Anticholinergic burden and comorbidities in patients attending treatment with trospium chloride for overactive bladder in a real-life setting: results of a prospective non-interventional study.

BACKGROUND: Elderly people are representative for the patients most likely to be treated with anticholinergics for overactive bladder (OAB). They often receive further drugs with anticholinergic properties for concomitant conditions. This increases the risk for side effects, including central nervous system disorders. Data on comorbidities and baseline anticholinergic burden of OAB patients seen in urological practice is scarce. Therefore, we included an epidemiological survey on these issues in our study which assessed the effectiveness and tolerability of trospium chloride (TC) in established dosages under routine conditions. METHODS: Outpatients (≥ 65 years of age), for whom treatment with TC was indicated, were eligible to participate in this non-interventional, prospective study performed in 162 urological practices in Germany. Epidemiological questions were evaluated by the Anticholinergic Burden (ACB) scale and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) at baseline. Efficacy was assessed by changes in symptom-related variables of OAB after treatment. Dosage regimen, duration of treatment, adverse events, withdrawals, and ease of subdivision of the prescribed SNAP-TAB tablet were documented. Patients and physicians rated efficacy and tolerability of treatment. Statistics were descriptive. RESULTS: Four hundred fourty-five out of 986 (47.54%) patients in the epidemiological population had a baseline ACB scale score > 0, 100 (24.72%) of whom a score ≥ 3. The median CIRS-G comorbidity index score for all patients was 5. 78.55% (608/774) of patients in the efficacy population received a daily dose of 45 mg TC. 60.03% (365/608) of them took this dose by dividing the SNAP-TAB tablet in three equal parts. Before-after-comparisons of the core symptoms of OAB showed clear improvements. An influence of the dosage scheme (1 × 45 mg TC/d vs 3 × 15 mg TC/d) on clinical outcome could not be observed. Most urologists and patients rated TC treatment as effective and well tolerated. 44 (4.37%) out of 1007 patients in the safety collective ended their treatment prematurely, while 75 patients (7.45%) experienced adverse events. CONCLUSIONS: Anticholinergic burden and comorbidities in elderly OAB patients are frequent. The acceptance of the SNAP-TAB tablet, which facilitates flexible dosing with TC, was high, which is supportive in ensuring adherence in therapy. TRIAL REGISTRATION: This non-interventional study was registered on October 29, 2014 with the number DRKS00007109 at the German Register of Clinical Studies (DRKS).

Exploring effects of a natural combination medicine on exercise-induced inflammatory immune response: A double-blind RCT.

Traumeel (Tr14) is a natural, combination drug, which has been shown to modulate inflammation at the cytokine level. This study aimed to investigate potential effects of Tr14 on the exercise-induced immune response. In a double-blind, randomized, controlled trial, healthy, untrained male subjects received either Tr14 (n = 40) or placebo (n = 40) for 24 h after a strenuous experimental exercise trial on a bicycle (60 min at 80%VO2 max). A range of antigen-stimulated cytokines (in vitro), white blood cell count, lymphocyte activation and apoptosis markers, and indicators of muscle damage were assessed up to 24 h following exercise. The area under the curve with respect to the increase (AUCI ) was compared between both groups. The Tr14 group showed a reduced exercise-induced leukocytosis and neutrocytosis (P < 0.01 for both), a higher AUCI score of antigen-stimulated IL-1ß and IL-1α (absolute and per monocyte, all P < 0.05), a lower AUCI score of antigen-stimulated GM-CSF (P < 0.05) and by trend a lower AUCI score of antigen-stimulated IL-2 and IL-4 as well as a higher AUCI score of antigen-stimulated IL-6 (all P < 0.1). Tr14 might promote differentiated effects on the exercise-induced immune response by (a) decreasing the inflammatory response of the innate immune system; and (b) augmenting the pro-inflammatory cytokine response.

Reduction in cortisol inactivation is part of the adrenal stress response to cardiac and noncardiac pediatric surgery: a prospective study using gas chromatography-mass spectrometry analysis.

We examined the hypothesis that major cardiac surgery triggers a more intense adrenal stress response than less intensive noncardiac surgery, which then alters cortisol inactivation. Urinary excretion rates of glucocorticoid metabolites were determined before and after surgery using gas chromatography-mass spectrometry in 29 children undergoing scheduled major cardiac surgery and 17 control children undergoing conventional noncardiac surgery in a prospective observational study. Excretion rates of glucocorticoid metabolites were summed and corrected for creatinine excretion to calculate cortisol production rates (mg/mmol creatinine/m(2) body surface area). Precursor/product ratios from individual metabolites were calculated to characterize cortisol inactivation (11ß-hydroxysteroid dehydrogenase). Postoperatively, median cortisol production rates increased in both groups ( MCS: from 2.7 to 9.3; controls: from 2.7 to 5.8; p<0.001) with no significant difference between groups (p=0.12). Ratios of cortisol to cortisone metabolites, indicating the overall activity of 11ß-hydroxysteroid dehydrogenase, increased postoperatively in both groups (p<0.001). In conclusion, surgery resulted in a distinct postoperative increase in cortisol production. In contrast to our hypothesis, children undergoing major cardiac surgery did not show an increased adrenal stress response compared to children undergoing conventional surgery. Furthermore, the reduction in cortisol inactivation appears to be an essential part of the stress response to pediatric surgery in general.

IABP before cardiac surgery: clinical benefit compared to intraoperative implantation.

BACKGROUND: The aim of this study was to determine whether preoperative compared to intraoperative intra-aortic balloon counterpulsation (IABP) is advantageous regarding 30-day and 2-year survival in high-risk patients (acute myocardial infarction, severely impaired left ventricular ejection fraction (LVEF), low output syndrome) undergoing coronary surgery. METHODS: In the years 2004 to 2008, 156 consecutive patients undergoing coronary surgery with IABP support (119 preoperative, 37 intraoperative IABP) were observed. Applying Fisher's exact test, as well as Wilcoxon and median tests, possible group differences were evaluated. After univariate analysis, models of logistic regression and Cox-regression were built. RESULTS: Preoperative hemodynamic state and risk profile of the two patient groups were comparable: patients with preoperative IABP showed a similar level of urgency (21.9% vs. 18.9% emergencies), cardiogenic shock (8.4% vs. 10.8%), inotropes (8.4% vs. 8.1%), impaired LVEF (30.3% vs. 29.7%) and ventilation (5.9% vs. 5.4%) compared to patients with intraoperative IABP. Nevertheless, patients with intraoperative IABP demonstrated a significantly higher 30-day mortality rate (37.8% vs. 5.9%) and 2-year mortality rate (54.0% vs. 18.1%) compared to patients with preoperative IABP. Logistic regression revealed that patients with intraoperative IABP have a 16-times higher 30-day mortality rate after coronary surgery (OR: 16.386, 95% CI: 4.858-55.266) than patients with preoperative IABP. Two-year mortality (OR: 9.317, 95% CI: 3.430 to 25.311) and survival time were significantly better in patients with preoperative IABP therapy. CONCLUSION: Considering the significant benefit for patients with preoperative compared to intraoperative IABP and the absence of vascular problems after IABP insertion, the results of this study indicate a more liberal indication for IABP in high-risk patients before coronary bypass surgery.

Production of interleukin-13 is influenced by the interleukin-4 -34TT and -590TT genotype in patients with aggressive periodontitis.

Aggressive periodontitis (AgP) is a specific form of periodontal disease, with rapid destruction of the tissues supporting the teeth in otherwise young healthy individuals. We recently showed a higher frequency of the interleukin-4 (IL-4) -34TT and -590TT genotype in AgP patients compared to controls (P<0.05). Herein, we demonstrated that this specific IL-4 genotype exerts its function by increasing expression of IL-4 and STAT6, and producing higher concentrations of IL-4 in activated CD4+ cells of patients with AgP. In the present study, we investigated the effects of the IL-4-specific genotype on IL-13, IL-2 and IFN-γ expression and production in activated CD4+ cells of patients with AgP and healthy controls. Results revealed higher IFN-γ and IL-2 expression and significantly increased IL-13 production in the cells of the patients who were homozygous for the -34T and -590T alleles in comparison with the patients who were homozygous for the -34C and -590C alleles (P<0.05). Results of controls with the -34C and -590C alleles were similar to those of AgP with the same genotype. To our knowledge, the present study is the first to show an effect of the -34TT and -590TT genotype on IL-13 production. There is an increased production of IL-13 by the T cells of aggressive periodontitis patients with the IL-4 genotype.

Octogenarians undergoing combined aortic valve replacement and myocardial revascularization: perioperative mortality and medium-term survival.

OBJECTIVE: Aim of the study was to answer the question whether the mortality and morbidity of octogenarians undergoing combined aortic valve replacement and myocardial revascularization (AVR + CABG) is higher than that of younger patients. PATIENTS AND METHODS: Between 01/1995 and 12/2002, 242 patients underwent AVR + CABG in our institution. 37 patients were older than 80 years (16 male, 21 female, median pressure gradient over the aortic valve: 53 mmHg, median EF: 62%), 205 patients were younger than 80 years (133 male, 72 female, median gradient 48 mmHg, median EF: 61%). NYHA class, aortic valve area and valve calcification were worse in the 80+ group. Biological valve prostheses were implanted in 94.6% of the older and in 45.4% of the younger patients (p < 0.001). RESULTS: Perioperative complications occurred more often (p = 0.0188) in the 80+ group (86.5% experienced 1 or more complications) than in the 80- group (66.3%). Similarly, the MACE (Major Adverse Cardiovascular Events) rate was higher (p = 0.0448) in the 80+ group than in the 80- group. Bleeding occurred (p = 0.092) more often in younger (9.3%) than in older (0%) patients, while renal insufficiency was more frequent (p = 0.0164) in older (21.6%) than in younger patients (7.8 %). The 30-day mortality was higher (p = 0.0045) in older (21.6%) than in younger patients (5.8%). Multivariate analysis revealed an odds ratio for early death of 2.9 (CI 1.014-8.397) for patients older than 80 years. The late death rate within the first 5 years after surgery was comparable in both groups (80- group 24.4%, 80+ group 24.3%). Postoperative quality of life was significantly worse in the 80+ group in 4 out of 8 functions. CONCLUSIONS: Octogenarians undergoing AVR + CABG have a relatively high perioperative complication rate and mortality, but show a stable medium-term survival. The perioperative complication rate is higher in older than in younger patients, and the postoperative quality of life with regard to bodily functions is acceptable but significantly worse than that of younger patients.

Single-nucleotide polymorphisms in the IL-4 and IL-13 promoter region in aggressive periodontitis.

INTRODUCTION: IL-4 and IL-13 polymorphisms have been shown to influence the susceptibility to systemic diseases. In this study, possible associations between the IL-4 -590 C-->T, IL-4 -34 C-->T, IL-13 -1112 C-->T and IL-13 -1512 A-->C promoter polymorphisms were investigated in subjects with generalized aggressive periodontitis (AgP) compared with healthy individuals. MATERIAL AND METHODS: Fifty-eight patients with diagnosis of generalized AgP and 51 matched healthy controls participated in the study. Blood samples were collected and DNA isolated. Molecular analyses were performed by PCR-RFLP in a blind fashion. Genotype and allele frequencies among study groups were compared using Fisher's exact test (alpha value: 0.05). Pearson's chi(2) test was used for analysis of Hardy-Weinberg equilibrium. RESULTS: The frequency of the IL-4 -590 T/T and IL-4 -34 T/T genotypes differed significantly between groups (p=0.05, 0.02, respectively), although the allele frequencies were similar. There was a higher frequency of the IL-4 -590 T/T and IL-4 -34 T/T genotypes in patients with AgP compared with controls. The genotype and allele frequencies of the IL-13 polymorphisms did not differ between groups. CONCLUSIONS: This study demonstrated an association between the IL-4 -590 T/T and IL-4 -34 T/T genotypes and AgP. Further research is necessary to prove if there is an association of these polymorphisms with AgP, and if the polymorphisms have a functional effect.

Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?

OBJECTIVE: To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. PATIENTS AND METHODS: Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. RESULTS: Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors.

INTRODUCTION: The aim of the study was to determine the prevalence of vitamin D deficiency, secondary hyperparathyroidism (sHPT), generalized bone pain and predictors of vitamin D deficiency in a cohort of 994 healthy adult urban residents (589 males, 405 females; age range: 16-69 years) consisting of 101 Germans, 327 Turkish residents of Turkey and 566 Turkish immigrants living in Germany. METHODS: The mean (+/- standard deviation) for 25-hydroxyvitamin D [25(OH)D] and biointact parathyroid hormone (BioPTH) for the German men and women was 68.4 nmol/l and 26.7 pg/ml, respectively. Turkish residents of Turkey had a mean 25(OH)D and BioPTH of 40.6 nmol/l and 27.5 pg/ml, respectively, whereas Turkish residents of Germany had a 25(OH)D of 38.1 nmol/l and a BioPTH of 35.6 pg/ml. RESULTS: Vitamin D insufficiency was common among Turkish nationals independent of whether they lived in Turkey or Germany; 75% had 25(OH)D levels of <50 nmol/l. Turkish females had a higher prevalence of 25(OH)D deficiency (<25 nmol/l) than Turkish males: 30 and 19% of Turkish females living in Germany and Turkey were severely vitamin D deficient compared to 8% and 6% of Turkish males living in Germany and Turkey, respectively. With respect to BioPTH levels, 31% of Turkish females and 21% of Turkish males had elevated BioPTH levels in contrast to only 15% of females and 4% of males living in Turkey. Unconditional logistic regression analysis identified the most important predictors for low 25(OH)D levels as sex, body mass index, lack of sun exposure and living at a higher latitude. Additionally, wearing a scarf and number of children were found to be an independent risk factor for vitamin D deficiency in Turkish women living in Turkey and Germany. A strong correlation between low 25(OH)D levels and higher rates and longer duration of generalized bone and/or muscle aches and pains (often diagnosed as fibromyalgia) was observed. CONCLUSION: Secondary hyperparathyroidism and vitamin D deficiency was found to be common among Turkish immigrants living in Germany, especially in veiled women. Therefore, the monitoring of vitamin D status--i.e. 25(OH)D and PTH--in Turkish immigrants is warranted and once a deficiency is identified, it should be appropriately treated.

Changes in extracranial arteries in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is linked with increased cardiovascular morbidity and mortality, possibly through an enhancement of atherosclerotic vascular changes. Up to now, however, only a few studies have tried to evaluate the occurrence of atherosclerosis in patients with OSA. In the present study, ultrasonography of the large extracranial vessels was performed in a group of consecutively admitted OSA patients (n = 35) and a control group of non-OSA patients (n = 35). Common carotid artery-intima media thickness (CCA-IMT) was measured at the far wall of both proximal carotid arteries. Furthermore, the presence of plaques and stenoses of the extracranial vessels was determined. All measurements were carried out blinded to the status of the patients. In the OSA group, CCA-IMT was significantly increased when compared with the non-OSA patients and was related to the degree of nocturnal hypoxia. Additionally, the formation of plaques was more pronounced and extracranial vessel stenosis was more common in the OSA patients. In conclusion, these findings are in favour of an independent influence of obstructive sleep apnoea on atherosclerotic changes of the arterial wall, and represent further strong arguments for obstructive sleep apnoea being a risk factor on its own for the emergence of cardiovascular disease.

Analysis of genetic polymorphisms at the interleukin-10 loci in aggressive and chronic periodontitis.

BACKGROUND/AIMS: Different cytokine genotypes have been described in periodontal disease. The aim of the present study was to investigate the genetic association of two previously described interleukin-10 (IL-10) polymorphisms in patients with aggressive (AP) and chronic periodontitis (CP) and to investigate possible associations with clinical manifestations. METHODS: Based on clinical parameters and radiographs, 23 patients with CP and 18 patients with AP were included in the study. Additionally, 21 age-matched healthy subjects served as a control group. Genomic DNA was isolated from whole blood samples and the IL-10 promoter sequences from positions - 597 to - 824 were amplified by polymerase chain reaction (PCR). Polymorphisms were detected by restriction-enzyme cleavage. The A and C alleles at the - 597 position were associated with the T and C alleles at the - 824 position, respectively. Fisher's exact test was used for the statistical analysis. RESULTS: No significant differences were observed in the allele frequencies between controls and AP patients (p = 0.70) or CP patients (p = 0.43), although the previously reported association between allele A at position - 597 and allele T at position - 824 was observed in our population. CONCLUSION: We conclude that the investigated polymorphisms are not associated with periodontal disease.

[Immunomodulation by herbal agents. A double-blind study in a medical university hospital involving a hepatitis B vaccine adjuvant model]. / Immunmodulation durch pflanzliche Wirkstoffe. Doppelblindstudie an einer medizinischen Universitätsklinik am Adjuvansmodell zur Hepatitis-B-Impfung.

AIMS: Using the hepatitis B vaccination as a model, to investigate the extent to which the herbal immunomodulator, Esberitox N, supports seroconversion. METHOD: 346 medical students participated in the placebo-controlled, randomized double-blind study. They took 3 x 2 tablets of the test substances daily, beginning 3 days prior to the injection and ending two weeks after it. The target outcomes were seroconversion and the level of the anti-HBs titer. RESULTS: The data of 157 volunteers treated with the test substance, and 161 treated with placebo were analysed. After the first injection, the seroconversion rate was 22% in both test substance and placebo groups, and showed no advantage for the volunteers receiving the test substance. After the second injection, 89% of all members of each group revealed seroconversion. After the first injection, anti-HBs titers were appreciably higher in the test substance group (n = 34) than in the placebo group (n = 36; PWilcoxon = 0.003). The respective median values were 37.0 IU/L (95% CI: 18-68) and 15.5 IU/L (95% CI: 8-30). CONCLUSION: The immunomodulator tested has negligible influence on seroconversion, but does enhance the immune response of subjects experiencing seroconversion.

Interobserver and intraobserver reliability of venous transcranial color-coded flow velocity measurements.

BACKGROUND AND PURPOSE: Venous transcranial color-coded duplex sonography is a new technique for noninvasive evaluation of the intracranial venous system. However, the interobserver and intraobserver reliability of this method is unclear. METHODS: In 23 healthy volunteers (30 +/- 7.3 years of age), the deep middle cerebral vein (dMCV), basal vein (BV), vein of Galen (VG), and straight (SRS), transverse (TS), and superior sagittal (SSS) sinuses in addition to the arterial segments of the circle of Willis were insonated through the temporal bone window on 2 consecutive days by 2 experienced examiners. The examiners were blinded to each other's results. The interobserver and intraobserver reliability was calculated using a method described by Bland and Altman, resulting in 2-SD confidence intervals. RESULTS: Non-angle-corrected and angle-corrected systolic and end diastolic venous flow velocities (FV) were in good accordance with published normal values, ranging between 8.6 and 19.2 cm/s. The interobserver reliabilities for non-angle-corrected systolic FVs in the dMCV, BV, VG, SRS, and TS were +/- 1.8, 2.4, 2.6, 3.3, and 4.6 cm/s; for angle-corrected systolic FVs, the interobserver reliabilities were +/- 2.5, 3.1, 13.9, 11.6, and 7.7 cm/s. The intraobserver reliabilities for non-angle-corrected systolic FVs in the dMCV, BV, VG, SRS, and TS were +/- 2.9, 3.2, 2.6, 3.2, and 6.1 cm/s; for angle-corrected systolic FVs, the intraobserver reliabilities were 3.2, 3.7, 13.9, 11.6, and 7.5 cm/s. Angle correction was not attempted for the SSS. The interobserver and intraobserver reliabilities for systolic FVs in the SSS were +/- 3.3 and +/- 3.3 cm/s, respectively. CONCLUSIONS: Intracranial venous FVs can be measured with a high interobserver and intraobserver reliability in healthy human subjects. Intraobserver reliability was higher for cerebral veins than for dural sinuses, predisposing them for follow-up examinations; however, angle correction for venous FVs in the VG and the SRS is not advisable.

[Multiple carcinomas in the upper aerodigestive tract. 1. Oral cavity and oropharynx]. / Mehrfachkarzinome im oberen Aerodigestivtrakt. Teil 1: Mundhöhle und Oropharynx.

BACKGROUND: During the last years an absolute increase of tumour incidence of squamous cell carcinoma as well as an increase in the occurrence of synchronous and metachronous multiple primaries in the upper aerodigestive tract can be observed. This study analyses the so-called "multi-centric cancerization" in patients with primary carcinoma of the oral cavity and the oropharynx. METHODS: During 2 observation periods of 5 years each, from 1985 to 1994, we retrospectively analyzed 235 patients with squamous cell carcinoma of the oral cavity and 232 patients with tumour localisation in the oropharynx. Besides age, sex, tumour localization, TNM-stage and grading, the risk factors tobacco and alcohol were added as causes for the development of multiple primaries. RESULTS: In the primary localisation of the oral cavity synchronous and metachronous double tumours increased from 7% to 17% besides the absolute increase in tumour incidence. In the oropharynx a total increase of second carcinomas from 3% to 20% was found. At the same time a growing abuse of tobacco and alcohol could be observed. CONCLUSIONS: Panendoscopy during pre-therapeutical staging should be obligatory. Regular oncological controls are mandatory, especially for younger patients with smaller tumours and good prognosis, but a high risk of second primaries. In the long run, prevention has to play a decisive role in the fight against second primary tumors of the upper aerodigestive tract. Possible improvements of early diagnosis, genetical examinations, information campaigns as well as research of carcinogenic environmental pollutants are of foremost interest to the clinician.

Lack of association between alpha 1-antichymotrypsin polymorphism, Alzheimer's disease, and allele epsilon 4 of apolipoprotein E.

We investigated the possibility that a polymorphism of alpha 1-antichymotrypsin modifies the risk for Alzheimer's disease (AD). Testing 147 AD patients and 74 controls, we did not find evidence of an association between alpha 1-antichymotrypsin polymorphism and AD and also failed to detect a modifying effect of this polymorphism in patients carrying at least one epsilon 4 allele of apolipoprotein E.

[The pT-classification of primary vocal cord carcinomas and its significance for T-classification]. / Die pT-Klassifikation von primären Stimmlippenkarzinomen und ihre Bedeutung für die T-Klassifikation.

Since the pretherapeutic T and pT classification of vocal cord cancer according to the UICC has often been found to fail in a high percentage of cases, frequently resulting in an insufficient separation of the different T categories, the pT classification proposed by Glanz was applied in order to obtain a more exact and better reproducible pretreatment system. In a histopathological investigation of 223 previously untreated carcinomas of the vocal cord dating from 1978 to 1988, specimens from total and partial laryngectomies were examined by subserial sectionings. The extension of each lesion was ascertained by measuring tumor in three dimensions per millimeter and determining affected histopathological structures. Neck lymph nodes were also examined for metastases. The different tumor stages were then evaluated with the UICC T/pT classification of Glanz's pT classification. The survival rates and recurrence-free rates of both classification systems were compared. Our evaluation showed that 24% of all the vocal cord cancers studied had to be classified to a higher tumor stage. The pT classification developed by Glanz was better able to separate the different tumor categories than the UICC T/pT classification. Glanz's pT classification system, staging a glottic cancer according to its exact size and laryngeal structures involved, is a significant improvement on the UICC T and pT classification used to date.

[Absorption and renal elimination of bismuth from 6 different bismuth salts after a single dosage]. / Resorption und renale Elimination von Bismut aus sechs verschiedenen Bismutsalzen nach einmaliger Dosierung.

The absorption and renal excretion of bismuth from seven pharmaceutical bismuth preparations was studied in five healthy volunteers. Following a single oral dose of colloidal bismuth subcitrate (CBS), basic bismuth salicylate (BSS), basic bismuth gallate (BSG), basic bismuth carbonate (BSC), bismuth aluminate (BA) and two different basic bismuth nitrate (BSN) preparations, ingested one hour prior to the breakfast, containing 350 mg bismuth in all but one bismuth subnitrate compound, the latter was given in a 1480 mg dose laid on granulated gum karaya, the bismuth serum concentrations (0 to 6 h) and urinary excretion (for 2 days) were measured. Slight amounts of bismuth were rapidly absorbed in all experiments with low transient mean peak concentrations between 0.6 (BSN) and 9.1 micrograms/l (CBS)--reached within 20-60 min--with a wide intra- und interindividual variability. The highest peak serum bismuth concentration was 18 micrograms/l in response to CBS. The median integrated 6-hour serum bismuth concentration after dosing with CBS and BSG was 49 and 32 ng h/ml, respectively, after dosing with BSC, BA, BSS, BSN and BSN1480 13, 11, 3, 0 and 5 ng h/ml, respectively. The values for CBS were significantly greater than after BSS and BSN350. There was a very strong overall correlation between 48-h urinary bismuth excretions and the corresponding integrated 6-hour serum bismuth concentrations (p < 0.001).