Sildalist

Benjamin M. Brucker, MD

• Assistant Professor, Urology
• New York University

Guidelines for systematic reviews of health promotion and public health interventions impotence related to diabetes purchase sildalist 120mg without a prescription. A multitude of syntheses: a comparison of five approaches from diverse policy fields erectile dysfunction pills in pakistan discount 120 mg sildalist with visa. Criteria for the systematic review of health promotion and public health interventions erectile dysfunction drugs history order 120mg sildalist with visa. Evaluating the effectiveness of public health interventions: the role and activities of the Cochrane Collaboration diabetes obesity and erectile dysfunction order sildalist with amex. Providing affordable family housing and reducing residential segregation by income erectile dysfunction icd 9 purchase sildalist 120 mg with mastercard. Realist review: a new method of systematic review designed for complex policy interventions erectile dysfunction pump images generic sildalist 120 mg otc. Do urban regeneration programmes improve public health and reduce health inequalitiesfi Systematic review of the effectiveness of stage based interventions to promote smoking cessation. Exploring the potential effectiveness of workplace exercise and physical activity interventions [PhD thesis]. School feeding for improving the physical and psychosocial health of disadvantaged students. Road traffic crashes: operationalizing equity in the context of health sector reform. Inequalities and the mental health of young people: a systematic review of secondary school-based cognitive behavioural interventions. Reconsidering community-based health promotion: promise, performance, and potential. Information retrieval in systematic reviews: challenges in the public health arena. Systematic overview of population tobacco control interventions and their effects on social inequalities in health. Data collection instrument and procedure for systematic reviews in the Guide to Community Preventive Services. Ottawa, Canada: Cochrane Effective Practice and Organisation of Care Review Group; 2002. A systematic review of the effectiveness of health promotion interventions in the workplace. An instrument for reviewing the effectiveness of health education and health promotion. Program integrity in primary and early secondary prevention: are implementation effects out of controlfi A new tool to incorporate implementation data into systematic reviews: applying the Oxford Implementation Index [abstract]. The harvest plot: a method for synthesising evidence about the differential effects of interventions. Applicability and transferability of interventions in evidence-based public health. Many adverse effects can be explained by the mode of action of the intervention and can therefore be anticipated and explained. Others may be unexpected, occurring only where unique combinations of genetic factors or personality and environment combine. Some adverse effects may be extensions of the expected response to an intervention; for example severe constipation following the use of an anti-diarrhoeal (loperamide). Others may occur where the response to an intervention is unexpectedly negative; for example phocomelia (limb abnormalities) following the use of thalidomide for pregnancy induced nausea. Health care professionals and patients need information about both intended and unintended effects of an intervention in order to make an informed decision about its adoption. Systematic review of adverse effects and consideration of adverse effects within reviews of effectiveness therefore needs to be encouraged. Many systematic reviews have attempted to review all adverse effects of an intervention,10 but this can be problematic given the often large numbers of different associated adverse effects/events some of which may be poorly documented. It is important to balance comprehensiveness against clinical relevance and in practical terms the outcomes chosen should be those that are important in guiding decisions related to the intervention. The basic principles for carrying out a systematic review, as described in Chapter 1 also apply to reviews of adverse effects. This chapter focuses on the differences in approach and specific issues related to assessment of the safety and tolerability of an intervention. Given that, to date, much development has been around adverse effects of pharmacological interventions, this chapter refiects this emphasis. However, the principles also apply to other types of intervention, such as surgical procedures and medical devices. Any resulting adverse effects may be experienced across conditions or may be population specific. Decisions will need to be made about whether the review will focus on a specific population with a particular diagnosis or whether all patient populations who have received the intervention will be included. For example, a review assessing the effect of statins on cancer risk did not specify why the patients in the studies were taking statins. Overall, broader inclusion criteria make the findings more generalisable, whereas narrower inclusion criteria are likely to produce more homogenous results. Boundaries will in part depend on the type of intervention and the type of adverse effects being investigated. However it is important to recognise that there can be problems with grouping drugs together in a class; even within a class there can be differences between drugs, and assumptions should be avoided. As for reviews of effectiveness, defining nonpharmacological interventions can be difficult. Surgical procedures and medical devices are frequently modified by surgeons/ manufacturers and the researcher has to decide when such modifications might constitute a separate intervention. Complex interventions may be even more difficult to define in the context of potential adverse effects. However, sometimes it is important to explore differences between active treatments. A reliable investigation of the differences between active treatments can only be undertaken for specific adverse effects within well-defined populations. An analysis of three systematic reviews indicated that two included a broad range of events, but generated a large volume of work and yielded little useful information for decision making. Primary studies that report on adverse events may differ, for example in the definitions of a specific adverse event, severity (or intensity); the reporting (or not) of events of differing degrees of severity; the terminology used to describe similar events. The review team will need to decide whether outcomes from different studies are similar enough to group together in the review. However, primary studies may define serious adverse events differently, for example those that the investigator (or the patient) considers serious. An adverse event may be severe in intensity (as opposed to mild or moderate) without necessarily being serious. Rare events almost never occur in controlled trials, with their limited participant numbers and follow-up duration. However, even published observational studies are seldom large enough to provide definitive estimates of incidence. The lack of evidence of a rare adverse effect is therefore not proof that such an adverse effect is not associated with the intervention of interest. Taking a broad approach in specifying the review question, for example by including all adverse effects, could be considered hypothesis generating, whereas hypothesis testing should seek to clarify the statistical nature of the risk, and/or better define the characteristics of the adverse effect by having a more focussed question. They may not be generalisable having excluded patients at high or even medium risk of experiencing certain adverse effects, or may have only short-term follow-up and relatively small sample sizes. Post-marketing surveillance studies may be useful sources of7 adverse events/effects data for pharmaceuticals. Published case reports have significant limitations,24 for example they frequently fail to provide important information, including an assessment of likely causal relationship to the intervention being evaluated, and some investigations have concluded that stricter criteria and guidelines for reporting are required. Although any indication that a treatment might have a significant harmful effect should not be ignored, a balance has to be struck between responding to each report of an adverse effect and trying to eliminate uncertainty before acting. However, it should be noted that analysis of this type of8 information is more akin to primary research than systematic review; using such sources will require a properly designed study to yield information, see for example the study on the role of paroxitine in suicide. If adverse effects are a secondary outcome, then the way that searches are conducted will depend largely on how the effectiveness searches were carried out. For example, if a search for effectiveness studies included only terms for the population and intervention with no search filters for study design, no terms for the outcomes, and the definition of the population has not changed, then it may be sufficient to scan the results of the effectiveness searches for information on adverse effects. These searches would be carried out in the sources already searched, as well as in additional sources specific to adverse effects. It should be noted, however, that due to the poor reporting and poor indexing of adverse effect data this method will not necessarily retrieve all the relevant papers. Consideration should be given to whether the adverse effect(s) of interest are common or rare, short or long-term, known or unknown as this will have implications for the choice of study design and therefore the most relevant sources of information and search filters. Problems in Pharmacovigilance the Australian Adverse Drug Reactions Bulletin, or Reactions Weekly (via PharmaNewsFeed) are also useful sources. Potential sources of unpublished information on adverse effects are listed in Table 4. Very few evaluations have been carried out of the comparative usefulness of these sources in terms of yield of relevant information. The way in which adverse events were monitored or recorded may affect the reported frequency and so should also, if possible, be extracted. For example, noting whether the data were collected at follow-up (and if so how frequently), and whether collected by patient diary or checklist, or relied on spontaneous reporting. In studies using patient diaries, adverse effects were found to be significantly more common in the active treatment than control groups. Withdrawals and drop-outs should be extracted where possible, together with the reason if known. However, withdrawals and drop-outs are not reliable surrogates for safety or tolerability; withdrawals may be for other reasons than adverse events, for example unpleasant or inconvenient study procedures, lack of improvement or earlier than expected recovery. For example, some studies only report the number of adverse events, not the number of patients with adverse events. It is possible to derive the number of patients from the number of adverse events or use the number of adverse events. Such differences are commonly related to the sample size and study duration, which may be adequate for the primary efficacy/effectiveness variable but not for adverse effects. However, different criteria should be used for different study designs, and the criteria should have been validated by empirical evidence wherever possible. Examples include active or passive surveillance, questionnaire derived data, clinical laboratory and pharmacokinetic and pharmacodynamic data. The choice of instrument can significantly affect the identification, measurement and reporting of adverse effects. For example, were the adverse effects assessed independently by someone other than the surgeon performing the procedurefi Similarly, the Brighton Collaboration has developed guidelines for reporting adverse effects following immunisation. Studies should make clear how they identified that the harm was related to the intervention, who made the attribution. A variety of terms are used to identify adverse effects, with some of the terms remaining ill-defined and the boundaries between them not clearly described. In particular the severity of adverse effects should be adequately defined by either detailed description of severity or reference to a known scale of severity. Ideally, study results should be reported according to the methods section of the study protocol. The timing of events should also be reported, particularly when the follow- up period is prolonged. The report should specify the number of patients withdrawn from the study because of adverse effects by study arm and by type of adverse effects and detail who decided to withdraw (participant or physician) and whether attribution was blinded to the assigned treatment. Sometimes more than one adverse effect may occur in a patient but this is not always reported clearly. It is most helpful when both the number of affected participants and the total number of adverse effects are reported, with the denominators and incidence or prevalence rates. It may however, underestimate adverse effects particularly when there is a high rate of nonadherence with allocated treatment. There are a number of factors associated with bias in the reporting of adverse effects data. It is important to be clear about whether a paper includes all adverse effects that occurred or just a selected sample. It should also be clear whether the selection was made on the basis of frequency. Where critical or otherwise significant adverse effects have been reported they should ideally have been investigated and the findings included in the report. For example if the study is of healthy individuals and the main focus is prevention, even minor harms might be important in the balance of harms and benefits. Alternatively, if the main study outcome is survival, only major or life- threatening harms might be relevant.

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Inicialmente tida como uma complicacao exclusiva da osteomielite verte- bral erectile dysfunction vacuum pumps australia buy sildalist 120mg low price, as discites podem se desenvolver por invasao hematogenica e por contaminacao durante cirurgias discais impotence world association purchase sildalist overnight delivery. A caracteristica clinica desta condicao e o longo periodo entre o inicio dos sintomas de dor cer- vical erectile dysfunction treatment natural way buy sildalist in india, espasmo muscular e limitacoes de movimentos e o diagnostico definitivo(62) impotence biking discount sildalist express. A nevralgia pos-herpetica erectile dysfunction medication risks buy sildalist 120mg on line, uma complicacao frequente desta infeccao erectile dysfunction proton pump inhibitors generic sildalist 120mg with visa, e causa de morbidade significativa, com dor cervical persistente, principalmente em idosos. Em fase tardia, pode ocorrer polirradiculite afetando as ex- tremidades superiores(63). Teigland J, Magnaes B: Rheumatoid backward dislocation of the atlas with compression of the spinal cord. Lehtinen K: 76 patients with ankylosing spondylitis seen after 30 years of disease. Moller P, Vinje O, Kass E: How does Bechterewfis syndrome (ankylosing spondylitis) startfi Jenkinson T, Armas J, Evison G, et al: the cervical spine in psoriatic arthri- tis: a clinical and radiological study. Salvarani C, Macchioni P, Cremonesi W, et al: the cervical spine in patients with psoriatic arthritis: a clinical, radiological and immunogenetic study. A lombociatalgia surge quando esta dor se irradia para as nadegas e um ou ambos os membros inferiores. So nos Estados Unidos, seu custo total de tratamento esta estimado atualmente em mais de 50 bilhoes de dolares ao ano. Somente cerca de 30% dos pacientes sintomaticos apresentam alteracoes da coluna lombar na mielografia, tomografia computadorizada ou res- sonancia nuclear magnetica. Como a maioria dos casos nao necessita cirurgia, ha poucas informacoes que comprovam a existencia da le- sao tecidual correlacionada com os sintomas dolorosos. Alem disso, a inervacao da coluna e difusa e entrelacada e torna dificil localizar a lesao apenas com base nos dados da historia e exame fisicos do pa- ciente. Finalmente, existem, frequentemente associados, espasmos mus- culares reativos que protegem a coluna de outros danos e muitas vezes mascaram a verdadeira causa da dor. Infelizmente, na maioria dos pacientes, os medicos nao conse- guem identificar qual a estrutura especifica que origina a lombalgia. Etiopatogenia As lombalgias e lombociatalgias podem ser primarias ou secundarias, com e sem envolvimento neurologico, sendo classificadas em: fi. Classificacao Causas Mecanico-Degenerativas Na coluna vertebral existe um equilibrio mecanico entre o segmento anterior da unidade anatomo funcional (corpos vertebrais e disco) e fififififififififi fi fifififififififififififififi fifi o segmento posterior (articulacoes interapofisarias ou zigoapofisarias). Quando ocorre a acao de forcas mecanicas sobre essas estruturas, pode haver um desequilibrio levando a dor por estimulacao direta de terminacoes nervosas ai existentes, ou pela liberacao de substancias do nucleo pulposo que desencadeiam dor e processo inflamatorio pela degeneracao do disco intervertebral. O disco degenerado tem sua capacidade de nutricao pela difusao passiva reduzida, levando a um acumulo de ion hidrogenio que estimula receptores quimicos de dor, situados na parte externa do anel fibroso. As discopatias compreendem as fissuras, rupturas, abaulamentos, diminuicao da altura do disco e hernias que podem ser protrusas e extrusas. Essas alteracoes degenerativas do disco intervertebral acrescen- tam um esforco adicional nas outras estruturas de suporte da coluna como as articulacoes das facetas, ligamentos e capsulas articulares. Consequentemente, espessamento da membrana sinovial e capsula articular, formacao de tecido cicatricial, diminuicao do espaco articu- lar nas articulacoes facetarias, formacao de osteofitos e esclerose do osso subcondral. Essas alteracoes sao responsaveis pela dor em 10% a 15% dos pacientes com lombalgia cronica e lombociatalgia. Psicossomaticas Causas emocionais que podem levar a lombalgia ou agravar outras causas ja existentes. Como Repercussao de Doenca Sistemica Doencas sistemicas que podem acometer estruturas intra e extra-ra- quideanas, a fibromialgia e a sindrome miofascial que podem causar contraturas musculares e hipoxia tecidual gerando dor. Diagnostico Clinico A historia clinica e essencial para avaliacao diagnostica do paciente com lombalgia e lombociatalgia. A idade do paciente podera indicar a causa de sua dor, pois a incidencia de certas doencas varia de acor- do com a idade e com o sexo. Trabalho e lazer, isto e, esportes prati- cados, tambem sao importantes para o diagnostico, pois com base nos achados de Nachemson (1965, 1985), a flexao e rotacao da colu- na lombar aumenta a pressao no segmento motor inferior. Quando uma pessoa de 70kg, com um peso de 20kg nas maos, curva para a frente somente 20 graus, a pressao no disco aumenta de 150kg para 210kg na posicao ereta e para 275kg na posicao sentada. Kelsey et alii fififififififififi fi fifififififififififififififi fifi (1984), ao investigarem os fatores de risco para prolapso agudo do disco intervertebral referiram que, se se curvar mais de 20 vezes ao dia, com um peso superior a 10kg, este sera o maior fator de risco. O elevado numero de horas dirigindo veiculos motorizados e o uso de carros mais velhos tambem foram considerados fatores de alto risco para prolapso de disco intervertebral. O tabagismo influencia a nutricao do disco intervertebral e au- menta a chance de sua degeneracao; por conseguinte, torna mais frequente a incidencia de dor lombar. Atualmente, o excesso de peso corporal tambem tem sido pes- quisado e confirmado por alguns autores, como fator predisponente na genese da dor lombar. O Primeiro Consenso Brasileiro sobre Lombalgias e Lombocia- tagias estabeleceu as seguintes diretrizes: fi. Deve-se avaliar se a dor aparece de manha ou no decorrer do dia, lembrando que nas hernias discais e lombalgias de causa inflamatoria ela ocorre pela manha. No canal estreito artrosi- co pode tambem iniciar de manha e piorar ao longo do dia. Nas espondiloartropatias a dor e matinal, projeta-se nas nade- gas, melhora ao longo do dia, e as vezes desaparece a tarde. Na lombalgia mecanico-degenerativa a dor aparece com os movimentos, no fim da tarde apos o trabalho e se relaciona com estresse fisico e emocional. A dor raquidiana geralmente tem relacao com os movimentos da coluna; a extra-raquidiana nao tem (p. Exame Fisico O paciente com lombalgia ou lombociatalgia deve ser examinado levando-se em conta que a pressao intradiscal varia em funcao dos movimentos e das posicoes do corpo. Tratamento Uma abordagem terapeutica correta da lombalgia aguda com a com- binacao de tratamento conservador, escolas de coluna, orientacao ergonomica e fisioterapica e capaz de influenciar sua evolucao evitan- do a cronicidade. Duracao: em media 3 a 4 dias, maximo 5 a 6 dias, nao deve ser prolongado, pois a inatividade tem acao dele- teria sobre o parelho locomotor. Paracetamol (acetaminofen) 500mg de 4 a 6 vezes ao dia, nas dores leve a moderada. Cautela em pacientes com hepatopati- as e associado a antiinflamatorio nao hormonal. Analgesicos Opioides: Usados em lombalgia aguda e lombociatalgia por hernias discais re- sistentes a outros analgesicos, fraturas e metastases. Ciclobenzaprina: 5 a 10 mg/dia, relaxante muscular de acao central estruturalmente relacionados com os antidepressivos triciclicos. Antidepressivos: Indicados nas lombalgias cronicas com componente psicossomatico e nas fibromialgias. Deve-se lembrar de que nao existem evidencias cientificas de sua eficacia no tratamento da dor lombar. Restauracao da amplitude dos movimentos articulares e alongamento dos tecidos moles. Exercicios de extensao podem reduzir a com- pressao radicular, assim como exercicios de flexao reduzem a tensao nas facetas articulares e o espasmo da musculatura dorso lombar. Exercicios de treinamento para melhorar e fortalecer a estrutura musculoligamentar, bus- cando minimizar o risco de lesao das estruturas envolvidas na fififififififififi fi fifififififififififififififi fifi dor (disco intervertebral, articulacoes interfacetarias e estrutu- ras ligamentares). Exercicios dinamicos com atividade coor- denada de grupos musculares que proporcionam o controle da postura e da funcao muscular com estabilidade da coluna. Atraves de programas de cami- nhada, atividades aquaticas, bicicleta ou esteira pode-se aumentar os niveis de endorfina, promovendo sensacao de bem-estar e diminuicao da percepcao dolorosa. Pratica de exercicios em casa que devem ser programados de acordo com a tolerabilidade e habilidade do paciente. Exercicios (Base Fisiologica) O exercicio aumenta o nivel de fi endorfina no sangue periferico e diminui o pH no interior do disco intervertebral por aumentar a concentracao de O2, diminuindo assim, o estimulo doloroso. Na fase aguda das lombalgias e lombociatalgias os exercicios devem ser considerados com cautela, sendo, no entanto, im- portantes para o tratamento da lombalgia cronica, podendo ser feitos: 1. Exercicios de Extensao Indicados nas hernias, protrusoes difusas e focais do disco, fora do periodo agudo. Meta-analises demonstram evidencias de resultados em curto pra- zo comparados com outras formas de tratamento e moderada evi- dencia em lombalgias ocupacionais. Nao ha evidencias cientificas que comprovem o beneficio da acu- puntura na lombalgia e lombociatalgia. Alivia a dor e promove o relaxamento muscular por diminuir o estresse raquidio atraves do aumento da pressao intra- abdominal com acao de um cilindro semi-rigido ao redor da coluna lombar. Abrange desde o estiramento suave (mobilizacao) ate a aplicacao de forca ma- nual (manipulacao). Terapia Comportamental Nas lombalgias cronicas pode-se reduzir a incapacidade atraves da mudanca dos padroes comportamentais. Ha evidencias obtidas por meio de meta-analises que demonstram melhora da dor e capacidade funcional na lombalgia cronica, porem nao existem evidencias de melhora a curto prazo. Tratamento Cirurgico Deve ser baseado no diagnostico clinico e nos exames por imagens. Na lombalgia mecanica e indicado apenas nos casos resistentes ao tratamento conservador com evolucao atipica, podendo ser feitas infiltracoes nas discopatias, dos pontos dolorosos e perifacetarias alem de denervacao facetaria e artrodese do segmento vertebral. Nas hernias discais e indicado nos casos de deficit neurologico grave agudo com ou sem dor, nas lombociatalgias de dificil controle algico apos tres meses de tratamento conservador e na sindrome da cauda equina. Na sindrome do canal estreito e realizado em carater individual nos casos incapacitantes e progressivos. Nas lombalgias inflamatorias como a espondilite anquilosante in- dica-se raramente o tratamento cirurgico nos casos de dor por com- pressao do canal vertebral e instabilidade. Nas espondilodiscites (lombalgias infecciosas) e indicado nos ca- sos de evolucao desfavoravel com o tratamento clinico, recomen- dando-se a biopsia diagnostica fechada ou aberta. Biering-Sorensen F: Physical measurements as risk indicators for low-back trouble over a one-year period. Haldeman S: Presidential Address, North American Spine Society: failure of the pathology model to predict back pain. Holm S, Nachemson A: Nutritional Changes in the Canine Intervertebral Disc after Spinal Fusion. Holm S, Nachemson A: Variations in the Nutrition of the Canine Interver- tebral Disc Induced by Motion. An epidemiologic study with special reference to driving automobiles and cigarette smoking. Malmivaara A, Hakkinen U, Aro T, et al: the treatment of acute low back pain: bed rest, exercises, or ordinary activityfi Scientific approach to the assesse- ment and manegement of activity-related spinal disorders: a monograph for clinicians. Philadelphia Panel Evidence-Based Clinical Practice Guidelines on Selected Rehabilitation Interventions for Low Back Pain. A systematic review of randomi- zed controlled trials of the most common interventions. Tuder M Van, Assendelft W, Koes B, Bouter L: Spinal radiographic findings and non specific low back pain: a systematic review of observational studi- es. Primeiro Consenso Brasileiro sobre Lombalgias e Lombocitalgias, Socieda- de Brasileira de Reumatologia, julho de 2000. Nas outras situacoes deve ser usado o valor correlaci- onado com populacao da mesma idade, o Z-score. Das vitimas de fraturas de quadril 20% vao a obito em ate um ano e apenas 30% recuperam o nivel funcional previo. Metade das fraturas por osteoporose ocorre na coluna verte- bral, mas apenas um terco delas e sintomatica. Assim, o calculo de 15,4% de risco de fratura vertebral apos os 45 anos provavelmente e subestimado pois sao consideradas apenas as fraturas clinicamente significantes. Mas a partir da ocorrencia de fraturas o quadro clinico pode ser vasto a depender do local da lesao, do tipo de fratura e das possiveis deformidades osseas e compressoes de tecidos. Isso pode gerar elevado consumo de me- dicacoes, internacoes e cirurgias, com importantes consequencias eco- nomico-sociais. Quadro Clinico da Fratura Vertebral Pacientes com fraturas de coluna podem apresentar um quadro agu- do de dor intensa na regiao toracica posterior ou lombalgia, por ve- zes com irradiacao em faixa para a regiao anterior. A dor tende a desaparecer den- tro de tres meses, no entanto existe a possibilidade de refratura, bem como de aparecimento de problemas biomecanicos decorrentes da fratura que prolongam o quadro algico.

Shortly thereafter erectile dysfunction drugs for heart patients quality sildalist 120mg, he traveled to Haftar returned to Chad in 1987 erectile dysfunction desensitization cheap 120mg sildalist free shipping, al-Rif was oversee- Egypt to study its military organization erectile dysfunction treatment massage discount sildalist 120 mg with visa. One prisoner causes of erectile dysfunction in youth discount generic sildalist uk, using the said he asked Habre to introduce him to Muham- pseudonym Omar al-Mukhtar erectile dysfunction treatment philippines order cheap sildalist on-line, wrote that his Chad- mad Yusuf al-Magariaf erectile dysfunction doctor in virginia buy sildalist with paypal, head of the exiled opposition ian jailers broadcast Qadhafi speeches in which he I do not know quently acknowledged by the State Department81 and anyone with this name [Khalifa Haftar]. Tese tactics fostered an environment in which in exchange for harboring the Libyans. In reality, these operations were being carried Chad and that he was equally harsh with Libyan sol- out by the Libyan Islamic Fighting Group. These leaders apparently con- influence over the extremists to persuade them to change their ideas. For In November 2011, 150 ofcers met to select Haf- tar as the military chief of staff. Violence prevented 2012, he criticized politicians for preventing military voting in Darnah, and Berbers boycotted the February ofcers from participating in discussions to rebuild elections, leaving four of its sixty seats unflled. He further pressed for ing the armed forces, and supporting the civil state the creation of a defense council that would take con- institutions. Haftar has claimed that 70,000 that provided a range of potential identities at diferent 161 times than as a base for sustained collective action. His Obeidat tribe, attempts have been made against military and secu- one of the largest in Cyrenaica, threatened to avenge 163 his murder several times, but it never did. Other titular fgures, factors that persuaded them to join forces with Haf- such as Tripoli military police chief Mukhtar Farnana, tar was their mutual animosity toward Qatar and the have thrown their support behind Haftar, but they do influence allotted to its local Islamist allies such as 164 Abdul Hakim Belhaj and the Salabi family. Several tribal militias have joined Haftar as well, Marshalled against Haftar is a coalition of disparate but their support and cohesion are suspect. Its mem- as the Warfallah and Warshefana, which have seen bers do not appear to have the unit cohesion born of their influence wane in the post-Qadhafi era, have battle because they did not fght together during the joined Haftar. Journalist Mary Fitzgerald estimated the The importance of tribal identity in Libya should branch to have 250-300 fghters. Unlike the tribes of Iraq and gade, with its maybe 1,500-3,000 troops, is likely the Yemen, a single Libyan tribe is frequently spread out strongest fghting force in the east, given its modern across the country, thus diluting links and loyalty. In contrast to formed after the revolution, have taken up the banner Iraq and Lebanon, sectarian afliations are not strong, against Haftar but face serious limits on their force since Sunni Arabs make up approximately 91 percent projection. It remains to be Viewing the confict as Islamists against non-Islamists seen how efective an air force that used U. Many of its leaders, Mistratan brigades have come out against Haftar, a such as Abu Bakr Buera, are disgruntled ofcials who number of units remain on the sidelines. Spurned in favor of other the parvenus, Benghazi and Tobruk, he can efectively partition the Buera joined the federalist movement to express his country. But socio- fict is primarily an age-old power play between those economic appeasement via subsidies and wage hikes who have it and those who do not. A ber of hospital beds compared to other countries in video link connects his Zintan prison to the Tripoli the region. And unless courts poses a problem, with physicians simply failing to and judges are protected from the hand of rogue jihad- show up at health facilities during worker strikes. In countries like Yemen, where courts are is in dire need of everything from specialized systems distrusted and cases wait years for trial, citizens turn to basic medical tools. Only 13 percent of all medi- to jihadists who can provide them prompt and equi- cal facilities have an adult scale, stethoscope, ther- table mediation. This For all these reasons, many Libyans are forced to would allow the ministry to centrally aggregate travel abroad for complicated procedures. Libya needs experts to instruct medical care equipment market is an oligopoly that prevents technicians in the use of specialized equipment. And competition, allowing existing operators to price- a comprehensive study needs to be done to eliminate gouge as they please. For example, one German frm that agreement whereby Rome would invest $5 billion arranges such treatment takes 30 percent of the costs over twenty-fve years as reparations for occupying and sends kickbacks to the Libyans who refer the the country. Specialty machines lie idle because gas from Tripoli,213 Libyan stability is of paramount they lack minor parts. And because Africans migrants equipment is frequently stolen for sale on the black traverse Libya to get to Italy, any instability is likely to market, many facilities lack the tools they need to lead to an infux. In 2000, the parliament abolished the defense contractors have reportedly been negotiating Health Ministry, delegating most of its authority to sales ranging from air defense systems to naval patrol the regional level. Today, Tripoli simply does not know the pro- agreement and a memorandum under which Paris cedures outlying facilities are ofering and the extent promised to train doctors and paramedics, provide to which Libyans bypass primary health facilities and technical expertise, and supply medical equipment. Expanding the scope of this agreement to include To remedy these challenges, the international eliminating corruption and providing administrative community could usefully help Libya develop a training would be benefcial to both sides. But until an empowered chief of staf is appointed, Libyans are frustrated when they must go abroad for these goals will be difcult to achieve. Respected by his troops, he has the military plete revamping of state institutions is necessary, and skills and combat experience necessary to create only expert training can accomplish this. But most important, he is the sole Security reform is an integral part of this process. Libyan willing to take on the Islamist militias that But, as in other areas, Western nations have favored are preventing the establishment of a modern state. Beyond rather than as individuals, unwilling to transfer their his campaign against the militias, Haftar understands loyalties beyond the narrow confines of tribe and the challenges Libya faces. A top-down strategy would be more suitable to reconciliation and referenced the lack of state institu- this environment. His draconian many officers remaining loyal until his demise, few streak has emerged far too often. Haftar must of those who remained with Qadhaf until his ship temper these excesses if he is to succeed. Washing- sank nor from the exiled dissidents whose links to ton can nudge him on the right path by explaining the community are tenuous. Until then, it will remain mired in the violence that of law, and appointing a military chief of staf can guide threatens not only Libya but all of North Africa. Muhammad Abd al-Razzaq Mani, Al-Ansab al-Arabiyya f Libiya [The Arab Genealogy in Libya] (Alexandria: al-Mukhtar, 1991): pp. Al-Inqadh was the maga- zine of Libyan National Salvation Front, the leading opposition group. Qadhaf told former foreign minister Musa Kusa that he entered the academy in October 1963. Revolutionary Command Council member Abdel-Mouneim al-Houni noted that Qadhaf enlisted in August 1963. See, for example, Ruth First, Libya: The Elusive Revolution (Middlesex: Penguin Books, 1974), p. Omar al-Muhayshi and Muhammad al-Muqaryif graduated in the eighth class with Haftar. It is unclear why Qadhaf recruited al-Muqaryif rather than a fellow graduate from the seventh cadet class. Dirk Vandewalle, A History of Modern Libya (Cambridge: Cambridge University Press, 2006), pp. Vandewalle likely follows but does not quote Ruth First, Libya: The Elusive Revolution (Middlesex: Penguin Books, 1974), p. Qadhaf, however, stated that he recruited from the seventh to the twelfth classes. Younis played a key role in the revolution, accompanying Qadhaf to seize the Benghazi radio station where he announced the coup. It is unclear if Haftar was commander of the city of Tobruk or of the entire region.

In some surveys that we did erectile dysfunction medicines cheap 120 mg sildalist fast delivery, you would get about 100-fold difference erectile dysfunction doctor mumbai buy sildalist 120 mg on-line, with different people doing titres impotence grounds for divorce states purchase sildalist no prescription. So that the only contribution made by that measurement erectile dysfunction 18-25 generic sildalist 120mg fast delivery, in terms of micrograms erectile dysfunction doctor nyc sildalist 120 mg on-line, was that by radioactively-labelling the anti-D molecule erectile dysfunction treatment mumbai buy sildalist american express, it did make the assay more accurate. Dr Derek Bangham: First let me explain that I am a medical innocent of specialized haematology. Yes, we ran a study to assess the accuracy of that method (which was believed to measure milligrams of anti-D immunoglobulin) in assays of coded samples. When Nevin Hughes-Jones learned of the international approach he then readily collaborated with us. The long-proven procedure is to prepare a large batch of selected material, ampouled in stable form, against which other preparations can be assayed in appropriate comparison biological methods. An international collaborative study was run in which coded (that is, unknown) ampoules of this and several other preparations were assayed by 97 23 expert haematologists in 11 countries. When commercial preparations (for example, anti-D) became licensed for clinical administration, it was essential to have attested the internationally accepted methods with which to control their potency and quality. I am explaining all this to set the record straight and show how research on assay methods is evaluated internationally. So this is another example of biological standardization in which this country has led intellectually, scientifically, and in hard practice. Weatherall: I just wonder, while we are on the subject of international collaboration, we have not said much about the Freda and Gorman team in New York who were racing you, if it was a race. Finn: I first found out about it when I went to see Philip Levine, when I was working at Hopkins, and he said you must go up and give a seminar at Columbia on medical genetics, and I got there and gave the seminar. At the 99 end of it, three young men [John Gorman, Bill Pollock and Vince Freda], my 97 Bangham et al. But it became obvious that they were also working on it independently, but using a different theoretical concept. Of course, John and I both worked at the Hopkins for a time, so Julie Krevans in the blood bank there played a part in this as well. When I was in Baltimore I paid several visits to John Gorman in New York and there was always a pleasant and free exchange of ideas and experience. I remember an excellent conference on Rh prophylaxis organized by Bill Pollack at Princeton. He was browsing through a general textbook of pathology and came across a reference to Theobold Smith, who in 1909 was 101 working on the induction of immunity with diphtheria toxoid. He had found that if too much antitoxin were given with the toxoid, active immunity failed to develop. Even prior to this, two pupils of Paul Ehrlich had reported in 1900 that if ox red blood cells were injected into rabbits an antibody response resulted but if specific antiserum were given with the red 102 blood cells, the antibody response did not occur or was very weak. Then I thought, from my memory of the Liverpool days, that this must have been the most shoestring research ever done. Registrars worked for nothing; the technicians, Bill Donohue was working in the department; 100 the Ortho Research Foundation. Weatherall: So this whole programme and all the basic work was done without one grant. Rodeck: I would say that in all likelihood this so-called bunch of amateurs, if they had applied to the W ellcome Trust for funding, would have been rejected. In the short time that we have got left, we have two other items before asking Pat M ollison to put the Rh locus into its present perspective. You have several of your colleagues here and there have been major advances in our understanding of the rhesus system since we left off in about 1960. Professor David Anstee: the critical experiments that opened up the route to identifying the structure of the protein were made by Stephen M oore, who 105 worked in the Edinburgh centre of the Scottish Blood Transfusion Service, and at the same time independently by Carl Gahmberg in Helsinki in 1982, 106 when they showed that they could immune-precipitate the Rh proteins. This grant made possible the construction of a building and the support of many different lines of research on medical genetics. At about the same time, monoclonal anti-D was becoming available from the culture of B lymphocytes transformed with Epstein-Barr virus. Nevin was involved in that work in Cambridge, and Belinda Kumpel, who is also here, in Bristol. They provided enough antibody to purify sufficient protein for sequence characterization. By that time, we knew that there were at least two Rh proteins from immune precipitation studies. Subsequently it emerged that there were two genes: one that encodes D and the other that encodes C and E. That characterization in 1990 established the nature of the proteins that give rise to the antigen and since then a great deal of work has been done to characterize the nature of the polymorphisms that give rise to the variety of antigenic structures upon those proteins. I think that was the critical phase: the identification of the molecules themselves by Stephen M oore and Carl Gahmberg originally, and then the cloning of the genes around 1990. Gene structures have been purported to be correct as the two Rh genes, which are in reverse orientation to each other, are on chromosome number one. So the idea that the human genome sequence is complete, I think, is premature, especially in Rh genetics. Professor Ian Franklin: Is there any advantage in being rhesus-negative or positive on a population basisfi The point was initially made by Peter Agre at Johns Hopkins and Jean-Pierre Cartron in Paris. They are extremely rare individuals that completely lack Rh proteins from their red cells. They have distinct biochemical anomalies which are not found in RhD-negative individuals. It has arisen as two different genetic polymorphisms: the Caucasian D gene deletion and the black D-negative phenotype that is due to a mutated Rh-D gene. So there are two separate ways of being D-negative and there are many others that we know of as well. So 111 about 7 per cent is D-negative in black populations and 15 per cent in whites. Weatherall: this is a kind of general situation with a lot of blood group genetics at the moment. Before I ask the fetal medicine folk to summarize the impact they think all this has made on fetal medicine, could you update us on the management of the prophylaxis over recent years in terms of the role of monoclonal antibodies, source of anti-D material, and so onfi Anstee: There has been a programme for more than 15 years to develop and trial monoclonal anti-D as an alternative to the use of polyclonal anti-D. There was a period when availability of anti-D in this country was a problem, but that was when we were using our own donor material to provide the product, in a drive for self-sufficiency for such products. The cost of bringing the human monoclonal alternative to market is extremely high. To v e y: When we had to produce a lot of anti-D from our own resources, this produced a major problem in Britain, because obviously our main source was mothers with antibody, and that was decreasing with the success. This meant taking a donation from a donor with high levels of antibody, centrifuging it, removing the plasma and returning the red blood cells to the donor. Later this technique could be performed by a 114 machine, a technique pioneered by my colleague, Dr Angela Robinson. The second way was deliberately to immunize Rh-negative male volunteers, and this was obviously an ethical dilemma. As I will explain later, we did everything possible to avoid these complications, but we could not guarantee 100 per cent protection. However, in many centres we did succeed in obtaining considerable numbers of male volunteers and, as far as I know, there has been only one case that has caused problems. The donor red blood cells were chosen from donors who had donated at least 40 times and the patients receiving their blood had suffered no ill effects. The red blood cells did not contain antigens such as little c or Kell, which often cause antibodies to develop, and the cells were washed to remove white cells. So, over a long time, we did our best in Britain in order to raise enough anti-D to allow not only post-delivery prevention, but also antenatal prevention. One other interesting point about, I think 115 it was Ronnie Finn, who changed the formulation to avoid serum hepatitis. I suppose there are always going to be question marks over allogeneic blood- derived products, and I think a monoclonal product would be infinitely preferable, as far as I am concerned. Dr Angela Robinson: I would like to comment on the development in the clinical trials of the monoclonal antibody. Last week I was at the Bio Products Laboratory where they were telling us about these trials with a recombinant monoclonal antibody. The numbers that they want, to give the study sufficient statistical power to prove effectiveness, are just so huge. You would have thought that there would be a strong impetus to be doing the same for pregnant women with anti-D. Kumpel: I would like to say that we all know how effective the polyclonal product is, and it has been proved to be extremely safe by nearly all the manufacturers. If there was any compromising of the supply from North America, either a new virus or something or another factor that reduces the supply, then there is nothing in the pipeline as a reserve. M y understanding is that a monoclonal antibody has been tried in experimental circumstances and found not to be very effective. W hat I am going to suggest is that if you do eventually make monoclonal antibodies, they should be mixed together afterwards and not simply rely on a single monoclonal. Although I think there is some evidence that if you have the right antibody one will work. To make a product comprising a large number of different monoclonal antibodies would add greatly to the cost of the development programme.

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