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Biomedical subjects

R F Jacobs

Publications and source records attributed to R F Jacobs.

At least 55 records · Page 3Linked to original sources

Tuberculosis in children.

The dramatic resurgence and increase in the total number of cases of tuberculous infection and disease in children is alarming in the United States. With poverty, poor access to health care, overcrowding (predominantly in inner-city areas), and an increase in immigration from areas with high endemic rates of TB, the problem in children will continue to increase. If the impact of coinfection with HIV and M. tuberculosis becomes significant in children, as it has in adults in the United States, the increase in the total number of cases of tuberculous disease in children could be staggering. The impact of multidrug-resistant strains of M. tuberculosis and the current crises in availability of effective anti-TB drugs will need a similar resurgence.

AIDS-Related Opportunistic Infections↗

Viral meningitis. Tips to rapidly diagnose treatable causes.

Viral meningitis is a common illness among children and is most often caused by enteroviruses. Diagnosis is made on the basis of clinical findings and analysis of the cerebrospinal fluid. Important conditions to consider in diagnosis are partially treated bacterial meningitis, tuberculous meningitis, fungal meningitis, other infections, and central nervous system tumor. Ruling out treatable causes early is important. Treatment of enteroviral meningitis is supportive, and the prognosis is usually very good, although significant neurologic sequelae have been reported.

Cerebrospinal Fluid↗

Tularemia: treatment failures with outpatient use of ceftriaxone.

Tularemia, an infection caused by the coccobacillus Francisella tularensis, can be a difficult disease process to diagnose and treat. The difficulty in treating this disease is related to the pathophysiology of the infection and the toxicity of the antimicrobial agents presently recommended for treatment. Recent in vitro data have suggested that antimicrobial drugs other than standard agents (streptomycin, gentamicin, chloramphenicol, or tetracycline) may be effective. We present eight cases of documented failure of outpatient use of ceftriaxone in the treatment of tularemia. Our data suggest that while ceftriaxone may have excellent MICs in vitro, these MICs do not necessarily correlate with successful in vivo outcomes.

Adolescent↗

Adverse effects of newer cephalosporins. An update.

While classifications into generations according to antimicrobial activity has helped clinicians incorporate the increasing number of cephalosporins into their pharmacological repertoire, adverse effects among the different agents fail to follow similar categories. In general, cephalosporins are fairly well tolerated antibiotics, and toxicity has been limited to specific agents. Subtle differences in chemical structure and pharmacokinetics can influence the potential for adverse effects. The route of administration may result in minor adverse reactions, including thrombophlebitis and pain. The most common adverse effects of cephalosporins are allergic reactions, occurring in 0.9 to 3.2% of patients. Cephalosporins have very rarely been associated with haematological toxicity (less than 1% of patients), but specific agents have been associated with neutropenia, hypoprothrombinaemia, haemolytic anaemia, and problems with platelet production and function. Other reactions include localised gastrointestinal disturbances, hepatotoxicity (e.g. biliary sludging), nephrotoxicity and mild central nervous system effects. The cephalosporins are generally well tolerated in the paediatric population. Very few interactions have been observed between cephalosporins and other drugs, largely because cephalosporins do not affect the microsomal P450 hepatic enzyme system. While cephalosporins are considered to be relatively 'safe' drugs, the introduction of newer members warrants continued careful observation for reporting of adverse drug reactions.

Cephalosporins↗

Childhood tuberculosis.

The dramatic resurgence and increase in the total number of cases of tuberculous infection and disease in children is alarming in the United States. With poverty, poor access to health care, overcrowding (predominantly in inner-city areas), and an increase in immigration from areas with high endemic rates of tuberculosis, the problem in children will continue to increase. If the impact of coinfection with HIV and M. tuberculosis becomes significant, as it has in adults in the United States, this increase in the total number of cases of tuberculous disease could be staggering. The impact of multiple drug-resistant strains of M. tuberculosis and the current crises in availability of effective antituberculous drugs will need to undergo basic and clinical research. Although the possibility for eradication of M. tuberculosis as a human pathogen in the United States still exists, clinicians must reeducate themselves regarding the epidemiology, pathophysiology, diagnostic work-up, and effective treatment of children with tuberculosis in the current situation of increasing tuberculous disease and resistant organisms in children.

Child↗

Macrophage membrane glycoprotein binding of Griffonia simplicifolia I-B4 induces TNF-alpha production and a tumoricidal response.

Thioglycollate-elicited macrophages (m phi), upon binding the lectin Griffonia simplicifolia IB4 (GSIB4) at the plasma membrane, are induced to secrete several low molecular weight proteins. In this investigation, results from specific ELISA and immunoprecipitation analysis of these molecules confirmed that the cytokine, tumor necrosis factor-alpha (TNF-alpha), belongs to the group of elicited proteins. This specific m phi response is directly influenced by the dose of GSIB4 used and the time in contact with the cells. At 40 micrograms/ml GSIB4, the maximum dose of lectin used, the m phi activity was equal to that achieved when the cells were incubated with an interferon-gamma/lipopolysaccharide (IFN/LPS) stimulus alone. Moreover, the data showed that TNF-mediated tumoricidal activity was significantly influenced by GSIB4 binding to the m phi membrane. When the lectin was incubated alone or in sequence with IFN/LPS, this ligand-receptor binding promoted the lysis of WEHI 164 tumor target cells. However, concurrent incubation of both IFN/LPS and GSIB4 with m phi significantly diminished the tumoricidal response. This suggested that one of the metabolic pathways utilized subsequent to receptor-ligand binding was altered by these interactions. When cyclic AMP (cAMP) and inositol triphosphate (IP3) levels were examined, the results showed that the concentration of cAMP was unchanged despite the fact that IP3 levels were significantly enhanced upon m phi-GSIB4 binding. Collectively, the data show that GSIB4 binding to specific glycoproteins in the m phi membrane induces TNF-alpha production and facilitates TNF-alpha dependent tumoricidal responses. It also appears that the transduction of the signal, in part, at least utilizes the phosphatidyl inositol pathway. Finally, it is noteworthy that m phi activity is influenced by the sequence in which GSIB4 is presented to the m phi relative to the IFN/LPS treatment.

Animals↗

Otitis media due to blastomycosis: report of two cases.

Blastomycosis as a causative agent in cases of otitis media has not previously been reported. Two patients recently presented with otitis media and head and neck masses due to Blastomyces dermatitidis. Initial evaluation suggested neoplastic disease, but biopsy confirmed a fungal etiology for the masses in both patients. Relapse after administration of ketoconazole was noted in one patient, who was an adult; the other patient was a child. Otitis media and masses of the head and neck are unusual features of blastomycosis. Blastomycosis should be considered in the differential diagnosis for patients with such mass lesions and for patients with otitis media.

Adult↗

Safety profile and efficacy of cefotaxime for the treatment of hospitalized children.

Cefotaxime has been used to treat serious bacterial infections in children since 1982. With the predominant use of cephalosporins in pediatrics, reports of adverse effects of certain compounds have increased. A retrospective review is presented of 2,243 cases of children receiving therapy with cefotaxime in order to evaluate the safety profile and efficacy of cefotaxime in the treatment of serious infections in hospitalized children. Overall, 57 (2.5%) children experienced adverse reactions. These included local reactions in 6 (0.3%), rash in 28 (1.2%), diarrhea in 15 (0.97%), vomiting in 10 (0.7%), abdominal pain in 1 (0.1%), headache in 3 (0.4%), and drug fever in 1 (0.1%). No cases of hemolytic anemia, bleeding, or hyperbilirubinemia were found. Efficacy of treatment for different disease categories ranged from 90.5% to 100%. The percentage of children in any treatment group with a particular laboratory abnormality following initiation of cefotaxime therapy ranged from 0% to 2.6%, and rates of superinfection with bacteria or Candida were 0.4% to 1.7%. Cefotaxime has the distinct advantage of high rates of efficacy and low rates of complications and superinfection among children hospitalized for serious infections.

Adolescent↗

Intensive short course chemotherapy for tuberculous meningitis.

This nonrandomized, open clinical investigation of tuberculous meningitis evaluated 53 children with Stage I (n = 8), Stage II (n = 29) and Stage III (n = 16) disease. The overall mortality was 20.8% (11 of 53) with a rate of sequelae of 35.7% (15 of 42) in survivors reflecting the advanced stages of children at diagnosis. Various combinations of standard antituberculous drugs including isoniazid, rifampin, pyrazinamide, streptomycin and ethambutol were given. Three treatment durations used during various time periods were evaluated: 12, 9 and 6 months with only the 6-month regimen receiving pyrazinamide (PZA). This prospective evaluation demonstrated that: (1) severe disease at presentation is highly associated with early mortality (P less than 0.05), regardless of drug regimen; and (2) intensive short course chemotherapy (6 months) with PZA, regardless of stage of disease at presentation, is more efficacious than longer course therapy (9 or 12 months) without PZA in preventing total negative outcomes and sequelae (P less than 0.05). This study demonstrates that a 6-month regimen containing PZA can be used in treating children with tuberculous meningitis.

Antitubercular Agents↗

Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections.

A randomized, single-blind, multicenter study was conducted to evaluate the safety and efficacy of cefuroxime axetil and cefadroxil suspensions for the treatment of skin or skin structure infections in 287 children. Each drug was given at a dosage of 30 mg/kg of body weight per day in two divided doses. Staphylococcus aureus and Streptococcus pyogenes, or a combination of the two, were the primary pathogens isolated from infected skin lesions. A satisfactory bacteriological response (cure or presumed cure) was obtained in 97.1 and 94.3% of children in the cefuroxime axetil and cefadroxil groups, respectively (P greater than 0.05). Satisfactory clinical responses (cure or improvement) were more likely to occur in cefuroxime axetil recipients than in cefadroxil recipients (97.8 versus 90.3%; P less than 0.05). Both regimens were equally well tolerated, with adverse events occurring in 7.9 and 6.1% of cefuroxime axetil and cefadroxil recipients, respectively. There were more patients who refused to take cefuroxime axetil (7 of 189) than there were who refused to take cefadroxil (0 of 98), but the difference was not statistically significant (P = 0.1). In this study, cefuroxime axetil was at least as effective as cefadroxil in resolving skin and skin structure infections in children.

Cefadroxil↗

Cefotaxime dosage in infants and children. Pharmacokinetic and clinical rationale for an extended dosage interval.

Cefotaxime is a third generation cephalosporin antimicrobial agent which has received wide acceptance as a first-line antibiotic for many infections in neonates, infants and children. With an average elimination half-life of about 1 h, cefotaxime is not considered to be a 'long half-life cephalosporin' like ceftriaxone. For this reason, currently accepted dosage regimens for cefotaxime in infants and children employ a dosage of 50 mg/kg every 6 h. Re-examination of the paediatric pharmacokinetic data for cefotaxime and use of simple multiple-dose pharmacokinetic simulation of alternative dosage regimens was performed. From this analysis, regimens administering 75 mg/kg of the drug every 8 h or every 12 h were projected to produce serum cefotaxime concentrations adequate to effectively kill many of the common pathogens against which the drug is currently indicated for use in children. The clinical utility of these alternative dosage regimens was supported by a review of the medical literature and examination of the clinical results from studies in neonates, infants and children where cefotaxime was administered in 2 to 3 divided doses daily. It would appear, therefore, that increasing the cefotaxime dosage to 75 mg/kg administered at 8 h intervals would result in less frequent drug administration which would not be expected to compromise safety and efficacy. Alternative dosage regimens for cefotaxime merit further consideration and clinical evaluation before they become commonly used in paediatric therapeutics.

Cefotaxime↗

Surface matrix binding alters murine peritoneal mononuclear phagocyte TNF-alpha and IL-6 induction.

Interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) are important promotors of mononuclear phagocyte (MO) activation. Signals derived from binding to a surface matrix also participate in promoting the activation process of MO. In this study, we examined the relative contribution of adherence in augmenting murine MO activation for cytokine production. Kinetic studies compared the production and secretion of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) by MO cultured as adherent monolayers to those of MO cultured as suspended cells in teflon vessels. All cells were maximally stimulated in vitro with IFN-gamma and LPS prior to analysis. Immunoprecipitation analysis of protein and RNA slot blots showed that both secreted protein and mRNA representing TNF and IL-6 are delayed two to six hours in nonadherent MO cultures compared to adherent MO cultures. Moreover, data from bioassays confirmed that these cytokines were completely functional in both systems examined. Although IFN-gamma/LPS were able to stimulate production and secretion of TNF and IL-6 in the nonadherent cells, without cell-matrix interaction, the process was significantly delayed. These data support the hypothesis that the physical event of adherence significantly facilitates the production of specific cytokines by activated MO.

Animals↗