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R L Baehner

Publications and source records attributed to R L Baehner.

At least 37 records · Page 2Linked to original sources
PubMed1985

Platelet-derived growth factor promotes human peripheral monocyte activation.

Like in the polymorphonuclear leukocyte (PMN), the platelet-derived growth factor (PDGF) purified to homogeneity is capable of inducing monocyte activation responses as evaluated by generation of superoxide anion (O-.2) from membrane-associated oxidase system, release of granule enzymes, and enhanced cell adherence and cell aggregation. Superoxide anion release was maximized at 10 ng/mL PDGF and was comparable to that induced by 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine. The potency of PDGF to induce this response in monocytes was of the same magnitude as that observed in PMNs. Similarly, lysozyme release and monocyte adherence were also increased in a dose-dependent manner and achieved maximal responses at 40 ng/mL concentration of PDGF. The PDGF concentration required to achieve maximal monocyte aggregation was two-fold (60 ng/mL) of that found for PMNs. In contrast to PMNs, a positive correlation (gamma = .93; P less than .01) was observed between the increases of PDGF concentration and beta-glucuronidase release. These findings indicate that PDGF can induce the full sequence of cell activation events in human monocytes similar to human PMNs.

Cell Adhesion↗
PubMed1985

In vitro detection of endothelial cell damage using 2-deoxy-D-3H-glucose: comparison with chromium 51, 3H-leucine, 3H-adenine, and lactate dehydrogenase.

To develop a sensitive in vitro assay for detecting endothelial cell damage, we radiolabeled endothelial cell monolayers with tracer amounts of 2-deoxy-D-[1-3H]-glucose (3HDOG). We damaged identical cohorts of endothelial cells radiolabeled with 3HDOG or chromium 51 by exposing monolayers to toxic oxygen radicals generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), a surface active agent (Triton X-100), and anti-HLA antibodies and complement. With each mechanism of injury, the 3HDOG assay detected significant (P less than 0.01) endothelial cell damage at lower concentrations of the injurious agent than the 51Cr assay. When endothelial monolayers were damaged by xanthine-xanthine oxidase or PMA-activated PMNs, efflux of 3HDOG was reduced (range 71% to 94% reduction) by superoxide dismutase and catalase, indicating that efflux of 3HDOG was mediated by toxic oxygen radicals. When monolayers were damaged with xanthine oxidase in the absence of glucose, a much lower concentration of xanthine oxidase was required to initiate efflux of 3HDOG as compared with xanthine oxidase injury in the presence of glucose. Additional studies compared the 3HDOG assay with 3H-adenine, 3H-leucine, and lactate dehydrogenase (LDH) release when endothelial cells were exposed to toxic oxygen radicals generated by PMA-activated PMNs and xanthine-xanthine oxidase. Again, the 3HDOG assay was more sensitive in detecting in vitro endothelial cell damage. We conclude that the 3HDOG assay is more sensitive than the 51Cr, 3H-adenine, 3H-leucine, or LDH release assays in detecting endothelial cell damage in vitro.

Adenine↗
PubMed1984

Mediastinal mass in acute lymphoblastic leukemia.

Patients with acute lymphoblastic leukemia who have a mediastinal mass at the time of diagnosis are said to have a poor prognosis. However, many factors which may not be independent contribute to the success of treatment. We compared the disease characteristics and results of therapy in children having large mediastinal masses and lymphoblastic leukemia without mediastinal mass. Patients with a mediastinal mass had less evidence of marrow failure but were burdened with considerably more leukemic cells as measured by peripheral blood white count and extent of lymphadenopathy. Since the presence of mediastinal mass was strongly associated with these and other poor prognostic characteristics, we used multivariate techniques to determine which characteristics were independently associated with an increased risk for relapse. White count, extent of lymphadenopathy, age, and sex were significant predictors of early relapse, but when controlled for these variables the presence of a mass did not predict prognosis.

Adolescent↗
PubMed1984

Leukemic infiltration of the testes in acute nonlymphocytic leukemia.

Two children with ANLL in complete remission developed testicular relapse 18 and 34 months after diagnosis. Their clinical presentation was similar to that observed in patients with ALL. Although the testicular leukemia responded to between 2,400 and 3,000 rads, bone marrow relapse occurred within 4 months and death within 6 months of the testicular relapse. This points out the need for surveillance of the testicles in males with ANLL, and raises the question of need for testicular biopsy among long-time male survivors.

Acute Disease↗
PubMed1984

Vitamin E attenuates the effects of FMLP on rabbit circulating granulocytes.

Exposure of circulating rabbit granulocytes to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) in vivo results in transient granulocytopenia, hypotension, and cardiorespiratory distress. The effectiveness of vitamin E in attenuating these responses was tested. Vitamin E accelerated the rate of return of granulocytes to the peripheral circulation after FMLP-induced granulocytopenia and mitigated the hypotension. The reversible adherence of FMLP-stimulated granulocytes to endothelium offers a plausible mechanism to explain the transient granulocytopenia. From in vitro studies it was found that FMLP-activated granulocytes from animals treated with vitamin E showed decreased adherence to cultivated aortic endothelial monolayers when compared with FMLP-activated granulocytes from control animals.

Agranulocytosis↗
PubMed1984

Platelet-derived growth factor promotes polymorphonuclear leukocyte activation.

The platelet-derived growth factor (PDGF) has several well defined important biologic activities. Platelet-derived growth factor is the major mitogen in human serum for cells of mesenchymal origins; it is a potent chemoattractant protein for human monocytes, neutrophils, fibroblasts, and smooth muscle cells; and has been implicated in transformation by simian sarcoma virus and perhaps in transformation by other agents as well. In this article, PDGF has been shown to stimulate activation of human peripheral blood neutrophils defined by loss of membrane associated calcium as reflected by loss of chlortetracycline fluorescence, release of superoxide anion and specific granule enzymes, and enhanced neutrophil adherence and aggregation. These responses occurred in a dose-dependent fashion at concentrations of PDGF between 10 ng/mL (0.4 nmol/L) and 40 ng/mL (1.5 nmol/L) and were comparable to effects obtained with optimal concentrations of fMLP and C5a. Degranulation induced by PDGF was selective for secondary (specific) granules and not primary (azurophil) granules. Platelet-derived growth factor thus is ideally suited for a pivotal role in attracting inflammatory cells locally and initiating neutrophil activation at sites of blood vessel injury. Platelet-derived growth factor or a closely related protein also may play an important role in attracting and activating neutrophils in association with inflammatory tumors.

Calcium↗
PubMed1984

Comparative responses of human polymorphonuclear leukocytes obtained by counterflow centrifugal elutriation and Ficoll-Hypaque density centrifugation. II. Membrane potential changes, membrane receptor analysis, membrane fluidity, and analysis of the effects of the preparative techniques.

Standard preparative techniques for human polymorphonuclear leukocytes involves the sequential exposure of the PMN to dextran, Ficoll-Hypaque (FH) gradient centrifugation, and hypotonic stress. Counterflow centrifugal elutriation (CCE) allows isolation of PMN from whole blood without exposure to these potentially toxic substances. We have previously reported that PMN isolated by CCE release more superoxide on stimulation than do PMN isolated by standard techniques (FH PMN). In this report, we extend these observations and show that CCE and FH PMN have similar binding kinetics for the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and similar membrane fluidity. CCE PMN, however, were noted to have a more marked membrane depolarization on stimulation with FMLP than FH PMN. We show that exposure of purified CCE PMN to dextran increases their superoxide release on stimulation, as well as the available FMLP binding sites. Exposure of FH PMN to elutriation buffer increased their superoxide release on stimulation. It was also noted that both CCE and FH PMN re-exposed to FH increased available binding sites for FMLP. The possible reasons for these findings are discussed.

Adult↗
PubMed1984

Treatment of Pneumocystis carinii pneumonitis. A comparative trial of sulfamethoxazole-trimethoprim v pentamidine in pediatric patients with cancer: report from the Children's Cancer Study Group.

Pentamidine isethionate and sulfamethoxazole-trimethoprim are effective in the treatment of Pneumocystis carinii pneumonia in the immunosuppressed pediatric patient. To compare their efficacy and toxicity, 25 pediatric cancer patients with biopsy-proved P carinii pneumonia were randomly assigned to receive either pentamidine intramuscularly or sulfamethoxazole-trimethoprim orally for 14 days. No differences in response or frequency of side effects were noted between the two drug regimens, with recovery occurring in 24 (96%) of 25 children. Skin eruptions and hematologic abnormalities were the most common side effects of sulfamethoxazole-trimethoprim therapy, while local reactions at injection sites, abnormal renal function, and hypoglycemia were the most frequent complications of pentamidine treatment. The ease of administration and less serious side effects of sulfamethoxazole-trimethoprim make it the drug of first choice for treating P carinii pneumonia. Pentamidine remains an important drug for patients who fail to respond to this initial therapy.

Acute Disease↗
PubMed1984

Plasma lactoferrin reflects granulocyte activation via complement in burn patients.

Complement activation and neutropenia have been observed in thermally injured animals. In burn patients, granulocyte chemotaxis and morphological loss of specific granules occur. We conjectured that complement is activated in humans and, in turn, induces granulocytes to secrete lactoferrin (LF), a marker of granulocyte activation. Twenty burn patients were evaluated for absolute granulocyte count (AGC), plasma levels of anaphylatoxins (C3a, C4a, C5a), and lactoferrin. The AGC directly correlated with the extent of the burn on day 1. Similarly, plasma LF on day 1 correlated with the percent burn. Those with greater than 30% burn had plasma LF between 10 and 40 micrograms/ml (normal LF = 1.5 +/- 1.8 micrograms/ml). In five patients without further complications followed serially, plasma LF did not return to normal until 2 to 5 weeks. In all patients, there was evidence of complement activation; C4a ranged between 283 and 13,064 ng/ml and C3a between 19 and 852 ng/ml. In some patients, C5a was detectable, but the values correlated inversely with the extent of burn. On the other hand C3a and C4a levels did not correlate with the extent of burn but threefold to fivefold rises of C3a levels on days 7 and 9 predicted gram-negative sepsis. Although plasma LF did not predict sepsis, levels greater than 12 micrograms/ml on day 1 heralded the onset of neutropenia on day 3 in 60% of patients with 30% burn. Six of 20 patients developed pulmonary radiographic changes and, in five of the six, the changes occurred by day 3. Plasma LF in all six patients on day 1 was greater than 17 micrograms/ml. In two patients with greater than 50% burn, depletion of granulocyte LF was demonstrated histochemically. These studies indicate that complement is activated in burn patients, which is associated with granulocyte secretion. Measurement of plasma anaphylatoxins and LF may serve as useful aides in clinical management of these patients.

Adult↗
PubMed1983

Effect of nutrition staging on treatment delays and outcome in Stage IV neuroblastoma.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life-table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P less than 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P less than 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.

Abdominal Neoplasms↗
PubMed1983

Neutropenia, recurrent bacterial infections, and congenital deafness in patients with monocytopenia. Absence of peripheral blood colony-stimulating activity.

The factors that regulate granulopoiesis in vivo are unclear, but recent evidence suggests a role for monocytes; these cells produce a leukopoietin termed colony-stimulating activity (CSA), which stimulates growth of colonies of myeloid cells in vitro. We describe a family in which three of four siblings had neutropenia with myeloid marrow hypoplasia, deafness, and monocytopenia. Two of the three affected siblings died of bacterial septicemia; the third sibling, who resided in a long-term care facility, remained relatively free of infections. Studies of this patient's peripheral blood disclosed deficient CSA production consistent with the virtual absence of monocytes. These findings support the purported role of monocytes as a source of peripheral blood leukopoietic factors.

Agranulocytosis↗
PubMed1983

The effect of vitamin E on rabbit neutrophil activation.

Chemoattractants such as N-formylmethionyl leucyl phenylalanine (FMLP) cause neutropenia in vivo. The sequestered neutrophils may block the microvasculature and contribute to respiratory distress. Neutrophils from humans receiving 1600 units vitamin E per day have reduced oxidative activity. To test whether vitamin E attenuates the responses of neutrophils to FMLP in vivo we gave rabbits four daily intramuscular injections of 100 mg vitamin E. Serum levels of the vitamin were 2.34 +/- 0.15 mg% compared to 0.19 +/- 0.04 mg% in control rabbits receiving placebo injections. On the fifth day testing was done before and after injecting FMLP. Variables monitored were the absolute granulocyte count (AGC), systolic, diastolic and mean blood pressures (MBP), heart rate, PO2, PCO2, pH and respiratory rate. When 0.5 microgram FMLP was injected intravenously the AGC decreased (at 2.5 min the percentage change was -89.7 +/- 8.0 with vitamin E and -97.0 +/- 2.7 without vitamin E; P = 0.2). MBP decreased also (% change, -29.0 +/- 13.0 with vitamin E and -36.3 +/- 16.0, without vitamin E). By 15 min recovery was seen (AGC % change, -26.0 +/- 17 with vitamin E and -78.7 +/- 10.5, without vitamin E; P = 0.01; MBP % change, -9.3 +/- 3.8 with vitamin E and -52.3 +/- 10.1 without vitamin E). Chromatographic analysis of serum extracts revealed increases in 6-keto-PGF1 alpha after stimulation. Studies with [3h]thymidine-labelled neutrophils showed that the sequestered cells return to the circulation. Vitamin E might facilitate this return by altering the adherence of neutrophils to endothelium. This possibility was tested by measuring the adherence to cultivated rabbit aorta endothelial monolayers of FMLP-stimulated neutrophils from vitamin E-treated rabbits. The percentage of neutrophils adhering was 32.5 +/- 3.5 with vitamin E and 60.0 +/- 7.1, without vitamin E. Thus vitamin E promotes the return of neutrophils to the circulation after chemotactic challenge and may do so by reducing their adherence to endothelium.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Immunologic studies of three family members with the immunodeficiency with hyper-IgM syndrome.

We report the results of immunologic studies in a family in which the father (III-5) and his two daughters (IV-7 and IV-8) had the hyper-IgM syndrome (IHIS). Repeated immunoglobulin levels done on III-5 showed a typical IHIS pattern: low IgG, traces of IgA, and high IgM. IV-7, who also had stage IIA Hodgkin's disease, had a similar pattern except after irradiation therapy to sites of disease, when IgM dropped to normal range while IgG and IgA remained low. IV-8, on the other hand, had normal IgG and IgA and moderately elevated IgM until age 18 months, when she gradually developed the IHIS pattern. All three patients had normal numbers of B cells (sIg) and of T cells, although IV-7 had increased suppression. Finally, all three patients shared the A3,B7 haplotype and none was blood type O. IHIS is not necessarily X linked, is not associated with blood type O, and appears to be heterogeneous even within the same family. Inheritance in this family is apparently autosomal dominant and the father may represent a new mutation.

Adult↗
PubMed1983

Superoxide dismutase: a cellular protective enzyme in bowel ischemia.

Recent data suggest that the free-radical anion superoxide (O-2), an unstable, cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel injury. This study evaluates the role of superoxide dismutase (SOD), an enzyme specific for enzymatic conversion of O-2 in protecting the bowel from an ischemic insult. At laparotomy, the superior mesenteric artery was occluded for 1 min in 90-g weanling rats (n = 144). Animals were divided into four groups: I, untreated controls (n = 41); II, received aminophylline (AMN) 40 mg/kg ip, a substrate for (O-2) generation (n = 21); III, received superoxide dismutase (SOD) 2.5 mg/kg iv (n = 20); IV, received both AMN and SOD (n = 22). Rats were evaluated for bowel infarction, perforation, and mortality over a 7-day observation period. In 40 additional rats (10 per group) bowel ultrastructure was evaluated by scanning electron microscopy (EM) during occlusive ischemia and at various time intervals following reperfusion. Mortality was 63.4% in controls (26/41) with necrosis noted in 19 and perforation in 7. AMN resulted in a 90% mortality (19/21) (chi 2, P less than 0.05 vs control), with necrosis in 15 and perforation in 4. SOD reduced mortality to 25% (5/20) with necrosis in 4 and perforation in 1 (chi 2, P less than 0.02 vs controls) and, when added to AMN, 45.5% (10/22) (chi 2, P less than 0.01 vs AMN alone). On EM, tissue damage was minimal during occlusive ischemia, worsened by duration of reperfusion, enhanced by AMN, and reduced by SOD. These data suggest that following hypoxia, the injured bowel may be unable to appropriately handle reoxygenation. Tissue damage was related to duration of reperfusion and was worse following AMN, a xanthine derivative that might generate (O-2), a cytotoxic free radical. SOD detoxifies O2-, increases survival, and protects the bowel during reperfusion.

Aminophylline↗
PubMed1983

Rhabdomyosarcoma in childhood: analysis of survival in 98 cases.

Ninety-eight infants and children with rhabdomyosarcoma were analyzed for age, stage, site, and therapy as they relate to survival. Age and sex were not factors. Survival was 91% (10/11) for Stage I, 86% (13/15) for Stage II, 35% (12/34) for Stage III, and 5.2% (2/38) for Stage IV. Overall survival was 37% (37/98); however, 75% had advanced disease at diagnosis. Primary tumor site was genitourinary (GU) (31), extremity (17), head-neck (14), trunk (14), orbit (8), paratesticular (4), retroperitoneal (3), paraspinal (3), buttocks (3), and perianal (1). Survival was favorable in orbital, paratesticular, and (GU) sites. Survival was 20% (9/45) before and 52% (28/53) after chemotherapy and irradiation. The only survivors had embryonal cell histology. Tumor stage and site are important prognostic indicators. Chemotherapy improves survival in Stage I (91%) and Stage II (86%) and shrinks bulky Stage III tumors allowing less radical procedures in selected sites (e.g., GU). Survival is poor in Stage III (35%) and dismal in Stage IV (5.2%) despite combined therapy. Relapse was fatal despite attempts at second-look resection, and altered chemotherapy and irradiation.

Adolescent↗
PubMed1983

Invasive aspergillosis of paranasal tissues in children with malignancies.

Paranasal aspergillosis was encountered in five children with relapsed malignancies. All had received broad-spectrum antibiotics within two weeks of development of aspergillosis, and all had absolute granulocyte counts less than 200/mm3 for at least three weeks. None had received prior antifungal therapy. There was an average delay of eight days before the correct diagnosis was established by either biopsy or culture. These data emphasize the need to obtain surveillance cultures of the upper respiratory tract passages in severely neutropenic patients receiving prolonged antibiotic therapy, and raise a question concerning prophylactic use of antifungal therapy in this group.

Adolescent↗
PubMed1983

Effectiveness of central parenteral nutrition versus peripheral parenteral nutrition plus enteral nutrition in reversing protein-energy malnutrition in children with advanced neuroblastoma and Wilms' tumor: a prospective randomized study.

The effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) plus enteral nutrition in reversing protein-energy malnutrition was evaluated in 19 children (nine CPN, 10 PPN) with advanced neuroblastoma or Wilms' tumor. Weekly dietary, anthropometric, and biochemical measurements were compared for 15 patients (eight CPN, seven PPN) who completed more than 25 days of nutrition support. The groups had similar mean energy and protein intakes (CPN: 95 +/- 5% of healthy children, 2.5 +/- 0.3 g/kg; PPN: 102 +/- 5% of healthy children, 2.9 +/- 0.3 g/kg). Increases in weight (p less than 0.001), subscapular skinfold thickness (p less than 0.001), albumin (p less than 0.05), and transferrin (p less than 0.05) for the first 28 days were significant and did not differ between groups. Fever, sepsis, elevated SGOT, and severe anemia occurred with both CPN and PPN. PPN resulted in subcutaneous infiltrations and more psychological trauma. PPN with enteral nutrition seems most appropriate for short term intravenous nutrition support or as a temporary substitute for CPN; CPN is preferred for long-term support.

Body Weight↗