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Biomedical subjects

D Orr

Publications and source records attributed to D Orr.

At least 19 recordsLinked to original sources

Comparison of an antigen capture enzyme-linked assay with reverse transcription--polymerase chain reaction and cell culture immunoperoxidase tests for the diagnosis of ruminant pestivirus infections.

A study to compare the merits of three different tests for the diagnosis of ruminant pestivirus infections was carried out. Sensitivity studies using reference strains of bovine viral diarrhoea virus (BVDV) and buffy coat samples from persistently infected (PI) carriers showed the reverse transcription-polymerase chain reaction (RT-PCR) had a greater sensitivity than the other tests. The antigen capture enzyme-linked immunosorbent assay (ELISA) was least sensitive and could only be used on samples containing cells (tissue or blood). When 169 clinical samples were examined, the RT-PCR detected the most positives (42) compared to the ELISA (32) and the immunoperoxidase test (IPT) (20). The RT-PCR was more successful when specific antibody was also present in the sample. The lower sensitivity of the IPT was related to the use of a 1 passage (4-day) test and the testing of toxic or contaminated samples. The ELISA was found to be most suitable for large-scale testing for the diagnosis and control of pestivirus infections.

Animals

Psychosocial variables that affect the psychological adjustment of IVDU patients with AIDS.

The influences of coping strategies and of perceived social support from family and friends on the psychological adjustment of intravenous drug users (IVDUs) with Acquired Immunodeficiency Syndrome (AIDS) were investigated. Twenty-seven male AIDS patients with a history of intravenous drug use completed a demographic questionnaire, Trails-B, the Ways of Coping Questionnaire, Perceived Social Support from Family, Perceived Social Support from Friends, and the Mental Health Inventory. Unexpected results were obtained: The only coping strategy to correlate significantly with psychological adjustment was "Seeking Social Support," and perceived social support from family correlated positively with psychological adjustment, but perceived social support from friends did not. Interpretations and implications of these findings are presented.

Acquired Immunodeficiency Syndrome

Influence of body position on pressure and airflow generation during hypoxia and hypercapnia in man.

1. Inspiratory oesophageal pressure and ventilatory responses to hyperoxic, progressive hypercapnic rebreathing (HCVR) and isocapnic, progressive hypoxic rebreathing (HVR) were studied in five normal males in both supine and upright seated positions. 2. No significant differences were found in the ventilatory response to hypercapnia between the supine and upright position. The slopes of the relationship between minute ventilation (VI) and the increase of end tidal PCO2 (delta P(ET), CO2) were 3.27 +/- 0.23 and 2.76 +/- 0.24 1 min-1 mmHg-1 supine and upright, respectively. However, the change in oesophageal pressure from the end expiratory level observed during quiet breathing to that at peak inspiration (delta P(oes), I) in relationship to delta P(ET),CO2 was greater supine than upright (1.23 +/- 0.07 versus 0.79 +/- 0.11 cmH2O mmHg-1, P < 0.01). 3. In contrast, during hypoxia-stimulated breathing the slope of the minute ventilation versus oxyhaemoglobin saturation curve (VI-Sa,O2) was flatter supine than upright (1.00 +/- 0.03 versus 1.75 +/- 0.05 l min-1 (percentage fall in Sa,O2)-1, P < 0.0001), but delta P(oes), I in relation to Sa,O2 during hypoxic rebreathing was similar supine and upright (0.38 +/- 0.03 versus 0.40 +/- 0.04 cmH2O (percentage fall in Sa,O2)-1, respectively. 4. It is concluded that body position does not affect the ventilatory response to progressive hyperoxic hypercapnia but does affect the relationship between delta P(oes), I and delta P(ET),CO2. In contrast, body position affects the ventilatory response to isocapnic progressive hypoxia, but does not affect the relationship between delta P(oes), I and Sa,O2.

Adult

The acute and chronic toxicity of ten chlorinated organic compounds to the American flagfish (Jordanella floridae).

The acute toxicity (96-hr median lethal concentrations (LC50s) of ten chlorinated isomers of benzene, phenol, ethane, and ethylene to the American flagfish (Jordanella floridae) were determined in both static and flow-through systems. Chronic toxicity to embryo-larval fish was also estimated from hatching success and post-hatch survival as well as fry growth rates and survival. Maximum acceptable toxicant concentrations (MATC) were estimated where possible. In general, for both acute and chronic toxicity tests, the order of increasing relative toxicity based on the water-borne exposure concentrations was: chloroethanes, chloroethylenes, chlorobenzenes, and chlorophenols. Within groups, more highly chlorinated isomers were usually more toxic. The presence of suspended or colloidal 1,2,4,5-tetrachlorobenzene was observed in acute toxicity testing and affected toxicity estimates.

Animals

Chemical and postural influence on scalene and diaphragmatic activation in humans.

The electromyographic activity of the diaphragm (EMGdi) and scalene muscle (EMGsc) was studied in the supine and upright positions, respectively, during hyperoxic progressive hypercapnic rebreathing (HCVR) in five healthy males. End-expiratory esophageal pressure (EEPes) was quantified on a breath-to-breath basis as a reflection of altered end-expiratory lung volume. There was no significant difference in the slopes of EMGdi, expressed as a percentage of maximum at total lung capacity vs. minute volume of ventilation (VI), between the supine and upright positions [0.79 +/- 0.05 (SE) vs. 0.92 +/- 0.17, respectively]. In contrast, the slope of the regression line relating EMGsc to VI was steeper in the upright than in the supine position (0.69 +/- 0.05 vs. 0.35 +/- 0.04, respectively; P less than 0.005). Positive EEPes at comparable VI at the ends of HCVRs were of greater magnitude upright than supine (3.27 +/- 0.68 vs. 4.35 +/- 0.60 cmH2O, respectively, P less than 0.001). We conclude that altering posture has a greater effect on scalene and expiratory muscle activity than on diaphragmatic activity during hypercapnic stimulation.

Adult

Characteristics of patients attending an HIV-related psychiatric clinic.

Demographic and clinical data were recorded for 324 patients who visited an AIDS-related psychiatric outpatient clinic over a three-year period. Seventy-five percent of the patients had a diagnosis of AIDS, AIDS-related complex, or asymptomatic HIV seropositivity. Intravenous drug use and heterosexual relations were the most common HIV transmission risk factors. Seventy-three percent of the patients were black or Hispanic; 51 percent were female. In all stages of HIV infection, adjustment disorder was the most common diagnosis; one third to one half of the patients had substance abuse diagnoses. Only 5 percent were diagnosed with dementia, with the incidence highest (12 percent) in patients with AIDS. On the basis of their experience with the clinic, the authors discuss issues that have proved important in the treatment of patients with the triple diagnoses of medical illness, mental illness, and substance abuse.

Adolescent

Characterization of Andante, a new Drosophila clock mutant, and its interactions with other clock mutants.

A new clock mutant, named Andante, has been identified on the X chromosome of Drosophila melanogaster. Andante lengthens the period of the circadian eclosion and locomotor activity rhythms by 1.5-2.0 hours. The phase response curves for the eclosion and activity rhythms, indicating light-induced phase shifts, show a similar degree of lengthening. Andante also lengthens the periods of other clock mutants, including Clock, and alleles of the period locus. Analysis of locomotor activity rhythms reveals that Andante is semi-dominant, and Andante rhythms are highly temperature compensated. The sine oculis mutation, which eliminates the outer visual system, has no effect on the period of Andante. Deficiency mapping indicates that Andante is located in the 1OE1-2 to 1OF1 region of the X chromosome, close to the miniature-dusky locus. Whereas Andante flies have a dusky wing phenotype, dusky flies do not have an Andante clock phenotype.

Activity Cycles

Phenotypic and genetic analysis of Clock, a new circadian rhythm mutant in Drosophila melanogaster.

Clock is a semidominant X-linked mutation that results in shortening the period of Drosophila melanogaster's free-running locomotor activity rhythm from ca. 24.0 to ca. 22.5 hr. This mutation similarly shortened the phase response curve, determined by resetting activity rhythms with light pulses. Eclosion peaks for Clk cultures were separated by only 22.5 hr instead of the normal 24 hr. Clk was mapped close to, but separable from, another rhythm mutation--period01--by recombination. The estimated distance between these two mutations was short enough to suggest that Clk could be a per allele. If this is the case, the new mutant is unique in that it, unlike other per variants, is associated with essentially normal 1-min courtship song rhythms when Clk is expressed in males. Also, the new rhythm variant could not, in contrast to a short-period per mutation, have its effects on free-running activity rhythms uncovered by deletions. This result, and the lack of coverage of Clk's effects by duplications, suggest that it is not a simple hypomorphic or amorphic mutation.

Animals

Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro.

We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD

Sleep apnea in patients with left ventricular dysfunction: beneficial effects of nasal CPAP.

Five patients with congestive heart failure (CHF) and 1 with left ventricular dysfunction but without CHF were found to have sleep apnea. Central sleep apnea (CSA) related to Cheyne-Stokes respiration was seen in 4 cases while obstructive sleep apnea (OSA) was seen in 2. All patients had symptoms of sleep apnea. Nasal continuous positive airway pressure (NCPAP) was effective in reversing CSA and OSA in all patients with improvement in sleep structure and alleviation of symptoms of sleep apnea. In addition, all experienced a reduction in cardiac dyspnea. This was associated with a 5% or greater increase in left ventricular ejection fraction while on NCPAP, compared to baseline value off NCPAP in 5 patients and resolution of chronic pleural effusion and pulmonary edema in the sixth. We conclude that Cheyne-Stokes respiration during sleep may give rise to a CSA syndrome that is reversible by NCPAP. In addition, NCPAP therapy may lead to a reduction in cardiac dyspnea and improvement in left ventricular function in patients with left ventricular dysfunction and sleep apnea.

Arousal

Effect of hypercapnia and hypoxia on respiratory muscle activation in humans.

We studied the electromyographic activity of the diaphragm (EMGdi) and abdominal external oblique (EMGeo) muscles in response to progressive hypercapnia (HCVR) and hypoxia (HVR) in five normal males. The slopes of the regression lines relating log EMGdi activity to minute volume of ventilation (VE) were steeper during HVR runs than HCVR runs (mean +/- SE, 0.03201 +/- 0.00724 vs. 0.02729 +/- 0.00676, P less than 0.03). Phasic expiratory EMGeo activity was seen in 15 of 15 HCVR runs but in only 6 of 15 HVR runs. Furthermore, the maximum level of VE attained before the onset of EMGeo activity was significantly lower during HCVR runs than during HVR runs (23.1 +/- 2.5 vs. 34.8 +/- 4.01/min, P less than 0.003). We conclude that in awake humans 1) the diaphragm is activated to a greater extent by hypoxia than hypercapnia at a given VE and 2) hypercapnia causes a more consistent recruitment of abdominal expiratory activity at lower VE than does hypoxia.

Adult

Effect of nasal continuous positive airway pressure on sleep apnea in congestive heart failure.

We studied five patients with chronic stable congestive heart failure (CHF), all of whom demonstrated recurrent apneas in association with Cheyne-Stokes respiration (CSR) during sleep. All five patients had symptoms consistent with a sleep apnea syndrome. Nasal continuous positive airway pressure (NCPAP) was administered at 8 to 12.5 cm H2O to all patients during sleep. The number of apneas fell from (mean +/- SE) 60 +/- 12/h of sleep on the control night to 9 +/- 7/h of sleep (p less than 0.01) on the NCPAP night, whereas mean nocturnal SaO2 rose from 88 +/- 2% on the control night to 92 +/- 2% (p less than 0.025) while on NCPAP. This was associated with resolution of symptoms of sleep apnea. In addition, resting left ventricular ejection fraction (LVEF) as measured by radionuclide angiography (RNA) rose from 31 +/- 8% while off NCPAP to 38 +/- 10% (p less than 0.05) while on NCPAP. Furthermore, all five patients experienced marked improvement in symptoms of heart failure from functional classes III and IV (New York Heart Association Classification) prior to NCPAP therapy to class II after NCPAP therapy was instituted. We conclude that, in certain patients, CSR during sleep associated with chronic CHF constitutes a sleep apnea syndrome, which can be alleviated by NCPAP. In addition, NCPAP therapy may lead to a reduction in cardiac dyspnea and improvement in left ventricular function.

Aged

Reciprocal behaviour associated with altered homeostasis and photosensitivity of Drosophila clock mutants.

The circadian oscillators of genetically short-period and long-period Drosophila exhibit reciprocal behaviour in four distinct ways: (1) with respect to the dependence of period on temperature, (2) in the change of period during constant darkness after ten days of constant light, (3) in the change of period during the second ten days of darkness as compared with the period during the first ten days, and (4) in the period change resulting from exposure to low-intensity constant light. The homeostatic control of the dependence of period length on temperature is impaired in the mutants as compared with wild-type flies. The normal Drosophila pacemaker may comprise two mutually coupled oscillators, whereas the mutants may represent a reduction in activity of one or the other constituent oscillator.

Animals

Phase I trial of mitomycin C immunoconjugates cocktails in human malignancies.

Nineteen patients with refractory solid malignancies received individualized combinations of mitomycin C conjugated murine monoclonal antibodies selected by immunohistochemical and flow cytometric screening of tumor specimens. There were no responses in this Phase I study. Thrombocytopenia precluded escalation above a mitomycin C dose of 60 mg per treatment cycle. Preclinical, clinical, and toxicity experiences with this investigational approach to the treatment of cancer are discussed.

Adult

Multiple cycles of constant infusion recombinant interleukin-2 in adoptive cellular therapy of metastatic renal carcinoma.

Twenty patients were treated with metastatic renal cell cancer with 5-day cycles of constant infusion recombinant interleukin-2 (rIL-2) at 3 X 10(6) U/m2/day and with infusion of in vitro activated autologous mononuclear cells. The initial eight patients completed all rIL-2 and cellular therapy in a single 25-day treatment period. The subsequent 12 patients entered a 6-month treatment program involving two separate 15-day cycles of cellular therapy followed by four monthly cycles of maintenance rIL-2. Among eight patients in the 25-day treatment program, there were two with partial response (PR) and one with minor response (MR). None of these responses exceeded 2 months in duration. Among the 12 patients undergoing recycling of therapy, there were two with complete response (CR), two with PR, and one with MR. All four patients with CR or PR in this group demonstrated continuing response with recycling of treatment and none relapsed while receiving maintenance interleukin-2. Three remain in remission at 10, 11, and 12 months. These pilot data confirm that patients can tolerate multiple cycles of adoptive immunotherapy involving constant infusion rIL-2 and suggest that recycling of therapy is necessary to achieve clinically meaningful results.

Adult

Vasectomy as a contraceptive method.

The paper reports a series of 1,000 consecutive vasectomies, mostly self referrals, performed at a family planning clinic. Comprehensive counseling was a mandatory prerequisite, the average time spent considering vasectomy prior to counseling was 22 months. The couples characteristics were as follows: age 30-39 years, married 11.3 years, with 3.4 children, upper social class preponderance. To minimise the risk of recanalisation (0.2%), 20 mm of vas deferens was resected. In the early part of the series, inflammatory tissue reaction due to slow absorption of synthetic suture posed a minor problem which was subsequently eliminated by use of a soft gut variety. The majority (99%) was pleased with the procedure and did not suffer complications. One per cent experienced some psycho-sexual problems such as decreased libido, ejaculatory problems, depression. Based on data collected from other centres we estimate that 3,303 sterilizations were performed in Ireland in 1986 with a male:female ratio of 3.2.

Contraception