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Biomedical subjects

L White

Publications and source records attributed to L White.

At least 127 records · Page 7Linked to original sources

Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates.

Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Association of education with incidence of cognitive impairment in three established populations for epidemiologic studies of the elderly.

We analyzed the association of education, occupation, and sex with incidence of cognitive impairment using data from three communities in the Established Populations for Epidemiologic Studies of the Elderly (EPESE) projects (New Haven, East Boston, and Iowa). Participants were initially interviewed in 1981-1983, with follow-up 3 and 6 years later. Incident cognitive impairment was defined on the basis of either: (1) increase in the number of errors in Short Portable Mental Status Questionnaire (SPMSQ) (i.e. from a baseline level below the cutoff value to a score above the cutoff), or (2) inability to respond to interview questions at a follow-up contact (requiring a proxy informant), or (3) death with a recorded diagnosis of a dementing illness. In multiple logistic regression models, the major factors predicting the development of cognitive impairment were advanced age, any errors on baseline SPMSQ, 8 or fewer years of education, and occupation. Education and occupation remained significant predictors after controlling for age, site, sex, stroke, and baseline SPMSQ score.

Aged↗

Ocular penetration of topical ciprofloxacin and norfloxacin drops and their effect upon eyelid flora.

A double blind, prospective study was undertaken to compare aqueous humour penetration of topical 0.3% norfloxacin and 0.3% ciprofloxacin and their effect upon normal eyelid flora in 39 patients undergoing cataract surgery. Lid swabs were taken before and after six 1 hourly applications of single drops of ciprofloxacin or norfloxacin given before surgery. Aqueous humour was aspirated at surgery and antibiotic concentration assayed using high performance liquid chromatography. The mean aqueous humour concentrations were: ciprofloxacin 220 ng ml-1, norfloxacin 140 ng ml-1. Although this difference was not statistically significant (p = 0.112) the trend demonstrated may be relevant clinically, especially considering the greater activity of ciprofloxacin. Both coagulase negative staphylococcal (p = 0.004) and total bacterial (p = 0.019) lid counts dropped sixfold after ciprofloxacin treatment but the smaller reductions noted after norfloxacin application did not achieve statistical significance (p > 0.1). The reduction of external eye flora experienced with ciprofloxacin suggests that this may be a useful presurgical prophylactic agent.

Administration, Topical↗

Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: a phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group.

PURPOSE: This pilot study of the Australia and New Zealand Childhood Cancer Study Group investigated the effectiveness and toxicity of a regimen incorporating vincristine (VCR), etoposide, and divided-dose, escalating cyclophosphamide (CPA) (VETOPEC) in 23 patients aged 1 to 20 years with solid tumors. PATIENTS AND METHODS: Seventeen patients (group A) had recurrent or refractory tumors after prior multiagent therapy, and six patients (group B) with adverse prognostic indicators were treated at initial presentation. Treatment cycles were 21 to 28 days and consisted of vincristine (0.05 mg/kg) on days 1 and 14, with etoposide (2.5 mg/kg/d) plus escalating CPA on days 1, 2, and 3. The CPA dosage was escalated from 30 mg/kg/d in cycle no. 1 by 5 mg/kg/d in each cycle to a maximum of 55 mg/kg/d in cycle no. 6. RESULTS: Of 20 patients assessable for tumor response, 19 (95%) responded after two to six cycles of VETOPEC: seven complete responses (CRs); eight very good partial responses (VGPRs); and four partial responses (PRs). In group A, 13 of 14 (93%) assessable patients responded (five CRs, four VGPRs, four PRs), and in group B, five stage IV and one stage III patient achieved two CRs and four VGPRs. The principal toxicity was myelosuppression. Grade IV neutropenia occurred after 98% of cycles, and the incidence of grade IV thrombocytopenia increased from 37% after cycle no. 1 to 91% after cycle no. 6 (P = .002). A total of 115 cycles delivered were followed by 62 febrile admissions (54%), and showed a significant rise with increasing cycles (P = .001). One patient died of septicemia. CONCLUSION: This combination and scheduling produced a high response rate in patients with recurrent, refractory, or advanced solid tumors of childhood. Further studies of this regimen and of strategies to reduce hematologic toxicity are warranted.

Adolescent↗

Who's in charge here? The General Hospital School of Nursing, St. John's, Newfoundland, 1903-30.

This essay examines the effect of the political economy of the General Hospital, St. John's, Newfoundland, on the development of the General Hospital School of Nursing from 1903 to 1930. The General Hospital was the only government-funded hospital in Newfoundland providing health care for the entire colony of 124,000 people. The School of Nursing was the only nurses' training program in Newfoundland until 1929 when a second school opened. Two conflicting personalities who played an important role in the development of nursing at these institutions were Mary Southcott, Superintendent of Nurses from 1903 to 1916, and Lawrence Keegan, Medical Superintendent of the hospital. The resulting tension between these two people led to a major crisis at the hospital in 1914 with the government instigating a Royal Commission to examine the struggle between the nurses and the administration (doctors and government officials) over who had the power and authority to determine the nurses' role and status within the hospital. After a year of investigation, the Royal Commission agreed with Keegan's view and subsequently organized the hospital along new lines. Southcott was fired and a new, more compliant nurse put in her place. The second period, 1916 to 1930, saw the recommendations of the Royal Commission implemented, including establishment of a Board of Governors to run the hospital on a more businesslike footing.

Canada↗

The experience of a single Australian paediatric oncology unit. 1000 patients 1964-1987.

OBJECTIVE: To determine the survival for children with malignant disease diagnosed in the period 1964-1987 and treated in a single paediatric oncology unit. DESIGN: Records of patients treated by the Department of Haematology and Oncology at the Prince of Wales Children's Hospital were reviewed to determine the survival of children with cancer according to decade of diagnosis and diagnostic group. PATIENTS: Patients were eligible for the study if referred for treatment at or soon after diagnosis of malignancy. One thousand patients were treated during the study period. There were 363 with acute lymphoblastic leukaemia (ALL), 126 with tumours of the central nervous system (CNS), 86 with acute non-lymphoblastic leukaemia (ANLL), 81 with lymphoma, 79 with neural crest tumours, 69 with renal tumours, 66 with bone sarcomas, 53 with soft tissue sarcomas, and 77 with various other diagnoses. Age range was one day to 20.75 years. INTERVENTIONS: Treatment included surgery, radiotherapy and chemotherapy in a variety of protocols. RESULTS: Ten-year survival for the 1960s, 1970s and 1980s was 15%, 51% and 64% respectively (P < 0.001), excluding tumours of the CNS. From 1985 onwards, actual survival at five years has been 79%. Survival from Wilms' tumour and Hodgkin's disease remained high throughout the study period, and significant improvement in survival occurred with ALL, non-Hodgkin's lymphoma (NHL) and osteogenic sarcoma. Survival remained poor with neuroblastoma and ANLL. CONCLUSIONS: Significant improvement in outcomes for childhood malignancy has been achieved over the last three decades, with five-year survival currently at 79% (excluding tumours of the CNS). Some diagnostic groups have had only small improvements in outcome and require new strategies.

Adolescent↗

Heterotransplantation of early B-lineage acute lymphoblastic leukemia using a solubilized attachment matrix (Matrigel).

Maintenance of long term culture and conventional xenografting of early B-lineage acute lymphoblastic leukemia cells is most difficult. Matrigel, a solubilized attachment matrix shown to aid growth of anchorage dependent solid tumors, was studied in heterotransplantation. Material for xenografting was derived from 5 patient bone marrow aspirates and 5 cell lines previously established and maintained by intraocular inoculation in nude mice. Specimens were injected by 3 methods: intraocular (n = 397); s.c. in medium (n = 78); and s.c. in medium supplemented by Matrigel (n = 69). With intraocular injection, 6 of 10 cell sources grew with respective ingraftment rates of 29-76%. Using the conventional s.c. method, no tumors resulted. The addition of Matrigel produced s.c. ingraftment from 8 of 10 cell sources (ingraftment rate, 50-100%). Immunophenotype, histopathology, and karyotype of the cells derived after Matrigel dependent ingraftment correlated with the cells of origin. It is concluded that Matrigel enables establishment and maintenance of early B-lineage acute lymphoblastic leukemia cell growth in a s.c. xenograft model.

Animals↗

The Diego blood group locus is located on chromosome 17q.

The Diego blood group locus (DI) is tightly linked to the erythrocyte surface protein band 3 locus (EPB3) with z = 5.42 at theta = 0.00 for combined paternal and maternal meioses. Looser linkage between DI and D17S41 (z = 3.14 at theta = 0.09) for combined paternal and maternal meioses was also established. Taken together, these results indicate that the Diego blood group locus is located on the long arm of chromosome 17.

Anion Exchange Protein 1, Erythrocyte↗

Postoperative chemotherapy without radiation in young children with malignant non-astrocytic brain tumours. A report from the Australia and New Zealand Childhood Cancer Study Group (ANZCCSG).

Young children with malignant brain tumours have particularly poor survival and manifest severe sequelae of radiation therapy. A multi-institutional pilot study of post-operative primary chemotherapy for children under 3 years with primitive neuroectodermal tumours (PNET) or ependymoma was initiated in 1987. The chemotherapy protocol comprised carboplatin, vincristine and the "eight drugs in 1 day" regimen. Radiation was recommended only if tumour progression or recurrence was documented. A total of 14 patients between 5 and 36 months of age were enrolled. Seven had supratentorial tumours (PNET, pinealoblastoma, intracranial retinoblastoma) with multiple predictors of adverse outcome. Four of these responded to initial chemotherapy but subsequently progressed and all had died by 16 months from diagnosis. The seven patients with infratentorial tumours (three medulloblastomas, four ependymomas) had more favourable predictors of outcome: no meningeal dissemination and gross macroscopic resection in six of the seven cases. One patient progressed rapidly and died within 5 months. The other six are alive at 37-57 months from diagnosis. Four are in continuous complete remission at 57, 51, 41 and 37 months, respectively from the time of their tumour resection. One is described as having stable disease with a persistent radiographic lesion at 41 months from diagnosis. One has relapsed on two occasions and is the only surviving patient to have been irradiated. Intelligence scores for the six long-term survivors have thus for remained within the normal range. It is suggested that some infants with standard-risk ependymoma and, possibly, medulloblastoma may be cured without radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Alveolar-arterial oxygen gradients in elderly patients with suspected pulmonary embolism.

STUDY OBJECTIVE: To determine the usefulness of the alveolar-arterial oxygen gradient for detecting pulmonary embolism in elderly patients presenting to the emergency department. DESIGN: Retrospective cohort analysis. SETTING: Two university-affiliated community hospitals. TYPE OF PARTICIPANTS: Consecutive patients more than 64 years old who underwent pulmonary angiography for the presumed diagnosis of acute pulmonary embolism. INTERVENTIONS: Arterial blood gas samples were chosen for comparative analysis only if obtained when the pulmonary embolism first was suspected clinically (before lung scans or angiograms) and the patient was breathing room air. Predicted PaO2 and alveolar-arterial gradients were calculated for each patient. MEASUREMENT AND RESULTS: A total of 123 patients met all study criteria; mean +/- SD patient age was 74 +/- 6 years. Fifty-four patients (44%) had angiographically documented emboli. In this cohort, the mean PaO2 was 61.4 mm Hg (range, 34.3 to 83.8 mm Hg), and the mean alveolar-arterial gradient was 46.6 mm Hg (range, 19 to 75 mm Hg). In three patients, the alveolar-arterial gradient was normal for their age. However, in comparison with the 69 patients with normal pulmonary angiograms, there was no significant difference in PaO2 (mean, 59.9 mm Hg) or the alveolar-arterial gradient (mean, 46.0 mm Hg). CONCLUSION: An elevated alveolar-arterial oxygen gradient is entirely nonspecific in the elderly population and is of minimal use in the diagnosis of acute pulmonary embolism. A normal alveolar-arterial gradient should not preclude further diagnostic procedures if there is a high index of suspicion.

Aged↗

A pilot study of EVAP/ABV chemotherapy in 25 newly diagnosed children with Hodgkin's disease.

Twenty five children with newly diagnosed Hodgkin's disease were clinically staged and treated with a chemotherapy protocol designed to reduce delayed toxicity. Four patients without macroscopic residual disease after biopsy received three cycles of hybrid EVAP/ABV. All remain in CR 31-46 months from diagnosis. One other developed fever and rash considered to be due to Ara-C and was treated with MOPP. Twenty patients had macroscopic residual disease after biopsy and were treated with two cycles of EVAP alone and reassessed with imaging and gallium scans. Twelve achieved CR, seven PR and one was not evaluable. Patients in CR were subsequently treated with 2-4 cycles of hybrid EVAP/ABV, while those in PR received 3-4 cycles. At a median follow up of 37 months the overall survival was 100%, relapse free 79% and treatment failure free 60%. Eight patients had mediastinal widening > 1/3 thoracic width. At the completion of the protocol five achieved CR, two PR and one was withdrawn from study at investigator preference. One patient has subsequently relapsed. Of the evaluable ten patients without a mediastinal presentation all achieved CR but three relapsed at 10, 13 and 18 months from diagnosis. Patients who achieved a PR only, relapsed or were withdrawn from study have been salvaged with MOPP or Ch1VPP chemotherapy.

Adolescent↗

Cluster headache: the ventilatory response to transient hypoxia with pure nitrogen.

To determine whether the carotid body plays a pathogenetic role in cluster headache, 20 cluster headache patients have been studied. Of these, 11 patients were in the interparoxysmal cluster phase, and 9 were in remission. Comparison was made with healthy subjects matched for sex, age, and smoking habits. Transient hypoxia was induced by inhalation of 1-8 breaths of 100% nitrogen (N2), until the arterial oxygen saturation (SaO2) decreased to around 80%. Changes in ventilation (tidal volume, inspiratory minute ventilation (VI), and end-tidal PCO2 (PETCO2)), were analyzed breath-by-breath. Under basal conditions, cluster headache patients had a slightly higher SaO2 and VI when compared to controls. PETCO2 was significantly lower (P < 0.05) during the cluster period as measured by Wilcoxon signed rank test for paired data, and during remission, according to the Student's paired t-test, in comparison with controls. After exposure to N2, no significant difference was found in the rate of reduction of SaO2 between any of the groups. A higher absolute increase in VI, but a relative (%) decrease in VI at moderate hypoxia were measured, the differences between patients and controls being on the border of the level of significance. Chemoreceptor sensitivity of the carotid body, expressed as the slope of a regression curve obtained by plotting the increase in VI against the reduction in SaO2, showed no statistical difference between the groups. The results do not support the hypothesis of a pathogenetic role for the carotid body in cluster headache.

Administration, Inhalation↗

A novel method for the detection of TNF-alpha in gingival crevicular fluid.

This paper reviews results on the cytokine TNF and its role as a mediator in the pathway leading from bacteria to tissue destruction. Also reviewed is the immunoadsorption-magnetic separation technology used for the capture of TNF from the sulcus and the cluster assay used for quantification of the bead-bound TNF. A comparison of the results obtained with this technique revealed recovery of TNF in a higher percent of sites than when using the paper strips. Furthermore, the cluster assay was found to be as sensitive as the ELISA. Finally, TNF values in crevicular fluid were compared to TNF in other body fluids. The recovery of TNF at aseptic sites suggests that TNF production might be initiated by factors other than bacteria, and therefore that, through their ability to initiate TNF production, other processes might be responsible for the tissue destruction of periodontitis.

Gingival Crevicular Fluid↗

The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development.

The rhombotin (RBTN1 or Ttg-1) gene was first identified at a chromosome translocation in a T-cell acute leukaemia and later used to isolate two related genes (RBTN2 or Ttg-2 and RBTN3). Complete characterization of these genes in man and mouse shows that all three encode cysteine-rich proteins with typical LIM domains. RBTN1 and RBTN3-derived proteins have 98% identity in the LIM domains but are located on separate chromosomes in man and in mouse while RBTN1 and RBTN2, both located on human chromosome 11p but are on separate chromosomes in mouse, are only 48% identical in this part of the protein. The exon organization of RBTN1 and RBTN3 genes are similar, both having an intron, absent from the RBTN2 gene, in the LIM2-encoding region. The remarkable similarity between rbtn-1 and rbtn-3 proteins is parallelled in their expression patterns in mouse development, since both genes show high expression in restricted areas of the brain, but little lymphoid expression. rbtn-2 expression, however, is more ubiquitous. This gene shows a low level of thymus expression but high expression in fetal liver, adult spleen and B-cell lines, consistent with a role in B-cell development. These results suggest multiple cellular targets for the action of these proteins during development.

Adult↗