Vascular depression: a new view of late-onset depression

We have suggested that cerebrovascular disease may predispose, precipitate, or perpetuate some late-life depressive syndromes. The mechanisms of "vascular depression" include disruption of cortico-striato-pallido-thalamo-cortical (CSPTC) pathways or their modulating systems. This view is supported by the presentation of vascular depression, which consists of depressive symptoms, cognitive abnormalities, as well as neuroimaging findings that may result from CSPTC impairment. Moreover, clinical and electrophysiological evidence of CSPTC impairment, an abnormality frequently found in patients with vascular depression, appears to be associated with poor response to antidepressant treatment and early relapse and recurrence. The vascular depression hypothesis provides the conceptual background for studies that may have clinical and theoretical impact. Agents influencing dopamine, acetylcholine, and opioid neurotransmitters may be studied in vascular depression, since these are essential neurotransmitters of the frontostriatal circuitry. Drugs used for prevention and treatment of cerebrovascular disease may be shown to reduce the risk for vascular depression or improve its outcomes. The choice of antidepressants in vascular depression may depend on their effect on neurological recovery from ischemic lesions. Finally, identification of specific relationships between specific symptoms, cognitive deficits, and disability may lead to interventions that target the patients' deficits as well as their interactions with psychosocial factors known to contribute to depression. Research can clarify the pathways to vascular depression by focusing on the site of lesion, the resultant brain dysfunction, the presentation of depression and time of onset, and the contribution of nonbiological factors.     

Depression in late life: psychiatric-medical comorbidity

The links between late-life depression and the medical comorbidities that are often associated with it can be divided into two paths. The path from medical illness to depression reflects general mechanisms related to stress, disability, and loss, as well as more specific physiological mechanisms, including those related to subclinical cerebrovascular disease, adverse drug effects, and endocrine/metabolic effects. Similarly the path from depression to medical illness includes general mechanisms related to self-neglect, decreased adherence to medical treatments, maladaptive health-related behaviors, and, possibly, more specific physiological mechanisms including those related to altered endocrine and autonomic functions, in the clinical context, these two paths can interact to constitute a vicious cycle. With further research, it should be possible to translate current understanding in these areas into advances in both basic knowledge and treatments that could initiate virtuous cycles with beneficial effects for both menial and physical health.     

A method for the follow-up of clusters of adverse reproductive outcomes

Clusters of adverse reproductive outcomes are reported with increasing frequency to public health authorities. Most are random events and only a very small proportion is likely due to identifiable environmental agents. Often, a preliminary study confirms the existence of a spatial and temporal excess but no biologically plausible cause is found. These cases require a follow-up of incidence to identify any continuing excess. A conceptually simple fixed window technique of follow up is proposed. The power of the test is mainly influenced by the magnitude of the increase in rate, the number of adverse outcomes selected for observation and the acceptable false alarm rate. This technique has several advantages compared with other currently used methods. From a public health point of view, two important factors are to be considered in setting the parameters of the test: the delay in providing an answer for the community and the availability of resources for conducting environmental investigations.     

SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: ANGIOTENSIN II-INDUCED TYROSINE PHOSPHORYLATION IN MESANGIAL AND VASCULAR SMOOTH MUSCLE CELLS

• 1 Angiotensin II (AngII)-induced, activation of phospholipase C (PLC) and Ca²⁺-dependent Cl^? channels is an important signal transduction pathway for the regulation of vascular smooth muscle cell (VSMC) and glomerular mesangial cell contraction and growth. While AT receptors are traditionally thought to be G-protein coupled to the β isoform of PLC, recent evidence suggests that in some tissues AT receptors may also activate the PLC-γ isoform via tyrosine phosphorylation.
• 2 By western analysis, we identified PLC-γ1 in the above cell types. We found that within 3 min of exposure to 10^?7 mol/L AngII, tyrosine phosphorylation of PLC-γ1 was observed; however, peak response (> 3-fold increase) occurred within 0.5 min. In addition, pre-incubation of these cells with the tyrosine kinase inhibitor genistein blocked the tyrosine phosphorylation of PLC-γ1 by AngII. In contrast, preincubation with the tyrosine phosphatase inhibitor sodium vanadate increased the levels of tyrosine phosphorylation of PLC-γ1. Similar results were found when intracellular levels of 1,4,5-IP₃ were measured after AngII exposure.
• 3 By using patch clamp techniques on cultured rat mesangial cells exposed to AngII, we found that the release of 1,4,5-IP₃-sensitive intracellular Ca²⁺ stores stimulated low conductance Cl^? channels. Preincubation with genistein, abolished the usual 10-fold increase in Cl^? channel activity observed with AngII.
• 4 Therefore, we conclude that in VSMC and glomerular mesangial cells (i) AngII transiently stimulates PLC activity via tyrosine phosphorylation of the γ1 isoenzyme, (ii) tyrosine phosphorylation of PLC-γ1 and production of 1,4,5-IP₃ in response to AngII is dramatically inhibited by tyrosine kinase inhibition and stimulated by tyrosine phosphatase inhibition, (iii) activation of Ca²⁺-dependent Cl^? channels by AngII-induced release of 1,4,5-IP₃-dependent intracellular Ca²⁺ stores is also abolished by tyrosine kinase inhibition. In summary, this AngII-induced signal transduction cascade provides a possible mechanism for both the contractile and growth-stimulating effects of AngII on VSMC and glomerular mesangial cells.

     

Hypertension in the elderly: Age- and disease-related complications and therapeutic implications

Summary Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an aging process on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of muted hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.Proceedings of a symposium held in Atlanta, Georgia on March 2, 1991.     

Diffusion of information about genetic risk within families

Recent developments in genetics are likely to exacerbate the ethical issues in clinical practice, especially with regard to privacy and disclosure of genetic information. To evaluate the behaviour of patients with respect to transmitting carrier information, we undertook a survey of 283 families with a balanced chromosomal rearrangement as a model. In these families, 1816 relatives were considered at risk and 806 of them were karyotyped (44.4%). The percentage of karyotypes performed is significantly related to the number of living children of the index couple, the reason for referral, the nature of the anomaly, the training of the counsellor and the age of the index case. This study shows the limits of the screening of at risk individuals within families, based on the willingness of the patients, and addresses practical and ethical issues around family disclosure in medical genetics.     

Cerebral venous angiomas: Surgery as a mode of treatment for selected cases

Summary Eleven patients with venous angiomas, 6 males and 5 females ranging in age from 4 to 58, are presented. Four patients presented with intracerebral haematoma and 3 patients had associated cavernous angioma, respectively. Patients with intracerebral haematoma had signs and symptoms due to the localication of the haematoma. The other patients presented with headache, seizures, vertigo, ataxia and mental disturbances. Pre-operative diagnosis was based on computerized tomography, magnetic resonance imaging and cerebral angiography. In 9 surgical cases it was confirmed by histopathological examination of operative specimens.After establishing the type, size and location of the lesion decision for operative treatment was made in nine cases, in four of them because of the presence of an intracerebral haematoma and in 5 of them due to severe disability. Eight of these 9 patients recovered completely and one improved. No severe cerebral oedema was encountered after converging medullary veins were excised and main draining veins partially coagulated.In this small series we encountered an unexpectedly large percentage of venous angiomas causing intracerebral haemorrhage which are commonly considered more benign than other vascular malformations. After reviewing previously reported cases of venous angiomas causing intracerebral haemorrhage and severe neurological deficit we think that the term benign is worth reconsidering. We propose a thorough examination of each case of venous angioma and the operative treatment when appropriate taking into account patients state and location of angioma.     

Metallurgical evaluation of the compatibility of surgical clips with their appliers

Summary Five aneurysm clips and their respective appliers (Heifetz, Vari-Angle, McFadden, Scoville, and Yaargil) were tested for the production of small metal shards that could provoke a foreign body reaction or increase the risk of a stresscorrosion failure. Pivot and Vari-Angle-McFadden clips produced numerous large shards, the Scoville clip produced a few fine shards, and the Yaargil and Heifetz clips produced none. Metal shard production due to cold metal transfer is attributed to the abrasive mechanical interaction between clips and appliers made from metals with different degrees of hardness.     

Giant aneurysm of the calloso-marginal artery

A giant aneurysm of the right callosomarginal artery is reported in a 3-month-old child. This location is rare: including our case reported here, only three cases have been described. Clinicoradiological findings are presented and the surgical procedure is illustrated.     

可溶性血管细胞黏附分子1在妊高征发病中的作用

目的　研究可溶性血管细胞黏附分子 1(solublevascularcelladhesionmolecule - 1,sVCAM - 1)在妊高征发病中的作用。方法　用酶联免疫吸附法 (ELISA)测定 6 7例孕妇血清中sVCAM - 1水平 ,其中正常妊娠组 15例 ,妊高征组 5 2例。结果　中、重度妊高征患者血中sV CAM - 1水平显著高于正常妊娠组 (P <0 .0 1) ;轻度妊高征患者与正常妊娠组相比 ,虽无统计学差异 ,但有升高趋势 ;妊高征组产后该指标下降 ,与正常妊娠组比较无显著性差异 (P >0 0 5 )。sVCAM - 1浓度与平均动脉压呈正相关 (r =0 .5 4 2 ,P <0 .0 1)。结论　妊高征患者血中sVCAM - 1水平升高 ,表明内皮细胞损伤在妊高征的发病中起重要作用。