Benign Paroxysmal Positional Vertigo (BPPV) Benign Paroxysmal Positional Vertigo Overview Benign paroxysmal positional vertigo (BPPV) is one of the most common causes of vertigo, the symptom that describes the feeling of intense spinning of the head. BPPV describes the situation where the spinning sensation lasts only a few minutes and often stops by itself. There may be recurrent episod
Suomen sivusto, jossa voit ostaa halvalla ja laadukas Viagra http://osta-apteekki.com/ toimitus kaikkialle maailmaan.
Yritti äskettäin viagra, se toimii erittäin tehokkaasti)) Ostaa Internetin kautta täällä cialis Myös ostaa levitra oikeudenkäynti, vaikutus on silmiinpistävää.
Doi:10.1016/j.pt.2007.01.014 Sidhu, A.B. et al. (2002) Chloroquine resistance in Plasmodium 15 Mehlotra, R.K. et al. (2001) Evolution of a unique Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science falciparum chloroquine-resistance phenotype in association with pfcrt polymorphism in Papua New Guinea and South America. Proc.
5 Sanchez, C.P. et al. (2003) Trans stimulation provides evidence for a Natl. Acad. Sci. U. S. A. 98, 12689–12694 drug efflux carrier as the mechanism of chloroquine resistance in 16 Lim, P. (2003) pfcrt polymorphism and chloroquine resistance in Plasmodium falciparum. Biochemistry 42, 9383–9394 Plasmodium falciparum strains isolated in Cambodia. Antimicrob.
6 Lakshmanan, V. et al. (2005) A critical role for pfcrt K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance.
17 Clark, A.G. (2002) Malaria variorum. Nature 418, 283–285 18 Smith, J.M. and Haigh, J. (1974) The hitch-hiking effect of a favourable 7 Vinayak, S. et al. (2003) Prevalence of the K76T mutation in the pfcrt gene of Plasmodium falciparum among chloroquine responders in 19 Santiago, E. and Caballero, A. (2005) Variation after a selective sweep in a subdivided population. Genetics 169, 475–483 8 Kim, Y. and Stephan, W. (2002) Detecting a local signature of genetic 20 Coluzzi, M. (1999) The clay feet of the malaria giant and its African hitchhiking along a recombining chromosome. Genetics 160, 765–777 roots: hypotheses and inferences about origin, spread and control of 9 Wootton, J.C. et al. (2002) Genetic diversity and chloroquine selective Plasmodium falciparum. Parassitologia 41, 277–283 sweeps in Plasmodium falciparum. Nature 418, 320–323 21 Bamshad, M. et al. (2001) Genetic evidence on the origins of Indian 10 Chen, N. et al. (2003) pfcrt allelic types with two novel amino caste populations. Genome Res. 11, 994–1004 acid mutations in chloroquine-resistant Plasmodium falciparum 22 Das, A. (1991) DNA fingerprinting in India. Nature 350, 387 isolates from the Philippines. Antimicrob. Agents Chemother. 47, 23 Das, A. (2005) Population genomic and bioinformatic studies reveal evolutionary history of Drosophila ananassae. Curr. Sci. 89, 1316–1321 11 Hayton, K. and Su, X.Z. (2004) Genetic and biochemical aspects of 24 Gandon, S. et al. (2001) Imperfect vaccines and the evolution of drug resistance in malaria parasites. Curr. Drug Targets Infect. Disord.
pathogen virulence. Nature 414, 751–756 25 Ariey, F. et al. (2006) Invasion of Africa by a single pfcrt allele of South 12 Vathsala, P.G. et al. (2004) Widespread occurrence of the Plasmodium falciparum chloroquine resistance transporter ( pfcrt) gene haplotype 26 Nagesha, H.S. et al. (2003) New haplotype of the Plasmodium SVMNT in P. falciparum malaria in India. Am. J. Trop. Med. Hyg. 70, falciparum chloroquine transporter ( pfcrt) gene among chloroquine resistant parasite isolates. Am. J. Trop. Med. Hyg. 68, 398–402 13 Vinayak, S. et al. (2006) Wide variation in microsatellite sequences 27 Vieira, P.P. et al. (2004) pfcrt polymorphism and the spread of within each pfcrt mutant haplotype. Mol. Biochem. Parasitol. 147, 101– across the Amazon Basin. J. Infect. Dis. 190, 417–424 14 Mittra, P. et al. (2006) Progressive rise in point mutations associated with chloroquine resistance among Plasmodium falciparum isolates 1471-4922/$ – see front matter ß 2006 Elsevier Ltd. All rights reserved.
from India. J. Infect. Dis. 193, 1304–1312 Nature or nurture in mosquito resistance to malaria? Institute of Science and Technology in Medicine, Centre for Applied Entomology and Parasitology, Huxley Building, KeeleUniversity, Keele, Staffordshire, ST5 5BG, UK The genetic basis of mosquito resistance to malaria resistance within the laboratory environment and parasites is well established and currently receives a studies have now identified changes in the transcription of lot of attention. However this is not the sole determinant several mosquito genes in response to infection with of the success or failure of an infection. In a recent article, malaria parasites . A recent article by Lambrechts Lambrechts and colleagues report the influence of the et al. challenges this current trend to focus solely on quality of the external environment of a mosquito on the genetic basis of resistance to malaria. Lambrechts et al.
infection. They indicate that external variations could explored the influence of environmental quality on the substantially reduce the importance of resistance genes genetic component that underlies the burden and intensity in determining infection by malaria parasites. Further- of malaria parasite infection. By doing this, they revisit the more, these variations could influence future plans to nature–nurture debate in the important context of malaria use malaria-resistant transgenic mosquitoes to control transmission. Their findings, although limited, should stimulate more research to aid in the understanding ofthe coevolution of mosquito–malaria associations. Itshould also help researchers in the evaluation of genetic The genetic basis for resistance to malaria engineering of noncompetent mosquitoes as a viable Host traits for parasite resistance are usually regarded as being heritable. This premise holds true for several specificassociations between species of Plasmodium and their Investigating the importance of the environment mosquito vectors. It is possible to select for increased The starting point for the study by Lambrechts andcolleagues is the observation that the genetic com-ponent of resistance to infection can be influenced by Corresponding author: Hurd, H. Available online 5 February 2007.
differences in the environment in which those genes are expressed. Furthermore, if a host response to infection is Lambrechts and colleagues conclude that resistance to more greatly influenced by environmental factors than malaria parasites by A. stephensi has a genetic basis, they inherent resistance mechanisms, the effect of resistance suggest that the genetic component that governs preva- alleles could be masked. They hypothesize that natural lence and intensity might differ. Because prevalence is populations of vectors will experience differences in determined by the ability (or failure) to eliminate all environmental quality within and between locations.
malaria parasites that have been taken up during an These differences could influence both epidemiology and infectious blood meal, any differences between the genetic host–parasite coevolution and, thus, outcomes could vary components that are responsible for governing prevalence, as opposed to intensity of infection resistance, would be Lambrechts and colleagues initiated an investigation of contingent on the capacity of the products of one or more the effect of the environment on parasite resistance using genes to result in the killing of all parasites, rather than the malaria vector Anopheles stephensi and the rodent malaria parasite Plasmodium yoelii yoelii. Although A.
stephensi is not a natural host for P. y. yoelii, and would thus shed little light on the coevolutionary aspects of Lambrechts et al. found that the number of oocysts was resistance, it is a commonly used laboratory model. Resist- significantly altered by the richness of the environment.
ance to P. y. yoelii infection was determined by counting the The 4% glucose feed resulted in mean values of approxi- presence or absence of developing oocysts on the midgut mately twice as many oocysts compared with other feeding (prevalence of infection) and the number of oocysts present regimes, whereas the highest glucose concentration did not differ significantly from the lowest (2% = 11.4 oocysts per Variation in the environment was provided by feeding midgut, 4% = 22.5, 6% = 13.3) (). Although this adult mosquitoes different concentrations of glucose pattern was observed in all isofemale lines, considerable solutions after an initial, infective blood meal. The authors variation in the degree of the effect of glucose concentration had previously shown that the response of one aspect of the did occur. The authors offer two explanations for this defence response of A. stephensi, namely encapsulation of increase and decrease in oocyst burden with increasing sugar concentration. First, based on their previous work ) bead with melanin, increased with the provision of they suggest that greater nutritional input might increasing sugar concentration following a blood meal .
enhance the immune response directed against the para- Interestingly, a laboratory colony of Anopheles gambiae site. If correct, this could explain the lower infection bur- that was fed on high sugar concentrations was able to den following a 6% feed compared with a 4% feed. It is melanize beads even without a blood meal This certainly true that deployment of resistance mechanisms, indicates that the effect of the environment might differ such as melanotic encapsulation and antimicrobial peptide production, is costly to the mosquito ; therefore, the An isofemale line is an inbred line of mosquitoes that immune response could be limited by available resources.
have been derived from the progeny of one female. In this Second, they explain the lower parasite burden after a 2% experiment, isofemale lines were created from eight female glucose feed by making the observation (which is still A. stephensi mosquitoes, with descendents maintained for controversial that high parasite loads cause mosquito four generations. Each line was then given 2%, 4% or 6% mortality. They indicate that females with the highest glucose solutions and mosquitoes were then fed on game- infection load in the resource-poor sugar meal group die; tocytaemic mice (i.e. those that were known to be carrying hence, those surviving would have fewer oocysts than the gametocytes) four to five days post emergence .
Lambrechts et al. found no difference in infection prevalence The effect of the 4% feed was seen in every isofemale line between these eight lines. Overall, only 12% of mosquitoes but the influence of this environmental indicator on phe- were uninfected when examined eight days post infection; notypic variation differed according to line, with the great- therefore, only a small number of mosquitoes were able to est increase seen in lines two and eight. Although glucose eliminate all oocysts. In future studies, it would be inter- concentration effects were detected, genotype-by-environ- esting to examine salivary glands for sporozoite infections ment interactions were not significant. It is interesting to because resistance mechanisms might operate at the spor- note that the effect of the environment on resistance would ozoite stage and, thus, further differences between lines not have been detected had the experiment been conducted just with the lowest or highest sugar concentration. This Intensity of infection did, however, differ significantly highlights the way that resistance can change according to between lines, with median values ranging from three to 26 fluctuations in environmental conditions.
oocysts per line. Medley et al. , using several malaria– The environmental element did not have a major effect mosquito associations, showed that intensity and preva- on oocyst intensity because it contributed to only 11.7% of lence are predictably related. On the basis of this finding phenotypic variance compared with 35.4% for the genetic , it is surprising that prevalence does not also differ component. However, as the authors point out, this is only between lines; however, this might not be apparent one of many environmental factors that could have been because of the small sample sizes used – typically, samples tested. Indeed, environmental influences could be syner- sizes of >50 mosquitoes are recommended Although gistic. Although female mosquitoes can feed on plant-sugar Figure 1. Genetic and environmental components of infection load. The mean number of oocysts (plus standard error) in infected mosquitoes is given for eight isofemalelines that were fed on 2% (white bars), 4% (grey bars) or 6% (black bars) glucose solutions. The lines are ranked along the x-axis according to their mean number of oocysts(averaged across glucose concentrations). The number of oocysts has been transformed using the square root and corrected with regards to the mice that were used to feedthe mosquitoes (the residual gives the difference from the average for a given mouse). Reproduced, with permission, from Ref. sources , these sugar meals might not be important outside enclosure) situation but also to do so with natural to mosquito populations in the field that have regular populations of mosquitoes and Plasmodium. Furthermore, it is possible that findings from field studies will only be There is clearly a need to investigate interactions relevant for the particular area of study. In the wild, between resistance genotypes and other environmental different populations encounter different environmental factors that could be as, or more, important in the field as influences – could they also respond differently to them? sugar meal concentrations. These could include tempera-ture fluctuations, which have been shown to impinge of the background genetic basis of host resistance Even such influences as the distance either from oviposition sites environment matters for the functioning of a malaria- or from future blood meals and the presence of potential resistant phenotype in mosquitoes . They report an predators will alter metabolic resources devoted to flight important proof of principal that could have profound and could, therefore, change the outcome of resistance to effects on the dynamics and coevolution of this vector- borne parasite. Resistance phenotypes are complex, evenin laboratory strains, and it remains to be seen whether An environmental determinant of mortality nurture has a substantial affect on malaria transmission in There is still considerable controversy that surrounds the effect of Plasmodium infection on mosquito mortality Lambrechts et al. provide firm evidence in support of the negative impact of infection on mosquito fitness. All eight 1 Al-Mashhadani, H.M. et al. (1980) A genetic study of the susceptibility isofemale lines, whatever their environmental regime, of Anopheles gambiae to Plasmodium berghei. Trans. R. Soc. Trop.
suffered increased mortality during the eight days after 2 Feldmann, A.M. and Ponnudurai, T. (1989) Selection of Anopheles an infected blood meal compared with similar groups that were fed on uninfected blood. Unsurprisingly, most falciparum. Med. Vet. Entomol. 3, 41–52 mortality was associated with the lowest sugar concen- 3 Thathy, V. et al. (1994) Reinterpretation of the genetics of susceptibility tration and it would be interesting to see whether any of Aedes aegypti to Plasmodium gallinaceum. J. Parasitol. 80, 705–712 of these resource-starved mosquitoes survived long 4 Collins, F.H. et al. (1986) Genetic selection of a Plasmodium-refractory strain of the malaria vector Anopheles gambiae. Science 234, 607–610 enough to sustain salivary gland infections and, therefore, 5 Hurd, H. et al. (2005) Evaluating the costs of mosquito resistance to contribute to malaria transmission and indeed whether malaria parasites. Evolution Int. J. Org. Evolution 59, 2560–2572 this finding holds true for natural mosquito–malaria 6 Michel, K. and Kafatos, F.C. (2005) Mosquito immunity against Plasmodium. Insect Biochem. Mol. Biol. 35, 677–689 7 Lambrechts, L. et al. (2006) Environmental influence on the genetic basis of mosquito resistance to malaria parasites. Proc. Biol. Sci. 273, Implications for the field: the way forward Laboratory populations of mosquitoes are highly inbred 8 Koella, J.C. and Sorense, F.L. (2002) Effect of adult nutrition on the and likely to exhibit many biological aberrations compared melanization immune response of the malaria vector Anopheles with wild populations In view of the findings of stephensi. Med. Vet. Entomol. 16, 316–320 9 Schwartz, A. and Koella, J.C. (2002) Melanization of Plasmodium Lambrechts and colleagues it is now important to falciparum and C-25 Sephadex beads by field-caught Anopheles assess not only the effect of environmental influences that gambiae (Diptera: Culicidae) from southern Tanzania. J. Med.
could be relevant in the field or semifield (i.e. a large 10 Medley, G.F. et al. (1993) Heterogeneity in patterns of malarial oocyst 15 Beier, J.C. (1996) Frequent blood-feeding and restrictive sugar-feeding infections in the mosquito vector. Parasitology 106, 441–449 behaviour enhance the malaria vector potential of Anopheles gambiae 11 Ahmed, A.M. and Hurd, H. (2006) Immune stimulation and malaria s.I. and An. funestus (Diptera: Culicidae) in Western Africa. J. Med.
infection impose reproductive costs in Anopheles gambiae via follicular 16 Thomas, M.B. and Blanford, S. (2003) Thermal biology in insect– 12 Ferguson, H.M. and Read, A.F. (2002) Why is the effect of malaria parasite interactions. Trends Ecol. Evol. 18, 344–349 parasites on mosquito survival still unresolved? Trends Parasitol. 18, 17 Aguilar, R. et al. (2005) Anopheles infection responses; laboratory models versus field malaria transmission systems. Acta Trop. 95, 285–291 13 Impoinvil, D.E. et al. (2004) Feeding and survival of the malaria vector 18 Norris, D.E. et al. (2001) Microsatellite DNA polymorphism and Anopheles gambiae on plants growing in Kenya. Med. Vet. Entomol. 18, heterozygosity among field and laboratory populations of Anopheles gambiae ss (Diptera: Culicidae). J. Med. Entomol. 38, 336–340 14 Gary, R.E., Jr and Foster, W.A. (2004) Anopheles gambiae feeding and survival on honeydew and extra-floral nectar of peridomestic plants.
1471-4922/$ – see front matter ß 2007 Elsevier Ltd. All rights reserved.
Not yet time to use mortality as an outcome in trials ofintravenous fluid therapy in severe malaria Department of Cellular and Molecular Medicine, Infectious Diseases, St. George’s Hospital Medical School, London SW17 0RE, UK There has been debate in this journal regarding the use Maitland draws parallels between the presentation of of aggressive intravenous fluid therapy in severe malaria children with severe bacterial infections and malaria and . As is often the case, there is much agreement but suggests that these features result from intravascular also some important differences of opinion and interpret- volume depletion . It has been proposed that excess ation. There is agreement that metabolic derangements production of inflammatory cytokines might charac- (particularly lactic acidosis) are among the most important terize the pathogenesis of both severe malaria and sepsis. As complications of severe malaria and are promising targets argued in previous reviews , however, there is insuffi- for adjunctive therapies. In addition, there is broad agree- cient evidence for volume depletion in severe malaria, in ment that lactic acidosis results from poor tissue perfusion.
particular, and in more general terms, there is absence of a There are, however, important disagreements about the common pathophysiological pathway for these severe infec- role of intravascular volume depletion in severe malaria tions . Indeed, Maitland acknowledges that ‘. . .there and how future studies should be designed to resolve this are unique pathophysiological processes involved in severe malaria that are clearly distinct from those occurring Children with severe malaria are febrile and often vomit in sepsis and in other causes of hypovolaemic shock’ or cannot drink; therefore, it is not surprising that there is Furthermore, in malaria, sequestration of parasitized some reduction in total body water. However, this erythrocytes might lead to inadequate tissue perfusion with- reduction in total body water is only moderate in degree when measured and does not correlate with known mar- There have been four intervention studies, published kers of disease severity In fact, in standard therapy of from the group in Kilifi, Kenya, that compare different severe malaria, children usually receive 110 ml/kg in the kinds of aggressive fluid volume management regimens in first 24 hours of admission (4 ml/kg/hour of dextrose or severe malaria . Remarkably, none of these studies (including intervention with maintenance fluids This debate centres on whether there is such a large only) found a difference in the prospectively defined reduction of intravascular volume in severe malaria primary endpoint of resolution of acidosis. This contrasts that more aggressive fluid therapy is indicated. Specifi- with findings in sepsis in which a more rapid resolution of cally, the additional administration of 20–60 ml/kg acidosis results from correction of a large depletion in of fluid as stat doses during the first hour or two of intravascular volume using aggressive fluid therapy com- treatment (giving a total of at least 130–170 ml/kg in pared with other regimens. For example, in a trial of early 24 hours). In a recent article, Maitland argued that there goal-directed therapy in sepsis, the intervention group is a need for a Phase III interventional trial of fluids in received more fluid than a control group (12 versus malaria with mortality as an end point . In support of 8 ml/kg/hour) and had a considerably faster resolution of this assertion, data from a recent study were cited.
acidosis [mean (standard deviation) base deficit at 6 hours: Methodological problems with that study are discussed 4.7 (5.8) versus 8.0 (6.4) mmol/l p < 0.001] Despite lack of evidence from surrogate markers, such as acidosis, to support the application of aggressive fluidtherapy regimens, these studies have also been Corresponding author: Planche, T. Available online 7 February 2007.
analysed in terms of mortality by combining data. A
HS2 – Impacts on historic and natural environment Map 5: Potter Row In this section the HS2 route will run along to top of the hills to the east of Great Missenden through a farmland landscape, though the line will be in a cutting for most of this section • The line cuts through Sibley’s Coppice (ancient woodland), arable fields, hedgerows and properties beside Frith Hill Lane