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Biomedical subjects

F Jacobs

Publications and source records attributed to F Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pteridium aquilinum (bracken fern) toxicity in cattle in the humid Chaco of Tarija, Bolivia.

We studied the toxicity caused by chronic ingestion of Pteridium aquilinum (bracken) in cattle in the humid Chaco of Tarija, Bolivia. Bovine enzootic haematuria (BEH) and Carcinoma of the esophagus (CE) affected the herds. Sick animals showed caquexia, anemia, leucopenia and urine that turned from pink to intense red color with the presence of blood clots. Cattle grazed in the humid forests of the mountains where P aquilinum represented more than 50% of the plants. P aquilinum var arachnoideum and P aquilinum var Caudatum were present. Toxic norsesquiterpene, ptaquiloside, was identified in both varieties. Carcinomas were in the urinary bladders and esophagus of 100% and 50% of the cattle, respectively. Control of the intoxication could be difficult due to geographic characteristics of this Bolivian region.

Animals↗
PubMed2000

Durable remission after aggressive chemotherapy for very late post-kidney transplant lymphoproliferation: A report of 16 cases observed in a single center.

PURPOSE: Posttransplant lymphoproliferative diseases (PTLDs) represent a group of potentially lethal lymphoid proliferations that may complicate the course of solid organ transplantation. Although early-onset PTLDs frequently have a favorable outcome, late-onset PTLDs behave more alike aggressive lymphoma. We report a monocentric retrospective study that focused on PTLDs occurring later than 1 year after kidney transplantation (very late-onset PTLDs) to define their incidence, clinical presentation, pathologic features, and outcome. We particularly emphasized the follow-up of patients treated with conventional chemotherapy. PATIENTS AND METHODS: The medical histories of all patients who developed very late-onset PTLD in our institution were reviewed, and diagnostic biopsy materials were retrospectively studied. RESULTS: Very late-onset PTLDs were diagnosed in 16 (1.1%) of 1,421 patients. Mean (+/- SD) time to tumor onset was 103.93 +/- 70.88 months. Most tumors were Epstein-Barr virus-related monomorphic large-cell PTLDs of B phenotype. Ten patients received conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone regimen). Two of them died within 2 months, two achieved partial remission, and six achieved definitive complete remission. Overall median survival time was 13 months and rose to 27 months in the treated group. The main cause of mortality was sepsis. None of the treated patients experienced rejection despite withdrawal of immunosuppressive treatment. CONCLUSION: Despite characteristics of aggressive lymphoma, very late-onset PTLDs after renal transplantation may respond to conventional chemotherapy. However, because a high rate of infectious complications occurred, new therapeutic strategies, such as combinations of anti-CD20 monoclonal antibodies and lower doses of chemotherapy, are warranted.

Adult↗
PubMed1999

Impact of infectious diseases specialists and microbiological data on the appropriateness of antimicrobial therapy for bacteremia.

Antimicrobial therapy for 428 episodes of bacteremia in an 850-bed university hospital was prospectively evaluated for 1 year to measure the impact of two factors--blood culture results and the therapy chosen by infectious diseases specialists (IDSs)--on quality of treatment and outcome. Initial shock, a simplified acute physiology score of >15, and inappropriateness of the empirical treatment were independently associated with increased mortality. Empirical treatment was appropriate in 63% of the episodes. This proportion reached 78% for the episodes treated by IDSs, compared with 54% for the others (P < .001). After availability of blood culture results, the proportion of appropriate treatments increased to 94%, with 97% for IDS-treated patients and 89% for other patients (P = .008). IDSs more frequently shifted to oral antibiotics and used fewer broad-spectrum drugs. This study underlines the impact of blood culture results and of IDSs on the prescription of appropriate treatment for bacteremia and on the better use of antimicrobial drugs.

Administration, Oral↗
PubMed1999

Levofloxacin in the empirical treatment of patients with suspected bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial.

An open, randomized, multinational, multicentre study was conducted to compare the efficacy, safety and tolerability of levofloxacin 500 mg twice daily with imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized adult patients with clinically suspected bacteraemia/ sepsis. Levofloxacin patients could change from iv to oral administration after a minimum of 48 h iv treatment if clinical signs and symptoms of sepsis had improved. The primary efficacy analysis was based on the clinical and bacteriological response at clinical endpoint. A total of 503 patients were randomized and 499 included in the intent-to-treat population. The per-protocol population comprised 287 patients with bacteriologically proven infection. Clinical cure rates at clinical endpoint in the intent-to-treat population and per-protocol population were 77% (184/239) and 89% (125/140), respectively, for levofloxacin and 68% (178/260) and 85% (125/147), respectively, for imipenem/cilastatin. At follow-up, the cure rates in the per-protocol population were 84% for levofloxacin and 69% for imipenem/cilastatin. The 95% confidence interval for both populations showed that levofloxacin was as effective as imipenem/cilastatin. A satisfactory bacteriological response was obtained in 87% (96/110) of levofloxacin patients and 84% (97/116) of imipenem/cilastatin patients at clinical endpoint. Adverse events possibly related to the study drug were reported in 74 (31%) levofloxacin patients and 79 (30%) imipenem/cilastatin patients. There were no clinically appreciable differences between the treatment groups. Levofloxacin 500 mg twice daily, either iv or as sequential iv/oral therapy, was as effective and well tolerated as imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized patients with suspected bacteraemia/sepsis.

Adolescent↗
PubMed1999

Penetration of meropenem in lung, bronchial mucosa, and pleural tissues.

Lung, bronchial mucosa, and pleural tissue samples were obtained from 14 patients undergoing lung surgery 1 to 5 h after administration of 1 g of meropenem. The mean (range) peak concentrations of meropenem were 3.9 (0.2 to 8.2), 6.6 (3.0 to 13.3), and 2.8 (0.6 to 7.8) mg/kg of tissue, respectively, exceeding the MICs at which 90% of isolates are inhibited for most respiratory pathogens.

Adult↗
PubMed1999

CD40 ligation prevents Trypanosoma cruzi infection through interleukin-12 upregulation.

Because of the critical role of the CD40-CD40 ligand (CD40L) pathway in the induction and effector phases of immune responses, we investigated the effects of CD40 ligation on the control of Trypanosoma cruzi infection. First, we observed that supernatants of murine spleen cells stimulated by CD40L-transfected 3T3 fibroblasts (3T3-CD40L transfectants) prevent the infection of mouse peritoneal macrophages (MPM) by T. cruzi. This phenomenon depends on de novo production of nitric oxide (NO) as it is prevented by the addition of N-nitro-L-arginine methyl ester, a NO synthase inhibitor. NO production requires interleukin (IL)-12-mediated gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) synthesis as demonstrated by inhibition experiments using neutralizing anti-IL-12, anti-IFN-gamma, and anti-TNF-alpha monoclonal antibodies (MAb). We found that an activating anti-CD40 MAb also directly stimulates IFN-gamma-activated MPM to produce NO and thereby to control T. cruzi infection. To determine the in vivo relevance of these in vitro findings, mice were injected with 3T3-CD40L transfectants or 3T3 control fibroblasts at the time of T. cruzi inoculation. We observed that in vivo CD40 ligation dramatically reduced both parasitemia and the mortality rate of T. cruzi-infected mice. A reduced parasitemia was still observed when the injection of 3T3-CD40L transfectants was delayed 8 days postinfection. It was abolished by injection of anti-IL-12 MAb. Taken together, these data establish that CD40 ligation facilitates the control of T. cruzi infection through a cascade involving IL-12, IFN-gamma, and NO.

3T3 Cells↗
PubMed1999

Design and evaluation of a human immunodeficiency virus type 1 RNA assay using nucleic acid sequence-based amplification technology able to quantify both group M and O viruses by using the long terminal repeat as target.

Currently available human immunodeficiency virus type 1 (HIV-1) RNA quantification assays can detect most viruses of the group M subtypes, but a substantial number are missed or not quantified reliably. Viruses of HIV-1 group O cannot be detected by any commercially available assay. We developed and evaluated a quantitative assay based on nucleic acid sequence-based amplification (NASBA) technology, with primers and probes located in the conserved long terminal repeat (LTR) region of the HIV-1 genome. In 68 of 72 serum samples from individuals infected with HIV-1 subtypes A to H of group M, viruses could be detected and quantified. In serum samples from two patients infected with HIV-1 group O viruses, these viruses as well could be detected and quantified. In contrast, the currently used gag-based assay underestimated the presence of subtype A viruses and could not detect subtype G and group O viruses. The discrepancy between the results of the two assays may be explained by the number of mismatches found within and among the probe and primer regions of the subtype isolates. These data indicate that LTR-based assays, including the NASBA format chosen here, are better suited to monitoring HIV-1 therapy than are gag-based assays in an era in which multiple HIV-1 subtypes and groups are spreading worldwide.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Gastric perforation due to mucormycosis after heart-lung and heart transplantation.

BACKGROUND: Gastrointestinal complications are a well-documented source of morbidity and mortality after heart and lung transplantation. METHODS: We report on two patients who presented with gastric perforation caused by mucormycosis during the first 2 months after heart-lung and heart transplantation. RESULTS: In the first patient, the clinical presentation was insidious and the diagnosis was made at an advanced stage of the disease. Despite surgery and aggressive antifungal treatment, the patient died. In the second patient, the diagnosis was made promptly, but despite antifungal treatment, he presented with gastric perforation within a week. CONCLUSIONS: These cases illustrate that fungal invasive disease may be a cause of early gastrointestinal perforation after solid organ transplantation.

Adult↗
PubMed1998

IL-10 up-regulates nitric oxide (NO) synthesis by lipopolysaccharide (LPS)-activated macrophages: improved control of Trypanosoma cruzi infection.

We examined the effects of IL-10 on tumour necrosis factor-alpha (TNF-alpha) and NO production by LPS-activated macrophages and on the ability of these cells to control Trypanosoma cruzi infection. We first observed that the addition of rIL-10 to macrophages of the J774 cell line decreased their synthesis of TNF-alpha but increased their release of NO in a dose-dependent manner. In parallel, treatment of J774 cells with rIL-10 resulted in a better control of T. cruzi infection involving up-regulation of NO synthesis, as it was not observed in presence of N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. The enhancing effect of rIL-10 on NO production was not observed on peritoneal macrophages from wild-type C57Bl/6 mice, but well on macrophages from IL-10 knock-out mice. The control of NO production by endogenous IL-10 was confirmed by the demonstration that neutralization of IL-10 secreted by LPS-activated macrophages from wild-type mice inhibited their production of NO and, in parallel, their ability to control T. cruzi infection. Taken together, these data demonstrate that both exogenous and endogenous IL-10 up-regulate the production of NO by LPS-activated macrophages and improve thereby their ability to clear T. cruzi infection.

Animals↗
PubMed1998

Vocal cord immobilisation in diffuse idiopathic skeletal hyperostosis (DISH).

Advanced forms of diffuse idiopathic skeletal hyperostosis or Forestier's disease can induce dysphagia and significant respiratory symptoms such as hoarseness, dyspnea, snoring and laryngeal stridor. Severe respiratory distress is very rare. Two identical cases of chronic respiratory distress due to bilateral vocal cord adduction-fixation in conjunction with skeletal pathology in the cervical area are presented. The clinical, diagnostic and therapeutic work-up and the prognostic outcome of the laryngeal pathology are discussed.

Aged↗
PubMed1997

[Renal venous thrombosis: a forgotten complication of acute pyelonephritis].

BACKGROUND: Renal vein thrombosis, long recognized as a classical complication of acute pyelonephritis, has become exceptional since the advent of antibiotics. CASE REPORT: An 85-year-old woman was hospitalized for acute Escherichia coli nephritis. Computed tomography with contrast agent injection was performed due to clinical improvement after an 8-day course of antibiotics and demonstrated purulent urine collection on an obstructive calicial stone as well as homolateral thrombosis of the renal vein. Duplex Doppler confirmed the diagnosis. Pulmonary embolism was evidenced by pulmonary scintigraphy. The clinical course was satisfactory after urine drainage and efficacious antibiotics. CONCLUSION: Renal vein thrombosis remains a severe though uncommon complication of acute pyelonephritis. Computed tomography with iodine, contrast agent or duplex Doppler allows noninvasive diagnosis.

Acute Disease↗
PubMed1997

A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients.

One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9)/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 0.01) of test-drug-related side-effects, compared to c-AMB. Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 0.01). Analysis was by intention-to-treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 0.5 x 10(9)/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3. A statistically significant difference was found between c-AMB and L-AMB3 (P = 0.03) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms. It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open-label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.

Adult↗
PubMed1996

Administration of anti-CD3 monoclonal antibody during experimental Chagas' disease induces CD8+ cell-dependent lethal shock.

The injection of the 145-2C11 anti-CD3 MoAb in mice induces a polyclonal T cell activation resulting in the release of several cytokines, including interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). As these cytokines are known to be involved in the host defence against Trypanosoma cruzi, we measured serum levels of IFN-gamma and TNF-alpha after injection of the 145-2C11 MoAb in the course of experimental murine Chagas' disease. Compared with control mice, T. cruzi-infected BALB/c mice were found to be primed to secrete very high levels of IFN-gamma and TNF-alpha from the second and the first week of infection, respectively, up to the chronic phase. In vivo cell depletion experiments indicated that CD8+ T cells were responsible for these dramatic hyperproductions of IFN-gamma and TNF-alpha. While all control mice survived anti-CD3 MoAb injection, a high lethality rate was observed in T. cruzi-infected mice within 24 h after anti-CD3 MoAb challenge. Pretreatment with neutralizing anti-IFN-gamma MoAb or depletion of CD8+ T cell population dramatically decreased the mortality induced by anti-CD3 MoAb in T. cruzi-infected mice. Finally, we showed that anti-CD3 MoAb injection in T. cruzi-infected mice was followed by a massive release of nitric oxide (NO) metabolites, which was partially reduced by IFN-gamma or TNF-alpha neutralization. The administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before anti-CD3 MoAb challenge did not prevent and even enhanced lethality in T. cruzi-infected mice, suggesting that NO overproduction and lethal shock are not causally related. We conclude that injection of anti-CD3 MoAb in the course of experimental Chagas' disease induces a CD8+ cell-dependent shock mediated by IFN-gamma and TNF-alpha.

Animals↗
PubMed1996

Construction and expression of bi-functional proteins of single-chain Fv with effector domains.

We fused various polypeptide extensions to the C-termini of single chain Fv (scFv) and disulfide-stabilized Fv (dsFv) fragments to facilitate detection of bi-functional proteins or to add biological effector domains, which included the human metallothionein (HMT) motif and biotin mimetic sequence. These bi-functional proteins were expressed and secreted in a recombinant Pichia pastoris system and showed specific anti-idiotype binding activity, as determined by competitive radioimmunoassaying. However, the fusion protein constructed with dsFv- HMT, but not scFv-HMT, had lost this binding activity. The interruption of the structural conformation as a result in dsFv-HMT may be explained by the interactions between the cysteines engineered in dsFv domains and the cysteines in the HMT region.

Amino Acid Sequence↗
PubMed1996

Creatinine clearance as predictor of tobramycin elimination in adult patients with cystic fibrosis.

Assessment of renal function and relating this parameter to amino-glycoside clearance is important for an appropriate individualization of dosage regimens in patients with impaired renal function. However, it has been suggested that in cystic fibrosis (CF), creatinine clearance (CrCl) is not a good predictor of tobramycin clearance because of a lack of correlation. The aim of this study was to investigate the correlation between the tobramycin clearance and the measured CrCl. In addition, because most pharmacokinetic computer models use an a priori relationship between CrCl and tobramycin elimination rate constant [k(el)], regression analysis of k(el) on CrCl was performed. Eighteen CF patients (12 men, 6 women, ages 21-55 years) were treated with intravenous tobramycin. Blood and urine samples were collected for tobramycin analysis and determination of the CrCl. For each patient, CrCl was also estimated using the formulas of Cockcroft and Gault (C/G), Jelliffe I (J I), and Jelliffe II (J II). Predictive performance of these formulas was evaluated using mean error and mean squared error as reflections of bias and precision. Tobramycin total body clearance as well as renal clearance correlated significantly with CrCl (r = 0.52; p = 0.02 and r = 0.78; p = 0.02, respectively). Regression of the tobramycin k(el) versus CrCl gave the following equation: k(el) = 0.135 + 0.00134*CrCl/1.73 m2 (r = 0.64; p = 0.004). The 95% confidence interval of intercept and slope of the regression line were 0.019-0.251 and 0.00049-0.00219, respectively. The formulas of C/G, J I, and J II all overpredicted CrCl. Bias was 19, 24, and 8 ml/min, and precision was 37, 42, and 33 ml/min, respectively, for the C/G, J I, and J II formulas. In our CF population the J II formula gave the best estimation of the CrCl but calculated estimates deviated -25(-)+62% from measured values.

Adult↗