Generation of a glycosylated asparagine residue through chemoselective acylation of a glycosylhydrazide.

Herein, we report the first selective anomeric N-acylation of a glycosylhydrazide. We show that this transformation can be harnessed to generate amino acid building blocks including FmocAsn(GlcNAc)OH (1), a residue that has been previously shown to be a competent reagent in the solid-phase peptide synthesis of N-linked glycopeptides.

Use of the FAB criteria for the diagnosis of acute erythroleukaemia (AEL).

The criteria proposed by the French-American-British (FAB) Group for the diagnosis of acute erythroleukaemia (AEL), including the requirement for greater than or equal 30% marrow myeloblasts, were used in a review of patients with erythroleukaemia. Ten patients with AEL were identified, and a further twelve patients with marrows suggestive of AEL but having less than 30% myeloblasts were classified as having refractory anaemia with excess of blasts (RAEB). The AEL patients had a poor prognosis, poor response to chemotherapy, and none showed evolution to myeloblastic or monoblastic leukaemia. In contrast, the patients with RAEB appeared to survive longer, respond better to chemotherapy, and several evolved into typical myelogenous leukaemia. The FAB criteria subdivides patients with erythroleukaemia into groups with apparent clinicopathological and prognostic differences. Further studies using these or equally strict criteria are required.

Severe megaloblastic bone marrow change associated with unsuspected mild vitamin B12 deficiency.

Two patients are reported who developed peripheral blood abnormalities and marked megaloblastic bone marrow change within eleven days of cardiac bypass surgery. The patients were shown to have unsuspected mild vitamin B12 deficiency due to Addisonian pernicious anaemia. The megaloblastic changes were presumed to be precipitated by the increased demand for erythrocytes and platelets after surgery.

Chemotherapy and immunotherapy for acute myelogenous leukemia.

Eighty-six consecutive untreated adults with acute myelogenous leukemia were treated with a combination of Adriamycin, vincristine, prednisolone, Cytosine Arabinoside, and BCG. Complete remission was achieved in 39 (45%) patients; these patients were then allocated on an alternate basis to receive BCG and monthly chemotherapy with or without weekly irradiated allogeneic blast cells. The median duration of remission was eight months and was the same for both groups. The median survival of those achieving complete remission was 19 months compared with two months for those not achieving complete remission. Nine patients are still alive without relapse and five of these patients have been disease free for more than three years.

Plasma cell leukemia (PCL): A report on 15 patients.

Fifteen patients presenting with plasma cell leukemia (PCL) are reported in detail. The clinicopathologic features of PCL differ from typical myeloma and resemble those of acute leukemia: patients with PCL have less bone disease but a much higher incidence of organomegaly and tissue infiltration as well as diffuse marrow involvement and more pronounced pancytopenia. One of the reported patients developed meningeal plasma cell leukemia and is reported in detail. Cytomorphologic assessment of PCL cells showed nuclear immaturity and obvious nuclear/cytoplasmic asynchrony. Despite the use of cytotoxic agents known to be effective in myeloma, the prognosis in PCL is poor, and the median survival of the reported patients was only 2 mo.

Combination chemotherapy for acute lymphoblastic leukaemia in adults.

Fifty-one adults with acute lymphoblastic leukaemia were entered into a trial of intense initial chemotherapy and early "prophylaxis" of the central nervous system (CNS). Initial treatment with OPAL (Oncovin (vincristine), prednisolone, adriamycin (doxorubicin), and L-asparaginase (colaspase)) followed by craniospinal or cranial irradiation and intrathecal methotrexate produced remission in 36 patients (71%). Seventeen of these patients relapsed three to 18 months after the start of remission; the remainder had been in remission for 12 to 52 months by the end of the study. The predicted median duration of complete remission was 18.5 months. None of the four patients who initially had clinical evidence of CNS disease, three of whom also had leukaemic cells identical to those found in Burkitt's lymphoma, achieved remission. Those patients who initially had hepatomegaly or splenomegaly had a shorter remission than those without. The predicted median survival was 27 months in those who achieved complete remission, one month in those who did not, and 21 months overall. The addition of colaspase and doxorubicin to vincristine and prednisolone and the use of early CNS treatment clearly improved the remission rate among adults with acute lymphoblastic leukaemia, though the presence and length of remission was affected by the extent of disease at presentation. Burkitt-like leukaemia, which had a poor prognosis, is probably a separate disease and may benefit from a different therapeutic approach.

Impairment of platelet function by growth-hormone release-inhibiting hormone.

Synthetic cyclic growth-hormone release-inhibiting hormone (G.H.-R.I.H.) impaired platelet aggregation in each of four healthy men given 6-hour infusions. The effects lasted over 24 hours in three of them. There was no consistent change in platelet-counts during the infusions, but 18 hours after the end of the infusions there was a slight but significant increase in platelet-count. There was no change in prothrombin-time, partial thromboplastin-time, fibrinogen titres, and fibrinogen-degradation products. Incubation of G.H.-R.I.H. with blood in vitro did not affect platelet aggregation. Similar impairment of platelet function has been reported by others in baboons given linear G.H.-R.I.H. Infusions in the four healthy men studied also produced abdominal pain, dizziness, and diarrhoea in three, as have been reported in patients similarly infused. Although other side-effects or impairment of platelet-counts or bleeding-tendencies have not been reported in patients infused for up to 72 hours, caution should be exercised when using G.H.-R.I.H. over extended periods until further data on its toxicity are available.