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1.
Thorac Cardiovasc Surg ; 59(1): 25-9, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21243568

ABSTRACT

OBJECTIVE: Deep sternal wound infections are serious complications after cardiac surgery. The aim of the present study is to compare the outcome after vacuum-assisted wound closure to that after primary rewiring with disinfectant irrigation. The study additionally focuses on defining predictors for the failure of primary rewiring and its impact on postoperative outcome. METHODS: Retrospective analysis was performed in 5232 patients who underwent cardiac surgery with a median sternotomy. 192 patients postoperatively developed deep sternal wound infections and were distributed into 2 therapy groups: a vacuum-assisted wound closure (= VAC) group and a primary rewiring (= RW) group, which was subdivided into healing after rewiring (= RW-h) and failure of rewiring (= RW-f). These groups were compared statistically to reveal coincidental pre-, intra- and postoperative parameters. RESULTS: Compared to the VAC group, the RW group showed a poorer outcome, although RW baseline characteristics were apparently beneficial. Primary rewiring failed in 45.8 % of all cases, which led to even worse outcomes. Important predictors for failure of primary rewiring were morbid obesity, diabetes mellitus type II, chronic obstructive pulmonary disease, preoperatively impaired left ventricular function, postoperatively positive blood and wound cultures, bilateral harvesting of internal thoracic arteries and the need for surgical reexploration. CONCLUSIONS: In spite of patients being in a worse condition, vacuum-assisted wound closure therapy resulted in improved outcomes and thus should be preferred to primary rewiring. Moreover we report on predictors which may indicate whether there is a high risk of rewiring failure.


Subject(s)
Anti-Infective Agents, Local/administration & dosage , Bacterial Infections/therapy , Negative-Pressure Wound Therapy , Sternotomy/adverse effects , Surgical Wound Infection/therapy , Therapeutic Irrigation , Aged , Bacterial Infections/complications , Cardiac Surgical Procedures/adverse effects , Equipment Design , Humans , Length of Stay , Negative-Pressure Wound Therapy/instrumentation , Negative-Pressure Wound Therapy/methods , Retrospective Studies , Risk Assessment , Risk Factors , Surgical Wound Infection/microbiology , Surgical Wound Infection/mortality , Survival Analysis , Therapeutic Irrigation/methods , Treatment Outcome , Wound Healing
2.
Thorac Cardiovasc Surg ; 58(8): 463-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21110268

ABSTRACT

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious complication after cardiac surgery. The aim of the present study was to identify pre- and intraoperative predictors for the postoperative occurrence of HIT. The study additionally focused on the impact of HIT on postoperative outcome. METHODS: Retrospective analysis was performed for 5073 patients who had required extracorporeal circulation during cardiac surgery. Patients were divided into 3 groups: 1) patients who had postoperative HIT (HIT+); 2) patients with postoperative thrombocytopenia but without HIT (HIT-); and 3) patients with normal platelet count (C). The groups were statistically compared with regard to pre-, intra- and postoperative parameters. RESULTS: Statistically significant predictors were renal insufficiency, intravenous application of heparin for more than 3 days, previous percutaneous coronary intervention within the last 4 weeks, urgency/emergency operation, combined surgery, prolonged extracorporeal circulation or cross-clamping time, and low cardiac output syndrome. Postoperative HIT was associated with an enhanced risk of renal failure, infectious and thromboembolic complications and in-hospital mortality. CONCLUSION: Postoperative HIT increases morbidity and mortality. The predictors presented in this study can be used to identify patients at risk of developing HIT.


Subject(s)
Anticoagulants/adverse effects , Cardiac Surgical Procedures/adverse effects , Heparin/adverse effects , Thrombocytopenia/chemically induced , Aged , Aged, 80 and over , Cardiac Surgical Procedures/mortality , Chi-Square Distribution , Extracorporeal Membrane Oxygenation/adverse effects , Female , Germany , Hospital Mortality , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Platelet Count , Retrospective Studies , Risk Assessment , Risk Factors , Thrombocytopenia/blood , Thrombocytopenia/mortality , Time Factors , Treatment Outcome
3.
Thorac Cardiovasc Surg ; 58(7): 398-402, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20922622

ABSTRACT

BACKGROUND: Due to an increasing number of comorbidities there is still a significant incidence of respiratory failure after primary postoperative extubation in patients who undergo cardiosurgery. We wanted to study whether nCPAP could improve pulmonary oxygen transfer and avoid the necessity for reintubation after cardiac surgery. Additionally, we compared this protocol to noninvasive positive pressure ventilation (NPPV). PATIENTS AND METHODS: Over a period of 3 years we analyzed all patients who were extubated within 12 hours after cardiac surgery, and in whom pulmonary oxygen transfer (PaO2/FIO2) deteriorated without hypercapnia so that all these patients met predefined criteria for reintubation. There were three groups of patients: A = patients required immediate reintubation (n = 125); B = patients had nCPAP with intermittent mask CPAP (n = 264); and C = patients had NPPV (n = 36). RESULTS: 25.8 % of patients in Group B and 22.2 % of patients in Group C were also intubated after a period of CPAP or NPPV. All other patients of Groups B and C could be weaned from these devices (B: 33.4 ± 5.8 hours, C: 26.2 ± 4.2 h; P < 0.05) and were well oxygenated using a face mask at ambient pressures (PaO2/FIO2: B: 136 ± 12, C: 141 ± 12). In Group A, we found a higher mortality (8.8 %) than in Group B (4.2 %) and Group C (5.6 %). The ICU stay and in-hospital stay were significantly prolonged in Group A. The incidence of pulmonary infections (A: 24 %, B: 10.6 %, C: 13.8 %; P < 0.05) and the need for catecholamines were significantly increased in Group A, whereas nCPAP patients suffered significantly more often from impaired sternal wound healing (A: 4.8 %, B: 8.3 %; P < 0.05). CONCLUSIONS: We conclude that reintubation after cardiac operations should be avoided since nCPAP and NPPV are safe and effectively improve arterial oxygenation in the majority of patients with nonhypercapnic oxygenation failure. However, it is of great importance to pay special care to sternal wound complications in these patients.


Subject(s)
Continuous Positive Airway Pressure , Coronary Artery Bypass , Intubation, Intratracheal , Positive-Pressure Respiration/methods , Respiratory Insufficiency/therapy , Aged , Chi-Square Distribution , Continuous Positive Airway Pressure/adverse effects , Coronary Artery Bypass/adverse effects , Critical Care , Female , Germany , Humans , Length of Stay , Male , Middle Aged , Positive-Pressure Respiration/adverse effects , Recurrence , Respiratory Insufficiency/etiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
4.
Thorac Cardiovasc Surg ; 58(4): 200-3, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20514573

ABSTRACT

OBJECTIVE: Aim of the study was to clarify the impact of different pre- and perioperative conditions on outcome in octogenarians undergoing cardiac surgery. METHODS: We retrospectively analyzed preoperative risk factors and intraoperative adverse events and studied in-hospital morbidity and mortality in 646 patients > or = 80 years of age (82.5 +/- 3.5 years) and in 6081 younger patients (70.3 +/- 3.4 years) who underwent cardiac surgery between 1/2001 and 12/2006. RESULTS: Preoperatively, octogenarians suffered significantly more from arterial hypertension, renal failure, previous neurological problems, unstable angina and NYHA class IV than younger subjects. The incidence of combined valve and coronary procedures and of urgent operations was also significantly higher in patients > or = 80 years (27.7 % vs. 18.2 %, P < 0.05, and 7.3 % vs. 4.2 %, P < 0.05, respectively). In-hospital mortality was higher (7.4 % vs. 3.7 %, P < 0.05), and average ICU and total in-hospital stay was longer in the older age group. Postoperative complications occurred in 15 % of patients > or = 80 years compared to 7.6 % of patients < or = 79 years ( P < 0.05). NYHA class IV, female sex and preoperative renal failure correlated with perioperative morbidity. Multivariate analysis could identify urgent procedures, redo surgery, mitral valve surgery and prolonged cross-clamping times as predictors of mortality. CONCLUSIONS: Cardiac surgery in octogenarians can be performed with an acceptable risk but an increased mortality and morbidity compared to younger patients. High-risk octogenarians, who require intensive perioperative management, should be identified to reduce the incidence of postoperative complications.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Postoperative Complications/etiology , Age Factors , Aged , Aged, 80 and over , Cardiac Surgical Procedures/mortality , Comorbidity , Critical Care , Female , Hospital Mortality , Humans , Incidence , Length of Stay , Logistic Models , Male , Odds Ratio , Patient Selection , Postoperative Complications/mortality , Postoperative Complications/prevention & control , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Survival Analysis , Time Factors , Treatment Outcome
5.
Thorac Cardiovasc Surg ; 58(1): 23-7, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20072972

ABSTRACT

BACKGROUND: It is still unclear whether biological or mechanical valves should be preferred in patients on chronic dialysis therapy. PATIENTS AND METHODS: We retrospectively analyzed data from 104 patients (66.5 +/- 8.6 years) with end-stage renal failure (RF) who underwent aortic or mitral valve replacement between 2002 and 4/2008. Mechanical valves were implanted in 44 (42 %) patients and bioprostheses in 60 (58 %). The two groups were comparable with regard to preoperative data, age and incidence of additional CABG procedures. We studied in-hospital morbidity and mortality, major postoperative complications and length of ICU and hospital stay. Additionally, parameters predicting a poor outcome were analyzed with multivariate regression analysis. RESULTS: The overall hospital mortality was 12.5 % and did not differ between the two groups (mechanical: 13.6 %, biological: 11.7 %, n. s.). In the postoperative course, duration of ventilation and ICU stay were similar, whereas hospital stay was significantly longer for patients with mechanical prostheses (19.5 +/- 5.4 vs. 15.6 +/- 4.1 days, P < 0.05). Mechanical valve patients had a significantly higher rate of postoperative cerebrovascular incidents (18.2 vs. 8.3 %, P < 0.05) and bleeding complications (15.9 vs. 11.7 %, P < 0.05). Reoperation, obesity, left ventricular ejection fraction < 30 % and previous neurological complications were independent predictors of hospital mortality. CONCLUSIONS: Our results demonstrate that in patients with end-stage RF, the use of mechanical valves is associated with a significant risk of complications. Because of the poor overall survival of patients on dialysis, bioprosthesis degeneration will not be a limiting factor. Therefore, preference should be given to biological valves in these patients.


Subject(s)
Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis , Mitral Valve/surgery , Postoperative Complications , Aged , Aged, 80 and over , Female , Humans , Kidney Failure, Chronic , Male , Middle Aged , Retrospective Studies , Treatment Outcome
6.
Chirurg ; 79(9): 874-6, 2008 Sep.
Article in German | MEDLINE | ID: mdl-18209992

ABSTRACT

Intrathoracic enlarged lymph nodes in patients with malignant diseases always arouse suspicion of lymphatic metastases. Despite modern diagnostic investigation, surprising findings sometimes emerge. The present case of a young man with intrathoracic lesions in association with a germ-cell tumor of the testis turned out to have sarcoidosis mimicking testicular cancer relapse.


Subject(s)
Germinoma/complications , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/diagnosis , Testicular Neoplasms/complications , Adult , Antineoplastic Combined Chemotherapy Protocols , Bleomycin , Chemotherapy, Adjuvant , Cisplatin , Diagnosis, Differential , Etoposide , Germinoma/drug therapy , Germinoma/pathology , Germinoma/surgery , Humans , Laparoscopy , Lymph Node Excision , Lymphatic Diseases/diagnostic imaging , Male , Neoplasm Staging , Positron-Emission Tomography , Radiography, Thoracic , Sarcoidosis, Pulmonary/pathology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Testis/pathology , Thoracotomy , Tomography, X-Ray Computed
7.
JSLS ; 11(3): 394-7, 2007.
Article in English | MEDLINE | ID: mdl-17931527

ABSTRACT

BACKGROUND: A 67-year-old woman with a gastrointestinal stromal tumor (GIST) of the stomach presented to our outpatient clinic. Preoperative computed tomographic scans and endoscopic examination revealed a spherical submucosal tumor (7.7 x 6.1 x 6 cm) in the posterior wall of the stomach less than 1cm away from the cardia, on the small curvature side. METHODS: The tumor, which endosonographically had a volume of 282 cm(3), was completely resected by a full-thickness laparoscopic wedge excision without discontinuous gastric resection. The whole procedure was performed using 4 working ports (one 12-mm and three 5-mm ports) and 1 camera port (12 mm). Because the resection margins were tumor free on frozen sections and the distance between the resection margin and cardia was wide enough not to compromise food passage, there was no need for total gastrectomy or upper discontinuous gastric resection. The patient was discharged on the fourth postoperative day after an uneventful clinical course. RESULTS: Histological examination revealed a malignant gastrointestinal stroma tumor of the stomach. The patient was therefore enrolled for Imatinib adjuvant therapy. Careful and long-term follow-up of 21 months showed no signs of local or distant tumor recurrence. However, further follow-up is needed to monitor for signs of possible recurrence or distant metastases. CONCLUSION: The described technique prevented proximal gastric resection and a risk of anastomosis without compromising the food passage and radicality.


Subject(s)
Gastrointestinal Stromal Tumors/surgery , Laparoscopy/methods , Aged , Antineoplastic Agents/therapeutic use , Benzamides , Endosonography , Female , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Tomography, X-Ray Computed
8.
Endoscopy ; 39(8): 715-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17661247

ABSTRACT

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is generally established as the most sensitive diagnostic tool for the assessment of locoregional tumor stage in esophageal carcinoma. It therefore has a crucial impact on the decision whether patients should undergo surgery as primary treatment or should receive neoadjuvant therapy. This study retrospectively evaluates the accuracy of EUS in tumor and nodal staging of prospectively evaluated patients with esophageal carcinoma in relation to tumor type, tumor grading, tumor site, and the influence of dilation. PATIENTS AND METHODS: All 214 patients included in the study underwent surgery without neoadjuvant therapy and had tumor-free resection margins with no evidence of distant metastasis. EUS investigations were done at our Department of Interdisciplinary Endoscopy. EUS results were compared with the pathological findings. RESULTS: EUS correctly identified T status in 141 patients (65.9 %). The sensitivity and specificity in relation to T status were 68.1 % and 98.2 % respectively for T1, 40.9 % and 83.4 % for T2, 84.3 % and 64.6 % for T3, and 14.3 % and 98.8 % for T4. The overall diagnostic accuracy of EUS in relation to N status was 64.5 % (n = 138); sensitivity and specificity for the diagnosis of N1 were 93.8 % and 20 %, respectively. Sixty-eight (80 %) of 85 pN0-staged tumors were overstaged as uN1. Dilation had a significant influence on the accuracy of EUS staging in advanced tumors ( P = 0.02), whereas tumor grading impacted on EUS staging in early tumors ( P = 0.01). Tumor site and tumor type did not show any influence. CONCLUSIONS: Endosonographic staging of esophageal carcinoma is still unsatisfactory. An improvement in staging accuracy may be achieved by adding fine-needle aspiration biopsy (FNA) to EUS, because FNA improves N-stage accuracy, but it has no bearing on T-stage accuracy.


Subject(s)
Endosonography/methods , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Neoplasm Invasiveness/pathology , Neoplasm Staging/methods , Adult , Aged , Biopsy, Needle , Cohort Studies , Confidence Intervals , Esophageal Neoplasms/surgery , Female , Germany , Humans , Immunohistochemistry , Male , Middle Aged , Predictive Value of Tests , Preoperative Care/methods , Probability , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Total Quality Management
9.
J Physiol ; 537(Pt 1): 27-34, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11711558

ABSTRACT

1. Low threshold, T-type, Ca(2+) channels of the Ca(v)3 family display the fastest inactivation kinetics among all voltage-gated Ca(2+) channels. The molecular inactivation determinants of this channel family are largely unknown. Here we investigate whether segment IIIS6 plays a role in Ca(v)3.1 inactivation as observed previously in high voltage-activated Ca(2+) channels. 2. Amino acids that are identical in IIIS6 segments of all Ca(2+) channel subtypes were mutated to alanine (F1505A, F1506A, N1509A, F1511A, V1512A, F1519A, FV1511/1512AA). Additionally M1510 was mutated to isoleucine and alanine. 3. The kinetic properties of the mutants were analysed with the two-microelectrode voltage-clamp technique after expression in Xenopus oocytes. The time constant for the barium current (I(Ba)) inactivation, tau(inact), of wild-type channels at -20 mV was 9.5 +/- 0.4 ms; the corresponding time constants of the mutants ranged from 9.2 +/- 0.4 ms in V1512A to 45.7 +/- 5.2 ms (4.8-fold slowing) in M1510I. Recovery at -80 mV was most significantly slowed by V1512A and accelerated by F1511A. 4. We conclude that amino acids M1510, F1511 and V1512 corresponding to previously identified inactivation determinants in IIIS6 of Ca(v)2.1 (Hering et al. 1998) have a significant role in Ca(v)3.1 inactivation. These data suggest common elements in the molecular architecture of the inactivation mechanism in high and low threshold Ca(2+) channels.


Subject(s)
Calcium Channels, T-Type/physiology , Amino Acid Sequence/genetics , Animals , Calcium Channels, T-Type/genetics , Kinetics , Molecular Sequence Data , Mutation/physiology , Oocytes , Time Factors , Xenopus
11.
J Clin Oncol ; 17(4): 1200, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10561179

ABSTRACT

PURPOSE: Neuroblastoma screening during the first half-year of life is associated with a two- to three-fold overdiagnosis. Because regression processes seem to be confined to infancy, we investigated whether screening at 1 year would be associated with fewer overdiagnoses, and we investigated the characteristics of thus-detected and not-detected patients. PATIENTS AND METHODS: Thin-layer chromatography was used for semiquantitative assessment of urine samples dried on filter paper and obtained when patients were 10 to 14 months old (sample 1) and 17 to 19 months old (sample 2). Abnormal results were reanalyzed quantitatively from the same specimen by high-performance liquid chromatography and/or gas chromatography-mass spectrometry. RESULTS: A total of 200,054 children of the German federal states Lower Saxony, Northern Rhine-Westphalia, and Bremen were screened from May 1992 to April 1995. Of 229,078 investigated samples (100%), 228,245 (99.6%) were first, 657 (0.3%) were second, and 176 (0.08%) were third urine specimens. The compliance rate was 27.8%, but it continued to increase throughout the study period and in the last year it was 43. 3%. The second screening offered at 18 months was accepted by only 12.1% (24,259) of the children. Thirty children underwent clinical examination, and nine asymptomatic neuroblastoma cases were detected (stage 1, n = 4; stage 2, n = 2; stage 3, n = 2; stage 4, n = 1; detection rate, 1:22,228). The results of 21 tests were false-positive. Ten children with false-negative test results presented 8 to 35 months later with neuroblastoma (stage 1 tumor, n = 1; stage 2, n = 1; stage 3, n = 1; stage 4, n = 7; five of nine tumors were N-myc-amplified tumors). Three children were nonsecretors at the time of diagnosis. Fifty-two patients were "missed" (not screened), and 37 children developed neuroblastoma before the age of screening (early cases). During the same period, a total of 23.6 cases per million children within the screening area and 24.0 cases per million children outside the screening area were diagnosed as neuroblastoma cases (not significant [NS]). In prescreening times in the area of the later screening states, 20.7 cases per million children were found (NS). CONCLUSION: Screening at 1 year of age demonstrated a lower detection rate than earlier screening programs and did not produce a "halo effect." The good prognostic features of early-detected cases and the poor characteristics of not-detected-but-late-presenting cases corresponded to those of the related age groups.


Subject(s)
Mass Screening/methods , Neuroblastoma/diagnosis , Biomarkers, Tumor/urine , Chromatography , Female , Germany/epidemiology , Homovanillic Acid/urine , Humans , Incidence , Infant , Male , Neoplasm Staging , Neuroblastoma/epidemiology , Neuroblastoma/urine , Predictive Value of Tests , Survival Rate , Vanilmandelic Acid/urine
12.
Anticancer Res ; 19(3B): 2205-9, 1999.
Article in English | MEDLINE | ID: mdl-10472332

ABSTRACT

Human genes NY-ESO-1, MAGE-1 and MAGE-3 code for antigens which are expressed in malignancies of various histological types but not in normal tissues except testis. These antigens might therefore represent potential targets for specific immunotherapy. We studied the expression of genes NY-ESO-1, MAGE-1 and MAGE-3 in 98 neuroblastoma tumors by reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1 was expressed in 66%, NY-ESO-1 in 36% and MAGE-3 in 33% of the tumors. NY-ESO-1 gene expression was associated with age older than one year (p = 0.017), more differentiated tumor histology (p = 0.044), elevated urinary vanillylmandelic acid (VMA, p = 0.018) and normal serum ferritin levels (p = 0.023). MAGE-1 expression correlated significantly with normal serum ferritin levels (p = 0.009) and absence of MycN amplification (p = 0.007) while MAGE-3 expression was associated with absence of metastasis (p = 0.027). We conclude that approximately 70% of the neuroblastoma tumors express at least one of the genes coding for NY-ESO-1, MAGE-1 or -3, respectively.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Membrane Proteins , Neoplasm Proteins/genetics , Neuroblastoma/genetics , Neuroblastoma/pathology , Proteins/genetics , Adult , Age Factors , Antigens, Neoplasm/genetics , Brain Neoplasms/mortality , Brain Neoplasms/surgery , Ferritins/blood , Humans , Melanoma-Specific Antigens , Middle Aged , Neoplasm Metastasis , Neoplasm Proteins/analysis , Neoplasm Staging , Neuroblastoma/mortality , Neuroblastoma/surgery , Proteins/analysis , Reverse Transcriptase Polymerase Chain Reaction , Vanilmandelic Acid/urine
17.
J Neurol Neurosurg Psychiatry ; 48(10): 1049-53, 1985 Oct.
Article in English | MEDLINE | ID: mdl-4056806

ABSTRACT

Luria has described a syndrome of disinhibited and impulsive behaviour, in which the patient is unable to follow sequential instructions. This he attributes to localised frontal lobe damage. However, group studies of patients with focal lesions of the frontal lobes fail to reveal such a syndrome. A patient is described who displayed a form of Luria's syndrome temporarily. Psychometric and post mortem evidence indicate that the syndrome arises only under conditions of more global cerebral dysfunction.


Subject(s)
Brain/pathology , Frontal Lobe , Meningeal Neoplasms/diagnosis , Meningioma/diagnosis , Brain Diseases/diagnosis , Brain Diseases/psychology , Female , Humans , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Syndrome
18.
Atherosclerosis ; 56(3): 313-21, 1985 Sep.
Article in English | MEDLINE | ID: mdl-3863623

ABSTRACT

Timefurone was evaluated in several animal models for cholesterol-lowering and anti-atherosclerotic activity. In normal male rats, a dose-response study with timefurone (3, 10, 30, 50 and 100 mg/kg/day) was conducted for 7 days. Significant activity was observed only at 50 and 100 mg/kg/day, where very low and low density lipoprotein cholesterol [(VLDL + LDL)-C] and total-C levels were reduced (mean 27 and 20%). High density lipoprotein cholesterol (HDL-C) was lowered 24% by the high timefurone dose. Timefurone (10, 20, 50 and 100 mg/kg/day in the diet) was then examined in normocholesterolemic SEA japanese quail. beta-lipoprotein cholesterol (VLDL + LDL)-C was reduced at all doses (mean 58%), while alpha-lipoprotein cholesterol (HDL-C) was elevated by all doses of timefurone (mean 45%). Male weanling rats made moderately hypercholesterolemic represented a 3rd phase of timefurone (2.5, 5, 10, 20, 50, 100 mg/kg/day) testing. After 4 days of drug treatment, marked hypocholesterolemic activity was observed for (VLDL + LDL)-C (mean decrease 49%) and total-C (mean 33%). HDL-C levels were increased with 10 and 100 mg/kg/day doses. Timefurone (25 and 100 mg/kg/day in the diet) also caused a significant reduction in atherosclerotic development in hypercholesterolemic SEA japanese quail. Atherosclerotic involvement (determined by visual assessment of plaque), arterial weight, and arterial cholesterol (total and mg/g artery) were clearly lowered by both doses of timefurone. There was no evidence of significant drug toxicity in any of these experiments. On the basis of these data, timefurone has excellent therapeutic potential and additional study of the drug's hypocholesterolemic and anti-atherosclerotic properties appears warranted.


Subject(s)
Benzopyrans/pharmacology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cholesterol/blood , Diet, Atherogenic , Lipoproteins, VLDL/blood , Animals , Body Weight/drug effects , Cholesterol, VLDL , Coturnix , Dose-Response Relationship, Drug , Male , Rats , Species Specificity
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