Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 41
Filter
1.
HNO ; 2024 Apr 09.
Article in German | MEDLINE | ID: mdl-38592481

ABSTRACT

BACKGROUND: Results of neurotological function diagnostics in the context of interdisciplinary vertigo assessment are usually formulated as free-text reports (FTR). These are often subject to high variability, which may lead to loss of information. The aim of the present study was to evaluate the completeness of structured reports (SR) and referrer satisfaction in the neurotological assessment of vertigo. MATERIALS AND METHODS: Neurotological function diagnostics performed as referrals (n = 88) were evaluated retrospectively. On the basis of the available raw data, SRs corresponding to FTRs from clinical routine were created by means of a specific SR template for neurotological function diagnostics. FTRs and SRs were evaluated for completeness and referring physician satisfaction (n = 8) using a visual analog scale (VAS) questionnaire. RESULTS: Compared to FTRs, SRs showed significantly increased overall completeness (73.7% vs. 51.7%, p < 0.001), especially in terms of patient history (92.5% vs. 66.7%, p < 0.001), description of previous findings (87.5% vs. 38%, p < 0.001), and neurotological (33.5% vs. 26.7%, p < 0.001) and audiometric function diagnostics (58% vs. 32.3%, p < 0.001). In addition, SR showed significantly increased referring physician satisfaction (VAS 8.8 vs. 4.9, p < 0.001). CONCLUSION: Neurotological SRs enable a significantly increased report completeness with higher referrer satisfaction in the context of interdisciplinary assessment of vertigo. Furthermore, SRs are particularly suitable for scientific data analysis, especially in the context of big data analyses.

2.
Eur Arch Otorhinolaryngol ; 281(8): 4143-4151, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38607387

ABSTRACT

PURPOSE: Cochlear implantation is a standard approach to hearing rehabilitation and encompasses three main stages: appropriate patient selection, a challenging surgical procedure, which should be as atraumatic as possible and preserve cochlear structures, and lifelong postoperative follow-up. Computed tomography (CT) is performed to assess postoperative implant position. The Siemens Advanced Radar Target Identification System (ARTIS) Pheno provides fluoroscopic imaging during surgery and has so far been mainly used by cardiologists, neurosurgeons and trauma surgeons. METHODS: Six patients with difficult anatomy or a challenging medical history were selected for a surgical procedure, during which we planned to use the ARTIS Pheno to accurately position and assess implant position under fluoroscopy during and immediately after surgery. In all six cases, the ARTIS Pheno was used directly in the surgical setting. The procedures were performed in cooperation with the neuroradiology department in an interdisciplinary manner. RESULTS: In all six patients, fluoroscopy was used to visualise the procedure at different stages of surgery. In five patients, the procedure was successfully completed. This approach allowed us to finally assess implant position and confirm the correct and complete insertion of the electrode while the patient was still under anaesthesia. CONCLUSION: These cases showed positive surgical outcomes. Although the procedure is more complex than a standard approach, patients can be managed in a safe, effective and appropriate manner. The assessment of implant position in real time during surgery leads to greater patient and surgeon satisfaction. The approach presented here ensures a high quality of cochlear implant surgery even in difficult surgical situations and meets the requirements of modern surgery.


Subject(s)
Cochlear Implantation , Tomography, X-Ray Computed , Humans , Cochlear Implantation/methods , Male , Female , Fluoroscopy/methods , Middle Aged , Aged , Cochlear Implants , Adult , Surgery, Computer-Assisted/methods
3.
Sleep Med ; 111: 21-27, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37714032

ABSTRACT

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a very prevalent disease and its diagnosis is based on polysomnography (PSG). We investigated whether snoring-sound-, very low frequency electrocardiogram (ECG-VLF)- and thoraco-abdominal effort- PSG signal entropy values could be used as surrogate markers for detection of OSA and OSA severity classification. METHODS: The raw data of the snoring-, ECG- and abdominal and thoracic excursion signal recordings of two consecutive full-night PSGs of 86 consecutive patients (22 female, 53.74 ± 12.4 years) were analyzed retrospectively. Four epochs (30 s each, manually scored according to the American Academy of Sleep Medicine standard) of each sleep stage (N1, N2, N3, REM, awake) were used as the ground truth. Sampling entropy (SampEn) of all the above signals was calculated and group comparisons between the OSA severity groups were performed. In total, (86x4x5 = )1720 epochs/group/night were included in the training set as an input for a support vector machine (SVM) algorithm to classify the OSA severity classes. Analyses were performed for first- and second-night PSG recordings separately. RESULTS: Twenty-seven patients had mild (RDI = ≥ 5/h but <15/h), 21 patients moderate (RDI ≥15/h but <30/h) and 23 patients severe OSA (RDI ≥30/h). Fifteen patients had an RDI <5/h and were therefore considered non-OSA. Using SE on the above three PSG signal data and using a SVM pipeline, it was possible to distinguish between the four OSA severity classes. The best metric was snoring signal-SE. The area-under-the-curve (AUC) calculations showed reproducible significant results for both nights of PSG. The second night data were even more significant, with non-OSA (R) vs. light OSA (L) 0.61, R vs. moderate (M) 0.68, R vs. heavy OSA (H) 0.84, L vs. M 0.63, M vs. H 0.65 and L vs. H 0.82. The results were not confounded by age or gender. CONCLUSIONS: SampEn of either snoring-, very low ECG-frequencies- or thoraco-abdominal effort signals alone may be used as a surrogate marker to diagnose OSA and even predict OSA severity. More specifically, in this exploratory study snoring signal SampEn showed the greatest predictive accuracy for OSA among the three signals. Second night data showed even more accurate results for all three parameters than first-night recordings. Therefore, technologies using only parts of the PSG signal, e.g. sound-recording devices, may be used for OSA screening and OSA severity group classification.

5.
Herzschrittmacherther Elektrophysiol ; 28(2): 212-218, 2017 Jun.
Article in German | MEDLINE | ID: mdl-28488109

ABSTRACT

Ventricular tachycardias (VT) in patients with structural heart diseases have predominantly a scar-associated reentry mechanism so that substrate-based ablation approaches also have to be used in nearly all procedures. In many VT cases-especially in nonischemic cardiomyopathy (NICM) and arrhythmogenic right ventricular cardiomyopathy-a critical epicardial substrate can be identified as an essential component of the reentry circuit so that for the ablation-based modification of the substrate in these cases an epicardial approach is necessary. In cases of redo-VT ablation procedures in ischemic cardiomyopathy (after a previously endocardial ablation), an epicardial approach should also be considered. There are also cases in whom no endocardial substrate can be identified and an isolated epicardial substrate can be identified. Worldwide epicardial VT ablations are usually performed after gaining epicardial access using subxyphoidal puncture. The results of recent studies show a higher efficiency with stabilization of cardiac rhythm and reduction of recurrent VT episodes (about 70% event-free survival at the 2­year follow-up) after endo-plus epicardial substrate modification. In electrical storm cases, an early epicardial VT ablation approach also appears to be relevant, especially in NICM. Epicardial instrumentation and ablation represents a complex procedure which should only be performed in experienced centers with cardiac surgery back-up. In these experienced centers, the complications rate is less than 5%.


Subject(s)
Catheter Ablation , Pericardium/surgery , Tachycardia, Atrioventricular Nodal Reentry/surgery , Cardiomyopathies/diagnosis , Cardiomyopathies/physiopathology , Cardiomyopathies/surgery , Cicatrix/diagnosis , Cicatrix/physiopathology , Cicatrix/surgery , Coronary Angiography , Epicardial Mapping , Guideline Adherence , Humans , Magnetic Resonance Imaging , Pericardium/physiopathology , Reoperation , Tachycardia, Atrioventricular Nodal Reentry/diagnosis , Tachycardia, Atrioventricular Nodal Reentry/physiopathology , Treatment Outcome
6.
HNO ; 65(5): 434-442, 2017 May.
Article in German | MEDLINE | ID: mdl-28078405

ABSTRACT

Management of vestibular schwannoma (VS) should always be interdisciplinary and results better than the natural course. Particularly in small VS, either microsurgical resection or radiosurgery (RS) can be employed. RS is a special method (initially only possible stereotactically) for delivering high-precision radiation from many directions to the target point (the isocenter) in a single high dose. With the development of three different systems-Gamma Knife (Elekta, Stockholm, Sweden), special linear accelerators, and CyberKnife (Accuray, Sunnyvale, CA, USA)-the options were extended to 1-5 fractions for RS and multisession RS (msRS), and to up to 6 weeks of conventional fractionation as stereotactic radiotherapy (SRT). Whereas RS uses high ablative single doses, SRT is based on the well-known radiobiological effects of multiple fractions comprising lower single doses up to a required much higher total dose. Evaluation showed that RS and SRT achieve similarly high rates of tumor control of around 90% and low rates of side effects (1-7%). Therefore, SRT is unnecessary for small but clearly progressing VS, which has made RS a very comfortable, effective treatment option. In addition to SRT, larger VS can be treated comparably effectively with CyberKnife-based msRS. Since modern MRI frequently discovers small VS as "incidental findings", the initial biding strategy (wait and scan) is of particular importance. Only with increasing symptoms and detectable tumor growth is the treatment indication established, at which time the decision for surgery and RS/SRT should be taken interdisciplinary under consideration of the patient's wishes.


Subject(s)
Dose Fractionation, Radiation , Hearing Loss/etiology , Neuroma, Acoustic/radiotherapy , Radiation Injuries/etiology , Radiosurgery/adverse effects , Radiosurgery/methods , Evidence-Based Medicine , Hearing Loss/prevention & control , Humans , Neuroma, Acoustic/complications , Radiation Injuries/prevention & control , Radiotherapy Dosage , Treatment Outcome
7.
Sci Rep ; 6: 32812, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27600997

ABSTRACT

In 2011, a severe outbreak of hemolytic-uremic syndrome was caused by an unusual, highly virulent enterohemorrhagic E. coli (EHEC) O104:H4 strain, which possessed EHEC virulence traits in the genetic background of human-adapted enteroaggregative E. coli. To determine magnitude of fecal shedding and site of colonization of EHEC O104:H4 in a livestock host, 30 (ten/strain) weaned calves were inoculated with 10(10) CFU of EHEC O104:H4, EHEC O157:H7 (positive control) or E. coli strain 123 (negative control) and necropsied (4 or 28 d.p.i.). E. coli O157:H7 was recovered until 28 d.p.i. and O104:H4 until 24 d.p.i. At 4 d.p.i., EHEC O104:H4 was isolated from intestinal content and detected associated with the intestinal mucosa. These results are the first evidence that cattle, the most important EHEC reservoir, can also carry unusual EHEC strains at least transiently, questioning our current understanding of the molecular basis of host adaptation of this important E. coli pathovar.


Subject(s)
Cattle Diseases/microbiology , Escherichia coli Infections/veterinary , Escherichia coli O104/physiology , Animals , Bacterial Adhesion , Cattle , Cattle Diseases/epidemiology , Disease Outbreaks , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli O104/pathogenicity , Feces/microbiology
8.
J Agric Saf Health ; 22(1): 13-32, 2016 Jan.
Article in English | MEDLINE | ID: mdl-27024990

ABSTRACT

This article summarizes data gathered on 246 documented cases of children and youth under the age of 21 involved in grain storage and handling incidents in agricultural workplaces from 1964 to 2013 in the U.S. that have been entered into the Purdue Agricultural Confined Space Incident Database. The database is the result of ongoing efforts to collect and file information on documented injuries, fatalities, and entrapments in all forms of agricultural confined spaces. While the frequency of injuries and fatalities involving children and youth in agriculture has decreased in recent years, incidents related to agricultural confined spaces, especially grain storage and handling facilities, have remained largely unchanged during the same period. Approximately 21% of all documented incidents involved children and youth (age 20 and younger), and more than 77% of all documented incidents were fatal, suggesting an under-reporting of non-fatal incidents. Findings indicate that the majority of youth incidents occurred at OSHA exempt agricultural worksites. The states reporting the most incidents were Indiana, Iowa, Nebraska, Illinois, and Minnesota. Grain transport vehicles represented a significant portion of incidents involving children under the age of 16. The overwhelming majority of victims were male, and most incidents (50%) occurred in June, October, and November. Recommendations include developing intervention strategies that target OSHA exempt farms, feedlots, and seed processing facilities; preparing engineering design and best practice standards that reduce the exposure of children and youth to agricultural confined spaces; and developing gender-specific safety resources that incorporate gender-sensitive strategies to communicate safety information to the population of young males with the greatest risk of exposure to the hazards of agricultural confined spaces.


Subject(s)
Accidents, Occupational/statistics & numerical data , Agriculture , Adolescent , Age Distribution , Agriculture/statistics & numerical data , Child , Child, Preschool , Confined Spaces , Databases, Factual , Female , Humans , Infant , Infant, Newborn , Male , United States , Young Adult
9.
Cardiology ; 115(3): 212-6, 2010.
Article in English | MEDLINE | ID: mdl-20197660

ABSTRACT

OBJECTIVES: Atrial fibrillation (AF) is one of the most frequent heart rhythm disorders. It potentially influences cardiac function and its measurement. Cardiac magnetic resonance imaging (CMR) has become the new gold standard for non-invasive assessment of cardiac output (CO). A novel inert gas rebreathing (IGR) device based on the Fick Principle also proved promising in patients in sinus rhythm (SR). The aim of our study was to compare the agreement of non-invasive CO measurements between CMR and IGR in AF patients. METHODS: A total of 68 patients, 34 with AF and 34 pair-matched controls in SR, were included. RESULTS: Bland-Altman analysis showed good agreement between both methods, with an average deviation of 0.2 +/-1.2 l/min in the AF group versus 0.3 +/-1.0 l/min in the SR group (p = 0.77). IGR demonstrated good agreement for CO between 2.0 and 5.4 l/min. However, in hyperdynamic circulatory conditions (CO >5.5 l/min), the increasing disagreement of IGR and CMR measurements reached statistical significance. CONCLUSIONS: Non-invasive CO measurements using CMR and IGR are feasible in patients suffering from AF. Good agreement was found between the two methods in an unselected cohort. Hyperdynamic circulatory conditions can lead to significant measurement differences which, however, do not affect the reproducibility of IGR.


Subject(s)
Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Blood Gas Analysis/methods , Cardiac Output/physiology , Heart Function Tests/methods , Magnetic Resonance Imaging/methods , Nitrous Oxide , Noble Gases , Sulfur Hexafluoride , Administration, Inhalation , Adolescent , Adult , Aged , Female , Humans , Indocyanine Green , Male , Middle Aged , Predictive Value of Tests , Reference Values , Young Adult
10.
Herz ; 35(4): 252-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-22086476

ABSTRACT

Tako-Tsubo cardiomyopathy (TTC) predominantly affects elderly people with a high prevalence of cardiovascular risk factors. Therefore, one would expect to encounter incidental coronary artery disease in a significant number of cases. In fact, the prevalence of mild coronary artery disease (CAD), by angiography, has been reported to be in the range of 30%-60%. Similarly, more severe stenotic lesions in at least one coronary vessel were incidentally found in 10%-35% of patients with the disease. Using intravascular ultrasound in a series of 10 patients with TTC, coronary atherosclerosis was demonstrable in all patients, although five patients had normal coronary angiograms. Therefore, TTC and CAD are not mutually exclusive disease entities. The incidental finding of coronary lesions, even if significant, should not automatically lead to a dismissal of the diagnosis of TTC. Rather, a case-by-case approach using additional imaging modalities should be endorsed.


Subject(s)
Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Takotsubo Cardiomyopathy/diagnosis , Takotsubo Cardiomyopathy/epidemiology , Comorbidity , Diagnosis, Differential , Female , Humans , Incidence , Middle Aged , Risk Assessment , Risk Factors
11.
Zentralbl Neurochir ; 69(1): 14-21, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18393160

ABSTRACT

OBJECTIVE: Microsurgical resection is still the treatment of choice for skull base meningiomas. But the risk of postoperative neurological deficits is high, and in many of these cases complete tumor removal cannot be achieved. Therefore recurrences are even more probable. Stereotactically guided radiation therapy - radiosurgery (RS) or stereotactic radiotherapy (SRT) - offers an additional or alternate treatment option for those patients. We evaluated local control rates, symptomatology, and toxicity. PATIENTS AND METHODS: 224 patients were treated with stereotactically guided radiation techniques in two departments between 1997 and 2003. 129 of 224 had recurrences after 1 to 3 prior tumor resections and 95 of 224 were treated with SRT/RS alone. 87.9% of cases had benign, 7.8% had atypical and 4.3% had malignant meningiomas. RS was only applied in 11 cases. Tumor volumes ranged from 0.16 ccm to 3.56 ccm. The other 213 patients had larger tumor volumes of up to 135 ccm or a meningioma close to optical structures. Therefore 183 cases were treated with SRT in normal fractions of 1.8-2 Gy in single doses up to 60 Gy. Hypofractionated SRT with single fraction doses of 5 or 4 Gy was applied in 30 cases. Follow-up data were available in 181 skull base meningiomas and the progression-free and overall survival rates, the toxicity and symptomatology were evaluated. RESULTS: The median follow-up was 36 months. The overall survival and the progression-free survival rates for 5 years were 92.9%, and 96.9%, respectively. Two tumor progressions have occurred to date but further follow up is required. Tumor volumes (TV) had shrunk about by 19.7% at 6 months (p<0.0001) and by 23.2% at 12 months (p<0.01) after SRT/RS. In 95.6% the symptoms had improved or were stable. Clinically significant acute toxicity (grade III) was seen in only 1 case (2.7%). Some patients developed late toxicity: 8.8% had grade I, 4.4% had grade II and 1.1% had grade III. No other neurological deficits occurred during follow-up. CONCLUSION: SRT and RS offer an additional or alternative treatment option with a high efficacy and few side effects for the tumor control of skull base meningiomas. An individual and interdisciplinary decision respecting treatment is needed for each patient. In cases of large TV (>4 ccm), tumors adjacent to critical structures (<2 mm) or in high-risk patients the use of SRT offers greater benefits.


Subject(s)
Meningioma/surgery , Neurosurgical Procedures , Radiosurgery , Skull Base Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Meningioma/pathology , Middle Aged , Neurosurgical Procedures/adverse effects , Quality of Life , Radiosurgery/adverse effects , Skull Base Neoplasms/pathology , Survival Analysis , Tomography, X-Ray Computed
12.
Cell Physiol Biochem ; 11(4): 219-30, 2001.
Article in English | MEDLINE | ID: mdl-11509830

ABSTRACT

BACKGROUND AND AIMS: The Ca(2+)-activated K(+) channel rSK4 is the rat homologue of the human SK4/IK1 (KCNN4) channel. In colonic mucosa rSK4 plays a key role during acetylcholin-induced secretion. This study was aimed to characterize the properties of the rat SK4 channel. METHODS: Electrophysiological measurements were performed on rSK4 expressing Xenopus laevis oocytes and rat colonic crypts. Intracellular Ca(2+) activity was assessed by Oregon Green fluorescence measurements. RESULTS: The 10 pS rSK4 expressed in oocytes was Ca(2+)-sensitive and inhibited by calmodulin antagonists. 1-ethyl-2-benzimidazolinone (1-EBIO), a known activator of SK4/IK1 channels, also activated rSK4. 1-EBIO affected the current neither at saturating Ca(2+) activities nor under Ca(2+)-free conditions, but increased the Ca(2+) sensitivity of rSK4. rSK4 was strongly activated by cytosolic ATP. However, PKA itself, PKA inhibitors and mutation of the PKA phosphorylation site (S332A) did not affect channel activity. The PKC activator 1,2-dioctanoyl-sn-glycerol and the PKC inhibitor bisindolylmaleimide also failed to influence rSK4. CONCLUSION: The Ca(2+)-sensitive rSK4 is activated by 1-EBIO probably via facilitation of the Ca(2+)-calmodulin-rSK4 interaction. The strong ATP-activation of rSK4 is likely to be caused by phosphorylation via a yet unknown kinase and might involve additional subunits.


Subject(s)
Intestinal Mucosa/metabolism , Potassium Channels, Calcium-Activated , Potassium Channels/metabolism , Potassium/metabolism , 1-Methyl-3-isobutylxanthine/pharmacology , Adenosine Triphosphate/pharmacology , Animals , Benzimidazoles/pharmacology , Calcium/metabolism , Calcium/pharmacology , Calmodulin/antagonists & inhibitors , Calmodulin/metabolism , Charybdotoxin/pharmacology , Colforsin/pharmacology , Colon/metabolism , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/genetics , Cyclic AMP-Dependent Protein Kinases/metabolism , Enzyme Activation , Intermediate-Conductance Calcium-Activated Potassium Channels , Ionomycin/pharmacology , Oocytes/metabolism , Patch-Clamp Techniques , Phosphorylation , Potassium Channels/drug effects , Protein Kinase C/metabolism , Rats , Recombinant Proteins/metabolism , Sulfonamides/pharmacology , Xenopus laevis
14.
Pflugers Arch ; 438(4): 437-44, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10519135

ABSTRACT

Colonic crypt cells possess basolateral Ca(2+)-regulated K+ channels which support Cl- secretion by providing the necessary driving force. The pharmacological characteristics of these channels were examined in Ussing chamber experiments of rat and rabbit colon mucosa by the use of blockers. The chromanol 293B, a blocker of KVLQT1 channels, and clotrimazole (CTZ), a blocker of small Ca(2+)-activated K+ channels, blocked stimulated Cl- secretion completely. Small-conductance Ca(2+)-activated K+ channels (SK) in excised basolateral patches of rat colonic crypts were inhibited concentration dependently by the imidazoles CTZ, NS004 and NS1619 and activated by 1-EBIO. These properties are similar to those of the known human SK channel (hSK4). hSK4-expressing Xenopus laevis oocytes showed ionomycin-activated and CTZ-inhibited K+ currents. When P2Y2 receptors were coexpressed these currents were also activated by ATP. The concentration/response curve was identical to that of rat SK channels. In human colonocytes (T84) exposed to hSK4 antisense probes, but not to sense probes, carbachol-induced K+ currents were attenuated. With RT-PCR an hSK4 could be demonstrated in human colon and in T84 colonocytes. By homology cloning the SK of the rat colon (rSK4) was identified. This protein has a high homology to hSK4 and mouse IK1. These data indicate that the Ca(2+)-activated and imidazole-inhibited basolateral K+ current in the colon is caused by SK4 channels.


Subject(s)
Colon/metabolism , Potassium Channels, Calcium-Activated , Potassium Channels/genetics , Potassium Channels/metabolism , Animals , Carbachol/pharmacology , Cell Line , Chlorides/metabolism , Clotrimazole/pharmacology , Colon/cytology , Colon/drug effects , Electric Conductivity , Humans , Imidazoles/pharmacology , Intermediate-Conductance Calcium-Activated Potassium Channels , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Oocytes/metabolism , Potassium Channel Blockers , RNA, Messenger/metabolism , Rabbits , Rats , Xenopus laevis
15.
Hautarzt ; 49(2): 131-4, 1998 Feb.
Article in German | MEDLINE | ID: mdl-9551336

ABSTRACT

Annular erythema of infancy is a rare and little-known entity. Since its initial description by Peterson and Jarratt in 1981 only 4 further cases have been reported. We present the first case in the German literature. A 4-year-old boy developed non-itching erythematous papules on the trunk which evolved into annular and gyrate erythemas within weeks. The condition showed a relapsing course with disease-free intervals of several months duration. There were no general complaints. Laboratory investigations including detailed serological tests for infectious diseases were normal. Histopathology showed a striking eosinophilic inflammatory infiltrate predominantly in perivascular areas, without peripheral blood eosinophilia. The clinical differential diagnosis of annular erythema of infancy includes erythema annulare centrifugum, while microscopically one must exclude eosinophilic cellulitis (Wells' syndrome). The etiology is unknown and there is no effective therapy. In our case, as well as in all previously published cases, the disease resolved spontaneously. Therefore, it may be considered benign and self-limited.


Subject(s)
Dermatitis/diagnosis , Eosinophilia/diagnosis , Erythema/diagnosis , Biopsy , Child , Child, Preschool , Dermatitis/pathology , Diagnosis, Differential , Eosinophilia/pathology , Erythema/pathology , Follow-Up Studies , Humans , Male , Remission, Spontaneous , Skin/pathology
16.
Cancer Chemother Pharmacol ; 31(5): 369-75, 1993.
Article in English | MEDLINE | ID: mdl-8431970

ABSTRACT

Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance-modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten patients with advanced breast cancer were given EPI (40 mg/m2 in a daily i.v. bolus for 3 consecutive days), and five of them also received VPL (4 x 120 mg/daily p.o. for 4 consecutive days). The data indicated a significant interaction between these two drugs that affected their metabolism. The areas under the concentration-time curves (AUC) obtained for epirubicin glucuronide, epirubicinol glucuronide, and both of the 7-deoxy-aglycones were higher in the EPI + VPL group as compared with the EPI group. The AUC, terminal half-life, mean residence time, volume of distribution at steady state, and plasma clearance of EPI alone as compared with EPI + VPL did not differ significantly. These results suggest either an induction of enzymes necessary for drug metabolism or an increase in the liver blood flow, resulting in an enhanced generation of metabolites with time or in an inhibition of excretion processes. Comparisons of the AUC values obtained for EPI and its metabolites after the first, second, and third injections of EPI revealed a cumulative effect for the metabolites that was more pronounced in the EPI + VPL group, being significant (P < 0.05) for epirubicin glucuronide in both treatment groups and for epirubicinol glucuronide in the EPI + VPL group. Maximal concentrations of VPL and nor-VPL reached 705 +/- 473 and 308 +/- 122 ng/ml, respectively, with the steady-state concentrations being 265 +/- 42 ng/ml for VPL and 180 +/- 12 ng/ml for nor-VPL.


Subject(s)
Epirubicin/pharmacokinetics , Verapamil/pharmacology , Chemotherapy, Adjuvant , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Interactions , Epirubicin/metabolism , Female , Glucuronates/metabolism , Humans , Verapamil/metabolism
17.
Cancer Chemother Pharmacol ; 29(6): 490-4, 1992.
Article in English | MEDLINE | ID: mdl-1568293

ABSTRACT

We studied single doses of intravesical idarubicin (IDA) given as 1-h instillations to 33 patients with bladder tumors. The dose was escalated from 5 to 30 mg and the concentration, from 0.25 to 1.5 mg/ml for evaluation of the importance of both the total amount of drug and the drug concentration on the levels of IDA found in different tissues (tumor, mucosa and muscle). Additionally, plasma uptake over 24 h was studied. The results demonstrated that (1) the levels of IDA in extracts of bladder tumors were significantly higher than those in normal bladder tissue, (2) the incorporation of IDA into tumors depended on the total amount of drug instilled and on the concentration of drug in the instillation fluid, (3) cytotoxic concentrations of IDA were noted in all tumors when the total amount of drug instilled was greater than 15 mg and the drug concentration in the instillation fluid was greater than 0.33 mg/ml, and (4) plasma levels of IDA were negligible.


Subject(s)
Idarubicin/pharmacokinetics , Urinary Bladder Neoplasms/metabolism , Administration, Intravesical , Adult , Aged , Aged, 80 and over , Female , Humans , Idarubicin/blood , Male , Middle Aged , Tissue Distribution , Urinary Bladder Neoplasms/blood
19.
Eur J Cancer ; 26(11-12): 1156-62, 1990.
Article in English | MEDLINE | ID: mdl-2149998

ABSTRACT

25 patients, mostly pretreated, received 55 courses of iododoxorubicin as a single intravenous bolus every 2 weeks. The starting dose was 2 mg/m2 with seven steps to reach the dose-limiting toxicity level. 3 patients treated with 90 mg/m2 had WHO grade 4 myelotoxicity; 2 of these patients had not had cytostatic chemotherapy. 3 of 7 patients treated with 75 mg/m2 had grade 3-4 myelotoxicity; 4 had grade 1-2. Non-haematological toxicities were minor. Acute cardiotoxicity and objective tumour responses were not observed. Plasma and urine levels of iododoxorubicin and five metabolites were assayed in 16 patients. Metabolism to iododoxorubicinol was rapid and plasma clearance was dose-dependent and rapid. Plasma levels and the area under the curve for iododoxorubicin increased with dose. The mean residence time was 3.9 h in patients without liver metastasis and 10.4 h in patients with liver metastasis. Renal excretion was minor. The maximally tolerated dose was 90 mg/m2.


Subject(s)
Doxorubicin/analogs & derivatives , Neoplasms/metabolism , Adult , Aged , Dose-Response Relationship, Drug , Doxorubicin/pharmacokinetics , Doxorubicin/therapeutic use , Doxorubicin/toxicity , Female , Hematologic Diseases/chemically induced , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasms/drug therapy
20.
Eur J Clin Pharmacol ; 39(5): 507-13, 1990.
Article in English | MEDLINE | ID: mdl-2076745

ABSTRACT

The pharmacokinetics of doxorubicin (DOX), iodo-doxorubicin (I-DOX) and their metabolites in plasma has been examined in five patients each receiving 50 mg/m2 of both anthracyclines as a bolus injection. Terminal half-life, mean residence time (MRT), peak plasma concentration Cmax, and area under the curve (AUC) appeared smaller for I-DOX, whereas its plasma clearance (CLP) and volume of distribution at steady state (Vss) were larger than for DOX. The major metabolite of I-DOX was iodo-doxorubicinol (I-AOL) followed by doxorubicinol aglycone (AOLON). The AUC of I-AOL was 6-times larger than that of its counterpart AOL, which is the major metabolite of DOX. AOLON generated after I-DOX administration is a further important metabolite, as its AUC was 10-times larger than that of AOLON generated from DOX. The other aglycones, such as doxorubicin aglycone (AON) and the 7-deoxy-aglycones were only minor metabolites after either I-DOX or DOX injection. The ratio AUCI-AOL/AOL/AUCI-DOX/DOX was 27 in the case of I-DOX and 0.4 after DOX. The terminal half-lives of the cytostatic metabolites I-AOL and AOL were similar, although a longer MRT for AOL was calculated. Both metabolites had much longer MRTs than their parent drugs. The MRTs of the aglycones AOLON and AON were greater than those of the 7-deoxy-aglycones after both I-DOX and DOX. Approximately 6% DOX and less than 1% I-DOX were excreted by the kidneys during the initial 48 h. About 5% of I-DOX was excreted via the kidneys as I-AOL. Aglycones were not detected in significant amounts.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Doxorubicin/analogs & derivatives , Doxorubicin/pharmacokinetics , Aged , Doxorubicin/metabolism , Half-Life , Humans , Middle Aged , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...