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Biomedical subjects

L White

Publications and source records attributed to L White.

At least 163 records · Page 9Linked to original sources
PubMed1991

Chemotherapy for retinoblastoma: where do we go from here? A review of published literature and meeting abstracts, including discussions during the Vth International Symposium on Retinoblastoma, October 1990.

The history of the application of chemotherapy in the management of retinoblastoma (RB) may conveniently be divided into three eras: initial enthusiasm (from early 1950s to mid 1970s), realism (from late 1970s to mid 1980s) and possibility (from mid 1980s to the future). Available data from each of these eras are reviewed in the clinical categories of: intraocular RB, micrometastatic RB and overt dissemination. The latter is further sub-classified into: orbital invasion, central nervous system involvement and systemic metastases. Experimental models are described with particular emphasis on future directions. Early reports led to initial optimism subsequently dampened by a more critical approach. Recent results with increasingly effective chemotherapeutic regimens offer the possibility of a valid contribution in each of the above clinical settings. A multi-modality approach is recommended optimizing a combination of the most active drugs with continuing refinements of other techniques. In selected patients with intraocular, and particularly bilateral RB, visual outcome may be enhanced by the combined use of non-surgical modalities. Adjuvant treatment of presumed micrometastases needs to be studied within risk categories defined by prognostic factors. Invasion of the ocular coats and/or of the optic nerve are the most relevant factors but there are continued difficulties in defining the extent of involvement and eligibility criteria for such a strategy. Overt dissemination has recently been demonstrated to be curable in each of the three subgroups above. Intensive regimens incorporating cyclophosphamide, vincristine, cisplatinum, etoposide and possibly doxorubicin, plus intrathecal agents in combination with radiation therapy and, in some instances supplemented by bone marrow transplantation have produced promising results. Multi-institutional collaboration has been encouraged by the recently formed International Committee for the Staging and Management of Retinoblastoma, opening the way for prospective clinical trials. At the same time both laboratory and clinical experimental studies are being pursued and may produce further improvements in currently available strategies.

Drug Therapy↗
PubMed1991

Sister chromatid exchange analysis of human cells exposed to diagnostic levels of ultrasound.

Lymphocyte and lymphoblastoid cells were exposed in vitro to diagnostic levels of ultrasonic beams delivered by a Hewlett-Packard CE 30001 and a GE system with a 5 MHz linear transducer for 20 sec, 1 min, 5 min, and 20 min. Temperature and cavitation effects were controlled and there were matched sham exposures. The synergistic effects of theophylline with ultrasonography also were investigated. Small increases in sister chromatid exchange levels were observed after ultrasonic exposure, but increases were so small as to be unlikely to have clinical relevance. Theophylline was found to have no effect and ultrasonography had no effect on cell viability.

Adult↗
PubMed1991

A study of chromosome 11p13 translocations involving TCR beta and TCR delta in human T cell leukaemia.

A frequent site of translocation damage in human T-ALL has been localized to a specific region of chromosome band 11p13. Five new T-ALL cases are described which break in the major T-ALLbcr region of 11p13, two involving a novel translocation t(7;11)(q35;p13), with breakage at the T cell receptor (TCR) beta gene from 7q35, and three involving TCR delta from 14q11 in the more common t(11;14)(p13;q11). Analysis of the mechanism of one T-ALLbcr/TCR beta translocation and a previously described t(11;14)(p13;q11) was conducted by genomic cloning of translocation breakpoints, using the polymerase chain reaction (PCR). Both seem to have occurred by recombinase error, but only the t(7;11) showed sequence-specific joining. Nonetheless recombinase mediation of the t(11;14) is implied by the presence of N-region addition (a hallmark of recombinase joins) on both derivative chromosomes. These observations reinforce the view that translocations in the T-ALLbcr region of chromosome 11p13 are a major lesion in human T-ALL. In addition, these can occur by mimicry of VDJ joining, but sequence specificity is not obligatory.

Base Sequence↗
PubMed1991

Chemotherapy in retinoblastoma: current status and future directions.

In the past, chemotherapy has had only a minor role in the treatment of retinoblastoma. There are three clinical settings in which chemotherapy may be useful, namely, in intraocular retinoblastoma, in cases of micrometastatic spread, and where there are overt extraocular metastases. Clinical trials in all three settings have been impeded by biological, statistical, and ethical limitations. Extensive review of the literature, including case reports, small retrospective series, and occasional prospective studies, does not lead to any clear conclusions. However, responsiveness of retinoblastoma to chemotherapy in each of the above categories has been documented, and cyclophosphamide is consistently the most effective single agent. For small intraocular tumors, there may be a role for a combination of nonoperative treatment modalities. Whether decreased occurrence of extraocular relapse is produced by the use of adjuvant chemotherapy for presumed micrometastatic disease remains controversial A prospective randomized study of stratified high-risk categories of patients needs to be done on an international level. The most widely accepted regimen in this setting is the combination of cyclophosphamide and vincristine. Improving the survival of patients with overt metastases is a major challenge, which is especially relevant to the less developed parts of the world. Several multiagent regimens, particularly in combination with bone marrow transplantation, offer some promise. Experimental models are being used to overcome some of the limitations of clinical studies. Evaluations of responsiveness to chemotherapy, both in cell culture and animal models, are being conducted. Other areas being investigated include pharmacologic enhancement of radiotherapy and hematoporphyrin photodynamic therapy, use of tumor cell targeting techniques, differentiating agents, vitamin D, and immunotherapy. The nude mouse intraocular xenograft model appears to confirm clinical observations for responsiveness to conventional therapeutic agents.

Animals↗
PubMed1990

Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine.

90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV.

Antibodies, Viral↗
PubMed1990

Trisomy 4 in a case of acute biphenotypic leukemia.

Trisomy 4 was the sole chromosome anomaly in a 5-year-old girl with acute leukemia. Morphologically, there appeared to be distinct myeloid and lymphoid blast cells on presentation. Immunophenotyping, however, showed extensive overlap of myeloid and lymphoid markers, confirming the leukemia to be biphenotypic rather than true "bilineal." She attained remission only after lymphoid-cell-specific induction was added to the initial "myeloid type" induction. She relapsed 4 years later with morphologically acute lymphocytic leukemia (French-American-British L2 type) despite still retaining the original immunophenotypic characteristics. She was successfully reinduced and subsequently received an autologous bone marrow transplant. Second relapse, morphologically and immunophenotypically similar to the first, occurred 5 months after transplant.

Acute Disease↗
PubMed1990

Heterotransplantation of human lymphoid neoplasms using a nude mouse intraocular xenograft model.

There are few effective models for the study of human lymphoid neoplasms, including in vivo xenografts in immunocompromised animals. Exploiting the additional immune privilege of the anterior chamber of the nude mouse eye, a novel method of direct heterotransplantation of cells from childhood leukemias and lymphomas has been developed. The establishment and characterization of 18 lymphoid xenograft cell lines maintained in the nude mouse intraocular model are reported. Cell sources for heterotransplantation were specimens of bone marrow, peripheral blood, or lymphomatous masses obtained at either diagnosis or recurrence of disease in the patients. The 18 patients and resultant cell lines were grouped into four immunophenotypic categories: Category 1, B-lineage (pre-B and early pre-B), "common" acute lymphatic leukemias; Category 2, cell lines of similar immunophenotype derived from patients with unusual features; Category 3, B-cell neoplasms and cell lines; and Category 4, neoplasms and cell lines in part or totally of T-cell origin. With reference to these groupings, rates of ingraftment from clinical specimens varied according to immunophenotype and disease status: Category 1, 1 of 15 at diagnosis, 5 of 7 at relapse; Category 2, 1 of 1 at diagnosis, 2 of 2 at relapse; Category 3, 6 of 6 at diagnosis; and Category 4, 2 of 9 at diagnosis, 1 of 1 with persistent disease. Rearrangements of the genes for immunoglobulin heavy chain or kappa light chain and for beta subunit of the T-cell receptor gene were demonstrated according to immunophenotype, with the exception of one cell line which showed no rearrangements. Evidence of Epstein-Barr virus DNA was shown in only one cell line, of B-cell immunophenotype. Cytology, histopathology, and electron microscopy in representative patient and xenograft samples demonstrated correlations between the specimens of origin and cells or sections from ingrafted tumors in mice. It is concluded that the direct heterotransplantation of cells from childhood leukemias and lymphomas to the anterior chamber of the nude mouse eye provides a relevant and reproducible model for the maintenance and study of human lymphoid neoplasms.

Animals↗
PubMed1990

Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse.

Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo.

Actuarial Analysis↗
PubMed1990

Intraperitoneal ciprofloxacin for the treatment of peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD).

Ciprofloxacin was evaluated as single-agent therapy for the empirical treatment of patients presenting with CAPD peritonitis in an open, uncontrolled trial. Seventy-five episodes of peritonitis in 44 patients receiving continuous ambulatory peritoneal dialysis were entered in the study. The antibiotic was administered intraperitoneally, at a dose of 50 mg/l in each bag of dialysate, for seven days. Treatment with ciprofloxacin was appropriate (organisms isolated sensitive to ciprofloxacin) and successful (clinical and bacteriological cure of peritonitis) in 62 (83%) of the 75 episodes. The mean ciprofloxacin concentrations in serum and effluent were 1.1 mg/l (range 0-2.9 mg/l) and 10.0 mg/l (range 0.2-33.4 mg/l), respectively, with no evidence of accumulation. Side effects were seen in two patients only, and were mild and transitory.

Adult↗
PubMed1990

An unusual type of hangman's fracture.

An unusual fracture of the axis was best displayed using three-dimensional reconstruction. The fracture was noted to differ significantly from the usual "hangman's fracture" as it involved the body of C2 with subluxation of the anterior part of C2 forward on C3 and without "decompression" of the spinal canal at the C2 level. Better understanding made feasible by three-dimensional reconstruction had important treatment implications in this case.

Adult↗
PubMed1990

Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants.

Phase I studies of an oral quadrivalent rotavirus vaccine were conducted in 130 Venezuelan infants 10 to 20 weeks of age. The vaccine consists of a mixture of equal amounts of rhesus rotavirus (RRV) vaccine (serotype 3 [VP7]) and each of three human rotavirus-RRV reassortant strains: D x RRV (serotype 1 [VP7]), DS1 x RRV (serotype 2 [VP7]), and ST3 x RRV (serotype 4 [VP7]). Three different doses of the quadrivalent vaccine (0.25 x 10(4), 0.5 x 10(4), and 10(4) PFU of each component) were evaluated sequentially for safety and antigenicity in placebo-controlled, double-blind trials. Starting the day after vaccination, the infants were monitored by daily home visits for 7 days. Only minor reactions were observed during this period; these were limited to mild transient febrile episodes which began day 2 or 3 after vaccination and lasted 1 to 2 days in 15 to 30% of the infants. Serological studies demonstrated that 68 to 96% of the infants developed a rotavirus serum immunoglobulin A response following vaccination. However, when tested by plaque reduction neutralization assay against individual human rotavirus serotype 1, 2, 3, or 4, the response rates ranged from 4 to 23% with the low dose, 21 to 33% with the medium dose, and 32 to 58% with the high dose. Most (73 to 79%) infants developed neutralizing antibodies to RRV following administration of each dose schedule. Vaccine virus shedding was analyzed by utilizing tissue culture isolation of virus from stool. All of the infants who received the lower of medium dose and 89% of those fed the high dose shed one or more components of the vaccine. Analyses of rotavirus serotypes isolated from the stool of infants who received the 0.25 x 10(4) -PFU dose revealed that DS1 x RRV was the most commonly shed vaccine component, followed by RRV, D x RRV, and ST3 x RRV in that order.

Administration, Oral↗
PubMed1990

Identification of human rotavirus serotype by hybridization to polymerase chain reaction-generated probes derived from a hyperdivergent region of the gene encoding outer capsid protein VP7.

We have synthesized 32P-labeled hybridization probes from a hyperdivergent region (nucleotides 51 to 392) of the rotavirus gene encoding the VP7 glycoprotein by using the polymerase chain reaction method. Both RNA (after an initial reverse transcription step) and cloned cDNA from human rotavirus serotypes 1 through 4 could be used as templates to amplify this region. High-stringency hybridization of each of the four probes to rotavirus RNAs dotted on nylon membranes allowed the specific detection of corresponding sequences and thus permitted identification of the serotype of the strains dotted. The procedure was useful when applied to rotaviruses isolated from field studies.

Antigens, Viral↗
PubMed1990

Prenatal nutrition protocol.

This Protocol contains basic nutrition concepts relevant to the prenatal period. It is intended for use in a prenatal clinic as a base from which to provide nutrition counseling for the normal prenatal patient.

Clinical Protocols↗
PubMed1990

Responsiveness of retinoblastoma to local diaziquone. Studies in a xenograft model.

The benefits of chemotherapy in the management of early or bilateral retinoblastoma are doubtful and are difficult to study. A xenograft model has been developed in which the therapeutic response of retinoblastoma heterotransplanted to the anterior chambers of nude mouse eyes can be evaluated. Cyclophosphamide has been shown to be the most effective of the conventional agents. The new drug diaziquone was tested in the model against five patient-derived xenografted cell lines, using both systemic (intraperitoneal) and local (eye drops) methods of administration. A total of 359 xenograft tumors in 229 experimental animals were monitored after treatment with intraperitoneal cyclophosphamide, intraperitoneal diaziquone, or local diaziquone. Responses to all three regimens were demonstrated in each of the five xenograft lines. Diaziquone compared favorably with cyclophosphamide as systemically administered chemotherapy. Local diaziquone was as effective as intraperitoneal injection in producing tumor responses. It is suggested that methods for local administration of diaziquone may be adapted to the clinical setting, and that a role for this modality may be found in a combination of nonoperative approaches to the management of small, intraocular tumors.

Animals↗
PubMed1989

Atypical multidrug resistance in a therapy-induced drug-resistant human leukemia cell line (LALW-2): resistance to Vinca alkaloids independent of P-glycoprotein.

Near diploid leukemic T-cells (LALW-2), exposed to cytotoxic drugs only as a consequence of therapy administered to the donor patient, have been maintained by serial xenograft in nude mice. In comparison with the leukemic line CCRF-CEM, using a growth inhibition assay, LALW-2 cells were resistant to Vinca alkaloids and actinomycin D (relative resistance, 200-fold or more), were slightly resistant to Adriamycin (relative resistance, 4-fold), and showed no resistance to daunorubicin or teniposide. By comparison, a vincristine-resistant CEM subline developed in our laboratory (CEM/VCR R) was resistant to all these agents by at least 30-fold. The VCR R subline served as a positive control, confirming the previously reported correlation between multidrug resistance and amplification of the P-glycoprotein gene. Comparison of CEM, CEM/VCR R, and LALW-2 cells establish that the P-glycoprotein gene was not amplified or overexpressed in the LALW-2 cells; neither could the gene product be detected by immunoblotting in extracts from these cells. The LALW-2 cells were further distinguished from CEM/VCR R cells due to the lack of increased vincristine efflux by the xenografted cells, an effect readily demonstrable in the CEM/VCR R cells. However, although LALW-2 cells efflux vincristine at the same rate as CCRF-CEM cells, the xenografted cells exhibited a reduced rate of vincristine accumulation. Uptake of daunorubicin by LALW-2 cells was not distinguished from that by CEM cells, consistent with similar 50% inhibitory dose levels for this drug in both cell populations, and differentiating both from CEM/VCR R cells. Thus, clinical resistance in this case appears to be an "atypical" form of multidrug resistance specifically distinguished by resistance to Vinca alkaloids and actinomycin D occurring in the absence of increased amounts of P-glycoprotein and manifesting decreased drug uptake.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Therapy-induced drug resistance in a human leukemia line (LALW-2). A clinically relevant model.

A human leukemic T-cell line, LALW-2, established by xenografting in nude mice, has been maintained through 14 serial passages. The cells display consistent morphologic features, immunophenotype, and karyotypic aberrations (including an 11;14 translocation) and exhibit rearrangement of the T-cell receptor beta-chain gene. The growth rate of LALW-2 xenografts was differentially affected by drugs administered to host mice, the cells being resistant to cytotoxic agents (particularly methotrexate and doxorubicin) used in treatment of the donor patient. In short-term in vitro culture, LALW-2 cells exhibited extreme resistance to methotrexate and were also resistant to vincristine, vinblastine, dactinomycin, and doxorubicin. The findings differ from those obtained with laboratory-derived methotrexate or multidrug-resistant cell lines. The response of LALW-2 cells, in both the nude mouse model and in vitro, is consistent with acquisition of drug-resistance as a result of clinical treatment.

Animals↗