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Biomedical subjects

N Phillips

Publications and source records attributed to N Phillips.

At least 19 recordsLinked to original sources

Mucosal vaccination against schistosomiasis using liposome-associated Sm 28 kDa glutathione S-transferase.

A variety of experimental models have shown that immunization using the glutathione S-transferase from Schistosoma mansoni (Sm28GST) can induce protective immunity against this parasite. This immunity has been related to the production of Th2 type antibodies against the antigen in both mice and humans. The work presented in this paper describes the development of a mucosal immunization protocol using liposomes which is designed to promote production of specific antibodies of isotypes related to a Th2 immune response. The liposomes were multilamellar and composed of various synthetic phospholipid mixtures. The liposome vector was used to convey the Sm28GST antigen to gut associated lymphoid tissue. The association of the Sm28GST antigen with liposomes containing different lipid mixtures was initially studied. The degree of interaction of the antigen was found to increase with the hydrocarbon chain length of the lipids used. It was demonstrated that the protein was present on both the inner and the outer membranes of the liposome vesicles. It was also shown that the major epitopes of Sm28GST were accessible to specific antibodies, confirming a conservation of its main antigenic features. Additionally, enzymatic activity of the protein/liposome complex was also demonstrated, indicating a conservation of the tertiary structure of the protein. An optimal Sm28GST/ liposome complex was established and administered orally to mice. This treatment resulted in both a mucosal and systemic immune response to the antigen Sm28GST. This was demonstrated by the detection of specific IgA in gut washes and specific IgG1, IgG2b in sera. Immunization by Sm28GST/liposome complex followed by challenge with parasite showed that Sm28GST given orally in these conditions bore protective activity. This last result opens the possibility of mucosal vaccination against schistosomiasis.

Administration, Oral

Psychological morbidity in obstetric-gynaecology patients: testing the need for expanded psychiatry services in obstetric-gynaecology facilities.

OBJECTIVE: The present study set out to determine general levels of distress, anxiety and depression in an obstetric-gynaecology inpatient population and to ascertain levels of patient satisfaction with services. METHOD: 200 English-speaking consecutive admissions to the hospital filled out a package of questionnaires consisting of a demographic data form, the 30-item General Health Questionnaire, the Speilberger State-Trait Anxiety Inventory, the Inventory to Diagnose Depression and a Patient Satisfaction with Services Questionnaire. 134 packages were fully completed. RESULTS: The most significant findings were: first, that high levels of anxiety prevailed, with approximately 1/3 of patients at or above the 75th percentile for anxiety levels; and second, that those patients born in non-English speaking countries were significantly more dissatisfied with their care. CONCLUSIONS: The results of this study suggest that there is a need for increased awareness of and further research into the psychological needs of obstetric-gynaecology patients.

Adult

Progress and evaluation of a consultation-liaison psychiatry service to an obstetric-gynaecology hospital.

OBJECTIVE: Recently we described the establishment and first 6 months of a psychiatric consultation-liaison service to a Melbourne obstetric-gynaecology teaching hospital. The follow-up report evaluates the service in two ways: first, it compares referral data for the 12 months of 1992 with that of the first 6 months of operation in 1990; and second, it reports on results of a survey of referrer and patient satisfaction with the service. METHOD: Referral data were collected for the data comparison from the consultation-liaison referral book and patients' files. Referrer and patient satisfaction was evaluated by questionnaires sent to 45 medical staff, 7 charge nurses, and 100 consecutive patients. RESULT: A fairly constant referral rate for inpatients has emerged at 0.8%, this very low referral rate being some cause for concern. An internal shift in the type of referrals over time has developed, with an increase in obstetric and a decrease in gynaecology referrals. High referrer satisfaction, with 86% of the doctors finding the consultation(s) "very" or "quite" helpful, and high patient satisfaction, with 83% of respondents having found the consultation(s) "very" or "quite" helpful, was found. CONCLUSIONS: Despite high referrer and consumer satisfaction, and objective evidence of need, this pioneering consultation-liaison service in obstetric-gynaecology continues to be grossly under-utilised. Increasing the referral rate will be one of the greatest challenges in the future of this service.

Adaptation, Psychological

Oximeter reliability in a subzero environment.

BACKGROUND: Pulse oximeters optimize care in the pre-hospital setting. As British Columbia ambulance teams often provide care in subzero temperatures, we conducted a study to determine the reliability of 3 commercially-available portable oximeters in a subzero environment. NULL HYPOTHESIS: We hypothesized that there is no significant difference between SaO2 readings obtained using a pulse oximeter at room temperature and a pulse oximeter operating at sub-zero temperatures. METHODS: Subjects were stable normothermic children in intensive care on Hewlett Packard monitors (control unit) at room temperature. The test units were packed in dry ice in an insulated bin (temperature - 15 degrees C to -30 degrees C) and their sensors placed on the subjects, contralateral to the control sensors. Data were collected simultaneously from test and control units immediately following validation of control unit values by co-oximetry (blood gas). RESULTS: No data were unacceptable. Two units (Propaq 106EC and Nonin 8500N) functioned well to < -15 degrees C, providing data comparable to those obtained from the control unit (p < 0.001). The Siemens Micro O2 did not function at the temperatures tested. CONCLUSIONS: Monitor users who require equipment to function in subzero environments (military, Coast Guard, Mountain Rescue) should ensure that function is reliable, and could test units using this method.

Analysis of Variance

Recombinant interleukin-2 infusions and decreased IgG2 subclass concentrations.

The administration of low doses of recombinant interleukin-2 (rIL-2) in vivo to patients with malignant neoplasms has been demonstrated to selectively increase the number of circulating natural killer (NK) cells in these patients. Recent evidence from SCID mouse models suggests that IgG subclass levels can be influenced by the presence and activity of NK cells. Therefore, we sought to examine the effect of rIL-2 infusions on human serum IgG subclass concentrations. We determined serum IgG subclass concentrations in 27 cancer patients receiving low-dose rIL-2 by daily continuous intravenous infusion. Eleven of these patients had active, metastatic, nonhematologic tumors; 16 patients had received IL-2 when they were in a minimal residual disease state after autologous or allogeneic bone marrow transplantation. Samples obtained before beginning IL-2 therapy and 8 to 10 weeks into therapy were tested. Treatment with IL-2 resulted in an increase in the percentage of CD56+ NK cells from 18% to 54% (P = .0001). A significant decrease in geometric mean IgG2 concentration from 2,017 micrograms/mL to 1,655 micrograms/mL was noted over this time interval (P = .03). Furthermore, the geometric mean IgG2 concentration after treatment was significantly lower than that of healthy controls (P = .026). In contrast, no significant changes in serum IgG1, IgG3, or IgG4 were noted during r-IL2 infusions. Our data suggest that rIL-2 treatment selectively decreases serum IgG2 concentrations. We speculate that increased NK cells mediate downregulation of human serum IgG2.

Adult

Physical activity, medical history, and risk of testicular cancer (Alberta and British Columbia, Canada).

In order to evaluate risk factors for germ cell cancers, we conducted a case-control study of 510 men with testicular cancer aged 15 to 79 years and 996 randomly selected age-matched controls in the provinces of British Columbia and Alberta, Canada. Subjects completed a mailed questionnaire providing data on education level, ethnic origin, medical history, smoking, occupation, and recreational and sports activity. The response rate among cases was 80.3 percent and among controls was 68.1 percent. After controlling for age and ethnic origin, undescended testis was associated positively with risk of testicular cancer (odds ratio [OR] = 3.5; 95 percent confidence interval [CI] = 2.2-5.7) as was inguinal hernia requiring surgery (OR = 2.0, CI = 1.3-2.9), and hydrocoele (OR = 2.6, CI = 1.4-5.1). Risk of testicular cancer increased with height, with subjects taller than 180 cm having a significantly increased risk compared with those 174 cm or less (OR = 1.5, CI = 1.1-2.1). A moderate to high level of recreational activity level was associated inversely with testicular cancer risk (OR = 0.6, CI = 0.5-0.8).

Adolescent

The Kropp-onlay procedure (Pippi Salle procedure): a simplification of the technique of urethral lengthening. Preliminary results in eight patients.

OBJECTIVE: To lengthen the urethra to increase bladder outlet resistance in adolescent girls with a neurogenic bladder. PATIENTS AND METHODS: During a 2-year period (1992-94), eight girls (mean age 13.5 years, range 9-19) underwent a Kropp-onlay urethral lengthening associated, for six of them, with a bladder augmentation. Seven of the eight patients patients were spina bifida and confined to a wheelchair. One patient had had a previous transverse myelitis. A Benchekroun hydraulic value (in three cases) and a Malone procedure (in two cases) were performed at the same stage. The technique of Kropp-onlay urethral lengthening, which creates a flap value mechanism which leaks when the bladder is too full, is described and illustrated. RESULTS: Seven of eight patients were dry during the day and four were occasionally damp during the second part of the night. One could not be dry for more than 2 h during the day but had a very hyperactive detrusor. She developed two bladder stones which required an open vesicotomy. One developed a urethral fistula requiring a second Kropp-onlay procedure and became dry afterwards. Two patients, who did not undergo a bladder augmentation, needed oxybutinin therapy to obtain a satisfactory result. Post-operative urodynamic measurements are discussed. CONCLUSION: The Knopp-onlay urethral lengthening is easier to perform than the original Kropp procedure. The preliminary results are similar to those of alternative techniques (e.g. urethral suspension) but long-term reliability of this technique remains unknown.

Adolescent

Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes.

Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model.

Animals

Peptic ulcer disease and Jamaican patients' awareness of their disorder.

In the management and prevention of recurrence of peptic ulcer disease, patients' awareness of their disorder is essential. Fifty-one patients with peptic ulcer disease were studied regarding their awareness of their disorder and compliance with medications. There were 30 women and 21 men with a mean age of 45 years. Thirty-five per cent had secondary school education; 22% had tertiary training and 10% had no formal education. Sixty-three per cent of patients knew their ulcer location but 37% were unaware of their diagnosis. Twenty-nine per cent received most of their information from their pharmacists. Twenty per cent of patients smoked cigarettes; 31% drank alcohol, and 14% took non-steroidal analgesics. Seventy-six per cent thought that poor eating habits were a contributory cause of their ulcer; 39% thought that stress was a cause and 16% implicated heredity. Seventy-six per cent of patients took their medications daily, and 24% only when symptomatic. Jamaican patients' awareness of their ulcer disease is inadequate. There is a need for more physician education of their patients as well as public health promotion about peptic ulcer disease.

Adolescent

Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles.

To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner-city hospitals.

Adult

Isolation of two contigs of overlapping cosmids derived from human chromosomal band 3p21.1 and identification of 5 new 3p21.1 genes.

Consistent loss of DNA sequences from several regions on the short arm of human chromosome 3 has suggested that multiple tumor suppressor genes reside on chromosome 3p in various types of cancer cells. We have focused our efforts on an analysis of chromosomal band 3p21.1 since aminoacylase-1 (ACY1), which is localized to this band, has been shown to have lower levels of expression in several small cell and non-small cell lung cancer cell lines. Starting with two cosmids within 3p21.1, D3S92 and D3S93, we have isolated two separate contigs of overlapping cosmids within 3p21.1, by screening a library of 5700 chromosome 3-specific cosmid clones. Detailed restriction maps for these two contigs show that they contain multiple clusters of rare cutting restriction endonuclease sites. One contig extends for 100 kb and encompassed both ACY1 and D3S92, and the other extends about 80 kb around the D3S93 locus. Many different restriction fragments derived from these two contigs were found to be evolutionarily conserved and hybridized to distinct message transcripts. These fragments were used to identify homologous cDNAs from an adenogastric cDNA library, and several of these cDNAs were partially sequenced. We have identified five new genes from these two contigs and there is evidence to suggest that several additional genes reside within these cosmid contigs. The genes identified from 3p21.1 were then hybridized to DNA, isolated from a series of lung cancer cell lines and matched normal and tumor DNA from lung cancer patients. No alterations were detected with any of these probes, both at the DNA or RNA levels. A similar analysis with DNA fragments derived from these two genomic regions also failed to detect any alterations.

Animals

The Vancouver sedative recovery scale for children: validation and reliability of scoring based on videotaped instruction.

We originally developed and tested the Vancouver Sedative Recovery Scale (VSRS) to measure recovery from sedation following paediatric open heart surgery and reported excellent clinical inter-observer reliability. We now report a new study using videotape instruction of novice raters and videotaped case examples to determine whether the instruction produces adequate skill with the VSRS. Inter-rater reliability was assessed using videotapes of 16 children across a range of ages (six months to six years), and all levels of sedation (unresponsive to fully awake). Variably randomized subsets of six of the 16 test cases were randomly assigned to be rated by each of 16 video-instructed ICU staff volunteers, according to a balanced incomplete block design, such that every pair of raters assessed two children in common. The validity of the ratings from the video-instructed raters was assessed by comparison with "gold standard" scores from two experts who rated all 16 children clinically as the test cases were videotaped. The experts were in agreement themselves (intraclass correlation of 0.976). The correlation between the novice scores (average of six ratings per video) and the live clinical scores (average of two expert ratings) was 0.977 over the 16 test cases. On average, the mean expert rating was slightly higher, but the difference was negligible. (The differences between the mean ratings of the experts and novices for 13 of the 16 videos are very close to zero, while the other three differences, from technically less good videos, are two standard deviations away from zero). The VSRS, video instruction method and incomplete block design may be of use to other clinicians and investigators.

Anesthesia Recovery Period

Allelic loss on chromosome 17 in human ovarian cancer.

In order to identify a common region of deletion on chromosome 17 potentially containing a tumor-suppressor gene, 27 ovarian carcinomas and 3 ovarian tumors of low malignant potential (LMP) were examined for loss of heterozygosity (LOH) at 6 p arm and 10 q arm loci. Ninety percent of all tumors had deletions at one or more loci. On the p arm, there was a single near-common region of deletion on 17p13.3 (D17S30/pYNZ22.1; 86% LOH), an intervening locus with a low LOH rate, and a more proximal locus on 17p11.2 (D17S58/pEW301; 82% LOH) with a high LOH rate. In less aggressive tumors, LOH at D17S30 was not accompanied by LOH at p53. The q arm had a common region of deletion for high-stage carcinoma at D17S579 (Mfd188; 74% LOH) on q21, a locus tightly linked to the familial breast-ovarian-cancer syndrome (BRCAI) locus. D17S579 was lost in all informative high-stage carcinomas and retained in all low-stage carcinomas and tumors of LMP. There may be at least 2 tumor-suppressor genes, an early-acting gene on the p arm and a gene on the q arm involved in tumor progression and metastasis.

Adult

Schwann cell induction in the ventral portion of the spinal cord.

Schwann cell development can be induced in a predictable manner in the dorsal aspect of the lumbosacral spinal cord of the immature rat by exposing that structure to ionizing radiation. This development occurs in essentially all animals and becomes evident between 2 and 3 weeks postirradiation (P-I). Occasionally, intraspinal Schwann cells were observed ventrally at later intervals following irradiation, usually more than 45 days P-I. The present study focused on the development of Schwann cells within the ventral portion of the lumbosacral spinal cord in 53 animals followed for periods up to 7 months P-I. Ventrally located intraspinal Schwann cells developed in approximately 40% of these animals, in contrast to the development dorsally in all animals. The ventrally located aggregates were generally smaller than those dorsally and occurred more frequently in gray matter than in white matter. An interesting feature of the ventrally located Schwann cells was that they were often associated with blood vessels, which raised the possibility that these cells developed from undifferentiated cells of the vascular walls or used the vessels as a pathway for migration.

Animals

Study design for microgravity human physiology experiments.

In some areas of research, such as microgravity life sciences, both the number of subjects and the opportunity for repeated observation under experimental conditions are limited. Small N study designs are appropriate for these situations since they require few subjects and few observations in the experimental condition. Small N studies compare treatment conditions separately for each subject so that between-subject variability does not obscure treatment effects. Multiple observations are collected for each individual in the baseline condition to ensure a stable reference point for comparison with the smaller number of observations collected under the experimental conditions. Individual differences can be overlooked in large N studies, but in small N studies the focus is on the individual, and differences observed between particular individuals can be suggestive of underlying causal processes. We present a step-by-step approach to designing and conducting a small N study.

Evoked Potentials, Somatosensory

Regulation of estrogen sulfotransferase by estrogen in MCF-7 human mammary cancer cells.

The importance of the steroid hormone microenvironment within cells is now recognised in studies on endocrine-related neoplasms such as breast cancer. This focuses attention on enzymes which control the intracellular levels of estradiol-17 beta (E2). One such enzyme, estrogen sulfotransferase, which converts E2 to inactive E2-3 sulfate, has now been shown to be regulated by estrogen in MCF-7 human mammary cancer cells. Hydroxysteroid sulfotransferase, which sulfurylates the adrenal-derived estrogen 5-androstene-3 beta,17 beta-diol, is also under estrogen control. Evidence is provided which shows that one function of these enzymes may involve elimination of estrogen from the cell following processing of the ligand-charged estrogen receptor (ER).

Breast Neoplasms