Adenosine, a potent natural suppressor of arachidonic acid release and leukotriene biosynthesis in human neutrophils.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Austin.
Explore the source record for details and available documents.
The purpose of this study was to examine whether acute stress exposure would alter the ataxic properties of midazolam or ethanol in rats. Rats were administered either vehicle or FG 7142 (10 mg/kg) and placed back in their home cages, or placed in restraining tubes for 90 min. Three and one-half or 24 h following injection all subjects were then administered an ataxic dose of either ethanol or midazolam and after 10 min, motoric impairment was assessed by rotarod performance. Neither FG 7142 administration nor restraint had an impact on rotarod performance 3-1/2 h later for ethanol nor 24 h later in response to midazolam. However, midazolam-induced ataxia was significantly modified 3-1/2 h following both restraint and FG 7142 exposure. Similarly, at the 24-h time point, both manipulations had a significant effect on ethanol-induced motor incoordination. Importantly, prior exposure to FG 7142 and restraint was without effect on rotarod performance in saline-treated subjects. Functional alterations in behavioral reactivity to low doses of two classes of CNS depressants by the acute stress of restraint and/or FG 7142 administration suggest the anxiogenic nature of these stressors may be the critical factor.
Explore the source record for details and available documents.
PURPOSE: A single blind prospective randomised study to determine the effect of Viscoat retained in the eye on intraocular pressure (IOP) after phacoemulsification. METHODS: 82 patients were randomly selected to receive either Viscoat, a viscoelastic composed of 3% sodium hyaluronate (mol wt 500,000 daltons), and 4% chondroitin sulfate (mol wt 25,000 daltons) or Provisc, a viscoelastic compound composed of 1% sodium hyaluronate (mol wt 4,00,000 daltons) during phacoemulsification. In those patients receiving Viscoat the viscoelastic in the anterior chamber only was removed, whereas in those receiving Provisc attempts were made to remove the material entirely. The IOP was measured on the first postoperative day, 16-20 hours after surgery. RESULTS: The mean postoperative IOP in the Viscoat group was 22.37 +/- 9.0 mmHg and in the Provisc group was 19.67 +/- 6.95 mmHg. Five patients in the Viscoat group had pressure elevations above 30 mmHg as opposed to three in the Provisc group. CONCLUSIONS: The two viscoelastics cause equivalent pressure elevations postoperatively. In the Viscoat group there were five patients with IOPs above 30 mmHg. We recommend that Viscoat should be aspirated from both the anterior chamber and the capsular bag following routine phacoemulsification.
Mouse NK cells may use both cytokine, e.g. IFN-gamma, tumor necrosis factor (TNF)-alpha and IL-12, and cytotoxic, e.g. perforin and Fas-FasL, pathways to reject incompatible bone marrow cell (BMC) grafts. To begin a dissection of these two major pathways, mice bearing deletional mutations of IFN-gamma, TNF-RI/II or perforin, or mice treated with mAb to IL-12, IFN-gamma or NK1.1 were irradiated and challenged with class I-deficient BMC grafts, a system in which only NK cells are the effector cells. Proliferation of the donor-derived cells was judged in terms of splenic incorporation of [125I]iododeoxyuridine 5 or 7 days after cell transfer. All of these mice maintained in a specific pathogen-free (s.p.f.) environment were able to reject the BMC, except those treated with anti-NK1.1 mAb. However, perforin deficient mice maintained in a conventional breeding facility failed to reject class I (Tap-1)-deficient marrow cells. Transfer of mice from the pathogen-free to the conventional facility resulted in a slow and incomplete loss of the ability to reject marrow cells. Thus, the breeding colony environment can elicit otherwise undetectable defects in the rejection ability of perforin-deficient NK cells. This report will hopefully alert those investigators who have only studied immune gene knockout mice in s.p.f. facilities and found no significant abnormalities.
Orbital-sinus foreign bodies traverse the orbit and lay, at least partially, within the paranasal sinuses. Most of these injuries occur as a result of facial trauma. In most cases, history alone is not sufficient to rule out a retained foreign body. Early magnetic resonance imaging is necessary to evaluate the full extent of injury. Since these foreign bodies may cause a severe orbital infection and threaten the patient's vision, surgical removal is recommended. Endoscopic sinus surgery provides a safe and effective approach for extraction of these foreign bodies that can be used alone or in conjunction with other surgical approaches. The case of an orbital-sinus foreign body is presented together with a comprehensive approach for diagnosis and management of this type of injury.
BACKGROUND: Twenty-seven ovarian cancer patients who failed chemotherapy entered a phase I/II trial of intraperitoneal 177Lu-CC49 antibody. METHODS: Patients had disease confined to the abdominal cavity +/- retroperitoneal lymph nodes, adequate organ function, and no previous radiation. RESULTS: The most common side effects were delayed, transient arthralgia (10/27) and marrow suppression with 1.665 GBq/m2 (45 mCi/m2), which was considered the maximum tolerated dose. One of thirteen patients with gross disease had >50% tumor reduction after therapy, whereas most others with gross disease progressed (one went off study with stable disease at 11 weeks). Seven of nine patients with <1-cm nodules progressed in < or =21 months, and two of nine remain without evidence of disease at 4 to 5 months. Of patients with microscopic or occult disease, one relapsed at 10 months and four of five remain without evidence of disease at >6 to 35 months. CONCLUSIONS: Marrow suppression was the dose-limiting toxic effect of intraperitoneal immunotherapy with 177Lu-CC49. Antitumor effects were noted against chemotherapy-resistant ovarian cancer, even at lower dose levels, and resulted in prolonged disease-free survival of most patients with microscopic disease. This form of treatment deserves further study.
Explore the source record for details and available documents.
The purpose of the study was to determine whether blood glucose monitoring strips influence the management of patients with non-insulin dependent diabetes (NIDDM) in the primary care setting. The medical records of 115 patients with NIDDM taking a sulfonylurea drug (oral hypoglycemic agent) during the review period were randomly selected for review. Patients were divided into two groups: those who did not receive a prescription for blood glucose monitoring strips during 1995 and 1996 and those who did for the same 2 years. The main outcome measures were hemoglobin A1c, blood sugar, number of laboratory tests ordered, and number and type of treatment interventions. No statistically significant differences between groups were noted for any measured parameter. Glucose control was independent of number of strips dispensed. Home glucose monitoring strips did not affect the management of patients with NIDDM taking a sulfonylurea agent in the primary care setting.
We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor). We have recently reported that HIV-IT(V) administered intramuscularly to male mice localizes primarily to the site of injection. In this study, we have investigated more extensively the localization and biological activity of HIV-IT(V) administered intramuscularly to female mice. Consistent with our previous findings, retroviral DNA was detected by PCR at the site of injection. Retroviral DNA was also detected in proximal lymph nodes, a tissue not examined previously. Potential for drainage of vector particles to regional lymph nodes was indicated by experiments showing that intramuscular injection of fluorescein-labeled latex beads concentrated in the regional lymph nodes in mice. The localization of retroviral DNA to the injection site and regional lymph nodes may play a role in the induction of the HIV-specific CTL responses detected in splenocyte populations isolated from mice 21 days after injection with HIV-IT(V).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The cytotoxic T-lymphocyte (CTL) response plays an important role in controlling the severity and duration of viral infections. Immunization by direct in vivo administration of retroviral vector particles represents an efficient means of introducing and expressing genes and, subsequently, the proteins they encode in vivo in mammalian cells. In this manner foreign proteins can be provided to the endogenous, class I major histocompatibility complex antigen presentation pathway leading to CTL activation. A nonreplicating recombinant retroviral vector, encoding the human immunodeficiency virus type 1 (HIV-1) IIIB envelope and rev proteins, has been developed and examined for stimulation of immune responses in mouse, rhesus macaque, and baboon models. Animals were immunized by direct intramuscular injection of the retroviral vector particles. Vector-immunized mice, macaques, and baboons generated long-lived CD8+, major histocompatibility complex-restricted CTL responses that were HIV-1 protein specific. The CTL responses were found to be dependent on the ability of the retroviral vector to transduce cells. The vector also elicited HIV-1 envelope-specific antibody responses in mice and baboons. These studies demonstrate the ability of a retroviral vector encoding HIV-1 proteins to stimulate cellular and humoral immune responses and suggest that retrovector immunization may provide an effective means of inducing or augmenting CTL responses in HIV-1-infected individuals.
Physical performance and haemodynamic parameters at rest and with exercise were compared in a prospective, cross-over fashion in 12 anaemic haemodialysis patients (Hb 6.4 +/- 0.5, mean +/- SEM) at two levels of haemoglobin (Hb 9 and 12 g/dl) before and after long-term treatment with recombinant human erythropoietin (rHuEpo). Patients were divided into two groups and measurements made prior to treatment, upon reaching, and after 4 months at the first target Hb (9 g/dl group A, 12 g/dl group B), and after 4 months at the alternative target Hb. Tests included an exercise radionuclide ventriculogram, Doppler echocardiogram, and respiratory function exercise test. Compared to pretreatment, there was a significant reduction in resting pulse rate (P < 0.001), and in pulse rate (P < 0.001) and arterial lactate (P < 0.01) concentrations at specified levels of exercise. Work capacity improved 60% (P < 0.001), and left ventricular mass fell by 26% (P < 0.001). Although cardiac output (CO) during and after exercise was reduced (P < 0.05), resting CO, cardiac index, stroke volume and ejection fraction (rest and exercise) were not significantly altered. There appeared little benefit in having the higher target Hb: no significant difference could be found between target levels for almost any measure. In addition, despite marked improvement from pretreatment levels, performance parameters were still below those of non-uraemic age-matched controls. These results demonstrate the beneficial but incomplete effect of rHuEpo on resting and exercise-related factors, and suggest that most improvement is achieved with modest increments in haemoglobin.
OBJECTIVE: To measure the unmet need of patients with regular urinary incontinence (incontinence twice or more a month) treatable by a nurse. DESIGN: Self completed postal questionnaire and randomised controlled trial of assessment and intervention by a nurse. SETTING: One urban and one rural general practice in Somerset. SUBJECTS: 7300 adults randomly selected from 10,300 aged 35 and over on the combined practice lists. 515 women and 185 men with regular incontinence were offered assessment and treatment, of whom 134 women and 49 men had no intervention for three months (historical controls). They then joined the assessment and treatment programme. INTERVENTION: Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence. MAIN OUTCOME MEASURES: Number of patients desiring treatment; self reported cure, improvement, or deterioration in continence after three months. RESULTS: The questionnaire achieved a 79% response. Validated responses showed a prevalence of 4.4% in men and 16.4% in women aged 35-64. 315 (45%) of the 700 patients offered assessment refused it and seven had moved away or died, 64 men and 41 women were referred to their general practitioner. 197 of 292 treated women (68%) reported cure or improvement compared with seven (5%) of controls. 22 of the 86 men desiring treatment were suitable for intervention by the nurse. Seventeen were cured or improved compared with none of the men in the control group. CONCLUSIONS: About half the people with regular urinary incontinence took up the offer of treatment (9.2% of women and 3.4% of men in the study population). This condition can be effectively managed by a nurse with limited training.