Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Effect of neoadjuvant chemoradiation on preoperative pulmonary physiology, postoperative respiratory complications and quality of life in patients with oesophageal cancer.

BACKGROUND: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer. METHODS: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose-volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship. RESULTS: Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96·8(17·7) to 91·5(20·4) per cent (-3·6(10·6) per cent; P < 0·001), FVC from 104·9(15·6) to 98·1(19·8) per cent (-3·2(11·9) per cent; P = 0·005) and DLCO from 97·6(20·7) to 82·2(20·4) per cent (-14·8(14·0) per cent; P < 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P < 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (P = 0·001). On multivariable analysis, post-treatment DLCO predicted CCI (P = 0·006), respiratory failure (P = 0·020) and reduced physical function in survivorship (P = 0·047). CONCLUSION: These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk.

ANTECEDENTES: El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V20 < 25% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18). RESULTADOS: Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P < 0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P < 0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.

British children's performance on the listening in spatialised noise-sentences test (LISN-S).

Objective: To investigate whether British children's performance is equivalent to North American norms on the listening in spatialised noise-sentences test (LiSN-S). Design: Prospective study comparing the performance of a single British group of children to North-American norms on the LiSN-S (North American version). Study sample: The British group was composed of 46 typically developing children, aged 6-11 years 11 months, from a mainstream primary school in London. Results: No significant difference was observed between the British's group performance and the North-American norms for Low-cue, High-cue, Spatial Advantage and Total Advantage measure. The British group presented a significantly lower performance only for Talker Advantage measure (z-score: 0.35, 95% confidence interval -0.12 to -0.59). Age was significantly correlated with all unstandardised measures. Conclusion: Our results indicate that, when assessing British children, it would be appropriate to add a corrective factor of 0.35 to the z-score value obtained for the Talker Advantage in order to compare it to the North-American norms. This strategy would enable the use of LiSN-S in the UK to assess auditory stream segregation based on spatial cues.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

The influence of dietary supplementation with cranberry tablets on the urinary risk factors for nephrolithiasis.

PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n = 5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p = 0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.

Ireland's recent contribution to the radiological literature; a bibliometric analysis.

The aim of this study was to identify and analyse all articles published by Irish radiology departments in the medical literature since the year 2000. The PubMed database was searched to identify and review all articles published by radiologists based in the Republic of Ireland or Northern Ireland. Citation counts were then obtained and the top ten most cited articles were identified. There were 781 articles published during the study period. Of these, 558 (71%) were published in radiology journals and the remaining 223 (29%) were published in general medical journals. Abdominal radiology was the most represented sub-specialty (33% of all articles). There was a general trend of increased publications per year. Only 75 (9.6%) of articles were collaborative efforts by more than one radiology department. Irish radiology departments have a considerable research output and this has increased since the year 2000. More collaborative research between Irish radiology departments is encouraged.

The use of ultrasonography and digital mammography in women under 40 years with symptomatic breast cancer: a 7-year Irish experience.

BACKGROUND: Breast cancer in women under 40 years of age is rare and typically presents symptomatically. The optimal imaging modality for this patient group is controversial. Most women undergo ultrasonography with/without mammography. Young women typically have dense breasts, which can obscure the features of malignancy on film mammography, however, initial studies have suggested that digital mammography may have a more accurate diagnostic performance in younger women. Ultrasound generally performs well in this age group, although it is poor at detecting carcinoma in situ (DCIS). AIMS: To evaluate the comparative diagnostic performance of ultrasonography and digital mammography in the initial diagnostic evaluation of women under 40 years of age with symptomatic breast cancer. METHODS: Retrospective review of all women under the age of 40 years managed at our symptomatic breast cancer unit from January 2009 to December 2015. RESULTS: There were 120 patients that met the inclusion criteria for this study. The sensitivity of ultrasonography and digital mammography for breast cancer in this patient group was 95.8 and 87.5 %, respectively. The patients with a false negative mammographic examination were more likely to have dense breasts (p < 0.01). Five patients had a false negative ultrasonographic examination, withal of whom were diagnosed with DCIS detected by mammography. CONCLUSION: This study demonstrates the superior sensitivity of ultrasound for breast cancer in women under the age of 40 years, however, the results show that digital mammography has an important complimentary role in the comprehensive assessment of these patients, particularly in the diagnosis of DCIS.

Generalization of temporal order detection skill learning: two experimental studies of children with dyslexia.

The objective of this study was to investigate the phenomenon of learning generalization of a specific skill of auditory temporal processing (temporal order detection) in children with dyslexia. The frequency order discrimination task was applied to children with dyslexia and its effect after training was analyzed in the same trained task and in a different task (duration order discrimination) involving the temporal order discrimination too. During study 1, one group of subjects with dyslexia (N = 12; mean age = 10.9 + or - 1.4 years) was trained and compared to a group of untrained dyslexic children (N = 28; mean age = 10.4 + or - 2.1 years). In study 2, the performance of a trained dyslexic group (N = 18; mean age = 10.1 + or - 2.1 years) was compared at three different times: 2 months before training, at the beginning of training, and at the end of training. Training was carried out for 2 months using a computer program responsible for training frequency ordering skill. In study 1, the trained group showed significant improvement after training only for frequency ordering task compared to the untrained group (P < 0.001). In study 2, the children showed improvement in the last interval in both frequency ordering (P < 0.001) and duration ordering (P = 0.01) tasks. These results showed differences regarding the presence of learning generalization of temporal order detection, since there was generalization of learning in only one of the studies. The presence of methodological differences between the studies, as well as the relationship between trained task and evaluated tasks, are discussed.

Generalization of temporal order detection skill learning: two experimental studies of children with dyslexia

The objective of this study was to investigate the phenomenon of learning generalization of a specific skill of auditory temporal processing (temporal order detection) in children with dyslexia. The frequency order discrimination task was applied to children with dyslexia and its effect after training was analyzed in the same trained task and in a different task (duration order discrimination) involving the temporal order discrimination too. During study 1, one group of subjects with dyslexia (N = 12; mean age = 10.9 ± 1.4 years) was trained and compared to a group of untrained dyslexic children (N = 28; mean age = 10.4 ± 2.1 years). In study 2, the performance of a trained dyslexic group (N = 18; mean age = 10.1 ± 2.1 years) was compared at three different times: 2 months before training, at the beginning of training, and at the end of training. Training was carried out for 2 months using a computer program responsible for training frequency ordering skill. In study 1, the trained group showed significant improvement after training only for frequency ordering task compared to the untrained group (P < 0.001). In study 2, the children showed improvement in the last interval in both frequency ordering (P < 0.001) and duration ordering (P = 0.01) tasks. These results showed differences regarding the presence of learning generalization of temporal order detection, since there was generalization of learning in only one of the studies. The presence of methodological differences between the studies, as well as the relationship between trained task and evaluated tasks, are discussed.

How auditory temporal processing deficits relate to dyslexia.

Studies have shown that dyslexic children present a deficiency in the temporal processing of auditory stimuli applied in rapid succession. However, discussion continues concerning the way this deficiency can be influenced by temporal variables of auditory processing tests. Therefore, the purpose of the present study was to analyze by auditory temporal processing tests the effect of temporal variables such as interstimulus intervals, stimulus duration and type of task on dyslexic children compared to a control group. Of the 60 children evaluated, 33 were dyslexic (mean age = 10.5 years) and 27 were normal controls (mean age = 10.8 years). Auditory processing tests assess the abilities of discrimination and ordering of stimuli in relation to their duration and frequency. Results showed a significant difference in the average accuracy of control and dyslexic groups considering each variable (interstimulus intervals: 47.9 +/- 5.5 vs 37.18 +/- 6.0; stimulus duration: 61.4 +/- 7.6 vs 50.9 +/- 9.0; type of task: 59.9 +/- 7.9 vs 46.5 +/- 9.0) and the dyslexic group demonstrated significantly lower performance in all situations. Moreover, there was an interactive effect between the group and the duration of stimulus variables for the frequency-pattern tests, with the dyslexic group demonstrating significantly lower results for short durations (53.4 +/- 8.2 vs 48.4 +/- 11.1), as opposed to no difference in performance for the control group (62.2 +/- 7.1 vs 60.6 +/- 7.9). These results support the hypothesis that associates dyslexia with auditory temporal processing, identifying the stimulus-duration variable as the only one that unequally influenced the performance of the two groups.

How auditory temporal processing deficits relate to dyslexia

Studies have shown that dyslexic children present a deficiency in the temporal processing of auditory stimuli applied in rapid succession. However, discussion continues concerning the way this deficiency can be influenced by temporal variables of auditory processing tests. Therefore, the purpose of the present study was to analyze by auditory temporal processing tests the effect of temporal variables such as interstimulus intervals, stimulus duration and type of task on dyslexic children compared to a control group. Of the 60 children evaluated, 33 were dyslexic (mean age = 10.5 years) and 27 were normal controls (mean age = 10.8 years). Auditory processing tests assess the abilities of discrimination and ordering of stimuli in relation to their duration and frequency. Results showed a significant difference in the average accuracy of control and dyslexic groups considering each variable (interstimulus intervals: 47.9 ± 5.5 vs 37.18 ± 6.0; stimulus duration: 61.4 ± 7.6 vs 50.9 ± 9.0; type of task: 59.9 ± 7.9 vs 46.5 ± 9.0) and the dyslexic group demonstrated significantly lower performance in all situations. Moreover, there was an interactive effect between the group and the duration of stimulus variables for the frequency-pattern tests, with the dyslexic group demonstrating significantly lower results for short durations (53.4 ± 8.2 vs 48.4 ± 11.1), as opposed to no difference in performance for the control group (62.2 ± 7.1 vs 60.6 ± 7.9). These results support the hypothesis that associates dyslexia with auditory temporal processing, identifying the stimulus-duration variable as the only one that unequally influenced the performance of the two groups.

Cognitive impairment in bipolar disorder in old age: literature review and findings in manic patients.

BACKGROUND: Descriptions of aged patients with bipolar (BP) disorder have commented on cognitive impairments. However, the literature regarding cognitive test performance in this population has apparently been scant. METHOD: 1. We reviewed studies reporting cognitive performance in aged BP patients. 2. We compared the performance of elderly BP manic patients and aged community comparison subjects on the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS). RESULTS: 1. Seven published studies of cognitive measures in aged BP patients were identified. They utilized different assessment methods and addressed different illness states, but they indicate impairments in these patients. 2. In our sample, the manic patients (n=70) had lower MMSE scores and DRS scores than did the comparison subjects (n=37). In these patients, cognitive scores were not significantly associated with Mania Rating Scale scores. LIMITATIONS: The patients in our study were assessed cross-sectionally, and they were treated naturalistically. CONCLUSIONS: Manic or depressed BP elders have impaired cognitive function; in some patients these impairments may persist. Research characterizing these impairments and their clinical implications is warranted.

Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines.

LNCaP lineage-derived human prostate cancer cell lines C4-2 and C4-2B4 acquire androgen independence and osseous metastatic potential in vivo. Using C4-2 and C4-2B4 the goals of the current investigation were 1) to establish an ideal bone xenograft model for prostate cancer cells in intact athymic or SCID/bg mice using an intraosseous route of tumor cell administration and 2) to compare prostate cancer metastasis by administering cells either through intravenous (i.v.) or intracardiac administration in athymic or SCID/bg mice. Subsequent to tumor cell administration, prostate cancer growth in the skeleton was assessed by radiographic bone density, serum prostate-specific antigen (PSA) levels, presence of hematogenous prostate cancer cells and histopathologic evaluation of tumor specimens in the lymph node and skeleton. Our results show that whereas LNCaP cells injected intracardially failed to develop metastasis, C4-2 cells injected similarly had the highest metastatic capability in SCID/bg mice. Retroperitoneal and mediastinal lymph node metastases were noted in 3/7 animals, whereas 2/7 animals developed osteoblastic spine metastases. Intracardiac injection of C4-2 in athymic hosts produced spinal metastases in 1/5 animals at 8-12 weeks post-injection; PC-3 injected intracardially also metastasized to the bone but yielded osteolytic responses. Intravenous injection of either LNCaP or C4-2 failed to establish tumor colonies. Intrailiac injection of C4-2 but not LNCaP nor C4-2B4 cells in athymic mice established rapidly growing tumors in 4/8 animals at 2-7 weeks after inoculation. Intrafemoral injection of C4-2 (9/16) and C4-2B4 (5/18) but not LNCaP (0/13) cells resulted in the development of osteoblastic bone lesions in athymic mice (mean: 6 weeks, range: 3-12 weeks). In SCID/bg mice, intrafemoral injection of LNCaP (6/8), C4-2 (8/8) and C4-2B4 (8/8) cells formed PSA-producing, osteoblastic tumors in the bone marrow space within 3-5 weeks after tumor cell inoculation. A stepwise increase of serum PSA was detected in all animals. Reverse transcription-polymerase chain reaction (RT-PCR) to detect hematogenously disseminated prostate cancer cells could not be correlated to either serum PSA level or histological evidence of tumor cells in the marrow space. We have thus established a PSA-producing and osteoblastic human prostate cancer xenograft model in mice.

Working memory for nonverbal auditory information in dementia of the Alzheimer type.

Previous studies have revealed working memory impairments in individuals with dementia of the Alzheimer type (DAT) using visually and auditorily presented verbal materials, and visually presented nonverbal materials. Based on findings from behavioral and neuropathological studies, impairments in working memory for auditorily presented nonverbal materials have been hypothesized as well. Results of a study conducted by Kurylo, Corkin, Allard, Zatorre, and Growden (1993), however, failed to support this hypothesis. In the current investigation, perception and working memory for nonverbal auditory information (tones) were assessed using same-different discrimination tasks. Participants included individuals with no dementia, very mild DAT, and mild DAT. Unlike the findings from the study conducted by Kurylo and colleagues, our results suggest intact tone perception but a progressive decline in working memory for auditory nonverbal information with advancing DAT. A similar decline was also noted on a task assessing working memory for auditorily presented verbal information.

Environmental cueing may effect performance on a road test for drivers with dementia of the Alzheimer type.

This paper examines the impact of environmental cueing on a road test for persons with dementia of the Alzheimer type (DAT). In an earlier study, we demonstrated the reliability and stability of the Washington University Road Test in a sample of 58 healthy elderly controls and 65 subjects with DAT. We found that dementia adversely affects driving performance even in its mild stages. Here were elaborate on the results of a follow-up road test conducted 1 month after the baseline test (n = 63) explore possible reasons why the stability of the follow-up road test was lower than expected. We conclude that environmental cueing may affect performance on a road test in DAT.

Reliability of the Washington University Road Test. A performance-based assessment for drivers with dementia of the Alzheimer type.

OBJECTIVE: To assess the reliability and stability of a standardized road test for healthy aging people and those with dementia of the Alzheimer type (DAT). DESIGN: A prospective study involving patients with DAT and age-matched healthy controls in which subjects' driving performance was evaluated by several raters in an initial and a follow-up road test. SETTING: Urban medical school and urban highways and streets. SUBJECTS: A convenience sample of 58 controls, 36 subjects with very mild DAT, and 29 subjects with mild DAT. RESULTS: Analysis of road test ability of controls (2 subjects [3%] failed the test), very mild DAT subjects (7 subjects [19%] failed), and mild DAT subjects (12 subjects [41%] failed) disclosed a significant association between driving performance and dementia status (chi 2[4] = 20.65 [N = 123]; P < .001; Kendall tau-b = 0.306). Interrater reliability for assessment of driving performance ranged from kappa = 0.85 to 0.96. One-month test-retest stability on the road test was 0.76 (quantitative scoring) and 0.53 (clinical judgment). CONCLUSIONS: Dementia adversely affects driving performance even in its mild stages, although some persons with DAT seem to drive safely for some time after disease onset. A traffic-interactive, performance-based road test that examines cognitive behaviors provides an accurate and reliable functional assessment of driving ability.

Contribution to heart rate variability by mechanoelectric feedback. Stretch of the sinoatrial node reduces heart rate variability.

BACKGROUND: Heart rate variability is an important prognostic indicator for sudden death. An increased risk of sudden death and arrhythmia is associated with reduced heart rate variability in heart failure. In heart failure, there is also dilatation of the atria, which raises the prospect that there could be some physiological basis to possibly link heart rate variability with atrial dilatation. We therefore investigated whether sustained atrial stretch could modulate heart rate variability directly. METHODS AND RESULTS: Pigs were anesthetized and their hearts exposed. A specially built device stretched the sinoatrial node before and after vagal section and then after administration of propranolol. Stretch of the sinoatrial node decreases heart rate variability in the following ways: The standard deviation of the beat-to-beat interval decreases (4.2 to 2.6 ms; P = .004), and the high-frequency components are reduced (control, 6.5 +/- 2.2 ms2, during stretch, 1.4 +/- 0.3 ms2, P = .003). After section of both vagi, the high-frequency components are reduced by stretch of the sinoatrial node (2.8 +/- 0.9 ms2 for control versus 1.2 +/- 0.3 ms2 during stretch; P = .05). Similarly, after both vagal section and beta-blockade, stretch of the sinoatrial node reduces the high-frequency components (10.6 +/- 3.5 ms2 for control verses 3.0 +/- 1.5 ms2 during stretch; P = .01). CONCLUSIONS: We conclude that stretch of the sinoatrial node reduces high-frequency heart rate variability. This may account in part for the reduced heart rate variability seen in clinical conditions in which the right atrium is dilated, such as congestive cardiac failure.

Cycle length dependence of the electrophysiological effects of increased load on the myocardium.

BACKGROUND: Mechanoelectric feedback, the process by which changes in mechanical activity change the electrophysiology of the myocardium, has been linked to the genesis of arrhythmias. We investigated possible arrhythmogenic mechanisms by measuring changes in steady-state action potential duration and, more particularly, electrical restitution on a transiently applied load change, because action potential recovery may provide clues to arrhythmogenesis. METHODS AND RESULTS: Pigs were anesthetized and their hearts exposed. A snare was placed around the aorta, and the right atrium was paced. Ventricular pressure, monophasic action potential, and segment motion were recorded from the left ventricle. The action potential duration was measured before and during transient aortic occlusion. Electrical restitution curves were constructed from the records obtained during normal loading or during transient aortic occlusion. The degree of shortening of action potential duration on aortic occlusion decreased with decreases in the steady-state beat-to-beat interval (P = .0008). Control restitution curves had the typical configuration, with a rapid initial, usually monotonic, rise toward a plateau. Some curves showed a marginal "supernormal" section. Increased load reduced the action potential duration at the plateau of the restitution curve (9.4 ms, P < .0001) but increased the action potential duration at the start of the restitution curve (8.7 ms, P = .03). Increased loading increased the maximum slope of the electrical restitution curve by 32 ms/100 ms (P = .04). Increased load also increased the supernormal period of the electrical restitution curves. CONCLUSIONS: Mechanoelectric feedback produces changes in rate-dependent electrophysiology, which could favor a matrix conducive to arrhythmogenesis.

Electrical alternans and the onset of rate-induced pulsus alternans during acute regional ischaemia in the anaesthetised pig heart.

OBJECTIVES: Electrical alternans and mechanical alternans are both associated with cardiac ischaemia and in the case of electrical alternans there is a strong link with serious ventricular arrhythmia. We elected to investigate the relationship between electrical and mechanical alternans in control and acutely ischaemic myocardium in the intact porcine heart to determine the nature of their interaction and in particular to determine if abnormal mechanical events play a role in arhythmogenesis as has been suggested in non-ischaemic preparations. METHODS: We used rapid atrial pacing to induce regional mechanical alternans and pulsus alternans before and then at 5-min intervals after the onset of acute ischaemia induced by a 30-min ligation of a diagonal branch of the left anterior descending artery. Regional mechanical activity is measured with epicardial tripodal strain gauges and regional electrical activity is measured using suction-based monophasic action potential electrodes. To test whether alternate stretching of ischaemic segments during pulsus alternans contributed to electrical alternans we simulated pulsus alternans by clamping the proximal aorta on alternate beats. RESULTS: In control areas there was a constant discordant relationship between peak systolic pressure during alternans and action potential duration. In contrast, the ischaemic areas showed electromechanical alternans that was most frequently concordant. Clamping the proximal aorta on alternate beats produced an electrical alternans in control areas but not in the ischaemic area. CONCLUSIONS: Pulsus alternans during acute ischaemia is associated with electrical alternans that can be out of phase in control and ischaemic areas. This could increase electrical dispersion which may be pro-arrhythmic.