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Biomedical subjects

M J Buckley

Publications and source records attributed to M J Buckley.

At least 55 records · Page 3Linked to original sources

Comparison of propofol and methohexital continuous infusion techniques for conscious sedation.

PURPOSE: Methohexital and propofol have been shown to be effective agents for continuous intravenous infusion to produce conscious sedation during oral surgical procedures. The current study was conducted to compare these techniques for intraoperative cardiopulmonary stability, patient cooperation, amnesia, comfort, recovery time, and postoperative nausea and vomiting. METHODS: Seventy ASA Class I or Class II patients between the ages of 18 and 40 years, scheduled for surgical extraction of impacted third molars, were entered into the study. Thirty-five patients were assigned to group A (methohexital) and 35 were assigned to group B (propofol). Intravenous sedation was accomplished using premedication with 1.5 microg/kg of fentanyl and 0.05 mg/kg of midazolam followed by the continuous infusion of methohexital or propofol at a rate of 50 microg/kg/min. The infusion was then titrated to 100 microg/kg/min to accomplish a level of sedation in which the eyes were closed and the patients were responsive to verbal commands. Subjects were monitored for variability of heart rate, blood pressure, oxygen saturation, amnesia, comfort, cooperation, nausea and vomiting, and recovery time based on cognitive, perceptual, and psychomotor tests. RESULTS: There was no statistical difference between the two medication groups except for heart rate, which was found to increase by 11 beats/min for group A and only three beats/min in group B. CONCLUSION: A continuous infusion technique using either methohexital or propofol (50 to 100 microg/kg/min) was found to be safe and effective, with no clinically significant differences in cooperation, cardiopulmonary stability, recovery time, amnesia, comfort, and the incidence of nausea or vomiting. However, the cost-effectiveness of methohexital is superior to that of propofol.

Adolescent↗

First report of association of chronic pancreatitis, primary biliary cirrhosis, and systemic sclerosis.

We report an original observation of chronic pancreatitis associated with primary biliary cirrhosis and systemic sclerosis. The diagnosis of each of these conditions was unequivocally confirmed. Pancreatic involvement in this case was asymptomatic. The association of chronic pancreatitis with primary biliary cirrhosis has been previously reported and pancreatitis has been associated with other autoimmune disorders. We hypothesize about the underlying pathogenic mechanisms of chronic pancreatitis in our case.

Aged↗

Learning and transfer of object-reward associations and the role of the perirhinal cortex.

Perirhinal cortex ablation has previously been shown only to impair new postoperative object discrimination learning with large stimulus set sizes (> or = 40 problems). In this study, 3 cynomolgus monkeys (Macaca fascicularis) with bilateral perirhinal cortex ablations were impaired relative to 3 normal controls on concurrent discrimination learning tasks with only 10 problems with the objects presented in different orientations in each trial to increase the demands placed on object identification. This supports the hypothesis that perirhinal cortex damage impairs the ability to identify multiple individual objects. Fewer errors were made to digitized images of objects than toward real objects. Both groups subsequently transferred specific object-reward associations from real objects to digitized images of the respective objects and vice versa, providing evidence that cynomolgus monkeys can recognize photographic representations of objects with experience.

Animals↗

The role of therapeutic endoscopy associated with extracorporeal shock-wave lithotripsy and bile acid treatment in the management of Caroli's disease.

BACKGROUND AND STUDY AIMS: Caroli's disease causes relapsing episodes of cholangitis due to the presence of intrahepatic lithiasis. Strategies for cholangitis prevention are still widely debated. Ursodeoxycholic acid, hepaticojejunostomy, partial hepatectomy, or transplantation, have all been proposed as therapeutic options. The aim of this study was to evaluate the role of therapeutic endoscopy, and especially endoscopic sphincterotomy (ES), in the management of Caroli's disease. PATIENTS AND METHODS: Between 1983 and 1995, six patients with Caroli's disease (mean age 52, range 17-75) underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis. Sphincterotomy was performed if common bile duct stones were present. Extracorporeal shock-wave lithotripsy, (ESWL) or intraductal electrohydraulic lithotripsy (IEL) were performed if necessary. RESULTS: The mean number of endoscopic sessions per patient was four (range three to seven). Sphincterotomy was performed in five patients and cholangioscopy in three. ESWL was performed twice in each of four patients. A Strecker expandable metal stent was placed in one patient to maintain sphincterotomy patency. In one patient, two sessions of IEL and pulsed laser were carried out. Complete clearance of intrahepatic stones was achieved in four of the six subjects (66.6%) and partial clearance in two patients. No morbidity or mortality was observed. During the follow-up (mean 6.2 years; range: 2.1-16.3), only two patients had acute cholangitis at nine months and three years, respectively, after the endoscopic treatment. Both had residual intrahepatic stones left after the initial endoscopic attempt at clearance. CONCLUSION: ERCP is a necessary diagnostic procedure which should always be carried out in patients with Caroli's disease. Our experience shows that ES does not result in an increased incidence of cholangitis and that therapeutic endoscopy allows complete clearance of intrahepatic stones in the majority of patients with unresectable symptomatic Caroli's disease. Nevertheless, the oncological risk in these patients remains unchanged, and they still have an increased risk of cholangiocarcinoma.

Caroli Disease↗

Helicobacter biology--discovery.

The presence of gastric spirochaetal organisms was first documented over a century ago. Though repeatedly reported in the medical literature, it was felt that these spiral bacteria were merely contaminants and the reports were generally ignored by the medical community. On 22 October 1982, at a meeting of the Royal Australian College of Physicians, successful culture of these 'Campylobacterlike organisms' from gastric biopsy specimens was reported for the first time. Moreover, it was shown that their presence was associated with gastritis and, possibly, with peptic ulceration. The subsequent discovery of the pivotal role of Helicobacter pylori in a wide range of conditions has revolutionised our understanding of gastroduodenal diseases. Improvements in diagnostic and therapeutic options, combined with the gradual acceptance of the aetiological role of an infective agent in peptic disease, have led to a remarkable change in the management of gastroduodenal conditions in the past decade.

Gastritis↗

A community-based study of the epidemiology of Helicobacter pylori infection and associated asymptomatic gastroduodenal pathology.

OBJECTIVES: To document the epidemiology of Helicobacter pylori infection in a normal population, to assess asymptomatic H. pylori positive individuals for the presence of gastroduodenal disease, and to compare the macroscopic and microscopic findings at endoscopy in this group with those of patients presenting with dyspepsia. DESIGN/METHODS: Serum was collected from blood donors and assessed for the presence of anti-H. pylori IgG antibodies. A randomly selected group of asymptomatic blood donors and dyspeptic patients underwent endoscopy. RESULTS: The seroprevalence of H. pylori in 1000 subjects was 43.0%. The prevalence of infection increased from 29% in 18-30 year olds to 62% in 46-60 year olds (P < 0.01). The infection was more prevalent in individuals from social classes IV and V (50.0%) than social classes I and II (36.9%) (P < 0.01). There was no difference between the H. pylori positive asymptomatic individuals (n = 37) and matched dyspeptic patients (n = 29) at endoscopy with regard to duodenal ulcer (13.5% vs. 17.2%) or gastroduodenal erosions (24.3% vs. 20.7%) while 5.4% of the former had gastro-oesophageal reflux compared to 27.6% of the latter. Overall, 56.8% of the H. pylori positive asymptomatic group had a normal macroscopic endoscopy compared with 31% of the dyspeptic group. Histology of the gastric mucosa did not reveal any significant differences between the two groups. In H.pylori negative asymptomatic individuals (n = 13) 92.3% had a normal endoscopy (7.7% had grade I gastro-oesophageal reflux) compared with 61.5% of a matched dyspeptic group (n = 13). CONCLUSION: H.pylori infection, symptomatic and asymptomatic, is associated with significant pathology, and screening for the infection may be indicated for the prevention of gastroduodenal diseases.

Adolescent↗

Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.

An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.

Acute Disease↗

Autoregulation of periodontal ligament cell phenotype and functions by transforming growth factor-beta1.

During orthodontic tooth movement, mechanical forces acting on periodontal ligament (PDL) cells induce the synthesis of mediators which alter the growth, differentiation, and secretory functions of cells of the PDL. Since the cells of the PDL represent a heterogeneous population, we examined mechanically stress-induced cytokine profiles in three separate clones of human osteoblast-like PDL cells. Of the four pro-inflammatory cytokines investigated, only IL-6 and TGF-beta1 were up-regulated in response to mechanical stress. However, the expression of other pro-inflammatory cytokines such as IL-1 beta, TNF-alpha, or IL-8 was not observed. To understand the consequences of the increase in TGF-beta1 expression following mechanical stress, we examined the effect of TGF-beta1 on PDL cell phenotype and functions. TGF-beta1 was mitogenic to PDL cells at concentrations between 0.4 and 10 ng/mL. Furthermore, TGF-beta1 down-regulated the osteoblast-like phenotype of PDL cells, i.e., alkaline phosphatase activity, calcium phosphate nodule formation, expression of osteocalcin, and TGF-beta1, in a dose-dependent manner. Although initially TGF-beta1 induced expression of type I collagen mRNA, prolonged exposure to TGF-beta1 down-regulated the ability of PDL cells to express type I collagen mRNA. Our results further show that, within 4 hrs, exogenously applied TGF-beta1 down-regulated IL-6 expression in a dose-dependent manner, and this inhibition was sustained over a six-day period. In summary, the data suggest that mechanically stress-induced TGF-beta1 expression may be a physiological mechanism to induce mitogenesis in PDL cells while down-regulating its osteoblast-like features and simultaneously reducing the IL-6-induced bone resorption.

Adolescent↗

ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization.

The antinociceptive effects of ABT-594, a novel nicotinic acetylcholine receptor (nAChR) ligand, were examined in rats in models of acute thermal (hot box) and persistent chemical (formalin test) pain. Also, the effects of ABT-594 treatment on motor function and electroencephalogram (EEG) were determined. In the hot box and formalin test (i.e., phase 1 and 2), acute treatment with ABT-594 (0.03, 0.1 and 0.3 mumol/kg i.p.) produced significant dose-dependent antinociceptive effects. In the hot box, the efficacy of ABT-594 was maintained after a repeated dosing paradigm (5 days b.i.d.i.p.). ABT-594 was fully efficacious in the formalin test when administered before formalin, and also retained significant efficacy (0.3 mumol/kg i.p.) when administered after formalin injection. The antinociceptive effects of ABT-594 in the hot box and formalin tests were attenuated by pretreatment with the nAChR antagonist, mecamylamine, and in animals treated with the nAChR antagonist chlorisondamine, given centrally (10 micrograms/rat i.c.v. 5 days before), but not in animals pretreated with the opioid receptor antagonist, naltrexone. Acute treatment with ABT-594 produced an initial decrease in open-field locomotor activity, which was absent in animals dosed repeatedly (5 days b.i.d.) with ABT-594. Also, acute treatment with ABT-594 decreased body temperature and decreased the amount of time the animals could maintain balance in an edge-balance test. These effects were no longer present in animals dosed repeatedly with ABT-594. At antinociceptive doses, ABT-594 produced activation of free running EEG in contrast to the sedative-like effects of morphine. Full antinociceptive efficacy was maintained in both the hot box and formalin tests after oral administration, whereas the effects on motoric performance were attenuated. In conclusion, these data demonstrate that ABT-594 is a potent antinociceptive agent with full efficacy in models of acute and persistent pain and that these effects are mediated predominately by an action at central neuronal nAChRs. In addition, antinociceptive effects were maintained after repeated dosing, whereas effects of ABT-594 on motor and temperature measures were attenuated in animals treated repeatedly with ABT-594. Thus, compounds acting at nAChRs may represent a novel approach for the treatment of a variety of pain states.

Administration, Oral↗

Endoscopic retrograde cholangiopancreatography in patients with Billroth II gastrectomy.

AIM: Endoscopic retrograde cholangiopacreatography and associated therapeutic procedures are widely used in routine clinical practice. The changes in the upper gastrointestinal anatomy after a Billroth II anastomosis may present technical difficulties at endoscopic retrograde cholangiopacreatography. METHODS AND PATIENTS: The case records of all patients who underwent endoscopic retrograde cholangiopacreatography at our Unit from January 1985 to December 1995 were reviewed. All patients who had had a previous Billroth II anastomosis or gastroenteroanastomosis were included in this analysis. Of the 5994 procedures performed, 124 patients with Billroth II surgery and 10 with a gastroenteroanastomosis were identified. RESULTS: In these patients, the papilla was located in 89% of cases from 1985 to 1990 and in 100% of cases from 1991 to 1995. Overall, the success rates for pancreatography, cholangiography, and endoscopic sphincterotomy were 94%, 97.7%, and 100%, respectively. The morbidity and mortality rates were 7.4% and 0%, respectively. CONCLUSIONS: The success rate for endoscopic retrograde cholangiopacreatography in patients with Billroth II gastrectomy is similar to that of a normal population.

Adult↗

Eosinophilic pancreatitis mimicking pancreatic neoplasia: EUS and ERCP findings--is nonsurgical diagnosis possible?

Eosinophilic pancreatitis is a rare disease with, to date, only 10 reported cases. We report two patients whose presentation was suggestive of a pancreatic tumor. An 18-year-old man presented with a short history of obstructive jaundice, epigastric pain, and weight loss. Endoscopic ultrasonography revealed a 12-mm round, hypoechoic lesion in the head of the pancreas, suggestive of a pancreatic endocrine tumor. A duo-denopancreatectomy was performed, and the patient made an uneventful recovery. A 64-year-old man was referred with weight loss and obstructive jaundice due to a stricture of the common bile duct. Retrograde pancreatography demonstrated a very narrow, regular main pancreatic duct and early parenchymography. Endoscopic retrograde cholangiopancreatography revealed a tight, regular stenosis of the intrahepatic portion of the common bile duct. A gastrojejunal anastomosis and biliary-digestive bypass were performed without postoperative complications. In both cases, the diagnosis of eosinophilic pancreatitis was revealed after surgical resection. The features of eosinophilic pancreatitis, including eosinophilic infiltration of the digestive wall, a history of atopy, and the radiological characteristics are described. If these are of sufficient discriminatory value, unnecessary surgery may be avoided.

Adolescent↗

Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties.

2-Methyl-3-(2(S)-pyrrolidinylmethoxy)pyridine, ABT-089 (S-4), a member of the 3-pyridyl ether class of nicotinic acetylcholine receptor (nAChR) ligands, shows positive effects in rodent and primate models of cognitive enhancement and a rodent model of anxiolytic activity and possesses a reduced propensity to activate peripheral ganglionic type receptors. The profiles of S-4, its N-methyl analogue, and the corresponding enantiomers across several measures of cholinergic channel function in vitro and in vivo are presented, together with in vitro metabolism and in vivo bioavailability data. On the basis of its biological activities and favorable oral bioavailability, S-4 is an attractive candidate for further evaluation as a treatment for cognitive disorders.

Administration, Oral↗

Cardiac operations in patients 80 years old and older.

BACKGROUND: Because the elderly are increasingly referred for operation, we reviewed results with cardiac surgical patients 80 years old or older. METHODS: Records of 600 consecutive patients 80 years old or older having cardiac operations between 1985 and 1995 were reviewed. Follow-up was 99% complete. RESULTS: Two hundred ninety-two patients had coronary grafting (CABG), 105 aortic valve replacement (AVR), 111 AVR + CABG, 42 mitral valve repair/ replacement (MVR) +/- CABG, and 50 other operations. Rates of hospital death, stroke, and prolonged stay (> 14 days) were as follows: CABG: 17 (5.8%), 23 (7.9%) and 91 (31.2%); AVR: 8 (7.6%), 1 (1.0%), and 31 (29.5%); AVR + CABG: 7 (6.3%), 12 (10.8%), and 57 (51.4%); MVR +/- CABG: 4 (9.5%), 3 (7.1%), and 16 (38.1%); other: 9 (18.0%), 3 (6.0%), and 23 (46.0%). Multivariate predictors (p < 0.05) of hospital death were chronic lung disease, postoperative stroke, preoperative intraaortic balloon, and congestive heart failure; predictors of stroke were CABG and carotid disease; and predictors of prolonged stay were postoperative stroke and New York Heart Association class. Actuarial 5-year survival was as follows: CABG, 66%; AVR, 67%; AVR + CABG, 59%; MVR +/- CABG, 57%; other, 48%; and total, 63%. Multivariate predictors of late death were renal insufficiency, postoperative stroke, chronic lung disease, and congestive heart failure. Eighty-seven percent of patients believed having a heart operation after age 80 years was a good choice. CONCLUSIONS: Cardiac operations are successful in most octogenarians with increased hospital mortality, postoperative stroke, and longer hospital stay. Long-term survival is largely determined by concurrent medical diseases.

Actuarial Analysis↗

Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.

OBJECTIVES: A total of 4756 cases of intraaortic balloon pump support have been recorded at the Massachusetts General Hospital since the first clinical insertion for cardiogenic shock in 1968. This report describes the patterns of intraaortic balloon use and associated outcomes over this time period. METHODS: A retrospective record review was conducted. RESULTS: Balloon use has increased to more than 300 cases a year at present. The practice of balloon placement for control of ischemia (2453 cases, 11.9% mortality) has become more frequent, whereas support for hemodynamic decompensation (congestive heart failure, hypotension, cardiogenic shock) has been relatively constant (1760 cases, 38.2% mortality). Mean patient age has increased from 54 to 66 years, and mortality has fallen from 41% to 20%. Sixty-five percent (3097/4756) of the total patient population receiving balloon support underwent cardiac surgery. Placement before the operation (2038 patients) was associated with a lower mortality (13.6%) than intraoperative (771 patients, 35.7% mortality) or postoperative use (276 patients, 35.9% mortality). Independent predictors of death with balloon pump support were insertion in the operating room or intensive care unit, transthoracic insertion, age, procedure other than angioplasty or coronary artery bypass, and insertion for cardiogenic shock. Independent predictors of death with intraoperative balloon insertion were age, mitral valve replacement, prolonged cardiopulmonary bypass, urgent or emergency operation, preoperative renal dysfunction, complex ventricular ectopy, right ventricular failure, and emergency reinstitution of cardiopulmonary bypass. CONCLUSIONS: Balloons are being used more frequently for control of ischemia in more patients who are elderly with lower mortality. An institutional bias toward preoperative use of the balloon pump appears to be associated with improved outcomes.

Age Distribution↗

Monkeys can associate visual stimuli with reward delayed by 1 s even after perirhinal cortex ablation, uncinate fascicle section or amygdalectomy.

In the present experiment monkeys learned concurrent associations of two-dimensional objects (presented on a computer screen) with delayed reward. Hypothetical mechanisms of associative memory, such as long-term potentiation (LTP), required coincidental activation of two population of neurons: one representing the object and the other signalling the reward. In monkeys neurons in area TE of temporal cortex show object-specific activity during object presentation but only fraction of those neurons remain active after stimulus offset. In a delayed reward condition the majority of object-specific neurons in TE cease firing before reward is given and can be detected. In the present study the rate of learning with 1000 ms delay of reward was no slower than learning with immediate reward. This indicates that information about the object is somehow retained across the delay, possibly somewhere outside TE. In the present study we tested that assumption. Area TE projects to the perirhinal cortex and, via uncinate fascicle, to the prefrontal cortex. In our hands, ablations of perirhinal cortex or disconnection of prefrontal cortex from TE (by transection of uncinate fascicle) did not impair learning with delayed reward. Ablation of amygdala, a structure involved in reward-learning, slowed down learning equally with and without delay. We conclude that retaining information about the visually perceived objects across a delay does not exclusively depend upon integrity of perirhinal cortex, or uncinate fascicle, or amygdala. Parallel involvement of those structures remains a possibility and establishment of the role of residual activity of TE neurons requires further neurophysiological investigation.

Amygdala↗