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Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 145 records · Page 8Linked to original sources

Neuroendocrine carcinoma of the colon. Correct diagnosis is important.

Neuroendocrine carcinomas of the colon and rectum are unusual and have in the past been misrepresented as either carcinoid tumors or undifferentiated cancers. Colorectal neuroendocrine tumors comprise a clinicopathologic spectrum that ranges from indolent to highly aggressive. The case discussed illustrates the importance of the right diagnosis because it will affect treatment and may better predict the clinical course.

Adult↗

Role of beta-hemolytic group C streptococci in pharyngitis: incidence and biochemical characteristics of Streptococcus equisimilis and Streptococcus anginosus in patients and healthy controls.

The biochemical characteristics and the isolation rates of the two Lancefield group C streptococcal species (S. equisimilis and S. anginosus) from patients with pharyngitis and asymptomatic controls were compared. Some 239 strains of beta-hemolytic group C streptococci were isolated from 1,480 patients (209 strains) with pharyngitis and 227 controls (30 strains). A total of 44 strains displayed broad hemolysis, were Voges-Proskauer test negative, and produced glucuronidase. Some 72.7% of these strains also fermented ribose. A second group of 159 strains was Voges-Proskauer test positive and glucuronidase negative; 98.8% also displayed minute hemolysis and only 3.7% fermented ribose. These two groups represent typical large-colony S. equisimilis and small-colony S. anginosus, respectively. A small number of strains (36 in total) exhibited intermediate characteristics; morphologically, all 36 strains resembled S. anginosus, but 6 strains biochemically resembled S. equisimilis. No strains of S. equisimilis fermented sorbitol (unlike S. zooepidemicus) and all fermented trehalose (unlike S. equi). The structural carbohydrate profiles of S. equisimilis and S. anginosus both included galactosamine (consistent with their being group C organisms), but the profiles were not distinguishable. In total, 78.5% of strains from controls and 83.3% of strains from patients were determined to be the species S. anginosus. S. equisimilis was isolated from 3.0% of patients and 2.2% of controls, and S. anginosus was isolated from 11.1% of patients and 11.0% of controls. Thus, S. equisimilis and S. anginosus are both members of the normal flora of asymptomatic individuals. The incidence and biochemical characteristics of these two species are similar in patients who are healthy and those who have disease. However, a companion article provides clinical evidence associating S. equisimilis (but not s. anginosus) with pharyngitis.

Adult↗

Role of group C beta-hemolytic streptococci in pharyngitis: epidemiologic study of clinical features associated with isolation of group C streptococci.

All Lancefield group C beta-hemolytic streptococci isolated over 12 months from college students with clinical pharyngitis and age-matched healthy controls were identified. Clinical features of upper respiratory tract infection and pyogenic pharyngitis as well as colony counts were tabulated for each patient according to throat culture results. Of 1,480 patients, Lancefield group C Streptococcus equisimilis was isolated from 45 (3%) patients and Streptococcus anginosus ("Streptococcus milleri") was isolated from 164 (11.1%) patients. Patients from whom S. equisimilis was isolated had clinical features more suggestive of pyogenic infection than did patients from whom S. anginosus was isolated. Colony counts on primary throat culture plates from patients from whom S. equisimilis and Streptococcus pyogenes were isolated were higher than those from patients from whom S. anginosus was isolated. This study presents epidemiologic evidence supporting a role for S. equisimilis in causing pharyngeal infection and for S. anginosus as representing part of the normal oropharyngeal flora.

Adult↗

Determination of carbohydrate profiles of Bacillus anthracis and Bacillus cereus including identification of O-methyl methylpentoses by using gas chromatography-mass spectrometry.

Bacillus anthracis and Bacillus cereus are closely related pathogenic organisms that are difficult to differentiate phenotypically or genotypically. It is well known that vegetative and spore forms of bacilli are quite distinct both morphologically and chemically, but spore-specific chemical markers allowing these species to be distinguished have not been previously described. By using gas chromatography-mass spectrometry, vegetative cells and spores of the two species were shown to exhibit distinct carbohydrate profiles. Profiles of vegetative B. anthracis typically contained high levels of galactose but did not contain galactosamine, whereas B. cereus contained galactosamine and generally low levels of galactose. Spore cultures exhibited unique carbohydrate profiles compared with those of vegetative cultures. B. anthracis spore profiles contained rhamnose alone, whereas B. cereus spore profiles contained rhamnose and fucose. Additionally, two spore-specific O-methylated methylpentoses were discovered. Both B. anthracis and B. cereus spores contained 3-O-methyl rhamnose, whereas B. cereus spores also contained 2-O-methyl rhamnose. Carbohydrate profiling is demonstrated to be a powerful tool for differentiating the two closely related species. Differentiation does not depend on whether organisms are in the vegetative or spore stage of growth.

Bacillus anthracis↗

Endothelium dependent and independent responses in coronary artery disease measured at angioplasty.

OBJECTIVE--To investigate the effects of substance P and papaverine, two drugs that increase coronary blood flow by different mechanisms, on vasomotion in stenotic coronary arteries at percutaneous transluminal coronary angioplasty (PTCA). DESIGN--Coronary blood flow responses to substance P and papaverine were measured in stenotic coronary arteries at the time of PTCA with quantitative angiography and a Doppler flow probe. SETTING--A cardiothoracic referral centre. PATIENTS--15 patients undergoing elective PTCA of a discrete epicardial coronary artery stenosis. INTERVENTIONS--Pharmacological coronary flow reserve was determined with papaverine 5-10 minutes before and after successful PTCA. Endothelium dependent responses to 2 minute infusions of substance P (10-15 pmol.min-1) were assessed immediately before PTCA. MAIN OUTCOME MEASURES--Coronary blood flow responses and changes in epicardial coronary artery area at stenotic, proximal, and distal sites with papaverine and substance P. RESULTS--Stenotic sites dilated with papaverine before PTCA (17.7%(6.9%) (mean (SEM)) area increase, p < 0.05 v baseline). Substance P dilated stenotic sites (16.8%(5.7%) area increase, p < 0.05) and proximal (14.3%(5.4%), p < 0.05) and distal sites (41.7%(9.3%), p < 0.005). Coronary flow reserve increased but did not reach normal values after PTCA (2.3(0.4) before PTCA v 3.0(0.4) after PTCA, p < 0.05) and was associated with an increase in peak flow with papaverine. Angioplasty did not alter baseline flow. After PTCA papaverine caused significant vasoconstriction at the stenotic site (-13.6%(4.3%) area decrease, p < 0.05). There was a negative correlation (r = -0.68, p < 0.05) between the dilator response with papaverine before PTCA and the constrictor response after PTCA. CONCLUSIONS--Substance P causes endothelium dependent dilatation in atheromatous coronary arteries, even at sites of overt atheroma. The cause of the paradoxical constrictor response to papaverine after PTCA is uncertain, but unopposed flow mediated vasoconstriction (the myogenic response) after balloon induced endothelial denudation may be one of several contributory factors.

Angioplasty, Balloon, Coronary↗

Prognostic significance of transient ST segment changes after coronary artery bypass surgery: a long-term (4-10 year) follow up study.

OBJECTIVE: To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: 76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. RESULTS: During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. CONCLUSIONS: Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance.

Adult↗

Coronary flow reserve in patients with chest pain and normal coronary arteries.

BACKGROUND: Many studies have shown that coronary flow reserve is reduced in patients with chest pain and angiographically normal coronary arteries. The methods used to assess coronary blood flow have varied, but in nearly all reports dipyridamole has been used to bring about vasodilatation. This study was designed to assess whether the apparent impairment of coronary flow reserve seen with dipyridamole could be reproduced with either papaverine or adenosine, which induce maximum coronary blood flow by different mechanisms. METHODS: 25 patients with chest pain and angiographically normal coronary arteries were studied with an intracoronary Doppler flow probe and quantitative angiography to determine epicardial coronary artery area, coronary blood flow velocity, coronary flow reserve, and coronary vascular resistance index (CVRI, the ratio of resistance after intervention to basal resistance). All patients received papaverine 8 mg. Eight patients with positive exercise tests received intracoronary papaverine (8 and 10 mg), intracoronary adenosine (6, 20, 60 micrograms), and high-dose intravenous dipyridamole (0.84 mg/kg). RESULTS: The velocity ratio (peak after intervention: baseline) (mean (SEM)) after 8 mg papaverine was 3.3 (0.2) (n = 25) and the coronary flow reserve was 4.1 (0.3) (n = 25). There were no differences between patients with a positive (n = 16) or negative (n = 9) exercise test. In eight patients coronary flow reserve was measured after increasing doses of papaverine, adenosine, and dipyridamole. Coronary flow reserve was 4.5 (0.3) with papaverine, 4.8 (0.3) with adenosine, and 3.5 (0.4) with dipyridamole (p = 0.08 v papaverine and adenosine). CVRI was 0.22 (0.01) with papaverine, 0.21 (0.02) with adenosine, and 0.29 (0.03) with dipyridamole (p < 0.05 v papaverine, p = 0.09 v adenosine). CONCLUSIONS: These results indicate that measurement of coronary flow reserve and CVRI in patients with chest pain and normal coronary arteries depends on the pharmacological stimulus. Normal values were obtained with papaverine in all patients, irrespective of the exercise test response. In patients with a positive exercise test significantly lower values were obtained with dipyridamole than with papaverine, or adenosine. The reported impairment of coronary flow reserve in patients with angina and normal coronary arteries may reflect the variability in response to different pharmacological agents. The mechanism underlying this variability is unknown, but may involve an abnormality of adenosine metabolism in the myocardium.

Adenosine↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗