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Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2005. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (4.12 points on the 100 point SIB , 95% CI 2.14 to 5.74, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 NPI, 95% CI 0.88 to 4.63, P = 0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.45, P = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, P = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, P = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine appeared to be less likely to develop agitation (93/1167 [8%] versus 134/1141 [12%] (Peto odds ratio (OR): 0.65, 95% CI 0.49 to 0.86, P = 0.002). This was consistently seen in moderate to severe dementia. There were no data which suggested an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not detectable on global assessment at six months. Whether memantine has any effect in mild to moderate AD is unknown.

Activities of Daily Living↗

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8th February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal beneficial effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition.3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

Activities of Daily Living↗

Thoracic epidural anesthesia reduces infarct size in a canine model of myocardial ischemia and reperfusion injury.

OBJECTIVE: To determine the effects of thoracic epidural anesthesia on myocardial infarct size, regional myocardial blood flow (RMBF), and plasma norepinephrine in an anesthetized canine model of ischemia reperfusion injury with infarction. DESIGN: Blinded, randomized, placebo-controlled animal study. SETTING: Experiments were performed in the cardiothoracic research laboratory at Wake Forest University Baptist Medical Center. PARTICIPANTS: Anesthetized, open-chest mongrel dogs were used in these studies. METHODS: Dogs were instrumented for measurement of aortic pressure (AP) and left ventricular systolic pressure (LVSP), dP/dt, and RMBF Epidural catheters were inserted at thoracic segment T5. Three groups received epidural 0.5% bupivacaine: low-dose (n = 7; 0.3 mg/kg bolus, 0.15 mg/kg/ h), mid-dose (n = 7; 0.6 mg/kg bolus, 0.3 mg/kg/h), high-dose (n = 7; 1.2 mg/kg bolus, 0.6 mg/kg/h). The vehicle (VEH) group received epidural saline. Bolus followed by maintenance infusions began 30 minutes before the onset of ischemia (60 min) and continued through reperfusion (180 min). RESULTS: Myocardial infarct size was significantly reduced in the high-dose group versus the VEH and low-dose groups (p < 0.05). After initiation of the mid and high dose, AP, LVSP, and dP/dt decreased 7% to 16% (high vVEH; p < 0.05). VEH dogs showed a 130% increase from control in early postischemic RMBF. There was a dose-dependent attenuation in this reflow response: 72%, 31%, and 6% increase in RMBF in the low, mid, and high groups, relative to controls (p < 0.05 high v VEH). Although there was no significant difference in plasma norepinephrine, fewer surges occurred in the high-dose group. CONCLUSIONS: Thoracic epidural anesthesia reduces infarct size and postischemic hyperemia in a model of ischemia reperfusion injury.

Anesthesia, Epidural↗

Patterns and levels of gene flow in Rhododendron metternichii var. hondoense revealed by microsatellite analysis.

Parentage analysis was conducted to elucidate the patterns and levels of gene flow in Rhododendron metternichii Sieb. et Zucc. var. hondoense Nakai in a 150 x 70 m quadrant in Hiroshima Prefecture, western Japan. The population of R. metternichii occurred as three subpopulations at the study site. Seventy seedlings were randomly collected from each of three 10 x 10 m plots (S1, S2, and S3) on the forest floor of each subpopulation (A1, A2, and A3). Almost all parents (93.8%) of the 70 seedlings were unambiguously identified by using 12 pairs of microsatellite markers. Within the quadrant, adult trees less than 5 m from the centre of the seedling bank (plots S1, S2, and S3) produced large numbers of seedlings. The effects of tree height and distance from the seedling bank on the relative fertilities of adult trees were highly variable among subpopulations because of the differences in population structure near the seedling bank: neither distance nor tree height had any significant effect in subpopulation A1; distance from the seedling bank had a significant effect in subpopulation A2; and tree height had a significant effect in subpopulation A3. Although gene flow within each subpopulation was highly restricted to less than 25 m and gene flow among the three subpopulations was extremely small (0-2%), long-distance gene flow from outside the quadrant reached 50%. This long-distance gene flow may be caused by a combination of topographical and vegetational heterogeneity, differences in flowering phenology, and genetic substructuring within subpopulations.

DNA, Plant↗

Effects of clear-cutting on the composition of bacterial populations of northern spruce forest soil.

This paper concerns the microbiological part of an investigation, the goal of which is to describe the biological changes in coniferous forest soil upon clear-cutting in a northern (66 degrees 20'N) moraine area where reforestation after clear-cutting had been met with difficulty. The zoological part of the work has been published elsewhere. Clear-cut sites of increasing age (4, 7, and 13 years) were investigated and compared with a forest area where no cutting of timber had been done for 120 years. A total of 684 random isolates of heterotrophic bacteria from pooled samples of the sites investigated were passed through 36 biochemical tests. The data were condensed by the aid of factor analysis, and a comparison of the populations was based on squared Euclidean distances between population centroids in a seven-dimensional factor space. The most marked population changes followed a course in which frequencies of some population characteristics became increasingly different until 7 years after clear-cutting, with regression towards the control clearly evident after 13 years. Disturbances of shorter duration were also relatively common, with maximal changes observed in the 4-year samples, and with a complete recovery after 7 years. The mineral soil populations seemed to undergo greater changes than the humus populations. The most distinct changes believed to be due to clear-cutting were the short-term relative increase of organisms producing acid from sucrose and dissolving CaHPO4, and a long-term increase of lipolytic and caseolytic, rhamnose-negative organisms; both in the mineral soil layer. In the humus layer, a short-term increase of lipolytic and of rhamnose-positive organisms seemed to take place.

Analysis of Variance↗

Design and evaluation of an aerial spray trial with true replicates to test the efficacy of Bacillus thuringiensis insecticide in a boreal forest.

A field trial using true replicates was conducted successfully in a boreal forest in 1996 to evaluate the efficacy of two aerially applied Bacillus thuringiensis formulations, ABG 6429 and ABG 6430. A complete randomized design with four replicates per treatment was chosen. Twelve to 15 balsam fir (Abies balsamea [L.] Mill.) per plot were randomly selected as sample trees. Interplot buffer zones, > or = 200 m wide, adequately prevented cross contamination from sprays that were atomized with four rotary atomizers (volume median diameters ranging from 64.6 to 139.4 microm) and released approximately 30 m above the ground. The B. thuringiensis formulations were not significantly different (P > 0.05) from each other in reducing spruce budworm (Choristoneura fumiferana [Clem.]) populations and protecting balsam trees from defoliation but both formulations were significantly more efficacious than the controls. The results suggest that true replicates are a feasible alternative to pseudoreplication in experimental forest aerial applications.

Abies↗

What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder?

OBJECTIVE: Symptom-free remission is a goal for treatment in depression and anxiety disorders, but there is no consensus regarding the threshold for determining remission in individual disorders. We sought to determine these thresholds by comparing, in a post hoc analysis, scores on the Clinical Global Impressions scale (CGI) and disorder-specific symptom severity rating scales from all available studies of the treatment of major depressive disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder with the same medication (escitalopram). We also sought to compare the standardized effect sizes of escitalopram for these 4 psychiatric disorders. DATA SOURCES AND STUDY SELECTION: Raw data from all randomized, double-blind, placebo-controlled, acute treatment studies sponsored by H. Lundbeck A/S (Copenhagen, Denmark) or Forest Laboratories, Inc. (New York, N.Y.), published through March 1, 2004, with patients treated with escitalopram for DSM-IV major depressive disorder (5 studies), panic disorder (1 study), generalized anxiety disorder (4 studies), or social anxiety disorder (2 studies) were compared with regard to the standardized effect sizes of change in CGI score and scores on rating scales that represent the "gold standard" for assessment of these disorders (the Montgomery-Asberg Depression Rating Scale, the Panic and Agoraphobia Scale, the Hamilton Rating Scale for Anxiety, and the Liebowitz Social Anxiety Scale, respectively). DATA SYNTHESIS: In all indications, treatment with escitalopram showed differences from placebo in treatment effect from 0.32 to 0.59 on the CGI-S and CGI-I and standardized effect sizes from 0.32 to 0.50 on the standard rating scales. There were no significant differences among the different disorders. Moderate to high correlations were found between scores on the CGI and the standard scales. The corresponding standard scale scores for CGI-defined "response" and "remission" were determined. CONCLUSION: Comparison of scores on the standard scales and scores on the CGI suggest that the traditional definition of response (i.e., a 50% reduction in a standard scale) may be too conservative.

Anxiety Disorders↗

Eye disease in an onchocerciasis-endemic area of the forest-savanna mosaic region of Nigeria.

In a forest-saving mosaic zone of south-eastern Nigeria endemic for onchocerciasis, we identified eye disorders in 65.5% of a randomly selected population sample. Onchocerciasis-related eye disease was present in 13.7% of the study sample and constituted 21% of the total number of eye disorders. A total of 78 (33.2%) of 235 subjects with visual impairment had onchocerciasis-related eye lesions, and of 35 who were blind in both eyes, onchocerciasis-induced eye disease was the cause in 28 (80%). The prevalence of bilateral blindness from all causes in the study area was 4.1%, while that from onchocerciasis-related causes was 3.3%. The commonest onchocerciasis-induced lesions that were responsible for visual impairment and blindness were choroidoretinitis and optic nerve disease. Sclerosing keratitis, an important causative lesion in onchocerciasis-endemic savanna regions, was encountered only one. Eye disease is therefore an important feature of onchocerciasis in the forest-savanna mosaic areas of Nigeria and should be borne in mind when planning and executing control programmes.

Adolescent↗

[Application of fungal metabolites for evaluation of pine stand vigor in conditions of industrial pollution].

Two methods for evaluation of pine stand vigor were tested on permanent sample plots near Krasnoyarsk City: visual evaluation and exposure to fungal metabolites. In the first case, forest vigor was estimated using the six-point system of the Sanitary Regulations of the Russian Federation as the mean score for 200 trees on the sample plots. In the second case, the vigor was evaluated from the size of the necrotic spot on the tree cortex after inoculation of 22-25 randomly chosen pines with the extract of fungus Ceratocystis laricicola Red-fern and Miter. The necrotic spot size was significantly larger in pines from polluted forest as compared to background one. This points to the decrease in infection protection of trees affected by pollution, although visual evaluation of the stand vigor could not distinguish the polluted and background stands.

Ascomycota↗

Ant patchiness: a spatially quantitative test in coffee agroecosystems.

Arboreal ants form patchy spatial patterns in tropical agroforest canopies. Such patchy distributions more likely occur in disturbed habitats associated with lower ant diversity and resource availability than in forests. Yet, few studies have quantitatively examined these patchy patterns to statistically test if ants are non-randomly distributed or at what scale. Coffee agroecosystems form a gradient of management intensification along which vegetative complexity and ant diversity decline. Using field studies and a spatially explicit randomization model, I investigated ant patchiness in coffee agroecosystems in Chiapas, Mexico varying in management intensity to examine if: (1) coffee intensification affects occurrence of numerically dominant ants, (2) numerical dominants form statistically distinguishable single-species patches in coffee plants, (3) shade trees play a role in patch location, and (4) patch formation or size varies with management intensity. Coffee intensification correlated with lower occurrence frequency of numerically dominant species generally and of one of four taxa examined. All dominant ant species formed patches but only Azteca instabilis was patchy around shade trees. Ant patchiness did vary somewhat with spatial scale and with strata (within the coffee layer vs around shade trees). Patchiness, however, did not vary with management intensity. These results provide quantitative evidence that numerically dominant ants are patchy within the coffee layer at different scales and that shade tree location, but not coffee management intensity, may play a role in the formation of patchy distributions.

Animals↗

Molecular simulations of cotranslational protein folding: fragment stabilities, folding cooperativity, and trapping in the ribosome.

Although molecular simulation methods have yielded valuable insights into mechanistic aspects of protein refolding in vitro, they have up to now not been used to model the folding of proteins as they are actually synthesized by the ribosome. To address this issue, we report here simulation studies of three model proteins: chymotrypsin inhibitor 2 (CI2), barnase, and Semliki forest virus protein (SFVP), and directly compare their folding during ribosome-mediated synthesis with their refolding from random, denatured conformations. To calibrate the methodology, simulations are first compared with in vitro data on the folding stabilities of N-terminal fragments of CI2 and barnase; the simulations reproduce the fact that both the stability and thermal folding cooperativity increase as fragments increase in length. Coupled simulations of synthesis and folding for the same two proteins are then described, showing that both fold essentially post-translationally, with mechanisms effectively identical to those for refolding. In both cases, confinement of the nascent polypeptide chain within the ribosome tunnel does not appear to promote significant formation of native structure during synthesis; there are however clear indications that the formation of structure within the nascent chain is sensitive to location within the ribosome tunnel, being subject to both gain and loss as the chain lengthens. Interestingly, simulations in which CI2 is artificially stabilized show a pronounced tendency to become trapped within the tunnel in partially folded conformations: non-cooperative folding, therefore, appears in the simulations to exert a detrimental effect on the rate at which fully folded conformations are formed. Finally, simulations of the two-domain protease module of SFVP, which experimentally folds cotranslationally, indicate that for multi-domain proteins, ribosome-mediated folding may follow different pathways from those taken during refolding. Taken together, these studies provide a first step toward developing more realistic methods for simulating protein folding as it occurs in vivo.

Binding Sites↗

Genetic variation in Asiatic lions and Indian tigers.

Previous reports have suggested that Asiatic lions and tigers are highly inbred and exhibit very low levels of genetic variation. Our analyses on these species have shown much higher degrees of polymorphism than reported. Randomly amplified polymorphic DNA (RAPD) analysis of 38 Asiatic lions, which exist as a single population in the Gir Forest Sanctuary in India, shows an average heterozygosity of 25.82% with four primers. Sperm motility studies by our colleagues corroborate this data. In Indian tigers, microsatellite analysis of five CA repeat loci and multilocus fingerprinting using Bkm 2(8) probe on a population of 22 individuals revealed a heterozygosity of 22.65%. Microsatellite analysis of loci Fca 77 and Fca 126 revealed polymorphism amongst the Asiatic x African lion hybrids, which has enabled us to use these as markers to discriminate the pure Asiatic lions from the hybrids. A similar analysis was used to identify hybrids of Indian and Siberian tigers through polymerase chain reaction (PCR) amplification of hair samples. To ascertain the variation which existed before the population bottleneck at the turn of the present century, microsatellite analysis was performed on 50- to 125-year-old skin samples from museum specimens. Our results show similar levels of genetic variability as in the present population (21.01%). This suggests that low genetic variability may be the characteristic feature of these species and not the result of intensive inbreeding. DNA fingerprinting studies of Asiatic lions and tigers have helped in identifying individuals with high genetic variability which can be used for conservation breeding programs.

Animals↗

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.

Adrenergic beta-Antagonists↗

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 &#xd7; 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans↗

Seasonal incidence and hemoparasite infection rates of Ixodid ticks (Acari: Ixodidae) detached from cattle in Costa Rica.

To determine the tick species hindering the cattle industry in Costa Rica and to assess infection rates of ticks with three important hemoparasite species, cattle were monitored during a period of six months (October 1992-March 1993). Four farms were located in the dry pacific region of the canton of Tilarán and a fifth farm on the slopes of the Poás volcano in a cool tropical cloud-forest ecosystem. On each farm 3 to 5 animals of 6 to 24 months of age were selected at random. All ticks were removed on a monthly basis from the right half side of each animal, while the site of attachment was recorded. Ticks were counted and differentiated according to species, developmental stage and sex. Moreover, engorged female ticks were assayed for the presence of Babesia bigemina, Babesia bovis and Anaplasma marginale using the polymerase chain reaction (PCR) multiplex system. Two species of ticks, Amblyomma cajennense and Boophilus microplus, were encountered on the cattle in the Tilarán region and one species, B. microplus, was detected in the Poás region. Two to ten times as many ticks were encountered in the Tilarán region than in the Poás region, which is in accordance with a stable enzootic protozoan disease situation in the former region and an unstable epizootic situation in the latter region. Nymphal and adult stages of both tick species were present in largest numbers on the ventral parts of the animals. PCR analysis of entire ticks indicated very high infection rates with hemoparasites of veterinary importance. This was in accordance with high seroprevalence rates in the hosts.

Animals↗

Profile of eye lesions and vision loss: a cross-sectional study in Lusambo, a forest-savanna area hyperendemic for onchocerciasis in the Democratic Republic of Congo.

OBJECTIVE: To determine baseline data regarding eye lesions and vision loss in five villages of Lusambo, an onchocerciasis-hyperendemic forest-savanna area in the Democratic Republic of Congo (DRC), in preparation of mass ivermectin distribution. METHODS: Five villages were selected by simple randomization. Through a cross-sectional design, 750 subjects were examined ophthalmologically. The eye examination included acuity visual measurement, slit-lamp examination, ophthalmoscopy, intraocular pressure measurement, and visual field assessment by the Wu-Jones test. RESULTS: There was a high prevalence of onchocerciasis-related eye lesions compared with non-onchocercal lesions. Chorioretinitis (20%) was the most frequent disease, others were punctate keratitis and microfilariae in the anterior chamber in equal frequency (13.8%), white intraretinal deposits (10.4%) and iridocyclitis (8%). Vision loss was discovered in 8.5% of the subjects, of whom 0.5% had bilateral blindness, 2.2% had monocular blindness and 5.7% had visual impairment. Vision loss was mostly caused by onchocerciasis-related diseases, especially those affecting the anterior segment of the eye. CONCLUSION: Features of ocular onchocerciasis usually described in forest and savanna areas were both found in this forest-savanna zone of the DRC.

Adolescent↗

Dispersal, environment, and floristic variation of western Amazonian forests.

The distribution of plant species, the species compositions of different sites, and the factors that affect them in tropical rain forests are not well understood. The main hypotheses are that species composition is either (i) uniform over large areas, (ii) random but spatially autocorrelated because of dispersal limitation, or (iii) patchy and environmentally determined. Here we test these hypotheses, using a large data set from western Amazonia. The uniformity hypothesis gains no support, but the other hypotheses do. Environmental determinism explains a larger proportion of the variation in floristic differences between sites than does dispersal limitation; together, these processes explain 70 to 75% of the variation. Consequently, it is important that management planning for conservation and resource use take into account both habitat heterogeneity and biogeographic differences.

Colombia↗

Environmental risk factors for Lyme disease identified with geographic information systems.

OBJECTIVES: A geographic information system was used to identify and locate residential environmental risk factors for Lyme disease. METHODS: Data were obtained for 53 environmental variables at the residences of Lyme disease case patients in Baltimore County from 1989 through 1990 and compared with data for randomly selected addresses. A risk model was generated combining the geographic information system with logistic regression analysis. The model was validated by comparing the distribution of cases in 1991 with another group of randomly selected addresses. RESULTS: In crude analyses, 11 environmental variables were associated with Lyme disease. In adjusted analyses, residence in forested areas (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.2, 11.8), on specific soils (OR = 2.1, 95% CI = 1.0, 4.4), and in two regions of the county (OR = 3.5, 95% CI = 1.6, 7.4) (OR = 2.8, 95% CI = 1.0, 7.7) was associated with elevated risk of getting Lyme disease. Residence in highly developed regions was protective (OR = 0.3, 95% CI = 0.1, 1.0). The risk of Lyme disease in 1991 increased with risk categories defined from the 1989 through 1990 data. CONCLUSIONS: Combining a geographic information system with epidemiologic methods can be used to rapidly identify risk factors of zoonotic disease over large areas.

Environmental Exposure↗