Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

Factors affecting physicians' decisions on caring for an incompetent elderly patient: an international study.

OBJECTIVES: To determine what treatment decisions physicians will make when faced with a hypothetical incompetent elderly patient with life-threatening gastrointestinal bleeding and to examine the relative importance of physician characteristics and factors (legal and ethical concerns, hospital costs, level of dementia, patient's age, physician's religion, patient's wishes and family's wishes) in making those decisions. DESIGN: Survey. SETTING: Family practice, medical and geriatrics rounds in academic medical centres and community hospitals in seven countries. PARTICIPANTS: Physicians who regularly cared for incompetent elderly patients. MAIN OUTCOME MEASURES: A self-administered questionnaire describing the elderly patient. Respondents were asked to choose one of four levels of care and to identify the level of importance factors had in making that decision. Older physicians, those less concerned about litigation, those for whom the level of dementia was important and those for whom the patient's age was important were expected to give less aggressive care than the other physicians. MAIN RESULTS: Supportive care was chosen by 8.1% of the respondents, limited therapeutic care by 41.5%, maximum therapeutic care without admission to the intensive care unit (ICU) by 32.2% and maximum care with admission to the ICU by 18.2%. The patient's wishes were reported by 91.0% as being extremely or very important in choosing the treatment. Stepwise logistic regression analysis revealed that the following variables independently predicted the level of treatment: level of dementia, country of residence, duration of practice, legal concerns, patient's age and ethical concerns. These factors were significantly correlated with the physicians' treatment choices (p less than 0.05). CONCLUSIONS: The importance that the physicians placed on the level of dementia was the strongest predictor of the level of care that would be provided. A societal consensus on the influence of cognitive function on the appropriate level of care as well as training of physicians in ethical issues are required.     

Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations.

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ > La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ > Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.     

An anaphylactic reaction to succinylcholine. A clinical case

A case of severe anaphylactic reaction provoked by suxamethonium during the induction of general anaesthesia is reported. Diagnosis of reaction and the trigger effect of suxamethonium was identified by intradermal testing. Diagnosis of anaphylactic reaction was confirmed on serial blood estimations of IgE and C3-C4 of complement fractions.     

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.     

Human cytomegalovirus UL144 gene polymorphisms in congenital infections

The human cytomegalovirus (HCMV) UL144 gene is a tumor necrosis factor-like receptor with the potential to affect HCMV virulence. HCMV strains display genetic variability in the UL144 region, and the analysis of a potential link between UL144 gene polymorphisms and disease severity has scarcely been studied. However, a correlation between the UL144 genotype and congenital-disease outcome has been reported in one previous study, with the observation that all asymptomatic infants had a single UL144 genotype. In order to confirm or refute this finding, we determined the UL144 polymorphisms of HCMV strains recovered from the amniotic fluids of 38 infected fetuses and compared them to HCMV strains obtained from 30 viremic adult controls. The UL144 sequences were distributed among five genotypes (A, B, C, AC, and AB), as previously described. We observed similar percentages of the three major genotypes A (37%), B (33%), and C (27%) in our population. The UL144 genotype distributions were similar among the group of infected adults and the group of infected fetuses and among symptomatic and asymptomatic fetuses (P < 0.05). In our series, all five UL144 genotypes could be vertically transmitted from mothers to fetuses, and all could cause symptomatic congenital infection. We concluded that determination of UL144 polymorphisms in cases of congenital infection is not relevant, since it is unlikely to help predict the outcome of the infection.