Search PubMed⌕ Search

Biomedical subjects

C Kennedy

Publications and source records attributed to C Kennedy.

At least 145 records · Page 8Linked to original sources
PubMed1995

The effects of suramin on purinergic and noradrenergic neurotransmission in the rat isolated tail artery.

Intracellular microelectrode recording was used to examine the effects of suramin, a P2-purinoceptor antagonist, on the electrical responses evoked by sympathetic nerve stimulation in the rat isolated tail artery. Field stimulation (10 or 20 pulses at 0.5, 1 and 2 Hz) evoked a biphasic electrical response, consisting of fast, transient excitatory junctional potentials (e.j.p.s) and a slow, prolonged depolarisation. Suramin (100 microM) abolished the e.j.p.s and significantly increased the amplitude of the slow depolarisation at all frequencies. In contrast, phentolamine (2 microM) abolished the slow depolarisation, but had no effect on the magnitude of e.j.p.s. Neither drug altered the resting membrane potential of cells. The ability of suramin to inhibit e.j.p.s in rat tail artery is consistent with the proposal that it is a P2X-purinoceptor antagonist and supports a role for ATP as an excitatory cotransmitter from the sympathetic nerves innervating this tissue. Suramin is also able to increase the alpha-adrenoceptor-mediated slow depolarisation by an unknown mechanism.

Adenosine Triphosphate↗
PubMed1995

Gallbladder stone recurrence after medical treatment. Do gallstones recur true to type?

Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5-74 months (mean +/- SEM, 26 +/- 4 months) after being rendered stone-free with dissolution therapy (N = 15) or percutaneous cholecystolithotomy (N = 6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids +/- extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of < 100 Hounsfield units (HU) (mean 45, range 10-84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100-969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16-98 HU, P < 0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids +/- lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.

Bile Acids and Salts↗
PubMed1995

How should P2X purinoceptors be classified pharmacologically?

When ATP is released as a neurotransmitter from central and peripheral nerves it acts at P2X purinoceptors to produce postsynaptic depolarization and excitation. The P2X purinoceptor was originally classified on the basis of the relative agonist potencies of ATP and a number of its structural analogues. However, it is now clear that the potency of some agonists is greatly decreased by breakdown by ectonucleotidase enzymes, leading to an incorrect determination of agonist potency order. In this article, Charles Kennedy and Paul Leff discuss recent results that indicate that the established classification of P2X purinoceptors is no longer valid and needs redefinition.

Adenosine Triphosphate↗
PubMed1995

Role of the cerebellar fastigial nucleus in the physiological regulation of cerebral blood flow.

Local cerebral blood flow (ICBF) was measured with [14C]iodoantipyrine in conscious, unrestrained rats during electrical stimulation of the fastigial nucleus (FN). Electrode position in the FN was determined by blood pressure (MABP) responses to stimulation under anesthesia. In nine rats in which MABP responses had been variable under anesthesia, bipolar stimulation (50 Hz, 0.5 ms, 1 s on/1 s off) with currents of 30-100 microA after recovery from anesthesia produced stereotypic behavior but little effect on MABP and ICBF. In seven other conscious rats currents could be raised to 75-200 microA without inducing seizures, resulting in sustained MABP elevations during the ICBF measurement and significantly increased ICBF in the sensory-motor (+45%), parietal (+31%), and frontal cortices (+56%) and the caudate-putamen (+27%) above control values (n = 9). Glucose utilization, measured with [14C]deoxyglucose, in rats similarly stimulated was significantly increased in six structures, including some of the above, indicating increases in ICBF due to metabolic activation. Unilateral or bilateral electrolytic lesions of the FN, placed 6-7 days before ICBF measurement, had negligible effects on resting ICBF and on autoregulation in conscious rats. These results fail to support a specific role for the FN in physiological regulation of cerebral blood flow in unanesthetized rats.

Anesthesia↗
PubMed1995

Lack of effects of inhibition of nitric oxide synthesis on local glucose utilization in the rat brain.

The effects of chronic treatment with NG-nitro-L-arginine methyl ester, a potent inhibitor of nitric oxide synthase activity, on local cerebral glucose utilization were examined in conscious rats. Intraperitoneal injections of 50 mg/kg of the nitroarginine twice daily for 4 days have been found to result in almost complete inhibition of nitric oxide synthase activity in brain. Local cerebral glucose utilization was determined by means of the quantitative autoradiographic [14C]deoxyglucose method in an experimental group (n = 7) of rats that were treated with the nitroarginine according to this schedule and in a normal control group (n = 7) treated similarly with saline. The rats were conscious but partially restrained during the determinations of local cerebral glucose utilization. The nitroarginine treatment raised mean arterial blood pressure statistically significantly to 147 +/- 3 mm Hg (mean +/- SEM) from a level of 120 +/- 5 mm Hg in the saline controls (p < 0.001 by grouped t test), but there were no statistically significant effects on glucose utilization in any of 39 brain structures examined. It is concluded that nitric oxide normally exerts no significant influence on energy metabolism in the rat brain.

Animals↗
PubMed1995

Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.

Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.

Acromegaly↗
PubMed1995

Ultrasound-guided percutaneous fine needle puncture of the gallbladder for studies of bile composition.

Ultrasound-guided percutaneous fine needle puncture of the gallbladder (PFNP-GB) is invaluable for diagnostic and research purposes, but there are few reports about its safety. We therefore describe the efficacy and side-effects of 43 consecutive gallbladder punctures in 39 patients. PFNP-GB was successful in 40/43 (93%), but failed in three. Bile was completely aspirated in 28 of the 40 (70%) successful procedures. After 36 of the 43 punctures (84%), the patients remained asymptomatic, although on seven occasions (16%) the patients complained of right upper quadrant pain 0.5-12 h after the procedure. In six of these, the pain resolved in 2-24 h, although one developed a leucocytosis (22 x 10(9) 1(-1)). The seventh patient developed pyrexia and signs of generalized peritonism, which settled with conservative therapy. Ultrasonographic abnormalities of the gallbladder wall were seen in five of the seven symptomatic patients, consisting of: (i) an increase in the thickness of the gallbladder wall (n = 5) from less than 2 mm to 4-14 mm; (ii) peri-cholecystic collections (n = 2) measuring 5 and 11 mm in diameter; (iii) an intraluminal mucosal flap (n = 1); (iv) an intraluminal echogenic layer (n = 1); and (v) a 12 cm intraabdominal haematoma in the patient with generalized peritonism. Predictors of pain were: (i) the number of needle "passes" (3.7 +/- 0.8, range 2-8, in patients with pain vs 2.0 +/- 0.2, range 1-6, in pain-free patients, p < 0.02); (ii) the absence of gallbladder stones (p < 0.03); and (iii) incomplete aspiration of bile from the gallbladder (p < 0.02). PFNP-GB is an effective way of sampling fresh gallbladder bile, although there is a 16% risk of inducing pain and/or ultrasonographic changes in the gallbladder.

Adult↗
PubMed1995

Percutaneous cholecystolithotomy: risks, benefits, and long-term outcome.

BACKGROUND: For symptomatic patients with gallbladder stones and a patent cystic duct who wish to retain their 'functioning' gallbladders, percutaneous cholecystolithotomy (PCCL) offers an alternative to open or laparoscopic cholecystectomy. However, there are few data on the risks and benefits of this approach or on the long-term outcome. METHODS AND RESULTS: In 21 patients with symptomatic calcified gallstones, PCCL was successful (gallstone clearance) in 17 (81%). Four to 62 (median, 35) months after clearance 9 of the 17 remained symptom-free and stone-free, whereas 4 developed biliary sludge at 7, 30, 32, and 35 months, 2 of whom subsequently developed gallstones. In four other patients gallstones recurred without evidence of preceding biliary sludge at 9, 16, 19, and 27 months, corresponding to an actuarial gallstone recurrence rate at 36 months of 53.4 +/- SEM 15.1%, and a combined stone/sludge recurrence rate of 63.4 +/- 13.5%. CONCLUSIONS: PCCL is moderately effective but, because of the frequency of complications and sludge/stone recurrence, is likely to have only a limited residual role in the era of laparoscopic cholecystectomy.

Cholecystostomy↗
PubMed1995

The impact of state approval requirements on elective cholecystectomy patients.

A total of 215 cholecystectomies were performed at Kern Medical Center over a 20-month period from 10/92 to 5/94 and were retrospectively reviewed. Twenty-four males and 191 females ranged in age from 15-70 years. Of the total 215 cholecystectomies, 119 were performed electively and were separated into two groups. Group 1 (79) consisted of patients awaiting state authorization for cholecystectomy. Group 2 (40) consisted of patients who did not require state authorization. Date of diagnosis was defined as the date when the positive gallbladder ultrasound was completed which, in context with the clinical presentation, confirmed the need for cholecystectomy. The average number of days between diagnosis and cholecystectomy differed significantly between Group 1 and 2 (116 vs 23 respectively, P < .01). The average number of preoperative emergency room (ER) visits differed significantly between Group 1 and 2 (1.48 vs 0.76 respectively, P < .01). The average number of preoperative surgery clinic visits also differed between the two groups (2.88 vs 1.96 in Group 1 and 2 respectively, P < .01). Patients with symptomatic cholelithiasis requiring state approval for cholecystectomy had to wait longer for their operation, and preoperatively visited the ER and outpatient surgery clinic more often. Delay increases patient discomfort and adds additional strain to an already overcrowded ER and clinic. Finally, the economic impact is most likely significant as lost work hours, and additional ER and clinic visits cost taxpayers money.

Adolescent↗
PubMed1994

Transfer of arachidonyl groups within the lipids of two human neuroblastoma cell lines.

The incorporation and mobilization of [3H]arachidonic acid in lipids of human neuroblastoma cell lines, SK-N-SHF and LA-N-5, was studied. Essentially similar results were obtained with these two cell lines. Except for phosphatidylinositol which displayed the highest specific activity, the incorporation patterns within phospholipid classes tended to reflect phospholipid composition initially. However at later stages, counts in the acid-stable phosphatidylcholine plateaued and/or decreased while those of plasmenylethaniolamine and acid-stable phosphatidylethanolamine increased steadily. When cells were pulse-labelled with [3H]arachidonic acid and chased with fresh medium, there was a movement of label from diacyl (acid-stable) phosphatidylcholine to plasmenylethanolamine and diacyl (acid-stable) phosphatidylethanolamine. Plasmenylcholine did not appear to be involved in the arachidonyl group transfer. Under these chase conditions there was extensive turnover in the 32P-labelled polar headgroup of phosphatidylinositol but not in that of the other phospholipids. In both incorporation and chase studies involving [3H]arachidonic acid, a movement of arachidonyl groups from triacylglycerol to phospholipid could be observed. The results indicated that the patterns of incorporation and redistribution of arachidonic acid in human neuroblastoma cells were effectively regulated to favor lipids such as phosphatidylinositol and the subclasses of phosphatidylethanolamine. Possible mechanisms involved in these enrichment processes are discussed.

Arachidonic Acid↗
PubMed1994

The role of regulatory genes nifA, vnfA, anfA, nfrX, ntrC, and rpoN in expression of genes encoding the three nitrogenases of Azotobacter vinelandii.

Several regulatory gene mutants of Azotobacter vinelandii were tested for ability to synthesize functional nitrogenase-1 (Nif phenotype), nitrogenase-2 (Vnf), or nitrogenase-3 (Anf). While nifA mutants were Nif-, Vnf+, and Anf+/-, and ntrC mutants were Nif+, Vnf+, and Anf+, nifA ntrC double mutants were Nif-, Vnf-, and Anf-. A vnfA mutant was Nif+, Vnf+/-, and Anf+/-, and an anfA strain was Nif+, Vnf+, and Anf-. lacZ fusions in the nifH, vnfH, vnfD, anfH, and nifM genes of Azotobacter vinelandii were constructed and introduced into wild-type and regulatory mutants of A. vinelandii. Expression of these operons correlated with the growth phenotype of the regulatory mutants. Apparently either NifA or NtrC can activate expression of nifM. Also, expression of the anf operon required the NifA transcriptional activator, although there are no NifA binding sites at appropriate locations upstream of anfH (or anfA). The results confirm previous reports that VnfA and AnfA are required for expression of vnf and anf genes, respectively, and that VnfA is involved in repression of the nifHDK operon in the absence of molybdenum and of the anfHDGK operon in the presence of vanadium.

Amino Acid Sequence↗
PubMed1994

The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones.

BACKGROUND/AIMS: Treatment of acromegaly with octreotide inhibits cholecystokinin release and gallbladder contraction and induces gallbladder stones. However, little is known about the effects of octreotide on bile composition. METHODS: Fresh gallbladder bile was obtained from three groups: (1) 11 nonacromegalic patients with cholesterol gallstones, (2) 6 acromegalic patients with octreotide-associated stones (treatment, 300-600 micrograms/day for 3-66 months), and (3) 8 acromogalic patients with no stones before octreotide treatment, 5 of whom were reexamined after 3-24 months of therapy. RESULTS: Compared with stone-free acromegalic patients untreated with octreotide, bile from patients with cholesterol stones and from acromegalic patients with octreotide-associated stones had greater saturation indices (mean +/- SEM) (1.52 +/- 0.17 and 1.32 +/- 0.14 vs. 0.90 +/- 0.05, respectively; P < 0.01); more cholesterol in vesicles (61.2% +/- 4.5% and 67.7% +/- 7.2% vs. 37.7% +/- 3.5%; P < 0.009); more unstable vesicles (cholesterol/phospholipid ratios, 0.97 +/- 0.12 and 0.81 +/- 0.16 vs. 0.52 +/- 0.05; P < 0.02); more rapid nucleation (< 5 and < 5 days vs. > 18 days; P < 0.003); and more deoxycholic acid (22.8% +/- 2.4% and 23.6% +/- 4.8% vs. 13.9% +/- 1.4%; P < 0.05). In the paired studies, the saturation indices increased from 0.89 +/- 0.07 before octreotide treatment to 1.12 +/- 0.03 during octreotide treatment (P < 0.02), as did the percentage of deoxycholic acid from 13.3% +/- 2.1% to 24.9% +/- 2.7% (P < 0.03). CONCLUSIONS: Acromegalic patients with octreotide-associated gallstones and stone-free acromegalic patients treated with octreotide have similar changes in bile composition to those in patients with "conventional" cholesterol gallstone disease.

Acromegaly↗
PubMed1994

Local cerebral blood flow during hibernation, a model of natural tolerance to "cerebral ischemia".

The breakdown of cellular homeostasis and progressive neuronal destruction in cerebral ischemia appears to be mediated by a complex network of causes that are intricately interrelated. We have investigated a physiological state existing normally in nature in which mammals appear to tolerate the ordinarily detrimental effects of ischemia with reduced oxygen availability and to resist activation of self-destructive processes, i.e., mammalian hibernation. Ground squirrels (Spermophilus tridecemlineatus) were chronically implanted with arterial and venous catheters and telemetry devices for electroencephalography, electrocardiography, and monitoring of body temperature. The animals were placed in an environmental chamber at an ambient temperature of 5 degrees C. Entrance into hibernation was characterized by a drop in heart rate followed by a gradual decline in body temperature and an isoelectric electroencephalogram. Cold-adapted active animals that were not hibernating served as controls. Cerebral blood flow (CBF) was measured in both groups with the autoradiographic [14C]iodoantipyrine method. Mean (+/- SD) mass-weighted CBF in the brain was 62 +/- 18 ml 100 g(-1) min (-1) (n = 4) in the control group but was reduced to ischemic levels, 7 +/- 4 ml 100 g(-1) min (-1) (n = 4), in the hibernating animals (p < 0.001) [corrected]. No neuropathological changes were found in similarly hibernating animals aroused from hibernation. Hibernation appears to be actively regulated, and hormonal factors may be involved. The identification and characterization of such factors and of the mechanisms used by hibernating species to increase ischemic tolerance and to blunt the destructive effects of ischemia may enable us to prevent or minimize the loss of homeostatic control during and after cerebral ischemia in other species.

Adaptation, Physiological↗
PubMed1994

Comparative effects of calcipotriol (MC903) solution and placebo (vehicle of MC903) in the treatment of psoriasis of the scalp.

The efficacy and safety of calcipotriol solution in the treatment of scalp psoriasis was compared with placebo (vehicle solution), in a multicentre double-blind, randomized, parallel-group study of 49 adult patients. Calcipotriol solution (50 micrograms/ml), or placebo, was applied twice daily over a 4-week period. At the end of the study period 60% of patients on calcipotriol showed clearance or marked improvement of their psoriasis compared with 17% on placebo. Overall assessment of treatment response showed that calcipotriol was superior to placebo in both investigator (P < 0.001; 95% confidence interval for difference 19.0-67.6) and patient (P < 0.001; 95% confidence interval for difference 18.3-68.0) assessments. Total sign score for psoriasis (i.e. the sum of the scores for redness, thickness and scaliness) decreased by 48.9% in the calcipotriol group, and by 18.6% in the placebo group (P = 0.005). Calcipotriol was significantly superior to placebo in reducing redness, thickness, scaliness and extent of psoriasis, and in the patients' assessment in reducing scalp flaking and itching. No statistically significant changes in blood biochemistry were detected during the study, and the solution was generally well tolerated.

Adult↗
PubMed1994

Investigation of the actions of PPADS, a novel P2x-purinoceptor antagonist, in the guinea-pig isolated vas deferens.

1. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) was investigated for its ability to act as an antagonist at P2x-purinoceptors which mediate neurogenic excitatory junction potentials (e.j.ps) and contractions in the guinea-pig isolated vas deferens. 2. PPADS (10(-7) M) caused a small potentiation of the phasic, predominantly purinergic component of contractions evoked by symapthetic nerve stimulation, but higher concentrations of PPADS (3 x 10(-6)-3 x 10(-5) M) elicited a substantial and significant concentration-dependent inhibition. In contrast, over the same concentration-range, PPADS had no effect on the tonic, predominantly noradrenergic phase. 3 PPADS (3 x 10(-5) M) also inhibited contractile responses to exogenous alpha,beta-methyleneATP (10(-8)-10(-3)M), a P2x-purinoceptor agonist, without affecting the responses to exogenous noradrenaline (10(-8)-10(-3) M), carbachol (10(-5) M) or histamine (10(-4) M). 4. PPADS (10(-7)-3 x 10(-5) M) produced a concentration-dependent reduction in e.j.p. magnitude and resting membrane potential. The maximum effect was seen at 10(-5) M PPADS, which reduced e.j.p. magnitude from 13.7 +/- 0.6 mV (n = 12) to 1.8 +/- 0.7 mV (n = 12) and membrane potential from -64.8 +/- 0.6 mV (n = 51) to -55.0 +/- 1.8 mV (n = 12). 5. The PPADS-induced depolarization was not inhibited by the P2x-purinoceptor antagonist, suramin (10(-4) M). This indicates that the depolarization was not due to an agonist action of PPADS at P2x-purinoceptors. 6. The results support the proposal that PPADS is a selective antagonist at P2x purinoceptors as opposed to non-P2-purinoceptors in the guinea-pig vas deferens, but its ability to cause membrane depolarization independently of P2x-purinoceptors and also, at a low concentration, to potentiate the phasic component of the neurogenic contraction indicates that it has other actions.

Adenosine Triphosphate↗