Acute porphyria, though rare, has well-known neurological sequelae. Vasospasm rarely complicates exacerbations of acute intermittent porphyria, but has not been previously reported in hereditary coproporphyria. We describe a porphyric crisis in a woman with previously undiagnosed hereditary coproporphyria (triggered by rifampicin), leading to vasospasm and stroke.

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This study was instituted to determine the mechanism of enhanced natural killer (NK) lymphocyte activity during surgery. Natural cytotoxicity of whole blood to K562 target cells was assayed before anesthesia and during anesthesia and surgery in patients with benign and malignant gastrointestinal disease. Those patients with benign conditions and localized primary tumors showed enhanced NK lymphocyte cytotoxicity during surgery (p less than 0.025 and p less than 0.0025, respectively) but not patients with disseminated tumors. In patients with localized tumors, enhancement of NK lymphocyte cytotoxicity was an interferon-independent phenomenon but appeared to be related to a significant rise in the percentage of cells bearing the Leu 7 monoclonal antibody marker for NK cells (p less than 0.02). Exogenous leukocyte interferon caused further enhancement of NK cytotoxicity in patients with benign disease and some cancer patients. Enhancement of NK lymphocyte activity during surgery may be of significance in reducing tumor metastases by stimulation of natural cytotoxic mechanisms to circulating tumor emboli.

The calmodulin antagonist W7 and 4 of its analogues were examined for their ability to inhibit human NK cell mediated cytotoxicity. With the exception of one of these compounds, which is extremely hydrophobic, there was a good correlation between the ability of drugs to inhibit human NK antitumour cytotoxicity and calmodulin-dependent phosphodiesterase activity in vitro. The most potent of the compounds, 5-iodo-1-C8, an analogue of W7, has an IC50 of 3 microM upon biological and biochemical assay. This particular compound is both more potent and specific than the parent compound W7, is non-toxic to cells over the range used and is also capable of inhibiting the biological activity of NK cells upon pre-treatment of the effector cells, inferring the mechanism of NK cytotoxicity to be calmodulin dependent.

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