CEP Group Research Articles

The Role of Insulin Resistance in the Development of Complications after Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease.

Patients with coronary artery disease who underwent CABG (n = 383) were examined to determine glycemic status, free fatty acid and fasting insulin levels, and insulin resistance indices (Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), McAuley index, Quantitative Insulin Sensitivity Check Index (QUICKI), Revised-QUICKI). Patients were assessed for the development of perioperative complications and their length of stay in the hospital. Two groups were formed: group 1, patients with a combined endpoint (CEP, any complication and/or duration of hospital stay >10 days), n = 291; and group 2 (n = 92) without a CEP. Perioperative characteristics were analyzed, and predictors of hospital complications and prolonged hospital stay were evaluated. Patients in the CEP group were older, and there were more women among them (p = 0.003). Additionally, in this group, there were more patients with diabetes mellitus (37.5% vs 17.4%, p < 0.001), obesity (p < 0.001), and a higher percentage of combined operations (p = 0.007). In the group with a CEP, the levels of glucose (p = 0.031), glycated hemoglobin (p = 0.009), and free fatty acids (p = 0.007) and the Revised-QUICKI (p = 0.020) were higher than in the group without complications. In a regression analysis, the independent predictors of complications were combined operations (p = 0.016) and the predictors of a long hospital stay (>14 days) were female gender, the left atrium size, and diabetes mellitus (p < 0.001). The predictors of a composite endpoint included female gender, age, the left atrium size, and free fatty acid levels (p < 0.001). In the group with in-hospital complications after CABG, not only was the presence of diabetes mellitus more often detected, but there were also higher levels of free fatty acids and a higher Revised-QUICKI. Therefore, additional assessments of insulin resistance and free fatty acid levels are advisable in patients before CABG.

Safety and efficacy of cerebral embolic protection devices for patients undergoing transcatheter aortic valve replacement: An updated meta‐analysis

AbstractBackground and AimsCerebral embolic protection (CEP) devices are employed to capture embolic debris and reduce the risk of stroke during transcatheter aortic valve replacement (TAVR). Evidence is mixed regarding the safety and efficacy of CEP. We aimed to summarize the safety and effectiveness of CEP use during TAVR.MethodsElectronic databases, including PubMed, PubMed Central, Scopus, Cochrane Library, and Embase, were searched using relevant search terms for articles relating to CEP. All relevant data from 20 studies were extracted into a standardized form. Statistical analyses were performed using Revman 5.4. Odds ratio (OR) or mean differences (MDs) were used to estimate the desired outcome with a 95% confidence interval (CI).ResultsTwenty studies (eight randomized controlled trials [RCTs]) involving 210,871 patients (19,261 in the CEP group and 191,610 in TAVR without the CEP group) were included. The use of CEP was associated with a lower odds of 30‐day mortality by 39% (OR: 0.61, 95% CI: 0.53–0.70) and stroke by 31% (OR: 0.69, 95% CI: 0.52–0.92). Comparing devices, benefit in terms of mortality and stroke was observed with the use of the Sentinel device (Boston Scientific), but not among other devices. No differences were observed in the outcomes of acute kidney injury, major or life‐threatening bleeding events, or major vascular complications between groups. When only RCTs were included, there were no observed differences in the primary or secondary outcomes for CEP versus no CEP use during TAVR.ConclusionsThe totality of evidence suggests a net benefit for the use of CEP, weighted by studies in which the Sentinal device was used. However, given the RCT subanalysis, additional evidence is needed to identify patients at the highest risk of stroke for optimal decision‐making.

Cepharanthine Inhibits Doxorubicin-Induced Cellular Senescence by Activating Autophagy via the mTOR Signaling Pathway.

Doxorubicin (Dox) is a clinical first-line broad-spectrum anticancer agent. A dose-dependent cardiotoxic and myelosuppressive response limits the clinical use of Dox. Recent research indicates that Dox-induced cardiotoxicity is associated with senescent cell accumulation and that antiaging therapy can alleviate aging-related disorders. Cepharanthine (Cep) is commonly used to treat various acute and chronic illnesses, including leukopenia, snakebites, dry mouth, and hair loss. Whether Cep alleviates Dox-induced senescence is unknown. The expression of genes and proteins associated with aging was examined using NIH3T3 cell lines. The experiments were divided into a control group, a Dox group, and a Cep group on different days. NIH3T3 senescent cells were detected by senescence-β-galactosidase (SA-β-Gal) staining, and Western blotting was used to detect the protein levels of p16, p53, AMP-activated protein kinase (AMPK), mammalian target of the rapamycin (mTOR), p62, and Light Chain 3 (LC3). Fluorescence was used to detect the expression of monomeric red fluorescence protein-green fluorescence protein-Light Chain 3 (mRFP-GFP-LC3) and LC3 puncta in NIH3T3 cells. Real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) was used to test the expression of senescence-associated secretory phenotypes (SASP: Interleukin 6 (IL-6), Interleukin 1 beta (IL-1β), and Interleukin 8 (IL-8)). Cell Counting Kit-8 (CCK-8) was used to assess NIH3T3 cell viability. Here, we reported that Cep reversed the Dox-induced increase in the proportion of SA-β-Gal-positive cells and the high expression of aging-related proteins (p53, p < 0.05; p16, p < 0.05) and aging-related genes (IL-6, p < 0.05; IL-1β, p < 0.05; IL-8, p < 0.05) on the 3rd day. Mechanistically, Cep reduced the increase in the levels of phospho-mTOR (p < 0.05) on Days 1 and 3 and p62 protein (p < 0.05) caused by Dox on Day 1 and reversed the decline in LC3II/LC3I levels (p < 0.05) caused by Dox on Day 3, which is associated with the regulation of senescence. Additionally, the viability of NIH3T3 cells was significantly increased in the concentration range of 0.5-5 μM Cep (p < 0.05). We first found that Cep could suppress SA-β-Gal activity (p < 0.05) and the development of SASP. Additionally, in Cep-treated cells, Cep could restore autophagy dysfunction and suppress the mTOR signaling pathway. This research provides a new view on the mechanics of aging and autophagy and aids in developing novel antiaging drugs.

Skeletal muscle status, autonomic balance and short-term results of cardiac surgery

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Research Institute for Complex Issues of Cardiovascular Diseases The aim - investigate the association of the lower extremities skeletal muscle state, status autonomic nervous system (ANS) and short-term results of the cardiac operations. Design Study included 64 patients, who underwent planned cardiac surgery. All subjects before surgery performed a routine laboratory and instrumental examinations, six-minute walk test (6MWT), and static-dynamic tests on the training device. ANS was carried out, using ORTOexpert software. Were formed 2 groups – with the combined endpoint CEP (n = 9) and without CEP (n = 55). CEP included: perioperative development stroke, myocardial infarction, persistent arrhythmias and heart block, multiple organ dysfunction syndrome, death. Results Not found difference between the groups in gender, age, in main clinical data and laboratory tests indicators, and in endurance of the skeletal muscles or the 6MWT. In the CEP group, strength of skeletal muscles of the upper and lower extremities was lower, initially more pronounced sympathetic activation and larger values of the power of the frequency spectrum (TF). Stress index (IS) was lower in the CEP group, but after transitioning orthostatic position it surpassed the number without CEP. One-factor logistic regression analysis established factors associated with the development of CEP - poor muscle status, peripheral atherosclerosis; high EuroSCORE, cardiopulmonary bypass duration (CBD) and ANS disbalance. Multivariate regression analysis to establish the relationship of poor skeletal muscle status, pronounced sympathicotonia and a high incidence of postoperative complications. Logistic regression analisys Odds ratio [ -95%; +95%CL] p One-factor logistic regression Stenosis ICA ≥ 30% 9,545 [1,030; 88,467] ,043 Shoulder Girdle Muscle Strength (Kg) 0,893 [0,786; 1,001] ,048 Knee extensors strength (kg) 1,012 [0,997; 1,029] ,098 Amo (basic) 0,958 [0,920; 0,998] ,037 IS (basic) 0,996 [0,990; 1,000] ,096 EuroSCORE (points) 1,643 [1,003; 2,694] ,043 CBD (min) 1,010 [1,001; 1,022] ,068 Multiple-factor logistic regression p=,001 LF/HF 1,175 [0,972; 1,420] ,088 Amo (basic) 0,950 [0,905; 0,997] ,034 Shoulder Girdle Muscle Strength (Kg) 0,863 [0,750; 0,993] ,036 LF/HF-ratio Low frecuency/High frecuency Amo-mode amplitude

Comparison of shear bond strength and enamel surface changing between the two-step etching and primer and self-etch primer methods in rebonding of orthodontic brackets: An in vitro study

The aim of this study was to compare shear bond strength (SBS) and enamel surface changing of two methods of bonding in rebonding of orthodontic brackets. In this in vitro study, 30 human premolars were randomly classified into three equal groups. Two bonding systems were applied. At first bonding, Group 1 and 2 were bonded by conventional etching and primer technique (CEP) and Group 3 by self-etching primer (SEP). Thermocycling for 5000 cycles was done. Then, 30 brackets were debonded and SBS and Adhesive remnant index (ARI) were evaluated. One sample was selected from each group, for SEM, 30 new brackets were used for rebonding. Group 1 was bonded by CEP method and Group 2 and 3 were bonded by SEP method. Thermocycling, SBS, ARI, and scanning electron microscope (SEM) were done in the same protocol of the first bonding. One-way ANOVA, two-sample t-test, and Mann-Whitney U-test were used for statistical analysis. P < 0.05 was considered statistically significant. The mean SBS values were not significantly different between the three groups in the first bonding and rebonding stages (P = 0.22 and 0.24). Further, there was no significant difference between the first bonding and rebonding in SBS values of Groups 1, 2 and 3 (P = 0.44, P = 0.60, and P = 0.56). SEM examination showed obvious differences in the enamel surface between CEP and SEP samples in both first bonding and rebonding. With regard to the advantages of SEP methods, it seems this method can be properly used for rebonding of orthodontic brackets.

Cessation of pacing in super-responders of cardiac resynchronization therapy: A randomized controlled trial.

The consequence of cessation of biventricular pacing in super-responders of cardiac resynchronization therapy (CRT) has not been fully investigated. In this prospective, single-blinded clinical trial, 21 super-responders were randomly assigned to the ceased pacing (CeP, 11 patients) group or the continued pacing (CoP, 10 patients) group. Patients randomized to the CeP group underwent cessation of biventricular pacing. New York Heart Association (NYHA) class, quality of life (QOL) assessed with Minnesota questionnaire, 6-minute walking distance (6MWD), left ventricular end systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) were compared between groups at 3- and 6-month follow-up. No significant difference was observed between the CeP and CoP groups regarding NYHA class, QOL, 6MWD, LVESV, LVEDV, or LVEF after 3 months (all P > 0.05). After 6 months, there existed no significant difference between the CeP and CoP groups with regard to NYHA class, QOL, 6MWD, LVESV, and LVEDV (all P > 0.05); however, LVEF was significantly lower in the CeP group than that of the CoP group (0.49 ± 0.10 vs 0.60 ± 0.11, P = 0.04), and LVEF was significantly reduced in the CeP group compared with the baseline value at randomization (0.49 ± 0.10 vs 0.54 ± 0.06, P = 0.04). LVEF was significantly reduced in super-responders of CRT 6 months after cessation of pacing. Super-responders to CRT should receive continued, long-term pacing to preserve recovered LV function.

Cepharanthine alleviates liver injury in a rodent model of limb ischemia–reperfusion

ObjectivesLimb ischemia–reperfusion (I/R) causes remote organ injury (e.g., liver injury). Oxidation and inflammation are crucial mechanisms. We investigated the effects of cepharanthine, a potent antioxidative and anti-inflammatory drug, on alleviating liver injury induced by limb I/R. MethodsTwenty-four adult male Sprague-Dawley rats were randomized to receive sham operation (Sham), Sham plus cepharanthine, I/R, or I/R plus cepharanthine and designated as the Sham, Sham+Cep, I/R, or I/R+Cep group, respectively (n = 6 in each group). I/R was induced by applying rubber band tourniquets high around each hind limb for 3 hours followed by reperfusion for 24 hours. ResultsThe plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the Sham and Sham+Cep groups were low, and the levels of AST and ALT of the I/R group were significantly higher than those of the Sham group (both p<0.001). By contrast, the AST and ALT of the I/R+Cep group were significantly lower than those of the I/R group (both p<0.001). The hepatic levels of nitric oxide (NO), malondialdehyde (MDA), macrophage inflammatory protein 2 (MIP-2), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) of the Sham and Sham+Cep groups were also low. As expected, the NO, MDA, MIP-2, IL-6, and COX-2/PGE2 of the I/R group were significantly higher than those of the Sham group (all p<0.001). By contrast, the NO, MDA, MIP-2, IL-6, and COX-2/PGE2 of the I/R+Cep group were significantly lower than those of the I/R group (all p<0.05). ConclusionCepharanthine alleviates liver injury in a rodent model of limb I/R. The mechanisms may involve reducing oxidation and inflammation.

Lack of involvement of CEP adducts in TLR activation and in angiogenesis.

Proteins that are post-translationally adducted with 2-(ω-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others.

Efficiency of multi-round fluorescence in situ hybridization and its influencing factors in preimplantation genetic diagnosis

To investigate the efficiency of multi-round fluorescence in situ hybridization (FISH) and its influencing factors in preimplantation genetic diagnosis (PGD). A total of 48 couples accepted PGD because of various reasons: 24 with Robertsonian translocations, 16 with reciprocal translocations, 2 with pericentric inversions, one with advanced maternal age who had a previous liveborn of Down syndrome, 3 suffered from sex chromosome abnormalities and 2 repeated spontaneous miscarriages. After 72 retrieval cycles, 432 cleavage stage embryos with more than six cells were biopsied on day three. Only intact nuclei (396) were hybridized in order to verify the chromosomal status of the individual embryos. If previous FISH has failed to give conclusive results while the nuclei remained undamaged, the nuclei were hybridized once again. A total of 870 times of hybridization were conducted to 396 nuclei. Signal identification rates of each round as well as the influence of different probes to the hybridization efficiency were compared. Factors leading to inconclusive FISH results were analyzed as well. Five hundred and thirty five out of 870 hybridizations gave identifiable signals (61.5%). The second and third round FISH showed the best signals with an identification rate of 71.8% and 77.4%, respectively, which were significantly higher than those of the first round (52.8%, P < 0.01), the fourth round (55.8%, P < 0.05, P < 0.01), the fifth round (54.5%, P < 0.05) and the sixth round (27.3%, P < 0.01). The identification rate of centromere specific probe signals (CEP group) was 80.3% and the former three rounds in this group got the best quality of signals with an identification rate of 85.7%, 85.1% and 88.0%, respectively, which was significantly higher than that of the latter three rounds. The identification rate of other probe was much lower than with the CEP probe (55.2% vs. 80.3%, P < 0.01) and the best quality of signal in this group was achieved in the fifth round (72.7%), followed by the second round (66.1%) and the third round (63.8%). The identification rate of the first round (50.3%) and the sixth round (22.2%) were significantly lower compared with the second round (P < 0.01). During the 6 rounds of FISH, 335 hybridizations did not give conclusion results (38.5%, 335/870). The main cause of unidentification was weak signals (20.9%, 182/870). Other common factors included background interference (7.6%, 66/870) and failed hybridization (6.1%, 53/870). Rare causes included nucleus damage (1.8%, 16/870), nucleus loss (1.1%, 10/870) and signal split/overlap (0.9%, 8/870). Multi-round FISH can improve the utility of single nucleus in PGD and the former three rounds have the highest efficiency. The hybridization effect of CEP is better than other probe. Poor signal quality is the common cause of unidentification results.

Circulating chemerin decreases in response to a combined strength and endurance training

Chemerin is an adipokine that may mediate the link between obesity, inflammation, insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. In this study, we examined the association between chemerin and various cardiometabolic risk factors in cross-sectional setting and tested the hypothesis that a 6-month combined exercise program decreases serum chemerin in overweight or obese, non-diabetic individuals. Serum chemerin concentration was measured in a cross-sectional analysis including 98 individuals with a wide range of age and body mass index (BMI). In addition, chemerin was measured in 79 sedentary, overweight or obese, non-diabetic individuals who completed a 6-month combined endurance and resistance exercise program (CEP, n = 51) or served as controls (C, n = 28). Chemerin was significantly associated with total cholesterol (p = 0.04), triglycerides (p < 0.001), fasting insulin (p < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR, p < 0.001), systolic blood pressure (p = 0.04), highly sensitive C-reactive protein (p = 0.03), leucocytes count (p = 0.047), and leptin (p = 0.008) independently of age and BMI. In multiple regression analysis, chemerin was an independent determinant of HOMA-IR. As a result of the 6-month training program, serum chemerin decreased significantly in CEP group (-13.8 ± 13.2 ng/ml, p < 0.001). A significant association between the changes in chemerin and improved HOMA-IR were found even after adjustment for changes in waist circumference. Among non-diabetic individuals serum chemerin was associated with various cardiometabolic risk factors independently of BMI. In addition, the 6-month combined strength and endurance training program led to a significant reduction in circulating chemerin levels in overweight or obese individuals.

Influence of chemiotherapeutic protocol and neuroendocrine differentiation on metastatic non-small cell lung cancer treatment results

In 40-50% of patients with non-small cell lung cancer (NSCLC) at the time of making a diagnosis, the disease is yet at IIIb and IV stage. Standard in the treatment of these patient is the application of systemic chemiotherapy based on CIS/Carboplatin preparations. The aim of this study was to determine the influence of two different chemiotherapeutic protocols and neuroendocrine differentiation on treatment response and survival in patients with metastatic NSCLC. We examined 85 patients with metastatic NSCLC, of which 51 with stage IIIb, and 34 with stage IV of the disease. The histologic diagnosis of NSCLC was determined by tissue assays using hematoxylin eosin method. Neuroendocrine differentiation was determined by immunohistochemical analysis of neuron-specific enolase (NSE), chromogranin A, and synapthophysin expression using monoclonal mouse anti-human bodies (DAKO, Denmark). According to chemiotherapeutic protocol, the patients were randomly assigned into combined Taxol + Cisplatin group (Tax + Cis, n = 35), and Cyclophosphamide + Etoposide + Carboplatin group (CEP, n = 50). The treatment was conducted within 4-6 chemiotherapeutic cycles. The efficacy was assessed after the therapy regimen and median survival time was assessed after the randomization. A total of 31 (36.47%) patients had a favourable therapeutic response, both partial and complete response (54.2% in the Tax + Cis group and 24% in CEP group of patients, respectively, p < 0.001). The median survival time in both groups was 13.1 months (15.3 months in the Tax + Cis group and 10.6 months in the CEP group, respectively, p < 0.001). A one-year follow-up survival period was confirmed in 40% of patients (60% only in the Tax + Cis group). A total of 23 (27.05%) patients with metastatic NSCLC had neuroendocrine differentiation. The disease progression or stable disease was noted only in patient with NSCLC without neuroendocrine differentiation (n = 42, 67.7%, p < 0.001). The median survival time in patients with NSCLC and neuroendocrine differentiation was 14.8 months, without neuroendocrine differentiation 10.7 months (p < 0.001). The patients with NSCLC and neuroendocrine differentiation in the CEP group had a longer one-year follow-up survival period than patients in Tax + Cis group (p < 0.001). In Tax-Cis group of patients, there was no significant difference in one-year follow-up survival period with neuroendocrine differentiation. Better therapeutic response and longer median survival time in metastatic NSCLC was obtained using Tax + Cis as compared to CEP protocol. Similar effect was noted using CEP protocol in patients with NSCLC and neuroendocrine differentiation.

Comparison of Standard Carotid Endarterectomy with Dacron Patch Angioplasty versus Eversion Carotid Endarterectomy during a 4-Year Period

Currently, the two primary approaches to carotid endarterectomy for extracranial carotid stenosis are carotid endarterectomy with patch angioplasty and eversion carotid endarterectomy. In a retrospective study over a 4-year period from 1998 to 2002, we had an opportunity to compare the two approaches as two surgeons utilized carotid endarterectomy with Dacron patch angioplasty and two other surgeons utilized eversion carotid endarterectomy. During the 4-year period, 189 carotid endarterectomies were performed, 125 with Dacron patch angioplasty (CE-P) and 64 with eversion (EE) endarterectomy. There were no significant differences in age of the patients, operative indication, or associated risk factors between the two groups. Perioperative outcome measurement in the CE-P versus EE included stroke or transient ischemic attack, 1.6 per cent versus 1.56 per cent, cranial nerve injury, 2.4 per cent versus 3.13 per cent; death, 0.8 per cent versus 0 per cent; need for operative conversion or revision, 2.4 per cent versus 7.81 per cent, respectively. Only the need for operative conversion or revision reached significant difference (P < 0.05), although the need decreased to 4 per cent for the last 50 EE cases. Recurrent stenosis of 50 per cent to 79 per cent was 4.88 per cent versus 3.13 per cent and >80 per cent was 0.81 per cent versus 0 per cent in the CE-P versus EE group over a follow up of 16.3 months and 17.0 months, respectively. We conclude that both CE-P and EE are equally efficacious operative approaches to extracranial carotid occlusive disease.

Eversion endarterectomy of the carotid artery: Technical considerations and recurrent stenoses

Purpose: The purpose of this study was to examine the characteristics of residual and recurrent lesions after eversion endarterectomy of the carotid artery (E-CE) and compare these results with those following endarterectomy and patch closure (CE-P). Methods: We reviewed 274 patients who underwent carotid endarterectomy in 1998 with electroencephalographic monitoring, general anesthesia, completion duplex scan, and 1-year follow-up. CE-P was preferred for patients who required temporary shunting. In the E-CE group an additional proximal 2-cm arteriotomy was made in the common carotid artery (CCA) in 79 patients, a longer arteriotomy was made for extensive involvement of the CCA in 14 patients, and the internal carotid artery was advanced proximally as a patch for the CCA arteriotomy closure in 14 patients. Stenoses of > 50% that were present at 1 month were considered residual, and those of > 50% that were present at 1 year but not at 1 month were considered recurrent. Results: There were five (1.8%) postoperative strokes (four after CE-P and one after E-CE, P = not significant). At 30 days there were 28 patients (10.2%) with residual stenoses > 50% (11 patients [10.2%] in the E-CE group and 17 patients [10.1%] in the CE-P group; P = not significant). The incidence of recurrent lesions of more than 50% was similar (4.6% for E-CE vs 4.7% for CE-P). Conclusion: The pattern of residual lesions and recurrent stenoses differs with each technique of endarterectomy. Proximal stenoses are more common after E-CE, and distal stenoses are more common after CE-P at both 1 month and 1 year. The frequency of proximal lesions is reduced in E-CE when either the internal carotid artery is advanced proximally onto the CCA or a long CCA arteriotomy is made. Distal recurrences do not seem to be a problem after eversion endarterectomy. (J Vasc Surg 2000;32:1052-61.)

Efficacy and Tolerability of a Teicoplanin-Ciprofloxacin Combination in Severe Community-Acquired Pneumonia

Mortality from community-acquired pneumonia (CAP) is high in the elderly and in patients who have a number of underlying diseases. We evaluated the clinical efficacy of a new unusual combination, teicoplanin-ciprofloxacin, in comparison with ceftriaxone in the treatment of CAP severe enough to require hospital admission. The present multicentre (23 centres) study was an open, comparative, randomised trial using parallel groups, and was carried out according to Good Clinical Practice. All patients required admission to hospital for severe CAP, and all had a follow-up visit that included chest x-ray and a wide biochemical and, in some cases, microbiological profile. 240 patients were enrolled: 158 elderly (over 65 years), 82 with underlying disease (chronic obstructive pulmonary disease, pulmonary primary or metastatic cancer, congestive heart failure, ketoacidotic diabetes), and 71 previously pretreated with other antibiotics with no cure or improvement. 121 patients (mean age 68.4 ± 15.5 years) were randomised to treatment with single-dose teicoplanin 400mg intravenously on the first day followed by 200 (37 patients) or 400 mg/day (84 patients) according to the severity of the disease, plus ciprofloxacin 500mg twice daily orally (TEICO group). 119 patients (mean age 68.9 ± 12.1 years) were randomised to single-dose ceftriaxone 2 g/day intravenously (CEF group). The two groups were homogeneous with regard to gender, pretreatment with other antibiotics, underlying diseases or illness severity at enrolment. Treatment was given for 10.2 ± 3.1 days in the TEICO group and for 9.6 ±3.3 days in the CEP group. Cure or improvement was observed in 85.1% of patients in the TEICO group vs 73.1% in the CEF group, while failures occurred in 5.8% (7 of 121) in the TEICO group, and 23.5% (28 of 119) in the CEF group (the remaining patients were not evaluable for various reasons). Thus, the combination teicoplanin-ciprofloxacin was associated with a failure risk four times lower than ceftriaxone therapy (p < 0.001). Tolerability was good for both treatment regimens.

Induced triploidy by cold shock in Puntius gonionotus (Bleeker)

The effectiveness of different shock treatments applied to inhibit the first mitotic division was investigated in two populations (gold- and wild-coloured) of zebra fish (Brachydanio rerio) with regard to the production of homozygous gynogenetic fish. For inactivation of the paternal genome, eggs were activated by UV-irradiated sperm and exposed to one of the following shock treatments for inhibition of first mitosis: a combined ether-late pressure shock (CEP), a late heat shock (HS) and a late pressure shock without an additional ether treatment (LP). Each shock treatment was applied to egg batches produced by the same 16 females of each population. Haploid controls, chromosome preparations, recessive colour mutants and genetic markers were controls for the treatments. The CEP treatment was found to be the most effective with 30% of egg batches treated developing into swimup fry in both populations. For HS and LP, results were significantly poorer, reaching rates of 14% and 7%, respectively, in the gold-coloured population and no survival up to the swim-up stage in the wild population. A special sensibility or suitability of eggs derived from a particular female to HS or LP shock was observed. The repeated production of swim-up fry from eggs of the same female, especially in the CEP group, demonstrated the importance of the maternal genotype for obtaining viable homozygous gynogenetic offspring. All mature homozygous gynogenetic zebra fish obtained (N=9) were males.

Production of homozygous diploid zebra fish ( Brachydanio rerio)

The effectiveness of different shock treatments applied to inhibit the first mitotic division was investigated in two populations (gold- and wild-coloured) of zebra fish ( Brachydanio rerio) with regard to the production of homozygous gynogenetic fish. For inactivation of the paternal genome, eggs were activated by UV-irradiated sperm and exposed to one of the following shock treatments for inhibition of first mitosis: a combined ether-late pressure shock (CEP), a late heat shock (HS) and a late pressure shock without an additional ether treatment (LP). Each shock treatment was applied to egg batches produced by the same 16 females of each population. Haploid controls, chromosome preparations, recessive colour mutants and genetic markers were controls for the treatments. The CEP treatment was found to be the most effective with 30% of egg batches treated developing into swimup fry in both populations. For HS and LP, results were significantly poorer, reaching rates of 14% and 7%, respectively, in the gold-coloured population and no survival up to the swim-up stage in the wild population. A special sensibility or suitability of eggs derived from a particular female to HS or LP shock was observed. The repeated production of swim-up fry from eggs of the same female, especially in the CEP group, demonstrated the importance of the maternal genotype for obtaining viable homozygous gynogenetic offspring. All mature homozygous gynogenetic zebra fish obtained ( N=9) were males.

Randomised trial comparing combinations of cyclophosphamide and cisplatin without or with doxorubicin or 4′-epi-doxorubicin in the treatment of advanced ovarian cancer

Forty-eight patients with FIGO stage III and IV epithelial carcinomas of the ovary were entered in this randomised trial. Radical surgery was performed and no residual tumor with a diameter greater than 2 cm was left behind. Of these patients 62.5% (10/16) had a complete or partial response on cyclophosphamide + cisplatin (CP) 87.5% (14/16) on cyclophosphamide + doxorubicin + cisplatin (CAP) and cyclophosphamide + 4′-epi-doxorubicin + cisplatin (CEP). The median time to progression was 3.5 months on CP, 12.5 months on CAP and 11.0 months on CEP. Patients treated with CAP combination chemotherapy had generally longer progression-free survival (log rank χ 2 = 5.4; P = 0.04). No significant difference was found, however, between patients on CAP and CEP. The median survival times were 12.5 months on CP, 26.5 months on CAP and 14.0 months on CEP. Patients treated with CAP combination chemotherapy had generally longer survival (logrank χ 2 = 9.08; P = 0.0099). No significant difference was found, however, between patients on CAP and CEP in terms of survival. Asymptomatic mild-to-moderate laboratory test toxicity occurred in 6–12% of patients on CP, 6–12% on CAP and no toxicity of this type and grade on CEP. Nausea and vomiting were also less severe and less frequent in the CEP group. Cardiotoxicity was seen in 12.5% (2/16) only in the CAP group.