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Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 199 records · Page 11Linked to original sources
PubMed1990

Modulation of the blood-aqueous barrier by gram positive and gram negative bacterial cell wall components in the rat and rabbit.

Acute anterior uveitis in man is related to Gram negative bacterial infection occurring at sites distant to the eye. This could involve intraocular localization of inflammatory bacterial cell wall constituents. Modulation of the blood-aqueous barrier in rabbit and rat, by muramyl dipeptide (the monomer of peptidoglycan) and lipopolysaccharide (and its monomer lipid A) was studied. The rabbit eye was found to be highly susceptible to MDP and LPS, although without cellular infiltration. In contrast the rat eye was demonstrated to be totally refractory to MDP. The response to LPS in the rat was modest, required high dosages and ocular changes were slow to occur, but cellular infiltration was readily apparent. Since MDP is found in Gram positive (as well as Gram negative) bacterial cell walls it is hypothesized that Gram positive bacteria might also play a role in causing uveitis in man.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Inhibition of hormone-stimulated ornithine decarboxylase activity by lithium chloride.

Effects of Li+ on hormone-stimulated ornithine decarboxylase (ODC) activity were determined in kidney and liver of rats treated with dexamethasone or prolactin (PRL) and also in cultured, PRL-stimulated Nb2 lymphoma cells. In both systems, LiCl led to rapid and marked decreases in ODC activity. The inhibitory effect of Li+ in exponentially growing Nb2 lymphoma cell cultures, measured at 45 min, was dose-dependent, ranging from 10% at 0.1 mM LiCl to 95% at 10 mM LiCl. Surprisingly, on continued incubation with 10 mM LiCl, the lymphoma cells partially overcame the inhibition, showing ODC activities which reached a maximal value of ca 50% of the control at 4.5 h. The inhibition by Li+ could not be reduced by adding myo-inositol to the culture medium. LiCl did not inhibit ODC activity when added to cell-free extracts of rat tissues and Nb2 lymphoma cells indicating it did not act directly on the enzyme; however, there is evidence that, in intact cells, Li+ enhances the rate of inactivation of the enzyme.

Animals↗
PubMed1990

The effect of varying stimulus intensity on NMDA-receptor activity in cat visual cortex.

1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the visual responses of cells in different layers of the cat visual cortex at different levels of excitatory drive (which was varied by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells in area 17 of cat cortex. Cells were characterized to determine the optimal visual stimulus, the brightness of which was then varied relative to background luminance to construct a contrast-response (C-R) curve for each cell. Curves were made during control conditions and during application of agonists (NMDA and quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid components of the visual response. 3. Threshold responses were obtained with stimuli between 1/60 and 1.8 X background luminance. The cell response, measured by firing rate, was linearly related to stimulus contrast over 1-2 decades and saturated at higher contrasts. 4. Application of APV reduced the slope of the linear portion of the C-R curve for cells located in layers II and III (average reduction, 59% of control). APV did not decrease the threshold to stimulation. The "just suprathreshold" responses to stimulation were reduced by the same proportion as the saturation responses for individual cells. The principal effect was therefore to reduce the gain of the C-R curve in these layers. 5. Application of APV reduced the spontaneous activity of cells located in layers IV, V, and VI with little if any effect on the gain of the C-R curve. This suggests a tonic background level of NMDA-receptor activation in these layers, which is not directly related to the visual response. 6. Low levels of NMDA increased the gain of the C-R curve in layers II/III and V/VI. On the other hand, low levels of quisqualate increased the overall level of firing without affecting the gain of the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These experiments show that visual stimuli that produce just suprathreshold responses activate NMDA receptors. The degree of activation is proportionally the same for small responses and large responses for an individual cell. Rather than finding a threshold for NMDA-receptor activation, a continuous range of NMDA-receptor influence was observed over the entire response range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1989

Ischemia in the ambulatory setting--the total ischemic burden: relation to exercise testing and investigative and therapeutic implications.

To establish the relation between treadmill exercise testing and ambulatory St segment monitoring in the detection of ischemia in patients with coronary artery disease, and to assess whether standard medical therapy affects any such relation, 277 patients with stable angina and angiographically documented coronary artery disease were studied with treadmill exercise testing and 48 h ambulatory ST segment monitoring. One hundred forty-six patients (52%) were studied while receiving no routine antianginal therapy, and 131 (48%) while receiving standard medical therapy. In 187 patients (67%) the exercise test was positive for ischemia. During 11,964 h of ambulatory monitoring, 881 episodes of ischemia (645 [73%] silent) were recorded, of which 809 (92%) occurred in patients with a positive exercise test. The mean heart rate at the onset of ischemic episodes during ambulatory monitoring was significantly less than that at the onset of 1 mm ST segment depression during exercise testing (94.5 versus 105.9 beats/min, p less than 0.0001). However, the frequency of ambulatory ischemic episodes was strongly related to a positive exercise test (p less than 0.001), and this relation was similar for both silent and painful ischemia (p less than 0.0001 for both) and in patients who were and were not receiving therapy (p less than 0.0001 for both). The total duration of ischemia was similarly related to a positive exercise test (p less than 0.0001). Only one patient with a negative exercise test had frequent (greater than 5/day) episodes of ischemia on ambulatory monitoring and had documented coronary artery spasm. Thus, exercise testing identifies the majority of patients likely to have significant ischemia during their daily activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Bone mass in Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia.

Bone mass, as assessed by measurements of total subperiosteal diameter and medullary width of the second metacarpal bone on hand-wrist radiographs, was evaluated for 31 Guamanian patients (15 males, 16 females) with amyotrophic lateral sclerosis (ALS), 67 patients (39 males, 28 females) with parkinsonism-dementia (PD), and 66 (34 males, 32 females) nonaffected Guamanian controls. Comparisons between the two disease groups and between each disease group and the nonaffected controls were made taking into account the sex, age, and disability status of each participant. At all ages, ALS patients of both sexes had significantly lower percent cortical areas (PCA) than did nonaffected controls. The ALS males also had significantly lower PCA than PD males, although no significant differences were observed between female ALS and PD patients. The PD patients of either sex had a lower PCA when compared to controls, but the differences were not statistically significant. The observed differences in PCA were due solely to increased medullary width, suggesting that the diminished cortical bone thickness resulted from greater bone resorption rather than differential bone growth. Longitudinal studies support the cross-sectional findings of accelerated bone loss among ALS patients. It is not possible to determine from the present data whether the observed differences in PCA of the second metacarpal of the ALS patients are due to atrophy of the first interosseous muscle, to a generalized resorption process inherently associated with the development and progression of ALS, or to factors not accounted for by the present analysis.

Adult↗
PubMed1989

Circadian patterns of myocardial ischemia.

In this overview we studied evidence for the occurrence of silent myocardial ischemia, its pathophysiologic mechanisms, and the circadian distribution of ischemic episodes. The correlation between many hemodynamic parameters and their potential as drug targets was assessed. ECG evidence of myocardial ischemia (ST segment), a parameter often used in exercise tests, also occurs during ambulatory monitoring. Use of the isotope rubidium-82 and positron emission tomography helped confirm the significance of these changes in the ST segment, both painful and silent. Ischemia was detected by a reduction in the uptake of the isotope in a region of the heart reflecting a decrease in myocardial blood flow. Also it was shown that both painful and silent ischemia are caused by similar pathophysiologic mechanisms; such mechanisms include alterations in coronary blood flow and increases in myocardial oxygen demand. Episodes of ST segment depression show a circadian rhythm similar to that seen for heart rate and catecholamine release. The basic pattern shows a low incidence of ischemia at night, followed by a primary peak on rising, a decrease at midday, and then a secondary peak in the evening, with a final decrease again at night. Similar circadian rhythms have been described for acute cardiovascular events, and this may be important for treatment.

Angina Pectoris↗
PubMed1989

Clinical trials of WR-2721 and cis-platinum.

WR-2721 is an aminothiol compound; in the animal model it protects against the nephrotoxicity, neurotoxicity, and hematologic toxicity of cis-platinum. We initiated Phase I trials of WR-2721 and cis-platinum to determine toxicity when WR-2721 was given prior to escalating doses of cis-platinum. With mannitol diuresis and WR-2721, transient nephrotoxicity occurred in 9 of 30 (27%) patients treated with cis-platinum 150 mg/m2 and 7% of patients given with cis-platinum 120 mg/m2. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies occurred in 26% of patients courses following a mean cumulative cis-platinum dose of 725 mg/m2. Objective partial responses were observed in 53 of 118 (45%) patients with measurable disease. Antitumor responses were observed in 25 of 53 patients with metastatic melanoma, 12 of 22 patients with locally recurrent or metastatic head and neck cancer, and 7 of 13 patients with metastatic breast cancer refractory to conventional chemotherapy. Controlled studies of WR-2721 and cis-platinum will be performed in the Eastern Cooperative Oncology Group in these disease sites to better define the activity of this regimen and its toxicity.

Adult↗
PubMed1989

Ambulatory ST segment monitoring in the assessment of patients following PTCA.

In this article we discuss the place of ambulatory ST-segment monitoring in the investigation of the patient following coronary angioplasty. Particular attention is focused on the relationship between the results of exercise testing (the standard technique in the evaluation of the post-angioplasty patient) and ambulatory ST-segment monitoring, in order to assess whether ST-segment monitoring might contribute further information in the identification of residual or recurrent ischaemia.

Angioplasty, Balloon, Coronary↗
PubMed1989

Ceftriaxone compared with cefotaxime for serious bacterial infections.

Ceftriaxone was compared with cefotaxime for the treatment of serious bacterial infections in a prospective, randomized, double-blind clinical trial. The dose of ceftriaxone was 2 g once a day, and the dose of cefotaxime was 2 g every 4 h. Metronidazole was added if anaerobic infection was suspected. Explicit criteria were used to define infections, clinical response, and adverse effects. Ceftriaxone was given to 88 patients and cefotaxime to 83. The two treatment groups did not differ in types of infection, infecting organisms, and severity of underlying disease. The response rate was 81% (71/88) for ceftriaxone and 80% (66/83) for cefotaxime. The power of the study to detect a 15% difference in response rate at P less than .1 was 90%. The frequency of diarrhea, thrombophlebitis, prothrombin time, prolongation, colonization, and superinfection did not differ between treatment groups. Ceftriaxone 2 g once a day was as safe and effective as cefotaxime 2 g every 4 h for suspected serious bacterial infections.

Adult↗
PubMed1989

Silent myocardial ischaemia in patients referred for coronary bypass surgery because of angina: a comparison with patients whose symptoms were well controlled on medical treatment.

The frequency and characteristics of silent ischaemia were prospectively studied in 114 patients with confirmed coronary artery disease and angina. Fifty seven patients who had angina that was not adequately controlled by standard medications were referred for elective coronary artery bypass surgery (group 1). Fifty seven other patients had symptoms that were well controlled on medical treatment (group 2). Patients underwent treadmill exercise testing (n = 109) and 48 hours of ambulatory ST segment monitoring (total 5125 hours). Patients in group 1 had more severe coronary artery disease and a shorter time to 1 mm ST segment depression and maximal exercise. Twenty two patients in group 1 (38%) and 16 in group 2 (28%) had greater than or equal to 1 episode of silent ischaemia during 48 hours of ST monitoring. There was no significant difference in the mean frequency of silent ischaemic episodes in 24 hours between the two groups (group 1 0.72 v group 2 0.64); however, the mean frequency of painful ischaemic episodes in 24 hours was greater in group 1 patients (0.51) than in group 2 (0.11). In both groups the frequency of silent ischaemia was significantly related to a positive exercise test, as was the total duration of silent ischaemia. The circadian variation of silent ischaemia showed a peak of episodes in the evening in both groups. The frequency of silent ischaemia in patients with coronary artery disease and angina receiving standard antianginal medications was not related to the severity of symptoms, but was significantly related to a positive exercise test. Thirty three percent of the patients studied had evidence of silent ischaemia during 48 hours of ambulatory ST segment monitoring; however, only four patients (3.5%) had frequent (>/=5) daily episodes of silent ischaemia.

Adult↗
PubMed1989

Effect of electrical stimulation of locus coeruleus on the activity of neurons in the cat visual cortex.

1. We studied the effect of electrically stimulating the locus coeruleus (LC) and iontophoresing noradrenergic antagonists on visual responses and spontaneous activity of individual cells in the cat primary visual cortex. 2. A bilateral projection from LC to visual cortex was demonstrated anatomically, by retrograde labeling using horseradish peroxidase. Where electrical stimulation of both ipsilateral and contralateral LC affected a cortical neuron, the effect induced by stimulating each side was similar. 3. One hundred and two cells were recorded in area 17: 52% of them had their activity suppressed and 36% had their activity facilitated by LC stimulation. The suppressive effect was predominant in cortical layers II + III and IV, whereas most cells in layer V and one-half of the cells in layer VI were facilitated by LC stimulation. This suggests that LC neurons innervate each cortical layer in a different manner. 4. Simple and complex cells were equally sensitive to LC stimulation. For simple cells, the suppressive effect of LC stimulation was dominant throughout all layers. For complex cells, the suppressive effect was dominant in layers II + III and IV, whereas the facilitatory effect was dominant in layers V and VI. 5. The suppressive effect of LC stimulation was blocked by iontophoretic application of beta-adrenergic receptor antagonists and the facilitatory effect was blocked by either alpha- or beta-adrenergic receptor antagonists. 6. Nonselective alpha-, and selective alpha 1- and alpha 2-receptor antagonists suppressed visual and spontaneous activity in almost all neurons tested, suggesting that these receptors are either facilitatory at a postsynaptic site or inhibitory at a site presynaptic to an inhibitory synapse in the visual cortex. 7. beta-Receptor antagonists facilitated activity in 45% and suppressed activity in 36% of the cells tested, suggesting there are both suppressive and facilitatory types of beta-receptors. 8. The effectiveness of alpha- and beta-antagonists on the activity of neurons without LC stimulation also suggested that spontaneously released noradrenaline activated noradrenergic receptors in the visual cortex even in the anesthetized and paralyzed cat. 9. In most cells tested, both alpha- and beta-receptor antagonists exerted effects on single neurons suggesting that endogenous noradrenaline acts on both alpha- and beta-receptors on the same cell. 10. The activation of LC did not improve the signal- (visual response)to-noise (spontaneous discharge) ratio of neurons in the visual cortex. 11. LC seemed to control the activity of each cortical layer differently, by activating different kinds of noradrenergic receptors in different layers.

Adrenergic alpha-Antagonists↗
PubMed1989

Precision of determining compliance with prescribed fields from conventional portal films.

Three hundred and seventy measurements of field placement errors (FPEs) have been made by a total of 16 observers on 20 prescription-treatment film pairs taken during routine radiotherapy for cancer of the prostate. Analysis of the distributions of the measured FPEs has yielded the precision of the measurement under a variety of conditions. We report here the influence on the precision of determining FPEs of the following factors: the clinical duties of the observers, the quality of the treatment film, the relative magnification of prescription and treatment films, and whether double-exposure techniques were employed.

Humans↗
PubMed1989

The location and function of NMDA receptors in cat and kitten visual cortex.

The role of N-methyl-D-aspartate (NMDA) receptors in cat visual cortex was studied as a function of both layer and age by iontophoresis of the NMDA antagonist (D)-2-amino-5-phosphonovaleric acid (APV). Effects on both visual responses and spontaneous activity were observed. In superficial layers (II and III), D-APV reduced visual responses substantially at all ages. Iontophoresis of D-APV with 10 nA of ejecting current for 2-3 min was sufficient to reduce the response to approximately one third of control levels. The magnitude of the reduction did not vary with age. In granular and deep layers (IV, V, and VI), D-APV affected the visual response in young animals but only spontaneous activity in older animals. On average, visual responses were reduced to about half at 20-23 days of age and to about 75% at 4 weeks of age but in most cases were not significantly affected in adults. The rapid change in the functional effect of NMDA receptors over the third and fourth week in granular and deep layers suggests a role in development. There was a reasonable age correlation between the change in effect and the period of geniculocortical afferent segregation. Further experiments will be necessary to determine whether NMDA receptors are necessary for segregation to occur. The presence of an NMDA component to the visual response in the adult in layers II and III argues either that these layers retain some form of plasticity in the adult or that NMDA receptors play a role in the transmission of normal visual input to these layers.

2-Amino-5-phosphonovalerate↗
PubMed1989

Polio immunization and serological status in children and adolescents in Jamaica (1985).

A survey of immunization status and serological immunity to polio was carried out in 5 parishes in Jamaica in 1985. A sample of 2,506 children and adolescents aged 1-19 years was chosen by selecting clusters of children in enumeration districts (EDs) in each parish from the 1980 Census. Immunization status was verified by examining immunization records. Serological assay for antibodies to Polio Types 1, 2, and 3 was done. A positive neutralization test at dilution of 1:8 was taken as immunity to the polio virus. Of the 1,819 children whose immunization status was confirmed, coverage with 3 or more doses of oral polio vaccine was highest in the 1-4 year age group with 79.7% and lowest in the 15-19-year age group with 37.4%. Of the 2,506 children 81.4%, 94.7% and 72.3% were seropositive for Polio Types 1, 2 and 3 respectively. There was a significant difference in the prevalence of seropositives between individuals with and those without a history of vaccinations. No urban/rural or sex differences were noted. The study indicated a higher level of immunization status than previous surveys and a high level of serological immunity to polio.

Adolescent↗