Statin-associated memory loss: analysis of 60 case reports and review of the literature

OBJECTIVE: To review case reports of statin-associated memory loss as well as the available published evidence for and against such a link. METHODS: We searched the MedWatch drug surveillance system of the Food and Drug Administration (FDA) from November 1997-February 2002 for reports of statin-associated memory loss. We also reviewed the published literature (using MEDLINE) and prescribing information for these drugs. RESULTS: Of the 60 patients identified who had memory loss associated with statins, 36 received simvastatin, 23 atorvastatin, and 1 pravastatin. About 50% of the patients noted cognitive adverse effects within 2 months of therapy. Fourteen (56%) of 25 patients noted improvement when the statin was discontinued. Memory loss recurred in four patients who were rechallenged with the drug. None of the 60 reported cognitive test results. Two placebo-controlled trials found no benefits for statins on cognition or disability. One randomized controlled trial of simvastatin found no effects on cerebrospinal amyloid levels. In one small, randomized study, patients receiving statins showed a trend toward lower cognitive performance than those receiving placebo. Five observational studies found a lower risk of dementia among patients receiving statins. CONCLUSION: Current literature is conflicting with regard to the effects of statins on memory loss. Experimental studies support links between cholesterol intake and amyloid synthesis; observational studies indicate that patients receiving statins have a reduced risk of dementia. However, available prospective studies show no cognitive or antiamyloid benefits for any statin. In addition, case reports raise the possibility that statins, in rare cases, may be associated with cognitive impairment, though causality is not certain.     

Pharmacologic indicators of antitumor efficacy for oncolytic virotherapy

Central to the development of oncolytic virotherapies for cancer will be a better understanding of the parameters that influence the outcome of virotherapy to treat disseminated cancer by i.v. administration versus regional disease by local treatment. Intratumoral administration of 01/PEME, an oncolytic adenovirus, required approximately 1000-fold less dose than i.v. administration to induce similar tumor growth inhibition. Despite the short (<10 min) circulating half-life of the virus DNA, we could monitor virus distribution to the tumor site and observed virus replication by >1000-fold increase in virus DNA copies over time. There were doses of 01/PEME for which the virus DNA concentration in the tumor increased over time but did not result in antitumor efficacy. Oncolytic virus replication at a tumor site may not be a relevant indication of antitumor efficacy. Efficient distribution to the tumor site may be one of the most critical parameters for antitumor efficacy with oncolytic virotherapy.     

Oncogenic osteomalacia

Oncogenic osteomalacia is a rare paraneoplastic syndrome caused by bone and soft tissue tumors. The characteristic clinical, metabolic, and imaging findings are reviewed, as is the radiologist's role in evaluation and diagnosis. New insight into the pathophysiology of oncogenic osteomalacia is also presented.     

Treatment of an anterior communicating artery aneurysm through an anomalous anastomosis from the cavernous internal carotid artery

Cavernous internal carotid artery (ICA)-anterior cerebral artery (ACA) anastomoses are unusual anomalies in which a duplicated A, segment of the ACA arises from the infraoptic ICA. The authors report on a 30-year-old woman who presented with subarachnoid hemorrhage from an anterior communicating artery (ACoA) aneurysm associated with an extremely rare variant of this anastomosis. The extra A, segment emerged from the ICA within the cavernous sinus rather than at or above the level of the ophthalmic artery. The presence of the anomalous vessel provided a straightforward endovascular approach to the ACoA and allowed the use of coil placement rather than surgical clipping to treat the aneurysm successfully.     

Radiologic case study. Benign intraosseous lipoma

Intraosseous lipomas are uncommon lesions of bone most often diagnosed incidentally. They typically manifest a classic radiographic appearance, but CT or MRI may be useful in diagnosing lesions that are atypical or incompletely defined radiographically and avoid an unnecessary biopsy.     

Day care percutaneous renal surgery--is this viable?

Pros and cons of Percutaneous Nephrolithotripsy (PCNL) versus Extracorporeal Shockwave Lithotripsy (ESWL) have often been highlighted when one discusses on the management of renal stones. An oft quoted point is that PCNL entails a prolonged hospital stay whereas ESWL sessions are day surgical in nature. However, PCNL has superior stone clearance rate as compared to ESWL especially for lower pole stones. In addition, PCNL is more suitable for large bulk stones and when ancillary procedures are required e.g. endopyelotomy. The first 50 cases of successful tubeless PCNL were reported by Bellman et al in 1997. The remarkable recovery of patients in their series encouraged them to employ this technique as their technique of choice for the majority of their cases. A similar technique was employed on endopyelotomy by Liang et al and they concluded that this was a safe, less morbid and effective technique. We report our first case of tubeless PCNL.     

(-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. I. In vitro characterization

Alterations in the myogenic activity of the bladder smooth muscle are thought to serve as a basis for the involuntary detrusor contractions associated with the overactive bladder. Activation of ATP-sensitive K(+) (K(ATP)) channels has been recognized as a potentially viable mechanism to modulate membrane excitability in bladder smooth muscle. In this study, we describe the preclinical pharmacology of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a novel 1,4-dihydropyridine K(ATP) channel opener (KCO) that demonstrates enhanced bladder selectivity for the suppression of unstable bladder contractions in vivo relative to other reference KCOs. A-278637 activated K(ATP) channels in bladder smooth muscle cells in a glyburide (glibenclamide)-sensitive manner as assessed by fluorescence membrane potential assays using bis-(1,3-dibutylbarbituric acid)trimethine oxonol (EC(50) = 102 nM) and by whole cell patch clamp. Spontaneous (myogenic) phasic activity of pig bladder strips was suppressed (IC(50) = 23 nM) in a glyburide-sensitive manner by A-278637. A-278637 also inhibited carbachol- and electrical field-stimulated contractions of bladder strips, although the respective potencies were 8- and 13-fold lower compared with inhibition of spontaneous phasic activity. As shown in the accompanying article [Brune ME, Fey TA, Brioni JD, Sullivan JP, Williams M, Carroll WA, Coghlan MJ, and Gopalakrishnan M (2002) J Pharmacol Exp Ther 303:387-394], A-278637 suppressed myogenic contractions in vivo in a model of bladder instability with superior selectivity compared with other KCOs, WAY-133537 [(R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)cyclobut-1-enylamino]-3-ethyl-benzonitrile] and ZD6169 [(S)-N-(4-benzoylphenyl)3,3,3-trifluro-2hydroxy-2-methyl-priopionamide]. A-278637 did not interact with other ion channels, including L-type calcium channels or other neurotransmitter receptor systems. The pharmacological profile of A-278637 represents an attractive basis for further investigations of selective K(ATP) channel openers for the treatment of overactive bladder via myogenic etiology.     

Dietary intake does not account for differences in low iron stores among Mexican American and non-Hispanic white women: Third National Health and Nutrition Examination Survey, 1988-1994

We used nationally representative data from the third National Health and Nutrition Examination Survey (NHANES III) to examine the relationship between low iron stores (serum ferritin < 12 microg/L) and dietary patterns that might affect iron status among Mexican American (MA) and non-Hispanic white (NHW) girls and women of reproductive age (12-39 y). Dietary data from the qualitative food-frequency questionnaire were used to classify subjects into three categories (using the 25th and 75th quartile values for NHW) for intake of heme iron, nonheme iron, iron absorption enhancers, and iron absorption inhibitors. The prevalence of low iron stores was 17.4% among MA (n = 1368) and 7.9% among NHW (n = 1473). Compared with high intake, the adjusted odds ratio (OR) for low iron stores was 1.80 [95% confidence interval (CI), 1.24-2.62] for medium intake of heme iron and 0.48 (95% CI, 0.25-0.91) for low intake of nonheme iron (plus iron supplement). Compared with no use, use of vitamin C supplements was associated with half the risk of low iron stores (OR = 0.50; 95% CI, 0.29-0.87). Similar results were found after income and parity were controlled for, except that the protective effect of vitamin C supplements was no longer significant. Even after adjustment for sociodemographic and dietary factors, MA women remained at increased risk for low iron stores (OR = 1.80; 95% CI, 1.30-2.49) indicating that the reasons for the higher prevalence of iron deficiency in MA women warrants further investigation.     

Evaluation of the Integrated Management of Childhood Illness guidelines for treatment of intestinal helminth infections among sick children aged 2-4 years in western Kenya

Anthelmintic treatment of sick preschool-age children at health facilities is a potentially effective strategy for intestinal helminth control in this age-group. We conducted a study from July 1998 to February 1999 in western Kenya to determine whether the Integrated Management of Childhood Illness (IMCI) guidelines' clinical assessment can be used to identify helminth-infected children, and to evaluate the nutritional benefit of treating sick children without pallor with an anthelmintic (mebendazole is already part of IMCI treatment for sick children aged 2-4 years with palmar pallor in areas where hookworm and Trichuris trichiura infections are endemic). Sick children aged 2-4 years seen at 3 rural health facilities were clinically evaluated and tested for haemoglobin concentration, malaria parasites, and intestinal helminths. Children without pallor were randomly assigned to receive a single dose of 500 mg of mebendazole or a placebo and re-examined 6 months later. Among the 574 children enrolled, 11% had one or more intestinal helminths. Most infections were of light intensity. Selected clinical signs and symptoms available from the IMCI assessment, including palmar pallor and low weight-for-age, were not associated with helminth infection. Six months after enrollment, no differences in growth of children without pallor were observed between the mebendazole (n = 166) and placebo (n = 181) groups. However, there was a significantly greater mean increase in weight, height, and weight-for-age Z score among the helminth-infected children in the mebendazole group (n = 22) as compared with helminth-infected children in the placebo group (n = 20). We conclude that even lightly infected preschool-age children without palmar pallor benefit from anthelmintic treatment; however, in this study setting of low helminth prevalence and intensity, helminth-infected children could not be identified using the IMCI guidelines. Cost-effectiveness studies are needed to help define helminth prevalence thresholds for routine anthelmintic treatment of sick preschool-age children seen at first-level health facilities.