Biomedical subjects
Publications and source records attributed to G Rothstein.
Depletion of the mature marrow neutrophil stores occurs commonly in neonates with bacterial sepsis and correlates with a fatal outcome. This report discusses the feasibility and efficacy of neutrophil transfusions in such patients and describes two who received neutrophil transfusions and survived without adverse sequelae.
When neutropenia due to exhaustion of the marrow neutrophil reserve, develops in a neonate with bacterial sepsis the likelihood of survival is very small. We report such a case who was treated with a double-volume exchange transfusion using fresh unstored whole blood. We were able to determine a net gain of 5 x 10(8) neutrophils per kg. Then, in neutropenic neonatal animals, neutrophil transfusion by double-volume exchange transfusion with unstored blood was investigated.
A modified form of serum immunoglobulin G (pH 4.25) was tested for its effect on neutrophil kinetics and survival rates in neonatal rats with type III, group B streptococcal pneumonia and sepsis. Each of 30 animals received a transthoracic inoculation of 10(5) organisms/g of body weight; all died within 48 hr. When 100, 1,000, or 2,000 mg of immunoglobulin G/kg was administered intraperitoneally at the time of bacterial inoculation, survival rates rose to 20%, 90%, and 100%, respectively. Even when the immunoglobulin preparation was administered intraperitoneally 2 hr after transthoracic inoculation of bacteria, all 19 animals survived. Only seven of 15 animals survived when immunoglobulin administration was delayed for 22 hr. Immunoglobulin facilitated the neutrophil inflammatory response: when immunoglobulin (rather than an albumin control) was administered, neutrophils were released more rapidly from the storage pool and accumulated more quickly at the site of bacterial inoculation. Unlike infected control animals, immunoglobulin recipients did not develop neutropenia or depletion of the neutrophil storage pool.
In contrast to the attitude prevalent a decade ago, clinicians entertaining the diagnosis of neonatal bacterial sepsis now often place considerable reliance on the blood neutrophil count and degree of left shift. In this report we present four cases which illustrate that in some patients, no derangement of the complete blood count (CBC) is present early in the course of bacterial sepsis. In order to determine the length of time between bacterial inoculation and the appearance of changes in the CBC, we used an animal model of early onset Group B streptococcal sepsis. In adult animals we observed characteristic changes in the CBC within 1 hour of bacterial inoculation, but in neonates this latent period was considerably longer, lasting 4 hours. Thus a normal CBC might actually be expected during the first several hours of early onset neonatal sepsis. This delay in appearance of CBC changes constitutes a previously uninvestigated feature of neonatal neutrophil kinetics, the "latent period."
Because vincristine has immunosuppressive activity in animal models, has specific cytotoxic effects on lymphocytes, and does not have overlapping toxicity with other immunosuppressive agents, we designed a prospective randomized trial to evaluate the efficacy of the addition of vincristine to standard immunosuppressive therapy in heart transplantation. Patients received equine antithymocyte globulin for the first week or murine antihuman mature T cell (OKT3) monoclonal antibody for the first 2 weeks after transplantation and were maintained on azathioprine and cyclosporine. A steroid pulse was administered 1 day after completion of antithymocyte globulin or OKT3 monoclonal antibody and tapered off over 21 days. Vincristine was given at 0.025 mg/kg intravenously for eight dosages over 12 weeks, beginning 2 days after completion of antithymocyte globulin or OKT3 monoclonal antibody. Fifty-two patients were randomized (26 were given vincristine, and 26 were not). The addition of vincristine to the regimen of patients receiving antithymocyte globulin resulted in significantly fewer episodes of rejection at 1 month (vincristine, 0.2 +/- 0.1; no vincristine, 1.2 +/- 0.2; p less than 0.001), at 3 months (vincristine, 1.2 +/- 0.1; no vincristine, 2.5 +/- 0.3; p less than 0.001), and at 6 months (vincristine, 1.9 +/- 0.2; no vincristine, 2.9 +/- 0.3; p less than 0.001). It also resulted in significantly more patients being successfully weaned off daily steroids (vincristine, 67%; no vincristine, 20%; p = 0.04). The addition of vincristine to the regimen of patients receiving early rejection prophylaxis with OKT3 monoclonal antibody did not alter rejection incidence or steroid usage.(ABSTRACT TRUNCATED AT 250 WORDS)