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Biomedical subjects

J A Murray

Publications and source records attributed to J A Murray.

At least 19 recordsLinked to original sources

Supraesophageal reflux: validation of a symptom questionnaire.

OBJECTIVE: To develop and validate a questionnaire for supraesophageal manifestations of reflux (SER) that will facilitate its study in clinical and research settings. STUDY DESIGN: The Supraesophageal Reflux Questionnaire (SERQ) and previously validated Reflux Symptom Index (RSI) were subjected to multiple types of validity testing, including content validity, concurrent validity, reproducibility, and predictive validity. RESULTS: The concurrent validity and reproducibility of both instruments was good to excellent for most items tested. The predictive validity of the SERQ was superior to the RSI when it included the covariates of history of sinusitis, use of over-the-counter antacid medications, age, gender, and body mass index. CONCLUSIONS: The SERQ will serve as both a useful clinical and research tool by offering not only SER symptom information, like the RSI, but also information about the patient's medical history and medication usage that will facilitate use of the SERQ in research protocols. EBM RATING: B-2b.

Antacids↗

Thrombotic thrombocytopenic purpura: aetiology, pathophysiology and treatment.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder whose varied clinical manifestations result from the formation of platelet-rich thrombi within the microvasculature and consequent tissue ischaemia. This review will outline how, in the eighty years since its initial description, scientific discoveries have not only led to a deeper understanding of the fundamental pathophysiology of TTP, but have also contributed to advances in the clinical management of this condition. Current research in this field will hopefully provide the basis for the design and development of novel therapeutic strategies.

Female↗

A rare presentation of zygomycosis (mucormycosis) and review of the literature.

Zygomycosis (mucormycosis) is a rare fungal infection seen most often in association with prolonged neutropenia. Intestinal zygomycosis is extremely rare and difficult to diagnose, but it is important not to miss, because early medical and surgical treatment can improve survival. This report describes a 56 year old woman who developed this infection while receiving chemotherapy for acute lymphoblastic leukaemia. Medical and surgical measures proved unsuccessful because there was a delay in diagnosis and institution of appropriate treatment.

Female↗

Regional differences in oesophageal motor function.

We tested the hypotheses that oesophageal bolus transit and motor function vary regionally, with bolus viscosity and with body position. In healthy volunteers, we measured the bolus head advance time, bolus presence time and bolus transit time in the proximal and distal oesophagus using water and viscous materials. We compared concurrent manometric responses. Bolus head advance time, bolus presence time and bolus transit time were longer in the distal oesophagus during water and viscous swallows in the upright and supine positions. The total bolus head advance time and transit time, measured across the entire oesophageal body, were shorter for water than viscous swallows. The amplitudes of peristaltic pressure waves were lower for viscous swallows, and varied as a function of region. These studies demonstrated true functional differences between the proximal and distal oesophagus using multichannel intraluminal impedance and that the viscosity of the bolus is a determinant of oesophageal function.

Adolescent↗

Review article: the pathophysiology of gastro-oesophageal reflux disease - oesophageal manifestations.

The pathogenesis of gastro-oesophageal reflux disease (GERD) is multifactorial, involving transient lower oesophageal sphincter relaxations (TLESRs) as well as other lower oesophageal sphincter (LES) pressure abnormalities. GERD is associated with a decrease in LES pressure, which can be provoked by factors such as foods (fat, chocolate, etc.), alcohol, smoking and medications. These factors have also been shown to increase TLESRs. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury, which can potentially progress to oesophageal adenocarcinoma in a minority of patients with Barrett's metaplasia. In addition, duodenogastric contents can also contribute to oesophageal injury. Other factors contributing to the pathophysiology of GERD include hiatal hernia, poor oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia has a permissive role in the pathogenesis of reflux oesophagitis by promoting LES dysfunction. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of TLESRs, contributing to postprandial GER. The mucosal defensive factors have an important role in GERD. When excessive acid causes a breakdown in oesophageal epithelial defenses, epithelial resistance may be reduced. Nocturnal GERD is associated with prolonged acid exposure and proximal extent of acid contact, which elevates the risk for oesophageal damage and GERD-related complications. In sum, GERD is a complex problem caused by many factors that are exacerbated when the patient is in the supine position.

Esophageal Sphincter, Lower↗

CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms.

BACKGROUND: The rate of metabolic inactivation of proton-pump inhibitors is determined by polymorphisms of CYP2C19. It is not known if CYP2C19 variant alleles affect responses to proton-pump inhibitor therapy in gastro-oesophageal reflux disease (GERD). AIM: To determine if the CYP2C19 genotype is associated with clinical effectiveness of proton-pump inhibitors during GERD therapy. METHODS: GERD patients undergoing ambulatory gastric and oesophageal pH monitoring were genotyped for CYP2C19 polymorphisms. RESULTS: Sixty subjects were enrolled. Forty-four subjects had two wild-type alleles, 15 had one variant, and one had two variant CYP2C19 alleles. The presence of a variant allele was significantly associated with a lower odds of gastric acid breakthrough during proton-pump inhibitor therapy [odds ratio 5.14, 95% confidence interval (CI) 1.17-22.61]. The presence of a variant allele was not associated with a lower odds of significant oesophageal acid exposure (odds ratio 2.50, 95% CI 0.60-10.52), or the occurrence of symptoms (incidence rate ratio 1.06, 95% CI 0.54-2.06). CONCLUSIONS: These results indicate that factors other than gastric acid secretion are important determinants of reflux in GERD patients. This suggests that CYP2C19 genotype testing will not be useful in proton-pump inhibitor therapy of GERD, except perhaps in identifying patients at risk for hypochlorhydria and consequent hypergastrinemia.

Adult↗

Review article: The diagnosis of coeliac disease.

Coeliac disease is a chronic inflammatory condition associated with small intestinal injury that results in the malabsorption of different nutrients. The damaging factor is gluten present in wheat, barley and rye. The diagnosis relies on the clinical picture of the patient, serological markers for coeliac disease, characteristic findings of small intestinal biopsy and, eventually, clinical improvement on a gluten-free diet. Our strategies for the diagnosis of coeliac disease have changed dramatically within the last 10 years. The advent of serological markers with high sensitivity and specificity is changing our understanding of the disease and its prevalence. Treatment includes a life-long gluten-free diet to prevent the recurrence of symptoms and other potential consequences. Most coeliac disease remains under-diagnosed; the utilization of more accurate serological tests and a greater awareness of its many presentations will aid its identification.

Adult↗

An evaluation of the clinical implications of acid breakthrough in patients on proton pump inhibitor therapy.

BACKGROUND: Some patients with gastro-oesophageal reflux disease continue to experience symptoms despite therapy with proton pump inhibitors. One recently proposed cause is the occurrence of nocturnal acid breakthrough. AIM: : To investigate the relationship between acid breakthrough occurrence (nocturnal and daytime) and refractory symptoms among patients with gastro-oesophageal reflux disease on proton pump inhibitors. METHODS: Fifty-two consecutive patients with persistent symptoms of gastro-oesophageal reflux disease despite proton pump inhibitor therapy underwent 24-h pH study at the Mayo Clinic between January 1 and November 10, 1999. Relevant data were extracted and analysed. RESULTS: Fifty-two patients, 18 males and 34 females, were eligible for the study. The mean age was 53 +/- 2.2 years. Thirty-seven patients (71%) had nocturnal acid breakthrough, and 36 (69%) had daytime acid breakthrough. Sixty per cent of patients experienced both nocturnal and daytime acid breakthrough, whereas 19% had neither. Among those with nocturnal and daytime acid breakthrough, only 36% and 33% of symptoms, respectively, were associated with gastro-oesophageal reflux episodes. The proportion of patients with symptoms and the mean symptom scores were not significantly different between those with and without acid breakthrough. CONCLUSIONS: Gastric acid breakthrough occurs nocturnally and during the daytime in patients on proton pump inhibitor therapy. With less than 36% of refractory symptoms associated with gastro-oesophageal reflux, gastric acid breakthrough cannot explain symptom refractoriness to proton pump inhibitor therapy in a significant majority of patients evaluated by 24-h pH study.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The role of thyroid hormone administration in potential organ donors.

HYPOTHESIS: Levothyroxine sodium therapy should be used in brain-dead potential organ donors to reverse hemodynamic instability and to prevent cardiovascular collapse, leading to more available organs for transplantation. DESIGN: Prospective, before and after clinical study. SETTING: A surgical intensive care unit of an academic county hospital. PATIENTS: During a 12-month period (September 1, 1999, through August 31, 2000), we evaluated 19 hemodynamically unstable patients with traumatic and nontraumatic intracranial lesions, who were candidates for organ donation following brain death declaration. INTERVENTIONS: All patients were resuscitated aggressively for organ preservation by fluids, inotropic agents, and vasopressors. If, despite all measures, the patients remained hemodynamically unstable, a bolus of 1 ampule of 50% dextrose, 2 g of methylprednisolone sodium succinate, 20 U of insulin, and 20 microg of levothyroxine sodium was administered, followed by a continuous levothyroxine sodium infusion at 10 microg/h. RESULTS: There was a significant reduction in the total vasopressor requirement after levothyroxine therapy (mean +/- SD, 11.1 +/- 0.9 microg/kg per minute vs 6.4 +/- 1.4 microg/kg per minute, P =.02). Ten patients (53%) had complete discontinuation of vasopressors. There were no failures to reach organ donation due to cardiopulmonary arrest. CONCLUSIONS: Levothyroxine therapy plays an important role in the management of hemodynamically unstable potential organ donors by decreasing vasopressor requirements and preventing cardiovascular collapse. This may result in an increase in the quantity and quality of organs available for transplantation.

Adult↗

Healing of traumatic diaphragm injuries: comparison of laparoscopic versus open techniques in an animal model.

BACKGROUND: Minimally invasive surgical techniques have become routinely applied to the evaluation and treatment of patients with isolated diaphragmatic injuries due to penetrating trauma. The objective of the study was to compare the healing of diaphragm injuries as determined by macroscopic inspection, histologic appearance, and tensile strength following repair by open suturing, laparoscopic suturing, and laparoscopic stapling techniques in an animal model. METHODS: Using a pig model, three injuries were created and repaired in each hemidiaphragm of five animals, for a total of 30 lacerations. These injuries were repaired using single-layer open repair, single-layer laparoscopic repair, or laparoscopic stapling. After a 6-week healing period the animals were sacrificed. The gross integrity, histologic appearance using H+E and trichrome satins, and tensile strength of each repair were assessed. RESULTS: All injuries were grossly intact without dehiscence or herniation. Histologic examination revealed no difference in the collagen deposition between the three groups. The tensile strengths of each type of repair were similar. CONCLUSION: Laparoscopic techniques used to repair diaphragmatic injuries allow for adequate healing equivalent to open sutured repairs. Simple approximation of the peritoneum with laparoscopic staples allows full-thickness healing of these injuries.

Animals↗

Abdominal vascular injuries: injuries to the aorta.

This article discusses injuries to the abdominal aorta at its supra- and infrarenal positions, focusing on the surgical approaches to abdominal aorta injuries and renal vascular pedicles. The controversy regarding the use of bioprosthetic materials and the coLlective experience with these injuries as reported in the literature are reviewed. Primary renal artery repair versus nephrectomy also is examined.

Aorta, Abdominal↗

"Insignificant" mechanism of injury: not to be taken lightly.

BACKGROUND: Trauma resources should be spent rationally. The mechanism of trauma is used extensively to triage patients to appropriate levels of care. We examine the hypothesis that patients with "insignificant" mechanism of trauma may have major injuries that require expert trauma care. STUDY DESIGN: Over 9 months at a high-volume Level I trauma center, a prospective study was done on patients who sustained ground-level falls (GLF), low-level falls (LLF) from less than 10 feet, or were found down (FD) with no external evidence of significant trauma, and required evaluation by the trauma team. Of 301 patients included, 110 (37%) had GLF, 95 (31%) LLF, and 96 (32%) FD. Our main outcomes measure was significant injuries, defined as visceral or intracranial injuries, long-bone, pelvic, facial, or spinal fractures. RESULTS: One hundred ten patients (37%) had significant injuries, 20 (7%) were admitted to the ICU, 14 (5%) required an operation, and 4 (1%) died. The most common injuries were intracranial and skeletal. Almost all patients were evaluated by CT (95%), but only one-quarter had abnormal findings on it. LLF, age more than 55 years, and the absence of severe intoxication (blood alcohol level of less than 200 mg/dL) were independent risk factors for significant injuries. A statistical prediction model showed that, when all risk factors are present, the probability of significant injuries is 73%; when all risk factors are absent, there is still a 16% chance for significant injuries. Patients with significant injuries had more operations, longer hospital stays, and higher hospitalization costs compared with patients without significant injuries. CONCLUSIONS: Low-energy trauma may produce significant injuries, predominantly intracranial and skeletal. Trauma care providers should be cautious about dismissing such patients based on the trivial mechanism of injury. Patients with LLF who are older than 55 years and not severely intoxicated have a high likelihood for significant injuries. Resources should be spent rationally for patients who do not have these characteristics, because the probability of significant injuries among them is low, but not zero.

Abdominal Injuries↗

Cell cycle controls and the development of plant form.

The relationship between cell division and plant form has long been a battleground for the debate between those proclaiming and disclaiming an important role for cell division in morphogenetic and developmental processes. Recent evidence suggests that cell division and morphogenesis are intimately interconnected, and whereas overall architecture is determined by patterning genes, the elaboration and execution of developmental programmes require proper control of the cell-division cycle.

Cell Cycle↗

Effect of peroxynitrite on motor function of the opossum esophagus.

Nitric oxide (NO*) is a mediator of esophageal motility. Esophageal dysmotility accompanies esophagitis. During inflammation, superoxide and NO* form peroxynitrite (ONOO-), a reactive molecule that alters cellular function. We tested the hypotheses that ONOO- affects esophageal motility and is produced in association with esophagitis. Transverse muscle strips from the opossum esophagus were stimulated by an electrical field, and nitrotyrosine immunoblots were performed. Peroxynitrite, its decomposed form, or NaNO2 relaxed the lower esophageal sphincter (LES) and attenuated the off response. These effects were inhibited by oxyhemoglobin (Hgb). An antagonist of guanylate cyclase, 1H[1,2,4]oxadiazole[4,3]quinoxalin-1-one (ODQ), inhibited the LES relaxation produced by ONOO-. Nitrotyrosine, a footprint for ONOO- production, was detected in inflamed esophagus. These studies support the hypotheses that ONOO alters esophageal motor function and is formed in association with esophagitis. It is possible that some of the esophageal motor dysfunction seen with esophagitis may be related to the formation of ONOO-.

Animals↗