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D J Kearney

Publications and source records attributed to D J Kearney.

17 recordsLinked to original sources
PubMed2005

Is Helicobacter pylori seropositivity related to body mass index in the United States?

BACKGROUND: Helicobacter pylori infection may decrease serum ghrelin and increase gastric leptin levels, which may, in turn, decrease body mass index. AIM: To determine whether H. pylori seropositivity is associated with body mass index. METHODS: Serum H. pylori and cytotoxin-associated gene product A (CagA) antibody levels were measured on 6724 adult participants of the third National Health and Nutrition Examination Survey (1988-91). We evaluated the association between H. pylori/CagA antibody status [both negative (-/-), H. pylori-positive/CagA-negative (+/-), or both positive (+/+)] and body mass index, adjusting for sociodemographic factors. We also investigated whether H. pylori/cytotoxin-associated gene product A antibody status was associated with fasting serum leptin levels. RESULTS: H. pylori/CagA antibody status was not associated with obesity (body mass index > or = 30 kg/m(2)) [adjusted odds ratio (OR) 1.2, 95% CI: 0.9-1.6 comparing (+/+) to (-/-) and adjusted OR 1.1, 95% CI: 0.8-1.5 comparing (+/-) to (-/-)], overweight (body mass index 25 to <30 kg/m(2)) [adjusted OR 1.0, 95% CI: 0.7-1.2 comparing (+/+) to (-/-) and adjusted OR 1.0, 95% CI: 0.8-1.3 comparing (+/-) to (-/-)], or fasting serum leptin level in the USA population. CONCLUSIONS: H. pylori seropositivity and CagA antibody status are not associated with body mass index or fasting serum leptin level.

Adult↗
PubMed2001

Molecular basis of Celmer's rules: role of the ketosynthase domain in epimerisation and demonstration that ketoreductase domains can have altered product specificity with unnatural substrates.

BACKGROUND: Polyketides are structurally diverse natural products with a range of medically useful activities. Non-aromatic bacterial polyketides are synthesised on modular polyketide synthase multienzymes (PKSs) in which each cycle of chain extension requires a different 'module' of enzymatic activities. Attempts to design and construct modular PKSs that synthesise specified novel polyketides provide a particularly stringent test of our understanding of PKS structure and function. RESULTS: We show that the ketoreductase (KR) domains of modules 5 and 6 of the erythromycin PKS, housed in the multienzyme subunit DEBS3, exert an unexpectedly low level of stereochemical control in reducing the keto group of a synthetic analogue of the diketide intermediate. This led us to construct a hybrid triketide synthase based on DEBS3 with ketosynthase domain ketosynthase (KS)5 replaced by the loading module and KS1. The construct in vivo produced two major triketide stereoisomers, one expected and one surprising. The latter was of opposite configuration at three out of the four chiral centres: the branching alkyl centre was that produced by KS1 and, surprisingly, both hydroxyl centres produced by the reduction steps carried out by KR5 and KR6 respectively. CONCLUSIONS: These results demonstrate that the epimerising activity associated with module 1 of the erythromycin PKS can be conferred on module 5 merely by transfer of the KS1 domain. Moreover, the normally precise stereochemical control observed in modular PKSs is lost when KR5 and KR6 are challenged by an unfamiliar substrate, which is much smaller than their natural substrates. This observation demonstrates that the stereochemistry of ketoreduction is not necessarily invariant for a given KR domain and underlines the need for mechanistic understanding in designing genetically engineered PKSs to produce novel products.

Amino Acid Sequence↗
PubMed2001

Retreatment of Helicobacter pylori infection after initial treatment failure.

OBJECTIVES: Helicobacter pylori treatment regimens fail to cure the infection in at least 10-20% of patients undergoing initial treatment. Retreatment strategies for patients who have failed initial treatment for H. pylori infection remain poorly described. METHODS: The literature describing the frequency of H. pylori treatment failure and factors leading to failure is reviewed. The role of antibiotic resistance is discussed and clinical studies assessing success rates according to antibiotic resistance are described. Clinical trials evaluating the treatment success rates for a second episode of treatment are discussed. RESULTS: The literature describing retreatment of failed H. pylori infection remains limited. The existing data support the use of bismuth-based quadruple therapy or ranitidine bismuth citrate (RBC)-based triple therapy as the preferred agents after initial treatment failure. CONCLUSION: Further studies are needed to better define the optimal second treatment regimen after failed H. pylori treatment.

Anti-Ulcer Agents↗
PubMed2001

Key topics in Helicobacter pylori eradication in the management of the dyspeptic patient: a panel discussion.

A panel of international gastroenterologists and other specialists convened at a Takeda-sponsored symposium held during the XIIIth International Workshop on Gastroduodenal Pathology and Helicobacter pylori (October 2000, Rome) to discuss clinical management of H. pylori. Topics such as management strategies as alternatives to eradication, long-term outcomes, and the impact of antibiotic resistance to H. pylori were discussed in an interactive session. The panel concluded that 1) patients with ulcer-like or reflux-like dyspepsia do appear to benefit from proton pump inhibitor therapy, 2) eradication of H. pylori may reduce future morbidity and mortality from peptic ulcer disease and gastric carcinoma, outweighing the theoretical risk of developing gastro-oesophageal reflux disease, Barrett's oesophagus, and oesophageal adenocarcinoma, and 3) the epidemiology of resistance to H. pylori, and the impact of the percentage of eradication, should be considered when an eradication regimen is being planned for patients with non-ulcer dyspepsia. Susceptibility testing may be of help in areas where this investigation is cost effective.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Treatment of Helicobacter pylori infection in clinical practice in the United States: results from 224 patients.

Our objectives were to define treatment success, compliance, and side effects for treatment of Helicobacter pylori in clinical practice. In all, 224 consecutive patients received Helicobacter pylori treatment: 97 received two weeks of bismuth subsalicylate, metronidazole, tetracycline four times a day with a H2-receptor antagonist twice a day (BMT); 89 received one week of metronidazole, lansoprazole, and clarithromycin twice a day (MLC); and 38 received one week of BMT with lansoprazole twice a day (BMT-PPI). Cure rates were: BMT 81% (95% CI 74-89%), MLC 90% (95% CI 84-96%) BMT-PPI 87% (95% CI 81-92%). More patients prescribed a bismuth-based regimen discontinued medications due to side effects compared to MLC (P = 0.049). Nausea was more common for BMT compared to MLC (P = 0.04). In conclusion, treatment of Helicobacter pylori infection with a one-week course of MLC achieves a high rate of cure in clinical practice. Significantly fewer patients prescribed PPI-based therapy discontinue medications due to side effects as compared to bismuth-based triple therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Treatment of uninvestigated dyspepsia with cisapride for patients with negative Helicobacter pylori serologies.

OBJECTIVE: The aim of this study was to compare symptoms for patients with uninvestigated dyspepsia and a negative Helicobacter pylori serology who were treated with cisapride or placebo. METHODS: Helicobacter pylori-seronegative patients with chronic dyspepsia were randomized to receive cisapride 10 mg t.i.d. or placebo t.i.d. for 30 days. Symptom scores were performed 1 month and 3 months after randomization. Outcomes measured were dyspepsia symptom scores and a treatment "success" variable defined as absence of symptoms or decrease in the most severe individual symptom by two grades. RESULTS: A total of 60 patients were randomized; 56 completed the 1-month follow-up and 40 completed the 3-month follow-up interview. The mean score for all patients at the time of entry was 11.0 and declined to 8.3 and 8.2 at 1 and 3 months, respectively, after randomization. At 1 month and 3 months after randomization, there was no significant difference in the number of patients meeting the "success" variable for patients receiving cisapride as compared to placebo. The mean decline in symptom severity scores was not significantly different for patients receiving placebo or cisapride at 1 month (mean, -2.8 vs -3.1; difference = 0.3, p = 0.74) or 3 months (-3.1 vs -2.6, difference = -0.5, p = 0.58) after randomization. CONCLUSIONS: No significant difference in the severity of dyspeptic symptoms was found for patients receiving cisapride as compared to placebo in the setting of uninvestigated dyspepsia and a negative Helicobacter pylori serology.

Administration, Oral↗
PubMed2000

Gastric-juice ammonia assay for diagnosis of Helicobacter pylori infection and the relationship of ammonia concentration to gastritis severity.

OBJECTIVES: To determine the test characteristics of gastric-juice ammonia concentration as measured by an ion-selective electrode and a rapid ammonia detection device for the diagnosis of Helicobacter pylori infection and to assess the relationship between gastric-juice ammonia concentration and the severity of gastritis. METHODS: Patients undergoing upper endoscopy had collection of gastric juice that was tested for ammonia using an ion-selective electrode and a rapid ammonia assay device that uses a pH-indicating membrane. A receiver operating characteristic curve was calculated for ammonia concentration. Severity of gastritis was graded using the Sydney classification (1) and correlated to gastric-juice ammonia concentration. Patients also underwent H. pylori testing by IgG serology, rapid urease testing, and histological special stain. Ammonia testing results were compared with a reference standard of two of three positive tests and with a second reference standard of a positive serology. RESULTS: 73 patients underwent endoscopy and collection of gastric juice. The receiver operating characteristic curve indicated an optimal cutoff value of 5 mM, yielding a sensitivity of 67%, specificity of 93%, positive predictive value of 67%, and negative predictive value of 93% (compared with the combined reference standard). The rapid NH3-testing device yielded a sensitivity of 83%, specificity 63%, positive predictive value 31%, and negative predictive value 95%. The severity of neutrophilic (p = 0.001) and mononuclear cell (p = 0.003) infiltration were significantly correlated with gastric-juice ammonia concentration. CONCLUSIONS: Measurement of gastric-juice ammonia concentration by ion-selective electrode or rapid detection device is a relatively insensitive and nonspecific means of H. pylori diagnosis. Gastritis severity increases with gastric-juice ammonia concentration.

Ammonia↗
PubMed1999

Use of a dried plasma collection card for simplified diagnosis of Helicobacter pylori infection.

OBJECTIVES: To compare testing for Helicobacter pylori IgG antibodies using a dried plasma collection card device with specimens obtained by venepuncture. METHODS: Eighty-four patients underwent testing for H. pylori IgG antibodies by venepuncture and by fingerstick using a single drop of blood placed on each of two dried plasma collection card devices. The correlation of venepuncture results to dried plasma card results was assessed. RESULTS: There was a high degree of correlation of EIA results between venepuncture and dried plasma card specimens (r=0.98). The qualitative result of the first dried plasma card and venepuncture specimen testing differed in 7 of 84 patients and for the second dried plasma card differed in 7 of 82 patients. The first dried plasma card was 93% sensitive and 100% specific and the second was 93% sensitive and 98% specific as compared to the venepuncture result. There was a high degree of correlation between the first and second dried plasma cards (r=0.996). CONCLUSIONS: The dried plasma collection card has adequate sensitivity and excellent specificity as compared to venepuncture specimens and is a feasible alternative for H. pylori IgG antibody testing.

Antibodies, Bacterial↗
PubMed1999

A prospective study of endoscopy in HIV-associated diarrhea.

OBJECTIVE: Diarrhea commonly occurs in persons with human immunodeficiency virus (HIV) infection. The optimal use of endoscopic procedures remains poorly studied for patients with HIV-related diarrhea. The purpose of this study is to compare the diagnostic yield of a complete endoscopic work-up including an esophagogastroduodenoscopy and colonoscopy to a more limited approach of biopsies obtainable by flexible sigmoidoscopy. METHODS: A prospective study of 79 patients with HIV-related diarrhea. Upper endoscopy and colonoscopy were performed with tissue biopsies labelled according to location within the colon or small intestine. RESULTS: A new infection was diagnosed in 22 of 79 patients (28%). Biopsy of the left colon yielded an enteric pathogen in 17 of 22 patients (sensitivity: 77%) and in 15 of 15 patients with cytomegalovirus colitis (sensitivity: 100%). Combined left and right colonic biopsies had a sensitivity of 82%. Combined colonic and terminal ileum biopsies missed no pathogens. Duodenal biopsies yielded no additional pathogens beyond those identified by colonoscopy and terminal ileal biopsy. Patients with a new pathogen diagnosed had significantly lower CD4 lymphocyte counts as compared to patients without a new pathogen (p = 0.001). CONCLUSIONS: For patients with CD4 counts < 100/mm3 and unexplained AIDS-related diarrhea, flexible sigmoidoscopy with biopsy is a sufficiently thorough endoscopic evaluation.

AIDS-Related Opportunistic Infections↗
PubMed1994

Assessment of operative risk in patients undergoing lung resection. Importance of predicted pulmonary function.

OBJECTIVE: To evaluate the ability of preoperative variables to identify patients at increased risk for complications after lung resection and the usefulness of predicted postoperative FEV1 as a marker of risk for adverse outcomes. DESIGN: Prospective analysis of a cohort of patients undergoing pulmonary resection. Complication rates were analyzed according to preoperative pulmonary variables, demographic variables, procedure performed, and predicted postoperative FEV1. Predicted postoperative FEV1 was calculated using a formula estimating the decline in preoperative FEV1 based on the number of bronchopulmonary segments removed during surgery. SETTING: A major teaching hospital and tertiary referral center. PATIENTS: A consecutive series of patients undergoing pulmonary resection. MEASUREMENTS AND MAIN RESULTS: Medical complications were recorded as part of an ongoing clinical database. The overall complication rate was low (17 percent rate of any complication, 1 percent death rate). Univariate predictors of complications included age > or = 60, male sex, history of smoking, a pneumonectomy procedure, and a low predicted postoperative FEV1. Hypercarbia (> or = 45 mm Hg) on preoperative arterial blood gas analysis, desaturation on exercise oximetry (< or = 90 percent), and a preoperative FEV1 less than 1 L were not predictive of complications. When the effect of these variables was controlled for in a multivariate analysis, a low predicted postoperative FEV1 remained the only significant independent predictor of complications. For each 0.2 L decrease in predicted FEV1, the odds ratio for complications was 1.46 (95 percent confidence interval [CI] 1.2 to 1.8). CONCLUSIONS: A low predicted postoperative FEV1 appears to be the best indicator of patients at high risk for complications, and it was the only significant correlate of complications when the effect of other potential risk factors was controlled for in a multivariate analysis. Pulmonary resection should not be denied on the basis of traditionally cited preoperative pulmonary variables, and a prediction of postoperative pulmonary function by a technique of simple calculation may be useful to identify patients at increased risk for medical complications.

Age Factors↗
PubMed1993

Esophageal physiology and pathophysiology.

This article presents the normal physiology of esophageal peristalsis. It discusses current approaches to the diagnosis and treatment of primary disorders of the esophagus, including achalasia, nutcracker esophagus, diffuse esophageal spasm, as well as the secondary disorder, scleroderma.

Esophageal Motility Disorders↗
PubMed1992

A new technique for ureteral stent placement during pregnancy using endoluminal ultrasound.

Endoluminal sonography using the IVUS is a minimally invasive procedure performed using a flexible 6.2F catheter with a 20 megahertz transducer that can easily be passed endoscopically to image the urethra, bladder, ureter and renal pelvis. In the current study, a woman patient in her third trimester of pregnancy with a renal pelvic stone and persistent colic was safely treated with placement of an indwelling ureteral stent. Because it is minimally invasive and does not require the use of roentgenograms, we believe the IVUS will be a useful tool to assist with the management of ureteral colic in patients who are pregnant in whom intervention is required.

Adult↗
PubMed1988

Buffers for the reconstitution of aspartate aminotransferase.

The cofactor activation of the apoenzyme of pig heart cytosolic aspartate aminotransferase was studied in various buffers. Cationic buffers are shown to allow maximal reconstitution in the pH range of 5.0 to 9.0. Anionic buffers made up of mono- and dicarboxylates are found to affect reconstitution in a pH-dependent manner. At low pH, the carboxylates strongly inhibit reconstitution, but at high pH, they show less effect. In contrast, the more potent inhibitor Pi shows the opposite pH profile. Dicarboxylates are considerably more inhibitory than monocarboxylates. Substantial protection against inhibition by a number of carboxylates may be achieved by the addition of sodium chloride.

Animals↗
PubMedDate not supplied

Left ventricular function during respiratory failure.

Indirect measures of left ventricular function were studied in seven patients with respiratory failure secondary to chronic obstructive pulmonary disease to determine if there were a relationship between left ventricular function and treatment of the pulmonary disease. All patients were studied during acute episodes while in respiratory failure having arterial Pco2 (Paco2) values greater than 49 torr with no clinical evidence of left ventricular failure. Indirect methods to evaluate left ventricular function included the use of the Swan-Ganz catheter for pulmonary capillary wedge pressure measurement, systolic time intervals, and cardiac output. There was improvement in left ventricular function with treatment of the respiratory failure manifested by decreases in the wedge pressure and pre-ejection period/left ventricular ejection time ratio, and an increase in the dp/dt/pulmonary capillary wedge pressure with treatment of the chronic obstructive pulmonary disease. The improvement in left ventricular function suggests that there is a depression of left ventricular function in respiratory failure. The depressed function improved with therapy of the lung disease without additional medication directed at cardiac function.

Adult↗