PubMed Health⌕ Search

Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 163 records · Page 9Linked to original sources
PubMed1993

The role of NMDA receptors in information processing.

In this review, we have concentrated on the parallels between the cellular properties of the NMDA receptor and a variety of functional properties within sensory and motor systems. Of course, the NMDA channel exists within the cell in conjunction with a variety of other channels, including non-NMDA channels. Although the NMDA receptor is unique in a cellular sense--it is the only ligand-gated channel that is also voltage dependent and calcium permeable--it is not unique in a functional sense. A cell that has non-NMDA receptors and voltage-sensitive channels will also exhibit nonlinear behavior. Moreover, Buhrle & Sonnhof (1983) demonstrated some time ago that calcium flows into frog motor neurons through more than one type of calcium channel. The contribution to the inflow of calcium from NMDA channels may vary from cell to cell and could easily be a minor proportion of the total. Many authors have pointed out that the NMDA channel has a low conductance at a resting potential of -70 mV. However, many cells in the nervous system are depolarized from -70 mV by excitatory input. Thus, as pointed out above. NMDA receptors make a contribution to the tonic or spontaneous activity of cells in both visual cortex and spinal cord. In practice, many cells are probably working in a range of membrane potentials where the NMDA channels are always open to some extent. Even in the hippocampal slice where a substantial amount of afferent input is removed, NMDA receptors contribute to spontaneous activity (Sah et al 1989). Does the NMDA receptor act as a switch? Does it act as an AND gate? The suggestion that it may act as a switch comes from work on LTP in the hippocampus, which is readily produced by high-frequency stimulation and is abolished by APV. However, activation of the NMDA receptor is only the first in a sequence of reactions leading to LTP: In theory, switch-like behavior could also be produced by calcium-buffering systems within dendritic spines, or by enzymatic processes (Lisman 1985; Zador et al 1990). Fox & Daw (1992) have modeled the action of NMDA and non-NMDA receptors that are activated in parallel with each other, and shown that the occurrence of switch-like behavior depends on the relative density of NMDA versus non-NMDA receptors. Switch-like behavior is not seen in the visual cortex, but might be seen in the hippocampus if the relative density of NMDA receptors there was higher than in the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Hemoglobin inhibits endothelium-dependent relaxation to acetylcholine in human coronary arteries in vivo.

BACKGROUND: The endothelium can regulate vascular tone by releasing both endothelium-derived relaxing factor (EDRF or nitric oxide) and contracting factors. To date, there has only been circumstantial evidence to indicate EDRF activity in vivo in human coronary arteries. Using human hemoglobin as a specific inhibitor, the hypothesis that acetylcholine-induced coronary vasodilation is due to EDRF release was tested. METHODS AND RESULTS: We studied the response of normal coronary arteries to acetylcholine (an endothelium-dependent vasodilator) and isosorbide dinitrate (an endothelium-independent vasodilator) in seven patients. The specificity of any vasodilator response was assessed by the infusion of reduced free human hemoglobin. Hemoglobin 10(-5) M infusion alone had no effect on coronary artery diameter. Drugs were infused into the coronary artery, and the diameter changes were assessed by quantitative angiography. Acetylcholine 10(-7) M increased left anterior descending coronary artery diameter from control: 2.30 +/- 0.12 mm to 2.79 +/- 0.20 mm (mean +/- SEM, n = 7, p < 0.01). Hemoglobin both in a concentration of 10(-6) M and 10(-5) M reversed this vasodilator effect, causing constriction to 2.11 +/- 0.18 mm (p < 0.001 compared with acetylcholine 10(-7) M) and 2.29 +/- 0.14 mm (p < 0.05 compared with acetylcholine 10(-7) M). Isosorbide dinitrate in the presence of hemoglobin caused dilatation of the coronary artery in all cases to 3.04 +/- 0.24 mm (p < 0.001 compared with acetylcholine 10(-7) M and hemoglobin 10(-6) M). CONCLUSIONS: Using a specific inhibitor of nitric oxide, reduced free hemoglobin, we have demonstrated that basal EDRF release does not appear to play an important role in the maintenance of human epicardial coronary artery diameter in vivo but is responsible for the acetylcholine-induced dilatation.

Acetylcholine↗
PubMed1993

Silent ischaemia--to treat or not to treat?

The authors summarise published data concerning silent myocardial ischaemia: they review the studies showing the poor prognosis of this type of myocardial ischaemia but pose the question of whether this is due to the severity of the lesions causing the ischaemia or to the ischaemia itself. To answer this question, it would be necessary to set up a therapeutic trial showing that treatment preventing the electrocardiographic changes of silent ischaemia is associated with an improved prognosis. In the absence of solid evidence on this point, the authors present the case for and against treatment of silent ischaemia without drawing any formal conclusions.

Decision Making↗
PubMed1993

Abdominal fat deposition in 11-year-old children.

Although the metabolic complications accompanying visceral deposition of fat are well-established, the onset and extent of such fat patterning in children has not been fully documented. This has been due to the problem of computerized tomography exposing children to a prohibitive radiation risk. Nuclear magnetic resonance imaging (MRI) has provided a feasible alternative. Specifically, the purposes of this study were to use MRI (i) to assess the extent of intra-abdominal (IA) and subcutaneous abdominal (SA) fat deposition in 11-year-old boys and girls, and (ii) to identify the most useful anthropometric indicators of IA adiposity in children. Twenty-five boys and 25 girls were selected to represent, by quintiles, the body mass index range for their age. IA fat, SA fat, and total cross-sectional areas were measured from an MRI scan at the umbilicus. Body density was assessed by hydrostatic weighing, and skinfold thicknesses, circumferences and related ratios, and stage of sexual maturity were measured. Results showed that a wide variation in IA fat deposition was present with amounts ranging from 6 to 58 cm2 (mean = 17.8 +/- 10.0) for boys and 15 to 50 cm2 (mean = 24.8 +/- 8.8) for girls. Percentage of cross-sectional area taken up by visceral fat appears to be less than in normal weight adults. Fourteen children had intra-abdominal/subcutaneous abdominal fat ratios that have been associated with higher health risk in obese adults. Waist-hip circumference ratio (WHR), which is widely used as an indicator of IA deposition in adults, was not a useful predictor in these children.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1992

Comparison of the efficacy and safety of ketorolac and meperidine in the relief of dental pain.

A single-dose, randomized, double-blind study of parallel design was conducted to determine the analgesic efficacy and safety of ketorolac tromethamine in patients who experience moderate or severe pain after the surgical removal of three or more third molars, one of which was a bony-impacted mandibular molar. Meperidine hydrochloride was used as the control analgesic. In this 8-hour study, assessments were made of pain intensity, pain relief, and overall rating of the medication in 145 patients, each of whom had received an intramuscular injection of 10 mg, 30 mg, or 90 mg of ketorolac, or 50 mg or 100 mg of meperidine. The summed pain intensity and total pain relief scores showed that, at 3 and 8 hours, the effectiveness of 30 mg of ketorolac was similar to that of 90 mg ketorolac and that both of these doses were significantly more efficacious than 10-mg ketorolac, 50-mg meperidine, or 100-mg meperidine. Patients who received 30 mg or 90 mg of ketorolac gave the study medication significantly higher ratings overall than did patients who received 50 mg or 100 mg of meperidine. Significantly fewer patients treated with ketorolac reported adverse events in comparison with those treated with meperidine (17% and 59%, respectively), which suggests that it possesses a better therapeutic index than meperidine. Thus, ketorolac appears to represent an important advance in analgesic therapy.

Analgesics↗
PubMed1992

Can we really justify the treatment of silent ischemia in 1992? No!

Since the advent of ambulatory ST-segment monitoring, it has been established that silent ischemia is common in patients with various coronary artery disease syndromes, and such silent episodes represent up to 80% of all ischemic episodes. It appears to be associated with an adverse prognosis when compared with similarly characterized patients without silent ischemia during daily life. Silent ischemia does not, however, bother the patients, by virtue of the fact that it is silent, and therefore treatment of such ischemia must be justified by an improved outlook for the patient, rather than symptom relief. There is no direct evidence to date that silent ischemia is associated with acute myocardial infarction or sudden cardiac death in a cause-and-effect relationship, or that reduction or eradication of silent ischemia will lead to an improved prognosis for the patient; indeed, we have been unable to demonstrate any significant improvement in outlook when using the various antianginal/antiischemic agents at our disposal. Until we can demonstrate a benefit to the patient by detecting and treating silent ischemia, we should not waste large resources attempting to eradicate something whose significance we do not understand.

Coronary Disease↗
PubMed1992

Effects of coronary artery bypass surgery and angioplasty on the total ischemic burden: a study of exercise testing and ambulatory ST segment monitoring.

To assess the effects of standard therapeutic interventions on the total ischemic burden, 86 patients with stable angina underwent 48 hours of ambulatory ST segment monitoring and treadmill exercise testing before and at a mean of 10 weeks after coronary artery bypass surgery (CABG) (group 1, N = 46) or percutaneous transluminal coronary angioplasty (PTCA) (group 2, N = 40). There were 72 male and 14 female patients with a mean age of 56.4 years. All patients had documented coronary artery disease (24, single-vessel; 28, two-vessel; 34, three-vessel disease). Both groups were characteristically similar apart from more severe coronary artery disease (p less than 0.001) and more previous myocardial infarctions (p less than 0.05) in group 1. Groups with CABG and PTCA had significant prolongation of exercise time after intervention (group 1: 7.6 to 9.8 minutes, p less than 0.0001; group 2: 8.1 to 10.0 minutes, p less than 0.001), and both interventions led to a significant reduction in ischemic responses (group 1: 33 to 4, p less than 0.001; group 2: 20 to 13, p less than 0.05) to exercise. During a total of 7643 hours of ST segment monitoring, 253 episodes of ischemia were recorded in 3768 hours before and 44 ischemic episodes in 3875 hours after intervention (group 1, 113 episodes in 24 patients and 21 episodes in 10 patients; group 2, 140 episodes in 13 patients and 23 episodes in six patients). Both interventions reduced the mean frequency of ischemia per 24 hours (group 1: 1.24 to 0.22 episodes per 24 hours; p less than 0.01; group 2: 1.9 to 0.3 episodes per 24 hours; p less than 0.05). Almost 28% (N = 24) of resting electrocardiographic findings were altered as a result of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1992

Polypeptide profiles of normal and inflamed rabbit aqueous humor: identification of catabolic products of immunoglobulin G in the normal eye.

The anterior segment of the eye is isolated from the bloodstream by anatomic barriers. These barriers break down during inflammation elicited by muramyl dipeptide (MDP), a component of the cell walls of bacteria. The protein composition of normal aqueous humor and inflamed aqueous were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The presence of transferrin, albumin, IgG and IgM were demonstrated in normal and inflamed aqueous. Normal aqueous additionally contained seven polypeptides (35, 31, 29, 25, 22, 21 and 19 kDa, respectively) that were not observed in inflamed aqueous. Four of these peptides (31, 29, 25 and 19 kDa) were identified as fragments of IgG heavy chains based on their reactivity with anti-IgG antibodies and staphylococcal protein A. Immunoglobulin catabolism has been noted to occur in tissues diffusely throughout the body; this is the first report of it occurring in the eye. This phenomenon appears to be circumvented on breakdown of the blood-aqueous barrier. These observations may relate to the immunoprivilege of the eye and its modulation in inflammation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Stimulus control of predatory behavior in the brown tree snake (Boiga irregularis). IV. Effect of mammalian blood.

Brown tree snakes (Boiga irregularis) from Guam were exposed to mammalian (Rattus norvegicus) blood on cotton-tipped applicators. Water and other control substances were similarly presented. All trials lasted 60 s, and the dependent variable was the number of tongue flicks emitted by the snake during the trial. In five experiments, B. irregularis responded with greater numbers of tongue flicks to blood than to control substances. This is the first study to reveal an ophidian response to internal chemicals of potential prey organisms.

Amniotic Fluid↗
PubMed1992

Beta-lactam enhancement of aminoglycoside activity under conditions of reduced pH and oxygen tension that may exist in infected tissues.

Aminoglycoside activity is suppressed under conditions of low pH and oxygen tension that are likely to occur in infected tissues; the suppressive effects of these conditions are additive. Under aerobic conditions, the MIC of amikacin for 10 isolates of Escherichia coli was 4.8 +/- 0.7 micrograms/ml at pH 7.2 and increased to 40.0 +/- 8.2 micrograms/ml at pH 6.0. Under anaerobic conditions, the MIC of amikacin for E. coli was 30.0 +/- 1.5 micrograms/ml at pH 7.2 and greater than 50.0 micrograms/ml at pH 6.0. In vitro and in vivo studies of amikacin activity in an acidic and hypoxic milieu containing beta-lactamase demonstrated substantially enhanced bactericidal activity when amikacin and beta-lactams were used together. Under conditions of reduced pH and oxygen tension, cefotaxime enhanced [3H]-tobramycin uptake by E. coli 14-fold and [3H]amikacin uptake 7-fold and appeared to overcome the suppressive effect of those conditions on uptake of aminoglycosides by bacteria.

Abscess↗
PubMed1992

The pathogenesis of atheroma and the rationale for its treatment.

Several theories have been proposed to explain the mechanism causing atheroma; these include endothelial cell injury, smooth muscle cell proliferation, lipid deposition and an abnormality of the vasa vasorum. Based on these hypotheses, new therapies aimed at causing regression or preventing the development of atheroma include heparin, calcium antagonists, beta-receptor antagonists, lipid lowering agents and drugs that manipulate platelets.

Animals↗
PubMed1992

Analysis of disulphide bridge function in recombinant bovine prolactin using site-specific mutagenesis and renaturation under mild alkaline conditions: a crucial role for the central disulphide bridge in the mitogenic activity of the hormone.

We have previously described a method for isolating Escherichia coli-produced methionyl bovine prolactin (Met-bPRL) and its renaturation using thioredoxin. This report describes an alternative renaturation procedure in which extracted Met-bPRL is incubated in air at pH 10 and 20 degrees C. Within 1 h of such treatment essentially all of the reduced Met-bPRL was converted to the oxidized form; this was accompanied by an increase to full mitogenic activity in the Nb2 cell bioassay. It was also found that, to minimize contamination by high mol. wt Met-bPRL derivatives, it is essential to have a reducing agent (dithiothreitol) present during disruption of the bacteria and to extract the protein at neutral pH. The contribution of each of the three disulphide bridges in bPRL to its bioactivity was studied with Met-bPRL variants, prepared via site-specific mutagenesis, in which cysteines were replaced by serines to prevent disulphide bond formation. Variants lacking the C4-C11 bridge, the C191-C199 bridge or both these terminal bridges were as mitogenic as authentic bPRL. (Variants lacking the C191-C199 bridge had markedly increased solubility in the presence of deoxycholate.) In contrast, variants lacking the C58-C174 bridge had greatly reduced bioactivity, indicating that integrity of the large disulphide loop is crucial to the hormone's mitogenic activity.

Animals↗
PubMed1992

Critical period for monocular deprivation in the cat visual cortex.

1. Cats were monocularly deprived for 3 mo starting at 8-9 mo, 12 mo, 15 mo, and several years of age. Single cells were recorded in both visual cortexes of each cat, and the ocular dominance and layer determined for each cell. Ocular dominance histograms were then constructed for layers II/III, IV, and V/VI for each group of animals. 2. There was a statistically significant shift in the ocular dominance for cells in layers II/III and V/VI for the animals deprived between 8-9 and 11-12 mo of age. There was a small but not statistically significant shift for cells in layer IV from the animals deprived between 8-9 and 11-12 mo of age, and for cells in layers V/VI from the animals deprived between 15 and 18 mo of age. There was no noticeable shift in ocular dominance for any other layers in any other group of animals. 3. We conclude that the critical period for monocular deprivation is finally over at approximately 1 yr of age for extragranular layers (layers II, III, V, and VI) in visual cortex of the cat.

Aging↗
PubMed1992

Flow of excitation within rat barrel cortex on striking a single vibrissa.

1. Extracellular spike recordings were made from single cells in various layers of barrel cortex in adult rats anesthetized with urethan. Response magnitude and latency differences to brief 1.14 degrees deflections of mystacial vibrissae of center (principal) and surround receptive-field vibrissae were measured. Latency differences for pairs of cells in the same penetration to stimulation of the principal vibrissa were also collected. In separate experiments the domains of layer IV cells were mapped for their influence by a single vibrissa and their latencies to this vibrissa were recorded. In all experiments precise locations of layer IV cells in each penetration were identified using dye-lesioning and cytochrome oxidase staining of tangential sections. 2. The results suggest that principal vibrissa data are relayed radially in a column of neurons before parallel relay to adjacent columns. To the principal vibrissa, layers IV and Vb neurons discharged earliest, with layers II and III on average 2 and 3 ms later, respectively. Serial relay from layers IV to III to II was suggested to be the most common event. Although layer Va cells fired next, a single-column organization is not suggested for them because differences in latency or response magnitude to their principal and immediate surround vibrissae were not significant. Layer II, III and IV cells showed no statistical difference in latency to the nearest surround vibrissa but fired significantly later than to their principal input. 3. Because, from our previous studies, surround receptive fields of barrel cells in rat S1 cortex appear to be constructed intracortically, these data suggest a parallel column-column relay for their construction. Horizontal relay between barrels occurred first within the septae between barrels. Mean intracortical transmission velocities were calculated at approximately 0.05 m/s for column-column information transfer.

Animals↗
PubMed1992

The effect of visual experience on development of NMDA receptor synaptic transmission in kitten visual cortex.

We have studied the effect of dark rearing on the development of excitatory amino acid transmission in 6-week-old kittens. In normal kittens, the NMDA component of the visual response decreases between 3 and 6 weeks of age for cells located in layers IV, V, and VI (Fox et al., 1991). Dark rearing to 6 weeks of age prevents this decrease. Subsequent exposure to light allows the decrease to proceed. Ten days in the light after 6 weeks in the dark was sufficient to decrease the NMDA component of the visual response to the same levels seen in light-reared animals of the same age. Comparison of the effect of the non-NMDA antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione with the NMDA antagonist aminophosphonovalerate showed that the changes were due to the relative contributions of NMDA and non-NMDA receptors to the visual response rather than the overall contribution of glutamate receptors. We also studied the receptive field properties of the cells in the various groups of kittens. Cells given 4 d in the light after 6 weeks in the dark showed increased direction selectivity but little change in response firing rate. After 10 d in the light, visual responses did show some recovery toward adult values, but neither average firing rates nor the proportion of direction-selective cells reached the levels found in normal 6-week-old animals, contrary to the suggestion that a short period in the light can reverse the effect of dark rearing completely. These results show that the decrease in the NMDA component of the visual response seen during normal development of the cortex is caused by visual experience. Changes in NMDA receptors and developmental events such as geniculocortical afferent segregation and acquisition of orientation tuning covary as a function of visual experience rather than age, strongly suggesting that NMDA receptors are involved in experience-dependent developmental processes.

2-Amino-5-phosphonovalerate↗
PubMed1992

Analysis of clinical experience with a new twist lock connectology.

The DextroLyte II (Dex II) Peritoneal Dialysis System was designed to improve safety and convenience in dialysis therapy. Connectors introduced with this system have a threaded recessed male connector with a corresponding female counterpart. Products are provided for CAPD, Single Use Y, Long Life Y and CCPD. Safety and convenience features intended to reduce peritonitis rates and improve patient acceptance include the following: 1. Connectors with threaded male and corresponding female counterparts which provide a dual seal 2. Easy-to-break frangible which seals the solution bag until ready for use 3. A flange on the connector ensures proper hand placement by providing a safety shield to prevent contamination during connection 4. A hinged shield containing an impregnated povidone-iodine sponge easily snaps around the bag connector 5. A Quick Disconnect Clamp (QDC) provides external occlusion permitting safe disconnection for bagless techniques without opening the system 6. A standard medication port provides easy access for administration of intraperitoneal medication Results of a multicenter study performed in nine centers are as follows: Total patient participants 121 Total patient months 1207 Overall peritonitis rate 1 episode in 43 patient months We conclude that the Dex II peritoneal dialysis systems provide safe dialysis therapy as evidenced by the exceptional peritonitis rates. Patient acceptance has been excellent due to the inclusion of the safety and convenience features described.

Evaluation Studies as Topic↗
PubMed1992

Clinical experience and comparative analysis of the standard and fast peritoneal equilibration tests (PET).

The fast peritoneal equilibration test (PET) has been proposed as a substitute procedure for the standard PET because it is less expensive and less time consuming since fewer samples must be drawn. This study was undertaken to compare the fast and standard PETs to determine if the fast PET is a viable alternative. Fifteen patients participated in the study. Results from the standard PETs indicate 13 patients had average permeability and 2 patients had high transport. Corresponding fast PETs indicate 10 patients with average permeability, 2 patients with high transport, 1 patient had discrepancies between the D/P ratios and drain volume, and 2 patients were noncompliant and did not complete the fast PET. We conclude that the fast PET is a valid screening tool to evaluate peritoneal membrane permeability in patients who have previously undergone a standard PET. It is cost effective and timesaving. The test is easily invalidated if patients fail to comply with instructions for the test. The fast PET is primarily useful as a screening device to determine whether permeability has changed.

Adult↗