Intolerance of uncertainty as a mediator of reductions in worry in a cognitive behavioral treatment program for generalized anxiety disorder.

Growing evidence suggests that intolerance of uncertainty (IU) is a cognitive vulnerability that is a central feature across diverse anxiety disorders, including generalized anxiety disorder (GAD). Although cognitive behavioral therapy (CBT) has been shown to reduce IU, it remains to be established whether or not reductions in IU mediate reductions in worry. This study examined the process of change in IU and worry in a sample of 28 individuals with GAD who completed CBT. Changes in IU and worry, assessed bi-weekly during treatment, were analyzed using multilevel mediation models. Results revealed that change in IU mediated change in worry (ab = -0.20; 95% CI [-.35, -.09]), but change in worry did not mediate change in IU (ab = -0.16; 95% CI [-.06, .12]). Findings indicated that reductions in IU accounted for 59% of the reductions in worry observed over the course of treatment, suggesting that changes in IU are not simply concomitants of changes in worry. Findings support the idea that IU is a critical construct underlying GAD.

Trauma Exposure in Anxious Primary Care Patients.

The present study examined rates of trauma exposure, clinical characteristics associated with trauma exposure, and the effect of trauma exposure on treatment outcome in a large sample of primary care patients without posttraumatic stress disorder (PTSD). Individuals without PTSD (N = 1263) treated as part of the CALM program (Roy-Byrne et al., 2010) were assessed for presence of trauma exposure. Those with and without trauma exposure were compared on baseline demographic and diagnostic information, symptom severity, and responder status six months after beginning treatment. Trauma-exposed individuals (N = 662, 53%) were more likely to meet diagnostic criteria for Obsessive Compulsive Disorder and had higher levels of somatic symptoms at baseline. Individuals with and without trauma exposure did not differ significantly on severity of anxiety, depression, or mental health functioning at baseline. Trauma exposure did not significantly impact treatment response. Findings suggest that adverse effects of trauma exposure in those without PTSD may include OCD and somatic anxiety symptoms. Treatment did not appear to be adversely impacted by trauma exposure. Thus, although trauma exposure is prevalent in primary care samples, results suggest that treatment of the presenting anxiety disorder is effective irrespective of trauma history.

Anxiety disorders. How to recognize and treat the medical symptoms of emotional illness.

Anxiety symptoms in older patients frequently coexist with depression, medical illness, and dementia, which complicate diagnosis and treatment. Most anxiety disorders do not begin in later life but are a recurrence or worsening of a pre-existing condition. Anxiety should be considered in any older patient with depressive symptoms or somatic complaints that are not explained by physical examination. Older patients may benefit from cognitive-behavioral therapy and relaxation training. Antidepresants, particularly selective serotonin reuptake inhibitors, are the preferred medical treatment.

Social phobia: prevalence and diagnostic threshold.

This article reviews the literature on the prevalence and demographic features of social phobia in both community and general medical settings. The age at onset of social phobia is examined, as are comorbid conditions. Important differences between social phobia as it appears in the community and in primary care settings are explored. We conclude that social phobia is common and associated with significant impairment in a number of life areas. We discuss the diagnostic threshold of social phobia and potential difficulties in differentiating this disorder from other mental disorders.

Reactivity to interoceptive cues in nocturnal panic.

In this study, patients with panic disorder (PD) who suffered nocturnal panic (NP) attacks were compared with PD patients who never experienced NP attacks and healthy controls. Three tasks were chosen to evaluate attention to cardiac cues, reactivity to induction of respiratory cues, and reactivity to relaxation cues. Relative to healthy controls, PD groups reported more fear of all three tasks and showed more physiological arousal in response to the hyperventilation task. The only task on which the two PD groups differed was the relaxation task, where nocturnal panickers were significantly more distressed. These findings are consistent with the notion that nocturnal panickers are fearful of states involving a diminution of conscious awareness or vigilance.

A truncated cytoplasmic topoisomerase IIalpha in a drug-resistant lung cancer cell line is encoded by a TOP2A allele with a partial deletion of exon 34.

To study the problem of acquired resistance to widely used anti-cancer drugs that target the 170 kDa topoisomerase IIalpha (topo IIalpha), a drug-resistant human small-cell lung cancer cell line, H209/VP, was selected in VP-16. H209/VP cells express reduced levels of the 170 kDa topo IIalpha that is localized normally in the nucleus and also express lower levels of a 160 kDa topo IIalpha-related protein that is located predominantly in the cytoplasm. Band depletion immunoblotting experiments suggest that the H209/VP nuclear 170 kDa topo IIalpha is able to form ternary complexes with DNA and VP-16 in intact cells, but the ability of the cytoplasmic 160 kDa protein to do so is greatly diminished. Sequence analysis of the 3; end of the H209/VP mutant topo IIalpha mRNA and the TOP2A gene indicates that the mRNA is missing 200 nt that corresponds to exon 34 because the partial loss of the minimal 3; splice-acceptor sequence at the beginning of exon 34 results in splicing of exon 33 to exon 35. The protein predicted to be encoded by this mutant mRNA does not contain the COOH-terminal 109 amino acids of the wild-type enzyme that we have demonstrated contain a strongly functional nuclear localization signal sequence. Consequently, our data explain both the size and the cytoplasmic localization of the H209/VP mutant topo IIalpha. The mutant TOP2A allele in H209/VP cells differs from those in previously characterized cell lines with cytoplasmic topo IIalpha and extends the number of types of resistance-associated deletions in this region to 4. These findings indicate that this region of the TOP2A gene may be a hot spot for mutations.

Manipulations of exposure-based therapy to reduce return of fear: a replication.

Using exposure-based treatment for fear of heights, we tested two different manipulations, namely administering blocks of exposure trials on an expanding spaced schedule and varying the nature of the exposure, both of which have been shown to reduce return of fear [Rowe, M. K., & Craske, M. G. (1998a). Effects of an expanding-spaced versus massed exposure schedule on fear reduction and return of fear. Behaviour Research and Therapy, 36, 701-718; Rowe, M. K., & Craske, M. G. (1998b). Effects of varied-stimulus exposure training on fear reduction and return of fear. Behaviour Research and Therapy, 36, 719-734.]. The samples for these two studies included 23 and 34 undergraduates, respectively. Fear was assessed before, immediately after and one month after treatment using self-report and physiological measures. Study hypotheses were not strongly supported, but the manipulations did lead to different responses during treatment. The data suggest that physiological habituation is not necessary for fear reduction. Expanding spaced treatment may have increased generalization, and those in the constant and varied conditions responded to different aspects of the exposure. Reasons for the failure to replicate previous research and ideas for future research are discussed.

Driving simulation study: bilateral array multifocal versus bilateral AMO monofocal intraocular lenses.

PURPOSE: To determine whether differences exist in the driving performance of patients with bilateral Array multifocal intraocular lenses (IOLs) and those with bilateral AMO monofocal IOLs under low-contrast environmental conditions. SETTING: The Iowa Driving Simulator at the Center for Computer Aided Design, the University of Iowa, Iowa City, Iowa, USA. METHODS: This prospective study was a test-operator-masked, parallel-group comparison of the driving performance of 33 bilateral multifocal IOL patients and 33 bilateral monofocal IOL patients from the U.S. Array Multifocal study. Driving performance was evaluated under 3 poor visibility conditions (clear weather at night, clear weather at night in the presence of a glare source, and fog). Measures of performance included recognition rates and distances for signs, as well as detection rates, distances, and avoidance behaviors for hazards. Contrast acuity and sensitivity were also measured to evaluate possible correlations with driving performance. RESULTS: No statistically significant differences between the IOL groups were found in 26 of 30 comparisons (86.7%). The monofocal group performed better than the multifocal group in comparisons in which there were statistically significant differences: the percentage of correctly recognized warning signs at night in clear weather (P = .028), sign recognition distances for guide (P = .030) and warning (P = .036) signs in fog, and the detection distance for 1 of 4 hazards (suitcase; P = .026). Correlation coefficients between driving performance and low-contrast acuity and sensitivity were statistically significant; however, they were low and not likely predictive of driving performance. CONCLUSION: Differences between patients with bilateral multifocal IOLs and those with bilateral monofocal IOLs were detected; however, the results indicate no consistent difference in driving performance and safety.

Structural organization of the human TOP2A and TOP2B genes.

Eucaryotic topoisomerase II is an essential nuclear enzyme involved in processes such as chromosome condensation, chromatid separation, and in the relief of torsional stress that occurs during DNA transcription and replication. In cells from vertebrate species, there are two forms of the enzyme, designated alpha and beta. Human topoisomerase IIalpha (TOP2A) is encoded by the TOP2A gene on chromosome 17q21-22, and human topoisomerase IIbeta (TOP2B) is encoded by the TOP2B gene on chromosome 3p24. The protein products of these two genes are important cellular targets of several drugs widely used in the treatment of many human cancers, and a variety of mutations in TOP2A have been associated with the development of drug resistance. In the present study, we have defined the intron-exon structures of TOP2A and TOP2B. TOP2A is approx. 30kb whereas TOP2B is at least 49kb. TOP2A and TOP2B contain 35 and 36 exons, respectively, and both genes contain a high proportion of class 0 introns. Alignment of the amino-acid sequences of the two proteins indicates that the intron-exon organization of the two genes is highly conserved, except for the regions encoding the extreme NH2 and COOH termini of the proteins. These findings suggest strongly that the vertebrate isoforms evolved by duplication of an ancestral gene. Mutations in TOP2A associated with drug resistance show clustering in exons 12, 13, 19-21 and 34-35. Knowledge of the genomic organization of TOP2A and TOP2B will be useful for detection of mutations in clinical samples from patients with drug-resistant malignant disease.

Information processing in anxiety and depression.

Performance on explicit and implicit memory tasks was compared among non-clinical participants (N = 47) who reported low anxiety and low depression, high anxiety and low depression, or high anxiety and high depression. No differences were found among the groups in explicit memory. Differences in our measure of implicit memory were attributable to higher anxiety, regardless of depression. Increased implicit memory was specific to personally relevant information. The study highlights the need for further exploration of information processing in mixed anxiety and depression.

The "Expected Visual Outcome" (EVO) model: methodology and clinical validation.

PROBLEM: If changes are made to the optics of the eye (e.g., intraocular lens implants, contact lenses, etc.) how will they affect performance on clinical tests of vision? METHOD: A phenomenological method is presented based on in vitro optical transfer function (OTF) and a simple model of human threshold detection. RESULTS: The model is used to predict and the results are compared with clinical data (acuity, contrast sensitivity) obtained from pseudophakic patients implanted with a multifocal intraocular lens (IOL). A good qualitative agreement is found with the clinical data. SIGNIFICANCE: This model predicts the relative change in clinical performance for a given change in the optical components of the human eye. This simple phenomenological model permits numerical prediction of clinical tests and is easily calculable.

Lithium for irritability in post-traumatic stress disorder.

Irritability is often a problem for patients with Post-Traumatic Stress Disorder (PTSD). We describe two cases that illustrate the use of lithium in the treatment of veterans with PTSD who complained of serious problems with irritability or angry outbursts. These cases are discussed in the context of evidence that lithium may be useful in other patients with disorders of impulse control. The evidence linking disorders of anger and impulse control to a dysregulation in neurotransmitter regulation, particularly in serotonergic pathways, supports a psychopharmacologic approach to treatment. These findings should lead to further study of the role of lithium in the treatment of this symptom complex in patients with PTSD.

Phenomenological model for interpreting the clinical significance of the in vitro optical transfer function.

We describe a methodology to predict the outcome of clinical tests caused by changes made to the optical elements of the human eye. This formalism, called the expected visual outcome model, is based on in vitro measurements of the optical transfer function and takes into account a simple model of human threshold performance. The clinical tests under consideration are high-contrast visual acuity and contrast sensitivity. Using the expected visual outcome, we describe a useful performance index called the predicted visual acuity graph, which can be measured clinically. The theoretical results are compared with visual function measured in patients with pseudophakic (multifocal and monofocal) implants.

Effect of extracellular adenosine triphosphate on electrical properties of subconfluent Madin-Darby canine kidney cells.

1. The present study has been performed to test for an influence of extracellular ATP on the potential differences across the cell membrane (PD) in subconfluent MDCK cells utilizing conventional microelectrodes. 2. In the absence of ATP, the mean measured PD was -47.5 +/- 0.3 mV (+/- S.E.M., n = 320). Application of 10 mumol/l ATP leads to rapid (less than 2 s) hyperpolarization of the cell membrane by -18.5 +/- 0.4 mV (n = 221), reduction of input resistance by 14 +/- 1 M omega (n = 106) and increase of the sensitivity of PD to alterations of extracellular potassium. 3. The concentration needed for half-maximal effect (K1/2) of ATP is approximately 0.5 mumol/l. ATP-gamma-S (K1/2 approximately 0.4 mumol/l) aand ADP (K1/2 approximately 0.9 similarly effective, whereas up to 1 mmol/l AMP or adenosine does not significantly alter PD. Application of 10 mumol/l theophylline, 1 mumol/l phentolamine and 10 mumol/l indomethacin does not blunt the hyperpolarizing effect of ATP. 4. The ATP-induced hyperpolarization is completely abolished in the presence of 1 mmol/l quinidine but only incompletely by 0.1 mmol/l quinidine or 1 mmol/l barium. In calcium-free extracellular fluid (1 mmol/l EDTA added) PD is 18.5 +/- 1.7 mV (n = 18). With reduced extracellular calcium, the hyperpolarizing effect of ATP is blunted (-12.3 +/- 1.6 mV, n = 18) and only transient. 5. In conclusion, ATP hyperpolarizes MDCK cells by increasing the potassium conductance. The activation of potassium channels requires calcium.