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Biomedical subjects

J R Walker

Publications and source records attributed to J R Walker.

At least 73 records · Page 4Linked to original sources

Paroxetine in the treatment of generalized social phobia: open-label treatment and double-blind placebo-controlled discontinuation.

We conducted an 11-week forced-escalation open-label study of paroxetine in the treatment of 36 patients with generalized social phobia. At the mean dosage of 47.9 +/- 6.2 mg/day, 23 of 30 completers (77%) were deemed responders on the basis of a clinician rating of either "very much improved" or "much improved" on the Clinical Global Impressions scale. Duke Social Phobia Scale ratings declined from 35.5 +/- 13.1 at baseline to 19.7 +/- 17.4 at week 11 (p < 0.0005), and Liebowitz Social Anxiety Scale ratings declined from 75.1 +/- 25.4 at baseline to 37.2 +/- 32.5 at week 11 (p < 0.0005). Sixteen responders were randomized to an additional 12 weeks of either paroxetine (with no dosage change) or placebo (after a taper period) on a double-blind basis. To the best of our knowledge, this is the first controlled medication-discontinuation study in social phobia. One of eight patients randomized to continue paroxetine relapsed versus five of eight patients randomized to placebo. These findings call for a double-blind, placebo-controlled treatment study of paroxetine in generalized social phobia. They also suggest that relapse rates are high if medication is discontinued early and that further study is needed to determine (1) the optimal duration of maintenance pharmacotherapy for social phobia and (2) if specific psychotherapeutic interventions before medication discontinuation may prevent relapse.

Adult↗

Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample.

OBJECTIVE: The authors investigated whether histories of childhood physical or sexual abuse were reported more frequently in a clinical sample of patients with anxiety disorders than in a matched community comparison sample. METHOD: A standardized interview with an extensive series of trauma probes was administered to 125 patients with DSM-IV anxiety disorders (panic disorder, social phobia, or obsessive-compulsive disorder) and to 125 age- and gender-matched subjects drawn from a random community sample. RESULTS: Childhood physical abuse was higher among both men (15.5%) and women (33.3%) with anxiety disorders than among comparison subjects (8.1%). Childhood sexual abuse was higher among women with anxiety disorders (45.1%) than among comparison women (15.4%) and was higher among women with panic disorder (60.0%) than among women with other anxiety disorders (30.8%). CONCLUSIONS: These findings confirm the association between anxiety disorders and reported childhood physical and sexual abuse and extend earlier findings by pointing to a particular association between sexual abuse and panic disorder in women.

Adolescent↗

Social phobia in adults with stuttering.

OBJECTIVE: The authors evaluated features of social anxiety in a group of adult stutterers to explore the soundness of the DSM-IV requirement that social phobia not be diagnosed in patients who stutter if their phobia relates to their stuttering. METHOD: They conducted diagnostic interviews and verbal fluency assessments with 16 consecutive adults seeking speech therapy for stuttering. Patients also completed scales measuring social phobia symptoms and associated disability. RESULTS: When DSM-IV criteria were modified to permit a diagnosis of social phobia if phobic symptoms were clearly excessive in relation to the severity of stuttering, seven of the 16 patients were given a diagnosis of social phobia. All seven identified social anxiety as an important source of role impairment. Three of the seven patients entered cognitive-behavioral group therapy and benefited from this intervention. CONCLUSIONS: Many adults seeking treatment for stuttering have salient difficulties with social anxiety that may prove amenable to cognitive-behavioral interventions. By precluding a diagnosis of social phobia in these patients, DSM-IV may hinder the identification of social anxiety as a source of disability and may limit access to treatment.

Adult↗

Parental benefits, employment, and fertility dynamics.

"This paper investigates the effect of parental benefits on the timing and spacing of births and on employment dynamics of Swedish women. Using microdata on wages and incomes, I estimate a reduced-form multistate duration model of the bivariate life-cycle fertility and employment process. The paper provides an example of the application of empirical procedures to develop and evaluate multistate hazard models. Estimation results are mixed, with estimated wage effects generally consistent with theoretical predications while estimated effects of the benefits are not. The evaluation procedures offer valuable diagnostic information and suggest several avenues for future research."

Birth Intervals↗

What is new with inhaled anesthetics: Part 2.

Since the 1800s, inhaled agents have been administered to produce surgical anesthesia. Although inhaled anesthetics are commonly known to produce a state of sleep, they also influence many physiologic processes. This article explores the pharmacodynamics of the inhaled anesthetics used in current anesthesia practice. Equipped with this knowledge, the PACU nurse will be better prepared to anticipate the nursing care needs of patients recovering from inhaled anesthetics.

Anesthetics, Inhalation↗

Regulation of cytochrome c oxidase subunit mRNA and enzyme activity in rat brain reward regions during withdrawal from chronic cocaine.

A subtractive hybridization and differential screening procedure was used to detect up-regulation of cytochrome c oxidase (CO) subunits I, III, and IV mRNA in the nucleus accumbens (NAc) of rats chronically treated with cocaine. Northern blot analyses of mRNA isolated from individual rats confirmed that CO subunit I was up-regulated by chronic, but not acute, cocaine in two brain regions, the NAc (33%) and caudate-putamen (CP) (35%). CO activity, used as a measure of metabolic activity, was increased by 88% in the NAc, and decreased by 20% in the medial prefrontal cortex (mPFC), the day after chronic treatment was terminated. CO enzyme activity was not regulated in the CP, or in other brain regions not involved in drug reward. CO activity in both the NAc and mPFC showed unique time-dependent patterns of regulation during the week after chronic cocaine treatment.

Animals↗

Mutations in Escherichia coli dnaA which suppress a dnaX(Ts) polymerization mutation and are dominant when located in the chromosomal allele and recessive on plasmids.

Extragenic suppressor mutations which had the ability to suppress a dnaX2016(Ts) DNA polymerization defect and which concomitantly caused cold sensitivity have been characterized within the dnaA initiation gene. When these alleles (designated Cs, Sx) were moved into dnaX+ strains, the new mutants became cold sensitive and phenotypically were initiation defective at 20 degrees C (J.R. Walker, J.A. Ramsey, and W.G. Haldenwang, Proc. Natl. Acad. Sci. USA 79:3340-3344, 1982). Detailed localization by marker rescue and DNA sequencing are reported here. One mutation changed codon 213 from Ala to Asp, the second changed Arg-432 to Leu, and the third changed codon 435 from Thr to Lys. It is striking that two of the three spontaneous mutations occurred in codons 432 and 435; these codons are within a very highly conserved, 12-residue region (K. Skarstad and E. Boye, Biochim. Biophys. Acta 1217:111-130, 1994; W. Messer and C. Weigel, submitted for publication) which must be critical for one of the DnaA activities. The dominance of wild-type and mutant alleles in both initiation and suppression activities was studied. First, in initiation function, the wild-type allele was dominant over the Cs, Sx alleles, and this dominance was independent of location. That is, the dnaA+ allele restored growth to dnaA (Cs, Sx) strains at 20 degrees C independently of which allele was present on the plasmid. The dnaA (Cs, Sx) alleles provided initiator function at 39 degrees C and were dominant in a dnaA(Ts) host at that temperature. On the other hand, suppression was dominant when the suppressor allele was chromosomal but recessive when it was plasmid borne. Furthermore, suppression was not observed when the suppressor allele was present on a plasmid and the chromosomal dnaA was a null allele. These data suggest that the suppressor allele must be integrated into the chromosome, perhaps at the normal dnaA location. Suppression by dnaA (Cs, Sx) did not require initiation at oriC; it was observed in strains deleted of oriC and which initiated at an integrated plasmid origin.

Alleles↗

Cost-effectiveness of home relaxation training for tension headaches.

Taped home relaxation training was evaluated in a single-case replication design across three patients suffering from tension headaches. Data from daily headache diaries indicated that headache frequency decreased substantially for two of the patients. For the third patient who reported almost continual headache pain, intensity was reduced by over 50%. When compared with results of our previous research taped home relaxation training appeared as effective as (and therefore, more cost-effective than) live clinic relaxation training.

Adolescent↗

Panic disorder in patients attending a clinic for vestibular disorders.

In a study of the prevalence of panic and other anxiety disorders in persons with complaints of dizziness, 87 patients referred to a clinic for vestibular disorders completed self-rating measures of anxiety and depression; 32 also underwent a structured diagnostic interview. Thirteen (14.9%) of the patients met the DSM-III-R criteria for panic disorder, agoraphobia, or both. They rated themselves as much more disabled by their dizziness than the patients with no psychiatric disorder. Panic disorder was equally prevalent among patients with and without vestibular disease. In some cases panic disorder may provide an explanation for the dizziness, whereas in others it may be a comorbid condition compounding the disability attributable to the vestibular disorder.

Adult↗

Setting diagnostic thresholds for social phobia: considerations from a community survey of social anxiety.

OBJECTIVE: The goal of this study was to gain a broader perspective on social anxiety in the community than has been achieved by epidemiologic surveys to date. METHODS: The authors conducted a telephone survey of social anxiety among 526 randomly selected respondents in a medium-sized Canadian city. RESULTS: Sixty-one percent of the respondents reported being much or somewhat more anxious than other people in at least one of the seven social situations surveyed. Speaking to a large audience (i.e., public speaking) was the most frequently feared situation (endorsed by 55.0% of the respondents), followed by speaking to a small group of familiar people (24.9%), dealing with people in authority (23.3%), attending social gatherings (14.5%), speaking to strangers or meeting new people (13.7%), and eating (7.1%) or writing (5.1%) in front of others. When the threshold for caseness was systematically modified--by altering the required level of psychosocial interference or distress or by including or excluding subjects with pure public speaking phobia--the rate of "social anxiety syndrome" in the community varied from 1.9% to 18.7%; 7.1% was the prevalence when the criteria were set to conform with DSM-III-R. CONCLUSIONS: Social anxiety is common in the community, but precise delineation of the prevalence of "social phobia" depends heavily on where the diagnostic threshold is set. If DSM-III-R criteria had been applied in previous epidemiologic studies, it is likely that those studies would have documented prevalences of social phobia that are several times as high as the currently accepted rates.

Adolescent↗

Intratester and intertester reliability and validity of measures of innominate bone inclination.

Determination of innominate bone inclination in standing is frequently assessed in postural analysis of subjects. Currently, no goniometer for objective assessment of innominate bone inclination in standing is commercially available. The purpose of this study was to determine the intratester and intertester reliability and validity of measures taken with a pelvic inclinometer. The intraclass correlation coefficient (ICC) for repeated measures of the pelvic inclinometer fixed to a mechanical model was 0.99. The intertester reliability of using the hand-held pelvic inclinometer to determine inclination on a mechanical model was ICC = 0.99. In measures of 20 male subjects by three testers, the ICC for intertester reliability was 0.95 and the range of ICCs for intratester measures was 0.92-0.96. Measures by the inclinometer had a high degree of reliability compared with the criterion roentgenographic measure, ICC = 0.93. Measurement of the inclination of both left and right innominate bones of a subject required only 2 minutes, indicating clinical applicability.

Adult↗

Cognitive-behavioral treatment for panic disorder with gastrointestinal symptoms: a case study.

A 25-year-old woman with a 12-year history of panic disorder with agoraphobia and gastrointestinal symptoms was treated using a cognitive-behavioral program which included: (a) correcting misconceptions about normal bowel functioning, (b) graduated in vivo exposure to internal stimuli which she misinterpreted as precursors of loss of bowel control, (c) graduated in vivo exposure to external stimuli associated with fears of loss of bowel control, (d) establishment of regular eating patterns, and (e) bowel control training. Self-ratings of avoidance and distress, frequency of panic attacks, diazepam use, and negative cognitions decreased with treatment. Treatment gains were maintained at 18-month follow-up. Tailoring of cognitive-behavioral treatment to panic with fears of loss of bowel control was emphasized.

Adult↗

Sleep impairment in patients with social phobia.

Patient reports of sleep difficulty and sleep quality were systematically assessed in 30 nondepressed, untreated patients with the generalized subtype of social phobia and 30 sex-matched and age-comparable healthy control subjects. Sleep characteristics of the preceding month were assessed using a standardized, validated instrument: the Pittsburgh Sleep Quality Index (PSQI). Patients with generalized social phobia reported significantly poorer sleep quality, longer sleep latency, more frequent sleep disturbance, and more severe daytime dysfunction. Global PSQI scores did not differ significantly among social phobia with or without a lifetime history of major depression (48%), comorbid dysthymia (15%), or comorbid avoidant personality disorder (64%). These findings, which are reminiscent of those in other anxiety syndromes such as panic disorder, suggest that disturbed sleep may be a feature of the generalized subtype of social phobia that deserves further clinical and research attention.

Adult↗

Sleep in nondepressed patients with panic disorder: I. Systematic assessment of subjective sleep quality and sleep disturbance.

To systematically assess sleep complaints in panic disorder (PD), the Pittsburgh Sleep Quality Index (PSQI) was administered to 34 untreated patients with DSM-III-R PD and 34 age-matched healthy controls (HC). PD patients reported significantly more impaired sleep than HC as indicated by higher global index scores on the PSQI (6.9 +/- 2.9 versus 3.1 +/- 2.0; p < 0.0001) and on four of seven of its subscales; sleep was worst among those PD patients with a prior history of major depression. Sixty-eight percent of patients with PD reported moderately or severely impaired sleep compared to only 15% of HC (chi 2 = 17.5, p < 0.0005). Twenty-six percent of PD patients--but none of the HC--complained of frequent awakenings in the preceding month because they "could not breathe comfortably" (Fisher's exact test, p < 0.00625). One-month prevalence of sleep panic in the patients was 18%; lifetime prevalence was 68%. Whereas these findings confirm previous reports of frequent sleep complaints in patients with PD, they also raise the possibility that some of the findings might be trait phenomena attributable to a history of mood disorder.

Adult↗

The Escherichia coli DNA polymerase III holoenzyme contains both products of the dnaX gene, tau and gamma, but only tau is essential.

The replicative polymerase of Escherichia coli, DNA polymerase III, consists of a three-subunit core polymerase plus seven accessory subunits. Of these seven, tau and gamma are products of one replication gene, dnaX. The shorter gamma is created from within the tau reading frame by a programmed ribosomal -1 frameshift over codons 428 and 429 followed by a stop codon in the new frame. Two temperature-sensitive mutations are available in dnaX. The 2016(Ts) mutation altered both tau and gamma by changing codon 118 from glycine to aspartate; the 36(Ts) mutation affected the activity only of tau because it altered codon 601 (from glutamate to lysine). Evidence which indicates that, of these two proteins, only the longer tau is essential includes the following. (i) The 36(Ts) mutation is a temperature-sensitive lethal allele, and overproduction of wild-type gamma cannot restore its growth. (ii) An allele which produced tau only could be substituted for the wild-type chromosomal gene, but a gamma-only allele could not substitute for the wild-type dnaX in the haploid state. Thus, the shorter subunit gamma is not essential, suggesting that tau can be substitute for the usual function(s) of gamma. Consistent with these results, we found that a functional polymerase was assembled from nine pure subunits in the absence of the gamma subunit. However, the possibility that, in cells growing without gamma, proteolysis of tau to form a gamma-like product in amounts below the Western blot (immunoblot) sensitivity level cannot be excluded.

Alleles↗

Expression of the Escherichia coli dnaX gene.

The Escherichia coli dnaX gene encodes both the tau and gamma subunits of DNA polymerase III. This gene is located immediately downstream of the adenine salvage gene apt and upstream of orf12-recR, htpG, and adk. The last three are involved in recombination, heat shock, and nucleotide biosynthesis, respectively. apt, dnaX, and orf12-recR all have separate promoters, and the first two are expressed predominantly from those separate promoters. However, use of an RNase E temperature-sensitive mutant allowed the detection of lesser amounts of polycistronic messengers extending from both the apt and dnaX promoters through htpG. Interestingly, transcription of the weak dnaX promoter is stimulated 4- to 10-fold by a sequence contained entirely within the dnaX reading frame. This region has been localized; at least a portion of the sequence (and perhaps the entire sequence) is located within a 31-bp region downstream of the dnaX promoter.

Base Sequence↗

Treatment integrity of relaxation training for tension headaches.

Treatment integrity procedures, generally lacking in previous research, were employed for evaluation of relaxation training for tension headaches. Treatment integrity is the extent to which the therapist implements the relaxation procedure as described, and the degree to which the patients comply with the therapist's instructions. Objective compliance with the home practice of relaxation training was assessed using a microcomputer-based method which required the patient to squeeze a hand control when instructed to tense a muscle. A single-case replication design with three tension headache patients was used. The dependent variables were taken from patients' self-reported daily headache data. Results indicate that: (a) the therapist accurately adhered to the relaxation training protocol; (b) headache frequency decreased in all patients from baseline to 1-year follow-up (improvements ranged from 72.7% to 98.2%); and (c) improvement was greater with higher compliance.

Adult↗

Panic attacks in the nonclinical population: an empirical approach to case identification.

Although self-reports of panic attacks are common among student populations, it is not clear that their panic experiences are actually comparable to those of patients with clinical anxiety disorders. An empirical approach was taken to this problem by using a cluster analysis procedure to identify subjects within two samples of university students who reported panic attack symptom profiles that resembled those of patients with panic disorder. Such empirically defined "clinical" panic attacks were reported by 7.0% and 8.1% of the two samples. This predominantly female group accounted for most of the increased psychopathology that has been reported in previous studies of nonclinical panic.

Adolescent↗