC0) in NC6. A correlation was found between KYNA concentrations and the grade of cataract (r = 0.047, p < 0.001). KAT I activity in human cataracts was 0.44 +/- 0.16 pmol/mg protein- 1 hr- 1. Elevated KYNA concentrations in rat cataractous lenses were also observed (p < 0.05). CONCLUSIONS: KYNA levels are elevated in senile nuclear human cataracts and in cataractous lenses of rats with experimentally induced diabetes.     

Visual function and complications after cataract surgery with bilateral multifocal intraocular lens implantation

PURPOSE: To evaluate the visual function and complications after cataract surgery with bilateral Array SA 40N multifocal intraocular lens (IOL) implantation. MATERIAL AND METHODS: This prospective study comprised 40 eyes of selected 20 patients undergoing cataract surgery with bilateral implantation of Array SA 40N (AMO). multifocal IOL. Three months after bilateral surgery distance and near visual acuity, contrast sensitivity, complications and adverse effects were evaluated. Patients' satisfaction was assessed using a subjective TyPE Questionnaire. RESULTS: Thirty-five eyes (35/40 - 87.5%) achieved the uncorrected distance visual acuity 20/40 and the uncorrected near visual acuity of J5 or better. Eighty-two and a half percent of the operated eyes achieved UCDVA 20/20 and J4 or better. Contrast sensitivity for distance and near measured binocularly were within normal limits, although for higher spatial frequency, contrast sensitivity values for near were slightly above the lower limit of normal range. Intraoperative and postoperative complications were few and only in one eye, further surgical intervention was necessary (IOL recentration). Three patients (3/20 - 15%) reported moderate glare and halo. Overall visual satisfaction measured with TyPE Questionnaire was very high (8.7/10). CONCLUSIONS: Bilateral multifocal IOL implantation was effective and safe in selected cataract patients, providing very good uncorrected distance and near visual acuity. Slightly reduced contrast sensitivity and increased perception of glare/halo were an acceptable compromise for near, as well as distance vision improvement.     

VPS35 and DNAJC13 disease-causing variants in essential tremor

Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog (VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring disease-causing variants for Parkinson disease (PD). Owing to the suggested clinical, pathological and genetic overlap between PD and essential tremor (ET) we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N)) (rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients of European descent, and microsatellite markers were used to define the disease haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients. Both patients appear to share the disease haplotype previously reported. ET patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed. Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G (p.(N855S)) represents the first disease-causing variant identified in both, and suggests the regulation of clathrin dynamics and endosomal trafficking in the pathophysiology of a subset of ET patients.     

The effects of perinatal hypoxia on the behavioral,neurochemical, and neurohistological toxicity of the metabolic inhibitor 3-nitropropionic acid

3-nitropropionic acid (3-NPA) neurotoxicity and long-term effects of perinatal hypoxia were evaluated in 18 adult rats. Hypoxia-insulted (I) and noninsulted (NI) rats were delivered by cesarean section. Hypoxic insult was effected by submerging dissected uterine horns in warmed saline for 15 min. NI rats were delivered from the adjacent nonsubmerged horns. At postnatal day 90, I and NI rats were trained to perform tasks thought to measure behaviors dependent upon aspects of time estimation (TE), motivation, and learning. At 12 months of age, rats were injected i.p. with escalating doses of 3-NPA (5 mg/kg/day to a maximum of 30 mg/kg/day) immediately after each test session and sacrificed at the end of treatment. Additional male rats were used as untreated controls. Although 3-NPA produced a dose-dependent impairment of performance in each task, the effects were qualitatively similar for each group. A significant difference between I and NI rats was, however, observed in the TE task where NI rats completed less of the task at high doses of 3-NPA compared to I rats. Compared to untreated controls, dopamine concentrations were decreased in caudate nucleus of both I and NI rats after 3-NPA. Specific areas most frequently damaged included cerebral cortex, hippocampal subfield CA1, thalamus, caudate nucleus, and the cerebellum. Lesions usually were less extensive in the I rather than NI members of a littermate pair, suggesting a possible protective effect of perinatal hypoxia against subsequent 3-NPA neurotoxicity.