A phase II trial of huperzine A in mild to moderate Alzheimer disease.

OBJECTIVE: Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata that may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use for Alzheimer disease (AD). METHODS: We assessed the safety, tolerability, and efficacy of huperzine A in mild to moderate AD in a multicenter trial in which 210 individuals were randomized to receive placebo (n = 70) or huperzine A (200 µg BID [n = 70] or 400 µg BID [n = 70]), for at least 16 weeks, with 177 subjects completing the treatment phase. The primary analysis assessed the cognitive effects of huperzine A 200 µg BID (change in Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-Cog] at week 16 at 200 µg BID compared to placebo). Secondary analyses assessed the effect of huperzine A 400 µg BID, as well as effect on other outcomes including Mini-Mental State Examination, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change scale, Alzheimer's Disease Cooperative Study Activities of Daily Living scale, and Neuropsychiatric Inventory (NPI). RESULTS: Huperzine A 200 µg BID did not influence change in ADAS-Cog at 16 weeks. In secondary analyses, huperzine A 400 µg BID showed a 2.27-point improvement in ADAS-Cog at 11 weeks vs 0.29-point decline in the placebo group (p = 0.001), and a 1.92-point improvement vs 0.34-point improvement in the placebo arm (p = 0.07) at week 16. Changes in clinical global impression of change, NPI, and activities of daily living were not significant at either dose. CONCLUSION: The primary efficacy analysis did not show cognitive benefit with huperzine A 200 µg BID. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that huperzine A 200 µg BID has no demonstrable cognitive effect in patients with mild to moderate AD.

Amino acid transporters and nutrient-sensing mechanisms: new targets for treating insulin-linked disorders?

The IIS (insulin/IGF (insulin-like growth factor) signalling) cascade has an important role in regulating normal development and physiology, as evidenced by its effects in a host of major human diseases including cancer, Type 2 diabetes and neurodegeneration. Recently, it has become clear that multiple types of local nutrient-sensing mechanisms have an impact on cellular insulin-sensitivity through the downstream kinase TOR (target of rapamycin). In vivo analysis in flies has surprisingly highlighted PATs (proton-assisted amino acid transporters) as having a uniquely potent role in regulating IIS/TOR activity and growth, potentially via a novel signalling mechanism. Other molecules such as the heterodimeric amino acid transporter, CD98, which provides the principal route for cellular uptake of leucine, an amino acid implicated in regulating TOR, also appear to have important effects. As our understanding of how nutrient sensing has an impact on IIS/TOR increases, novel targets to modulate aberrant IIS in disease are likely to emerge, which could complement current strategies designed to block kinases in this pathway.

Effects of increased deposition of atmospheric nitrogen on an upland moor: nitrogen budgets and nutrient accumulation.

This study was designed to investigate the effect of long-term (11 years) ammonium nitrate additions on standing mass, nutrient content (% and kg ha(-1)), and the proportion of the added N retained within the different compartments of the system. The results showed that more than 90% of all N in the system was found in the soil, particularly in the organic (Oh) horizon. Added N increased the standing mass of vegetation and litter and the N content (kg N ha(-1)) of almost all measured plant, litter and soil compartments. Green tissue P and K content (kg ha(-1)) were increased, and N:P ratios were increased to levels indicative of P limitation. At the lowest treatment, most of the additional N was found in plant/litter compartments, but at higher treatments, there were steep increases in the amount of additional N in the underlying organic and mineral (Eag) horizons. The budget revealed that the proportion of added N found in the system as a whole increased from 60%, 80% and up to 90% in response to the 40, 80 and 120 kg N ha(-1) year(-1) treatments, respectively.

The phosphorus budget of the Thame catchment, Oxfordshire: 2. Modelling.

The phosphorus budget of the River Thame was modelled at a daily time scale, using estimates of diffuse and point source contributions of discharge. The model simulated suspended sediment (SS), soluble unreactive phosphorus (SUP), soluble reactive phosphorus (SRP) and particulate phosphorus (PP) concentrations within the main river and major tributaries. Diffuse source estimates of phosphorus loads were based on characteristic losses from identified main landscape classes, with hydrology described by a simple conceptual storage model. In-stream flow was modelled using a kinematic wave equation. Transfer of suspended sediment and phosphorus components was approximated by advection. In-stream sources and sinks included uptake and release of soluble reactive phosphorus by bed sediment, instant equilibration between SRP and the PP concentration on suspended sediment, and flow-related entrainment and deposition of suspended sediment. Simulations at sites within the catchment were compared with measurements made in 1998-1999. Results showed the P budget is dominated by mixing of diffuse and point source water, but some within-river processes have been shown to be capable of significantly influencing SRP concentrations. The development of a sediment entrainment and deposition component of the model has proved particularly valuable in emulating the hysteretic relationship between discharge and suspended sediment concentration in the river. It also provides a measure of available bed sediment.

A Canadian survey of cancer patients' experiences: are their needs being met?

Cancer patients (n = 913) who received treatment within the previous 2 years were interviewed to quantify reports of symptoms associated with cancer, measure the impact of symptoms on lifestyles, document experiences with accessing information and treatment for cancer and its symptoms, and record attitudes about the level of care received. Cancer patients were primarily recruited through newspaper ads placed throughout Canada and asked to complete a self-report questionnaire. Patients called a toll-free number and were interviewed to ensure eligibility. Most respondents were female (66%) with breast cancer (64%). Prostate cancer (40%) was the most common diagnosis among males. Almost all respondents (94%) reported experiencing one or more symptoms. Fatigue and anxiety were the most frequently reported symptoms (78% and 77%, respectively). Fatigue was most likely to be self-rated as moderate to severe and was most likely to interfere in normal daily activities. Respondents who experienced fatigue reported a more frequent use of healthcare services (including complementary therapies) than those who did not experience fatigue. Half of the respondents reported trying to find information on fatigue, but only half of these said they had obtained information. The most helpful sources of information were nurses, specialists, and other cancer patients. Respondents were more likely to be dissatisfied with their treatments for their symptoms than for their cancer. This survey indicates that most cancer patients experience symptoms related to the disease and its treatment. The most prevalent symptoms are fatigue and anxiety; fatigue is the most debilitating.

Power scalers: the new boom in contemporary periodontics.

The choice of which type of instrumentation to use remains the decision of the practitioner. It all depends on what goal the clinician hopes to achieve, the resources, and the physical set up within which they work. While speed in debridement, coupled with ease of use and comfort to the patient and practitioner are all important, the primary goal must always remain the optimal healing and success of the dental procedure. With improved tip designs and efficiency, power scaling has the ability to improve dental hygiene and periodontal care in the future.

Biofeedback and facilitation of erection in men with erectile dysfunction.

Thirty men with psychogenic erectile dysfunction were instructed to concentrate on cognitions that facilitate erection during one baseline and four training sessions. The subjects were divided into three groups that received either continuous feedback of erection changes plus segments of erotic film delivered contingent on erection increases, contingent film segments without continuous feedback, or noncontingent film segments. Although subjects who received noncontingent film segments initially showed greater erection increase than did subjects in the contingent feedback groups, the groups did not differ by the final training session. However, when subjects were instructed to facilitate erection without the aid of feedback or film segments during evaluation trials that followed each training session, subjects who had received contingent film without continuous feedback showed greater erectile responsivity than subjects in other groups. The groups did not differ in the amount of clinical improvement shown on self-report measures concerning erectile functioning during a 1-month follow-up period. Although these results indicate that the provision of erotic film feedback enhances the voluntary facilitation of erection in the laboratory, the therapeutic value of erectile feedback remains undemonstrated.