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Biomedical subjects

S Patterson

Publications and source records attributed to S Patterson.

At least 19 recordsLinked to original sources

Increase in dendritic cell numbers, their function and the proportion uninfected during AZT therapy.

The effects of AZT treatment on the numbers, level of infection and function of peripheral blood dendritic cells (DC) were examined in patients with HIV infection. This was a cross-sectional study of patients before AZT treatment and up to 20 months after initiation of treatment. Numbers of DC separated by density gradients were below the normal range in patients before treatment, but increased between 3 and 12 months of treatment. The numbers of DC per provirus copy rose from around 100 cells to 5000 cells and this decrease in viral load in DC was significant between 3 and 20 months of treatment. The capacity of DC to stimulate allogeneic T cell proliferation was low before treatment and significantly higher between 6 and 12 months after the start of AZT. This study indicated that AZT treatment produced beneficial effects on DC by increasing their numbers, reducing the provirus load and increasing their function in stimulating T cells. These results support the thesis that the function of these potent antigen-presenting cells is important in development of immunological defects in AIDS, and that effects of AZT treatment on DC may provide a measure of its therapeutic effect.

Anti-HIV Agents

Analysis of human immunodeficiency virus type 1 (HIV-1) variants and levels of infection in dendritic and T cells from symptomatic HIV-1-infected patients.

Dendritic cells (DC) are required to initiate primary cellular immune responses. Human immunodeficiency virus type 1 (HIV-1) infection of DC may be central to transmission and persistence of virus and in the pathogenesis of AIDS. In symptomatic HIV-1-infected patients the proportion of DC in the mononuclear cell population was reduced. Provirus load in the T cells was 3-100 times higher than in DC and there was no correlation between the levels of infection in the two cell types. Phylogenetic analysis of amino acids in the V3 loop and flanking regions indicated intermingling of sequences and thus provides the first evidence for transfer of virus between DC and T cells in vivo. In one of three patients analysed there were significant differences in amino acid residues in the V3 region. This may reflect reduced interactions between DC and T cells in infected individuals and for the existence of variants with a stronger tropism for DC, which could play a role in transmission by initiating infection in mucosal DC.

Acquired Immunodeficiency Syndrome

Idiopathic intracranial hypertension without papilledema: a case-control study in a headache center.

OBJECTIVE: To compare the clinical features of patients with chronic daily headache (CDH) with idiopathic intracranial hypertension without papilledema (IIHWOP) to those with normal CSF pressure. METHODS: A case-control study was conducted at a tertiary headache center. Cases consisted of 25 consecutive patients (24 women, 1 man, 38 +/- 6 years) with IIHWOP diagnosed between June 1989 and June 1996. IIHWOP was diagnosed if pressure was 200 mm CSF on two occasions and there was no papilledema. Control subjects consisted of patients with refractory CDH who had normal CSF pressure on lumbar puncture performed between June 1992 and June 1996 (n = 60, 50 women, 10 men, 36 +/- 11 years). A structured telephone follow-up was done from July 1996 to March 1997. Comparisons made between the two groups included demographics and headache profiles, both at the initial evaluation and at follow-up. RESULTS: The initial headache characteristics did not differ between the two groups: most had transformed migraine with analgesic overuse. Significant predictors of IIHWOP included pulsatile tinnitus (odds ratio [OR] = 13.0) and obesity (OR = 4.4). Visual symptoms did not differ significantly. The prognosis of the two groups of patients was similar. CONCLUSIONS: Pulsatile tinnitus and obesity suggest possible IIHWOP in patients with CDH. Treatment of patients with increased intracranial pressure was not satisfactory.

Adult

Dental screenings using telehealth technology: a pilot study.

BACKGROUND: This pilot study compared data obtained using traditional methods of visual dental screenings in a school setting with data obtained using an intraoral camera and transmitted to a distant location via telehealth technology. METHODS: For the study, 137 schoolchildren were screened using traditional methods. Two months later, 32 children were randomly selected and rescreened in a single day using the intraoral camera and the telehealth system. The measurement indices used were deft/DMFT. RESULTS: A comparison revealed no significant difference in the data collected by the two screening methods. The percentage agreement between the methods ranged from 89% to 100%. CONCLUSION: In under-serviced or remote areas, the telehealth system may allow for accurate identification of oral conditions and act as a means of consultation at a distance between specialists, general dental practitioners, dental hygienists and individual patients.

Alberta

Lymphocyte subset redistribution during acute laboratory stress in young adults: mediating effects of hemoconcentration.

Acute psychological stress is known to alter the distribution of circulating lymphocyte subsets and also to cause a reduction of plasma volume. Data were reanalyzed from 4 previously reported studies (E. A. Bachen et al., 1995; T. B. Herbert et al., 1994; A. L. Marsland, S. B. Manuck, T. V. Fazzari, C. J. Stewart, & B. S. Rabin, 1995; A. L. Marsland, S. B. Manuck, P. Wood, et al., 1995) to determine the extent to which changes in the concentration of lymphocyte subsets are attributable to such hemoconcentration. Meta-analytic procedures showed circulating concentrations of T-suppressor/cytotoxic (CD8) and natural killer (NK) cells to increase following acute laboratory challenge, whereas T-helper (CD4) and B- (CD19) cell populations did not change. Adjustments for concomitant hemoconcentration reduced the magnitude of stress-related increases in CD8 and NK cells significantly and revealed a decrease in CD4 and CD19 cell concentrations from baseline to stress measurements. These data provide evidence (a) that increases in circulating numbers of CD8 and NK cells following acute stress are partially attributable to hemoconcentration and (b) that CD4 and CD19 cell concentrations decrease during acute stress when hemoconcentration is taken into account.

Adult

Bone marrow-derived dendritic cells, infection with human immunodeficiency virus, and immunopathology.

Dendritic cells (DC) exposed to HIV-1 show nonproductive infection that may become productive as they mature. The distribution of DC within genital mucosa and their susceptibility to infection particularly with clade E viruses could be reflected in the ease of heterosexual transmission. Carriage of virus and viral antigen by DC into lymph nodes may allow clustering and activation of T cells and production of protective immune responses. However, secondary infection of activated T cells from infected DC could cause dissemination of virus and loss of infected DC and T cells. In asymptomatic infection, fewer dendritic cells with reduced capacity to stimulate CD4 T cell proliferation are found before evidence of T cell abnormalities, and these early changes in antigen-presenting cells may result in a decline in the production of CD4 memory T cells. However, DC fuel ongoing production of antibody to HIV-1. Signaling by DC to T cells may thus underlie two major features of early HIV infection--loss in CD4+ memory T cells and persistence of antibody production. In AIDS, infected dendritic and epithelial cells within the thymus may affect maturation and contribute to loss of the "naive" T cell population. Further loss of memory T cells may occur through syncytium formation with infected DC. Finally, in AIDS patients, there is a failure in the development and the function of DC from CD34+ stem cells. In conclusion, the infection of dendritic cells, loss in their numbers, and changed signaling to T cells may shape the pattern of immunity during infection with HIV-1. Conversely, treatments that reverse the defect in antigen presentation by DC may improve cell-mediated immunity.

Animals

Global regulatory considerations for unified assay specifications.

When developing a biotechnology product for global registration, there are several aspects to evaluate in an effort to unify specifications. These include differences between the United States, Europe and Japan, and Rest-of-World (ROW) countries with regard to the respective regulatory guidelines and pharmacopoeias in force, the state-of-the-art of product testing analytical methods, and the interval between submitting a registration dossier to different countries. In terms of regulatory guidelines, one country may have a monograph or required specifications for particular tests, for example the potency that a product has to meet before clinical trials can be initiated. For pharmacopoeias, different assay methods are required for sterility, general safety, and pyrogen testing, so that one may have to test a specific lot of a product at two or three different times to evaluate the same parameter, because of specific testing differences required for each country's pharmacopoeia. In addition, the state of analytical methods is always evolving and better analytical techniques become available. Sometimes, from starting with one set of tests, and based on the time in development, new tests may be added to the existing list of release specifications, because new analytical techniques have become available. Examining the global registration approval process for Betaseron, (interferon beta-1b) illustrates when specifications were able to be unified and when they were not.

Animals

Mechanism for dendritic cell dysfunction in retroviral infection of mice.

Dendritic cells (DC) from mice infected with the murine retrovirus Rauscher leukaemia virus (RLV) are poor stimulators of allogeneic and syngeneic T cells and express lower, but still significant, levels of MHC class II. In this paper we further investigated the mechanism of the dysfunction of DC. DC from infected animals did not cause anergy of T cells during coculture for 3 or 6 days. They did not release a substantial amount of soluble factors which could suppress T cell responses. The low T cell responses on stimulation using RLV-infected DC could be overcome by the addition of control DC. Pretreatment of these control DC with monoclonal antibody against MHC class II molecules completely blocked their ability to restore stimulation of T cells in the presence of infected DC. However, antibody against MHC class I or mismatched MHC class II molecules did not prevent restoration of function. The reduced labeling of surface MHC class II molecules previously reported was shown to reflect a loss in total class II molecules within the cells; MHC class I levels were unaltered by exposure to the virus. In DC from RLV-infected mice biosynthesis of MHC class II was decreased by around 50% at the transcriptional level in comparison with beta-actin. Thus, the down-regulation of surface class II molecules observed in DC following RLV infection is a consequence of a specific block in its biosynthesis and the failure of DC to stimulate T cells may be a direct consequence of the reduced class II levels. Since reduced stimulation by DC is also seen in HIV-1 infection in humans we speculate that a similar mechanism might operate in retroviral infection in man.

Animals

Health instruction responsibilities for elementary classroom teachers in Pennsylvania.

A joint committee comprised of representatives from the American School Health Association and the Association for the Advancement of Health Education delineated five areas of instructional responsibility and 31 competencies needed for elementary health educators. Practicing elementary educators in southeastern Pennsylvania were surveyed as to their usage and perceived importance of these health instruction responsibilities and competencies. Competency usage varied from a high of 98.6% to a low of 33.5%. The second area of instructional responsibility -- Assessing the Health Instruction Needs and Interests of Elementary Students -- had the highest mean usage per competency. Chi-square tests indicated a statistically significant relationship for competency usage and highest academic degree earned for two competencies, while competency usage and total number of years experience as an elementary educator indicated a statistically significant relationship for three competencies. The authors conclude with suggested strategies to improve the health education preparation of elementary educators.

Chi-Square Distribution

Intraoperative somatosensory evoked potential monitoring during acute pelvic fracture surgery.

Independent clinical neurological evaluation and intraoperative somatosensory evoked potential (SSEP) monitoring was performed on 30 vertically unstable hemipelvis fractures in 28 patients undergoing acute open reduction and internal fixation. Preoperative ipsilateral neurologic injury of the sciatic/lumbosacral plexus was noted in 15 of 30 fractures (50%). Significant unilateral SSEP changes occurred during manipulative reduction of two displaced sacroiliac joints and one sacral fracture. Because of the expeditious response of the surgical team, with release of traction/retraction, SSEP returned to baseline and no patient sustained an iatrogenic nerve injury or worsening of their preoperatie neurologic status. The incidence of postinjury lumbosacral plexopathy in unstable pelvic fractures is high (50%) when careful preoperative evaluation including SSEP is performed. The use of intraoperative SSEP monitoring is feasible in acute posterior pelvic fracture surgery and can help identify potential intraoperative iatrogenic lumbosacral neurological compromise.

Adolescent

CD4 expression on dendritic cells and their infection by human immunodeficiency virus.

Infection of dendritic cells (DC) by human immunodeficiency virus (HIV) has been disputed. Employing a fluorescence-activated cell sorter, DC, identified by the absence of membrane markers for T, B, natural killer (NK) and monocytic cells and by high levels of MHC class II DR antigen, were shown to express low levels of CD4. Immunomagnetic beads were used to separate blood low density cells, which are enriched for DC, into CD4-positive and -negative populations. Examination of these cells by electron microscopy showed an increase in the percentage of cells with DC morphology in the CD4-positive fraction and a reduction in the CD4-negative fraction. Electron microscopy of semi-purified DC preparations infected in vitro for 5 days with HIV-1 revealed morphologically distinct veiled DC with mature virions on the cell surface and virus budding through the cell membrane. Further evidence for the growth of HIV in DC was provided by experiments in which DC were extensively depleted of contaminating lymphocytes and monocytes prior to infection. Estimation of provirus load by a nested PCR indicated that after 5 days an infection level of one provirus copy per five cells could be achieved. After 7 days the provirus copy number could exceed the cellular genome copy number, suggesting that some cells had more than one provirus. Infectious virus could not be demonstrated in these cultures after 24 h but was detected after 5 or 7 days. Infection of DC in the presence of antibodies against CD4 was inhibited and suggests infection occurs via a CD4-dependent pathway. These results confirm that DC are susceptible to HIV infection in vitro. The immunological consequences of DC infection in vivo may be significant in the pathogenesis of AIDS.

Base Sequence

Murine retrovirus induces defects in the function of dendritic cells at early stages of infection.

The infection and function of lymph node dendritic cells (DC) were analyzed at different time points of Rauscher leukemia virus infection in mice (3, 7, 14, and 21 days). Infection of DC was apparent after 3 days and significant infection (1-10% of the DC population) was documented after 7 days. DC from infected mice as early as 3 days postinfection had a reduced ability to stimulate allogeneic normal T cells in the mixed lymphocyte reaction. T cells did become infected during the coculture but block of cross-infection of T cells by zidovudine did not abolish the inhibitory effect. Other DC-dependent responses were also reduced on infection including DC-stimulated responses to influenza virus. ConA and PMA induced an increase in [Ca2+]i level in DC from control mice. A low baseline level of [Ca2+]i in DC from infected mice and reduced calcium mobilization upon ConA stimulation was found at all periods of infection. Ultraviolet-inactivated Rauscher leukemia virus failed to provoke significant changes in DC function in vivo. Six or 7 days after RLV infection DC expressed lower levels of Iad but not H2Dd molecules in parallel with lower expression of some adhesion molecules (CD18, CD54, CD44). No differences in expression of B7 surface antigen between control and infected mice were obtained. We did not find any evidence for the induction of apoptosis of naive syngeneic or allogeneic T cells by infected dendritic cells. The changes in DC function may have implications for the pathogenesis of retroviral infections including HIV infection.

Animals

Evoked potential monitoring during posterior fossa aneurysm surgery: a comparison of two modalities.

The purpose of this study was to compare and assess the ability of two different evoked potential (EP) modalities, median nerve somatosensory evoked potentials (SSEP) and brainstem auditory evoked potentials (BAEP) in monitoring for cerebral ischaemia and in predicting neurological outcome during posterior fossa aneurysm surgery. During 70 procedures, patients were monitored with both SSEP and BAEP. Temporary occlusion of an artery was used in 52 patients and permanent occlusion in 21 patients. A change was defined as a greater than 50% decrease in amplitude and/or an increase in latency greater than 1 msec of the N20 (cortical waveform) for SSEP monitoring and of the fifth peak for BAEP monitoring. Neurological assessment of the patient was performed immediately on emergence, after 24 hr and at the time of discharge. In total, 14 patients had an SSEP change which predicted a neurological deficit in eight patients (57%). Ten patients had a change in BAEP; six had a neurological deficit (60%). Five patients had a change in both, two had a deficit (40%). The incidence of false negative results (a neurological deficit but no EP change) for both modalities was 20% (SSEP 47%, BAEP 60%). The incidence of false positive results (an EP change but no deficit) was 13% overall (SSEP 11%, BAEP 7%). All patients who had a permanent EP change developed a neurological deficit. We did not find a difference in the ability of SSEP compared with BAEP in predicting neurological deficits but, using both modalities, the incidence of false negative results was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Reliability of measurements of static weight distribution of manual wheelchairs.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the reliability of measurements of weight distribution among the wheels of wheelchairs using a commercial balance testing system. Reliable data may be useful in the wheelchair evaluation and adjustment process. SUBJECTS: Three male full-time manual wheelchair users aged 30, 26, and 27 years with cervical spinal cord injuries 7.5, 6.5, and 10 years in duration participated. METHODS: Calibration weights, unoccupied wheelchairs, and occupied wheelchairs were repeatedly placed on the force transducers of the balance testing system to obtain measurements of weight distribution. RESULTS: The intraclass correlation coefficients of the measurements were .99 for calibration weights, .96 for unoccupied wheelchairs and .98 for wheelchairs occupied by the subjects. CONCLUSION AND DISCUSSION: The described use of this instrumentation appears to generate reliable measurements of static weight distribution. With further testing, this system may provide useful information related to manual wheelchair prescription and adjustment.

Adult