Aging and intestinal motility: a review of factors that affect intestinal motility in the aged

Normal aging is associated with significant changes in the function of most organs and tissues. In this regard, the gastrointestinal tract is no exception. The purpose of this review is to detail the important age-related changes in motor function of the various parts of the gastrointestinal tract and to highlight some of the important motility changes that may occur, either in relation to common age-related disorders, or as a result of certain drugs commonly prescribed in the aged. A major confounding factor in the interpretation of motor phenomena throughout the gastrointestinal tract in this age group is the frequent coexistence of neurological, endocrinological and other disease states, which may be independently associated with dysmotility. Overall, current data are insufficient to implicate normal aging as a cause of dysmotility in the elderly. Normal aging is associated with various changes in gastrointestinal motility, but the clinical significance of such changes remains unclear. More important is the impact of various age-related diseases on gastrointestinal motility in the elderly: for example, long-standing diabetes mellitus may reduce gastric emptying in up to 50% of patients; depression significantly prolongs whole-gut transit time; hypothyroidism may prolong oro-caecal transit time; and chronic renal failure is associated with impaired gastric emptying. In addition, various, frequently used drugs in the elderly cause disordered gastrointestinal motility. These drugs include anticholinergics, especially antidepressants with an anticholinergic effect, opioid analgesics and calcium antagonists.     

Neodymium YAG contact laser in the treatment of cancer of the mobile tongue

The aim of this study was to evaluate the usefulness of a contact neodymium YAG laser for the treatment of squamous cell carcinoma (SCC) of the mobile tongue in 35 patients. The TNM stage and histologic grade were as follows: T1, n = 20; T2, n = 11; T3, n = 4; and N0, n = 33; N1, n = 2; G1, n = 20; G2, n = 10; and G3, n = 5. The surgical treatment consisted of a hemiglossectomy or resection with adequate margins in 28 cases, and an ipsilateral neck dissection was also performed in 7 patients. Radiotherapy to a mean tumor dose of 62-64 Gy and an elective dose of 50 Gy to the cervical lymph nodes was given to 14 patients. The radiotherapy was preoperative in 12 patients and postoperative in 2. Tongue resection was easily performed using the contact neodymium YAG laser, with a mean operation time of 31 min and intraoperative bleeding varying from negligible to 100 cm3. During postoperative follow-up no major complications occurred: cases with minor hemorrhage were easily controlled on the ward and 1 patient had a bleed on the 14th postoperative day necessitating hospitalization. The resection was histologically radical in all cases. During follow-up one patient had a local recurrence (T2N0, G3) and four failed in the neck (T1N0 G2, T1N0 G2, T1N0 G2, T2N0 G2), three of whom were successfully salvaged with a neck dissection and radiotherapy. One patient with osteoradionecrosis was diagnosed and treated curatively. Two patients died of their tongue cancer (T2N0 G3, T2N0 G2), 1 died from a second primary tumor (T2N0 G1) and 2 of intercurrent disease with no evidence of cancer; 30 patients (86%) are still alive with no evidence of disease. The function of the tongue in all patients in this sample was good to satisfactory. The major complaint was xerostomia in the irradiated patients. In conclusion, the contact neodymium YAG laser appears to be suitable for resection of T1-T2 SCCs of the oral tongue. In this limited patient sample T stage or grade did not predict failures in the neck. Biologic predictive markers need to be evaluated.     

Behavioral avoidance test for childhood obsessive-compulsive disorder: a home-based observation

Obsessive-compulsive disorder (OCD) is one of the most debilitating of the anxiety disorders. As our knowledge about this childhood condition continues to grow, there is a need for controlled treatment-outcome trials with precise assessments that are sensitive to treatment change, to guide the development of effective interventions. To evaluate the efficacy of a treatment protocol, it is necessary to have reliable and sensitive measures of OCD symptoms, including measures of obsessions, compulsions, and related levels of distress and avoidance. Whilst structured diagnostic interviews, semistructured clinical interviews, and self-report measures have been widely used in the assessment of childhood OCD, related levels of behavioral distress and avoidance have not been measured in treatment-outcome trials. This study investigated the sensitivity of a behavioral avoidance test (BAT), conducted in the home environment, in assessing treatment-outcome effects for children and adolescents with OCD following a 14-week cognitive-behavioral therapy (CBT) family intervention, in comparison to children in an 8-week "waitlist" control group. The results of the current study strongly support the sensitivity of a standardized BAT in assessing treatment-related changes in children and adolescents with OCD. Implications and future directions for research are discussed.     

Diagnostic concordance of ICD-10 personality and comorbid disorders: a comparison of standard clinical assessment and structured interviews in a clinical setting

OBJECTIVE: The diagnosis of personality disorders is one of the most problematic areas in psychiatric diagnosis. Diagnoses are usually made by standard clinical interview, but they have poor reliability. The aim of this study was to compare the concordance in diagnosis between structured assessment tools and assessment as usual in a clinical setting. METHOD: Diagnosis of 33 patients on the International Personality Disorder Examination (IPDE) and the Mini International Neuropsychiatric Interview (MINI) was compared to diagnosis made by standard assessment through clinical interview. RESULTS: There was poor concordance between structured measures and standard assessment by clinical interview, and poor levels of diagnostic sensitivity and specificity on standard assessment. CONCLUSION: Structured measures were more comprehensive, sensitive and specific in diagnosis than standard clinical assessment. Increased diagnostic accuracy is needed for effective understanding and treatment planning for personality disorders.     

Effects of early handling on basal and stress-induced sleep parameters in rats

Exposure of humans and animals to stressful events early in life leads to significant and often permanent behavioural, neuroendocrine and central alterations. Early handling consists of removing the litter from the nest for 15 min/day, from post-natal days 2 to 14 and results in lowered ACTH and corticosterone stress response and reduced anxiety-like and fear behaviours. Stress-induced sleep alterations usually consists of increased sleep time, known as sleep rebound. In the present study, basal and stress-induced sleep pattern of control non-manipulated (CTL) and early handled (EH) adult male rats was investigated. Sleep was evaluated by 21-h polysomnographic recordings (from 10:00 to 07:00 h of the next day) before and after a 1-h session of restraint stress. The results showed that in the first 3 h following stress, both CTL and EH animals exhibited an impairment of sleep, with a reduction of sleep efficiency, duration of slow wave sleep and of paradoxical sleep. On the contrary, time awake and awakening bouts were augmented in this period. Sleep rebound was observed mainly in the dark period of the light-dark cycle. Stress-induced sleep changes were similar between CTL and EH animals for most sleep parameters. However, EH animals exhibited more bouts of paradoxical sleep on the night following stress exposure and longer bouts of paradoxical sleep in the light period that followed restraint stress. These data indicate that stress-induced alterations of sleep in early handled animals are similar to that observed in control animals, except for some parameters related to paradoxical sleep.     

Hypobaric hypoxia modifies constitutive nitric oxide synthase activity and protein nitration in the rat cerebellum

Ischemic hypoxia provokes alterations in the production system of nitric oxide in the cerebellum. We hypothesize that the nitric oxide system may undergo modifications due to hypobaric hypoxia and that may play a role in high altitude pathophysiology. Therefore, changes in the nitric oxide system of the cerebellum of rats submitted to acute hypobaric hypoxia were investigated. Adult rats were exposed for 7 h to a simulated altitude of 8235 m (27000 ft.) and then killed after 0 h or 1, 3, 5 and 10 days of reoxygenation. Nitric oxide synthase calcium-dependent and -independent activity, immunoblotting and immunohistochemistry of neuronal, endothelial, and inducible nitric oxide synthase, and nitrotyrosine were evaluated. Immunoreactivity for neuronal nitric oxide synthase slightly increased in the baskets of the Purkinje cell layer and in the granule cells, after 0 h of reoxygenation, although no changes in neuronal nitric oxide synthase immunoblotting densitometry were detected. Calcium-dependent activity significantly rose after 0 h of reoxygenation, reaching control levels in the following points, and being coincident with a peak of eNOS expression. Nitrotyrosine formation showed significant increments after 0 h and 1 day of reoxygenation. Nitrotyrosine immunoreactivity showed an intracellular location change in the neurons of the cerebellar nuclei and in addition, an appearance of nitration in the soma of the Purkinje cells was detected. No changes in inducible nitric oxide synthase activity, immunoblotting or immunohistochemistry were detected. We conclude that at least part of the nitric oxide system is involved in cerebellum responses to hypobaric hypoxia.     

A Pseudomonas syringae type III effector suppresses cell wall-based extracellular defense in susceptible Arabidopsis plants

Bacterial effector proteins secreted through the type III secretion system (TTSS) play a crucial role in causing plant and human diseases. Although the ability of type III effectors to trigger defense responses in resistant plants is well understood, the disease-promoting functions of type III effectors in susceptible plants are largely enigmatic. Previous microscopic studies suggest that in susceptible plants the TTSS of plant-pathogenic bacteria transports suppressors of a cell wall-based plant defense activated by the TTSS-defective hrp mutant bacteria. However, the identity of such suppressors has remained elusive. We discovered that the Pseudomonas syringae TTSS down-regulated the expression of a set of Arabidopsis genes encoding putatively secreted cell wall and defense proteins in a salicylic acid-independent manner. Transgenic expression of AvrPto repressed a similar set of host genes, compromised defense-related callose deposition in the host cell wall, and permitted substantial multiplication of an hrp mutant. AvrPto is therefore one of the long postulated suppressors of an salicylic acid-independent, cell wall-based defense that is aimed at hrp mutant bacteria.     

Retinal endothelial cells are more susceptible to oxidative stress and increased permeability than brain-derived endothelial cells

Increased vascular permeability and oxidative stress are important in diabetic retinopathy. Because the cerebral microcirculation is much less affected in diabetes, our objectives are to compare: (1) glutathione peroxidase activity, (2) superoxide dismutase levels, (3) superoxide production, and (4) junctional protein (ZO-1) levels between retinal and brain-derived endothelial cells. Bovine brain and retinal endothelial cell cultures are incubated in medium containing either mM or 30 mM glucose for 5 days. Superoxide is measured in the medium and endothelial cells are then lysed and analyzed for glutathione peroxidase activity as well as levels of superoxide dismustase and ZO-1. The results demonstrate that, compared to brain-derived endothelial cells, retinal endothelial cells release high levels of superoxide, have less glutathione peroxidase activity and lower levels of superoxide dismutase, and ZO-1. Also, unlike brain-derived endothelial cells where ZO-1 levels increased in response to glucose, in retinal endothelial cells, ZO-1 levels are unaffected by glucose. These findings suggest that greater oxidative stress and lower junctional protein levels in retinal endothelial cells may contribute to blood/retinal barrier dysfunction in diabetic retinopathy.