Epidemiologic aspects of cancer prevention in Germany

In Germany, as in other highly industrialized countries, cancer is the second most common cause of death. With approximately 210,000 individuals dying each year from malignant tumours, roughly one in four deaths in Germany can currently be attributed to cancer. Only in the past few years has there been a slow decline in the age-standardized mortality rates for cancer, even among men. This follows a long period of some decades, during which the mortality steadily increased and then persisted at a high level. The reversal, however, does not mean that the situation is no longer a cause for concern. In fact, for the most common cause of death, namely the cardiovascular diseases, a much greater decrease in mortality has been observed for many years now. If this trend continues, cancer could become the largest killer in another 15 to 20 years. On the other hand, we have been aware since the end of the 1960s that the majority of cancers are caused by environmental influences and are thus, in principle, avoidable. In the present contribution we present: (a) the fundamental arguments to support the thesis that a large proportion of cancers, and of cancer deaths, could be avoided; and (b) an estimate for Germany of both the theoretical potential of primary cancer prevention and also the practically attainable potential. The estimates are based on very conservative assumptions. They yield, for the theoretical potential, values in the range 43–65% and for the reduction actually obtainable in the medium term due to primary prevention, values of 18–31%. Received: 9 March 1999 / Accepted: 26 April 2000     

Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group

BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). METHODS: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens. RESULTS: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders. CONCLUSIONS: Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.     

Geriatrie in Wissenschaft und Forschung

Zum Thema Die demographische Entwicklung in Deutschland zeigt eindeutig gesundheitspolitischen und wissenschaftlichen Handlungsbedarf. Sind gegenw?rtig 16,1% aller Deutschen 65 Jahre und ?lter, werden es nach Hochrechnungen im Jahre 2015 21,6% und im Jahre 2030 27,3% sein [13]. Durch diese Ver?nderungen in der Bev?lkerungszusammensetzung gewinnen die chronischen Krankheiten zunehmend an Bedeutung. Ganz abgesehen von der ?konomischen Tragweite (z. B. des Morbus Alzheimer) besteht bei den meisten Alterserkrankungen und den Faktoren, die sie bedingen, ein gro?es Wissensdefizit. Die Forschung weist hier einen gro?en Nachholbedarf auf. Der vorliegende Artikel beschreibt den gegenw?rtigen Stand der geriatrischen Wissenschaft und Forschung in Deutschland und leitet daraus Empfehlungen für die zukünftige Entwicklung ab.     

Complex level alterations of the 2<Emphasis Type="Italic">f</Emphasis><Subscript>1</Subscript>−<Emphasis Type="Italic">f</Emphasis><Subscript>2</Subscript> distortion product due to hypoxia in the guinea pig

It is controversially discussed inasmuch acute hearing disorders might originate from impaired cochlear circulation. Hypoxia-specific alterations of inner ear parameters measurable in patients with acute sensorineural hearing loss would therefore be of great interest. Aim of this study was to characterize hypoxia-related alterations of the 2f ₁−f ₂ distortion product. Nine guinea pigs were anaesthetized by i.m. administration of Midazolam, Medetomidin and Fentanyl. For introduction of hypoxia, the spontaneously breathing animals were offered a gas mixture of N₂O and O₂ containing either 21 or 12–13% O₂. Distortion product otoacoustic emissions (DPOAEs) were continuously monitored at f ₂ = 16 kHz; f ₂/f ₁ = 1, 2; DP-definition = 2f ₁−f ₂; L ₁ = 65 dB and L ₂ = 55 dB, while inhaled oxygen was switched from 21 to 12–13% and back. Oxygen saturation (SaO₂) was continuously monitored. Data from an hypoxic interval were only used for further data processing if DPOAE levels were stable before and after hypoxia. Six hypoxic intervals in five animals fulfilled the stability criterion. During the hypoxic interval with the highest measured SaO₂ (75%), no alterations of DPOAE levels were observed. During the remaining five hypoxic intervals, when SaO₂ ranged between 57 and 70%, DPOAE levels were on average lower with an increased standard deviation compared to mean pre-hypoxic levels. Mean decrease correlated with the decrease of SaO₂ (r = 0.90, P = 0.014). Alterations followed a characteristic time course—when hypoxia was started, DPOAE levels exhibited a short increase before they decreased and remarkably destabilized. After re-oxygenation DPOAE levels showed a pronounced level decrease, while SaO₂ already had recovered to pre-hypoxic values. After reaching a minimum, DPOAE levels slowly recovered to pre-hypoxic values. The decrease of DPOAE levels during hypoxia and the post-hypoxic level alterations have similarly been described by other authors before, while the distinct destabilization and transiently increased DPOAE levels have not been explicitly mentioned. A micromechanical mechanism that might explain a transient level increase and the post-hypoxic DPOAE level changes is discussed.     

Viral hepatitis in Germany: poor vaccination coverage and little knowledge about transmission in target groups

Background  

In Germany, vaccination against hepatitis B is recommended for infants, children and adolescents since 1995 and for specific target groups since 1982. Little is known about knowledge about viral hepatitis and attitudes toward hepatitis B vaccination-factors likely to influence vaccine uptake.     

Vertebral hemangioma late results of retrograde embolization—stabilization with methyl methacrylate in two cases

In two cases of hemangioma of the D7 and L1 vertebral bodies intraoperative posterior filling of the angioma was described. The technique allowed a conveniently bloodless operation, which resulted in stabilization. No other stabilization was necessary. Six months after the procedure an increase of vertebral body density was seen radiologically.     

Application of DNA filter hybridization and PCR to distinguish between human and non-human tissues of poor quality

Summary The present report describes a novel approach for the identification of human or non-human specimens after long-term storage in a badly preserved state. The application of the PCR-technique (polymerase chain reaction) using human-specific primers as well as Southern blot (filter) hybridization of the sample DNA to a primate-specific DNA probe enabled us to extend the positive identification beyond the limits of conventional methods such as serological or morphological examinations.     

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

Purpose The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [¹²³I]FP-CIT.Methods [¹²³I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [¹²³I]FP-CIT scans with bone metabolism and perfusion scans obtained with ^99mTc-DPD and ^99mTc-tetrofosmin, respectively. As these tracers do not pass the blood–brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [¹²³I]FP-CIT scans with images of brain perfusion obtained with ^99mTc-HMPAO.Results Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V₃) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (t test, two-tailed, p<0.0001). Cortical V₃ values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [¹²³I]FP-CIT accumulation.Conclusion The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [¹²³I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinsons and Huntingtons disease, may be feasible using SPECT radioligands and small animal imaging systems.     

Factors relating to the use of physical restraints in psychogeriatric care: A paradigm for elder abuse

The purpose of this study was to address one component of the complex topic "elder abuse". A prospective observational study in the psychogeriatric unit of an acute psychiatric hospital demonstrated that 30% (n=37) of all included patients (n=122) were physically restrained. The highest incidence (48%) was found in elderly patients with severe cognitive impairments (diagnosis of dementia and/or delirium) (n=60). The most commonly used devices of physical restraints were bed rails (100%), belts (trunk 93%, limbs 40%) and chair-tables ("gerichair") (41%). Most restraints occurred at the beginning of hospitalization (83%). Physical restraints were continued for many days and on average of many hours a day. Patients with low cognitive status and serious mobility impairments showed a very high risk of being restrained (p=0.015; OR 32.0 [95% CI:2.0-515.1]). Inability to perform ADL activities increased the frequency of restraint use (p=0.035; OR27.7 [95%CI: 1.3-604.1]). As possible co-factors repetitive disruptive behaviors were found. There was no significant difference between the frequency of falls in restrained or unrestrained patients during the observational period, but fall-related fractures (n=2) only occurred in restrained patients. It is possible that restraints increase the use of benzodiazepines and classical neuroleptics.These results confirm that physical restraints remain a common practice in psychogeriatric care. No evidence-based data support the value of restraints in regard to fall prevention and control of behavioral disturbances in elderly people with serious mental illness. In contrast, these devices can have serious adverse effects and mean one of the most severe interventions in fundamental human rights.     

Impaired expression of acyl-CoA synthetase 5 in sporadic colorectal adenocarcinomas

Several pathways of fatty acid metabolism have been shown to be associated with the pathogenesis of colorectal cancer. Fatty acid acyl-CoA thioesters are formed from free fatty acids and coenzyme A by the activity of acyl-CoA synthetases (ACSs). Whilst an increase in ACS4 expression has been associated with colorectal carcinogenesis, little is known about possible pathogenetic functions of other ACS isoforms, such as ACS5, in tumourigenesis. In the present study, gene expression, protein synthesis, and enzymatic activity of ACS5 in sporadic colorectal adenocarcinomas, adenomas, and established cell lines were analysed using RT-PCR, western blot analysis, immunofluorescence, and an enzymatic assay. Enhanced expression of ACS5 mRNA and protein as well as enzymatic activity was found in adenomas and in 11 (73%; group 1) of 15 colorectal adenocarcinomas investigated, while a decrease of ACS5 was seen in four tumours (27%; group 2). However, basal ACS5 enzymatic activity was increased as a percentage of the total activity of ACSs in both groups, arguing for an absolute (group 1) or relative (group 2) increase in ACS5 enzymatic activity in all adenocarcinomas investigated. These findings are reflected by in vitro analysis of three established colorectal adenocarcinoma cell lines, in which activity of ACS5 occurred. The results suggest the involvement of ACS5 in the early genesis of colorectal cancer, most likely by modification of the transport and pool formation of long-chain acyl-CoA thioesters, as recently demonstrated for other isoforms of the ACS family.