Search PubMed⌕ Search

Biomedical subjects

M J Buckley

Publications and source records attributed to M J Buckley.

At least 37 records · Page 2Linked to original sources

A prospective study of pancreatic disease in patients with alcoholic cirrhosis: comparative diagnostic value of ERCP and EUS and long-term significance of isolated parenchymal abnormalities.

BACKGROUND: The prevalence of pancreatic disease in patients with alcohol-related liver cirrhosis is uncertain. We assessed the prevalence of pancreatic abnormalities in patients with alcoholic cirrhosis, and we compared endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for the detection of chronic pancreatitis and other pancreatic lesions. In addition, we assessed the long-term significance of isolated pancreatic parenchymal abnormalities detected at EUS. METHODS: EUS and ERCP were performed in each patient. Subjects with minimal parenchymal changes at initial EUS underwent clinical follow-up and subsequent EUS and/or ERCP to document the occurrence, absence, or progression of these changes. RESULTS: Seventy-two patients with alcoholic cirrhosis were recruited. Chronic pancreatitis was diagnosed in 14 patients (19%) by both methods independently. Isolated parenchymal lesions were observed in 18 patients by EUS alone. After a mean follow-up of 22 months the EUS appearance was unchanged. Ten of the 18 patients underwent follow-up ERCP and this was normal in all cases. CONCLUSIONS: This study demonstrated that (1) 19% of patients with alcoholic cirrhosis have chronic pancreatitis, (2) an additional 25% have isolated pancreatic parenchymal changes at EUS, and (3) these parenchymal abnormalities do not progress during follow-up.

Aged↗

Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice.

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined. AIMS: To evaluate proton pump inhibitor-based triple therapies as first-line eradication regimens in clinical practice, and to establish the efficacy of second-line regimens in the context of an initial failed eradication attempt. METHODS: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first-line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2-week proton pump inhibitor-based triple therapy regimen as described, and 12 patients received a further 1-week proton pump inhibitor-based triple therapy regimen. RESULTS: Including 308 patients, the intention-to-treat (ITT) eradication rates for OAC and OMC as first-line regimens were 72% (95% CI: 63-80%) and 73% (95% CI: 67-79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow-up gives an initial eradication rate of 78% (95% CI: 69-86%) for OAC and 79% (95% CI: 73-85%) for OMC. There were 60 patients (21%; 95% CI: 17-26%) in whom the initial eradication attempt was unsuccessful. With second-line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58-73%) patients. The eradication rates with the quadruple regimen and 2-week triple therapy regimens were 75% (95% CI: 56-94%) and 80% (95% CI: 63-98%) respectively (P = 0. 71). The eradication rate with a repeat 1-week regimen was 33% (95% CI: 7-60%). CONCLUSIONS: The eradication rates achieved in this 'in practice' study with recommended first-line 1-week proton pump inhibitor-based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1-week proton pump inhibitor-based triple therapy regimen was not successful as a salvage therapy. Both the 2-week proton pump inhibitor-based triple therapy regimen and the 1-week quadruple therapy regimen were successful second-line treatments in >/=75% of patients.

Adolescent↗

The role of endoscopic retrograde cholangiopancreatography in the management of hepatic hydatid disease.

BACKGROUND AND STUDY AIMS: Hydatid disease of the liver, and its complications, causes serious morbidity and mortality. We evaluated the role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of hepatic hydatid disease. PATIENTS AND METHODS: This retrospective analysis includes 28 patients with hepatic hydatid disease who underwent ERCP. ERCP was performed preoperatively in 11 patients, for acute cholangitis (n =7), acute pancreatitis (n = 1) and right upper quadrant pain (n = 3), and in eight asymptomatic cases to search for fistulae between the cyst and the biliary tree. In a further nine patients ERCP was performed for early (< 30 days; n = 7) and late (n = 2) postoperative biliopancreatic problems. RESULTS: In all seven patients with cholangitis preoperative ERCP with EST and ductal clearance of daughter cysts and debris led to substantial clinical improvement, including four acutely ill elderly patients who stabilized and were later able to undergo surgery. EST in two of the three patients with pain who had papillary stenosis led to resolution of the abdominal pain. Six of the seven postoperative fistulae could be successfully treated endoscopically using EST. CONCLUSIONS: This study demonstrates the usefulness of ERCP in symptomatic patients with hepatic hydatid cysts; EST enables clearance of the common bile duct and allows healing of postoperative fistulae in the majority of patients. We do not, however, recommend performing routine preoperative ERCP in asymptomatic patients with the disease.

Aged↗

[Radiologic aspects of the complications of duodenal diverticula].

The duodenum is the second most common site, after the colon, for intestinal diverticulae. This condition is most often asymptomatic and is usually an accidental finding. Complications, with variable clinical presentations, may occur in up to 5% of such individuals. We report a retrospective analysis of 5 patients who presented with complicated duodenal diverticular disease. The complications, either isolated or multiple, consisted of bezoar formation (n = 2), diverticulitis (n = 2), extrinsic compression of the common bile duct (n = 3), perforation (n = 1), choledocholithiasis (n = 1), and an abnormality of the bilio-pancreatic ductal convergence (n = 1). The radiological aspects, in particular, the magnetic resonance imaging (MRI) features are reviewed. These are, to our knowledge, the first descriptions of MRI and magnetic resonance cholangiopancreatographic (MRCP) findings in complicated duodenal diverticular disease. MRI facilitates precise delineation of the complicated duodenal diverticulum while MRCP allows assessment of the effects on the biliary and pancreatic ducts.

Acute Disease↗

Atheroembolization in cardiac surgery. The need for preoperative diagnosis.

BACKGROUND: Atheroembolization is a recognized complication of cardiac surgical procedures, and has been implicated in postoperative stroke, renal failure, multiorgan failure, and death. Preoperative identification of patients at risk for developing atheroemboli is essential. The aim of this study was to determine preoperative risk factors for atheroemboli and to assess the postoperative course of the patients who developed atheroembolic syndrome. METHODS: A retrospective record review was conducted. From 1/1990 to 12/1994 5486 patients underwent coronary artery bypass grafting (CABG), valve operations, or other cardiac surgical procedures at Massachusetts General Hospital. Of this population, 107 patients (1.9%) developed atheroembolic syndrome. RESULTS: Patients who develop atheroemboli were older, with an increased incidence (p < 0.01) of hypertension, cerebrovascular disease, and aortoiliac disease. Many had a complicated course after catheterization, with renal insufficiency (35%) and evidence of peripheral emboli (12%). Average Intensive Care Unit stay, hospital stay, and hospital cost of these patients were respectively 16.8 days, 48.4 days, and $88,000, compared to 1.5 days, 9.6 days and $23,000 for a concurrent population undergoing CABG surgery. Of these 107 patients only 2 were discharged home, the others either died (48 patients, or 25% of all cardiac surgical deaths during this period), or went to rehabilitation or chronic hospital facilities. Twenty-seven autopsies were performed and invariably showed a diffusely diseased aorta, with calcification, mural thrombus, and ulceration. CONCLUSIONS: Atheroembolization during cardiac surgical procedures has profound medical and economic consequences. Because of the diffuse nature of aortic disease, measures approaching the disease as a local process are likely to be unsuccessful. Appropriate evaluation would ideally identify patients with extensive aortic atheromatous disease, prior to rather than during surgery.

Adult↗

Extensive aetiological investigations in acute pancreatitis: results of a 1-year prospective study.

BACKGROUND: Epidemiological data on acute pancreatitis are poorly defined. AIMS: To prospectively evaluate the aetiology of acute pancreatitis and to assess the benefits of intensive investigations. METHODS: In a prospective, 1-year study all cases of acute pancreatitis in the Nice catchment area were enrolled. Subjects underwent routine (serum calcium, phosphate and triglycerides; abdominal ultrasonography and CT scan) and additional, delayed intensive investigations (ERCP with bile sampling and/or endoscopy ultrasonography). RESULTS: One hundred and twenty-one cases were included. After routine investigations, a biliary, alcoholic, miscellaneous or unknown origin was diagnosed in 43%, 31.4%, 9.9% and 15.7%, respectively. In subjects with biliary pancreatitis, 43% had no previous history of biliary disease. In the alcohol-related subgroup, pancreatitis recurred in 18.5% during 114.5 days mean follow-up. In subjects with a first episode of alcoholic pancreatitis, delayed supplemental investigations revealed underlying chronic pancreatitis in 92.8%. After routine investigations, a diagnosis of pancreatitis of unknown origin was made in 15.7% (n = 19) of subjects. Additional investigations revealed an underlying cause in 57.8% of these patients (n = 11), including malignancy (n = 3) and biliary disease (n = 4), reducing the overall rate of pancreatitis with no apparent cause to 6.6%. CONCLUSIONS: Investigative techniques, particularly ERCP, will reveal the underlying aetiology of pancreatitis in the majority of patients presenting with 'idiopathic' pancreatitis and should be considered when routine tests are negative.

Acute Disease↗

Tissue engineering and dentistry.

This article assesses the current state of the art of tissue engineering and its applications in dentistry, especially in the reconstruction and repair of orofacial tissues, including bone and oral mucosa, for the restoration of function and improved cosmetics. The article discusses at length the tissue engineering of bone and cartilage, including guided tissue techniques, in which some of the most interesting advances in the field are being made.

Biocompatible Materials↗

Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice.

Analogs of A-98593 (1) and its enantiomer ABT-594 (2) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as 1 and 2. Analogs of 2 with one or two methyl substituents at the 3-position of the azetidine ring also were prepared and found to be substantially less active in both assays.

Alkaloids↗

Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice.

ABT-594 [5-((2R)-azetidinylmethoxy)-2-chloropyridine], a novel neuronal nicotinic acetylcholine receptor agonist, produced significant antinociceptive effects in mice against both acute noxious thermal stimulation--the hot-plate and cold-plate tests--and persistent visceral irritation--the abdominal constriction (writhing) assay (maximally-effective dose in each test 0.62 micromol/kg, i.p.). This effect was not stereoselective since the S-enantiomer, A-98593 [5-((2S)-azetidinylmethoxy)-2-chloropyridine], produced similar antinociceptive effects in this dose range. The effect in the hot-plate test peaked at 30 min after i.p. administration and was still present 60 min, but not 120 min, after injection. ABT-594 was orally active, but 10-fold less potent by this route than after i.p. administration. The antinociceptive effect of ABT-594 was prevented, but not reversed, by the noncompetitive neuronal nicotinic acetylcholine receptor antagonist mecamylamine (5 micromol/kg, i.p.). In contrast, the antinociceptive effect of ABT-594 was not prevented by hexamethonium (10 micromol/kg, i.p.), a neuronal nicotinic acetylcholine receptor antagonist that does not readily enter the central nervous system, nor by naltrexone (0.8 micromol/kg), an opioid receptor antagonist. Thus, initiation of antinociception by ABT-594 involves activation of central nicotinic acetylcholine receptors, but does not require activation of naltrexone-sensitive opioid receptors. The antinociceptive effects of morphine and ABT-594 in the mouse hot-plate test appeared to be additive, but ABT-594 did not potentiate the respiratory depression produced by morphine when the two compounds were coadministered. ABT-594 reduced body temperature and spontaneous exploration in the antinociceptive dose range, but did not reliably impair motor coordination in the rotarod test. Thus, it is unlikely that the antinociceptive effects result simply from impaired motor function. The compound also produced an anxiolytic-like effect in the elevated plus maze (at 0.019 and 0.062 micromol/kg, i.p.). Preliminary safety testing revealed an ED50 for overt seizure production of 1.9 micromol/kg, i.p. and an LD50 of 19.1 micromol/kg i.p. in mice, values 10 and 100 times the minimum effective antinociceptive dose of the compound. ABT-594 increased the duration of ethanol-induced hypnotic effects, tended to increase pentobarbital-induced hypnotic effects (P = 0.0502), and had no effect on pentobarbital-induced lethality. These data indicate that ABT-594 is a centrally acting neuronal nicotinic acetylcholine receptor agonist with potent antinociceptive and anxiolytic-like effects in mice.

Analgesics, Non-Narcotic↗

Perirhinal cortex ablation impairs visual object identification.

Impairments in both recognition memory and concurrent discrimination learning have been shown to follow perirhinal cortex ablation in the monkey. The pattern of these impairments is consistent with the hypothesis that the perirhinal cortex has a role in the visual identification of objects. In this study we compared the performance of a group of three cynomolgus monkeys with bilateral perirhinal cortex ablation with that of a group of three normal controls in two tasks designed to test this hypothesis more directly. In experiment 1 the subjects relearned a set of 40 familiar concurrent discrimination problems; the stimuli in each trial were digitized images of real objects presented in one of three different views. After attaining criterion they were tested on the same problems using similar, but previously unseen, views of the objects. In experiment 2 the subjects were tested on their ability to perform 10 of these familiar discriminations with each problem presented in the unfamiliar context of a digitized image of a unique complex scene. The subjects with ablations were significantly impaired on both tasks. These results demonstrate that the role of the perirhinal cortex is not restricted to memory, and they support the hypothesis that the perirhinal cortex is involved in visual object identification. We suggest that the perirhinal cortex is crucially involved in processing coherent concepts of individual objects. A deficit of this nature could underlie the pattern of impairments that follow perirhinal cortex damage in both visual object recognition memory and visual associative memory.

Animals↗

Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors.

New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (i.p.) or oral (p.o.) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.

Administration, Oral↗

Risk of reoperative valve replacement for failed mitral and aortic bioprostheses.

BACKGROUND: One factor influencing the choice of mechanical versus bioprosthetic valves is reoperation for bioprosthetic valve failure. To define its operative risk, we reviewed our results with valve reoperation for bioprosthetic valve failure. METHODS: Records of 400 consecutive patients having reoperative mitral, aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to March 1997 were reviewed. RESULTS: Reoperations were for failed bioprosthetic mitral valves in 219 patients, failed aortic valves in 153 patients, and failed aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute endocarditis, 153 operations (38%) were nonelective. One hundred nine patients (27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass grafting. The incidence of death in the mitral, aortic, and double-valve groups was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of prolonged postoperative hospital stay (>14 days) was, respectively, 57 (26.0%), 41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective, isolated, first-time valve reoperation died. Multivariable predictors (p < 0.05) of hospital death were age greater than 65 years, male sex, renal insufficiency, and nonelective operation; and predictors of prolonged stay were acute endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated pulmonary artery systolic pressure. CONCLUSIONS: Reoperative bioprosthetic valve replacement can be performed with acceptable mortality and hospital stay. The best results are achieved with elective valve replacement, without concurrent cardiac procedures.

Adult↗

Repeat aortic root replacement.

BACKGROUND: Aortic root replacement in patients who have undergone previous aortic root replacement presents a formidable technical challenge, which may lead to increased surgical mortality. METHODS: We reviewed our experience from January 1989 through November 1995. Seven consecutive patients (6 men and 1 woman) underwent eight repeat aortic root replacements. Mean follow-up was 19 months. Previous root replacement had been performed with homograft in 1 patient, with a bioprosthetic valve composite graft in 1 patient, and with a mechanical valve composite graft in 6 patients. The techniques used at the previous procedures were the Cabrol technique (2 patients), Bentall technique (3 patients), and the coronary button technique (3 patients). Reoperation was indicated for pseudoaneurysm formation in 4 patients and for endocarditis in the others. RESULTS: Aortic homografts were implanted in all patients with endocarditis and mechanical valve composite grafts were used in the others. In all reoperations, the coronary button technique was used. No procedures were done emergently. Concomitant procedures were performed in 2 patients, including mitral valve replacement and aortic arch aneurysm repair. One patient had recurrence of his endocarditis 36 months after operation because of continued intravenous drug use requiring a second successful homograft root replacement. There were no early deaths and one late death at 16 months after operation. CONCLUSIONS: Repeat aortic root replacement, even in the setting of endocarditis, can be done with low mortality.

Adult↗

A study of the effect of age on pancreatic duct morphology.

BACKGROUND: Interpretation of endoscopic pancreatograms is difficult in elderly patients. Age-related parenchymal changes and associated ductographic changes are ill-defined, and it is sometimes difficult to distinguish these from pathologic processes. METHODS: To define age-related pancreatogram changes, all endoscopic retrograde pancreatograms performed in patients older than 70 years of age over a 6-year period were analyzed and compared with those of a control group (younger than 50 years of age). RESULTS: Of the 136 elderly subjects included in the study, 31 (22.8%) were found to have definite pathology. Comparing the remaining 105 subjects with the control group, the mean main pancreatic duct diameter (in millimeters) was larger in the head (5.3 vs. 3.3), body (3.7 vs. 2.3), and tail (2.6 vs. 1.6) (p < 0.05). The duct diameter also increased significantly in each of the age cohorts (70 to 79, 80 to 89, and 90 to 99 years). Only 33 of 105 (31.4%) of the elderly patients had duct diameters within defined normal limits. In the majority (63.3%), dilatation was global but in a minority it was confined to the head and/or body. In 21 subjects the ductal diameter was greater than 2 standard deviations above normal, and in 5 subjects it was greater than 3 standard deviations above normal. Dilatation of secondary ducts was also observed. CONCLUSION: The majority of elderly patients who do not have pancreatic pathology have a dilated pancreatic duct by comparison with younger patients. Patient age must be considered when interpreting endoscopic pancreatograms.

Adolescent↗

Perirhinal cortex ablation impairs configural learning and paired-associate learning equally.

Combined damage to the perirhinal and entorhinal cortex has been implicated in the formation of stimulus-stimulus associative memories. We show in this article that relative to three normal controls three cynomolgus monkeys with ablations restricted to the perirhinal cortex were impaired on a visual paired associate learning task in which subjects had to learn which of two visual stimuli were associated with a cue stimulus. The subjects with perirhinal cortex ablations also showed an impairment of a similar magnitude on a visual configural learning task in which they had to learn which of two configurations of visual stimuli were associated with food-reward. The stimuli in both tasks were comprised of alphanumeric characters presented upon a touch-screen. Both groups made fewer errors on the configural learning task than on the paired associate learning task. We suggest that performance on both tasks relies critically on the perirhinal cortex due to the specialization of the perirhinal cortex in processing knowledge about objects. We argue that the specializations of this system and of other memory systems such as the hippocampal-fornix spatial/episodic memory system, are conferred by the specialization of their anatomical connections to other structures. We reject the notion that there are specific memory processes such as the hippocampal based configural associative system that was proposed to be critical for configural associative learning.

Animals↗

Correlation of inflammatory cytokines with arthroscopic findings in patients with temporomandibular joint internal derangements.

PURPOSE: The goal of this study was to evaluate the presence of the inflammatory cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) within the superior temporomandibular joint (TMJ) space in patients with internal derangements and to compare these values with the pathologic findings seen arthroscopically. PATIENTS AND METHODS: Thirty patients with symptomatic TMJ dysfunction and clinical and imaging evidence of internal derangements of the TMJ were evaluated. Before entering the superior joint space with the arthroscope, 2 mL sterile saline was injected and, after 30 seconds of equilibration, was aspirated for analysis. The surgeon then performed diagnostic arthroscopy. The degree of synovitis, degeneration, percent condylar roofing, and any pathologic changes, such as perforations, were recorded. The level of total protein in each sample was ascertained, as well as the levels of IL-1 beta, IL-6, and TNF-alpha. RESULTS: Of 30 samples tested, three were discarded because of failure to gain access into the superior joint space. Of the 27 remaining samples, IL-6 showed the closest correlation with the level of acute synovitis demonstrated arthroscopically. Two of the higher IL-6 levels (167 and 324 pg/microg protein) were seen with patients with a significant disc perforation. In patients with a high degree of vascularity, IL-6 was found to be between 0 to 581 pg/microg protein with an average of 80 pg/microg protein and a median value of 43 pg/mg. These values significantly correlated with the degree of vascularity (P < or = .02). This is in comparison with the 10 remaining patients, who showed significantly fewer vascular changes arthroscopically. In these patients, the range of IL-6 was 0 to 35 pg/microg protein, with an average of 19 pg/microg protein and a median value of 14.5 pg/microg. These values significantly correlated with the smaller degree of vascularity (P < or = .02). In seven patients, the role of nonsteroidal antiinflammatory drug (NSAID) use resulted in decreased levels of IL-6, which has been noted in previous studies. In patients with higher rated redundancy of the synovial tissue, the average IL-6 level was 92 pg/microg protein, whereas the median value was 44 pg/microg protein. In patients with little or no redundant synovial tissue, an average IL-6 level of 22 pg/microg protein was present. The median value in these same joints was 15 pg/microg protein. These IL-6 values significantly correlated with the degree of redundancy (P < or = .03). The degree of degenerative change (chondromalacia, fibrillation), disc displacement (roofing), and the presence or absence of adhesions did not significantly affect the levels of IL-6 within the patients studied. The presence of IL-1 beta and TNF-alpha was not found to correlate with the arthroscopic findings in the superior joint space. CONCLUSIONS: The presence of IL-6 correlated with the degree of acute synovitis. IL-1 beta and TNF-alpha were not found in significant levels within the superior joint space. These findings correlated with those reported by other investigators. The production of IL-6 by synovial cells and its role in TMJ disease warrants further investigation.

Adolescent↗