Biomedical subjects
C Gorman
Publications and source records attributed to C Gorman.
Relationships among age, conditioned stimulus-unconditioned stimulus interval, and neuropsychological test performance.
To evaluate the effect of age at various conditioned stimulus (CS)-unconditioned stimulus (US) intervals, 144 young, middle-aged, and older adults were tested on eyeblink classical conditioning at CS-US intervals of 500, 1,000, or 1,500 ms. Reaction time, response timing, motor learning, declarative memory, and attention were assessed to identify correlates of conditioning at various CS-US intervals. Previously reported middle-aged and older adults were impaired at a 400-ms CS-US interval, but the addition of 100 ms to the CS-US interval in this study enabled equal conditioning in middle-aged and young adults. At a 1,000-ms CS-US interval, older adults remained significantly impaired. It was only at the 1,500-ms CS-US interval that conditioning was equal for the 3 age groups. Measures of reaction time, timing, and motor learning were not correlated systematically with conditioning. Whereas the results of age differences at various CS-US intervals were clear and striking, patterns of relationships among neuropsychological and conditioning variables were not consistent in indicating sources of age differences.
In vivo studies of gene expression via transient transgenesis using lipid-DNA delivery.
As the sequencing of the human genome proceeds, the need for a new screen for in vivo function is becoming apparent. Many investigators are turning to various transgenic models as a means of studying function. However, these approaches are very time consuming, with a transgene-expressing mouse model often taking months to establish. We have developed an efficient system for delivering genes in vivo, which allows the gene product to be studied as early as 24 h after introduction into the mouse model. The delivery system employs a novel cationic lipid, 1-[2-(9-(Z)-octadecenoyloxy)ethyl]-2-(8-(Z)-heptadecenyl)-3- (hydroxyethyl)imidazolinium chloride (DOTIM), and a neutral lipid, cholesterol, complexed with an expression vector containing the reporter gene chloramphenicol acetyl transferase (CAT). After a single intravenous injection of these complexes, several tissues were seen to express the transgene. High, persistent expression in the vascular endothelial cells in the mouse lung was obtained. Delivery of DNA in vivo has been evaluated by quantitative polymerase chain reaction and protein expression by CAT activity assays. In vivo studies showed reproducible expression in more than 500 mice injected via the tail vein. An early peak of expression was followed by lower, but sustained, expression for > 50 days. Transgene expression of CAT could also be identified by immunohistochemistry staining in mouse lung and appeared to be located within the capillaries. The pattern of in vivo expression could be modulated and targeted to specific organs by altering the lipid-DNA formulation. New expression vectors with altered introns and polyadenylation sites further improved expression. The expression reported here may be sufficient in magnitude, duration, and flexibility to be an attractive alternative, in some cases, to establishing transgenic animals by stable gene transfer.
Vascular inflammation inhibits gene transfer to the pulmonary circulation in vivo.
We report gene transfer to the normal and injured murine pulmonary circulation via systemic (intravascular) and airway (intratracheal) delivery of novel polycationic liposomes (imidazolium chloride, imidazolinium chloride-cholesterol, and ethyl phosphocholine). With use of the reporter genes chloramphenicol acetyltransferase (CAT) or human placental alkaline phosphatase (hpAP), intravascular injection of lipid-DNA complexes resulted in gene expression primarily in the lung, with lesser expression in the heart (11% of lung, P < 0.05) and spleen (8% of lung, P < 0.05). Histochemical staining for the hpAP reporter gene showed localized transgene expression in the microvascular endothelium. Monocrotaline (80 mg/kg body wt sc) treatment produced endovascular inflammation and reduced lung CAT activity (2 days postintravascular transfection) by 75 +/- 8 and 86 +/- 6% at 7 and 21 days, respectively, after monocrotaline (P < 0. 05). Despite the apparent decrease in functional CAT protein, Southern blot analysis suggested maintained plasmid delivery, whereas quantitative PCR (TaqMan) showed decreased CAT mRNA levels in monocrotaline mice. In contrast, intratracheal delivery of lipid-DNA complexes showed enhanced CAT expression in monocrotaline mice. Transfection in alternate pulmonary vascular disorders was studied by inducing hypoxic pulmonary hypertension (4 wk at barometric pressure of 410 mmHg). Efficiency and duration of gene transfer, assessed by CAT activity, were similar in pulmonary hypertensive and normal lungs. We conclude that imidazolinium-derived polycationic liposomes provide a means of relatively selective and efficient gene transfer to the normal and injured murine microvascular circulation, although translation of transgene mRNA may be reduced by preexisting endothelial injury.
Medicare woes. Many HMOs are dropping patients over 65. Here's how to make sure you stay well covered.
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Facing the knife. Could eating potatoes affect your recovery from surgery? Maybe. Here's a list of dos and don'ts.
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Ask a cyberdoc. Need a fast answer to a medical question? AOL now lets you talk to physicans for free.
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Prevent crib death.
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Managed care 1998. Playing the HMO game.
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Caught in the act. A striking 3-D snapshot of the AIDS virus reveals weak spots in its armor.
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In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma.
In vivo transfection of established tumors with immunostimulatory genes can elicit antitumor immunity. Therefore, we evaluated the safety and efficacy of intratumoral injections of a bacterial superantigen with a cytokine gene in dogs with malignant melanoma, a spontaneous and highly malignant canine tumor. 26 dogs with melanoma were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin B and either GM-CSF or IL-2. Dogs were evaluated for treatment-associated toxicity, tumor responses, immunologic responses, and survival times. The overall response rate (complete or partial remissions) for all 26 dogs was 46% (12 of 26), and was highest in patients with smaller tumors. Toxicity was minimal or absent in all dogs. Injected tumors developed marked infiltrates of CD4+ and CD8+ T cells and macrophages, and tumor regression was associated with development of high levels of antitumor cytotoxic T lymphocyte activity in peripheral blood lymphocytes. Survival times for animals with stage III melanomas treated by intratumoral gene therapy were prolonged significantly compared with animals treated with surgical tumor excision only. Thus, local tumor transfection with superantigen and cytokine genes was capable of inducing both local and systemic antitumor immunity in an outbred animal with a spontaneously developing malignant tumor.
When did AIDS begin? A new study of the oldest known HIV suggests the virus jumped from animals to humans in the 1940s.
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Alterations in self-perceptions following childhood onset of spinal cord injury.
Most research into psychological aspects of spinal cord injury (SCI) has focused on adult onset. This is a retrospective study of self-perceptions following a childhood onset of SCI. Self-esteem, depression and self-perception were examined in 86 people who had a traumatic SCI before the age of 16. Depression was measured using the Beck Depression Inventory, and self-esteem using the Culture-Free Self-Esteem Inventory Self-perception was measured using a scale developed for this study, consisting of 20 adjectives, with participants themselves on dimensions of 'As I am', 'As I would be without the injury', and 'as I would be ideally'. The participants' self perceptions of the injured self and the uninjured self were found to be significantly different on only nine of the 20 adjectives. Low self-perception was found to be associated with low self-esteem and high depression levels, but independent of age at injury, level of injury and gender. The change noted by the participants between how they see themselves now and how they would have been without the injury is not as great as might have been expected.
Improving care for adults with asthma across the continuum.
Asthma affects approximately 14.6 million people in the United States. Despite the publication of multiple guidelines, the delivery of care has not substantially changed. This article describes a program at Advocate Health Care to improve the delivery of care to adults with asthma in a variety of settings. Using standard patient education materials and a variety of continuous quality improvement tools, this project enhances partnership between patients and health care providers.
Medium to long-term intraocular pressure control following small flap trabeculectomy (microtrabeculectomy) in relatively low risk eyes.
AIM: To determine the long-term efficacy of small flap trabeculectomy (microtrabeculectomy) in terms of intraocular pressure (IOP) control in relatively low risk eyes. METHOD: A review of a case series of small flap trabeculectomy procedures performed on 36 eyes from 36 patients with a minimum follow up of 24 months (mean 50.8). RESULTS: The mean (SD) intraocular pressures at presentation and preoperatively were 33.7 (7.5) and 24.6 (4.5) mm Hg. At 6 months, 1, 2, 3, 4, 5, and 6 years the mean (n, SD) IOPs (mm Hg) of those eyes followed to each time point were 11.9 (36, 4.6), 12.6 (36, 4.7), 13.2 (36, 4.6), 13.7 (29, 4.1), 13.2 (22, 4.0), 12.7 (15, 4.8), and 12.3 (8, 4.7) respectively. There was no significant difference in IOP levels at any of the analysis points by one way ANOVA. Kaplan-Meier analysis revealed survival rates of 80% at 4 years and 75% at 5 years when any postoperative IOP > 20 mm Hg is considered a failure, and 50% at 6 years when any IOP > 15 mm Hg is classed as a failure. CONCLUSION: Small flap trabeculectomy (microtrabeculectomy) is effective at reducing IOP in low risk glaucoma eyes with IOP control similar to previous reports of filtering surgery utilising larger scleral trapdoors.
Use of indomethacin for pain relief following scleral buckling surgery.
BACKGROUND/AIMS: Patients undergoing scleral buckling and cryotherapy suffer from mild to moderate postoperative pain. As good pain relief facilitates post-operative ocular examination, as well as patient comfort and recovery, the authors designed a prospective randomised double masked trial to evaluate the efficacy of indomethacin as a satisfactory analgesic for such patients. METHOD: Patients with a primary uncomplicated rhegmatogenous retinal detachment requiring scleral buckling and cryotherapy were randomly allocated to receive either indomethacin or placebo. A rectal suppository was administered 2 hours before surgery, followed by two capsules twice daily for 10 days. Pain relief was assessed with a linear graphic rating scale at the end of each day. Supplementary analgesia was allowed and recorded. RESULTS: 12 patients received indomethacin (group A) and 16 received placebo (group B). The extent of surgery was similar in both groups. One patient in group A, and two in group B withdrew after 3 days. The pain scores were converted to changes from the baseline (score on day 1), and the area under the curve calculated for each patient. The means of the areas were analysed with the Mann-Whitney test and showed that indomethacin caused a statistically significant reduction in pain score, both at 3 days (p = 0.04) and at 10 days (p = 0.014). There was no statistically significant difference in extra analgesic requirements between the two groups (p = 0.2). CONCLUSIONS: Indomethacin is recommended for short to medium term pain relief following scleral buckling and cryotherapy.
The odds grow longer. Doctors had hoped by now to have eliminated the AIDS virus from some patients. No such luck.
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Germ warfare. A drug-resistant staph strain has doctors on edge.
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