Cholesterol lowering therapy inhibits the low-flow mediated vasoconstriction of the brachial artery in hypercholesterolaemic subjects

1 We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia.
2 Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state.
3 Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40  mg orally) in 13 subjects and placebo in 15 others.
4 The significant decrease ( P <0.01) in diameter induced by wrist occlusion before (0.34±0.08  mm) placebo and pravastatin (0.39±0.10  mm) persisted after placebo (0.26±0.07  mm) but was abolished after pravastatin (0.07±0.05  mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin ( P <0.01) and lower after pravastin than after placebo ( P <0.05). Diameter during wrist occlusion was higher after pravastatin than after placebo (4.35±0.16 vs 3.89±0.09  mm); P <0.01).
5 These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol.     

A Comprehensive Approach to the Recognition, Diagnosis, and Severity-Based Treatment of Focal Hyperhidrosis: Recommendations of the Canadian Hyperhidrosis Advisory Committee

BACKGROUND: Hyperhidrosis can have profound effects on a patient's quality of life. Current treatment guidelines ignore disease severity. OBJECTIVE: The objective was to establish clinical guidelines for the recognition, diagnosis, and treatment of primary focal hyperhidrosis. METHODS AND MATERIALS: A working group of eight nationally recognized experts was convened to develop the consensus statement using an evidence-based approach. RECOMMENDATIONS: An algorithm was designed to consider both disease severity and location. The Hyperhidrosis Disease Severity Scale (HDSS) provides a qualitative measure that allows tailoring of treatment. Mild axillary, palmar, and plantar hyperhidrosis (HDSS score of 2) should initially be treated with topical aluminum chloride (AC). If the patient fails to respond to AC therapy, botulinum toxin A (BTX-A; axillae, palms, soles) and iontophoresis (palms, soles) should be the second-line therapy. In severe cases of axillary, palmar, and plantar hyperhidrosis (HDSS score of 3 or 4), both BTX-A and topical AC are first-line therapy. Iontophoresis is also first-line therapy for palmar and plantar hyperhidrosis. Craniofacial hyperhidrosis should be treated with oral medications, BTX-A, or topical AC as first-line therapy. Local surgery (axillary) and endoscopic thoracic sympathectomy (palms and soles) should only be considered after failure of all other treatment options. CONCLUSIONS: These guidelines offer a rapid method to assess disease severity and to treat primary focal hyperhidrosis according to severity.     

Sudden Cardiac Arrest: ECG Repolarization After Resuscitation

Sudden Cardiac Arrest and ECG Repolarization. Introduction: Early repolarization (ERep) abnormalities on electrocardiogram (ECG) are common immediately following cardiac arrest. We characterized and correlated electrocardiographic repolarization abnormalities immediately after cardiac arrest with acute coronary angiography. Methods and Results: We studied 225 consecutive patients presenting with out‐of‐hospital cardiac arrest. All these patients had successful cardiopulmonary resuscitation and acute coronary angiography. The first ECG recorded after successful resuscitation was analyzed by two independent cardiologists. Patients were categorized according to their repolarization pattern.

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Obsessive Compulsive Disorder in a Patient with Twiddler's Syndrome

Twiddler's or twist syndrome is the twisting of pulse generators around themselves. It may result from mechanical manipulation that can induce the malfunction of the device. In this case, twiddler's syndrome resulted from compulsive checking of the device. The implantable cardioverter‐defibrillator (ICD) triggered the development of an obsessive compulsive disorder (OCD). Two invasive procedures were required to replace the ICD. Psychiatric intervention prevented the recurrence of twiddler's syndrome in this patient for more than 2 years. We believe that preimplant psychiatric assessment should be the rule.     

Synthesis of a new dipeptide template,its X-ray structure,and modeling studies on its conformational features

The diastereoselective synthesis is reported of a dipeptide template which is closely related to H-Gly-Trp-OH. Intramolecular bond formation between α-C of Gly and ring position 2 of the Trp unit has been achieved by a Pictet-Spengler-type electrophilic aromatic substitution. The absolute configuration of the N-Moc protected dipeptide template 9·2H₂O was determined by single-crystal X-ray crystallography and found to be (2S,5S). The cis orientation of the amino and carboxy termini prompted us to investigate the potential of 9 as a β-turn mimic. MD calculations on the model pseudopeptide Ac-Ala-Gly-Trp-Ala-NHMe 11 suggest that an unusually tight turn should be favoured rather than a β-turn. The proper protective situation as a prerequisite for the incorporation of the template into a peptide has been established, and comments about its chemical properties are given. © Munksgaard 1995.     

Intracranial topography of event-related potentials (N400/P600) elicited during a continuous recognition memory task

To isolate the anatomical locus of the neural activity most important for generating or modulating the scalp-recorded N400 and P600 components elicited during continuous recognition memory tasks, intracranial event-related potentials (ERPs) were recorded from medial and lateral aspects of the temporal, frontal, parietal, and occipital lobes in 25 patients undergoing stereoelectroencephalography for seizure localization. Large-amplitude and polarity-inverted ERPs were recorded from various temporal, frontal, and parietal structures, whereas the memory-related ERP modulation assessed by the ERP repetition effect was present only in those brain areas that play the most important role in memory processing. These data suggest that the scalp-recorded N400 and P600 components may represent the most readily observable aspect of synchronous activity occurring across widely distributed brain structures and neural systems underlying different cognitive mechanisms, which all contribute to some aspect of information processing during recognition memory.     

COMPARISON OF POPULATION PHARMACOKINETIC MODELING METHODS USING SIMULATED DATA: RESULTS FROM THE POPULATION MODELING WORKGROUP

Statistical modeling methods have had increasing use in drug disposition studies, both to estimate pharmacokinetic parameters and to develop regression models that relate these parameter estimates to patient characteristics. These methods are particularly flexible as they allow non-linearity and sparse within-patient information. In the past few years, multiple analysis methods have become available, but there is a lack of systematic comparisons of their estimates on the same data sets. Two simulated data sets were therefore developed by the Population Modeling Workgroup of the Biopharmaceutical Section of the American Statistical Association. We analysed these data sets using seven population modeling programs, some of which contain multiple analysis methods. Although each data set represents a single replicate from a given model and data collection design, the results suggest that the behaviour of some methods differs from that of the others. © 1997 by John Wiley & Sons, Ltd.     

Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761)

Abstract— Investigation of [³H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT_1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (B_max) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane.