Leukocyte adhesion deficiency (LAD) is a rare disorder characterized by the congenital absence of CD18 resulting in the loss of expression of leukocyte CD11/CD18 integrins on myeloid cells with resultant life threatening infections. Hematopoietic stem cell transplantation currently provides the only available cure for this disorder. Although there have been reports of some success in transplantation using related family member donors or unrelated marrow donors with either myeloablative or non-myeloablative prepartative regimens, there is little experience with the use of umbilical cord SCT. We present here the first report of a patient transplanted with unrelated donor cord blood (UCB) for severe LAD type 1. The patient was diagnosed at 2 months of age when he presented with failure to thrive, fever, mastoiditis, and lethargy. Laboratory evaluation revealed a WBC of 165,000 (predominantly neutrophils) and flow cytometry documented the absence of neutrophil expression of CD11b and CD18. He was treated with antibiotics and surgical drainage of his mastoid bone. Since no family donors were identified, and given the need to proceed with transplant expeditiously and to minimize the risk of GVHD, unrelated donor cord blood transplant was pursued using a non-myeloablative preparative regimen. A large (16.5 × 107 TNC/kg and 9.5 × 105 CD34 cell/kg) 10 of 10 antigen matched unrelated donor cord blood unit was identified. The preparative regimen included Campath-1H3 (10 mg/d iv days -21 to – 19), fludarabine (30 mg/m2/d iv days -8 to -4) and melphalan (140 mg/m2 iv day -3). GVHD prophylaxis consisted of CSA + mycophenolate. He engrafted and was transfusion independent by day 16. He had no evidence of GVHD, and donor-host studies revealed 40% donor on day 15. His donor chimerism fell to 16% by STR on day 41 confirmed 100% recipient by VNTR. His cyclosporine was discontinued and an extensive viral screen showed no evidence of CMV, EBV, HHV6, adenovirus, or Hepatitis B. Over the next several months, his donor chimerism slowly rose to 48% where it has remained stable for the past 7 months with 44% of his granulocytes positive for CD11b/CD18. He remains clinically well off all immune suppression 13 months post-transplant with normal growth and development. Conclusion: UCB is a viable source of stem cells for LAD patients.

5-Methoxytryptophol (ML) is found in the pineal gland and is known to have biological activity especially as an antigonadotrophic agent, but methods have been lacking for its measurement in the circulation. A gas chromatography-mass spectrometry assay using a trimethylsilyl derivative has been developed for the routine measurement of ML in plasma. The assay is of great specificity and has a sensitivity of 20 pmol/l. Studies on the levels of pineal indoles in the circulation, however, have been hampered by the possibility that extraneous compounds are being cross-measured. Thus the specificity of the routine assay has been further validated by comparing it with an alternative assay system where all the major parameters were changed, i.e. derivatizing reagent, internal standard and mass number. Results that were obtained using both assay systems were closely comparable.

The pineal is the last organ in the human body, the function of which remains an almost total mystery. The pineal far from being a vestigial organ is an active secreting gland throughout life. Recent work has shown that the pineal hormone melatonin induces sleep in normal individuals while precipitating an exacerbation of psychotic symptoms in schizophrenic and severely depressed patients. The psychotomimetic drugs stimulate pineal activity whereas the antipsychotic medications suppress it. The progress of research into the function of the human pineal has been retarded by the absence of sufficiently sensitive and specific assays. The recent progress in measurement technologies has opened up the possibility of dynamic studies in pineal endocrinology. The paper outlines the background to current pineal investigations and present preliminary results on the gland's activity in man.