Biomedical subjects
Publications and source records attributed to R L Baehner.
Infants, children, and young adults who suffer chronic and recurrent bacterial or fungal infection despite adequate numbers of circulating granulocytes and normal or elevated levels of immunoglobulins should be suspected of having fundamental defects in granulocyte functioning. This article considers clinical disorders for which there is evidence for associated defects of polymorphonuclear leukocytes.
The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutrition status and/or reversing protein-energy malnutrition was evaluated in nine children, ages 1 to 7 years (eight female), with Wilms' tumors. At the onset of treatment, eight patients received comprehensive enteral nutrition (CEN) which included intense nutritional counseling and oral supplements while one received total parenteral nutrition (TPN). Despite CEN, the initial, intense treatment period was associated with a decreased energy intake (64 +/- 27% Recommended Dietary Allowances), dramatic weight loss (22 +/- 7% by 26 +/- 17 days from the beginning of treatment), decreased skinfold thickness (< 10th percentile), and decreased albumin concentrations (< 3.2 g/dl). Four of those who initially received CEN subsequently required TPN. A total of five patients received TPN for a mean of 31 days (range 11 to 60); kcal averaged 105 +/- 9% Recommended Dietary Allowances during weight gain. At onset of TPN, the mean albumin, transferrin, total lymphocyte count were 3.02 +/- 0.45 g/dl, 155 +/- 40 mg/dl, and, 655 +/- 437/mm3, respectively; all children had abnormal anthropometric measurements and anergy to recall skin test antigens. TPN for 28 or more days supported weight gain (+ 2.44 kg), increased serum albumin (+ 0.58 +/- 0.47 g/dl) and transferrin (+ 76 +/- 34 mg/dl), and reversed anergy despite low total lymphocyte counts. During maintenance treatment, nutritional status was maintained or restored with CEN in the group who responded. These preliminary data document the severity of protein-energy malnutrition which accompanies initial, intense treatment of children with Wilms' tumors, the nutritional and immunological benefits of TPN during continuing intense treatment and the effectiveness of CEN in maintaining a satisfactory nutritional status during maintenance treatment.
Although it has been suggested that psychosocial events may trigger bleeding in patients with hemophilia, few specific instances have been described. In this report we interpret a series of atypical bleeding episodes in a child with a factor VIII deficiency. Although the specific pathophysiologic events that led to bleeding into the elbow are unknown in this child, they are probably similar to those of "psychogenic purpura." It is likely that these episodes of atypical bleeding can be interpreted in terms of conversion model and that conversion reactions in children required involvement by at least one parent.
Explore the source record for details and available documents.
To investigate the biochemical and cellular basis for the rise in polymorphonuclear leukocyte (PMN) count during epinephrine administration, PMN from subjects receiving epinephrine were studied for their capacity to adhere to nylon wool fibers and endothelial cell monolayers. After administration of epinephrine, the PMN count increased by 80% at 5 min, and isolated PMN adherence to nylon fibers fell from a base line of 44+/-2-18+/-3%. In contrast, when subjects were infused with the beta-antagonist propanolol before receiving epinephrine, the PMN count failed to rise and PMN adherence was normal. Exposure of PMN endothelial cell monolayers to 0.1 muM epinephrine led to diminished PMN adherence that could be blocked by 10 muM propanolol but not by 10 muM phentolamine. Sera obtained from subjects 5 min after receiving epinephrine or from supernates derived from endothelial cell monolayers exposed to 90 nM epinephrine inhibited PMN adherence to nylon fibers. Addition of anticyclic AMP antisera but not anticyclic guanosine monophosphate antisera to the postepinephrine sera or to the postepinephrine supernate derived from the endothelial cell monolayers abolished their inhibitory effect of PMN adherence to nylon fibers. In contrast, direct exposure of PMN to epinephrine failed to affect their adherent properties. Because it has been previously shown that endothelial cells contain beta-receptors and respond to catecholamines by raising their intracellular concentrations of cyclic AMP, and that PMN adherence is attenuated by cyclic AMP, it would appear that diminished PMN adherence after epinephrine administration is mediated through endothelial cell beta-receptor activity, which in turn impairs PMN margination in vivo and could account for the rise in circulating PMN.
The adherence of human PMNs to nylon fibers or endothelial cells is inhibited by exposure in vitro of the phagocytic cells to PGl2. The impaired adherence is transient and correlates with a rise in intracellular levels of cyclic AMP. Similarly, stimulation of human endothelial cells with sodium arachidonate, a precursor of PGl2, leads to impaired PMN adherence. On the other hand, PGl2 failed to alter O2- release and the bactericidal capacity of the PMNs. These findings suggest that PGl2 may play a role in regulating PMN adhesiveness to endothelial cells without compromising host defense.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We investigated some of the metabolic requirements for FMLP-induced aggregation, monitored spectrophotometrically at 37 degrees C in human, rabbit, and guinea pig p]olymorphonuclear leukocytes. Exposure of guinea pig polymorphonuclear leukocytes to the anaerobic glycolytic inhibitors 5 mM 2-deosy-glucose and 5 mM iodoacetamide inhibited aggregation, whereas 1 mM KCN was without effect. Ca++ and Mg++ were required for optimal aggregation; Mg++ alone partially supported aggregation, whereas Ca++ alone failed to do so. Verapamil, a divalent cationic blocker, inhibited polymorphonuclear leukocyte aggregation of all species in a dose-dependent fashion in the presence of Ca++ and Mg++ and blocked pseudopodia formation as monitored by transmission electron microscopy. Rabbit polymorphonuclear leukocytes were most response to FMLP and aggregated at concentrations as low as 2 x 10(-13)M in the presence of cytochalasin B. Cytochalasin B enhanced aggregation of both human and rabbit polymorphonuclear leukocytes but not guinea pig polymorphonuclear leukocytes in the presence of divalent cations. Unlike polymorphonuclear leukocytes from other species, cytochalasin B rabbit pretreated polymorphonuclear leukocytes aggregated even in the absence of divalent cations, and this response was completely blocked by verapamil. Human and guinea pig polymorphonuclear leukocytes demonstrated aggregatiopn responses only to concentrations as low as 2 x 10(-10)M FMLP. These studies show the unique aggregating responses of rabbit, human, and guinea pig polymorphonuclear leukocytes to FMLP and indicate the requirement for divalent cation transport and formation of pseudopia in this response for all species.
Explore the source record for details and available documents.
The incubation of human leukocytes with ascorbic acid increased chemotaxis of the cells. In addition, ascorbic acid promoted the assembly of intracellular polymorphonuclear leukocyte (PMN) with colchicine blocked the effect of ascorbic acid on promoting microtubule assembly. Not only did ascorbic acid promote the assembly of microtubules in vivo, but it enhanced the assembly of bovine brain tubulin into microtubules in vitro as quantitated by a glass-fiber filtration assay and by promotion of viscosity changes. The enhancement in leukocyte mobility by ascorbate at concentrations achievable in normal tissues correlates with its ability to assemble microtubule organelles.
In 163 children with acute nonlymphocytic leukemia (ANLL), a D-ZAPO induction program consisting of daunomycin, 5-azacytidine, cytosine arabinoside, prednisone, and vincristine resulted in a remission rate of 71.8%. Immunologic therapy was employed during maintenance with the aim of prolonging remission and improving survival. The administration of immunotherapy consisting of a mixture of bacillus Calmette-Guérin (BCG) and allogenic acute myelomonocytic leukemic cells injected intradermally on day 14 of each of the first three monthly cycles of 6-thioguanine for ten days, 5-azacytidine and cytosine arabinoside for four days, and vincristine for one day did not improve remission duration or survival compared to that due to chemotherapy alone. Important prognostic factors identified in this study included a remission induction rate significantly better for females than males (P = 0.04), for children between the ages of 5 and 10 years compared to those greater than this age group (P = 0.01), and a prolonged remission duration (P = 0.04), and survival (P less than 0.01) for patients with initial white blood counts of less than 20 x 10(9)/liter.
The 18-year-old white male developed acute myeloblastic leukemia (AML) 25 months after diagnosis of poorly differentiated lymphocytic lymphoma, diffuse pattern (PDLL-D), involving cervical, supraclavicular, and mediastinal lymph nodes as well as bone marrow. Treatment of the lymphoma consisted of 2,000 rads to the mantel area and 18 months of chemotherapy with intravenous (IV) methotrexate (400 mg/m2), vincristine, and prednisone, alternating every two weeks with IV cyclophosphamide (1,000 mg/m2), vincristine, and prednisone plus monthly intrathecal methotrexate. Thereafter, a complete remission was maintained without therapy until the onset of AML. Several pseudodiploid clones containing multiple structural rearrangements and a hypodiploid clone were identified in the circulating blood at the time of diagnosis of AML. Induction therapy consisting of cytosine arabinoside, 5-azacytidine, vincristine, and prednisone was unsuccessful, and the patient died of sepsis two months after diagnosis. This case calls attention to the increased risk for subsequent acute nonlymphocytic leukemia in patients previously treated for nonhodgkin lymphoma.
Sister chromatid exchange (SCE) frequencies were studied in peripheral lymphocytes from 16 patients with newly diagnosed acute lymphoblastic leukemia (ALL) prior to the initiation of chemotherapy. The mean SCE frequency (mean +/- SE) for these patients was 12.2 +/- 0.2 per metaphase, which was significantly higher (P less than 0.001) than the mean SCE score for 14 age-matched controls, 7.6 +/- 0.2. Five of these patients were studied again while they were receiving maintenance therapy consisting primarily of daily 6-mercaptopurine and weekly methotrexate. Their remission SCE levels remained significantly higher than controls (P less than 0.005). In addition, SCE levels were studied in 7 long-term survivors of ALL. Three of these patients had been receiving continuous maintenance therapy for at least 3 years. Their mean SCE scores were significantly greater than controls (P less than 0.005). The other 4 patients had finished their final course of chemotherapy at least 8 months prior to the time of sampling, and their mean SCE scores were not significantly different from controls (P greater than 0.10). These data indicate that untreated patients with ALL have increased SCE levels which remain elevated during periods of remission maintained with chemotherapy. However, long-term survivors of ALL who are in remission and off chemotherapy do not demonstrate significantly increased SCE frequencies.
Fifty consecutive episodes of septicemia were studied in 41 children who had acute lymphoblastic leukemia. Seventy-six percent of these episodes occurred when the absolute granulocyte count was 200/mm3 or less and were caused by gram-negative enteric and gram-positive mucocutaneous bacteria. In eight patients, Streptococcus pyogenes was isolated at the time when ALL was diagnosed. Multiple anaerobic and aerobic isolates from a single blood culture were associated with abdominal distress, whereas Streptococcus pneumoniae and Hemophilus influenzae septicemia occurred in associated with respiratory illnesses. When patients with severe compromise of anatomic barriers or respiratory disease were excluded, 94% of all patients with septicemia had an AGC of less than 200/mm3. The data provide guidelines for treatment for febrile patients with ALL based upon the AGC, the phase of the disease, and on the presence of associated respiratory or abdominal findings.
The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutritional status and/or reversing protein-energy malnutrition was evaluated in 28 children, ages 1-19 (14 female) with advanced malignant disease (21 solid tumors, 7 leukemia-lymphoma). At the onset of treatment, 21 patients received intensive nutritional counseling (INC) and oral supplementation while seven received total parenteral nutrition (TPN). Sixteen of 21 patients who received INC had a decreased intake (x 48 +/- 24%) Recommended Dietary Allowances (RDA) for kilocalories and dramatic weight loss (x 16.4 +/- 12.4%). A total of 18 patients received TPN for a mean of 24 days (7-60); kcal averaged 90 +/- 26% RDA during weight gain. At onset of TPN, the mean serum albumin, transferrin and total lymphocyte counts were 3.06 +/- 0.38 g/dl, 175 +/- 62 mg/dl, and 1102 +/- 966/mm3 respectively, 15/18 children had subnormal anthropometric measurements and 17/18 patients were anergic to recall skin test antigens. TPN for less than 9-14 days neither repleted weight, skinfold reserves, nor serum albumin concentrations (greater than 3.2 g/dl) although an early increase (p less than .02) in transferrin concentration was observed. However, TPN for 28 days supported weight gain (3.27 kg, 16 +/- 6%), increased serum albumin (0.62 +/- 0.43 g/dl, p less than .001) and transferrin (62 +/- 42, p less than .002) to normal concentrations and reversed anergy in 7/11 patients retested. This study documents the severity of protein energy malnutrition which accompanies intense treatment of children with cancer and the nutritional and immunological benefits of a 28 day course of TPN.
It was previously shown that the abnormal surface characteristics and defective bactericidal function of polymorphonuclear leucocytes (PMN) in the Chediak-Higashi syndrome (CHS) are correlated with impaired microtubule assembly, and in one patient direct electron microscopic evidence for an anomaly in microtubule assembly following surface membrane activation by concanavalin A (Con A). We show that very few microtubules are visible in CHS leucocytes from two additional patients under conditions where normal PMNs contain abundant microtubules, and that both in vivo and in vitro exposure of the CHS leucocytes to ascorbic acid promotes the assembly of microtubules. This agent, which normalizes chemotaxis and degranulation in CHS leucocytes, is shown also to correct granulocyte adherence in these leucocytes. It is suggested that the improved clinical course of patients with CHS following treatment with ascorbic acid is related at least in part to improvement of microtubule assembly and PMN function by the ascorbic acid.