Dementia associated with alcohol and other drug use

The acute use of alcohol and several other licit and illicit drugs can affect mental state and cognitive function. The chronic use of certain drugs may also increase the risk of cognitive impairment and perhaps dementia in later life. This paper focuses on the long-term cognitive consequences of using alcohol, benzodiazepines, tobacco and cannabis. Currently available evidence indicates that mild to moderate alcohol consumption is not associated with increased risk of cognitive decline and may in fact have a protective effect against dementia, although heavy, long-term consumption is likely to have a negative impact on cognitive function. The degree that alcohol-related cognitive impairment must reach to be classified as dementia is currently obscure. Longer-term smoking is associated with increased risk of cognitive impairment and possibly dementia. The chronic use of benzodiazepines has been associated with increased risk of cognitive impairment but information relating to dementia remains inconclusive. The chronic use of cannabis may impair intellectual abilities but data on this topic remain sparse and difficult to interpret. In conclusion, there is evidence that some drugs contribute to the causal pathway that leads to the development of cognitive impairment but currently available data do not support the introduction of a separate diagnostic category of drug-induced dementia (such as alcohol-related dementia). Health promotion programs designed to decrease tobacco smoking and "harmful" alcohol use (and possibly other drug use) may decrease the burden of cognitive impairment and perhaps dementia in later life.     

Dementia associated with infectious diseases

At the turn of the last century, infectious diseases represented an important cause of health morbidity and behavioral changes. Neurosyphilis, for example, was relatively common at the time and often led to the development of cognitive impairment and dementia. With the advent of effective antibiotic treatment, the association between infectious diseases and dementia became increasingly less frequent, although a resurgence of interest in this area has taken place during the past 15 years with the emergence of acquired immunodeficiency syndrome (AIDS) and variant Creutzfeldt-Jakob disease (vCJD). This paper reviews the most frequent infectious causes of dementia, including prion diseases, as well as infections caused by herpes virus, human immunodeficiency virus (HIV), toxoplasmosis, cryptococcus, cytomegalovirus, syphilis, borrelia and cysticercosis.     

Hippocampus and remote spatial memory in rats

Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks. It has also figured prominently in theoretical treatments of memory and hippocampal function. Yet temporally graded retrograde amnesia has not been demonstrated following hippocampal damage in spatial tasks like the water maze. We have assessed recent and remote spatial memory following hippocampal lesions in three different tests of spatial memory: (1) the standard water maze; (2) the Oasis maze, a dry-land version of the water maze; and (3) the annular water maze, where training and testing occur within a circular corridor. Training protocols were developed for each task such that retention of spatial memory could be expressed after very long retention intervals. In addition, retention in each task was assessed with single probe trials so that the assessment of remote memory did not depend on the ability to relearn across multiple trials. The findings were consistent across the three tasks. In the standard water maze (Experiment 1), spatial memory was impaired after training-surgery intervals of 1 day, 8 weeks, or 14 weeks. Similarly, in the Oasis maze (Experiment 2), spatial memory was impaired after training-surgery intervals of 1 day and 9 weeks. Finally, in the annular water maze (Experiment 3), spatial memory was impaired after training-surgery intervals of 9 weeks and 14 weeks. Dorsal hippocampal lesions impaired performance to the same extent as complete lesions. The impairment in remote spatial memory could reflect disruption of previously acquired spatial information. Alternatively, it is possible that in these tasks hippocampal lesions might produce an impairment in performance that prevents the expression of an otherwise intact spatial memory.     

Ipratropium Bromide HFA

Ipratropium bromide is a nonselective antagonist of the muscarinic receptors located on airway smooth muscle, and is delivered via a metered-dose inhaler (MDI). Because of the requirement to phase out chlorofluorocarbon (CFC)-propelled MDIs, the ipratropium bromide inhalation aerosol MDI has been redesigned with a hydrofluoroalkane as the propellant (ipratropium bromide HFA). Ipratropium bromide HFA has recently been approved in the US for the maintenance treatment of bronchospasm associated with COPD. Ipratropium bromide HFA 42 microg four times daily (one dose [42 microg] is delivered via two puffs of the inhaler) demonstrated comparable efficacy to that of ipratropium bromide CFC 42 microg four times daily, as measured by spirometric testing, in a large, randomized, double-blind, placebo-controlled, 12-week trial in patients with stable COPD. Similarly, four-times-daily ipratropium bromide HFA 42 microg and ipratropium bromide CFC 42 microg provided a comparable degree of bronchodilation in patients with stable COPD during a 1-year, open-label study primarily designed to assess safety. In both studies, the tolerability profiles of ipratropium bromide HFA and ipratropium bromide CFC were comparable. The most common adverse events were related to respiratory system disorders. During the 1-year study, dry mouth was reported by 1.3% and 0.7% of patients in the ipratropium bromide HFA or ipratropium bromide CFC groups.     

Wireless home monitoring and health care activity management through the Internet in patients with chronic diseases

A project was developed for the creation of an Internet-based network aimed at improved management of home care activities in brain-injured children. At the patient's side, a home care unit was provided, made of a portable medical device, and a tablet PC. Measured clinical data were blood oxygen saturation, heart rate, breath rate and quantity of movement. Thanks to device portability, the patient was free to move while measurements were taken. At prescribed time intervals, measured data were automatically transmitted to the tablet PC via Bluetooth. From the tablet PC, data were transmitted remotely to a Service Centre (via ADSL or GPRS) and made available for consultation by health care professionals through the project Web portal. At the portal, other functionalities were also available, both for patients and families, and for professionals (such as weekly planning agenda, access to relevant information resources, communication tools). Information was delivered for the right participant through a workflow engine. A first trial involving nine patients was performed for two months. At the end, although some improvements were suggested, good acceptance was detected, and 78% of patients and families claimed to be interested in further use of the platform.     

Neurotrophin receptor-based strategies for Alzheimer's disease

The traditional perspective of applying neurotrophins in the context of Alzheimer's disease is based on the premise that neurotrophins are capable of upregulating cholinergic function and of rendering neurons less vulnerable to certain processes causing degeneration. Factors limiting the therapeutic application of neurotrophin proteins include their poor pharmacological properties and their pleiotropic effects mediated by interaction with Trk, p75NTR and sortilin receptors. Recent studies suggesting and that pro-forms of neurotrophins accumulating in Alzheimer's and other pathological states cause cell death, that p75NTR modulates amyloid beta- and injury-induced neurodegeneration and that small molecules can be created that bind specifically to individual neurotrophin receptors point to novel strategies by which neurotrophin receptors might be targeted in Alzheimer's and other neuropathological states.     

Time for a cool head-neuroprotection becomes a reality

Studies in encephalopathic infants have demonstrated a brief phase of normal cerebral energetics following hypoxia-ischaemia prior to development of delayed energy failure. In experimental models, mild hypothermia has shown a consistent neuroprotective action, although its efficacy is critically dependent on the severity of the primary insult, the delay in initiating cooling, and the duration and depth of hypothermia. Early electroencephalographic assessment of encephalopathic infants has the potential to provide objective information about the preceding insult, aiding the selection of infants for enrollment to clinical trials. Preliminary results from a large randomised trial of selective head cooling suggest that early intervention can lead to significantly improved outcome in a subgroup of encephalopathic infants with intermediate electroencephalographic abnormalities. Further research in established experimental models is essential to improve the identification of suitable infants for treatment, to investigate the importance of variations in regional brain temperature, and to examine the therapeutic potential of hypothermia combined with other neuroprotective agents.     

Vulnerable Baby Scale: development and piloting of a questionnaire to measure maternal perceptions of their baby's vulnerability

OBJECTIVES: To develop and provide initial data to validate a contemporary measure of maternal perceptions of infant vulnerability. METHODS: Questions that address current concerns of mothers regarding their young children (such as the risk of sudden infant death syndrome) were added to an existing Vulnerable Child Questionnaire. Questions not relevant to either current concerns or to young infants were removed. The modified questionnaire, along with standard measures of maternal anxiety and depressive symptoms, were administered to mothers of 39 healthy full-term babies, 17 mothers of 'medically fragile' babies and 19 mothers of jaundiced babies. Babies were approximately 12 weeks of age at the time of completion of the questionnaire. RESULTS: Three questions were removed from the questionnaire on the basis of poor item-total correlations, leaving the final version with 10 questions, scored on 1-5 rating scales. Cronbach alpha for the revised scale was 0.7. There was a significant difference (P = 0.002) in mean vulnerable baby scores between the control group and the 'medically fragile' group. There was a moderately strong correlation between vulnerable baby score and maternal state anxiety (r = 0.6) and a weaker correlation with maternal depressive symptoms (r = 0.3). CONCLUSIONS: The modified questionnaire has good internal consistency. The difference in mean scores between the three groups, and correlations with maternal anxiety and depressive symptoms, lend construct validity to the scale. The Vulnerable Baby Scale appears to be suitable for assessing maternal perceptions of the vulnerability of their young babies in clinical and research settings although further research, with larger samples, may be necessary to fully establish the scale's psychometric properties.     

Serum relaxin in systemic sclerosis

OBJECTIVE: To evaluate serum levels of relaxin (RLX), a hormone with acknowledged antifibrotic activity, in patients with systemic sclerosis (SSc). METHODS: We performed a pilot study of 50 outpatients with SSc and 50 healthy subjects. Serum RLX was measured using the relaxin ELISA. Statistical analysis was performed using Student's t test. RESULTS: Serum RLX appeared to be significantly higher (p < 0.001) in patients with SSc compared to controls. RLX appeared significantly increased (p < 0.001) in male patients compared to male controls, and in female patients compared to female controls. RLX was significantly higher (p < 0.001) in female patients and female controls compared to male patients and male controls. CONCLUSION: In patients with SSc, the increased level of RLX represents a defensive response against the fibrotic process.     

Efficacy and safety of recombinant urate oxidase (rasburicase) for treatment and prophylaxis of hyperuricemia in children undergoing chemotherapy

Rasburicase has been defined as a potent urolytic agent for management of malignancy-associated hyperuricemia. We reviewed the data of 26 children with malignancy at risk for TLS who received rasburicase for treatment or prophylaxis of acute hyperuricemia, producing a significant decrease in uric acid level in all the patients. Tolerance of treatment was excellent. Rasburicase is a safe, highly and rapidly effective agent in the treatment and prevention of malignancies-associated acute hyperuricemia.