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Biomedical subjects

A Young

Publications and source records attributed to A Young.

At least 199 records · Page 11Linked to original sources

Ca2+ antagonists effect an antidepressant-like adaptation of the NMDA receptor complex.

Chronic, but not acute treatment of mice with nimodipine and diltiazem produce significant increases in the IC50 of glycine to inhibit [3H]5,7-dichlorokynurenic acid binding in cerebral cortex. Such adaptive changes in the ligand binding properties of the NMDA receptor complex are also manifested following chronic treatment with antidepressants from every principal therapeutic class. These findings indicate voltage-dependent calcium channel antagonists would be strong candidates for rigorous clinical trials in depressive disorders.

Animals↗

The quadriceps strength of healthy elderly people remeasured after eight years.

Isometric quadriceps strength was remeasured in 14 healthy survivors of a group of elderly people first studied 8 years previously. There were 4 men (median age 81 years, range 79 to 84) and 10 women (82 years, range 79 to 89). They were selected for their health, not their levels of physical activity. Nevertheless, they were active when first studied and, with 1 exception, had maintained or increased their levels of physical activity. Isometric quadriceps strength was well preserved; the median change in the strength of the stronger quadriceps was only -0.3% per annum (95% confidence interval = -1.4 to +0.8).

Aged↗

CO2 reactivity in the ischaemic core, penumbra, and normal tissue 6 hours after acute MCA-occlusion in primates.

Testing vasoreactivity with CO2 or Diamox is a common diagnostic procedure for the study of haemodynamics in stroke patients. CO2 reactivity (CO2R) was tested in 5 baboons six hours after permanent occlusion of the left middle cerebral artery (MCA) in order to attain new insights into interpretation of vasoreactivity tests. Using the microsphere method, cerebral blood flow (CBF) was determined in the various vascular territories as well as in the centre of the ischemia, the penumbra and the remaining MCA-tissue. CBF decreased significantly in the affected MCA in all animals and in addition in the contralateral cerebellum in one animal (p < 0.05). In addition, the left anterior cerebral artery (ACA) demonstrated a similar decrease. During hypercapnia CBF increased in all areas with the exception of the left, occluded MCA territory. Thus CO2 enhanced the difference between ischaemic and non-ischaemic tissue (i.e., tissue with diaschisis). Mean CO2 R was 3.37 ml/100 g/min/mmHg in the right MCA, 0.16 in the left. While the left ACA demonstrated a decreased perfusion during normocapnia in a similar range to the MCA territory, only CO2R was able to identify precisely the territory of the occluded vessel. CO2 R was zero or negative in the ischaemic core, close to zero in the penumbra and profoundly decreased in the remaining MCA tissue. The overall CO2 R of the MCA was almost zero, suggesting vasoparalysis in response to hypercapnia in the core and penumbra and exhausted CO2 R even in non-infarcted, non-penumbral tissue. One animal displayed a negative CO2 R equivalent to an intracerebral steal-phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Structure and biology of amylin.

Amylin is a recently discovered 37 amino acid peptide secreted into the bloodstream, along with insulin, from pancreatic beta-cells. It is about 50% identical to calcitonin gene-related peptides (CGRP alpha and CGRP beta) and structurally related to the calcitonins. Amylin can elicit the vasodilator effects of CGRP and the hypocalcaemic actions of calcitonin, while these peptides can mimic newly discovered actions of amylin on carbohydrate metabolism. The different relative potencies of these peptides suggest that they act with different selectivities at a family of receptors. Amylin is deficient in insulin-dependent diabetes mellitus, while plasma levels are elevated in insulin-resistant conditions such as obesity and impaired glucose tolerance. In this Viewpoint article, Tim Rink and colleagues propose that amylin is an endocrine partner to insulin and glucagon; deficiency or excess of amylin may therefore contribute to important metabolic diseases.

Amino Acid Sequence↗

Factors predicting death, survival and functional outcome in a prospective study of early rheumatoid disease over fifteen years.

Sixty-four survivors from a prospective study of early rheumatoid disease were assessed again at a mean of 15.2 years from presentation and their status compared with 29 patients who had died. Eleven of the dead and only two of the survivors had been treated with steroids. There was a small increase in mortality due to the disease itself but only one death was directly caused by it. As might be expected, those who died were older. In the first year of disease, they had lower haemoglobin levels, a lower body mass, higher sedimentation rates and higher levels of blood urea. One-fifth at entry to the study and two-fifths by the time of death, had poor functional capacity. Of 64 survivors, six had poor functional capacity at entry and nine after 15 years. Discriminant analysis was performed to identify the most powerful combination of early features predicting a poor functional outcome. A combination including early erosive change, seropositivity, poor grip strength and cervical subluxation predicted the outcome correctly in 73% of survivors. Almost 60% of survivors remained with or improved to normal function at 15 years suggesting that morbidity is not as bad as has been suggested in the past.

Adult↗

Opsonic requirements of Helicobacter pylori.

The opsonic requirements of Helicobacter pylori were investigated in a series of experiments with human polymorphonuclear leucocytes (PMNL). Pre-incubation of H. pylori with pooled normal human serum (NHS) in concentrations of 5-20% significantly increased the uptake of radiolabelled bacteria by PMNL. Treatment of the bacteria with NHS 30% caused the release of radiolabel and this effect was abolished by heating serum to 56 degrees C, suggesting that H. pylori is serum-sensitive and that complement is involved. Opsonisation of H. pylori with NHS concentrations of 10-30% significantly increased PMNL chemiluminescence. Removal of specific antibody had no effect. Removal of either the classical or alternative complement pathways produced no significant change in PMNL chemiluminescence, indicating that either pathway is sufficient for opsonisation on its own. The results confirm that complement is the most efficient opsonin for H. pylori.

Analysis of Variance↗

Treadmill walking in old age may not reproduce the real life situation.

OBJECTIVE: In a preliminary study in our laboratory, healthy elderly people had a higher heart rate during treadmill walking than during corridor walking at the same speed. The objective of this study was to determine whether this initial observation, (1) persisted after repeated testing, (2) was present in younger adults, (3) was due to wearing a mouthpiece during treadmill walking, or (4) was due to a change in gait. DESIGN: A study of elderly and young volunteers undergoing repeated testing, with comparison of treadmill walking with corridor walking. SETTING: The Royal Free Hospital School of Medicine. PARTICIPANTS: Twelve healthy elderly (71-80 years) and 12 healthy young (21-37 years) volunteers. MAIN OUTCOME MEASURES: Heart rate (beats/min) and step rate (steps/min) during comfortable self-paced corridor walking and during treadmill walking at the same speed. MAIN RESULTS: The elderly subjects had higher heart rates during treadmill walking than during corridor walking at the same speed (mean difference = 6 beats/min, 95% Confidence Interval (CI) = 1 to 10). This difference increased (to a mean of 11 beats/min, 95% CI = 5 to 16) when a mouthpiece was worn on the treadmill. These differences persisted after repeated testing. The young subjects did not have higher heart rates on the treadmill, (with or without the mouthpiece). In both groups, step rate was lower (95% CI = -9 to -2, elderly; -5 to -2, young) during treadmill walking, corresponding to a 3% increase in stride length. CONCLUSION: The heart rate response to treadmill walking in healthy elderly people may be less representative of the "real life" situation than in younger adults.

Adult↗

Current issues in arthrogenous inhibition.

Joint disease commonly results in severe weakness of associated muscles. Efforts to restore strength are often unsuccessful, even in the absence of pain. This is because of the underlying inhibition of motoneurones by afferent signals from in and around the affected joint, 'arthrogenous inhibition'. This phenomenon has received scant scientific attention, but several experimental techniques are now available with which it can be studied in man. Animal studies suggest possible neurophysiological mechanisms. Selective atrophy of different muscle fibre types, perhaps implying selective inhibition of different types of motor unit, remains unexplained, however. The severity of arthrogenous inhibition can be temporarily reduced by silencing afferent traffic but none of the techniques is yet generally applicable in practice. An alternative therapeutic approach is to produce involuntary muscle contractions by electrical stimulation. The effectiveness of therapeutic electrical stimulation may depend on the frequency and other characteristics of the stimulus.

Animals↗

Gametic but not somatic instability of CAG repeat length in Huntington's disease.

Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD) chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD repeat showed no evidence of somatic instability in a comparison of blood, lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD twins displayed identical CAG repeat lengths suggesting that repeat size is determined in gametogenesis. In contrast with the fragile X syndrome and with HD somatic tissue, mosaicism was readily detected as a diffuse spread of repeat lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree of gametic mosaicism coinciding with the longest somatic CAG repeats. These data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.

Adolescent↗

Amma therapy: a holistic approach to chronic fatigue syndrome.

A significant number of people suffering with chronic fatigue syndrome have become more and more discouraged by the traditional medical approach, which seems to lack the proper perspective on the disease. Unfortunately, very little published information is available about specific holistic health management practices used for these patients. It is the purpose of this article to examine a specific holistic practice, called Amma Therapy, as an alternative approach for the management of this syndrome.

Complementary Therapies↗

Superoxide dismutase and allopurinol improve survival in an animal model of hemorrhagic shock.

We studied the efficacy of resuscitation with antioxidants in an animal model of hemorrhagic shock. Male Sprague-Dawley rats were anesthetized, and 27 mL/kg of blood was withdrawn from the carotid artery over 2 minutes. The animals remained in hemorrhagic shock for 45 minutes, followed by 1 hour of resuscitation. Experimental groups were as follows: 1) 15,000 u/kg superoxide dismutase (SOD) in 54 mL/kg lactated Ringer (LR); 2) 175,000 u/kg catalase (CAT) in LR; 3) 15,000 u/kg SOD+175,000 u/kg CAT in LR; 4) allopurinol in LR; 5) deferoxamine bound to pentafraction (DFO), 27 mL/kg; 6) pentafraction alone; and 7) LR alone. Compared with resuscitation with LR alone, SOD and allopurinol improved survival over 72 hours, P < 0.05. Survival with SOD+CAT was not different from LR alone. Deferoxamine bound to pentafraction did not increase survival over that with pentafraction alone. CAT had increased mortality compared to LR, P < 0.01. The efficacy of both SOD and allopurinol in decreasing mortality suggests the importance of superoxide radicals after hemorrhagic shock and resuscitation. These and other antioxidants are potential therapeutic agents in the clinical setting of trauma and hemorrhagic shock.

Allopurinol↗

Oncology nurses' attitudes regarding voluntary, physician-assisted dying for competent, terminally ill patients.

Euthanasia and "voluntary dying" are among the most controversial issues involved in cancer care. The purpose of this descriptive study was to explore oncology nurses' attitudes about physician-assisted death (PAD) for competent, terminally ill adults who request this assistance. Questionnaires were sent to 2,000 randomly selected members of the Oncology Nursing Society. The questionnaires included demographic questions, four vignettes describing patient care situations and possible responses based on beliefs about PAD, and questions that explored awareness of organizations and legislation that promote legalization of PAD. The response rate was 61% (1,210). Findings indicate that oncology nurses hold diverse views regarding the acceptability of PAD. Although many nurses favored PAD, they also expressed a reluctance to administer the medication that would cause death. Given that PAD is an ethical and legal issue in the United States for terminally ill patients, nurses are encouraged to become informed about the concept of PAD and be prepared to actively respond to the policy-making ramifications of the assisted-death movement.

Adult↗

Chronic treatment with 1-aminocyclopropanecarboxylic acid desensitizes behavioral responses to compounds acting at the N-methyl-D-aspartate receptor complex.

Functional antagonists at the N-methyl-D-aspartate (NMDA) receptor complex produce anti-depressant-like actions in preclinical models. Thus, an injection of a glycine partial agonist (1-aminocyclopropanecarboxylic acid; ACPC), a competitive NMDA antagonist (2-amino-7-phosphonoheptanoic acid; AP-7) or a use-dependent cation channel blocker (MK-801) reduced immobility in the forced swim test (FST) with efficacies comparable to imipramine (Trullas and Skolnick 1990). Seven daily injections of ACPC (200-400 mg/kg) abolished the effects of both this compound (200-1200 mg/kg) and AP-7 (200-300 mg/kg) in the FST. The loss in effectiveness of ACPC required 7 days of treatment to become fully manifest, and was reversed by discontinuing treatment. Other agents active in the FST (e.g. MK-801, imipramine, and nifedipine) were unaffected by this regimen. Moreover, ACPC and AP-7 remained active in the FST following repeated injections of MK-801, AP-7, or imipramine. Chronic treatment with ACPC did not affect its actions in the elevated plus-maze, but significantly attenuated the convulsant and lethal effects of NMDA (125 mg/kg). Tissue levels of ACPC indicate the modified behavioral responses produced by chronic treatment are not attributable to pharmacokinetic factors. These findings suggest repeated administration of ACPC may effect an "uncoupling" of NMDA and glycine receptors, resulting in an apparent desensitization of the behavioral actions of substances acting at these sites.

2-Amino-5-phosphonovalerate↗

Controlling and predicting monoclonal antibody production in hollow-fiber bioreactors.

A simple optimization strategy is described which enables monoclonal antibody (MCA) production in hollow-fiber bioreactors to be controlled and predicted. The MCA production rate is demonstrated to increase linearly with the uptake rates of glucose and glutamine and with the production rates of lactate and ammonia. The uptake and production rates of these metabolites can, in turn, be predicted from the pumping rates of basal medium to the bioreactor. We recommend a period of 2 weeks at the start of the cultivation when intensive assaying and monitoring should be carried out. After this period, the medium flow rate and MCA production rate may be predicted by linear extrapolation.

Ammonia↗