Physiologic and subjective changes from smokeless tobacco withdrawal

This study prospectively examined withdrawal symptoms in persons using Copenhagen smokeless tobacco and in persons smoking cigarettes. Smokeless tobacco chewers (N = 16) and cigarette smokers (N = 11) were examined during a 6-day period, during which time a number of measures were administered. Subjects used smokeless tobacco or smoked cigarettes on an ad libitum basis for a 3-day baseline period and then underwent tobacco deprivation. The significant changes that occurred relative to baseline after smokeless tobacco deprivation included decreased heart rate and orthostatic pulse change and increased craving for tobacco, confusion, eating, number of awakenings, and total scores on a withdrawal symptoms checklist for both self-rated and observer-rated measures. There were more changes and changes of greater severity among cigarette smokers.     

Serological markers of hepatitis B infection in Niue children

Hepatitis B infection is hyperendemic in the adult population of Niue. In order to determine the age at which infection is acquired and the contribution of vertical and horizontal transmission, the sera from 1055 children were tested for markers of hepatitis B infection. Eleven percent (11.0%) were found to be carriers of hepatitis B surface antigen (HBsAg) and a further 33.6% had antibody to hepatitis B surface antigen (anti-HBs). While less than 15% of the population were infected before the age of two years, these children had the greatest risk of becoming chronic carriers. The simplest method of controlling hepatitis B infection in Niue would be to immunise all newborn babies.     

Multimodal approach using oncolytic adenovirus,cetuximab, chemotherapy and radiotherapy in HNSCC low passage tumour cell cultures

Head and neck squamous cell carcinoma (HNSCC) is a common and often devastating disease without curative treatment when advanced or recurrent. The aim of this study was to assess whether capsid-modified oncolytic adenoviruses have therapeutic efficacy in HNSCC low passage tumour cell cultures and if it could be further improved by combination with cetuximab, radiotherapy and chemotherapy. We investigated which adenoviral capsid modifications allow best gene transfer and cell killing of HNSCC substrates. Gene transfer was assessed using replication-deficient adenoviruses expressing luciferase. Cell killing was studied in vitro and in vivo using oncolytic adenoviruses, which kill tumour cell by viral replication. The most effective capsid-modified oncolytic adenoviruses were combined with HNSCC standard therapies and their efficacy was assessed in vitro as well as in vivo. Cell killing was assessed in vitro by MTS assay and in vivo by HNSCC subcutaneous tumour growth follow-up in nude mice. Cetuximab treatment was found to enrich CD133+ and CD44+ tumour-initiating type cells in tumours grown in mice. Capsid-modified viruses showed increased transduction and oncolysis of HNSCC substrates in comparison to Ad5-based agents. Polylysine (pK7)-modified oncolytic virus resulted in significant tumour growth reduction in vivo. Combination of chemotherapy (cisplatin and 5-fluorouracil), radiotherapy and cetuximab with oncolytic adenovirus therapy resulted in further increases in cell killing effect in vitro and complete eradication of tumours in vivo. Our pre-clinical data suggest that it is feasible and efficacious to combine oncolytic adenoviruses with HNSCC standard therapies into a multimodality treatment regimen for clinical testing in HNSCC patients.     

Characterization of eight different tetracyclines: advances in fluorescence bone labeling

Polychrome sequential labeling with fluorochromes is a standard technique for the investigation of bone formation and regeneration processes in vivo. However, for human application, only tetracycline and its derivates are approved as fluorochromes. Therefore, the aim of this study was to determine the fluorescence characteristics of the different tetracycline derivates to assess the feasibility of sequential in vivo bone labeling using distinguishable fluorochromes. Eight different tetracycline derivates were injected subcutaneously into growing rats as a single dose or sequentially in different combinations. After preparation of resin-embedded undecalcified bone sections, the fluorescence properties of the tetracycline derivates in bone were analyzed using conventional fluorescence microscopy, spectral image analysis and confocal laser scanning microscopy. Each tetracycline derivate exhibited a characteristic fluorescence spectrum, but the differences between them were small. Chlortetracycline could be discriminated reliably from all other derivates and could therefore be combined with any other tetracycline derivate for reliably distinguishable double labeling. Tetracycline itself exhibited the brightest fluorescence of all the investigated derivates. Interestingly, in conventional microscopy the same tetracycline derivative can appear in different colours to the human eye, even if spectral analysis confirmed identical emission peaks. In conclusion, the data suggest that fluorescence double labeling of bone is feasible using appropriate tetracycline derivates in combination with spectral imaging modalities.     

Sekundäre Endoprothetik des Ellenbogengelenks nach distaler Humerusfraktur

Good short-term results have been reported for primary total elbow arthroplasty (TEA) but implant longevity is limited. Therefore, primary TEA should be reserved in particular for older patients with severe comminuted distal humeral fractures in whom successful osteosynthesis is often impossible. Angular locking compression plates afford stable fracture fixation even for a severe intra-articular fracture pattern. To date primary TEA for treatment of severe distal humeral fractures is rarely used. Secondary TEA is used in failed osteosynthesis of distal humeral fractures and in unstable post-traumatic elbow joints with osteoarthrosis. Additionally, secondary TEA has become more popular in younger patients for immediate pain reduction and functional improvement. However, weight bearing is limited to 5 kg, racket sports are prohibited and good patient compliance is mandatory. Long-term results of TEA are poorer for trauma patients than those with rheumatoid arthritis.