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Biomedical subjects

B L Pizer

Publications and source records attributed to B L Pizer.

16 recordsLinked to original sources

Establishment of functional B cell memory against parvovirus B19 capsid proteins may be associated with resolution of persistent infection.

Parvovirus B19 (B19) infection can occur during acute lymphoblastic leukemia and persistent viral infection can occur despite intravenous immunoglobulin administration. Here, evidence is presented that resolution of persistent B19 infection in an acute lymphoblastic leukemia patient may be associated with the simultaneous strengthening of antigen-specific B cell memory against the B19 capsid protein VP2 and diminution in the memory response against the B19 non-structural protein 1 (NS1). Determination of antigen-specific B cell memory status may enhance the serological and molecular analyses of persistent B19 infection.

B-Lymphocytes↗

A prospective study of septicaemia on a paediatric oncology unit: a three-year experience at The Royal Liverpool Children's Hospital, Alder Hey, UK.

Septicaemia in neutropaenic patients is predominantly due to gut translocation [endogenous septicaemia] and contamination of the central venous catheter by microorganisms not carried by the patient [exogenous septicaemia]. To control both types of infection, a protocol was implemented based on pre 1990's parenteral and enteral antimicrobials together with strict hygiene. Surveillance cultures of throat/rectum were taken to distinguish exogenous from endogenous septicaemia and enteral non-absorbable antibiotics are administered as part of selective decontamination of the digestive tract (SDD). This protocol was evaluated in a 14-bedded paediatric oncology unit over a period of 3 years. 313 Septicaemia episodes were recorded in 131 children. 28.4% of the septicaemias were caused by microorganisms associated with the unit, equivalent to 0.82 episodes per 100 patient days. Low-level pathogens such as coagulase-negative staphylococci caused more than 70% of infections. Amongst the potential pathogens, Pseudomonas species (7.8%) and Staphylococcus aureus (5.5%) were predominant. Antibiotic resistance was rare with no superinfections or outbreaks. Four patients (3%) died, two due to Candida species and two due to Pseudomonas aeruginosa. We believe that the addition of enteral non-absorbable antibiotics to systemic antibiotics maintained a low level of resistance and mortality but a randomised controlled trial is indicated to confirm these observations.

Adolescent↗

Magnetic resonance venography in assessing venous patency after multiple venous catheters.

BACKGROUND/PURPOSE: Venous thrombosis is a well-recognised complication of central venous catheters (CVC). The aim of the study was to assess the value of magnetic resonance venography (MRV) in assessing venous patency in children with suspected venous thrombosis. METHODS: Contrast studies through the CVC (linogram) and Doppler ultrasonography were the initial investigations performed in children with suspected CVC-related thrombosis. Two-dimensional gated inflow and phase contrast MRV also was performed to assess the extent of venous thrombosis and to locate patent veins for replacement CVC. When the MRV identified a suitable patent vein, the CVC was reinserted by direct venous cut down or the percutaneous method under a general anaesthetic. RESULTS: A total of 25 children (median age, 5 years; range, 2 months to 17 years) who had multiple CVC insertions (median, 3; range, 1-9), underwent MRV for suspected venous thrombosis. Of 10 patients in whom the catheter was completely occluded, MRV identified extensive thrombosis of the central veins in 6. In 7 other children the linogram showed adherent thrombus at the tip of the CVC only. In 5 of these 7 children MRV showed extensive thrombosis of the vein in which the catheters were placed. Doppler ultrasonography diagnosed thrombotic occlusion of the neck veins in 7 children. The MRV studies showed more extensive thrombosis in 4 of these 7 patients. Additionally, MRV showed thrombosis of the intrathoracic veins in 11 patients who had patent neck veins on ultrasound scan. MRV identified a patent vein for reinsertion of CVC in 22 of 25 children. At operation, venous patency was confirmed in 20 patients (91%). CONCLUSION: MRV in children with suspected CVC-related thrombosis is more accurate than Doppler ultrasonography, and contrast studies for defining the extent of venous thrombosis. MRV correctly shows venous anatomy and patency for reinsertion of CVC.

Adolescent↗

Chemotherapy for spinal cord astrocytoma: can natural history be modified?

Standard treatment of spinal cord astrocytomas is based upon surgery, followed by radiotherapy when resection is incomplete or when histology is of high grade. Owing to the major consequences of radiotherapy on the spine in childhood, alternative therapies must be explored. The potential role of chemotherapy in the management of spinal cord astrocytoma remains to be defined. Two patients are described. The first was a 19-month-old child with an anaplastic astrocytoma of the cervical spinal cord that progressed rapidly after initial partial resection. Chemotherapy was begun according to the UKCCSG Baby Brain Protocol, with marked clinical improvement. Reassessment by MRI at 4 months showed improvement, and at the end of treatment no evaluable disease remained. The second was a 4-year-old child with a recurrent low-grade astrocytoma. Chemotherapy according to the SIOP Protocol for Low Grade Gliomas was administered for 3 months, after which marked tumour regression was seen, with neurological recovery. These patients demonstrate the potential value and low morbidity of chemotherapy in spinal cord astrocytoma. The management of this rare tumour is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Congenital malignant rhabdoid tumour of the gum margin.

The case of an infant born with a large polypoid tumour arising from the mouth is described. The tumour had the histological, immunohistochemical and ultrastructural phenotype of an extrarenal malignant rhabdoid tumour and followed an aggressive clinical course. This is one of the few reported cases of malignant rhabdoid tumour to present at birth. The oral tumour was associated with a mass in the posterior cranial fossa. This was most likely to be a simultaneous second primary tumour.

Fatal Outcome↗

Pharmacokinetics and dose estimates following intrathecal administration of 131I-monoclonal antibodies for the treatment of central nervous system malignancies.

PURPOSE: Treatment of malignant disease in the central nervous system (CNS) with systemic radiolabeled monoclonal antibodies (MoAbs) is compromised by poor penetration into the cerebrospinal fluid (CSF), limited diffusion into solid tumors, and the generation of anti-mouse antibodies. To attempt to avoid these problems we have treated patients with diffuse neoplastic meningitis with radioimmunoconjugates injected directly into the intrathecal space. METHODS AND MATERIALS: Tumor-specific MoAbs were conjugated to Iodine-131 (131I) (629-3331 MBq) by the Iodogen technique, and administered via an intraventricular reservoir. A clinical response rate of approximately 33% was achieved, with better results in more radiosensitive tumors. Here, we present detailed pharmacodynamic data on patients receiving this intracompartmental targeted therapy. RESULTS: Elimination from the ventricular CSF appeared biphasic, with more rapid clearance occurring in the first 24 h. Radioimmunoconjugate entered the subarachnoid space and subsequently the vascular compartment. From this information, the areas under the effective activity curves for ventricular CSF, blood, and subarachnoid CSF were calculated to permit dosimetry. Critical organ doses were calculated using conventional medical internal radiation dose (MIRD) formalism. Where available, S-values were taken from standard tables. To calculate the doses to CSF, brain, and spinal cord, S-values were evaluated using the models described in the text. CONCLUSION: A marked advantage could be demonstrated for the dose delivered to tumor cells within the CSF as compared to other neural elements.

Antibodies, Monoclonal↗

Congenital astroblastoma: an immunohistochemical study. Case report.

Astroblastoma is a rare type of glial tumor, usually occurring in older children and young adults. It has a distinctive histological appearance that is characterized by a radiating arrangement of tumor cells that form perivascular pseudorosettes. The authors report only the second case of astroblastoma presenting in congenital form. Following subtotal tumor resection, the infant received 10 courses of chemotherapy consisting of vincristine, etoposide, and carboplatinum. Evidence is presented for a tumor response to chemotherapy, a previously unreported observation. The child is alive 2.5 years after diagnosis with satisfactory functional status. Immunohistological and ultrastructural features of this tumor are presented. The discussion focuses on the biology, natural history, and management of this unusual neoplasm.

Astrocytoma↗

Cystic metastatic cerebral neuroblastoma.

Intracerebral neuroblastoma is an exceedingly rare manifestation of intracranial neuroblastoma and has been described as a solid lesion. Cystic metastatic intracerebral neuroblastoma has not been described. We report a case of histologically proven metastatic intracerebral neuroblastoma presenting in a cystic form 1 year after diagnosis and treatment of a solid intra-abdominal neuroblastoma. The imaging and clinical appearance of this case was indistinguishable from that of intracerebral cystic lesions caused by infection or inflammation. It has been suggested that, due to more aggressive treatment of neuroblastoma, patients are surviving longer and consequently intracranial involvement is becoming more frequent. It is important to be aware of this cystic manifestation of the disease.

Abdominal Neoplasms↗

Rifampicin in pneumococcal meningoencephalitis.

The cases are reported of two infants with pneumococcal meningitis in whom initial antibiotic treatment was ineffective despite the organisms being sensitive to the drugs used. A clinical and radiological diagnosis of meningoencephalitis was made. A rapid improvement followed the addition of rifampicin treatment.

Anti-Bacterial Agents↗

Neonatal aortic arch thrombosis.

An infant presented shortly after birth with signs suggestive of aortic coarctation. Echocardiography revealed an extensive aortic arch thrombus, not amenable to surgery. Thrombolytic agents reduced thrombus size, enabling survival, but failed to prevent neurological damage secondary to cerebral embolisation.

Aorta, Thoracic↗

The potential of targeted radiotherapy in the treatment of central nervous system leukaemia.

We describe the results of clinical studies investigating the role of monoclonal antibody (MoAb) targeted radiotherapy in the treatment of central nervous system (CNS) leukaemia. Seven children, aged 3-16 years, in second or subsequent meningeal relapse of acute lymphoblastic leukaemia (ALL), have been treated. Each patient received a single injection into the cerebrospinal fluid (CSF) of between 629 and 1,702 MBq of 131-Iodine (131I) conjugated to MoAb HD37 (CD19, n = 2), WCMH 15.14 (CD10, n = 4) or both antibodies (n = 1). One patient underwent a course of repeated targeted therapy following his initial treatment. Acute toxicity was manifest in five patients by a transient aseptic meningitis. Myelosuppression was observed in four children. Pharmacokinetic studies investigated whole body, blood and CSF clearance of radioisotope. Progressively more rapid systemic clearance of 131I was noted in the patient receiving repeated therapy, indicating the development of the human anti-mouse Ig (HAMA) response. Dosimetric studies revealed a radiation dose to the red bone marrow of between 0.6 and 2.2 Gy. The dose to the subarachnoid CSF was between 12.2 and 25.3 Gy, over six times higher than that to the surface tissue of the brain and spinal cord and between 40 and 140 times higher than that to the whole brain. In all but one patient, a transient complete response, in terms of disappearance of lymphoblasts from the CSF, was observed. These studies demonstrate the feasibility of targeted radiotherapy in CNS ALL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry.

A pilot study was undertaken to determine the feasibility of infusing 131I labelled monoclonal antibodies (MoAbs) into either the cavity remaining after resection of malignant glioma or into glioma cysts. Of the seven patients recruited into the study, two had cystic lesions and five resection cavities. Six of the seven were treated after relapse from primary therapy. All patients apart from one, were given a single injection of 131I conjugated to a MoAb (ERIC-1) recognising the human neural cell adhesion molecule (NCAM). One patient received a further injection of 131I-MoAb after regrowth of their disease. Pharmacokinetic studies revealed that the MoAb remained predominantly in the tumour cavity with little leakage into the systemic compartment. This resulted in a high calculated dose of radiation being delivered to the tumour cells either lining or within close proximity to the cavity/cyst wall. In such a small study, it is not possible to determine accurately response rates, but individual patient responses were observed. This, along with the low toxicity noted, demonstrates the feasibility of using 131I-MoAbs in this way. With 131I, radiation dose is deposited in tissue to a depth of 1 mm from the source. The possibility of applying isotopes such as 90Yttrium which will irradiate tumour/tissue to a greater depth (6 mm) is discussed in context with the biology of glioma infiltration into normal brain parenchyma.

Adolescent↗

Prolonged positive airway pressure for severe neonatal tracheobronchomalacia.

A very low birthweight preterm baby with respiratory distress at birth was found to have severe congenital tracheobronchomalacia. Continuous positive airway pressure was given through an endotracheal tube without tracheostomy for 15 weeks before unassisted respiration could be maintained. Diagnosis was made and progress monitored by laryngobronchoscopy on three occasions.

Bronchial Diseases↗

A teratoid Wilms' tumor with raised serum alpha-fetoprotein level.

Tumor markers are used to diagnose certain cancers and can be useful in monitoring the response to treatment. We describe a renal tumor with the features of a teratoid nephroblastoma associated with a raised serum level of alpha-fetoprotein (AFP). The serum AFP remained high during chemotherapy but returned to normal after nephrectomy. AFP was demonstrated by immunohistochemistry in cysts lined by enteric-type epithelium within the tumor. Cytogenetic examination of the tumor showed a clone of cells with trisomy 8. Raised serum AFP has not previously been described in teratoid Wilms' tumor.

Blood Chemical Analysis↗