Dysphagia due to triple A syndrome: successful treatment of achalasia by balloon dilatation

Triple A syndrome is a rare autosomal recessive inherited disorder which is characterized by alacrima, adrenal insufficiency, and achalasia. We report on a 14-year old girl with dysphagia, regurgitation, and vomiting since 5 years. At the age of five years an Addison crisis was diagnosed and cortisone substitution was initiated. In addition, the patient had episodes of conjunctivitis. Severe esophagitis and candida infection were diagnosed by esophago-gastro-duodenoscopy and treated with omeprazole and fluconazole. The esophageal barium swallow was typical for achalasia. Medical treatment of achalasia with oral nifedipine resulted only in a partial and temporal improvement. But after seven balloon dilatations dysphagia and nocturnal coughing improved clearly and a remarkable gain of weight could be seen. Direct sequencing showed a homozygous nonsense mutation in exon 11 of the AAAS gene leading to truncation at position 342 of the 546 amino acid protein. CONCLUSION: Triple A syndrome has to be considered in patients with dysphagia. In our patient, the absence of tears since birth followed by adrenal insufficiency were early signs of the triple A syndrome. Balloon dilatation of the esophago-gastric junction is an effective treatment, which can avoid surgical interventions.

Cognitive functioning in the schizophrenia prodrome

In the last decade, there has been an increasing interest in cognitive alterations during the early course of schizophrenia. From a clinical perspective, a better understanding of cognitive functioning in putative at-risk states for schizophrenia is essential for developing optimal early intervention models. Two approaches have more recently been combined to assess the entire course of the initial schizophrenia prodrome: the predictive "basic symptom at-risk" (BS) and the ultra high-risk (UHR) criteria. Basic symptoms are considered to be present during the entire disease progression, including the initial prodrome, while the onset of symptoms captured by the UHR criteria expresses further disease progression toward frank psychosis. The present study investigated the cognitive functioning in 93 subjects who met either BS or UHR criteria and thus were assumed to be at different points on the putative trajectory to psychosis. We compared them with 43 patients with a first episode of psychosis and to 49 help-seeking patient controls. All groups performed significantly below normative values. Both at-risk groups performed at intermediate levels between the first-episode (FE) group and normative values. The UHR group demonstrated intermediate performance between the FE and BS groups. Overall, auditory working memory, verbal fluency/processing speed, and declarative verbal memory were impaired the most. Our results suggest that cognitive impairments may still be modest in the early stages of the initial schizophrenia prodrome and thus support current efforts to intervene in the early course of impending schizophrenia because early intervention may prevent or delay the onset of frank psychosis and thus prevent further cognitive damage.

The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation

PURPOSE: Activation of the double-stranded RNA-activated protein kinase (PKR) leads to the induction of various pathways including the down-regulation of translation through phosphorylation of the eukaryotic translation initiation factor 2alpha (eIF-2alpha). There have been no reports to date about the role of PKR in radiation sensitivity. EXPERIMENTAL DESIGN: A clonogenic survival assay was used to investigate the sensitivity of PKR mouse embryo fibroblasts (MEF) to radiation therapy. 2-Aminopurine (2-AP), a chemical inhibitor of PKR, was used to inhibit PKR activation. Nuclear factor-kappaB (NF-kappaB) activation was assessed by electrophoretic mobility shift assay (EMSA). Expression of PKR and downstream targets was examined by Western blot analysis and immunofluorescence. RESULTS: Ionizing radiation leads to dose- and time-dependent increases in PKR expression and function that contributes to increased cellular radiation resistance as shown by clonogenic survival and terminal nucleotidyl transferase-mediated nick end labeling (TUNEL) apoptosis assays. Specific inhibition of PKR with the chemical inhibitor 2-AP restores radiation sensitivity. Plasmid transfection of the PKR wild-type (wt) gene into PKR(-/-) MEFs leads to increased radiation resistance. The protective effect of PKR to radiation may be mediated in part through NF-kappaB and Akt because both NF-kappaB and Akt are activated after ionizing radiation in PKR+/+ but not PKR-/- cells. CONCLUSIONS: We suggest a novel role for PKR as a mediator of radiation resistance modulated in part through the protective effects of NF-kappaB and Akt activation. The modification of PKR activity may be a novel strategy in the future to overcome radiation resistance.

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

BACKGROUND: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. RESULTS: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. CONCLUSION: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.

Lung volume, breathing pattern and ventilation inhomogeneity in preterm and term infants

BACKGROUND: Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. METHODOLOGY/PRINCIPAL FINDINGS: We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. CONCLUSIONS: Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.

Retention of canopy trees as biological legacies for balancing woody biomass production and biodiversity in managed aspen forests of the Great Lakes Region

Green-tree retention under the conceptual framework of ecological forestry has the potential to provide both biomass feedstock for industry and maintain quality wildlife habitat. I examined the effects of retained canopy trees as biological legacies (“legacy trees”) in aspen (Populus spp.) forests on above-ground live woody biomass, understory plant floristic quality, and bird diversity. Additionally, I evaluated habitat quality for a high conservation priority species, the Golden-winged Warbler (Vermivora chrysoptera). I selected 27 aspen-dominated forest stands in northern Wisconsin with nine stands in each of three legacy tree retention treatments (conifer retention, hardwood retention, and clearcuts or no retention) across a chronosequence (4-36 years post-harvest). Conifer retention stands had greater legacy tree and all tree species biomass but lower regenerating tree biomass than clearcuts. Coniferous but not hardwood legacy trees appeared to suppress regenerating tree biomass. I evaluated the floristic quality of the understory plant assemblage by estimating the mean coefficient of conservatism (C). Mean C was lower in young stands than in middle-age or old stands; there was a marginally significant (p=0.058) interaction effect between legacy tree retention treatment and stand age. Late-seral plant species were positively associated with stand age and legacy tree diameter or age revealing an important relationship between legacy tree retention and stand development. Bird species richness was greatest in stands with hardwood retention particularly early in stand development. Six conservation priority bird species were indicators of legacy tree retention or clearcuts. Retention of legacy trees in aspen stands provided higher quality nest habitat for the Golden-winged Warbler than clearcuts based on high pairing success and nesting activity. Retention of hardwoods, particularly northern red oak (Quercus rubra), yielded the most consistent positive effects in this study with the highest bird species richness and the highest quality habitat for the Golden-winged Warbler. This treatment maintained stand biomass comparable to clearcuts and did not suppress regenerating tree biomass. In conclusion, legacy tree retention can enhance even-aged management techniques to produce a win-win scenario for the conservation of declining bird species and late-seral understory plants and for production of woody biomass feedstock from naturally regenerating aspen forests.

Air charged and microtip catheters cannot be used interchangeably for urethral pressure measurement: a prospective, single-blind, randomized trial

PURPOSE: We determined and compared urethral pressure measurements using air charged and microtip catheters in a prospective, single-blind, randomized trial. MATERIALS AND METHODS: A consecutive series of 64 women referred for urodynamic investigation underwent sequential urethral pressure measurements using an air charged and a microtip catheter in randomized order. Patients were blinded to the type and sequence of catheter used. Agreement between the 2 catheter systems was assessed using the Bland and Altman 95% limits of agreement method. RESULTS: Intraclass correlation coefficients of air charged and microtip catheters for maximum urethral closure pressure at rest were 0.97 and 0.93, and for functional profile length they were 0.9 and 0.78, respectively. Pearson's correlation coefficients and Lin's concordance coefficients of air charged and microtip catheters were r = 0.82 and rho = 0.79 for maximum urethral closure pressure at rest, and r = 0.73 and rho = 0.7 for functional profile length, respectively. When applying the Bland and Altman method, air charged catheters gave higher readings than microtip catheters for maximum urethral closure pressure at rest (mean difference 7.5 cm H(2)O) and functional profile length (mean difference 1.8 mm). There were wide 95% limits of agreement for differences in maximum urethral closure pressure at rest (-24.1 to 39 cm H(2)O) and functional profile length (-7.7 to 11.3 mm). CONCLUSIONS: For urethral pressure measurement the air charged catheter is at least as reliable as the microtip catheter and it generally gives higher readings. However, air charged and microtip catheters cannot be used interchangeably for clinical purposes because of insufficient agreement. Hence, clinicians should be aware that air charged and microtip catheters may yield completely different results, and these differences should be acknowledged during clinical decision making.

Evolution of sleep and sleep EEG after hemispheric stroke

The evolution of subjective sleep and sleep electroencephalogram (EEG) after hemispheric stroke have been rarely studied and the relationship of sleep variables to stroke outcome is essentially unknown. We studied 27 patients with first hemispheric ischaemic stroke and no sleep apnoea in the acute (1-8 days), subacute (9-35 days), and chronic phase (5-24 months) after stroke. Clinical assessment included estimated sleep time per 24 h (EST) and Epworth sleepiness score (ESS) before stroke, as well as EST, ESS and clinical outcome after stroke. Sleep EEG data from stroke patients were compared with data from 11 hospitalized controls and published norms. Changes in EST (>2 h, 38% of patients) and ESS (>3 points, 26%) were frequent but correlated poorly with sleep EEG changes. In the chronic phase no significant differences in sleep EEG between controls and patients were found. High sleep efficiency and low wakefulness after sleep onset in the acute phase were associated with a good long-term outcome. These two sleep EEG variables improved significantly from the acute to the subacute and chronic phase. In conclusion, hemispheric strokes can cause insomnia, hypersomnia or changes in sleep needs but only rarely persisting sleep EEG abnormalities. High sleep EEG continuity in the acute phase of stroke heralds a good clinical outcome.

Visual and spectral analysis of sleep EEG in acute hemispheric stroke

BACKGROUND: Reports on the effects of focal hemispheric damage on sleep EEG are rare and contradictory. PATIENTS AND METHODS: Twenty patients (mean age +/- SD 53 +/- 14 years) with a first acute hemispheric stroke and no sleep apnea were studied. Stroke severity [National Institute of Health Stroke Scale (NIHSS)], volume (diffusion-weighted brain MRI), and short-term outcome (Rankin score) were assessed. Within the first 8 days after stroke onset, 1-3 sleep EEG recordings per patient were performed. Sleep scoring and spectral analysis were based on the central derivation of the healthy hemisphere. Data were compared with those of 10 age-matched and gender-matched hospitalized controls with no brain damage and no sleep apnea. RESULTS: Stroke patients had higher amounts of wakefulness after sleep onset (112 +/- 53 min vs. 60 +/- 38 min, p < 0.05) and a lower sleep efficiency (76 +/- 10% vs. 86 +/- 8%, p < 0.05) than controls. Time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep and total sleep time were lower in stroke patients, but differences were not significant. A positive correlation was found between the amount of SWS and stroke volume (r = 0.79). The slow-wave activity (SWA) ratio NREM sleep/wakefulness was lower in patients than in controls (p < 0.05), and correlated with NIHSS (r = -0.47). CONCLUSION: Acute hemispheric stroke is accompanied by alterations of sleep EEG over the healthy hemisphere that correlate with stroke volume and outcome. The increased SWA during wakefulness and SWS over the healthy hemisphere contralaterally to large strokes may reflect neuronal hypometabolism induced transhemispherically (diaschisis).