Changing rates of physical and psychosocial impairments over 9 years in cohorts of school beginners in Germany

Objective  

The aim of this study was to investigate the prevalence of impairments of physical and psychosocial development in children commencing primary school and to analyse changes over 9 years in consecutive cohorts.     

Long-term upregulation of protein kinase A and adenylate cyclase levels in human smokers

Repeated injections of cocaine and morphine in laboratory rats cause a variety of molecular neuroadaptations in the cAMP signaling pathway in nucleus accumbens and ventral tegmental area. Here we report similar neuroadaptations in postmortem tissue from the brains of human smokers and former smokers. Activity levels of two major components of cAMP signaling, cAMP-dependent protein kinase A (PKA) and adenylate cyclase, were abnormally elevated in nucleus accumbens of smokers and in ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of the catalytic subunit of PKA were correspondingly higher in the ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of other candidate neuroadaptations, including glutamate receptor subunits, tyrosine hydroxylase, and other protein kinases, were within normal range. These findings extend our understanding of addiction-related neuroadaptations of cAMP signaling to tobacco smoking in human subjects and suggest that smoking-induced brain neuroadaptations can persist for significant periods in former smokers.     

Multidisciplinary treatment of chronic pain in the German federal state of Northrhine-Westphalia

BACKGROUND: Multidisciplinary treatment of patients with chronic pain in pain centers was studied. The conditions of all multidisciplinary pain centers in the German federal state of Northrhine-Westphalia (NRW), an area of about 17 million inhabitants, were investigated. METHODS: The study included data from the index of all registered multidisciplinary pain centers in the years 1992, 1994, 1996, and empirical data of a written (questionnaire) in 1993 from physicians and psychologists working as specialists in the pain centers studied. RESULTS: Several new pain centers (inpatient wards, outpatient pain clinics) had been built up in the last years in Northrhine-Westphalia. The pain centers are organized mostly as outpatients' departments. Departments of psychological treatment of chronic pain are usually integrated into pain clinics. In recent years, the use of qualified psychological pain treatment by psychologists has been under-represented. Pain treatment evaluation is carried out by considering the structure of supply in pain management, the qualification and specialization of physicians and psychologists and the amount of treated patients with chronic pain. The 57 pain centers in the investigated area reported on about 120,000 patients with chronic pain a year, who were treated in multidisciplinary pain centers. The estimated number of patients with chronic pain in Northrhine-Westphalia was approximately 850,000 patients (4 million in Germany). CONCLUSIONS: There is an existing network of multidisciplinary pain centers in Northrhine-Westphalia. If we consider the estimated number of 850,000 patients with chronic pain in this area, the low number of yearly treated patients (120,000) indicates, that the capacity of multidisciplinary pain centers is inadequate for the demand of multidisciplinary treatment of patients with chronic pain in Northrhine-Westphalia.     

Comparative health assessment among migrants and Germans: combined results of a school health examination and a health survey among parents

Objectives  

Previous studies on the health of migrants in Germany focus either on the health of children or on that of adults of ethnic minorities in comparison to the German population. In our study the health status of preschool-aged children and their parents among Germans and ethnic minorities was studied and interlinked.     

Effect of dietary curcumin and dibenzoylmethane on formation of 7,12- dimethylbenz[a]anthracene-induced mammary tumors and lymphomas/leukemias in Sencar mice

Female Sencar mice (6 weeks old) were administered 1 mg of 7,12- dimethylbenz[a]anthracene (DMBA) by oral gavage once a week for 5 weeks. At 20 weeks after the first dose of DMBA, 68% of mice developed mammary tumors (the average 1.08 tumors per mouse) and 45% had lymphomas/leukemias. Feeding 1% dibenzoylmethane (DBM) in AIN 76A diet, starting at 2 weeks before the first dose of DMBA and continuing until the end of the experiment, inhibited both the multiplicity and incidence of DMBA-induced mammary tumor by 97%. The incidence of lymphomas/leukemias was completely inhibited by 1% DBM diet. In contrast, feeding 2% curcumin diet had little or no effect on the incidence of mammary tumors, and the incidence of lymphomas/leukemias was reduced by 53%.      

Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice

Missense mutations in the beta-amyloid precursor protein gene (APP) co- segregate with a small subset of autosomal dominant familial Alzheimer's disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide and neurodegeneration are principal neuropathological hallmarks. To accurately examine the effect of missense mutations on APP metabolism and A beta production in vivo, we have introduced yeast artificial chromosomes (YACs) containing the entire approximately 400 kbp human APP gene encoding APP harboring either the asparagine for lysine and leucine for methionine FAD substitution at codons 670 and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high levels of A beta peptides are detected in the brains of YAC transgenic mice expressing human APP(K670N/M671L) that is associated with a concomitant diminution in the levels of apha-secretase-generated soluble APP derivatives. Moreover, the levels of longer A beta peptides (species terminating at amino acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171). These mice should prove valuable for detailed analysis of the in vivo effects of the APP FAD mutations in a variety of tissues and throughout aging and for testing therapeutic agents that specifically alter APP metabolism and A beta production.      

Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function

Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons.     

Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype–phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients. Mutation screening was performed by PCR amplification of exons 1-14 of the FAH gene, followed by SSCP analysis and direct sequencing of the amplified exons. Fourteen different mutations were found, of which seven were novel, viz. Three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g-t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g-a) were frequently found in countries around the Mediterranean and northerwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established. Hum Mutat 12:19–26, 1998. © 1998 Wiley-Liss, Inc.