Changes in ocular dimensions and refraction with accommodation

The purpose of this study was to measure the changes in ocular dimensions with accom-modation, with particular reference to the radius of curvature of the posterior surface of the crystalline lens. The increase in power of the eye with accommodation is considered to arise primarily from a decrease in the radius of curvature of the anterior surface of the lens, with the role of the posterior surface somewhat unclear. We measured the axial dimensions (A-Scan ultrasonography), cornea1 radius of curvature (keratometryl, refractive error (auto-refractor) and radii of curvature of the lenticular surfaces (video phakometryl for 11 subjects, mean age 21.2 + 2.6 years, for five levels of ocular accommodation up to 8.00D. At maximum accommodation the mean changes were a decrease in anterior chamber depth of 0.24 mm. an increase in lens thickness of 0.28 mm. a decrease in radius of curvature of the anterior surface of the lens of 4.95 mm and 1.34 mm for the posterior surface. The corres-pondtng increase in power of the lenticular surfaces for an equivalent refractive index of 1.422 for the lens was 5.53 D and 3.10 D for the anterior and posterior surfaces respectively. No significant changes were recorded in axial length or vitreous chamber depth. We conclude that when crystalline lens power is calculated on the basis of an equivalent refractive index, changes in the posterior surface of the lens contribute around one third of the Increase in lens power associated with 8.00 D of ocular accommodation.     

Childhood‐onset schizophrenia/autistic disorder and t(1;7) reciprocal translocation: Identification of a BAC contig spanning the translocation breakpoint at 7q21

Childhood‐onset schizophrenia (COS) is defined by the development of first psychotic symptoms by age 12. While recruiting patients with COS refractory to conventional treatments for a trial of atypical antipsychotic drugs, we discovered a unique case who has a familial t(1;7)(p22;q21) reciprocal translocation and onset of psychosis at age 9. The patient also has symptoms of autistic disorder, which are usually transient before the first psychotic episode among 40–50% of the childhood schizophrenics but has persisted in him even after the remission of psychosis. Cosegregating with the translocation, among the carriers in the family available for the study, are other significant psychopathologies, including alcohol/drug abuse, severe impulsivity, and paranoid personality and language delay. This case may provide a model for understanding the genetic basis of schizophrenia or autism. Here we report the progress toward characterization of genomic organization across the translocation breakpoint at 7q21. The polymorphic markers, D7S630/D7S492 and D7S2410/D7S646, immediately flanking the breakpoint, may be useful for further confirming the genetic linkage for schizophrenia or autism in this region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:749–753, 2000. Published 2000 Wiley‐Liss, Inc.     

Effects of isradipine on intravenous cocaine‐induced cardiovascular response: a pilot study

We examined the effects of isradipine, a dihydropyridine‐class calcium channel antagonist, and effective antihypertensive medication on the pressor effects of cocaine on cardiac function. Using continuous non‐invasive cardiovascular monitoring of heart rate, blood pressure, electrocardiographic recordings, and peripheral oxygen saturation, six healthy cocaine addicts received the following treatments in blinded, crossover fashion: (a) placebo; (b) intravenous cocaine (0·325 mg/kg iv), and (c) isradipine (10 mg p.o.)+cocaine. While cocaine‐taking was associated with a small increase in blood pressure, this effect was not significantly affected by isradipine. Isradipine pretreatment was, however, associated with a significant reflex rise in heart rate following cocaine. Cocaine administration with or without isradipine produced no clinically significant abnormalities of rhythm or conduction on the electrocardiogram and on peripheral oxygen saturation. While these results should be considered preliminary, they do suggest that this isradipine dose and/or dosing strategy does not have a clinically significant cardioprotective effect during cocaine‐taking. Copyright © 1999 John Wiley & Sons, Ltd.     

Targeting autophagy using natural compounds for cancer prevention and therapy

Autophagy, also known as macroautophagy, is a tightly regulated process involved in the stress responses, such as starvation. It is a vacuolar, lysosomal pathway for the degradation of damaged proteins and organelles in eukaryotic cells. Autophagy also plays a key role in various tissue processes and immune responses and in the regulation of inflammation. Over the past decade, three levels of autophagy regulation have been identified in mammalian cells: 1) signaling, 2) autophagosome formation, and 3) autophagosome maturation and lysosomal degradation. Any deregulation of the autophagy processes can lead to the development of diverse chronic diseases, such as diabetes, obesity, cardiovascular disease, neurodegenerative disease, and malignancies. However, the potential role of autophagy in cancer is rather complex and has been associated with both the induction and the inhibition of neoplasia. Several synthetic autophagy modulators have been identified as promising candidates for cancer therapy. In addition, diverse phytochemicals derived from natural sources, such as curcumin, ursolic acid, resveratrol, thymoquinone, and γ-tocotrienol, also have attracted attention as promising autophagy modulators with minimal side effects. In this review, the authors discuss the importance of autophagy regulators and various natural compounds that induce and/or inhibit autophagy in the prevention and therapy of cancer.     

Can intravenous antifungal therapy be safely used in the outpatient parenteral antimicrobial therapy (OPAT) setting?

Outpatient parenteral antimicrobial therapy (OPAT) is an established treatment option for patients with a variety of infections who require a period of intravenous therapy, are clinically stable, and do not require continuous monitoring. Many patients with fungal infections require prolonged therapy due to resistance or intolerance to oral antifungal agents. Despite the widespread use of OPAT by infection specialists, antifungal agents appear infrequently used in this setting. We suggest that with appropriate patient selection, patients with fungal infections could successfully be treated on OPAT.     

Functional MRI registration with tissue‐specific patch‐based functional correlation tensors

Population studies of brain function with resting‐state functional magnetic resonance imaging (rs‐fMRI) rely on accurate intersubject registration of functional areas. This is typically achieved through registration using high‐resolution structural images with more spatial details and better tissue contrast. However, accumulating evidence has suggested that such strategy cannot align functional regions well because functional areas are not necessarily consistent with anatomical structures. To alleviate this problem, a number of registration algorithms based directly on rs‐fMRI data have been developed, most of which utilize functional connectivity (FC) features for registration. However, most of these methods usually extract functional features only from the thin and highly curved cortical grey matter (GM), posing great challenges to accurate estimation of whole‐brain deformation fields. In this article, we demonstrate that additional useful functional features can also be extracted from the whole brain, not restricted to the GM, particularly the white‐matter (WM), for improving the overall functional registration. Specifically, we quantify local anisotropic correlation patterns of the blood oxygenation level‐dependent (BOLD) signals using tissue‐specific patch‐based functional correlation tensors (ts‐PFCTs) in both GM and WM. Functional registration is then performed by integrating the features from different tissues using the multi‐channel large deformation diffeomorphic metric mapping (mLDDMM) algorithm. Experimental results show that our method achieves superior functional registration performance, compared with conventional registration methods.     

The association between antidepressant use and orthostatic hypotension in older people: a matched cohort study

Orthostatic hypotension (OH) is often reported as a significant potential adverse effect of antidepressant use but the association between phasic blood pressure (BP) and antidepressants has not yet been investigated. This cross-sectional study compares continuously measured phasic BP and prevalence of OH in a cohort of antidepressant users ≥50 years compared with an age- and sex-matched cohort not taking antidepressants. OH was defined as a drop in systolic BP ≥ 20 mm Hg or in diastolic BP ≥ 10 mm Hg at 30 seconds after standing, measured using continuous beat-to-beat finometry. Multilevel time × group interactions revealed significantly greater systolic and diastolic BP drop in antidepressant users than nonusers at 30 seconds after stand. The prevalence of OH among antidepressant users was 31% (63/206), compared with 17% in nonusers (X² = 9.7; P = .002). Unadjusted logistic regression models demonstrated that selective serotonin reuptake inhibitor use was associated with OH at an odds ratio of 2.11 (95% confidence interval: 1.25–3.57); P = .005, and this association was not attenuated when covariates including cardiac disease and depressive symptom burden were added. There was no statistically significant association between serotonin noradrenaline reuptake inhibitor or tricyclic antidepressant use and OH in unadjusted models although the study was not powered to detect changes within these subgroups. Older people taking antidepressants have a two-fold higher prevalence of OH than nonusers, highlighting the importance of screening the older antidepressant user for OH and dizziness and rationalizing medications to reduce the risk of falls within this vulnerable cohort.