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Biomedical subjects

R F Jacobs

Publications and source records attributed to R F Jacobs.

At least 73 records · Page 4Linked to original sources
PubMed1992

The concurrent expression of Griffonia simplicifolia-IB4 binding and tumor necrosis factor-alpha differs between alveolar and peritoneal macrophages.

As a corollary to their anatomic location, alveolar macrophages (AM) have a lower threshold for generating some physiologic functions than peritoneal macrophages (PM). In this study, we examined both of these populations for their ability to bind the lectin Griffonia simplicifolia-IB4 (GSIB4) and to produce tumor necrosis factor (TNF)-alpha. The results showed that these two responses were concurrently expressed in activated macrophages, although they differed in magnitude when AM and PM were compared. Following in vitro incubation, AM from lipopolysaccharide-treated rats demonstrated a higher percentage of GSIB4 positivity and TNF production when compared with their respective PM. Since prostaglandin E2 can regulate the expression of some macrophage activities, experiments were conducted to determine whether this could also affect the ability of macrophages to bind the GSIB4 lectin. Neither the administration of indomethacin nor exogenous prostaglandin E2 altered the expression of this marker. Conversely, these treatments produced significant changes in TNF-alpha production in both alveolar and peritoneal macrophages. When the concurrent expression of GSIB4 lectin binding and TNF-alpha production was analyzed, AM from lipopolysaccharide-treated rats demonstrated both superior GSIB4 positivity and TNF-alpha production compared with all other macrophages examined. The results of this work show that AM and PM differ in their expression of GSIB4 binding and TNF-alpha production. These differential responses may be important in determining the level of activity of macrophages that are participating in an immune response.

Animals↗
PubMed1991

Efficacy and safety of cefotaxime in the management of pediatric infections.

The utilization of cephalosporins in serious bacterial infections in children has become more widely accepted by pediatric infectious disease specialists over the past five years. The use of cephalosporins has become increasingly popular in empiric antibiotic regimens. The recognition that age-specific bacterial pathogens in neonates, older infants and children can be effectively treated with cephalosporins alone, or in combination with ampicillin, has led to this increasing popularity. This review will discuss the use of cephalosporins in empiric antibiotic regimens and relate the efficacy and safety of specific cephalosporins in the treatment of serious bacterial infections in children.

Age Factors↗
PubMed1991

Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children.

Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of CFB in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral CFB dose of either 4.5 or 9.0 mg/kg of body weight. CFB was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average CFB pharmacokinetic parameters (+/- standard deviations) were as follows: apparent elimination half-life, 2.0 +/- 0.5 h; mean residence time, 3.9 +/- 1.1 h; apparent steady-state volume of distribution, 0.4 +/- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5 +/- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P < 0.05) negative correlations were found between patient age and CFB elimination half-life and CL/F and between the estimated creatinine clearance and renal clearance and CL/F. Apparent age dependence of CFB disposition was also reflected by a greater CL/F in children from 0.5 to less than or equal 5 years of age (3.1 +/- 1.1 ml/min/kg) than in children > 10 years of age (2.0 +/- 0.6 ml/min/kg; P < 0.005). The increased CL/f for CFB (3.0 +/- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0 +/- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3 +/- 0.6 ml/min/kg) of CFB occurred in children, a finding different from preliminary data for adults.

Adolescent↗
PubMed1990

Fc-gamma receptor-ligand interactions enhance macrophage GSIB4-binding activity.

Activated macrophages have an increased ability to bind the lectin Griffonia simplicifolia-IB4 (GSIB4). Since macrophages readily use the Fc-receptor (FcR) during several immunologic and inflammatory processes, it is important to determine whether interactions with this moiety affect GSIB4-binding ability. Peritoneal macrophages cultured in vitro with Fc fragments of immunoglobulin G (IgG), whole IgG, or heat-aggregated IgG demonstrate an increase in this function. Conversely, treatment of macrophages with (Fab')2 fractions alone has no direct effect on this activity. Although the GSIB4-binding response is minimally expressed by normal macrophages, it is more markedly apparent on macrophages from LPS-treated animals. In both cases, however, pretrypsinization of the cells renders them refractory to IgG-mediated induction of the GSIB4-binding response. Moreover, macrophages cultured independently with IgG subclasses 1, 2a, or 3 demonstrate that the magnitude of their response to this signal is directly associated with the type of subclass used. Although each subclass enhanced the response, in this study interactions with IgG2a produced the best results. Overall, however, the greatest GSIB4-binding activity is generated when FcRs are crosslinked by aggregated IgG rather than simply bound by independent monomeric interactions at the FcRs. This suggests that the event of appropriately interacting with the FcRs amplifies the GSIB4-binding function. Such a mechanism could play a key role in coordinating the humoral, cell-mediated, and innate responses of the immune system.

Animals↗
PubMed1990

Septic shock in children: bacterial etiologies and temporal relationships.

In a retrospective analysis of 2110 admissions to the pediatric intensive care unit, 564 cases of septic shock were identified (26.7% of the total admissions). Septic shock was defined in patients with: (1) clinical evidence of sepsis; (2) fever (greater than 38.3 degrees C) or hypothermia (less than 35.6 degrees C); (3) tachycardia; (4) tachypnea; and (5) inadequate organ perfusion. Inadequate perfusion was defined as hypotension or evidence of peripheral hypoperfusion (poor capillary refill or cyanosis with hypoxemia, oliguria, acidosis or altered mentation). Inotropic support was required to maintain an adequate blood pressure and perfusion in 268 of 564 patients (47.5%). Septic shock with confirmed bacterial infection occurred in 143 patients (143 of 564, 25.2%); these cases were caused by Haemophilus influenzae, type b (59 of 143, 41.3%), Neisseria meningitidis (26 of 143, 18.2%) and Streptococcus pneumoniae (16 of 143, 11.2%). Eight of 564 (1.4%) cases of septic shock were not clinically apparent on initial evaluation and were diagnosed within 24 hours after admission to the hospital. We conclude that septic shock occurs more frequently in children than previously appreciated and may develop after admission to the hospital.

Adolescent↗
PubMed1990

Epidemiology of acute respiratory infections in young children from Thailand.

A prospective evaluation of the epidemiology and presentations of acute respiratory infections in children younger than 5 years of age admitted to Children's Hospital Bangkok (1988 to 1989) was supported by the World Health Organization. There were 226 patients with the inclusion criteria: 1 to 5 years of age; duration of illness less than 2 weeks; no prior antibiotic therapy; and low socioeconomic status. The disease categories included: croup, 19 cases; bronchiolitis, 60 cases; and pneumonia, 147 cases. Pathogens isolated were: respiratory syncytial virus (40); parainfluenza III (1); influenza B (1); and adenovirus (1); bacterial infections were proved in 23 cases. No significant differences in clinical features between bacterial and viral pneumonia were found. Interstitial radiographic patterns were more common in viral pneumonia whereas alveolar patterns were more common in bacterial pneumonia. However, 91% of mixed radiographic patterns (interstitial and alveolar) in chest films were from viral pneumonia.

Acute Disease↗
PubMed1990

The immunology of sepsis and meningitis--cytokine biology.

Although antibiotics have reduced mortality, the most recent clinical trials in sepsis and meningitis have been directed at the host inflammatory response in an attempt to improve outcome. Endotoxin, cell wall constituents and toxins are potent inducers of small molecular weight proteins (cytokines) from a variety of host cells. Several lines of investigation have implicated tumor necrosis factor-alpha (TNF-alpha) as a cytokine mediator of sepsis and septic shock. A recent study has been able to measure plasma TNF-alpha concentrations in patients with meningococcemia and demonstrated a correlation with prognostic groups related to mortality. Therefore, TNF-alpha, probably through its effects on other mediators, has an effect in sepsis. New speculation regarding morbidity in bacterial meningitis focuses on cytokine activity in the central nervous system. Cerebrospinal fluid (CSF) from experimental animals with meningitis contains increased amounts of interleukin-1 beta (IL-1 beta) and TNF alpha. These IL-1 beta levels correlated directly with duration of fever and neurological sequelae. Children with Haemophilus influenzae, type b meningitis treated with dexamethasone had significantly reduced levels of CSF IL-1 beta compared to placebo-treated controls.

Bacterial Infections↗
PubMed1989

Differential induction of macrophage GSIB4-binding activity.

Activated macrophages display a terminal galactopyranosyl group on their membrane surface that binds the lectin Griffonia simplicifolia-IB4 (GSIB4). Using FITC-conjugated GSIB4, we examined the induction and subsequent expression of this corresponding marker on peritoneal macrophages from normal (NMO) and LPS-treated (LPS MO) mice. Although the percentage of fresh LPS MO explants that bound GSIB4 was always higher when compared to the NMO counterparts, marker expression on the latter was readily enhanced by culturing the cells in vitro either alone or with stimuli. Moreover, we found that an increase in this activity was promoted by either nonspecific phagocytosis of latex beads, or gamma-interferon (gamma-IFN) treatment. Further investigation showed that a prerequisite sequence of signal delivery to the macrophages was associated with maximal expression of the GSIB4 binding. When gamma-IFN treatment preceded latex bead ingestion, maximum GSIB4 binding occurred. Data obtained from using short-term (1 hr) and long-term (24 hr) exposure to latex beads showed that metabolic processing of induction signals was required to enhance the response over time. This yielded better GSIB4-binding activity when responses to these pulses were analyzed in freshly explanted macrophages. The overall results of this study demonstrated that macrophage binding of GSIB4 was differentially associated with stimuli induction. Moreover, select signals in the form of soluble mediators, or the mechanical events characteristic of internalization were capable of eliciting an increase in the percentage of macrophages that were positive for binding GSIB4. Thus, the enhanced affinity for binding this lectin may serve as a useful marker to determine the magnitude of macrophage responsiveness when these cells are examined following their exposure to different stimuli.

Animals↗
PubMed1989

Cefotaxime and desacetylcefotaxime pharmacokinetics in very low birth weight neonates.

The single-dose pharmacokinetics of cefotaxime (CTX) and desacetylcefotaxime (dCTX) after a 50.0 mg/kg intravenous dose were evaluated in 18 very low birth weight neonates (13 male; 1015.6 +/- 349.8 gm; 28.4 +/- 2.4 weeks gestational age) during the first week of life. Microanalytic high-performance liquid chromatography was used to quantitate both CTX and dCTX from serum. A two-compartment open model best characterized the disposition of CTX during a 24-hour post-dose period. The disposition of dCTX was adequately characterized by a one-compartment model. The elimination half-life, apparent steady-state volume of distribution, and total body clearance of CTX (mean +/- SEM) were 4.44 hours, 0.461 +/- 0.027 L/kg, and 0.074 +/- 0.003 L/hr/kg, respectively. Peak concentrations (mean +/- SD) of dCTX (17.96 +/- 5.54 mg/L) occurred at 0.6 to 8.3 hours (5.9 +/- 1.9 hours) after CTX administration, and the apparent elimination half-life of dCTX was 9.36 hours. Comparison of CTX and dCTX pharmacokinetic parameters between very low birth weight neonates who weighed less than 1000 gm (n = 9; 703.3 +/- 46.6 gm; 27.0 +/- 0.8 weeks gestational age) and greater than or equal to 1000 gm (n = 9; 1328.8 +/- 48.6 gm; 29.8 +/- 0.5 weeks gestational age) revealed no significant differences, but significant linear correlations were found between gestational age and weight versus CTX half-life and total body clearance. Because of the prolonged clearance of both CTX and dCTX in the very low birth weight neonate, a CTX dose of 50 mg/kg every 24 hours may provide effective serum concentrations for susceptible infections outside the central nervous system.

Cefotaxime↗
PubMed1989

Pseudomonas osteochondritis complicating puncture wounds of the foot in children: a 10-year evaluation.

From 1978 to 1988, microbiologically proven Pseudomonas osteochondritis and septic arthritis following nail puncture wound to the foot was diagnosed in 77 children aged 18 mo-19 y (77 and 17 cases, respectively). The syndromes were found in children with a history of wearing tennis shoes (70 cases), other shoes (5), and no shoes (2). All cases had surgical debridement of the infected cartilage or bone and drainage of infected joints. Pseudomonas aeruginosa was isolated in 38 cases and in conjunction with Staphylococcus aureus in 18. Anti-Pseudomonas antibiotics were initiated in all cases before surgical exploration; the average duration of treatment was 7.5 +/- 1.2 d postoperatively. Patient follow-up was 5.2 +/- 3.4 y (median, 4.8 y; range, 3 mo-10 y). Two relapses occurred; both patients had a previously undetected septic arthritis. These data suggest that with aggressive surgical management, Pseudomonas osteochondritis and septic arthritis can be treated effectively with postoperative antibiotics for 7 d.

Adolescent↗
PubMed1989

Timentin therapy for Staphylococcus aureus infections in children: results of a multicenter trial.

Multicenter trials of ticarcillin/potassium clavulanate (Timentin) for bone, joint, skin and soft tissue infections in children were performed from 1983 to 1986. Fifty children with culture-confirmed Staphylococcus aureus infections were identified. Sixteen children (ages 6.2 +/- 3.9 years) with bone and joint infections received Timentin for 8.7 +/- 2.4 days with 11 of 16 cures, 5 of 16 improved, 11 of 11 bacteriologic cures and 3.9 +/- 3.5 days of fever. Thirty-two children (ages 5.7 +/- 3.5 years) with skin and soft tissue infections received Timentin for 5.3 +/- 1.6 days with 22 of 32 cures, 10 of 32 improved, 32 of 32 bacteriologic cures and 1.4 +/- 1.3 days of fever. Three patients had S. aureus bacteremia; all were clinical and bacteriologic cures. All S. aureus isolates were susceptible to Timentin, 18 of 23 isolates tested produced beta-lactamase and 21 of 44 isolates tested were resistant to ticarcillin. The purpose of this report is to describe the clinical efficacy of Timentin in treating these types of S. aureus infections in children.

Child↗
PubMed1989

Elevated interleukin-1 release by human alveolar macrophages during the adult respiratory distress syndrome.

Interleukin-1 (IL-1), a modulatory protein with immune and inflammatory functions, is spontaneously released by tissue macrophages in lower concentrations compared with peripheral blood monocytes. Conversely, in idiopathic pulmonary fibrosis, sarcoidosis, and certain inflammatory diseases, increased amounts of IL-1 are released by alveolar macrophages (AM). We examined IL-1 production by AM from patients with adult respiratory distress syndrome (ARDS) and compared it with that in patients with severe pneumonia requiring assisted ventilation, patients with pneumonia requiring parenteral antibiotics, and healthy control subjects. In vitro, ARDS AM released significantly more total IL-1 and IL-1 beta than did ARDS AM in patients with pneumonia and in control subjects. Moreover, after stimulation of these cells with 10 micrograms/ml of lipopolysaccharide (LPS), ARDS AM significantly increased release of IL-1 and IL-1 beta. AM from patients with severe pneumonia also released greater amounts of both IL-1 and IL-1 beta as fresh explants and after LPS stimulation when compared with control subjects. Incubation of AM with 250 U/ml human interferon-gamma (gamma IFN) was associated with less IL-1 beta release. However, stimulating AM from patients with ARDS and severe pneumonia with gamma IFN plus LPS enhanced the release of IL-1 beta compared with that in patients with pneumonia and in control subjects. ARDS AM released significantly more IL-1 beta than did all of the other groups. These results demonstrate that AM from patients with ARDS are capable of releasing significantly greater amounts of IL-1, which may be related to the progression of acute lung injury.

Bronchoalveolar Lavage Fluid↗
PubMed1989

Immune cellular interactions during sepsis and septic injury.

The cellular activity generated by PMNs and macrophages in association with diverse cytokines has a profound impact on all major functional responses of host cellular components during sepsis and septic injury. It is the modulation of these cellular interactions and their effect on the continuum between appropriate and inappropriate responses during inflammation that will dictate the outcome of humans with sepsis.

Humans↗
PubMed1988

Effects of ibuprofen on neutrophil function and acute lung injury in canine endotoxin shock.

The role of the polymorphonuclear leukocyte in the development of acute lung injury has been the subject of much controversy. Experimental lung injury is associated with peripheral leukopenia and the intrapulmonary sequestration of leukocytes. We have previously shown that ibuprofen, a nonsteroidal anti-inflammatory drug, can improve the hemodynamic alterations of canine endotoxin shock. Ibuprofen has also been found to decrease leukocyte adherence. We investigated the dose response of ibuprofen on the increased neutrophil adherence and the extent of lung injury associated with canine endotoxin shock. Single doses of ibuprofen (1, 5, 10, and 20 mg/kg iv) were administered 15 min after Escherichia coli endotoxin. Endotoxemia resulted in leukopenia and an increased neutrophil adherence in both aortic and pulmonary artery blood. Endotoxin-treated animals exhibited increased neutrophils in the bronchoalveolar lavage fluid, a marker of lung injury. The 20-mg/kg ibuprofen dose decreased aortic granulocyte adherence at 30 min, while all ibuprofen doses decreased the aortic adherence at 120 min. The increased pulmonary artery neutrophil adherence was not affected by ibuprofen. Histologically, lung injury was manifested by intravascular leukostasis. Ibuprofen treatment did not affect the histologic or morphometric extent of the lung injury. The leukopenia and increased neutrophil adherence occur rapidly after endotoxemia and are associated with subsequent intravascular sequestration of leukocytes. Agents designed to prevent lung injury must either be given before the insult or be able to block the effects of the toxic products released by the activated granulocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Low dose ibuprofen reverses the hemodynamic alterations of canine endotoxin shock.

The dose response of the nonsteroidal anti-inflammatory drug, ibuprofen, was evaluated in order to determine the most efficacious dose in the treatment of canine endotoxin shock. Fifteen minutes after an infusion of Escherichia coli endotoxin, four groups of dogs were given a single iv dose of 1, 5, 10, or 20 mg/kg of ibuprofen. These groups were compared to endotoxin only and saline control groups. All ibuprofen doses significantly improved the systolic, diastolic, and mean systemic arterial BP. The improvement in systemic BP was accompanied by an increase in the systemic vascular resistance. Pulmonary vascular pressures and resistance also increased after ibuprofen administration. The lack of a dose response and the demonstrated beneficial effect of low dose ibuprofen in the reversal of the hypotension associated with experimental canine endotoxin shock lead us to recommend the use of low dose ibuprofen for future endotoxin and sepsis studies. Use of low dose ibuprofen might have less of an effect on renal perfusion and would therefore be more likely to produce the beneficial hemodynamic response without compromising renal function.

Animals↗