Biomedical subjects

B Widemann

Publications and source records attributed to B Widemann.

13 recordsLinked to original sources

PubMed2006

Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group.

BACKGROUND: [corrected] Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression. PATIENTS AND METHODS: Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg.min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle. RESULTS: Forty-one patients, age 2-19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n = 9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (>6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n = 8), medulloblastoma/PNET (n = 6) and low-grade glioma (n = 2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma. CONCLUSION: The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.

Adolescent↗

PubMed2001

Effect of probenecid on ventricular cerebrospinal fluid methotrexate pharmacokinetics after intralumbar administration in nonhuman primates.

PURPOSE: Intrathecal methotrexate (MTX) achieves high concentrations in the cerebrospinal fluid (CSF) following intralumbar administration. However, peak ventricular CSF MTX concentrations are highly variable and are < 10% of those achieved with intraventricular dosing. The objectives of this study were to evaluate the effect of intralumbar and intravenous probenecid on ventricular CSF MTX concentrations after intralumbar administration of MTX, and to compare the pharmacokinetics of MTX after intralumbar and intraventricular administration. METHODS: Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received 0.5 mg intraventricular (lateral ventricle) MTX, or 0.5 mg intralumbar MTX with and without intralumbar or intravenous probenecid. Animals were kept prone for 1 h after MTX administration, and ventricular CSF was sampled up to 48 h from a fourth ventricular Ommaya reservoir. MTX concentrations were measured using the dihydrofolate reductase enzyme inhibition assay. Area under the ventricular CSF MTX concentration-time curve (AUC) was used as a measure of MTX exposure. RESULTS: Peak ventricular CSF MTX concentrations and AUCs were highly variable after intralumbar MTX administration. Ventricular CSF MTX AUCs increased by a mean of 3.2-fold after the addition of intralumbar probenecid. Intravenous administration of probenecid did not result in an increase in ventricular CSF MTX AUCs. Asymptomatic pleocytosis was observed in all animals after intralumbar probenecid administration. Ventricular CSF MTX concentrations and AUCs were less variable after intraventricular administration of MTX. CONCLUSION: The administration of intralumbar but not intravenous probenecid increases the ventricular CSF MTX exposure after intralumbar MTX administration.

Animals↗

PubMed2001

Phase I trial of lobradimil (RMP-7) and carboplatin in children with brain tumors.

PURPOSE: To determine the maximum tolerated dose (MTD), the incidence and severity of toxicities, and the pharmacokinetics of lobradimil administered intravenously over 10 min in combination with carboplatin in children with refractory brain tumors. METHODS: A group of 25 children with primary brain tumors received carboplatin and lobradimil on two consecutive days every 28 days. The 10-min lobradimil infusion began 5 min before the end of the carboplatin infusion. Four lobradimil dose levels (100, 300, 450 and 600 ng/kg ideal body weight, IBW) were studied in cohorts of 4 to 13 patients. Carboplatin was adaptively dosed based on the glomerular filtration rate to achieve a target plasma area under the concentration-time curve (AUC) of 7.0 mg min/ml per course (5.0 mg min/ml for patients who had previously received craniospinal radiation or myeloablative chemotherapy). RESULTS: Lobradimil toxicity was immediate, tolerable and rapidly reversible. The most frequent toxicities were hypotension, flushing, headache and gastrointestinal complaints. One patient on the 600 ng/kg dose level had a seizure during the lobradimil infusion. The incidence and severity of lobradimil toxicities were not dose-related and the lobradimil dose was not escalated beyond the 600 ng/kg IBW dose level. Two patients had partial responses and ten patients had stable disease. Myelosuppression (thrombocytopenia more prominent than neutropenia) was the primary toxicity attributed to carboplatin. Lobradimil pharmacokinetics were characterized by rapid clearance from the plasma compartment and substantial interpatient variability. CONCLUSIONS: The combination of carboplatin and lobradimil is safe and tolerable. An MTD for lobradimil was not defined because toxicity was not dose-related. The recommended pediatric phase II dose of lobradimil is 600 ng/kg IBW.

Adolescent↗

PubMed1999

Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine.

Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase.

Aldehyde Oxidase↗

PubMed1995

Cytomegalovirus ureteritis as a cause of renal failure in a child infected with the human immunodeficiency virus.

Cytomegalovirus (CMV) infection is common in patients infected with human immunodeficiency virus. Hemorrhagic cystitis and tubulointerstitial nephritis have been recognized as complications of CMV infection, and these complications lead to hematuria and compromised renal function. We describe a case of CMV infection of the ureters in a child with vertically acquired human immunodeficiency virus infection; the child presented with severe suprapubic pain, and prolonged macroscopic hematuria and intermittent acute renal failure developed subsequently.

Acute Kidney Injury↗

PubMed1993

In vivo metabolism of childhood posterior fossa tumors and primitive neuroectodermal tumors before and after treatment.

BACKGROUND: Despite an increasing interest in the clinical application of positron emission tomography (PET) in tumors of the adult patient as a diagnostic and prognostic tool, only a few studies have been concerned with the usefulness of PET with [18F]2-deoxy-2-fluoro-D-glucose (FDG) in childhood tumors. METHODS: Fifteen children and young adults (0.5-26.0 years of age) with histologically confirmed brain tumors were studied with PET and FDG. Seven children with medulloblastoma (n = 5) or primitive neuroectodermal tumor (PNET) (n = 2) underwent repeated PET studies during their therapy. The other eight children with medulloblastoma (n = 5) or astrocytoma (n = 3) were studied only once before initiation of treatment. A close clinical follow-up was performed in every case. RESULTS: Comparison of local glucose metabolic rates obtained in the various tumor lesions revealed that the mean rates found in medulloblastomas (mean glucose metabolic rate, 42.8 +/- 14.03 mumol/100 g/min) were twice as high as the rates measured in either PNET (17.3 +/- 4.5 mumol/100g/min) or infratentorial gliomas (21.8 +/- 4.2 mumol/100g/min). The high metabolism of medulloblastomas enabled the observer to identify the tumor more easily and to clearly separate it from the surrounding unaffected brain tissue. In the seven patients with follow-up PET studies during therapy, decreasing or increasing ratios of tumor-to-white matter metabolic rate were not only commensurate with neuroradiologically defined tumor reduction or growth, but also corresponded to the duration of initial clinical improvement. CONCLUSIONS: These preliminary results suggest that PET with FDG may be a useful tool to evaluate metabolic activity of pediatric brain tumors over time and to assess response to treatment.

Adolescent↗

PubMed1993

Airway endoscopy in the diagnosis and treatment of bacterial tracheitis in children.

Children with bacterial tracheitis present with the symptoms of viral laryngotracheobronchitis or epiglottitis, but do not respond to appropriate therapy for these diseases and frequently develop acute respiratory decompensation. Since the treatment and outcome of bacterial tracheitis differ so much from those of viral laryngotracheobronchitis and epiglottitis, prompt and accurate diagnosis is essential. The aim of this study was to evaluate the significance of different diagnostic characteristics in a group of eleven patients and to compare the results to those recently reported in the pediatric and otorhinolaryngologic literature. The present study suggests that reliable predictive factors do not exist for bacterial tracheitis. No single clinical, radiological or laboratory feature was a reliable diagnostic predictor for bacterial tracheitis, nor was it any combination of these features. The only diagnostic procedure to distinguish bacterial tracheitis accurately and promptly from other forms of acute obstructive upper airway diseases was direct laryngo-tracheo-bronchoscopy. Following endoscopic removal of all tracheal secretions and pulmonary toilet, nasotracheal intubation provides sufficient airway maintenance and obviates the need for tracheostomy. Endoscopy is thus diagnostic and therapeutic at the same time. If bacterial tracheitis is suspected a direct laryngoscopy and rigid tracheobronchoscopy should be performed under general anesthesia, as prompt diagnosis and adequate treatment are essential to survival. The cultures of the purulent tracheal secretions frequently revealed Staphylococcus aureus in combination with various pathogens, particularly the involvement of Pseudomonas aeruginosa was noted in two patients. Our data imply a susceptibility of children with Down's syndrome or immunodeficiency to bacterial tracheitis.

Acute Disease↗

PubMed1992

Dysplastic gangliocytoma of cerebellum in a newborn. Diagnosis by ultrasonography and MRI.

A cerebellar lesion was detected by ultrasonography (US) in a symptomatic newborn. Magnetic Resonance Imaging (MRI) demonstrated this lesion as a gyriform structure. Therefore a rare dysplastic gangliocytoma was suspected, which was compatible with histopathology. Immunohistochemical studies (monoclonal antibody Ki-67) showed signs of progression.

Cerebellar Neoplasms↗

PubMed1992

The fibrous metaphyseal defect in early stage. Differential diagnosis to metaphysitis.

In a 22-month-old boy a fibrous metaphyseal defect (FMD) was diagnosed by radiological follow-up examinations. The initial radiological finding could not be differentiated from metaphysitis because of its early manifestation and stage. Eleven months later, magnetic resonance imaging (MRI) with Gadolinium (Gd)-DTPA demonstrated a small central area of increased signal intensity. Based on known angiographic findings with fibrous metaphyseal defects, one may hypothesize that this is best explained by a hypervascularized area.

Bone Diseases, Developmental↗

PubMed1990

[Bone marrow metastases of neuroblastoma: MRT in comparison with bone marrow cytology and mIBG scintigraphy].

Thirteen MRT investigations of the knee region of nine children with neuroblastoma stage IV/III were performed in order to demonstrate bone-marrow metastases. The MRT-findings were correlated with bone-marrow cytology, immunofluorescence, and mIBG-scintigraphy. MRT showed a high sensitivity in demonstrating bone-marrow abnormalities, although bone-marrow aspiration and mIBG-scintigraphy will still be needed to make a specific diagnosis. On the other hand, signs of bone-marrow involvement in MRT investigations without positive findings in bone-marrow cytology and mIBG-scintigraphy may be the first evidence of bone-marrow metastases.

3-Iodobenzylguanidine↗

PubMed1989

Mycoplasmal pneumonias in childhood. Roentgen features, differential diagnosis and review of literature.

The chest radiographs of 23 children, aged between 4.2 to 15.4 years with serologically proven mycoplasmal pneumonia were reviewed and correlated with the findings in literature. Three different patterns of infiltration were seen in equal frequency: 1) peribronchial and perivascular interstitial infiltrates, 2) patchy consolidations and 3) homogeneous acinar consolidations like groundglass. The lower fields of the lungs were mostly affected. Pattern 1 was always observed bilaterally. Enlargement of the hilar glands was a common finding. Pleural effusion was rare. Numerous differential diagnoses, especially viral pneumonias, feature the heterogeneity of the infiltration patterns. As no pattern is pathognomonic for mycoplasmal pneumonia clinical symptoms and signs, the epidemiological situation and laboratory data may confirm the diagnosis.

Adolescent↗

PubMed1987

[Is hip sonography meaningful as a screening method?].

The results of screening 162 non-selected neonates by sonography of the hips indicate that this is not a desirable screening method. Sonography is, however, indicted in neonatal groups which are considered to be at risk.

Female↗

PubMed1987

[Is hip sonography in premature infants necessary as a screening procedure?].

Screening sonography of the hip in 132 premature infants indicates that prematurity is not a risk for congenital dysplasia/dislocation of the hip. However, for reasons explained in the text, screening should be carried out before discharge from hospital. Follow-up examinations are necessary only for infants with known risk factors for dysplasia/dislocation of the hip.

Female↗