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While differences in acceptability of steroidal contraceptives from nation to nation are generally recognized, variations in safety and effectiveness have been given little attention. Cardiovascular hazards such as thromboembolic disease, myocardial infarction, and stroke, which create such concern in developed countries, may be insignificant problems in other parts of the world where these diseases are rare in women of reproductive age. On the other hand, the influence of nutritional deficiencies, anemia, intestinal parasitism, malaria, and other widespread health problems on the effects and/or metabolism of steroids, which may be of major concern in developing countries, is just coming under study. Side effects also vary greatly among religiously and ethnically different populations, and significant differences in pregnancy protection and bleeding patterns among different populations have been reported-even with injectables. It is, therefore, important to examine and define intergroup differences and especially to recognize that safety concerns in one geographic setting cannot be automatically assumed to apply equally in other areas.
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PMID:Perspectives in evaluating the safety and effectiveness of steroidal contraceptives in different parts of the world. 92 97

It is said that William Withering's discovery of digitalis arose out of curiosity engendered during a stage-coach journey, by witnessing an old woman collecting foxgloves by the side of the road. Whilst we are not aware of an analogous stroke of genius reported from ancient China, the story of qinghaosu has certain parallels. Just as foxgloves had been used traditionally for centuries to treat 'afflictions of the heart', the plant Artemesia annua has been used as a treatment for fever in China for almost two thousand years. Artemesia annua, also known as 'sweet wormwood', is found in many parts of the world, but it was not until the early 1970s that Chinese scientists recognized its potential for treating malaria and isolated the active principle, artemesinin or qinghaosu. This paper describes the evidence for the efficacy of this drug and some of its derivatives in the treatment of malaria and the potential of these drugs for the standard management of malaria in Papua New Guinea and elsewhere.
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PMID:A new look at an old drug: artemesinin and qinghaosu. 134 Oct 87

The changes in mental status during cerebral malaria, heat stroke, and recovery from major surgery are clinically similar, and are associated with high circulating concentrations of cytokines that can induce nitric oxide generation in vascular walls. This vascular nitric oxide could diffuse across the blood brain barrier, causing functional changes that include inhibition of glutamate-induced calcium entry, reduced activity of the calcium-dependent nitric oxide synthase, and thus reduced nitric oxide formation, in post-synaptic neurons. Certain general anaesthetics and ethanol reduce glutamate-induced calcium entry into post-synaptic cells, and so would also reduce the rate of formation of neuronal nitric oxide. In view of the apparent importance of glutamate-induced nitric oxide in excitatory neurotransmission, a reduction in neuronal nitric oxide could help explain why these otherwise unrelated influences alter central nervous system function in a similar manner. In particular, this reduction could rationalise why heat stroke, ethanol excess, morphine poisoning, and conditions with high blood ammonia concentrations are easily confused clinically with cerebral malaria.
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PMID:Possible central role of nitric oxide in conditions clinically similar to cerebral malaria. 138 58

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.
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PMID:Drug antioxidant effects. A basis for drug selection? 172 62

Thirty-two 4-week-old male Wistar rats were infected with Plasmodium berghei malaria. On Days 12 through 14, blood volume, arterial blood pressure, right ventricular pressure, heart rate, cardiac output, stroke volume, hematocrit, and vascular resistances were determined. All of the cardiovascular parameters measured, with the exception of calculated pulmonary vascular resistance, changed progressively as the peripheral blood parasitemia increased. With a rising parasitemia, cardiac output increased, despite a reduced heart rate. The highest parasitemia of 63% was accompanied by a doubling of the normal cardiac output. The relationship between parasitemia and cardiac output can be described by the equation, cardiac output = (6.14) x % parasitemia + 452 ml/min/kg. The mean arterial blood pressure was lower than controls when parasitemia exceeded 20%, whereas systolic right ventricular pressure was elevated only at the highest parasitemias. When noninfected control rats were compared with those animals having parasitemias greater than 40%, in the infected animals, mean arterial pressure was 28% lower (P less than 0.01) and systolic right ventricular pressure rose by 21% (P less than 0.02). A 50% decline was observed in the total peripheral vascular resistance (P less than 0.01), although the pulmonary resistance was apparently unchanged. With P. berghei infection, there is also a marked anemia, an increase in plasma volume, and a 16% increase in blood volume (% body weight). It is concluded from these results that although the hemodynamic changes previously reported in the literature indicate that infection with malaria may result in focal blockages in microvessels and poor tissue perfusion, the total systemic effect, in the rat, is an increase in cardiac output secondary to a reduced peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmodium berghei: malaria infection causes increased cardiac output in rats, Rattus rattus. 264 87

In a Nigerian town with a stable population of 20,000, a door-to-door survey was conducted, using a questionnaire involving a complete census and a simple neurological evaluation which had previously showed a 95% sensitivity and an 80% specificity for detecting neurological disease. Positive responders were evaluated and categorised, using agreed criteria for diagnoses. Nearly 100% cooperation was obtained. Life prevalence ratio for at least one episode of headache was 51/1000. Crude point prevalence ratio for migrainous headache was 5.3/100, and peak age-specific ratio was in the first decade. Prevalence ratio for epilepsy was 533/100,000 and peak age-specific prevalence ratio occurred in the 5-14 years age groups. The prevalence ratio for peripheral nerve disorders was 268/100,000, and age-specific prevalence ratio for tropical neuropathy increased with age. Prevalence ratio for stroke was rather low at 58/100,000, but was probably due to the people's attitude to the disabled elderly and high mortality of stroke which showed annual mortality rate of 70/100,000 which increased with age to 1519/100,000 per year in the eighth decade. Crude prevalence ratios (cases per 100,000) for others are 112 for neurological complications (including sciatica) of spondylosis, 15 each for poliomyelitis, motor neurone disease, development speech disorders, 10 each for syncope, hereditary neuropathies. Parkinson's disease, benign essential tremor, primary cerebellar degeneration, cerebral palsy, mental retardation, organic psychosis (probable intracranial tumor) and 5 each for muscular dystrophy, pyomyositis, spina bifida occulta, alcohol dependence and cerebral malaria. The implications of the findings are important for development of community neurological services in the developing countries.
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PMID:Neurological disorders in Nigerian Africans: a community-based study. 303 73

Traditionally, blood rheology tests have been used in diagnosis and monitoring of infection, rheumatic diseases and malignancy, and are still of clinical value in these conditions. In the last twenty years, clinical and epidemiological studies have shown that the haematological determinants of blood flow resistance (haematocrit, fibrinogen, white cell count and altered red and white cell rigidity) are also associated with nutritional, metabolic, endocrine and vascular disorders. Decreased red cell deformability may contribute to reduced red cell survival and anaemia in burns, malaria, liver disease and kidney failure. In trauma and inflammatory disease, overt hyperviscosity is usually prevented by vasodilatation and reduction in the haematocrit. However, low-flow states may arise systemically from haemoconcentration (contracted plasma volume, Chapter 3) in severe burns, inappropriate red cell transfusion, or dehydration due to illness; systemically in circulatory shock; and locally in venous thrombosis or arterial disease. In such circumstances, the intrinsic flow resistance of blood may perpetuate flow disturbance, ischaemia and thrombosis. Conversely, optimal levels of haematocrit, fibrinogen and white cell count may be lower than normal in low-flow states. Haemodilution by colloid infusion is beneficial in burns, shock, major surgery, prevention of postoperative venous thrombosis, chronic stable claudication and possibly in acute stroke and retinal vein thrombosis. Plasma exchange may be beneficial in severe Raynaud's phenomenon. Defibrination with ancrod is effective in prevention and treatment of venous thrombosis but its role in arterial disease is unproven. The benefits of streptokinase therapy in venous thrombo-embolism and acute myocardial infarction may be partly rheological, due to fibrinogen depletion. Drugs with rheological effects may be beneficial in intermittent claudication.
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PMID:Blood rheology in general medicine and surgery. 332 67

We describe the haemodynamic and oxygen transport response in a patient undergoing exchange transfusion for severe falciparum malaria. We found that exchange transfusion produced a significant increase in left ventricular stroke work index, systemic oxygen delivery and oxygen consumption. This potentially beneficial effect of exchange transfusion has not been reported previously.
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PMID:Haemodynamic and oxygen transport response during exchange transfusion for severe falciparum malaria. 782 13

The "Health Transition" describes the medical consequences which accompany the demographic transition and development. In many Asian countries, as the infectious diseases of infancy decline, such as diarrhea, acute respiratory disease, measles and malaria, so too, do infant mortality rates. As a consequence of falling infant mortality rates and declines in fertility, the age pyramid has become more rectangular. No longer is nearly half of the population under the age of 15 years. Diseases of adults are beginning to become predominant: trauma, heart disease, cancer, stroke and diabetes. Life expectancy has increased along with costs of the health care system. As a fraction of per capita gross domestic product, health care is beginning to become a major national expense. It is ironic that the one vector-borne infectious disease likely to bridge the health transition in tropical countries is dengue. As evidenced by the experience of Singapore and Taiwan, modern housing and commercial development provide more, rather than fewer breeding places for Aedes aegypti. Greater affluence often means less compliance with mosquito control programs. Meanwhile, the dengue viruses, heeding some unknown genetic imperative, cause ever more severe disease. Modern Asian societies must count dengue as a real and enduring threat. To prevent costly hospitalizations and a sense of social disorder, effective measures must be adopted to achieve a significant reduction of Aedes aegypti populations. Sustained dengue control requires source reduction which, in turn depends upon imaginative leadership, skilled man power, legislative authority, an authentic national research program and intersectoral cooperation. A leadership role beckons for new actors in the control of Aedes aegypti: large municipalities, environmental agencies and the private sector.
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PMID:Dengue in the health transition. 784 46

Thirty five children aged 5 months to 15 years suffering from stroke were studied from August 1984 to July 1990 from two hospitals in order to determine the incidence, the etiological factors and the short term outcome of the stroke. The average annual incidence was 1.85 per 1000 pediatric hospitalizations. There was a progressive rise in the number of cases from 1985, with a peak in 1990. Motor impairment of one half of the body was the commonest clinical feature seen in 97.1% of the cases. Other clinical signs were: facial paralysis (62.9%) and aphasia (28.6%). The main etiological factors were: homozygous sickle cell disease (31.4%), heart disease (17.1%), cerebral malaria (14.3%) and meningitis (14.3%). No causative factor was identified in 7 patients (20%). The mortality rate was low (2.9%) and all the children had neurological deficit after a mean hospital stay of 15 days. Laboratory investigations including lipid analysis, platelet count, and skull X-rays proved to be of no diagnostic value. However, computed tomography (CT) scan confirmed the diagnosis of ischemic stroke whenever it could be done.
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PMID:Stroke in children in Yaounde, Cameroon. 789 Mar 41


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