US national survey of physician practices for the secondary and tertiary prevention of ischemic stroke. Design, service availability, and common practices

BACKGROUND AND PURPOSE: Stroke is largely a preventable disease. However, there are little data available concerning the use of stroke prevention diagnostic and treatment modalities by practicing physicians. These data are critical for the rational allocation of resources and targeting of educational efforts. The purposes of this national survey were to gather information about physicians' stroke prevention practice patterns and their attitudes and beliefs regarding secondary and tertiary stroke prevention strategies. METHODS: We conducted a national survey of stroke prevention practices among a stratified random sample of 2000 physicians drawn from the American Medical Association's Physician Masterfile. The survey focused on the availability of services and the use of diagnostic and preventive strategies for patients at elevated risk of stroke. RESULTS: Sixty-seven percent (n = 1006) of eligible physicians completed the survey. Diagnostic studies considered readily available by at least 90% of physicians included carotid ultrasonography, transthoracic echocardiography, Holter monitoring, and brain CT and MRI scans. MR angiography was perceived as being readily available by 68% and transesophageal echocardiography by 74% of respondents. Twelve percent of physicians reported cerebral arteriography and 10% reported carotid endarterectomy as not being readily available. Multiple logistic regression analyses showed that the availability of services varied with physician specialty (noninternist primary care, internal medicine, neurology, surgery), practice setting (nonmetropolitan versus small metropolitan or large metropolitan areas), and for carotid endarterectomy, region of the country (South, Central, Northeast, and West). The odds of carotid endarterectomy being reported as readily available were approximately 2.5 to 3.5 times greater for physicians practicing in the central, northeastern, and western regions compared with those practicing in the South, independent of practice setting and specialty. With regard to stroke prevention practices, 61% of physicians reported prescribing 325 mg of aspirin for stroke prevention, while 33% recommend less than 325 mg and 4% use doses of 650 mg or more. Seventy-one percent of physicians using warfarin reported monitoring anticoagulation with international normalized ratios, and 78% reported monitoring anticoagulated patients at least once a month. Fewer than 20% of physicians reported knowing the perioperative carotid endarterectomy complication rates at the hospital where they perform the operation themselves or refer patients to have the procedure done. CONCLUSIONS: Although all routine and most specialized services for secondary and tertiary stroke prevention are readily available to most physicians, variation in availability exists. The use of international normalized ratios for monitoring warfarin therapy has not yet become universal. Physician knowledge of carotid endarterectomy complication rates is generally lacking. Depending on their causes, these problems may be addressed through targeted physician education efforts and systematic changes in the way in which services are provided.     

Stacking interactions of ApA analogues with modified backbones

CD spectra have been measured as a function of temperature for a number of ApA analogues with modified backbones. Oligonucleotides with these modified backbones are being used as antisense agents having potential as viral therapeutics. Results of these studies show that when a carbonyl is substituted for the phosphate to produce an uncharged backbone, the analogues that have either sugar or morpholino substitution do not stack. In contrast, when a morpholino group is substituted for the sugar and the phosphate is modified so as to be uncharged, there is strong base stacking. Stacking interactions in the phosphorus-linked morpholino analogues are at least as strong as those found in d(ApA). The stacking interactions in ApA are weak by comparison. Singular value decomposition demonstrates that the stacking is two state, and Taylor series decomposition yields a coefficient that measures base stacking interactions. The van't Hoff equation is applied to the base stacking coefficient from the Taylor series fitting to give thermodynamic parameters.     

Ocular migraine in an eight-year-old girl

BACKGROUND: A case of ocular migraine in an eight-year-old girl is presented. This is believed to be the youngest reported patient with ocular migraine. CONCLUSION: The choroid was noted to darken during an episode of visual loss, suggesting choroidal ischaemia as the cause of the visual loss.     

Effects of hypothyroidism on brown adipose tissue adenylyl cyclase activity

Hypothyroidism profoundly reduces the capacity of brown adipose tissue (BAT) to generate cAMP in response to adrenergic stimulation. Evidence obtained with isolated brown adipocytes suggests a postreceptor defect that offsets the hypothyroidism-induced increase in beta3-adrenergic receptors. The goal of the present studies was to identify the defect in the cAMP generation pathway for which we studied cAMP generation in isolated cells and purified BAT membranes from normal and hypothyroid rats. Studies with adenosine deaminase and the adenosine receptor-1 agonist r-phenyl isopropyl adenosine (R-PIA) show that hypothyroid cells are not more sensitive to adenosine (same EC50) but more inhibited by high concentrations of R-PIA. Pretreatment with pertussis toxin reduced the gap in cAMP generation between eu- and hypothyroid cells and the inhibition mediated by R-PIA, but did not normalize the cAMP response to forskolin in hypothyroid cells. Although purified euthyroid BAT membranes increased cAMP production with GTP concentrations up to submillimolar range, to plateau or slightly decrease at higher levels, hypothyroid membranes were weakly stimulated by low concentrations of GTP and markedly inhibited (>50%) at concentrations > or = 10(-4) M. When assayed at 0.3 mM ATP and 1 microM GTP, hypothyroid membranes actually generated more cAMP in response to forskolin, but this was reversed when GTP concentration was 1 mM. Immunoblotting studies showed no significant effects of hypothyroidism on the abundance of G(alpha)i or Gbeta subunits, and ADP ribosylation of G(alpha)i was only 45% increased in hypothyroidism in contrast to a 2.5-fold increase in hypothyroid white adipose tissue membranes from the same rats. Hypothyroid membranes also exhibited different kinetics regarding ATP, with higher cAMP generation at submillimolar concentrations but less at >1 mM ATP. Actually, at ATP concentrations >0.6 mM, cAMP generation was markedly inhibited in hypothyroid membranes. Fixing the concentration of free Mg++ in these experiments indicates that most of the inhibition seen in hypothyroid membranes is caused by ATP, whereas euthyroid membranes are more sensitive to changes in free Mg++. Ca++ +/- calmodulin did not stimulate adenylyl cyclase (AC) activity. On the contrary, AC activity was inhibited by Ca++ in a concentration-dependent manner, by as low as 100 nM free Ca++, and to greater extent in hypo- than in euthyroid membranes (maximal inhibition 60 vs. 25-30%). Our results suggest that, functionally, hypothyroidism causes a change in the AC of BAT membranes consistent with a relative or absolute increase in the type VI AC (AC-VI). The effects on this AC of nucleotides, Ca++, and Mg++ at concentrations prevailing in the hypothyroid brown adipocyte are probably the major factor in the reduced capacity of these cells to generate cAMP. These results also open the possibility of a novel, differential effect of thyroid hormone on AC expression, and support the concept that thyroid hormone affects the adrenergic signal transduction pathways in a tissue-selective manner.