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Biomedical subjects

A Gordon

Publications and source records attributed to A Gordon.

At least 127 records · Page 7Linked to original sources

Lack of role for nitric oxide (NO) in the selective destabilization of endothelial NO synthase mRNA by tumor necrosis factor-alpha.

The constitutive expression of endothelial nitric oxide (NO) synthase (cNOS) is essential for the physiological regulation of vascular tone and structure. The mechanism of downregulation of steady state cNOS mRNA in human umbilical vein endothelial cells exposed to tumor necrosis factor-alpha (TNF-alpha) was investigated by using Northern blot analysis of total cellular RNA. TNF-alpha produced a dose- and time-dependent decrease in cNOS mRNA expression that was near maximal at 10 U/mL and 6 hours of exposure, respectively. In contrast, steady state expression of endothelin-1 and plasminogen activator inhibitor-1 (PAI-1) mRNA was upregulated by TNF-alpha. The pharmacological generation of NO using sodium nitroprusside (10 mumol/L) and S-nitroso-acetylpenicillamine (100 to 400 mumol/L) had no effect on cNOS mRNA levels, and TNF-alpha-induced downregulation of cNOS was not prevented by coincubation with the inhibitors of NO synthesis N omega-nitro-L-arginine methyl ester (1 mmol/L) and NG-monomethyl L-arginine (10 mmol/L). Under control conditions, cNOS and PAI-1 mRNA were stable after treatment with actinomycin D for periods greater than 24 hours, whereas endothelin-1 message was rapidly degraded (half-life, < 1 hour). Pretreatment with TNF-alpha (30 U/mL) selectively reduced that half-life of cNOS mRNA to less than 12 hours without altering the stability of PAI-1 message. TNF-alpha-induced destabilization of cNOS mRNA could be partially prevented by coincubation with cycloheximide (1 mumol/L) but was not reproduced by addition of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance.

BACKGROUND: Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance. AIM: To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure. METHODS: With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens. RESULTS: Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05). CONCLUSIONS: One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.

Administration, Oral↗

Does patient semen quality alter during an in vitro fertilization (IVF) program in a manner that is clinically significant when specific counseling is in operation?

PURPOSE: It has been shown that the stress of infertility may impair semen quality. Whether counseling can attenuate this affect is unproven. This study examines, in an IVF program setting, where specific counseling is in operation, whether semen collected on the day of oocyte recovery is significantly different from that obtained during the prior clinical suitability assessment of the couple. RESULTS: In the 125 consecutive couples examined, there were no significant overall differences in semen volume or sperm density. There was a significant increase in sperm motility on the day of oocyte retrieval (P < 0.001). Twenty-three patients (18.4%) showed an increase in quality, and 21 (16.8%) a decrease, on the day of oocyte recovery. The environment of production appeared to exert no influence. Fertilization failure occurred in seven couples, three (14%) of whom presented for the first time with decreased semen parameters on the day of IVF. This compares with 1 of 23 (4%) fertilization failure in those whose parameters increased. CONCLUSION: The semen quality of the vast majority of the patients studied in this highly counseled program does not appear to be significantly affected by the superstress of participation in the day of oocyte recovery.

Adult↗

The role of sympathectomy in current surgical practice.

Historically sympathectomy has been employed in the treatment of a variety of disparate disorders but in most there is little if any objective clinical evidence of its efficacy. Review of the literature confirms that sympathectomy provides an effective and permanent cure for hyperhidrosis of the hands and feet, and at present palmar hyperhidrosis is the major indication for its regular use. Sympathetic denervation of the hands is currently most easily achieved with minimal morbidity by thoracoscopic ablation of the second thoracic ganglion. Some evidence testifies to the efficacy of sympathectomy in the rare patients with true major causalgia. Clinical experience suggests that Raynaud's phenomenon in the feet can be usefully ameliorated by sympathectomy but in the hands any benefit is short lived and there is no effect on the prognosis of the disease. A weak case can be made for sympathectomy for ischaemic rest pain when arterial surgery is impractical but there is no reliable evidence to support its use in Buerger's disease, intermittent claudication, diabetic vascular disease or ischaemic ulceration or gangrene.

Causalgia↗

An eight year experience of conservative management for aortic graft sepsis.

This paper describes the results of conservative management of 15 patients with aortic graft infection. The median time to presentation was 4 months. Six of eight grafts that were sent for culture grew organisms, of which the commonest were streptococci and coagulase negative staphylococci. Four patients did not receive intensive antibiotic treatment and all died of sepsis. Eleven patients received intensive intravenous and oral antibiotic therapy and appropriate surgical management; two of these died, one of a stroke and the other of an unknown cause. Two of the nine surviving patients had no surgery and the remainder had procedures to drain pus and unblock occluded grafts, including minimal graft excision in four patients, although two of these subsequently required total graft excision. The follow-up period for six of these nine patients is more than 4 years. For most patients with aortic graft infection aggressive antibiotic treatment supplemented by minimalist surgery is preferable to primary radical surgery.

Administration, Oral↗

The production of a monoclonal T3-antiidiotypic antibody (T3-MAAB) that mimics the effects of T3 on 2-deoxy-D-glucose uptake in chick embryo heart cells.

The Ig fraction of rabbit anti-T3 antibody was injected into the spleens of BALB/c mice. Four days later, the lymphocytes were recovered from their spleens and were fused with cells of the 653 myeloma cell line. Screening of the hybrid colonies was carried out in a T3 RIA system. Positive colonies were those whose supernatant displaced 125I-labeled T3 from its antibody. The positive cultures were recloned and one was injected ip into mice. The crude IgG fraction of the ascites fluid was affinity purified on an affigel-10 column containing a covalently bound rabbit anti-T3-IgG. In order to eliminate possible endogenous T3 contamination during the affinity purification, the column was stripped with a 40% solution of acetonitrile in 0.2 M acetic acid, neutralized, and then the purification proceeded as described. The affinity purified antibody was an IgG2a isotype. This monoclonal antibody (T3-MAAB) displaced labeled T3 from its antibody in an RIA system. It also mimicked T3 in the stimulation of [3H]2-deoxy-D-glucose (2-DOG) uptake in cultured chick embryo heart cells. After 6 h exposure, the dose-response curve of 2-DOG uptake to T3-MAAB was shifted to the left by at least one order of magnitude when compared to the dose-response curve obtained with T3. After 24 h exposure, T3 had the expected additional stimulatory effect that was dependent on neosynthesis of proteins, while T3-MAAB did not. Also at 24 h exposure, T3-MAAB did not stimulate the incorporation of labeled leucine and uridine into the heart cells while T3 at an equivalent concentration did. The MAAB activity could be abolished by boiling, while boiling did not affect the activity of an equivalent concentration of T3, thus excluding a T3 contamination-mediated effect. We conclude, therefore, that (a) a monoclonal hybridoma producing an antibody that mimics T3 was established; (b) this antibody competed with labeled T3 for anti-T3 antibody and, like T3, stimulated sugar uptake into cultured chick embryo heart cells; and (c) this antibody, unlike T3, did not stimulate the neosynthesis of proteins.

Animals↗

A statistical analysis of Modified Clinical Technique vision screening of preschoolers by optometry students.

Fourth year optometry students screened 745 preschoolers using a slightly altered Modified Clinical Technique (MCT) under the supervision of a faculty doctor. Children who failed the MCT were randomly selected and then matched by age, sex, and ethnic origin to children who had passed the screening battery. The 61 screening failures and 45 matched controls were later given full eye examinations with cycloplegia by University of Alabama at Birmingham faculty doctors who were unaware of the screening results. The positive predictive value (PPV) (0.52) and negative predictive value (NPV) (0.78) of the MCT were calculated directly from the 2 x 2 contingency table crossing screening results and a standard diagnosis. Sensitivity [0.50, k(1,0) = 0.29], specificity [0.79, k(0,0) = 0.30], efficiency [0.70, k(0.5,0) = 0.29] of the MCT, and the prevalence (0.30) of children failing the standard diagnosis were estimated using statistics appropriate to the prospective sampling design. The reproducibility of the diagnosis, estimated by analyzing multiple, independent diagnosis of each study child by seven doctors was moderate (kappa D 0.58). Statistics summarizing the agreement between the MCT and the diagnosis by the individual study doctor are similar to those obtained with comparison to the standard diagnosis. The characteristics of the MCT may be generalized only to similar populations that are screened by clinicians with similar experience, using the same tests.

Child↗

Leptomeningeal gliomatosis.

The diagnosis of leptomeningeal gliomatosis is discussed in relation to a single case studied in detail. Histology showed extensive subarachnoid spread of tumour that seemed to originate in an astrocytoma of the ventricular wall. The spinal fluid was xanthochromic with a high protein content. Reports of primary leptomeningeal gliomatosis are reviewed and the need for detailed histological study of the brain in such cases is emphasised.

Aged↗

Differentiation between musculoligamentous, dentoalveolar, and neurologically based craniofacial pain with a diagnostic questionnaire.

A self-administered questionnaire consisting of 21 questions, diagrams for chief pain location, and a digital pain scale was used prospectively to sort 92 patients with orofacial pain into three categories: (1) musculoligamentous (ie, temporomandibular disorders); (2) neurologically based (ie, migraine, trigeminal neuralgia, tension-type headache, cluster headache, and atypical facial pain); and (3) dentoalveolar pain. Sensitivity, specificity, as well as negative and positive predictive values suggest that this questionnaire may be used reliably to identify patients with orofacial pain that fits the above-described pain categories without prior knowledge of the clinical diagnosis. Digital pain scale findings indicated that on presentation, pain level could not be correlated with any particular pain category, but when using this scale to describe past pain experience, patients with neurologically based pain selected the highest digital pain scale values up to six times more frequently than patients with musculoligamentous or dentoalveolar pain. Patients with musculoligamentous or dentoalveolar pain selected the lowest digital pain scale values up to 15 times more frequently than those with neurologically based pain. Although this questionnaire may be used for initial categorization of pain, there is still no substitute for a thorough history and clinical examination.

Adult↗

Should gonadotropin-releasing hormone down-regulation therapy be routine in in vitro fertilization?

OBJECTIVE: To compare the classic clomiphene citrate (CC) and hMG regime for ovarian stimulation before IVF in women who received hMG post-long protocol down-regulation with either 3 mg triptorelin [INN] IM or 150 mg buserelin acetate four times daily intranasally. Furthermore, if possible, to determine the preferred method of down-regulation. DESIGN: A prospective study of 150 women randomized blind to the clinician to one of three alternative ovarian stimulation regimes when passing for the first time through an IVF program during 1992. RESULTS: Triptorelin [INN] down-regulated significantly more quickly than buserelin acetate. The non-down-regulated group CC and hMG used significantly less hMG in a shorter time. In these women LH levels at hCG administration were significantly higher. No other intergroup differences were found. Pregnancy and take-home baby rates for the overall study were, respectively, 32%:25% (per cycle) and 42%:33%; (per ET) for the triptorelin [INN] group 28%:22% and 39%:31%; the CC group 32%:24% and 46%:34%; and the buserelin acetate group 34%:28% and 42%:34%. CONCLUSIONS: Triptorelin [INN] and buserelin acetate were comparable in all parameters except down-regulation. The former was significantly quicker and more sure. In none of the clinical end points measured, however, was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used. These results therefore show that although indications for down-regulation before IVF exist, it should not be used on all patients.

Adult↗