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Biomedical subjects

D O'Rourke

Publications and source records attributed to D O'Rourke.

At least 19 recordsLinked to original sources
PubMed2000

Fatal hepatotoxicity after re-exposure to isoflurane: a case report and review of the literature.

A 76-year-old Caucasian woman developed fulminant hepatic necrosis 6 days after an uneventful operation under isoflurane anaesthesia. Laboratory findings included elevated bilirubin, grossly elevated transaminases and prolonged prothrombin time. Radiological investigation showed no evidence of extra-hepatic disease. Serological studies were negative for acute viral hepatitis and autoimmune disease. The patient may have been previously sensitized by exposure to isoflurane 3 years previously but antibodies to tri-fluoro acetate, present in 70% of cases of halothane hepatitis, were not detected in pre-operative or postoperative samples of blood. On the seventh postoperative day the patient died and postmortem examination demonstrated centrilobular necrosis of the liver, with a histological pattern similar to changes associated with halothane hepatitis.

Aged↗
PubMed2000

Cardiopulmonary effects of sevoflurane in Garnett's greater bush baby (Otolemur garnettii).

PURPOSE: A study was conducted to assess the cardiopulmonary and anesthetic effects of sevoflurane anesthesia on Garnett's Greater Bush Baby (Otolemur garnettii). METHODS: Anesthesia was induced in ten animals with 8% sevoflurane and was maintained by use of 2.5% sevoflurane for 30 minutes. Induction and recovery times were recorded. Heart and respiratory rates (RR), end-tidal carbon dioxide concentration (ET CO2), arterial blood pressures, relative arterial blood oxygen saturation (SpO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and pH were monitored. Pre- and poststudy CBC and serum biochemical values were compared. RESULTS: Anesthesia induction was rapid (75+/-8.7 seconds [mean +/- SEM]) and smooth. Heart rate significantly increased initially, then decreased significantly over the remaining 30 minutes. There were no significant changes in RR, SpO2, ETCO2, or arterial blood pressure. The PaO2 values significantly increased in the 10- to 30-minute samples. The PaCO2 values remained steady in the 10- to 30-minute samples. A significant decrease was seen in white blood count, calcium, and total protein (TP) values, compared with values in pre-anesthesia samples. Recovery from anesthesia was smooth and rapid, with extubation at 24+/-5.8 seconds. CONCLUSIONS: At the concentrations used in this study, sevoflurane appears to be a safe and effective agent for induction and maintenance of anesthesia in O. garnettii.

Anesthesia, Inhalation↗
PubMed1999

Cause of in-hospital death in 12,232 consecutive patients undergoing percutaneous transluminal coronary angioplasty. The Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Some deaths after percutaneous coronary angioplasty (PTCA) occur in high-risk situations (eg, shock), whereas others are unexpected and related to procedural complications. To better describe the epidemiologic causes of death after PTCA, we undertook a systematic review of all in-hospital PTCA deaths in Northern New England from 1990 to 1993. METHODS: The medical records of 121 patients who died during their acute hospitalization for PTCA were reviewed with a standardized data extraction tool to determine a mode of death (eg, low output failure, arrhythmia, respiratory failure) and a circumstance of death (eg, death attributable to a procedural complication, preexisting acute cardiac disease). Any death not classified as a procedural complication was reviewed by a committee and the circumstance of death assigned by a majority rule. RESULTS: Low-output failure was the most common mode of death occurring in 80 (66.1%) of 121 patients. Other modes of death included ventricular arrhythmias (10.7%), stroke (4.1%), preexisting renal failure (4.1%), bleeding (2.5%), ventricular rupture (2.5%), respiratory failure (2.5%), pulmonary embolism (1.7%), and infection (1.7%). The circumstance of death was a procedural complication in 65 patients (53.7%) and a preexisting acute cardiac condition in 41 patients (33.9%). Women were more likely to die of a procedural complication than were men. CONCLUSION: Procedural complications account for half of all post-PTCA deaths and are a particular problem for women. Other deaths are more directly related to patient acuity or noncardiac, comorbid conditions. Understanding why women face an increased risk of procedural complications may lead to improved outcomes for all patients.

Age Factors↗
PubMed1999

Percutaneous transluminal coronary angioplasty in the elderly: epidemiology, clinical risk factors, and in-hospital outcomes. The Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: To explore the relation between older age and clinical presentation, procedural success, and in-hospital outcomes among a large unselected population undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Although more elderly patients are receiving PTCA, studies of post-PTCA outcomes among the elderly have been limited by small numbers and exclusive selection criteria. METHODS: Data were collected as a part of a prospective registry of all percutaneous coronary interventions performed in Maine, New Hampshire, and from 1 institution in Massachusetts between October 1989 and December 1993. Comparisons across 4 age groups, (<60, 60 to 69, 70 to 79, and 80 years and above) were performed using chi-square tests, the Mantel-Haenzsel test for trend, and logistic regression. RESULTS: Twelve thousand one hundred seventy-two hospitalizations for PTCA were performed with 507 of them (4%) in persons at least 80 years old. Octogenarians were more likely to be women, have multivessel disease, high-grade stenoses, and complex lesions but were less likely to have hypercholesterolemia, a history of smoking, or have undergone a previous PTCA. In the elderly, PTCAs were more often performed urgently and for unstable syndromes compared with younger age groups. Advancing age is strongly associated with in-hospital death, and among the oldest old with an increased risk of postprocedural myocardial infarction. Despite differing presentation and procedural priority, angiographic success and subsequent bypass surgery did not vary by age. CONCLUSIONS: With the increasing age of the population at large as well as that segment at risk for cardiac revascularization, information about age-associated risks of the procedure, especially the substantially higher risk of death in octogenarians, will be critical for both physicians and patients considering PTCA.

Age Factors↗
PubMed1999

Carcinoid constrictive pericarditis.

A 78 year old man presented with diarrhoea, anorexia, and progressive lower limb oedema. He was in atrial fibrillation and had a right pleural effusion and ascites. Ultrasound of the abdomen and 24 hour urinary hydroxyindoleacetic acid output indicated metastatic carcinoid syndrome. Cardiac catheterisation revealed pericardial constriction, and pericardial exploration showed a greatly thickened pericardium with no evidence of tumour invasion. The patient died within 24 hours of surgery. Necropsy findings were consistent with a diagnosis of constrictive pericarditis secondary to metastatic carcinoid syndrome.

Aged↗
PubMed1998

Examination of determinants for intranuclear localization and transactivation within the RING finger of herpes simplex virus type 1 IE110k protein.

The herpesvirus regulatory protein IE110k possesses a cysteine-rich, RING finger motif required for its role in transactivation and virus replication. IE110k also localizes to subnuclear compartments termed PODs (PML oncogenic domains). Localization to PODs induces redistribution of the proteins associated with this nuclear compartment, including the cellular RING finger protein, PML. Here we construct a series of deletions, RING domain swaps and point mutations to analyse specific requirements within the IE110k RING finger for subnuclear localization, redistribution of PML and transactivation and we examine the relationship between these activities. We find that IE110k localizes to distinct nuclear subdomains that are more numerous than the cellular PODs and that mutation of two residues within a predicted loop of the RING finger, or replacing the IE110k RING finger with a RING finger from a cellular gene abrogates the ability of IE110k to localize to these extra compartments and traps IE110k in the original PODs. We further demonstrate that RING fingers from the cellular genes mdm-2 and Bmi I, when placed within IE110k, alter the nuclear distribution of IE110k, do not transactivate, and do not redistribute PML. We also demonstrate that the majority of wild-type IE110k, like PML, is associated with the nuclear matrix. Although substitutions and deletions within the RING finger abolish transactivation, these mutant proteins remain tightly associated with the matrix. These results further dissect the determinants involved in different aspects of nuclear compartmentalization of IE110k and are discussed in relation to PML, PODs and the IE110k RING finger.

Amino Acid Sequence↗
PubMed1997

Cognitive aspects of recalling and reporting health-related events: Papanicolaou smears, clinical breast examinations, and mammograms.

This paper reports an examination of cognitive processes used by 178 women aged 50 years and older in retrieving information about the frequency with which they received Papanicolaou smears, mammograms, and clinical breast examinations. Women were selected from a health maintenance organization in which they had been enrolled for at least 5 1/2 years. The literature suggested that reporting of regular events such as these kinds of tests is likely to be based on schemas, which is an estimation technique in which events are reported in a format with generic content. Thus, if the procedure is believed to occur annually, the respondent will report receiving five tests in 5 years. The study attempted to evaluate whether use of episodic recall, in which respondents are forced to report individual events, would be more accurate than reports based on estimation using a schema format. The results indicated that most of the errors occurred in Papanicolaou smear reporting, which is consistent with the literature, and that the fewest errors occurred with mammograms. Regardless of the questionnaire format, respondents persisted in using schemas based on the date of annual physical examination. Most reporting errors occurred because the interval between examinations was estimated incorrectly.

Aged↗
PubMed1997

Malignant eccrine spiradenoma with carcinomatous and sarcomatous elements.

A case of a 60 year old man with malignant eccrine spiradenoma involving the perineum is described. Areas of typical eccrine spiradenoma were admixed with carcinomatous and sarcomatous elements. Immunohistochemical and ultrastructural analysis revealed no evidence of epithelial differentiation in the sarcomatous areas. The tumour qualified for the designation carcinosarcoma arising in eccrine spiradenoma. The clinical course was aggressive with rapid development of nodal and pulmonary metastases.

Adenoma, Sweat Gland↗
PubMed1996

Marked improvement in recognition and completion of health care proxies. A randomized controlled trial of counseling by hospital patient representatives.

BACKGROUND: Advance directives provide a means for patients to retain influence on their medical care should decisional capacity be lost. Several studies have now demonstrated that advance directives that are completed in the ambulatory care setting are rarely available and recognized when patients are admitted to the acute care hospital. OBJECTIVE: To evaluate a generalizable model for improving recognition of previously completed advance directives and for promoting appointment of health care proxies in hospitalized patients. METHODS: Hospitalized elderly patients were randomly assigned to receive the intervention or usual care (n = 190). Intervention patients with capacity were counseled by hospital patient representatives about advance directives and encouraged to complete health care proxies. Patients with existing proxies had this information noted in their charts. For patients without capacity, counselors reviewed their charts for proxy documentation and if absent, contacted patients' next of kin and private physicians to determine proxy status. Usual care patients were not contacted by patient representatives. RESULTS: Forty-eight percent of intervention patients completed a new proxy or had a previously completed proxy identified compared with 6% of controls (P < .001). For patients with capacity, 22% of intervention patients had a previously appointed proxy agent identified compared with 6% of controls (P < .001). Thirty-six percent of intervention patients appointed a proxy decision maker compared with 0% of controls (P < .02). For patients without capacity, 31% of intervention patients had previously appointed proxies identified compared with 6% of controls (P < .001). CONCLUSIONS: Counseling by hospital patient representatives is an effective and generalizable means of improving recognition and execution of advance directives in the acute care hospital.

Advance Directives↗
PubMed1996

Flow cytometric analysis does not reliably differentiate benign from malignant phaeochromocytoma.

BACKGROUND AND OBJECTIVE: The differentiation of benign from malignant phaeochromocytoma is difficult. We have examined whether the use of flow cytometric determination of nuclear DNA content would be useful as a predictor of malignant behaviour in patients with phaeochromocytoma as some previous studies had suggested that a diploid cytometric DNA pattern indicated benign disease. DESIGN AND PATIENTS: DNA flow cytometry was performed on phaeochromocytoma tissue from 36 patients (19 female, 17 male; mean age at presentation 39.5 years). The results were correlated with clinical outcome after prolonged follow-up. MEASUREMENTS: DNA histograms were constructed following nuclear suspension analysis. RESULTS: Of 26 patients followed up for more than 5 years after initial removal of primary phaeochromocytoma, three have died from malignant recurrence. In these patients a diploid DNA cytometric pattern was observed in two and an aneuploid pattern in one. Twenty-one patients are still alive. DNA cytometry showed a diploid pattern in the one patient who developed recurrent phaeochromocytoma 4 years after removal of a primary tumour. CONCLUSION: In this study, three of nine patients with an apparently benign diploid cytometric pattern subsequently developed recurrent disease. Routine use of DNA flow cytometry did not reliably differentiate benign from malignant phaeochromocytoma. Prolonged clinical and biochemical follow-up is still necessary for all patients with this condition.

Adult↗
PubMed1996

The Galway Study of Panic Disorder. III. Outcome at 5 to 6 years.

BACKGROUND: The aim was to evaluate long-term outcome of DSM-III-R panic disorder at a mean of 5.3 years following a controlled trial of treatment that included antidepressants and behavioural counselling. METHOD: Sixty-eight (86%) subjects were evaluated by lengthy research interview. RESULTS: Thirty-four per cent recovered and remained well, 46% were minimally impaired and 20% had persistent panic disorder of whom half remained significantly impaired. Anxious-fearful personality dysfunction was the most important predictor of poor outcome, followed by poor clinical status at discharge and inability at baseline to recall vividly the initial panic attack. Those who dropped out from the original trial did badly. CONCLUSIONS: Complete recovery can occur even after many years of severe illness in a large minority of subjects who receive both antidepressants and behavioural counselling in the acute stage of treatment. The comparative prognostic value of personality, severity and chronicity need to be more fully addressed in future studies.

Adult↗
PubMed1996

The Galway Study of Panic Disorder. IV. Temporal stability of diagnosis by present state examination test-retest.

BACKGROUND: A long-term outcome study of DSM-III-R panic disorder included the Present State Examination (PSE) at baseline and follow up five to six years later. METHOD: PSE test-retest and individual within-patient change scores on various PSE syndromes were assessed for consistency with either a categorical view of panic disorder as a stable clinical entity or panic disorder as one facet only of a "general neurotic syndrome'. RESULTS: PSE profile at baseline was virtually identical with that at follow up. Few patients had changed in PSE syndrome diagnosis after five to six years. CONCLUSION: These data, although not conclusive, are supportive of the concept of DSM-III-R panic disorder as a stable clinical entity and are correspondingly difficult to reconcile with the view that panic disorder is but one facet only of a general neurotic syndrome.

Antidepressive Agents, Tricyclic↗
PubMed1995

Identification of a 140 kDa protein of rat presynaptic terminal membranes encompassing the active zones.

A polyclonal antiserum raised against the carboxy-terminal 17 amino acids of the rat p185c-neu (anct) reacted with a 140 kDa polypeptide in membranes of synaptosome fractions from neocortex and hippocampus of 11-day-old and adult rats. The same antiserum reacted with a 185 kDa polypeptide in microsome membranes from rat pheochromocytoma cells (PC12). By light microscopic immunocytochemistry, the anct antibodies against the 140 kDa protein were localized in the neuropile of brain, cerebellum and spinal cord of 11-day-old and adult rats. Especially prominent staining was obtained in the CA2-CA3 zones of the hippocampus, and in the substantia gelatinosa in the spinal cord. The finely granular and diffuse pattern of the immunostain was consistent with synaptic localizations. Interestingly, antibodies against the entire endodomain of p185c-neu (a-Bacneu) were localized in granular structures, probably representing axo-somatic and axo-dendritic synapses, on a subset of pyramidal neurons of the CA3 zone. By immunoelectron terminals in the giant mossy fiber type in the CA3 and CA4 regions. The immunolocalization of the anct antibodies was restricted in segments of the presynaptic membrane facing the synaptic cleft which include the active zone. The identify and function of the 140 kDa membrane protein of rat brain presynaptic terminals, detected by the anct antibodies, is unknown. The 140 kDa protein may be related to p185c-neu, a tyrosine kinase, or to other known or unknown kinases.

Amino Acid Sequence↗
PubMed1995

Sib-based detection of QTLs.

Association and transmission/nontransmission analyses were used in a split sample design to identify disease susceptibility alleles at two loci. Sib-pair analysis on various subsets of the data identified an additional four regions that yielded signals of disease predisposing quantitative trait loci (QTLs). Three of these four regions represented Type I errors. A new simulation indicates that a multiplex sampling strategy would substantially improve QTL detection for this oligogenic transmission model.

Alleles↗
PubMed1995

Inhibition of Helicobacter pylori urease by phenyl phosphorodiamidates: mechanism of action.

Helicobacter pylori urease is a nickel-containing enzyme that hydrolyzes urea to bicarbonate and ammonia. Andrews et al. (J. Am. Chem. Soc. 1986, 108, 7124) have shown that amides and esters of phosphoric acid are slow, tight-binding inhibitors of urease isolated from jack bean. We show that 4-substituted phenyl phosphorodiamidates (4-R-PhOP(=O)(NH2)2) are slow-binding inhibitors of H. pylori urease with no evidence of kinetic saturation. Their second-order rates of inhibition ki are strongly correlated with phenol pKa (e.g. R = NO2, ki = 2.5 x 10(5) M-1s-1; R = OMe, ki = 1.2 x 10(4) M-1s-1). The Bronsted beta for inhibition is 0.4, similar to that of model system SN2(P) reactions. Based on these observations, we suggest that urease inhibition is covalent but reversible, involving a common phosphoacyl enzyme intermediate.

Helicobacter pylori↗
PubMed1995

Point mutations in the herpes simplex virus type 1 Vmw110 RING finger helix affect activation of gene expression, viral growth, and interaction with PML-containing nuclear structures.

Herpes simplex virus type 1 immediate-early protein Vmw110 (also known as ICP0) has been implicated in the control of the balance between the lytic and latent states, but the precise mechanisms by which it exerts its effects are unknown. Vmw110 includes a characteristic zinc binding domain, termed the C3HC4 domain or RING finger, which is essential for its function. The solution structure of a related herpesvirus RING finger domain suggested that an amphipathic alpha helix might be an important functional component of the RING finger. In this paper, we show that the equivalent region of Vmw110 is important for virus growth in tissue culture and for the normal interaction of Vmw110 with nuclear structures which include the PML protein.

Amino Acid Sequence↗