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R F Jacobs

Publications and source records attributed to R F Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1988

Microanalytical high-performance liquid chromatography assay for cefpirome (HR 810) in serum.

We report a microanalytical high-performance liquid chromatography method for quantitation of cefpirome (HR 810) from serum. The drug was extracted from 0.05 ml of serum with 0.2 ml of isopropanol containing beta-hydroxypropyltheophylline, the internal standard. Separations were performed on a C18 column at ambient temperature with detection at 240 nm. The mobile phase consisted of acetate buffer (0.05 M sodium acetate) containing tetrabutylammonium hydroxide and methanol (pH 5.1; 70:30, vol/vol). The method was linear to 500 micrograms of cefpirome per ml and had a sensitivity of 0.6 micrograms/ml. Analytical recovery was greater than 86%, and the between-day coefficient of variation was less than 4.2%. The stability for 1 week at 4 to 8 degrees C and for 30 days at -20 degrees C was documented. Interference with commonly used antibiotics, analgesics, methylxanthines, and anticonvulsants was not found. The small sample volume and ease of preparation make this method suitable for use in pediatric pharmacokinetic investigations of cefpirome.

Cephalosporins↗
PubMed1988

Cefotaxime treatment of gram-negative enteric meningitis in infants and children.

18 infants and children (1 week to 3 months of age) were treated with cefotaxime 200 mg/kg/day for Gram-negative enteric bacillary meningitis. 17 of these patients (94.4%) survived, with a complication rate of 23.5% (4/17 patients). The follow-up cerebrospinal fluid cultures at 24 hours were sterile in all patients. Cefotaxime was safe and effective in treating Gram-negative enteric bacillary meningitis in infants and children and should be considered as a potential drug of choice in Gram-negative neonatal meningitis due to susceptible organisms.

Cefotaxime↗
PubMed1988

Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury.

Bacterial sepsis and pneumonia are common complications of lung injury and predispose the host to a poor resolution. We studied the functional integrity of pulmonary macrophages derived from minced lung preparations in a canine model of endotoxin-induced shock with acute lung injury. Dogs given 2 mg/kg of Escherichia coli endotoxin 055:B5 developed classic shock symptoms with concomitant acute lung injury; control animals given saline showed no physiological or pathological abnormalities. Compared to previous work with this canine model, the lung injury in this extended time period (6 h) had progressed to include alveolar edema. Six hours after endotoxin infusion, the left lung was lavaged, perfused, and the resulting lung minced for isolation of pulmonary macrophages. The endotoxic-model pulmonary macrophages showed several significant functional differences from controls. Although they elicited greater production of H2O2 (p less than 0.05), both phagocytosis of radiolabeled Staphylococcus aureus and E. coli (p less than 0.05) and bactericidal activity (p less than 0.05) were diminished compared to controls. Compared to alterations previously described in alveolar macrophages, these cells produced less H2O2 and demonstrated abnormal bacterial killing at all time points. These observations suggest that the functional alterations of pulmonary macrophages that follow acute lung injury contribute to the ineffective cell-mediated antimicrobial response. These derangements may promote an increased risk of nosocomial pneumonia, the high mortality often observed subsequent to pneumonia, or the propagation of acute lung injury that facilitates respiratory failure.

Animals↗
PubMed1988

Enhanced production of monokines by canine alveolar macrophages in response to endotoxin-induced shock.

The enhanced production of soluble mediators by alveolar macrophages may be responsible for promoting lung injury in canines administered endotoxin. One of the most prominent monokines, interleukin 1 (IL-1), has the potential to significantly influence the responses of host tissues. In this study we analyzed alveolar macrophages from canines that were experimentally administered endotoxin (AMEC) for their ability to produce IL-1. When concentrated AMEC supernatants from in vitro cultures were incubated with fresh C3H/HEJ thymocytes, a threefold greater incorporation of [3H]thymidine resulted as compared to the response produced by controls. Heat treatment of the experimental preparations ablated this difference. Conversely, the activity of AMEC intracellular lysates did not significantly differ from the controls. Silver-staining the preparations separated by SDS-PAGE revealed a low-molecular-weight species (17 kD) in the AMEC supernatant lane while a similar molecular distribution was absent in all of the control preparations examined. Moreover, using the L929 cell line in a cytolytic bioassay we found that these same AMEC supernatants also contained significantly elevated levels of tumor necrosis factor. Collectively, this study suggests that during endotoxin-induced canine lung injury, the alveolar macrophages generate soluble species that can substantially regulate the hosts cellular response. This activity in the canine lung may play a critical role in the development and/or maintenance of the pathology associated with exposure to endotoxin.

Animals↗
PubMed1988

Management of tuberculosis in pregnancy and the newborn.

Tuberculosis in pregnant women and their offspring is a serious and sometimes life-threatening infection. A high index of suspicion is a prerequisite for proper diagnosis. Early detection is essential since treatment is successful in these patients.

Antitubercular Agents↗
PubMed1987

Receptor-mediated ingestion responses by lung macrophages from a canine model of ARDS.

Receptor-mediated ingestion was examined in macrophages derived from a canine model of the adult respiratory distress syndrome (ARDS). The results showed that Fc-mediated ingestion by alveolar macrophages (AM) and macrophages from lung parenchyma (PM) was significantly diminished when compared with their respective controls. Pulsing all the experimental groups with lipopolysaccharide (LPS) for 1 hr in vitro failed to either enhance the response or return the activity to levels achieved by control cells. In parallel studies, an analysis of C3b-mediated ingestion showed that both the experimental AM and PM performed this function only at a magnitude equal to the control cells. Similar responses were observed when an LPS pulse was performed. Although there was a reduction in Fc-mediated ingestion and an apparent restraint of the C3b-mediated ingestion, both AM and PM expressed a significantly enhanced ability to spread. These results suggested that the canine model of ARDS alters at least one select macrophage function that may be important to subsequently protect the host. Such disturbances in the cellular immune response may contribute to the progression of infection and lung pathology associated with this disease process.

Animals↗
PubMed1987

Growth inhibition of Blastomyces dermatitidis in alveolar and peripheral macrophages from patients with blastomycosis.

Blastomyces dermatitidis evokes a pyogranulomatous disorder with organisms frequently found inside giant cells. Macrophages from bronchoalveolar lavage fluid and peripheral blood in monolayer cell cultures were challenged with live yeast organisms to examine phagocytosis and intracellular growth. A greater number of macrophages from patients recovering from blastomycosis had phagocytized Blastomyces compared with macrophages from healthy control donors. No differences were detected within the groups between alveolar and peripheral macrophages. Intracellular growth of the fungus was reduced in cultures of both cell types from patients compared with those from control subjects. Supernatants from specific Blastomyces antigen-stimulated lymphocyte cultures were collected, and treatment with the supernatant to control donors' macrophages resulted in increased phagocytosis and inhibition of intracellular growth. Antigen-induced lymphocyte stimulation as a correlate of cellular immunity is qualitatively related to alveolar or peripheral macrophage phagocytosis and growth inhibition of this fungus.

Blastomyces↗
PubMed1987

Cyclophosphamide-sensitive activity of suppressor T cells during treponemal infection.

When hamsters were infected with Treponema pallidum subspecies endemicum, the composition and activity of the cellular immune components were markedly altered compared to those of sham-infected controls. A population of suppressor T cells (Ts) developed that diminished the ability of the macrophage (M phi) to perform C3b receptor-mediated ingestion (C3bMI) of erythrocytes coated with antibody and complement. Using cyclophosphamide (CY) we examined node and peritoneal cells to determine their role in regulating M phi activity during this infection. In vitro the node and peritoneal T cells from treponemal-infected/CY-treated animals showed considerably less suppressive activity than treponemal-infected/untreated T cells when co-cultured with M phi from infected animals. This response was greater with node T cells compared to peritoneal T cells. Moreover, a quantitative analysis of the mononuclear leucocyte populations from each of these regions showed that CY-treated/uninfected animals had a decreased percentage of node T cells. Despite this reduction of node T cells, peritoneal T-cell populations were only minimally reduced. However, treponemal-infected hamsters concomitantly treated with CY had a significant reduction in the T-cell percentages in both compartments. These results imply that, during this infection, most Ts generated in the node remain there although some are dispersed to supplementary regions. Thus, the development of a suppressor system that effects M phi function may be one way in which treponemes escape total elimination by the host.

Animals↗
PubMed1986

Bacteremia during bronchoalveolar lavage.

We prospectively evaluated the incidence of bacteremia during fiberoptic bronchoalveolar lavage (BAL) and its relationship to postlavage symptoms in 12 volunteers. Qualitative and quantitative blood cultures were obtained before and during BAL. Three persons had qualitative blood cultures positive for organisms typical of normal skin flora. Quantitative blood cultures done simultaneously were negative. Approximately 42% of our subjects had postlavage symptoms, but no correlation was found between bacteremia and the occurrence of postlavage symptoms. Our results confirm the relative safety of BAL and the low incidence of BAL-associated bacteremia.

Adult↗
PubMed1986

Cerebrospinal fluid penetration of imipenem and cilastatin (primaxin) in children with central nervous system infections.

Cerebrospinal fluid (CSF) penetration of imipenem-cilastatin was evaluated in 20 children (aged 4 months to 11 years) with central nervous system infections. A total of 10 children received a single 25-mg/kg intravenous dose, and 10 received three 25-mg/kg intravenous doses at 6-h intervals. Blood and CSF were obtained 1.5 to 2.5 h after the last dose during the early (days 1 to 3) and the late (days 7 to 10) stages of infection. Imipenem concentrations after single-dose infusion in serum and CSF during the early phase of treatment (8.59 +/- 0.95 and 1.36 +/- 0.32 micrograms/ml, respectively) were similar to those during the late phase (9.96 +/- 2.36 and 2.08 +/- 1.14 micrograms/ml, respectively). Concentrations of imipenem in serum and CSF after multiple-dose infusion during the early phase (11.97 +/- 2.03 and 1.87 +/- 0.29 micrograms/ml, respectively) were similar to those during the late phase (9.57 +/- 1.76 and 1.22 +/- 0.11 micrograms/ml, respectively). There were no significant differences in the serum or CSF imipenem concentrations between the single- and multiple-dose groups during the early or late treatment stages. Cilastatin concentrations in serum and CSF were similar in all groups with the exception of the multiple-dose, early- versus late-phase evaluation of CSF cilastatin concentration. There was no correlation between age or absolute CSF neutrophil count and the serum or CSF concentrations of imipenem or cilastatin. We found a mean CSF penetration of 15 to 27% for imipenem and 16 to 66% for cilastatin in children. These findings suggest that imipenem-cilastatin sufficiently penetrates into CSF in children to warrant further investigation of this compound in pediatric central nervous system infections.

Central Nervous System Diseases↗
PubMed1986

Treponemal infection specifically enhances node T-cell regulation of macrophage activity.

Hamsters experimentally inoculated in the inguinal region with Treponema pallidum subsp. endemicum develop considerable pathology at that site. We examined the cell populations from these inguinal lymph nodes to determine their intercellular responses to infection. In vitro, syphilitic-node T cells markedly suppressed C3b receptor-mediated ingestion (C3bMI) in syphilitic macrophages derived from sites both proximal and distal to the inoculation. This activity was more pronounced when node T cells rather than peritoneal T cells were used. When treponemal preparations or live treponemes were added to the coculture system, the suppression was specifically enhanced, whereas the addition of heterologous agents did not promote this effect. Syphilitic macrophages from either compartment cultured alone showed no significant inhibition of C3bMI. In parallel studies on syphilitic macrophages, we observed that the expression of Ia quickly became elevated and was sustained throughout the infection. Moreover, in vitro culturing of the syphilitic-node T cells with these macrophages did not alter this function. These observations suggest that the syphilitic node contains a subpopulation of T cells that can selectively suppress macrophage C3bMI activity and concurrently regulate their cellular response to treponemal infection.

Animals↗
PubMed1986

Alveolar macrophage function in a canine model of endotoxin-induced lung injury.

Humans with bacterial sepsis are predisposed to acute lung injury with respiratory failure and have an increased risk of pulmonary infection. Because the alveolar macrophage is the resident phagocyte in the lung and a defect in antimicrobial activity could predispose to infection, we assessed the functional integrity of these cells in vitro in a canine model of Escherichia coli endotoxin-induced lung injury with respiratory failure. Dogs were given 2 or 20 mg/kg of E. coli endotoxin 055:B5, and alveolar macrophages from pulmonary lavage were compared with those from control dogs. The physiologic criteria for the adult respiratory distress syndrome and pathologic confirmation of acute lung injury were produced in all endotoxin-treated animals. The production of acute lung injury with respiratory failure by E. coli endotoxin was associated with several alterations in alveolar macrophage function. Adherence was significantly reduced for cells from the endotoxin groups. The alveolar macrophages from endotoxin-treated animals differed from those from control animals, with significantly greater production of hydrogen peroxide, significantly greater peaks in chemiluminescence, significantly reduced phagocytosis of Staphylococcus aureus and E. coli at all times, and a diminished ability to kill cell-associated S. aureus and E. coli over time. These derangements could play a role in the therapeutic failures of pneumonia, an increased risk for nosocomial pneumonias, or the propagation of acute lung injury with respiratory failure.

Animals↗