Induction of antigraft and antirecipient antibody responses after fully allogeneic and semiallogeneic rat small bowel transplantation

BACKGROUND: Given the potential influence of alloantibodies on organ graft outcome, this study investigated the induction of antigraft and antirecipient antibodies after allogeneic and semiallogeneic rat small bowel transplantation. METHODS: Fully allogeneic, unidirectional rejection and unidirectional graft-versus-host disease (GvHD) heterotopic small bowel transplantation was performed using DA, PVG, and (PVGxDA)F1 donor-recipient combinations. Serum was obtained before and at time points after transplantation and incubated with blood from untransplanted DA and PVG rats. Antibody binding to T cells was detected by whole blood flow cytometry using FITC-conjugated anti-rat IgM murine monoclonal antibody. Antibody levels were determined by reference to a standard curve of fluorescent intensity generated using a serum sample with known anti-target cell IgM activity. Data are presented as arbitrary units/ml (AU/ml). RESULTS: In the PVG-->DA combination, five of six DA recipients had detectable anti-graft (PVG) antibodies by day 4 after transplantation (mean 72 AU/ml) and all animals were positive by day 6 (976 AU/ml). Antirecipient (DA) antibodies were also induced, however, they were only apparent after 6 days in five of eight animals (90 AU/ml). Antigraft (DA) antibody responses were also induced in the DA-->PVG combination (day 6-218 AU/ml), however no antirecipient (PVG) response was apparent. Transplantation induced antirecipient (DA) antibodies in the unidirectional GvHD model (day 6-90 AU/ml) and an anti-graft (PVG) response in the unidirectional rejection model (day 6-60 AU/ml). However, the latter was quantitatively lower than that generated in the PVG-->DA combination (day 6-976 AU/ml). CONCLUSIONS: Antigraft and antirecipient antibody responses are simultaneously induced after fully allogeneic small bowel transplantation, despite rejection being the predominant clinical feature. Further studies are required to elucidate their influence on graft outcome.     

Workforce planning. Of one mind

The NHS is heavily reliant on locum doctors, many of whom trained overseas. It is important they are appropriately trained so they can be integrated into the workforce. A pilot nine-session course for consultant locum psychiatrists was well received by participants. Medical directors have expressed willingness to pay for locums to attend such courses.     

History of Varicella Zoster Virus

The earliest reports of vesicular rashes of the type we now recognize to be caused by herpes simplex and zoster date to the ancient civilizations. It was not until 1888, however, that a relationship between herpes zoster and chickenpox was suggested. Establishing this link represented one of the major hurdles in the history of varicella zoster virus. There was no animal host and this meant that much of the evidence needed to be obtained by clinical and epidemiological observation. Since the link was proven, in the 1950s, the advent of the live attenuated vaccine virus, in 1974, and aciclovir in the 1980s, has had a huge impact on prevention and treatment, respectively. The complete DNA sequence of VZV was established in 1986. A more complete understanding of the VZV genome and its gene products may enable recombinant vaccines and specific therapies to be advanced. We also need to determine the long-term effects of the use of the varicella vaccine. The ultimate aim: to prevent VZV infection completely.     

Understanding spontaneous output fluctuations of an amperometric glucose sensor: effect of inhalation anesthesia and use of a nonenzyme containing electrode

Implantable glucose sensors are often unstable in vivo. Possible causes include local oscillations of glucose or oxygen levels, fluctuation of interferants, and external electromagnetic interference. To better understand glucose versus nonglucose mediated fluctuations, we compared sensors fabricated with glucose oxidase versus blank electrodes without enzyme in rabbits. We also investigated the effect of general anesthesia. We used power spectral analysis to investigate transmitted signals from amperometric peroxide sensing devices 2-3 weeks after subcutaneous implantation. Fasted animals were studied for 90 minutes in the conscious state and for 90 minutes during halothane anesthesia. Animals exhibited almost no body movement during the studies. In the conscious state, enzyme active sensors demonstrated more oscillations than blank electrodes at almost all frequencies from 2 to > 8 cycles per hour. This finding suggested that the spontaneous fluctuations were secondary to local changes in glucose or oxygen. Because fluctuations were not seen in the blank electrode, periodic changes in interferant concentrations, electromyographic activity, or in external electromagnetic interference are unlikely. General inhalation anesthesia was associated with markedly reduced sensor output fluctuation at almost all frequencies in enzyme active sensors. We conclude that fluctuation of electrochemical glucose sensor output, unrelated to fluctuations in blood glucose, is likely secondary to spontaneous changes in the local concentration or vascular delivery of glucose or oxygen. Anesthesia may have stabilized blood flow, preventing normal spontaneous autoregulatory variation.     

Tympanometry and laser Doppler interferometry measurements on otitis media with effusion model in human temporal bones.

HYPOTHESIS: The aim of this study is to investigate the effect of middle ear fluid and pressure on tympanic membrane mobility by using laser Doppler interferometry and to compare these results with tympanometry. BACKGROUND: Tympanometry has been commonly used for evaluation of otitis media with effusion, a middle ear disease with fluid in the cavity. However, this test lacks specific interpretations of middle ear disorders based on tympanometric data. Laser interferometry, as an advanced research tool to measure middle ear function, may provide knowledge of how tympanic membrane mobility is affected by middle ear fluid and pressure. METHODS: An otitis media with effusion model was created in seven human temporal bones for conducting experiments with tympanometry and laser interferometry. Middle ear pressure varied from -20 to +20 cm water, and the amount of fluid in the middle ear was gradually increased to fill the cavity. RESULTS: The displacement of the tympanic membrane measured by laser interferometry at selected frequencies decreased significantly corresponding to the middle ear air pressure changes. Tympanometry detected middle ear pressure by the change of tympanometric peak location, but the tympanogram shape was not affected by the middle ear pressure. The middle ear fluid was detected by tympanometry with as little as 0.3 mL, and laser interferometry was able to measure the displacement change of the tympanic membrane with 0.2 or 0.3 mL fluid at different frequencies. CONCLUSION: Laser interferometry can detect the effect of middle ear pressure and fluid on tympanic membrane movement as well as tympanometry does.     

Informal carers of people with dementia: the new national carers framework

Carers of people with dementia themselves have to endure heavy physical and emotional burdens. This article examines the government's new strategy Caring About Carers (DoH 1999).