CONTEXT: EGb 761 is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementias is based on positive results from only a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior. OBJECTIVE: To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia. DESIGN: A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study. PATIENTS: Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions. INTERVENTION: Patients assigned randomly to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every 3 months with complete outcome evaluation at 12, 26, and 52 weeks. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC). RESULTS: From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. In the intent-to-treat analysis, the EGbgroup had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a 4-point improvement on the ADAS-Cog, compared with 14% taking placebo (P=.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P=.003). No difference was seen in the CGIC. Regarding the safety profile of EGb, no significant differences compared with placebo were observed in the number of patients reporting adverse events or in the incidence and severity of these events. CONCLUSIONS: EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers in the GERRI.

Activities of Daily Living↗

PubMedDate not supplied

Onset of antidepressant activity: reexamining the structure of depression and multiple actions of drugs.

The question of when antidepressant drugs (AD) initiate significant clinical actions in depressed patients is still unsettled. Findings from early studies on whether there is a lag in the onset of therapeutic actions were in disagreement. More recent results with the selective serotonin reuptake inhibitors (SSRIs) and other new ADs indicate that clinical actions occur within the first 2 weeks. In this paper, evidence from efficacy studies with the ADs is reviewed and the methodologic and conceptual obstacles to achieving definitive results about the onset issue are analyzed. Depression, formerly viewed as a homogenous disorder, is now seen as heterogenous and multifaceted in structure. Such major structural components as anxiety and disturbed psychomotor functioning can be as significant to the core of the disorder as depressed mood itself. Further, the ADs have been shown to act initially on different facets of the clinical disorder which then result in multiple clinical actions, e.g., an initial reduction in anxiety followed by stimulation of motor activity. Data from the NIMH Collaborative Study of the Psychobiology of Depression are used to illustrate: (1) the componential structure of severe depressive disorder; (2) the sequence of change in the major behavioral components of the disorder associated with the tricyclic drugs; (3) the consequent "multiple" onsets of clinical actions; and (4) measurement of the clinical significance and visibility of the early behavioral changes. Recent results describing new behavioral and methodological approaches, the use of early clinical changes to predict outcome, and strategies for designing sound studies of onset are discussed.

Affect↗

PubMedDate not supplied

Adrenomedullary function in depressed patients.

In this paper from the Collaborative Depression Study (CDS)--Biological, a set of data analyses are presented which indicate that depressed states and perhaps depressed mood are associated with a greater activation of the adrenomedullary system than the sympathetic nervous system [as measured by norepinephrine (NE) and normetanephrine excretion]. For the most part this finding of predominant activation of the adrenomedullary system is seen in unipolar and not bipolar patients.

Adrenal Medulla↗

PubMedDate not supplied

Mania. Diagnosis, state measurement and prediction of treatment response.

The phenomenology of the manic state and its response to lithium drug treatment were intensively studied as part of a larger NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression. In view of the weaknesses in current methods for measuring the components of the manic state, a new instrument was developed, the Manic Diagnostic and Severity Scale (MADS). Its sensitivity in diagnosis and in measuring change was compared to other scales already in use. Finally baseline clinical data is presented that suggests that the presence of a "mixed" manic state is a predictor of lack of clinical response to lithium treatment.

Adult↗

PubMedDate not supplied

The use of patch angioplasty to alter the incidence of carotid restenosis following thromboendarterectomy.

Eighty-nine consecutive patients were followed for twelve to twenty-four months after carotid thromboendarterectomy. Forty-seven underwent operations using a standard carotid closure; a second group of forty-two patients had a saphenous vein patch graft applied in closure. The patients were evaluated with carotid duplex scans at regular intervals to evaluate the incidence of early restenosis. Patients with positive duplex scans underwent arterial angiography or digital subtraction angiography. Operative mortality was zero. Twelve late deaths occurred; eleven due to cardiac disease. In the unpatched group, 19.1% of the patients developed significant restenosis (a luminal narrowing of greater than 50%) with only a 2.4% incidence occurring in the patched group, a statistically significant difference (p less that 0.05). There was a higher incidence of symptomatic restenosis in the unpatched group, though the results were not considered significant. Venous patch rupture was seen in three patients who have not been included in the study group. All of these had venous patches harvested from a distal greater saphenous vein site at the ankle. The authors recommend venous patch closure with a thicker patch taken from the proximal saphenous vein at the groin to reduce the incidence of early restenosis and to avoid venous patch rupture. Regular non-invasive evaluation is recommended to detect restenosis with careful clinical follow-up to evaluate neurologic complications.

Aged↗

PubMedDate not supplied

The possibility of passive transport of histamine through biological membranes.

The possibility of transport of free and heparin-bound histamine along the concentration gradient through bimolecular lipid membranes (BLM) and the influence of various factors on it was studied. It was shown that histamine is capable of diffusing through BLM in the form of a singly charged cation. In contrast to histamine, neither heparin nor the histamine-heparin complex (HsHC) penetrates through BLM. It was established that the action of histamine-liberating factors -- increasing the ionic strength to 0.15 and the addition of trypsin to the solution -- on HsHC leads to the appearance of transport of histamine through the BLM as a result of an increase in the concentration of free histamine in solution.

Biological Transport↗