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Biomedical subjects

C L Walters

Publications and source records attributed to C L Walters.

At least 19 recordsLinked to original sources
PubMed1998

Weakness of sympathetic neural control of human pial compared with superficial temporal arteries reflects low innervation density and poor sympathetic responsiveness.

BACKGROUND AND PURPOSE: The primary goal of these studies was to understand and investigate the capacity of perivascular nerves to influence the tone of human pial arteries and to compare them with other human cephalic arteries, the superficial temporal and middle meningeal. METHODS: Responses to electrical activation of intramural nerves and related features of fresh segments of human cephalic arteries-the pial (PA; 478+/-34 microm ID), middle meningeal (MMA; 540+/-41 microm ID), and superficial temporal (STA; 639+/-49 microm ID)-obtained from patients aged 15 to 82 years during surgical procedures were studied on a resistance artery myograph. RESULTS: The PA segment responses to electrical nerve activation and to norepinephrine (NE; 10[-5] mol/L) were 1% and 21% of tissue maximum, respectively, compared with 6% and 34% for the MMA and 14% and 90% for the STA. Tissue maximum was defined as the force increase to 127 mmol/L KCl plus arginine vasopressin (1 microm). All arteries dilated well to acetylcholine. Possible explanations for the PA marginal neurogenic responses were assessed. NE ED50 was 5.4+/-2.2 X 10(-7) mol/L and did not vary with age or diameter. NE responsiveness did not increase in vessels with spontaneous or raised potassium-induced tone. Relaxation to isoproterenol was variable and propranolol did not increase the neurogenic response. Neither N(G)-monomethyl-L-arginine, N(G)-nitro-L-arginine methyl ester, endothelium removal, nor indomethacin consistently influenced the contractions to NE or neurogenic reactivity. The weak PA neurogenic response is in keeping with its poor innervation. As determined by catecholamine histofluorescence, innervation in the PA is sparse, with density increasing in the order PA, MMA, and STA. The incidence of nerve structures in the PA adventitio-medial junction was only 3% of those in the STA, and these were situated more than 3 microm from the closest smooth muscle cell. CONCLUSIONS: We conclude that the weak neurogenic response of adult human pial artery reflects its poor innervation and responsiveness to NE, implying that these features are not important in the regulation of its diameter.

Acetylcholine↗
PubMed1998

Functional changes in human pial arteries (300 to 900 micrometer ID) within 48 hours of aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Animal studies of cerebral arteries 2 to 3 days after experimental subarachnoid hemorrhage (SAH) provide evidence of arterial change such as hyperresponsiveness to contractile agonists. There is evidence that small arteries, as well as those large enough to be seen on angiography, may be involved. To directly test these possibilities, the contractile and dilator responses of pial artery segments taken from patients up to 48 hours after SAH were compared with those from patients having elective surgery for an aneurysm (Clip) and with those from normal brain vessels overlying tumors (controls). METHODS: Segments were mounted on a resistance artery myograph for measurements of wall force changes. RESULTS: There were no differences in maximum contractility (Emax) of the 3 groups of segments. The responses of the SAH segments to K+ (30 mmol/L) were 60.7+/-4.6% of Emax (n [number of vessels]=18), which was significantly greater than those of controls (29.9+/-5% Emax) (n=20). Clip responses were the same as control. Contractions of SAH segments to norepinephrine (1 micromol/L) were 54.3+/-7.9% Emax (n=12), and these were significantly greater than those of controls (15.1+/-6.2% Emax) (n=25). All SAH segments showed spontaneous contractile activity of varying patterns. Spontaneous activity did not occur in the Clip group and occurred in only 50% of control segments. Dilation to acetylcholine was numerically less in SAH and Clip segments than in controls, but differences were not statistically significant. The change in agonist responsiveness could result from exposure to agents that damage the blood vessel wall, resulting in partial depolarization of endothelial and smooth muscle cells. CONCLUSIONS: Small human pial arteries are hyperresponsive to contractile agents and show spontaneous contractile activity within 48 hours of SAH. Such effects could result in narrowed resistance arteries and reduction in cerebral blood flow. These effects emphasize the wisdom of early therapeutic intervention.

Acetylcholine↗
PubMed1997

The source of urinary nitrosamines in patients with enterocystoplasties.

OBJECTIVE: To assess the factors influencing urinary nitrosamine production in patients with enterocystoplasties. PATIENTS, SUBJECTS AND METHODS: The study comprised 100 patients with an enterocystoplasty, 20 patients with interstitial cystitis, 30 with infective cystitis and 120 control subjects drawn from hospital staff and out-patients. Urinary nitrosamine levels were measured and the urine samples cultured for microorganisms. RESULTS: Nitrosamine levels were significantly higher only in patients with enterocystoplasties who also had higher urinary white cell counts or significant bacteriuria. CONCLUSION: Patients with an enterocystoplasty and significant bacteriuria are most at risk from potential nitrosamine-induced epithelial injury.

Bacteriuria↗
PubMed1997

Diameter dependence of myogenic tone of human pial arteries. Possible relation to distensibility.

BACKGROUND AND PURPOSE: Responses to changes in intraluminal pressure of isolated human pial arteries (200 to 1200 microns i.d.) obtained from patients undergoing neurosurgery were measured. METHODS: The vessels were cannulated and pressurized (60 mm Hg); vascular diameter and intraluminal pressure were recorded simultaneously. After spontaneous development of steady state tone, intraluminal pressure was changed to both higher and lower levels in random sequence. RESULTS: Human pial arteries exhibited myogenic responses and maintained their diameter over the pressure range of 20 to 100 mm Hg. The level of myogenic tone observed at 30 mm Hg did not vary significantly with artery diameter. In contrast, at 60 and 90 mm Hg, the extent of myogenic tone increased as the diameter decreased (up to 70% to 80% of maximum in 200-microns i.d. arteries). The arteries contracted to KCl 30 mmol/L, norepinephrine 1 mumol/L, and vasopressin 0.1 mumol/L and relaxed to acetylcholine 3 mumol/L. The extent of these responses did not vary with the diameter of the artery. Arterial distensibility, represented by the slope of the tangent of the passive pressure-diameter curve at lower pressures (5 to 50 mm Hg), increased as arteries became smaller. This is consistent with the possibility that the level of myogenic tone is related to vessel distensibility. Human omental arteries of comparable size did not develop myogenic tone but contracted to KCl and norepinephrine and relaxed to acetylcholine to an extent similar to pial arteries. CONCLUSIONS: There is a specific gradient of myogenic responsiveness in human pial arteries that varies inversely with their diameter. This tone does not develop in all vascular beds. These levels of tone in the pial circulation would be expected to be of profound functional significance by allowing blood flow to vary widely.

Adolescent↗
PubMed1997

Human vascular endothelium heterogeneity. A comparative study of cerebral and peripheral cultured vascular endothelial cells.

BACKGROUND AND PURPOSE: Hormones, neurotransmitters, and autacoids play a key role in the regulation of vascular tone as a result of their interaction with the endothelium. The aim of this study was to compare selected properties of three human endothelial cell lines isolated from cerebral pial arteries (PEC) and two peripheral vessels, the superficial temporal (SEC) and omental (OEC) arteries. METHODS: Intracellular free calcium concentration ([Ca2+]i) and receptor protein expression were measured in characterized primary cultures of human endothelial cells. RESULTS: All cell lines labeled positively for factor VIII/von Willebrand factor. Growth rate and constitutive release of endothelin-1, expressed as a function of protein, were both significantly lower in cerebral cells (PEC) than in endothelial cells derived from peripheral vessels. Basal [Ca2+]i measured with the fluorescent calcium indicator fura 2-AM (2 mumol/L) did not differ in either of the three cell lines. Although PEC responded to endothelin-1 (0.1 mumol/L) and vasoactive intestinal peptide (1 mumol/L) by a twofold to threefold increase in [Ca2+]i, OEC were unresponsive to these peptides. Moreover, the calcium response to alpha-thrombin (10 nmol/L) was greater in cerebral (PEC) than in peripheral (SEC, OEC) endothelial cells, while bradykinin (100 nmol/L) increased [Ca2+]i to a similar level in all three cell types. CONCLUSIONS: This study demonstrates that endothelial cells from different sites of the vasculature exhibit different growth rates and vary in their response to agonists.

Adolescent↗
PubMed1996

N-nitroso compounds in the gastric juice of normal controls, patients with partial gastrectomies, and gastric cancer patients.

BACKGROUND: It has been suggested that the variation of biochemical and microbiological parameters in the gastric juice may play a role in the development of gastric cancer. In the present study we concurrently assessed the presence of N-Nitroso compounds (NOC) and their precursors, bacteria and carcinoembryonic antigen (CEA) in the gastric juice of normal controls, patients with gastric resection, and advanced gastric cancer. METHODS: Detailed analyses of biochemical and microbiological parameters such as pH, nitrite (NO2) concentration, N-nitroso compounds (NOC) concentration, carcino-embryonic antigen (CEA) level, total viable counts (TVC), nitrate-reductase positive bacterial counts (NRPBC), and identification of micro-organisms were carried out. RESULTS: Significantly higher mean pH values, NO2, NOC and CEA concentrations, TVC, and NRPBC were found in partial gastrectomies compared with normal controls, and all these intragastric parameters were significantly higher in patients with gastric cancer than in those with partial gastrectomies. As far as surgical methods are concerned, higher mean pH values, NO2 and NOC concentrations, TVC, NRPBC, and anaerobic bacterial counts were observed in the juice of patients with Billroth II compared with Billroth I gastrectomies. Apart from the type of surgical reconstruction, higher mean NOC levels were recorded in patients with more severe histological changes and H. pylori infection. CONCLUSIONS: All these data suggest that the presence of high levels of NOC in the gastric juice of gastroresected patients can be considered a risk factor of gastric stump cancer.

Adult↗
PubMed1996

Electrical activity underlying rhythmic contraction in human pial arteries.

Human pial arteries obtained during surgery frequently exhibit spontaneous periodic contractions. Simultaneous measurements of membrane potential and vessel wall force were used to examine whether these contractions are associated with electrical activity of smooth muscle cells (SMCs). A total of 53 segments from 38 patients were studied, and of these, 26 showed spontaneous contractions related to periodic depolarization and generation of action potentials (APs). The resting membrane potential during the silent periods was -44.0 +/- 0.5 mV. APs without "overshoot'' were observed when spontaneous depolarization reached levels of -40 to -35 mV. Just over half of the arterial segments failed to exhibit spontaneous activity; however, APs could be generated during K+-induced depolarization. The mean SMC resting membrane potential of these vessels was -53.5 +/- 1.5 mV, and this value differed significantly from that of SMCs in spontaneously active arteries. Application of tetrodotoxin did not change the amplitude and duration of APs. Removal of Ca2+ from the bathing solution and addition of nifedipine completely inhibited the spontaneous APs and associated contractions. K+ depolarization failed to induce APs and contraction in the presence of nifedipine. We conclude that periodic spontaneous depolarization and AP generation underlie the periodic spontaneous contractions of human pial arteries. Both the APs and associated contractions are related to the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels. It is suggested that AP generation can be responsible for vasomotion of human pial arteries in vivo.

Adolescent↗
PubMed1996

Role of Ca(2+)-activated K+ channels in the regulation of membrane potential and tone of smooth muscle in human pial arteries.

Smooth muscle cells (SMCs) in 58% of human pial arteries obtained during surgery showed no spontaneous contractions and displayed a stable resting membrane potential (MP) of -54.7 +/- 1.5 mV. Those that exhibited periodic spontaneous contractions associated with periodic depolarization and generation of spontaneous action potentials (APs) had a less negative MP of -43.1 +/- 0.5 mV (42%). Inhibition of calcium-activated potassium (KCa) channels in the silent arteries by charybdotoxin (CTX) and tetraethylammonium ions (TEA) induced dose-dependent depolarization, AP generation, and contraction. TEA and CTX enhanced the spontaneous depolarization and force in arteries that exhibited spontaneous activity. They also prolonged the spontaneous APs up to several times and increased their upstroke amplitude. Both TEA and CTX failed to produce significant depolarization in arteries treated with nifedipine. It is concluded that KCa channels are important regulators of human pial artery SMC resting MP and tone. They are also involved in the control of AP amplitude and duration and the associated contractions. These data suggest that alterations in the activity of SMC KCa channels could be responsible for the appearance of spontaneous activity in human pial arteries in vitro and that impaired function of these channels might be related to vasospastic phenomena in human cerebral circulation.

Calcium↗
PubMed1991

Effect of ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer.

Ascorbic acid has been shown to decrease nitrosation in vivo, and epidemiological data suggest that the consumption of foods rich in this vitamin is associated with a reduced risk for gastric cancer. In order to study this suggestion further, fasting gastric juice samples were obtained from 62 high-risk patients (seven with atrophic gastritis, ten with pernicious anaemia, ten with partial gastrectomy, 21 with vagotomy and drainage and 14 with highly selective vagotomy), before, during four weeks' treatment with 1 g ascorbic acid four times daily, and four weeks after treatment. Samples were analysed for pH, total and nitrate-reducing bacterial counts, nitrite and N-nitroso compounds. Treatment with ascorbic acid lowered the median pH only in the vagotomized patients (p less than 0.001) but resulted in a reduction in median nitrate-reducing bacterial counts and in nitrite and N-nitroso compound concentrations in all groups, except for an increase in the nitrate-reducing bacterial count in atrophic gastritis patients and in nitrite in those with pernicious anaemia. These data suggest that treatment with a high dose of ascorbic acid reduces the intragastric formation of nitrite and N-nitroso compounds.

Adult↗
PubMed1989

Aminergic histofluorescence and contractile responses to transmural electrical field stimulation and norepinephrine of human middle cerebral arteries obtained promptly after death.

The responses of cerebral arteries to catecholamines and sympathetic nerve stimulation show wide variation between animal species. We examined the catecholaminergic histofluorescence and the contractile responses elicited by transmural electrical field stimulation and norepinephrine (NE) in proximal segments of human middle cerebral artery (MCA) obtained during autopsy. Twenty-four percent of the specimens were obtained within 2 hours and 76% within 4 hours of death. A moderately dense catecholaminergic histofluorescence was seen in all segments of human MCA using the glyoxylic acid technique, counterstained with pontamine sky blue. However, only seven of 35 (20%) MCA segments tested showed tetrodotoxin-blocked transmural electrical field stimulation contractions, and all of these were harvested within 4 hours of death. The responses were mostly seen in the most proximal MCA segments and, at 32 Hz, only achieved 6 +/- 1% of the maximal tissue contraction. NE caused two distinct responses in human MCA segments. At low concentrations, it acts via an alpha-like adrenoreceptor to cause contractions 20 +/- 3% of the maximal tissue response. The NE ED50s for the three successive segments were not different from each other; the value for the most-proximal segment was 7.9 +/- 0.2 x 10(-7) M. At concentrations above 10(-5) M, this catecholamine acts on low-affinity sites resistant to alpha-adrenergic antagonists causing contractions that at 10(-3) M reach 52 +/- 5% of the maximal tissue response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effects of one year's treatment with ranitidine and of truncal vagotomy on gastric contents.

Fifteen patients with peptic ulcer underwent 24 hour studies of gastric contents: before and on completing six weeks' treatment with oral ranitidine 150 mg bd, twice on maintenance treatment for nine to 12 months and one month after stopping the drug. For comparison, 11 patients underwent identical 24 hour studies three to 38 months after truncal vagotomy for duodenal ulcer. During treatment with ranitidine median 24 hour intragastric pH, nitrate concentration, and counts of total and nitrate reducing bacteria increased significantly regardless of dietary nitrate content; there was no significant increase in the median day time concentration of N-nitroso compounds. Despite these changes, an acid tide at some point in each 24 hour study period prevented persistent bacterial colonisation of the stomach. There were no significant differences between the biochemical and microbiological changes recorded during one year of treatment with ranitidine, and the observations on patients after truncal vagotomy. One month after stopping one year's treatment with ranitidine all variables examined returned to pretreatment levels. Treatment with ranitidine or vagotomy was associated with significant positive correlations among pH, nitrate concentration and bacterial counts. Correlations between pH and N-nitroso compound concentration and between concentrations of nitrite and N-nitroso compounds were not significant.

Adult↗
PubMed1987

Nitrosation of drugs under in-vivo conditions.

Application of the WHO Nitrosation Assay Procedure (NAP test) to a range of potentially nitrosatable drugs has given rise to considerable variations in the formation of volatile N-nitrosamines and N-nitroso compounds as a group. No nitrosation whatsoever was observed with 40 mM nitrite in some instances. In simulating more closely the conditions likely to be encountered in the human stomach, however, the order of susceptibility of the drugs to N-nitrosation has proved to be very different. At a constant nitrite concentration of 25 microM, which is considered to represent the upper limit of those likely to be encountered in the acidic human stomach, the drugs giving rise to the greatest yields of products reacting as N-nitroso compounds from a maximum adult dose were the penicillins, G, V, cloxacillin and ampicillin.

Chemical Phenomena↗
PubMed1986

The microflora of the gastric juice after Billroth I and Billroth II partial gastrectomy.

Detailed analyses of biochemical and microbiological variables such as pH, nitrite concentration, total viable counts (TVC), nitrate reductase-positive bacterial counts (NRPBC), and identification of microorganisms were carried out on 76 fasting gastric juice samples obtained at endoscopy from 64 patients previously submitted to partial gastrectomy (22 end-to-end Billroth I, 42 Billroth II/Reichel-Polya) and from 12 normal controls. Samples from normal controls were sterile, but bacteria were detected in the juice from all the operated patients. Significantly higher mean pH values and nitrite levels (p less than 0.001) were found in partial gastrectomies than in normal controls. In relation to surgical methods, higher mean pH values (p less than 0.005), nitrite levels (p less than 0.01), TVC (p less than 0.01), and NRPBC (p less than 0.005) were observed in the juice of patients with Billroth II as compared with Billroth I gastrectomies. Anaerobic bacteria, typical of faecal flora, and particularly Escherichia coli (p less than 0.05) characterized Billroth II samples. All these data suggest that the presence of bacteria in the gastric juice of gastroresected patients can be considered a risk factor of gastric neoplasia and that the type of operation used for the reconstruction of digestive continuity may influence the magnitude of this risk.

Adult↗
PubMed1985

Susceptibilities of drugs to nitrosation under simulated gastric conditions.

Drugs of differing structures and pharmacological actions have been incubated at 37 degrees C and pH 2.0 under conditions simulating those within the normal fasting stomach. The nitrite concentration (25 microM) was kept as constant as possible for 3 hr in an attempt to mimic its in vivo replenishment from the saliva. The extents of N-nitrosation varied widely, but were less than those observed by Gillatt et al. (Fd Chem. Toxic. 1984, 22, 269) using the WHO Nitrosation Assay Procedure, in which the initial nitrite concentration is 40 mM, 1600 times greater, and the pH (3.0) is close to the optimum for the N-nitrosation of secondary amines. The highest yield of N-nitroso compound was obtained with the benzathine salt of penicillin G whereas some drugs, including hydrochlorothiazide and chlorthalidone, produced no detectable N-nitroso derivative. The degree of N-nitrosation was consistently reduced when the initial nitrite concentration of 25 microM was not replenished during the incubations, underlining the importance of simulating the continuous supply of nitrite from the saliva. In all instances, the reactions of the drugs with nitrous acid were inhibited and, in most cases, completely prevented by the presence of ascorbic acid (125 mg).

Chemical Phenomena↗
PubMed1984

Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole.

Ten healthy volunteers were studied before, during, and after treatment with omeprazole 30 mg daily for two weeks. On the 14th night mean nocturnal (2100-0700) intragastric acidity was significantly decreased by 75% (p less than 0.001). At 0700, 22 hours after the last dose of omeprazole, there were significant increases in the bacterial count and the nitrite and N-nitrosamine concentrations in the gastric juice (p less than 0.001). Three days later these changes had resolved. Short term treatment of healthy volunteers with omeprazole is associated with a short lived increase in the gastric bacterial flora, with endogenous production of N-nitroso compounds.

Adult↗
PubMed1984

Susceptibilities of drugs to nitrosation under standardized chemical conditions.

Of 22 drugs with either a N,N-dimethylamino, N,N-diethylamino or N-morpholino group in the molecule, eight were converted to volatile N-nitrosamines by nitrosative cleavage in reactions of nitrite and drug in a molar ratio of 4:1 at pH 3. Under standardized conditions yields were greatest with aminopyrine and minocycline which contains two N,N-dimethylamino groups in the molecule. Oxytetracycline, chlortetracycline, tetracycline, promethazine, chlorpromazine, imipramine and disulfiram gave much lower yields and amitriptyline, clomiphene, clomipramine, dextropropoxyphene, diphenhydramine, disopyramide, erythromycin, mepyramine, methapyrilene, penicillin G procaine salt, procaine, tamoxifen, trimeprazine and tripelennamine yielded no detectable levels of volatile N-nitrosamines. Nitrosation products of 57 drugs were also examined by a group selective procedure estimating both volatile and non-volatile N-nitroso compounds. Virtually all of the yield obtained from aminopyrine or minocycline could be accounted for by N-nitrosodimethylamine (NDMA). However, compounds yielding excess N-nitrosamines compared to NDMA were obtained from the other three tetracyclines, presumably as a result of the cleavage of a methyl group from the N,N-dimethylamino substituent to form desmethyl-N-nitroso compounds. In general, the drugs giving the highest yields of N-nitroso compounds were those containing secondary rather than tertiary amino groups. A considerable range of susceptibilities towards nitrous acid was observed overall; ten drugs containing a secondary or tertiary amino- or amido- or hydrazido - group did not react with nitrous acid to form N-nitroso compounds.

Chemical Phenomena↗