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Biomedical subjects

D O'Rourke

Publications and source records attributed to D O'Rourke.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

The application of 5-bromodeoxyuridine in the management of CNS tumors.

A variety of clinical reports have described the application of the bromodeoxyuridine labeling index as an adjunct to conventional pathological examination of CNS tumors. This index has proven useful in predicting the clinical outcome associated with many such tumors. Furthermore, because of its efficacy as a radiosensitizing agent, bromodeoxyuridine (and the closely related iododeoxyuridine) has been used in combination with radiation therapy for malignant glial neoplasms, with some encouraging results. Although most studies suggest that bromodeoxyuridine is safe, there is evidence that this compound does have potential side-effects, including the observation that it is a mutagen and carcinogen in some experimental systems. A number of new alternative approaches for predicting the clinical outcome of CNS tumors has been developed based on an increased understanding of their molecular biology. However, until such approaches are better characterized, the clinical application of bromodeoxyuridine will continue to play an important role in predicting the clinical behavior of many CNS tumors.

Brain Neoplasms↗
PubMed1994

Community health nursing in the 1990s--risky business?

The atmosphere in which community health nurses (CHNs) work in city, suburban, and rural neighborhoods has become increasingly dangerous. Using Neuman's Systems Theory, four graduate students surveyed CHNs from three certified home health agencies to ascertain the real and perceived safety risks which these workers face daily. The response from all three agencies was similar as the nurses identified several situations in which they felt that their safety was compromised. As a result of the information gathered, a Community Risk-Reduction Plan was formulated.

Community Health Nursing↗
PubMed1994

Transcranial Doppler sonography in headache-free migraineurs.

We used transcranial Doppler ultrasonography to determine whether intracranial blood velocities in 182 headache-free migraineurs (60 with aura, 122 without aura) differed from velocities in 38 nonheadache prone control subjects. During the headache-free period, migraineurs with and without aura had significantly elevated mean velocities in all intracranial arteries except the right internal carotid artery at the level of the siphon. Velocities in migraineurs with aura did not differ significantly from velocities in those without aura. Markedly increased velocities were noted in a subset of interictal migraineurs. Two explanations are possible: 1) Blood flow velocities may increase in response to a decrease in the cross sectional area of a vessel at or near the point of insonation. 2) Alterations at the level of the cerebral arteriole may affect regional cerebral blood flow, thereby changing blood flow velocities at the point of insonation. Transcranial Doppler sonography alone cannot sort out which process is responsible for the vascular response. This work may have therapeutic as well as diagnostic implications. When interictal flow velocities are markedly increased, it is possible that therapeutic agents with vasoconstrictor action might cause an excessive response. Further study is needed to clarify the sites of vasoreactivity as well as the magnitude of drug-induced vasoconstrictor response.

Adult↗
PubMed1993

Mutually exclusive binding of two cellular factors within a critical promoter region of the gene for the IE110k protein of herpes simplex virus.

We have examined the cis- and trans-acting factors involved in constitutive transcription of the promoter for the IE110k protein of herpes simplex virus type 1. Our results indicate that while the IE110k gene is activated by Vmw65, it also exhibits very efficient constitutive expression approximating that from the simian virus 40 early enhancer-promoter region. We show that despite the presence of multiple copies of the octamer consensus site which mediate Oct-1 binding and subsequent Vmw65 activation, these upstream sequences have a minor effect on constitutive transcription. By progressive exonuclease digestion and subsequent site-directed mutagenesis of the promoter, we have identified a 15-bp region (termed the EC region), from position -89 to -74, which is required for efficient constitutive expression from the IE110k promoter. We demonstrate that two cellular proteins interact with this region and, by competition and methylation interference analyses, show they have distinct but overlapping sequence requirements for binding. One of these proteins is identified as NF-Y, a CCAAT box-binding factor, which binds an inverted CCAAT box located between positions -71 and -75. The second cellular factor, F2, appears to be novel and binds a region with the sequence CGCGCGGC CAT which overlaps the 3' end of the CCAAT box. The terminal AT of the recognition site for F2 represents, on the opposite strand, the terminal AT of the CCAAT box, and these and adjacent bases are critically required for the binding of both factors. These results together with further competition analysis indicate that these factors bind in a mutually exclusive manner to the EC region. The implications of these results for regulation of expression of the IE110k gene are discussed.

Animals↗
PubMed1992

The Galway Study of Panic Disorder. I: Clomipramine and lofepramine in DSM III-R panic disorder: a placebo controlled trial.

Among 79 volunteer, unpaid, family doctor-referred psychiatric out patients with DSM III-R panic disorder, with and without agoraphobia, 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months. All subjects received one hour per week concurrent behavioural counselling in the acute phase. Of 13 dropouts in the first 3 weeks, 9 (of 27) were on clomipramine, 2 (of 26) were on lofepramine and 2 (of 26) were on placebo. The high (30%) early dropout from the clomipramine group was largely due to medication intolerance. Both drugs were superior to placebo by the end of week 6 on several standard rating scales but not on panic attack frequency. No significant differences in efficacy were found between the two drugs tested to the end of 6 months. No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24. The study provides evidence that both drugs, in the dosages used, are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy.

Adult↗
PubMed1989

Nutrient imbalances in depressive disorders. Possible brain mechanisms.

We examined the utility of d-fenfluramine, a serotonin-releasing drug previously shown to diminish carbohydrate craving and weight gain in obese people, in treating patients with seasonal affective disorder (SAD), a variant of depression that occurs each fall and winter and is usually associated with hyperphagia and carbohydrate craving. Eighteen patients participated in a double-blind, placebo-controlled study in 1986-1987, each receiving, in random order, d-fenfluramine (15 mg p.o. twice daily) or a placebo for four weeks, separated by a two-week washout period. Symptoms of SAD were assessed before and after each treatment period using clinical interviews by a psychiatrist, and the Hamilton Depression Rating Scale (HDS) with a special SAD addendum (ADD). Subjects were also weighed. Patients' depression scores (mean +/- SEM) were identical before treatment with drug (20.9 +/- 1.3, HDS: 13.3 +/- 0.8 ADD) or placebo (21.4 +/- 1.2, HDS; 13.2 +/- 0.6 ADD). During placebo treatment, HDS scores declined by 22.6% (p less than 0.02) and ADD scores by 9% (p greater than 0.2). During d-fenfluramine treatment, HDS scores fell by 71% (p less than 0.0001) and ADD scores by 73% (p less than 0.0001). Thirteen of the subjects (72%) demonstrated complete reversal of their abnormal test scores on d-fenfluramine. In two others, test scores fell to normal levels with both the drug and its placebo; one subject responded only to placebo; and two failed to show therapeutic responses to either drug or placebo treatment. The group as a whole lost weight (1.2 kg) on d-fenfluramine (p less than 0.033) but not on placebo. A subsequent study on nine of the responders showed that improvements persisted for the full three-month duration of the SAD season. These results indicate that d-fenfluramine, a drug not previously identified as an antidepressant, may be useful in treating SAD. Moreover, since d-fenfluramine acts specifically to enhance serotonin-mediated neurotransmission, the data further suggest that serotonin is involved in both the affective and appetitive symptoms of SAD. Indeed, the carbohydrate craving of these patients may constitute a kind of substance abuse in which the nutrient is eaten precisely for its serotonin-mediated psychotropic effects.

Adult↗
PubMed1989

Treatment of seasonal depression with d-fenfluramine.

Eighteen patients with seasonal affective disorder (SAD) participated in a double-blind, placebo-controlled crossover study in 1986-1987. Each received, in random order, d-fenfluramine (15 mg p.o. twice daily)-a serotonin-releasing drug previously shown to suppress carbohydrate craving-or a placebo; these were given for 4 weeks separated by a 2-week washout period. Symptoms were assessed by means of clinical interviews and the Hamilton Rating Scale for Depression (HAM-D) with a special SAD addendum (AAD). Patients were also weighed. Depression scores (mean +/- SE) were identical before treatment with drug (20.9 +/- 1.3, HAM-D; 13.3 +/- 0.8, AAD) or placebo (21.4 +/- 1.2, HAM-D: 13.2 +/- 0.6, AAD). During placebo treatment, mean HAM-D scores declined by 22% (p less than .02) and AAD scores by 9% (p greater than .2). During d-fenfluramine treatment, HAM-D scores fell by 71% (p less than .001) and AAD scores by 73% (p less than .001). Thirteen (72%) of the patients demonstrated complete reversal of their abnormal test scores while taking d-fenfluramine. The group as a whole lost weight (mean = 1.2 kg) while receiving d-fenfluramine (p less than .033) but not when taking placebo. A second study, conducted in 1987-1988 with nine subjects who had previously responded to d-fenfluramine, showed that the drug remains effective for the full 3-month annual period of symptoms. These results indicate that d-fenfluramine may be useful in treating SAD and suggest that serotonin is involved in both SAD's affective and appetitive symptoms.

Adult↗