Identification of early relapsing patients with adult acute nonlymphocytic leukemia by bone marrow biopsy after initial induction chemotherapy

Bone marrow biopsies obtained from 69 adult patients with acute nonlymphocytic leukemia (ANLL) six to 10 days after initial induction chemotherapy were reviewed blindly to detect the presence of residual leukemia. Discrimination between the presence or absence of leukemic cells was provided by assessment of the numbers, clustering, and nuclear morphology of blasts and promyelocytes. Twenty-six patients had frank leukemia, 25 had no apparent leukemic cells, and 18 had focal residual leukemia. Of 25 patients whose bone marrow contained no detectable residual leukemic cells, 21 gained complete remission without further chemotherapy. These patients had a median duration of remission of 278 days, with five patients still remaining in remission for 578-882 days. Similarly, all of the 18 patients who had focal residual leukemia achieved complete remission without additional chemotherapy; however, all have relapsed with a median duration of remission of 163 days. This study indicates that patients with foci of residual leukemia in their one-week posttreatment bone marrow samples readily achieve remission, but carry a substantial leukemic burden that increases the likelihood of early relapse.     

Myelopoiesis following phorbol ester exposure in human long-term bone marrow cell culture

Phorbol esters have two opposing effects on bone marrow granulocyte/macrophage colony forming cells (CFC-GM): they reduce the number of CFC-GM which respond to colony-stimulating activity (CSA), and they also induce the release of CSA from accessory marrow cells. We questioned whether the direct inhibitory effect of phorbol esters on CFC-GM was reversible and whether phorbol ester-treated accessory bone marrow cells could increase the in vitro recovery of cultured CFC-GM. Normal human bone marrow cells were exposed to phorbol-12,13-dibutyrate (PDB) for 5 days in liquid cultures. Total nucleated cell counts decreased in a dose-dependent fashion to 42 ± 6% of control at 5 × 10^?8 M PDB, and CFC-GM decreased to 20 ± 8% of control. The cultures were then washed to remove PDB and continued for up to 8 weeks. Total cell counts and CFC-GM/ml remained reduced in PDB-pretreated cultures compared to control. To determine whether this was a direct effect of PDB on nonadherent, proliferating cells or whether PDB acted indirectly by affecting adherent, accessory cells, nonadherent bone marrow cells from control and PDB-preincubated cultures were co-cultured for 8 weeks with either control or PDB-preincubated adherent bone marrow cells. Nonadherent cells preincubated with PDB had a similar growth pattern whether or not the co-cultured adherent cells had been preincubated with PDB. In contrast, nonadherent cells preincubated in control medium and co-cultured with PDB-preincubated adherent cells displayed increased numbers of nucleated cells, CFC-GM and adherent hematopoietic islands compared to control. This was associated with increased amounts of CSA present in the culture supernatants. Thus PDB causes an irreversible decrease in CFC-GM in long term marrow cultures but enhances the ability of adherent stromal cells to support normal CFC-GM growth in culture.     

Effective levels of tetanus toxin can be made in a production medium totally lacking both animal (e.g., brain heart infusion) and dairy proteins or digests (e.g., casein hydrolysates)

We have developed a fermentation medium for Clostridium tetani that results in the formation of tetanus toxin and contains no meat (e.g., beef heart infusion) or dairy (e.g., casein digest) products, thus obviating the problem of possible prion diseases. Particular preparations of hydrolyzed soy proteins, especially Quest Hy-Soy, have been found to replace both the meat extract and casein digest components of traditional tetanus toxin production media and to yield even higher toxin titers. The comparison of the traditional versus the new medium has been carried out repeatedly by us and the superiority of our medium has been consistently observed. To our knowledge, this is the first time that such a medium has been devised.     

Assessing health status and health care utilization in adolescents with chronic kidney disease

Few validated health status measures have been assessed in children with chronic kidney disease (CKD). The objective was to assess the validity of a generic health status measure, the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), in adolescents with CKD. A case-control study was performed (1) to assess scores on the CHIP-AE in adolescents with CKD compared with two control groups of age-, socioeconomic-, and gender-matched peers and (2) to compare health of patients who had chronic renal insufficiency (CRI), were on dialysis, and were posttransplantation. Seven pediatric nephrology centers recruited 113 patients (mean age, 14 yr; 39 CRI, 21 dialysis, 53 posttransplantation). Compared with 226 control subjects, patients with CKD had lower overall satisfaction with health and more restriction in activity. Positively, patients with CKD had more family involvement, better home safety and health practices, and better social problem-solving skills and were less likely to participate in risky social behaviors or socialize with peers who engaged in risky behavior. Patients who received dialysis were less physically active and experienced more physical discomfort and limitations in activities than did transplant or CRI patients. It is concluded that patients with CKD have poorer functional health status than age-matched peers. Among CKD patients, dialysis patients have the poorest functional health status. These results suggest that the CHIP-AE can be used to measure functional health status in adolescent patients with CKD.     

Into the breach: emergency psychiatry in the general hospital.

In its position at the interface between the community and the general hospital, the emergency ward (EW) serves to reconcile the complex needs of the local population with the traditional organizational structure of the hospital. In recent years, the EW has been faced with the dilemma of managing increasing numbers of psychotic patients with chronic illness and psychosocial problems. In response to this impressive growth in the utilization of psychiatric emergency services, a variety of general hospitals have developed model programs of service delivery and methods for the evaluation of their effectiveness. This paper is an overview of utilization patterns, organization of services, and assessment of the evaluation and referral model. This issues facing general hospitals in the development of emergency care are clarified. The need for further research, program development, and clinical implementation is discussed.     

Artificial oxygen carriers as red blood cell substitutes: a selected review and current status

Two distinct approaches are being explored in red blood cell substitute (RCS) development: hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon-based oxygen carriers (PFBOCs). HBOCs are based on intra- and/or intermolecularly "engineered" human or animal hemoglobins (Hbs), optimized for O2 delivery and longer intravascular circulation. Some are currently being evaluated in Phase II/III clinical studies. PFBOCs are aqueous emulsions of perfluorocarbon derivatives that dissolve relatively large amounts of O2. A PFBOC based on a 60% (wt/vol) emulsion of perfluorooctyl bromide has been evaluated in Phase II/III clinical trials. Although current PFBOC products generally require patients to breathe O2 enriched air, they render certain advantages since they are totally synthetic. This article provides a short review of the basic principles, approaches, and current status of RCS development. Results of preclinical and clinical studies including recent Phase II/III clinical studies are discussed.