Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Public Financing of IVF: A Review of Policy Rationales

There is great diversity in in vitro fertilization (IVF) funding and reimbursement policies and practice throughout Europe and the rest of the world. While many existing reimbursement and regulatory frameworks address safety and legal concerns, economic factors also assume a central role. However, there are several problems with the evidence that is available on the economics of IVF. This suggests there is a need for more robust cost-effectiveness studies. It also indicates the need for alternative rationales to justify the reimbursement of IVF, which might more fully account for the social, political, ethical, and philosophical considerations embedded in notions of infertility and technology-driven reproductive treatments. The merits and limitations of five alternative rationales are discussed. The review suggests that while no existing single rationale provides a complete framework with which to support funding decisions, taken together they provide guideposts which signal important issues for consideration and highlight where further research, action, and debate are needed.     

Foreign body removal with fine-nosed forceps and assistance of image intensification

Foreign body removal has been developed as a routine radiology department service. Techniques, indications and hazards are described.     

The nature of focal areas of hyperfluorescence or hot spots imaged with indocyanine green angiography

PURPOSE: To clarify the frequency and nature of ICG angiographic "hot spots" seen in patients with neovascular age-related macular degeneration (ARMD). METHODS: A consecutive series of newly diagnosed patients with neovascular ARMD and fluorescein angiographic evidence of occult choroidal neovascularization (occult CNV) was imaged with ICG angiography. Eyes with ICG angiographic "hot spots" were identified and further classified. A hot spot was defined as any area of abnormal hyperfluorescence, in the mid to late stages of ICG angiography, measuring less than 1 disk area in size. RESULTS: From a total of 190 patients (220 eyes) with neovascular ARMD, 30 patients and 34 eyes (16%) with hot spots were identified. Hot spots were noted to be of three distinct patterns: polypoidal choroidal neovascularization (polypoidal CNV) in 21 of 34 eyes, or 62%; retinal angiomatous proliferation (RAP) in 11 of 34 eyes, or 30%; and focal occult CNV in 2 of 34 eyes, or 8%. CONCLUSIONS: A focal area of intense hyperfluorescence or so-called hot spot seen on ICG angiography in neovascular ARMD is due to one of three possible forms of neovascularization: most frequently polypoidal CNV, less commonly RAP, and infrequently nonspecific, focal occult CNV. Since neovascular ARMD may be caused by different types of neovascularization, each with distinct clinical manifestations, natural course, visual prognosis, and response to treatment, it is important to identify the precise nature of hot spots to establish an accurate diagnosis and, when appropriate, a specific form of management.     

Cu, Fe, Mn, and Zn chelates offer a medicinal chemistry approach to overcoming radiation injury

This review points out that treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates facilitate tissue repair processes required for recovery from radiation injury including survival of lethally irradiated mice and rats. Results of studies pertaining to successful uses of bioavailable essential metalloelement chelates and combinations of them as well as aminothiols, Ca-channel blockers, acyl Melatonin homologs, substituted anilines, and curcumin radioprotectants are included in this review to suggest their use as chelates in overcoming radiation injury. Additional reports document that non-toxic doses of essential metalloelement chelates are effective in increasing survival and repairing radiation injury when administered before irradiation, in the radiation protection paradigm, and effective in increasing survival when used to treat after irradiation, in the radiorecovery paradigm. There are no other agents known to be effective in increasing survival when they are used to treat after irradiation. These approaches to radioprotection and radiorecovery offer promising approaches to facilitating recovery from radiation-induced injury experienced by patients undergoing radiation therapy for their neoplastic disease and by individuals who experience environmental, occupational, or accidental exposure to ionizing radiation. These individuals include those exposed to radiation resulting from nuclear accidents, the use of depleted uranium missiles, and astronauts undertaking space travel. Since there are no existing safe and effective treatments of radiation injury, studies of essential metalloelement chelates and combinations of them, as well as combinations of them with existing radioprotectant aminothiols, Ca-channel blockers, acyl Melatonin homologs, substituted anilines, and curcumin as radioprotectants seem worthwhile.     

Amyotrophic lateral sclerosis in Olmsted County,Minnesota, 1925 to 1998

The authors sought to determine trends in the incidence of ALS in Olmsted County from 1925 to 1998. Seventy-seven cases of ALS were identified during the period studied. The incidence rate remained stable at 1.7 cases per 100,000 people per year. Mean age at onset was 63 years. Mean survival was 23 months from diagnosis. Mean survival for patients <60 years old was 31 months; for patients aged >or=60 years, it was 20 months (p = 0.02). Mean time from symptom onset to diagnosis was 13 months. Neither survival nor time to diagnosis changed significantly over time.     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.