Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors

BACKGROUND: Mixed allogeneic hematopoietic chimerism has previously been reliably achieved and shown to induce tolerance to fully MHC-mismatched allografts in mice and monkeys. However, the establishment of hematopoietic chimerism has been difficult to achieve in the discordant pig-to-primate xenogeneic model. METHODS: To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusion of pig bone marrow (BM). Monkey anti-pig natural antibodies were immunoadsorbed by extracorporeal perfusion of monkey blood through a pig liver, immediately before the intravenous infusion of porcine BM (day 0). Cyclosporine was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monkey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. RESULTS: Both monkeys recovered from pancytopenia within 4 weeks of whole body irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 days. Methylcellulose colony assays at days 180 and 300 revealed that about 2% of the myeloid progenitors in the BM of the cytokine-treated recipient were of pig origin, whereas no chimerism was detected in the BM of the untreated control monkey at similar times. The chimeric animal was less responsive by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that had rejected a porcine kidney transplant. CONCLUSION: To our knowledge, this is the first report of long-term survival of discordant xenogeneic BM in a primate recipient.     

Statistical "biases" in respiratory disability determinations

The manner in which pulmonary function test results are employed in the assessment of respiratory disability may be affected by 4 statistical choices: (1) choice of prediction equation(s), (2) adjustment factors (such as sex and race), (3) criterion values, and (4) method of comparison of observed to predicted normal test values. The records of 900 respiratory disability applicants were employed to estimate the direction and magnitude of the effect of these choices on the overall number of persons who would be declared "disabled" and upon the manner in which personal characteristics (e.g., sex, race, height, age) affect the likelihood of being declared "disabled." Choice of prediction equation had minor effects, and adjustment for race and sex had more significant effects. Choice of criterion value affected the overall number and, in certain instances (e.g., Social Security Disability Insurance), the distribution of "disability" declarations. Method of comparison (percent of predicted, difference of predicted minus observed or minimal value criterion) had major effects upon the distribution of "disability" declarations between population subgroups. Preliminary analysis therefore suggests that these statistical choices should be carefully manipulated in the design of a disability system to facilitate achievement of the system's goals.     

Simple pressure bandage technique for free skin grafts.

We applied sterile packed cellulose sponges in the dehydrated state as a pressure dressing from skin grafts by using the classic "tie-over" technique. At the end of the procedure, the sponges were hydrated, and provided flat, even pressure to a localized area. By using this simple technique, we obtained 26 of 27 successful free skin grafts with flat apposition.     

Leptomeningeal carcinomatosis from squamous cell carcinoma of the supraglottic larynx

Leptomeningeal carcinomatosis is an uncommon but devastating form of metastatic spread. To our knowledge, only 16 cases originating from a head and neck cancer have been reported. We describe the first case of a patient with leptomeningeal carcinomatosis arising from a laryngeal squamous cell carcinoma. Shortly after completing treatment for an advanced supraglottic laryngeal cancer, this 63‐year‐old man presented with lower limb neurological symptoms and signs. Radiological and cytological evidence of leptomeningeal carcinomatosis of the distal spinal canal was identified. He was treated with intrathecal methotrexate and palliative radiotherapy. Although his pain improved, his lower limb weakness worsened. He died 3 weeks after completing radiotherapy. Presumed mode of spread was via the haematogenous route. The natural history and management of leptomeningeal carcinomatosis are discussed. Clinicians should be aware of the uncommon possibility of leptomeningeal carcinomatosis in a patient presenting with an appropriate constellation of symptoms and signs, and a past history of cancer.