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Biomedical subjects

A J Fox

Publications and source records attributed to A J Fox.

At least 145 records · Page 8Linked to original sources
PubMed1994

Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND AND PURPOSE: The importance of carotid plaque ulceration as a cause of cerebral ischemic symptoms remains uncertain. Moreover, its prominence in symptomatic patients with severe carotid stenosis is unknown. METHODS: The association between angiographically defined plaque ulceration and risk of subsequent stroke was assessed using Cox proportional hazards regression in 659 patients with severe (70% to 99%) carotid stenosis from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Treatment assignment (medical versus surgical) and degree of ipsilateral stenosis were identified as having a significant influence on the results. The risk of ipsilateral stroke at 24 months for medically treated patients with ulcerated plaques increased incrementally from 26.3% to 73.2% as the degree of stenosis increased from 75% to 95%. For patients with no ulcer, the risk of stroke remained constant at 21.3% for all degrees of stenosis. The net result yielded relative risks of stroke (ulcer versus no ulcer) ranging from 1.24 (95% confidence interval, 0.61 to 2.52) to 3.43 (95% confidence interval, 1.49 to 7.88). Conversely, for surgically treated patients with antecedent presence of an ulcerated plaque, the risk of stroke increased slightly at the highest degrees of stenosis. Overall, carotid endarterectomy reduced the risk of ipsilateral stroke at 24 months by at least 50%. Similar results were obtained for risk of major ipsilateral stroke and risk of all strokes and death. CONCLUSIONS: The presence of angiographically defined ulceration for medically treated symptomatic patients is associated with an increased risk of stroke. The risk of stroke more than doubles at higher degrees of stenosis. Carotid endarterectomy is beneficial in substantially reducing the risk of stroke, regardless of plaque ulceration and degree of severe carotid stenosis.

Carotid Artery Diseases↗
PubMed1994

Angiographic detection of carotid plaque ulceration. Comparison with surgical observations in a multicenter study. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND AND PURPOSE: Carotid plaque ulceration is used as one of the determinants in deciding which patients should be submitted to carotid endarterectomy. Uncertainties about its importance persist. Its detection by angiography is an important consideration. METHODS: The detection of ulceration by angiography was compared with observations during endarterectomy in the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial. This represents the first multicenter compilation of data on this subject and the largest series of patients with both arteriographic and direct surgical observation. RESULTS: Sensitivity and specificity of detecting ulcerated plaques were 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%. These results remained unchanged with differing degrees of carotid stenosis and were confirmed by analyses based on receiver operating characteristic (ROC) methodology. The area under the ROC curve (Az) was estimated to be 0.61 (95% confidence interval, 0.55 to 0.67). CONCLUSIONS: These observations from a multicenter study confirm that little agreement exists between angiography and surgical observation in detecting carotid plaque ulceration.

Angiography↗
PubMed1994

Bilateral occipital infarctions associated with carotid stenosis in a patient with persistent trigeminal artery. The Collaborators of the North American Carotid Endarterectomy Trial (NASCET).

BACKGROUND: Embolization via a persistent trigeminal artery, one of the embryonic vascular connections that may persist between the carotid and basilar arteries, is an unusual occurrence. CASE DESCRIPTION: We describe a 76-year-old man with bilateral occipital infarctions presumably related to an ulcerated left carotid stenosis. Clinically, a left inferior homonymous quadrantanopia was present. CONCLUSIONS: Anomalous connections between the carotid and the usual posterior circulation territory should be considered in evaluating patients with vertebrobasilar stroke. When they are identified, patients with symptoms attributable to the pontine vertebrobasilar territory supplied by the anomaly may be considered for carotid endarterectomy in the presence of concomitant severe carotid stenosis detected angiographically. Proper identification and treatment of such cases would be expected to prevent recurrence of disabling strokes in the vertebrobasilar circulation. These anomalies will likely be overlooked by ultrasound techniques and depend on good intracranial arteriographic images.

Aged↗
PubMed1994

Direct sampling of the cavernous sinus in Cushing's disease.

Sampling of the petrosal sinus is a sensitive and accurate method of diagnosing Cushing's disease. Sampling of the inferior petrosal sinus has been performed with a steam-shaped no. 4 or 5 French soft catheter in some centres. However, a recent report described two patients who suffered major injury to the brain stem as a result such sampling. The authors describe a series of five patients who underwent simultaneous, direct sampling of the cavernous sinuses with a Tracker microcatheter (Target Therapeutics, Fremont, Calif.) for the diagnosis of Cushing's disease. No complications occurred in this small group. The authors conclude that this procedure is a safe and accurate means of diagnosing Cushing's disease; the technique is also helpful in locating adrenocorticotropin-producing microadenoma.

Adolescent↗
PubMed1993

Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model.

Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Gloucestershire, UK, and one German isolate. The isolates were all of serotype 15 subtype P1:7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype. The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion. In addition, the LOS L3,7,9 immunotype, when compared to the L1,8,10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates. Two case isolates which were unusual in possessing the L1,8,10 immunotype, established invasive infection, but this was associated with a switch to the L3,7,9 immunotype. The results confirm that LOS is a virulence factor for N. meningitidis and that immunotype L3,7,9 is associated with invasive disease.

Administration, Intranasal↗
PubMed1993

Campylobacter jejuni adapts to aerobic metabolism in the environment.

Campylobacter jejuni, when left on blood agar for prolonged periods, was found to survive better in air than under micro-aerobic conditions. After a period of 2-3 days in air, all strains of C. jejuni examined grew freely in air on subculture, and could be further subcultured apparently indefinitely in air. This adaptation to aerobic metabolism was accompanied by a change in colony morphology and some changes in outer-membrane protein patterns, but no change in serotyping reactions. The ability to colonise mice was unaltered as was the helical morphology of growing cells. The important survival phase of C. jejuni, when outside the animal gut, involves not only a change to coccal morphology but also fundamental changes in the metabolism of the organism. These changes are likely to be relevant to techniques required for culturing C. jejuni from foods and environmental sources.

Adaptation, Physiological↗
PubMed1993

An in vitro study of the properties of single vagal afferents innervating guinea-pig airways.

1. A novel preparation of the trachea and main bronchi with attached vagus nerve from the guinea-pig maintained in vitro was used to study the properties of single vagal afferent nerve fibres with identified receptive fields. 2. Recordings were made from twenty-eight C fibres with a mean conduction velocity of 0.9 +/- 0.1 m s-1 and twenty-four A delta fibres with a mean conduction velocity of 8.4 +/- 1.3 m s-1. Receptive fields for C and A delta fibres were of small diameter, distributed throughout the trachea and right bronchus and possessed very low mechanical thresholds of 2.2 +/- 0.4 and 1.1 +/- 0.3 mN respectively. 3. The chemosensitivity of isolated afferents was studied by applying drugs directly onto identified receptive fields. A delta fibres were insensitive to capsaicin (up to 3 microM), bradykinin (3 microM), histamine (10 microM) and 5-hydroxytryptamine (5-HT; 10 microM) applied for up to 1 min. Histamine (10 microM), 5-HT (10 microM) and m-chlorophenylbiguanide (10 microM) were also ineffective in exciting C fibres. 4. Capsaicin, at concentrations ranging from 30 nM to 3 microM, evoked a sustained firing of all C fibres tested when applied for a period of 30 s directly onto receptive fields. Bradykinin (0.1-1 microM) also potently excited C fibres in a concentration-related manner. The effect of bradykinin appeared to be mediated by a B2 receptor since it was not mimicked by the selective B1 receptor agonist [des-Arg9]-bradykinin (3 microM) and was abolished by prior application of the selective B2 receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (HOE 140; 0.1 microM). HOE 140 was without effect against capsaicin-evoked discharge of C fibres. 5. Capsaicin- and bradykinin-evoked discharge of C fibres was present to a similar degree in preparations pretreated with ibuprofen (1 microM), indicating that it was not dependent on, or influenced by, endogenous prostaglandin production. 6. These data demonstrate that single vagal afferents may be studied in vitro and provide the first examination of the properties of sensory fibres innervating guinea-pig airways. C and A delta fibres both exhibit low threshold mechanical sensitivity but show marked differences in terms of their chemosensitivity.

Amino Acid Sequence↗
PubMed1993

Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro.

Human airway smooth muscle possesses an inhibitory nonadrenergic noncholinergic neural bronchodilator response mediated by nitric oxide (NO). In guinea pig trachea both endogenous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase alpha-chymotrypsin on contractile responses evoked by electrical field stimulation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in trachea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism of this modulation we then studied the effects of endogenous NO on acetylcholine (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism of ACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways.

Acetylcholine↗
PubMed1993

Stenosis of the carotid bifurcation: subjective assessment compared with strict measurement guidelines.

Preliminary results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that endarterectomy is highly effective in preventing stroke in patients with 70% to 99% stenosis of the carotid bifurcation. These results are based on specific linear measurement criteria comparing the residual diameter of the lumen with that of the normal carotid beyond the bulb. These criteria may differ from subjective assessments of the severity of stenosis. Angiograms from 125 NASCET patients were analysed independently by three groups of reviewers. The first group consisted of three neuroradiologists, the second of two neurologists and one neurosurgeon and the third of three radiologists with neuroradiologic experience. The degree of stenosis was estimated, without measurement, as mild (1% to 29%), moderate (30% to 69%) or severe (70% to 99%), or the vessel was said to be occluded. These assessments were compared with the degree of stenosis as determined by the NASCET neuroradiologist on the basis of measurement. The subjective assessment of stenosis produced false-positive rates (for assessing stenosis of less than 70% as severe) ranging from 5% among the neuroradiologists to 16% among the radiologists. The false-negative rates (for assessing stenosis of 70% or more as less than severe) ranged from 12% to 22%. Therefore, a subjective rating of carotid stenosis may lead to erroneous estimation of the severity of disease. This problem has therapeutic implications, because carotid endarterectomy has been shown to benefit only patients with stenosis of greater than 70%, as assessed according to strict measurement guidelines.

Carotid Arteries↗
PubMed1992

The serum resistance of gonococci in the majority of urethral exudates is due to sialylated lipopolysaccharide seen as a surface coat.

Examined before subculture, gonococci in 18 urethral exudates collected from different patients were serum-resistant. For 15 exudates, the resistance was drastically reduced by treatment with neuraminidase and by one subculture on laboratory media. It was restored by incubation with cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). Electron microscopic examination of gonococci in eight exudates showed a surface structure stained by Ruthenium red which disappeared in most samples when they were treated with neuraminidase. These results were identical with those of previous studies on in vitro grown gonococci which had shown that serum resistance is due to sialylation of a 4.5-kDa conserved component of gonococcal lipopolysaccharide (LPS) by host CMP-NANA, which masks the target site for bactericidal IgM and renders surface LPS stainable by Ruthenium red. The serum resistance of gonococci in the remaining three exudates was not reduced by neuraminidase nor by subculture. The mechanism of this stable resistance is unknown.

Blood Bactericidal Activity↗
PubMed1992

The lipooligosaccharide immunotype as a virulence determinant in Neisseria meningitidis.

We have studied the antigenic (immunotype) and physical characteristics of the lipooligosaccharide (LOS) of epidemiologically related Neisseria meningitidis case (36) and carrier (76) isolates associated with a virulent clone of meningococci (ET-5 complex). LOS immunotypes were determined by dot blotting using immunotype specific monoclonal antibodies and physical characteristics were determined from silver stained SDS-PAGE following proteinase K digestion. The genetic similarity of the different isolates was confirmed by analysis of the restriction fragment length polymorphisms. An association between LOS immunotype expression and invasive disease was found; 97% of case isolates expressed the L3,7,9 immunotype, of which 13% additionally expressed the L1,8,10 determinant. The LOS immunotypes of carrier strains were much more heterogeneous. The predominant immunotype was L1,8,10 (70%) and only 24% expressed L3,7,9 alone. Genotypically related case isolates from Norway (6) and Austria (18) expressed the L3,7,9 immunotype with similar frequency to the U.K. isolates. The combination of LOS immunotype and capsule expression appears to be related to the virulence of these meningococcal strains.

Antibodies, Bacterial↗
PubMed1992

The cloning, sequencing and expression of a major antigenic region from the feline calicivirus capsid protein.

RNA purified from the feline calicivirus (FCV) F9 vaccine strain was used to prepare a cDNA library in the expression vector lambda gt11. The library was screened for expression of FCV antigen using a rabbit antiserum prepared against purified FCV. A 330 bp cDNA clone was identified and used as a probe to obtain a larger overlapping clone of 1369 bp. Comparative sequence analysis with the CFI and F4 strains showed that the clones were derived from the 3' open reading frame encoding the capsid protein. The region encoded by the 330 bp clone was shown to be variable in the three strains compared, and therefore the probable location of major antigenic variation. This clone was expressed in a bacterial system and antiserum to the recombinant protein was used in immunoblots to confirm that this clone was derived from the gene encoding the capsid protein. From these immunoblots, several other capsid-related polypeptides were identified. Comparison with immunoblots using post-vaccination cat sera showed the antibody response in the cat was directed mainly against the capsid protein. Antiserum to the recombinant protein was shown to be effective in neutralizing the infectivity of FCV, indicating that at least one major neutralizing epitope had been cloned.

Amino Acid Sequence↗
PubMed1991

Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis.

BACKGROUND: Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS: We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS: Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS: Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.

Aged↗
PubMed1991

Clinical correlates of white-matter changes on magnetic resonance imaging scans of the brain.

We report our observations on the clinical and radiologic correlates of changes in cerebral white matter based on 94 subjects undergoing magnetic resonance imaging in a prospective study of dementia. Periventricular hyperintensity occurred twice as often in patients with Alzheimer's disease as in healthy control subjects. Within the control group, the presence of periventricular hyperintensity correlated significantly with one measure of cerebral atrophy and with the presence of changes in the adjoining deep white matter. The significance of white-matter changes distinct from the ventricles (leuko-araiosis) remains unsettled. Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination. This is likely to reflect the heterogeneity of the changes detected with magnetic resonance imaging and their limited extent in our subjects.

Aged↗
PubMed1991

Mu and kappa opioid receptor modulation of 5-HT3 and NK-3 receptor-evoked release of acetylcholine from the guinea-pig ileum myenteric plexus.

The effects of three different opioid agonists on contractions and [3H]-acetylcholine (ACh) release evoked by 5-hydroxytryptamine3 (5-HT3) and neurokinin-3 (NK-3) receptor activation were examined in the guinea-pig ileum longitudinal muscle-myenteric plexus strip (LMMP) preparation. The selective mu (mu)-opioid receptor agonist (D-Ala2,NMe-Phe4,Gly-ol]-enkephalin (DAMGO; 1 nM-100 nM) and the selective kappa (kappa)-opioid receptor agonist U50488 (10 nM-1 microM) inhibited contractile responses to 5-HT and to the selective NK-3 receptor agonist senktide, producing a concentration-related progressive flattening of their concentration-response curves. IC50 estimates for DAMGO and U50488 were somewhat higher for inhibition of 5-HT-evoked as compared to senktide-evoked contractions, and overall lay in the range 6 nM-51 nM. The selective delta (delta)-opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE) inhibited contractile responses only at the highest concentration used (1 microM). 3H-overflow from LMMP preparations preincubated with [3H]-choline was measured as an indicator of [3H]-ACh release. DAMGO (1 nM-100 nM) and U50488 (10 nM-1 microM) inhibited the increases in release of [3H]-ACh evoked by 5-HT (10 microM) and by senktide (10 nM) in a concentration-dependent manner. IC50 estimates for DAMGO and U50488 were not significantly different for inhibition of 5-HT as compared to senktide-evoked increases in [3H]-ACh release and lay in the range 6 nM-23 nM. DPDPE again only inhibited these responses at the maximum concentration used (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

The surface structure seen on gonococci after treatment with CMP-NANA is due to sialylation of surface lipopolysaccharide previously described as a 'capsule'.

Phenotypic serum resistance of gonococci in urethral exudates is due to sialylation of lipopolysaccharide (LPS) by host cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). A surface structure was visible on gonococci [strain BS4 (agar)] that had been stained with ruthenium red after incubation with CMP-NANA. This structure was not visible after neuraminidase treatment, which released sialic acid but not LPS. The LPS profiles of strain BS4 (agar) had another in vivo-selected strain Gc40 (variant D1), were similar. A monoclonal antibody (mAb) which recognises epitope C on the LPS of 'capsulated' gonococci was shown by immunoblotting to react with several LPS components, including one of about 4.5 kDa which contains the probable site of sialylation by CMP-NANA. The reactions with the mAb were not affected by growing the strains with CMP-NANA nor by neuraminidase treatment of the sialylated LPS. The mAb also gold-labelled the surface of both strains before and after treatment with CMP-NANA. These data indicate that sialylation by CMP-NANA and staining with ruthenium red renders more visible the surface LPS which, sometimes in the past, has been seen as a 'capsule'.

Antibodies, Monoclonal↗