Mean Neutrophil Count Research Articles

Recombinant Human Erythropoietin in the Treatment of the Anemia of Prematurity: Results of a Double-Blind, Placebo-Controlled Study

To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity. A double-blind, placebo-controlled study was conducted on 80 preterm infants (< or = 32 weeks; postnatal age, 2 to 8 weeks; central hematocrit < or = 35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted. Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight, hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 +/- 4% vs 29.3 +/- 6.2%; P = .014) and absolute reticulocyte count (223 +/- 73 vs 124.9 +/- 73 x 10(9)/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months. Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants.

Effect of recombinant canine granulocyte colony-stimulating factor on peripheral blood neutrophil counts in normal cats.

Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously at a dosage of 5 micrograms/kg/day to five healthy, young adult cats for 42 days. Mean neutrophil counts +/- standard deviation increased significantly (P < 0.001) from 10,966/microL +/- 2324 to 30,688/microL +/- 5296 within 24 hours after administration of the first dosage of rcG-CSF. Mean neutrophil counts reached 52,978/microL +/- 11,207 on day 6, representing a second significant increase (P < 0.01) over the previous 5 days. Mean neutrophil counts continued to increase, reaching 66,994/microL +/- 12,419 on day 14, then remaining within a range of 66,994 to 87,839/microL throughout the remainder of the study. The maximum mean neutrophil count was 87,839/microL +/- 8,695 on day 42. Neutrophil counts remained high until the administration of recombinant canine granulocyte colony-stimulating factor was discontinued 42 days after initiation of therapy. Once the rcG-CSF administration was discontinued, neutrophil counts returned to pretreatment values within 5 days. There were no significant changes in numbers of any of the other cell lines. There was no clinically significant toxicosis associated with the administration of rcG-CSF.

Assessment of exposure to chloramphenicol and azathioprine among workers in a South African pharmaceutical plant

There have been very few published studies that have evaluated exposure to myelotoxic drugs among production workers in pharmaceutical plants. Previous studies have focussed mainly on nurses and evaluated exposure to cytotoxic drugs using urine mutagenicity as a marker of exposure. The aim of this study was to evaluate the exposure of workers involved in the production of chloramphenicol and azathioprine. Exposure was evaluated utilising biological monitoring, biological effect monitoring and environmental monitoring. Biological monitoring included plasma chloramphenicol levels, plasma 6-mercaptopurine and urine 6-thiouric acid levels. These were analysed using high performance liquid chromatography. Myelotoxic effect was assessed by measuring the haematological indices of bone marrow function. The exposed 17 workers were compared to matched controls of equal numbers. Neither substance could be detected in serum nor urine by the analytical methods employed. However, haematological indices demonstrated a significantly decreased mean reticulocyte and neutrophil count in the azathioprine exposed group. Industrial hygiene measurements demonstrated contamination of the air inside the airhood of exposed workers. In conclusion, it is evident that workers involved in the production of both these drugs are at risk of developing adverse health effects. Furthermore, more sensitive analytical methods need to be developed to evaluate absorption of myelotoxic chemicals among occupationally exposed workers.

Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level.

The purpose of this study was to optimize the dose, schedule, and timing of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administration that would best abrogate myelosuppression in patients with sarcoma. Sarcoma patients who had experienced severe myelosuppression after chemotherapy with Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dacarbazine ([CyADIC], cycle 1) were eligible. GM-CSF was administered during a 14-day period until 1 week before cycle 2 of CyADIC and was resumed 2 days after cycle 2 completion. The schedule subsequently was modified to allow the earlier administration of GM-CSF in which CyADIC was compressed from 5 days to 3 days, and GM-CSF was administered immediately after the discontinuation of CyADIC in cycle 2. To understand better the impact of GM-CSF on bone marrow stem cells, the proliferative status of bone marrow progenitors was examined during treatment. To evaluate the effects of GM-CSF on effector cells, select functions of mature myeloid cells were also examined. In the seven patients who were treated on the initial schedule, GM-CSF enhanced the rate of neutrophil recovery; however, severe neutropenia was not abrogated, By using the modified schedule in 17 patients, GM-CSF significantly reduced both the degree and the duration of neutropenia and myeloid (neutrophils, eosinophils, and monocytes) leukopenia. The mean neutrophil and mature myeloid nadir counts were 100/mm3 and 280/mm3 in cycle 1 and 290/mm3 and 1,540/mm3 in cycle 2 (P less than .01 and P less than .001). The duration of severe neutropenia (neutrophil count less than 500/mm3) and myeloid leukopenia (myeloid leukocyte count less than 1,000/mm3) were reduced from 6.2 and 6.8 days in cycle 1 to 2.8 and 1.4 days in cycle 2 (P less than .001). While 16 of 17 patients experienced severe myeloid leukopenia (less than 500/mm3) in cycle 1, only two of 17 experienced severe myeloid leukopenia in cycle 2 (P less than .001). Overall, severe neutropenia was abrogated in seven patients, which made them eligible for dose-escalation of Adriamycin. The fraction of cycling progenitors increased threefold on GM-CSF and decreased dramatically below the baseline within 1 day of GM-CSF discontinuation. The modified schedule improved the beneficial effects of GM-CSF by enhancing myeloprotection and permitting dose-intensification of chemotherapy. The increased myeloid mass and quiescent progenitors at the initiation of chemotherapy suggest that GM-CSF might allow further chemotherapy dose-rate intensification by shortening the interval between courses.

Tumor necrosis factor activity in serum from neonatal foals with presumed septicemia

Summary A study was performed to determine prevalence of tumor necrosis factor (tnf) activity in serum of equine neonates with presumed sepsis and to determine correlation between serum tnf activity and severity and outcome of disease. Twenty foals &lt;21 days old were considered suitable for inclusion in this study by satisfying clinical and laboratory criteria suggestive of septicemia. At admission, blood samples were collected from all foals for determination of serum tnf activity, then clinical course and outcome of disease were recorded. Thirty-one clinically normal foals &lt;21 days old served as controls for serum tnf activity. Serum tnf activity was estimated by use of an in vitro cytotoxicity bioassay and WEHI 164 clone-13 murine fibrosarcoma cells. Of the 20 foals with presumed sepsis, 5 had high serum TNF activity. Mean heart rate (P &lt; 0.005), mucosal petechial hemorrhages (P = 0.06), and death rate (P = 0.06) were greater in the group of foals with high serum TNF activity. These foals also had a lower mean neutrophil count (P &lt; 0.001), greater band-to-segmented neutrophil ratio (P &lt; 0.0001), and more prevalent neutrophil toxic changes (P = 0.07) than did foals without serum tnf activity (P = 0.02). Joint swelling was more prevalent in foals without serum tnf activity. Results of the study indicate that serum tnf activity is correlated with clinical criteria of sepsis in equine neonates. An association was apparent between disease severity and serum tnf activity in this group of foals with presumed septicemia.

In vivo administration of granulocyte‐macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.

Sequences of taxol and cisplatin: a phase I and pharmacologic study.

Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated.

Effects of recombinant human granulocyte colony‐stimulating factor on leucopenia in zidovudine‐treated patients with AIDS and AIDS related complex, a phase I/II study

Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II study. Treatment consisted of daily subcutaneous injections with G-CSF in a weekly increasing dose of 0.4, 2, 5 or 10 micrograms/kg body weight until a neutrophil count of more than 3 x 10(9) neutrophils/l was observed. This effective dose was continued for up to 4 weeks, followed by 4 weeks observation period without G-CSF treatment. Two patients (both with ARC) reached target neutrophil counts at the lowest G-CSF dose, whereas nine patients needed 2 micrograms/kg. One patient discontinued treatment before he reached target neutrophil counts. Mean (+/- SD) neutrophil counts before and after 1 and 4 weeks of effective dose treatment were 0.65(+/- 0.188) x 10(9), 6.016(+/- 2.595) x 10(9) and 5.54(+/- 4.237) x 10(9)/l respectively (P less than 0.01). The number of monocytes increased from 0.171(+/- 0.113) to 0.501(+/- 0.274) and 0.474(+/- 0.374) x 10(9)/l after 1 and 4 weeks of treatment (P less than 0.01). Other haematologic parameters did not change significantly. Two weeks post-treatment the numbers of neutrophils and monocytes had returned to pre-treatment values. Mild side effects consisting of bone, joint or muscle pain were observed in three patients. Two patients (both with AIDS) did not complete the study. One patient stopped treatment because of fever and malaise, attributable to a generalized cytomegalovirus (CMV) infection and one patient had to stop zidovudine treatment because of severe thrombocytopenia. We conclude that G-CSF increases the number of circulating neutrophilic granulocytes in zidovudine-treated patients at relatively low doses and with few side-effects.

Non-Hodgkin's lymphoma in patients with advanced HIV infection treated with zidovudine

We wished to determine the incidence of human immunodeficiency virus-related high-grade non-Hodgkin's lymphoma (NHL) and identify factors associated with the development of NHL in patients receiving zidovudine. Data are from a 2-year prospective, observational, multisite study of 1030 patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex who received zidovudine. Non-Hodgkin's lymphoma developed in 24 (2.3%) of 1030 patients who received zidovudine during 1463 person-years of follow-up (rate, 1.6 per 100 person-years of therapy). The relative hazard for development of NHL was stable throughout 2 years of therapy, with the risk of developing NHL 0.8% for each additional 6 months of therapy. Factors associated with development of NHL were a prior diagnosis of Kaposi's sarcoma, herpes simplex virus infection, or lower mean neutrophil count. Less strongly associated was a prior diagnosis of oral hairy leukoplakia or homosexual transmission of HIV. By Cox proportional hazards analysis, a prior diagnosis of Kaposi's sarcoma, cytomegalovirus disease, or oral hairy leukoplakia was most strongly associated with development of NHL. Our study demonstrates a relatively high incidence of NHL in patients with advanced human immunodeficiency virus disease who are undergoing antiretroviral therapy and suggests possible risk factors for development of NHL.

Non-Hodgkin's Lymphoma in Patients With Advanced HIV Infection Treated With Zidovudine

We wished to determine the incidence of human immunodeficiency virus-related high-grade non-Hodgkin's lymphoma (NHL) and identify factors associated with the development of NHL in patients receiving zidovudine. Data are from a 2-year prospective, observational, multisite study of 1030 patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex who received zidovudine. Non-Hodgkin's lymphoma developed in 24 (2.3%) of 1030 patients who received zidovudine during 1463 person-years of follow-up (rate, 1.6 per 100 person-years of therapy). The relative hazard for development of NHL was stable throughout 2 years of therapy, with the risk of developing NHL 0.8% for each additional 6 months of therapy. Factors associated with development of NHL were a prior diagnosis of Kaposi's sarcoma, herpes simplex virus infection, or lower mean neutrophil count. Less strongly associated was a prior diagnosis of oral hairy leukoplakia or homosexual transmission of HIV. By Cox proportional hazards analysis, a prior diagnosis of Kaposi's sarcoma, cytomegalovirus disease, or oral hairy leukoplakia was most strongly associated with development of NHL. Our study demonstrates a relatively high incidence of NHL in patients with advanced human immunodeficiency virus disease who are undergoing antiretroviral therapy and suggests possible risk factors for development of NHL.

Use of flow cytometry for determination of differential leukocyte counts in bovine blood

SUMMARY A flow cytometric method was developed to perform differential leukocyte counts on bovine blood. Blood specimens from 50 healthy Holstein cows were analyzed by use of a flow cytometer. The method entailed diluting blood with phosphate-buffered, hypotonic saline solution containing acridine orange, and performing a step-wise, 3-parameter analysis on the bases of cell size, cellular granularity, and granulocyte fluorescence. Initially, proportions of monocytes, granulocytes, and lymphocytes were determined by creating appropriate windows on dot plots of cell size (determined by forward light scatter) vs cellular granularity (determined by the logarithm of side light scatter). Eosinophils were resolved by analysis of granulocytes as dot plots of logarithms of green vs red fluorescence ascribed to acridine orange. Proportions of eosinophils and neutrophils were computed from data so generated. Microclumps of platelets spuriously affected counts of some granulocytes, particularly eosinophils. Differential leukocyte counts determined by flow cytometry generally compared favorably with those obtained by use of the conventional microscopic method, using Wright-stained blood films. Mean neutrophil and eosinophil counts determined by the 2 methods did not differ significantly, but lymphocyte counts determined by flow cytometry were significantly higher than those determined by microscopy (P &lt; 0.01). Correlation coefficients for counts of neutrophils, eosinophils, and lymphocytes determined by the 2 methods ranged from 0.519 to 0.833. Correlation between monocyte counts was low (r = 0.147), although mean monocyte counts determined by the 2 methods did not differ significantly. Total leukocyte counts determined by flow cytometry were significantly lower (P &lt; 0.01) than counts determined by use of an automated cell counter; correlation between the 2 counts was low (r = 0.350).

Evaluation of Recombinant Canine Granulocyte Colony‐Stimulating Factor as an Inducer of Granulopoiesis: A Pilot Study

Five healthy young adult dogs were given recombinant canine granulocyte colony-stimulating factor (rcG-CSF) at a dosage of 5 micrograms/kg/day subcutaneously for 4 weeks to evaluate the effect on complete blood cell counts. The mean neutrophil counts +/- standard deviation (SD) increased significantly (P less than 0.01) from 6,537/microliters +/- 1,726 (range, 4,950-9,512/microliters) to 26,330/microliters +/- 7,066 (range, 15,368-35,785/microliters) within 24 hours after the first injection of rcG-CSF. Mean monocyte counts +/- SD were significantly increased (P less than 0.05) from baseline values of 751/microliters +/- 168 (range, 444-891/microliters) to 2,514/microliters +/- 878 (range, 1,740-3,752/microliters) on day 5 of rcG-CSF administration. Mean neutrophil and monocyte counts (+/- SD) continued to increase reaching a maximum of 72,125/microliters +/- 15,073 (range, 50,915-96,278/microliters) and 3,972/microliters +/- 2,621 (range, 685-8,030/microliters), respectively by day 19. These increased neutrophil and monocyte counts were maintained until the administration of rcG-CSF was stopped. Blood counts returned to normal within 5 days after discontinuing the rcG-CSF. One week after discontinuing treatment, rcG-CSF was started again at 5 micrograms/kg/day subcutaneously. Within 48 hours following administration of rcG-CSF, mean neutrophil counts +/- SD increased from 5,860/microliters +/- 1,819 (range, 3,720-8,650/microliters) to 57,444/microliters +/- 8,173 (range, 43,983-68,278/microliters). Myeloid:erythroid ratios increased from a mean of 1.63:1 on day 1 prior to administration of rcG-CSF to 3.3:1 on day 10 in three dogs for which bone marrow samples were evaluated. Recombinant canine G-CSF did not cause clinically significant toxicosis in any of the dogs.

Effect of Marked Peripheral Leukocytosis on the Leukocyte Count in Ascites

Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis ( 20 × 10⁹/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 ± 9.3 ×10⁹/L, with a mean neutrophil count of 19.9±6.5×10⁹/L. The mean ascitic fluid neutrophil count was 0.064 ± 0.054 ×10⁹/L (range, 0.007 to 0.197 × 10⁹/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid. (<i>Arch Intern Med.</i>1991;151:509-510)

Effect of marked peripheral leukocytosis on the leukocyte count in ascites

Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x 10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid.

Leukocyte depletion results in excellent heart-lung function after 12 hours of storage

Extended preservation of the heart-lung bloc for 12 hours in a bovine model of heart-lung transplantation was achieved using donor core cooling, static hypothermic storage, and reperfusion on cardiopulmonary bypass with leukocyte-depleted (LD) blood. Orthotopic heart-lung transplantation was performed with (n = 4, LD group) or without (n = 4, control group) LD blood during cardiopulmonary bypass. Postoperative measurements of cardiopulmonary function were made at 2, 4, and 6 hours after reperfusion. Only 2 animals (50%) of the control group survived more than 2 hours, whereas all animals in the LD group survived the study period. Arterial oxygen tension on 100% oxygen was 535.63 ± 64.96 mm Hg and 146.45 ± 90.9 mm Kg in the LD and control groups, respectively, at 2 hours ( p < 0.5) and 524.3 ± 73.32 and 147.9 ± 255.67 mm Hg at 6 hours. Pulmonary artery systolic pressure-to-systemic pressure ratio was 0.49 ± 0.08 and 0.62 ± 0.35 at 2 and 6 hours in the LD group. Extravascular lung water was 17.81 ± 0.02 mL/kg (control group) and 11.28 ± 9.15 mL/kg (LD group) at 2 hours. At reperfusion, the mean neutrophil count was 27 ± 27 and 764 ± 635 × 10 9/L in the LD and control groups, respectively. This novel approach of leukocyte depletion during reperfusion after heart-lung preservation resulted in excellent cardiac and pulmonary protection.

Comparison of Acellular and Whole-Cell Pertussis-Component DTP Vaccines

An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.

Treatment of Cyclic Neutropenia with Granulocyte Colony-Stimulating Factor

Six patients with cyclic neutropenia were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months. All had a history of recurrent aphthous stomatitis, pharyngitis, lymphadenopathy, fever, and numerous infections during periods of neutropenia. Serial blood-cell counts, findings on bone marrow examination, and signs and symptoms were evaluated before and during the daily administration of G-CSF (3 to 10 micrograms per kilogram of body weight per day), either intravenously or subcutaneously. The kinetics of labeled autologous blood neutrophils and the migration of neutrophils to skin chambers were also measured. Recombinant human G-CSF increased the mean (+/- SEM) neutrophil counts from 717 +/- 171 per microliter to 9814 +/- 2198 per microliter (P = 0.009). In five of the six patients, the cycling of blood-cell counts continued, but the length of the period decreased from 21 to 14 days. The number of days of severe neutropenia was reduced (P = 0.002). Neutrophil turnover increased almost four-fold (P = 0.005), whereas neutrophil migration to a skin chamber was normal. G-CSF therapy reduced the frequency of oropharyngeal inflammation, fever, and infections in these patients. During the first 40 months of treatment, no typical mouth ulcers or bacterial infections occurred; recurrent gingivitis improved. We conclude that G-CSF is effective for the treatment of cyclic neutropenia in humans.

The effect of filtration on absolute and differential cell counts in fluid obtained at bronchoalveolar lavage

We have studied the effects of filtering mucus from bronchoalveolar lavage (BAL) fluid on its cellular contents. We examined BAL fluid from 18 patients without excessive endobronchial mucus, and from three patients with bronchiectasis. In the non-bronchiectatic subjects there was a fall of 18% in mean absolute cell count from 2.66 +/- SD 1.9 x 10(9) l-1 to 2.18 +/- 1.4 x 10(9) l-1 (P less than 0.05) as a result of filtration. This was due to a selective loss of macrophages and there were no significant changes in the absolute numbers of either lymphocytes or neutrophils. The differential macrophage count fell from a mean of 82 +/- 14% to 76 +/- 16%, while the mean differential lymphocyte count rose from 14 +/- 7% to 19 +/- 9% and the mean differential neutrophil count increased slightly from 4 +/- 4% to 5 +/- 4%. In the three patients with bronchiectasis the absolute cell counts were grossly raised, due almost entirely to an excess of neutrophils. In these patients, filtration reduced the absolute macrophage count by 61% and the absolute neutrophil count by 27%. Overall, change in absolute cell count correlated significantly with mucus volume (r = 0.76, P less than 0.05). Removal of mucus by filtration affects absolute cell count and may have a selective effect on cell numbers. If filtration of BAL fluid is unavoidable, its effect on cell counts should be clearly established if data from different centres are to be meaningfully compared.

Physiological, biochemical and haematological effects on horses of a phenylbutazone paste.

Five matched pairs of horses were used to investigate the biochemical, haematological and general clinical effects of a new dosage schedule of a phenylbutazone paste administered under controlled feeding conditions. One group of horses received a loading dose (8.8 mg/kg) on day 1, followed by doses of 3.3 mg/kg daily on days 2 to 8, 10 and 12 with no treatment on days 9 and 11. The second group received equivalent doses of a placebo paste. Bodyweight, skin temperature, respiratory rate, glutamate dehydrogenase activity, packed cell volume, mean corpuscular volume and neutrophil count were altered significantly in the drug-treated but not in the placebo-treated animals. From the direction and magnitude of the changes in these variables, it was concluded that they did not reflect toxic actions of phenylbutazone. Several variables were unaffected by either treatment both during and after dosing and others were significantly altered in both groups of horses. These changes were considered to be toxicologically insignificant.

Dialyzer reuse following manual reprocessing with a new sterilant, RenNew-D.

Dialysis patients are at risk for toxicity from formaldehyde used in the reprocessing of dialyzers for reuse; therefore, replacing formaldehyde as a dialyzer sterilant would be advantageous. The potential for RenNew-D as a sterilizing agent was investigated in seven stable in-center hemodialysis patients over 20 consecutive dialyses with cuprammonium cellulose hollow-fiber dialyzers. Treatment with RenNew-D showed no toxicity to patients or dialyzers except for two blood leaks occurring in one patient. The mean number of dialyzer uses was 4.9. In all the dialyzers that passed functional testing small solute clearances were maintained with reuse. The ability of RenNew-D to improve the biocompatibility of reused dialyzers was documented with mean neutrophil counts falling to only 78% of initial values during first reuse of dialyzers processed with RenNew-D compared with a decrease in neutrophil count to 2% of initial values during first use of the same dialyzers. Our results suggest that RenNew-D may be a useful alternative to formaldehyde for the purpose of dialyzer reuse. A reuse procedure that includes processing with RenNew-D is associated with improved biocompatibility, possibly because of maintenance of the blood-derived membrane coating established during prior dialysis.