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Biomedical subjects

A L Miller

Publications and source records attributed to A L Miller.

At least 55 records · Page 3Linked to original sources

Therapeutic considerations of L-glutamine: a review of the literature.

The most abundant amino acid in the bloodstream, L-glutamine fulfills a number of biochemical needs. It operates as a nitrogen shuttle, taking up excess ammonia and forming urea. It can contribute to the production of other amino acids, glucose, nucleotides, protein, and glutathione. Glutamine is primarily formed and stored in skeletal muscle and lungs, and is the principal metabolic fuel for small intestine enterocytes, lymphocytes, macrophages, and fibroblasts. Supplemental use of glutamine, either in oral, enteral, or parenteral form, increases intestinal villous height, stimulates gut mucosal cellular proliferation, and maintains mucosal integrity. It also prevents intestinal hyperpermeability and bacterial translocation, which may be involved in sepsis and the development of multiple organ failure. L-glutamine use has been found to be of great importance in the treatment of trauma and surgery patients, and has been shown to decrease the incidence of infection in these patients. Cancer patients often develop muscle glutamine depletion, due to uptake by tumors and chronic protein catabolism. Glutamine may be helpful in offsetting this depletion; however, it may also stimulate the growth of some tumors. The use of glutamine with cancer chemotherapy and radiotherapy seems to prevent gut and oral toxic side-effects, and may even increase the effectiveness of some chemotherapy drugs.

Digestive System↗

Cognitive dysfunction in schizophrenia and its importance to outcome: the place of atypical antipsychotics in treatment.

The neurocognitive impairment associated with schizophrenia has been well established. Such impairment may be present prior to the onset of the positive symptoms of schizophrenia and persist during periods of remission. Neurocognitive deficits predict multiple domains of outcome; treating such deficits is therefore regarded as highly important. Conventional antipsychotic agents do not appear to favorably affect cognitive function in schizophrenia. Indeed, their propensity to induce adverse effects such as extrapyramidal symptoms may further impair cognitive function. A growing body of evidence suggests that patients taking atypical antipsychotics perform better on some tests of neurocognitive ability than patients receiving conventional agents, with implications for adaptive functioning. The neurocognitive benefits of the atypical antipsychotic agents discussed in this article support their use as a first-line therapy for schizophrenia.

Adult↗

Executive-frontal lobe cognitive dysfunction in schizophrenia: a symptom subtype analysis.

Impairment of executive-frontal lobe functioning, affecting the planning, initiation and regulation of goal-directed behavior, is a common cognitive deficit in schizophrenia. However, it is unclear if deficits in these frontal-lobe-mediated abilities are differentially expressed across clinical subgroups. We analyzed executive-frontal abilities in relation to symptom expression in 53 hospitalized schizophrenic patients. Patients were assigned to one of three subgroups based on rank order analysis of Brief Psychiatric Rating Scale factors: Withdrawal-Retardation, Reality Distortion and Conceptual Disorganization. Executive-frontal tests included Visual Search, Verbal Fluency, Verbal Series Attention, Trail Making - Part B, Symbol Digit, Hopkins Verbal Learning, Digit Span, Wisconsin Card Sorting, Stroop Color-Word and Attentional Capacity. The schizophrenia group showed significant deficits relative to healthy control subjects (n = 20) on all tests. Exploratory factor analysis of test scores revealed three factors: (i) Verbal Processing/Memory; (ii) Cognitive Flexibility/Attention; and (iii) Psychomotor Speed/Visual Scanning. The three symptom subgroups were differentially impaired on executive-frontal abilities: Withdrawal-Retardation on psychomotor speed, verbal fluency, working memory, visual search and cognitive flexibility; Conceptual Disorganization on attention; Reality Distortion on verbal memory. The results have implications for syndrome definition, pharmacological intervention and prediction of outcome in schizophrenia.

Adult↗

Streptomycin inhibition of myogenic tone, K+-induced force and block of L-type calcium current in rat cerebral arteries.

1. Streptomycin has been demonstrated to inhibit mechanosensitive conductances in a wide variety of cell types, including muscle. The action of streptomycin on rat cerebral arteries that exhibit pressure-induced myogenic response was investigated. 2. Pressure-induced tone, measured using isobaric myography, in isolated pressurized cerebral arteries was reversibly and concentration-dependently inhibited by streptomycin with an IC50 of 2.6 mM. 3. Isometric K+-induced force, measured using isometric myography, is supported by voltage-gated Ca2+ entry. Streptomycin reversibly and concentration-dependently inhibited isometric force with an IC50 of 1.71 mM. 4. Voltage-gated macroscopic inward Ca2+ channel currents were recorded from freshly isolated rat basilar myocytes. These were reversibly and concentration-dependently inhibited by streptomycin with an IC50 of 1.79 and 0.47 mM when 10 and 1.8 mM CaCl2, respectively, was used as the charge carrier. 5. These data suggest that streptomycin inhibits myogenic tone and K+-induced isometric force largely by blockade of L-type, dihydropyridine-sensitive Ca2+ channels. In conclusion, streptomycin is not useful in the investigation of stretch-activated channels which may underlie the myogenic response of rat small cerebral arteries.

Animals↗

Non-specificity of chloride channel blockers in rat cerebral arteries: block of the L-type calcium channel.

1. The effects of chloride channel blockers on pressure-induced constriction, K(+)-induced force, and whole-cell calcium channel currents were tested in rat cerebral arteries using isobaric and isometric myography, and patch clamp. 2. Under isobaric conditions at 75 mmHg, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a chloride channel blocker, reversibly depressed the myogenic constriction with an IC50 of 32.8 +/- 0.52 microM (mean +/- S.E.M., n = 5). Blockers of Ca(2+)-activated chloride channels, flufenamic acid (100 microM) and 9-anthracene chloride (9-AC; 1 mM), and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel blocker, glibenclamide (100 microM), were without effect in this tissue (n = 3). 3. Under isobaric conditions at 20 mmHg, 37 degrees C, raising [K+]o to 45 mM induced a constriction which was unaffected by 100 microM NPPB (n = 4). In contrast, at 75 mmHg and 18-21 degrees C, 100 microM NPPB completely and reversibly blocked a 45 mM K(+)-induced constriction (n = 3). 4. Under isometric conditions, NPPB reversibly depressed a 45 mM K(+)-induced force with an IC50 of 10.0 +/- 0.76 microM (mean +/- S.E.M., n = 5). Indanyloxyacetic acid 94 (IAA-94), another chloride channel blocker, depressed the K(+)-induced force with an IC50 of 17.0 +/- 1.2 microM (mean +/- S.E.M., n = 4). 5. Using whole-cell patch clamp, 100 microM NPPB or 200 microM IAA-94 blocked calcium channel currents carried by 10 mM Ba2+ by 79.1 +/- 1.7 and 39.8 +/- 7.0%, respectively (mean +/- S.E.M., n = 6). 6. In summary, chloride channel blockers depress calcium channel currents in rat cerebral arteries, which could contribute to a reduction in myogenic contraction.

Animals↗

The effects of nicotine on the immune system.

Although considerable work has been done on the potential health effects of smoking, little is known about the contribution of nicotine to those effects. This paper presents an overview of the immune system, and a discussion of the existing literature on the effects of tobacco smoke and nicotine on immunity. Treatment with nicotine has been shown to influence all aspects of the immune system, including alterations in humoral and cellular immunity. In addition, preliminary data suggest that gender and genetic factors impact on the immunological effects of nicotine. Finally, the possible mechanisms that might mediate the effects of nicotine are discussed.

Animals↗

Calcium transients accompany ooplasmic segregation in zebrafish embryos.

Through the injection of f-aequorin (a calcium-specific luminescent reporter), and the use of an imaging photon detector, transient localized elevations of free cytosolic calcium in the forming blastodisc (BD) and animal hemisphere cortex were visualized that correlated with ooplasmic segregation. The introduction of an appropriate concentration of the weak (KD = 1.5 micromol/L) calcium buffer 5,5'-dibromo-BAPTA results in the dissipation of these calcium domains, and inhibits cytoplasmic streaming and the subsequent formation of a BD at the animal pole. These inhibitory actions are dependent on the final cytosolic concentration of buffer within the egg: > or = 1.3 mmol/L blocks ooplasmic streaming; < 1.3 mmol/L eggs segregate normally. Injection of 5,5'-dimethyl-BAPTA (KD = 0.15 micromol/L) to a final concentration of 1.5 mmol/L as a control has no effect on ooplasmic streaming. These results suggest that localized domains of elevated free cytosolic calcium are essential for ooplasmic segregation in zebrafish. Furthermore, a hypothetical model is presented linking these calcium transients to the contraction of a cortically located actin microfilament network as a possible mechanism providing the driving force for segregation.

Aequorin↗

Outpatient management of deep vein thrombosis.

OBJECTIVE: To assess whether patients with deep vein thrombosis (DVT) could be satisfactorily treated on an outpatient basis with low molecular weight (LMW) heparin and warfarin. DESIGN: A 22 month prospective study of adults attending St Peter's Hospital accident and emergency department with DVT. RESULTS: 1093 patients were referred and assessed; 160 were venogram positive, of which 159 patients between the ages of 22 and 89 years of age have now been treated with LMW heparin as outpatients. Direct liaison with community nurses has minimised the impact on general practitioner workload. CONCLUSIONS: 1272 bed days were saved during this period (an estimated 320,000 pounds). The outpatient treatment of thromboembolism has been shown to be effective and safe.

Adult↗

Log-jam in acid-base education and investigation: why make it so difficult?

Medical students frequently have difficulty in interpreting acid-base data particularly when pH values are used. The difficulty persists when students qualify and has implications for the safe management of patients who require investigation of acid-base status. Simplification of tuition is required together with a change of practice in the reporting of acid-base data by the laboratories. To improve understanding, we recommend that the teaching and reporting of acid-base status should be changed to use [H+] instead of pH, and a greater emphasis placed on the logical interpretation of primary measurements--that is [H+] and PCO2--with less reliance on derived variables.

Acid-Base Equilibrium↗

Ethnicity and negative symptoms in patients with schizophrenia.

The purpose of this study was to assess ethnic differences in the negative symptom profile of 25 Anglo American and 26 Mexican American subjects with schizophrenia. Subjects were rated at the end of a 1-2-week medication washout period (time 1) and at discharge (time 2) with the Negative Symptoms Assessment (NSA), Brief Psychiatric Research Scale, (BPRS), the [Diagnostic and Statistical Manual of Mental Disorders (4th edition)] DSM-IV negative factor score and LAECA acculturation scale. Total NSA scores were significantly higher among Mexican Americans both at time 1 and time 2. Among the five subscales of the NSA, ethnic differences were significant only for the Cognition subscale at time 1. Results indicate no ethnic differences in core negative symptoms (alogia, avolition, flat affect), but do suggest that a cognition-related factor differs between Mexican American and Anglo American schizophrenic patients.

Adult↗

St. John's Wort (Hypericum perforatum): clinical effects on depression and other conditions.

St. John's Wort (Hypericum perforatum), a perennial flowering plant, has been used medicinally for thousands of years, and has most recently been identified as an effective treatment for mild to moderate depression. Clinical studies on the use of this plant for depression have utilized liquid tinctures and standardized solid extracts (0.3% hypericin--300 mg three times a day). Severe depression may also respond to this botanical, although it appears a larger dose is needed (600 mg solid extract three times a day). Hypericum has been favorably compared to numerous antidepressant drugs, the studies having revealed equivalent results and a much more favorable incidence of side effects. Studies have also demonstrated its efficacy in treating seasonal affective disorder. In vitro investigations of Hypericum show antiviral activity, although there is evidence these promising results might not occur in vivo. Traditional actions and uses include enhancement of wound healing, as well as anti-inflammatory and analgesic activity.

Depression↗

Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity.

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Arsenic Poisoning↗

Botanical influences on cardiovascular disease.

Several botanicals, including Crataegus oxycantha, Terminalia arjuna, Inula racemosa, and Astragalus membranaceus, have been found to have therapeutic benefit for the treatment of cardiovascular disease. Crataegus oxycantha has been used traditionally as a cardiac tonic and current uses include treatment for angina, hypertension, arrhythmias, and congestive heart failure. Animal studies have also indicated that Crataegus extracts may also have potential use as anti-ischemic and lipid-lowering agents. The bark of the Terminalia arjuna tree has a long history of use as a cardiac tonic as well, and has been indicated in the treatment of coronary artery disease, heart failure, hypercholesterolemia and for relief of anginal pain. Additionally, it has been found to have antibacterial and antimutagenic properties. Inula racemosa, also known as Pushkarmoola, is another traditional Ayurvedic botanical that has potential cardioprotective benefit. In human trials, a combination of Inula racemosa and Commiphora mukul was shown to be superior to nitroglycerin in reducing the chest pain and dyspnea associated with angina. Astragalus membranaceus, a Chinese herb, is often used as a "Qi tonifier" and has been studied for its therapeutic benefit in treatment of ischemic heart disease, myocardial infarction, heart failure, and relief of anginal pain. Clinical studies have indicated that its in vitro antioxidant activity is the mechanism by which it affords its cardioprotective benefit.

Antioxidants↗

Localized calcium transients accompany furrow positioning, propagation, and deepening during the early cleavage period of zebrafish embryos.

Through the injection of f-aequorin (a calcium-specific luminescent reporter) and the use of an imaging photon detector, we see a distinct localized elevation of intracellular calcium that accompanies the appearance of the first furrow arc at the blastodisc surface: the furrow positioning signal. As the leading edges of the arc progress outward toward the margins of the blastodisc, they are accompanied by two subsurface slow calcium waves moving at about 0.2 micron/s: the furrow propagation signal. As these wave fronts approach the edge of the blastodisc, another calcium signal arises in the central region where the positioning signal originally appeared. Like the propagation signal, it extends outward to the margins of the blastodisc, but in this case it also moves downward, accompanying the deepening process that separates the daughter cells: the furrow deepening signal. Both of these furrow deepening progressions move at around 0.1 to 0.2 micron/s. The deepening signal begins to diminish from the center outward, returning to precleavage resting levels on completion of cytokinesis. The signaling sequence is repeated during the second cell division cycle. These localized transients do not require external calcium and they can be dissipated after they have begun by introducing calcium shuttle buffers, resulting in furrow delocalization and regression. They also occur in parthenogenetically activated eggs in which, in an attenuated form, they accompany abortive cleavages.

Aequorin↗

The functional significance of symptomatology and cognitive function in schizophrenia.

The relationships between positive and negative symptomatology, cognitive function, and the ability to perform basic activities of daily living in patients with schizophrenia were examined in two studies. In study 1, 112 medicated patients were assessed utilizing the Brief Psychiatric Rating Scale (positive symptoms), the Negative Symptom Assessment (negative symptoms and cognitive function), and the Functional Needs Assessment (activities of daily living). Study 2 (n = 41), utilized the same measures of symptomatology and added a comprehensive neuropsychological test battery. Regression analyses in both studies determined that symptomatology predicts a relatively small amount of the variance in the ability to perform basic activities of daily living. Cognitive function, whether assessed with the Cognition subscale of the Negative Symptom Assessment or a comprehensive neuropsychological test battery, predicted over 40% of the variance in scores on the Functional Needs Assessment. A path model in which cognition predicted both concurrent symptomatology and activities of daily living and where symptomatology had little direct impact upon activities of daily living fit the data. The importance of addressing cognitive deficits in psychosocial intervention programs is discussed.

Activities of Daily Living↗

Interactions between pulse separation and pulse polarity order in cochlear implants.

Interactions between pulse separation and pulse polarity order were examined using psychophysical studies of electrical detection thresholds in nonhuman primates. Subjects were trained using acoustic stimuli, then deafened in one ear and implanted with an electrode array for electrical stimulation of the cochlea. Threshold vs pulse separation functions for trains of biphasic electrical pulses were compared for constant and alternating leading phase polarity. When leading phase polarity was held constant, threshold vs pulse separation functions were nonmonotonic (U-shaped). Small polarity-dependent (cathodic vs anodic leading phase) differences in absolute thresholds were observed at long pulse separations, but function shape was independent of leading phase. When leading phase polarity alternated, there was a pronounced reduction in thresholds at short pulse separations (below about 1 ms), resulting in monotonically increasing threshold vs pulse separation functions. At long pulse separations, functions for alternating and constant polarity stimuli were similar. Polarity effects were most apparent for longer duration trains (20 pulses) at long pulse durations (1-2 ms/phase). For stimuli consisting of only two biphasic pulses, alternating polarity effects depended on whether cathodic or anodic phases were adjacent. The neural mechanisms underlying these effects probably include refractory properties and/or residual potentials.

Acoustic Stimulation↗

Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations.

Neuroleptic drugs block brain dopamine receptors and are effective in treating psychoses of diverse origins. This finding has become a cornerstone of the dopamine theory of schizophrenia, but clinical studies relating schizophrenia, per se, to brain dopamine metabolism have ranged from controversial to negative. This article presents new evidence that cerebrospinal fluid levels of the dopamine metabolite homovanillic acid are related to the severity of psychosis in schizophrenia. These results support the concept that homovanillic acid levels in cerebrospinal fluid vary as a function of psychosis rather than being related to the diagnosis of schizophrenia per se.

Adult↗