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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism and response to treatment of severe life-threatening hypoglycaemia (plasma glucose 1.15 +/- 0.73 mM/l [+/- SD]) was studied in eight Thai patients with falciparum malaria. Plasma insulin concentrations were inappropriately high (range 1.0-21.8 mU/l), lactic acidosis was common (arterial blood lactic acid concentration 1.44-17.8 mM/l), but the glucose counterregulatory response, indicated by plasma cortisol, growth hormone, catecholamines and glucagon concentrations, was intact. Hyperinsulinaemia was successfully treated in five patients by a continuous intravenous infusion of the long-acting somatostatin analogue Sandostatin (SMS 201-995), 50 micrograms/h. In volunteer studies a single intramuscular injection of Sandostatin (100 micrograms) suppressed quinine-induced hyperinsulinaemia within 15 min; this effect was maintained for 6 h. These results suggest that Sandostatin may be a safe and effective way of correcting the hyperinsulinaemic hypoglycaemia complicating quinine treatment of falciparum malaria. This treatment could be particularly useful in fluid-overloaded patients with recurrent hypoglycaemia despite dextrose infusions.
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PMID:Hypoglycaemia and counterregulatory hormone responses in severe falciparum malaria: treatment with Sandostatin. 832 38

Although malaria has been largely eradicated from temperate countries, it is on the increase in the tropics. Infection with Plasmodium falciparum affects a vast number of people and kills over a million annually. Severe malaria is a multisystem disease affecting particularly the central nervous system (causing coma and convulsions), the kidneys (resulting in acute tubular necrosis), and the liver (contributing to lactic acidosis and hypoglycaemia). Acute pulmonary oedema (acute respiratory distress syndrome) may occur in adults particularly in association with renal impairment. In children these symptoms are rare, whereas hypoglycaemia, lactic acidosis and severe anaemia are more common. Malaria should be suspected in any febrile patient living in or returning from the tropics, and a blood smear examined. Chloroquine has been the mainstay of antimalarial treatment for the past 40 years, but resistance in P. falciparum is now widespread throughout the tropics and has recently been recognised in P. vivax from Oceania. Sulfadoxine-pyrimethamine resistance is also common. Fortunately, quinine, and the newly introduced compounds, halofantrine and mefloquine, can be relied upon nearly everywhere. The most rapidly acting and effective of all antimalarial drugs, artemisinin and its derivatives, have come from China. They offer a genuine prospect of reducing mortality from malaria in the tropics.
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PMID:Clinical malaria in the tropics. 833 22

From January through December 1988 the causative factor of each case of childhood seizure seen in the Children's Emergency Room of the University of Calabar Teaching Hospital, Calabar, Nigeria, was prospectively studied with a focus on the relative importance of malaria-related seizures. Of the 134 seizure cases seen, febrile convulsion (FC) formed the majority (55%) with cerebral malaria (CM) as the only major (33%) rival. Other conditions such as meningitis, epilepsy, hypoglycaemia and drug poisoning together (12%) played a minor role. Malaria was the dominant cause (73%) of FC; 81% of these cases did not respond to chloroquine. On comparing the number of cases of CM accumulated in the same unit from 1986, there was a significant increase (P < 0.001) in the proportion of yearly CM admissions from 1986 through 1988. The study confirms the premier position of malaria in the causation of childhood seizures and also suggests a possible upsurge in the prevalence of CM in the environment. This upsurge probably derives from the emergence of chloroquine-resistant Plasmodium falciparum (CRPF) reported in Nigeria which appeared to have been identified in the present study. While more studies are needed to confirm this hypothesis, clinicians in areas of CRPF are alerted about a possible upsurge in CM in their locality.
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PMID:Upsurge of malaria-related convulsions in a paediatric emergency room in Nigeria. Consequence of emergence of chloroquine-resistant Plasmodium falciparum. 836 50

Hypoglycaemia is a relatively common cause for referral of patients to the accident and emergency departments of hospitals but most of it is iatrogenic. Occasionally, however, hypoglycaemia is due to any one of up to a hundred different disorders. In some, hypoglycaemia is the cause of intermittent neuroglycopenic symptoms that lead to their referral to medical outpatients for investigation. Only the most important are discussed here. Hyperinsulinism due to abnormal beta-cell function is an uncommon but important cause of spontaneous hypoglycaemia. The diagnosis is suspected from the history of episodes of altered consciousness confirmed by demonstrating raised plasma insulin, C-peptide and proinsulin levels in peripheral blood in the presence of hypoglycaemia. Differentiation of the various causes of endogenous hyperinsulinism before surgery is difficult if not impossible and the low predictive value of most of the localizing techniques that are available makes them an additional and unnecessary cost, producing little clinical benefit. Hypoglycaemia caused by non-islet cell tumours (NICTH) is seemingly rarer than hyperinsulinism from insulinoma and tends to occur in older patients. The clinical features are similar to those of hyperinsulinism but laboratory investigation reveals appropriately depressed plasma insulin, C-peptide and proinsulin levels in the presence of hypoglycaemia. The plasma IGF-II:IGF-I ratio is characteristically high and the concentration of the E-domain of proIGF-II is raised. Autoimmune hypoglycaemia is more common in some countries than others and is most often due to autoantibodies to insulin (AIS). It may also be caused by autoantibodies to the insulin receptor and possibly to autoantibodies that are stimulatory to pancreatic beta-cells. Contrary to popular belief, idiopathic reactive hypoglycaemia is rare and only one of the possible causes of the postprandial syndrome. It is characterized by a low blood glucose concentration in blood collected during a spontaneous symptomatic episode but not at other times. Its cause is unknown. Other causes of hypoglycaemia include endocrinopathies of various kinds; sepsis including malaria; congestive cardiac failure; hepatic and renal insufficiencies; diverse inborn errors of metabolism; and exogenous toxins, of which alcohol is probably the commonest.
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PMID:Hypoglycaemia in the adult. 837 12

Normally there is a very close relationship between maternal and fetal glucose concentrations during both early and late gestation. Maternal hypoglycaemia during pregnancy will therefore not only affect the mother herself but also the conceptus. As can be judged from the literature, acute hypoglycaemic episodes are only rarely seen in non-diabetic pregnancies. In recent years it has become increasingly evident that insulin-dependent diabetic patients, whether pregnant or not, run a much increased risk of having severe hypoglycaemia (SH) attacks (i.e. the patient needs the assistance of another person to relieve the attack) whenever attempts are made to introduce tight blood glucose control. Very high incidence rates of SH between 19% and 44% have been reported in diabetic pregnancy. Episodes of SH could have serious consequences; neuroglycopenia seems especially hazardous for the mother particularly during the performance of a critical task like driving a car. While hypoglycaemia has embryopathic effects in rodents, there are no data in the human to support a teratogenic effect. Insulin-induced hypoglycaemia in the last trimester of diabetic pregnancy may increase fetal body movement and decrease the fetal heart rate variability. A number of very rare conditions such as insulinoma, severe malaria, HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count), severe fulminating liver disease, and ACTH and/or growth hormone deficiency have been reported to be associated with SH. Relative hypoglycaemia--i.e. low fasting blood glucose and 'flat' glucose tolerance test--is frequently seen in normotensive pregnant women with intrauterine fetal growth retardation. This pattern of maternal carbohydrate metabolism could lead to fetal hypoglycaemia and hypoinsulinaemia and contribute to poor fetal growth.
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PMID:Hypoglycaemia in pregnancy. 837 13

In this study, we have identified a dominant glycolipid toxin of Plasmodium falciparum. It is a glycosylphosphatidylinositol (GPI). The parasite GPI moiety, free or associated with protein, induces tumor necrosis factor and interleukin 1 production by macrophages and regulates glucose metabolism in adipocytes. Deacylation with specific phospholipases abolishes cytokine induction, as do inhibitors of protein kinase C. When administered to mice in vivo the parasite GPI induces cytokine release, a transient pyrexia, and hypoglycemia. When administered with sensitizing agents it can elicit a profound and lethal cachexia. Thus, the GPI of Plasmodium is a potent glycolipid toxin that may be responsible for a novel pathogenic process, exerting pleiotropic effects on a variety of host cells by substituting for the endogenous GPI-based second messenger/signal transduction pathways. Antibody to the GPI inhibits these toxic activities, suggesting a rational basis for the development of an antiglycolipid vaccine against malaria.
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PMID:Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. 841 96

Plasmodium falciparum malaria is endemic in the northern KwaZulu areas of South Africa. The clinical morbidity produced by this parasite has not been studied since the institution of the present malaria control programme. Fifty-nine patients were prospectively studied at a peripheral clinic during the peak malaria season; symptoms and signs of the infection, parasite loads, haemoglobin values and leucocyte counts were recorded in all patients. Haemoglobin and leucocyte counts were also measured in 37 control subjects without malaria. The commonest symptoms were persistent headache (100%), rigors (98%) and myalgia (93%). None of the patients presented with coma, pulmonary oedema, hypoglycaemia or algid malaria. Splenomegaly was found in 49%, hepatomegaly in 20% and mental confusion in 5% of patients. Mean parasite load was 1.71% and 57% of patients had parasite loads of < 1%. Anaemia of < 10 g/dl was significantly more frequent (P < 0.0001) in the patient group than in the control group. Leucopenia (white cell count < 4.0 x 10(9)/l) was present in 12 of 50 patients in whom it was measured compared with 2 controls (P = 0.0175). The results show a wide range of morbidity, without severe complications as presenting manifestations. Symptomatic infection in the presence of low parasite loads suggests that there may be little or no immunity in this population.
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PMID:Morbidity from falciparum malaria in Natal/KwaZulu. 845 85

We have carried out a retrospective study on 100 children in hospital in Marseilles, France with a diagnosis of Plasmodium falciparum malaria. On admission, the main clinical features were anaemia (90 cases), fever (83 cases, > 40 degrees C in 22 cases), hepatomegaly (44 cases), vomiting (29 cases), neurological signs (22 cases), thrombocytopenia (13 cases), hyperparasitaemia (6 cases), jaundice (4 cases), shock (1 case) and hypoglycaemia (1 case). Severe malaria, as defined by the World Health Organization Malaria Action Programme, was rare in our study (only 2 cases) and the prognosis was good (no death, no sequela). The search for neurological signs such as impaired consciousness, prostration or convulsions is an effective and simple way to diagnose potentially severe cases. In the presence of these signs, intravenous quinine treatment resulted in a shortened duration of fever (30 h instead of 63 h) and thereby avoided patients becoming worse. In children without neurological signs or persistent vomiting, oral therapy may be used even if there is high fever or hyperparasitaemia, but close surveillance is required. Patients treated with halofantrine or mefloquine had a shorter stay in hospital than those treated with chloroquine (mean = 4 d instead of 5.7 d). The resistance of some strains to chloroquine may explain this difference.
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PMID:Choice of therapy for imported cases of falciparum malaria in children: a retrospective study of 100 cases seen in Marseilles, France. 846 3

Phospholipid-containing antigens of malaria parasites stimulate macrophages to secrete tumour necrosis factor (TNF), induce hypoglycaemia and are toxic to mice. This TNF induction is inhibited by antisera made against the antigens, the inhibitory activity of which can be removed specifically by adsorption to phosphatidylinositol (PI) liposomes. Although the same was true of antisera made against PI, the inhibitory activity of antisera made against some other phospholipids appeared to be directed against a common determinant, probably the phosphate ester head group. We have shown previously that the activity of all the antisera was associated mainly with IgM and was not boosted by repeated injections of the antigens. To try and induce a secondary response against the parasite antigens using non-toxic molecules, mice were immunized with various phosphorylated compounds coupled to keyhole limpet haemocyanin (KLH). Three injections of PI-KLH or of phosphatidylserine (PS) coupled to KLH induced significantly higher titres of inhibitory antibody than one; furthermore, the inhibitory activity was mainly in the IgG fraction. The antisera did not inhibit TNF induction by lipopolysaccharide (LPS) or lipoteichoic acid. However, antisera against PS-KLH, though not PI-KLH, inhibited the induction of TNF by the phospholipid, platelet-activating factor (PAF). These antisera, and antisera from mice immunized with phospho-threonine or galactosamine-1-phosphate conjugated to KLH, contained inhibitory antibodies of differing specificities. Mice immunized with PI-KLH, PS-KLH or phospho-threonine-KLH did not develop hypoglycaemia when challenged with the parasite toxic antigens. These results indicate that the antigenicity of non-toxic analogues can be dramatically enhanced by coupling to a protein carrier.
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PMID:Phospholipids coupled to a carrier induce IgG antibody that blocks tumour necrosis factor induction by toxic malaria antigens. 850 34

The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a fatal outcome. The differences in admission parasite counts in the blood, hematocrit, and opening cerebrospinal pressures for patients who died and survivors were not significant. A multiple logistic regression model identified neurological status (coma, particularly if associated with extensor posturing), stage of parasite development on the peripheral blood film, pulse rate of > 150 or respiratory rate of > 50, hypoglycemia, and hyperlactatemia (plasma lactate level, > 5 mmol/L) as independent indicators of a fatal outcome. Biochemical evidence of hepatic and renal dysfunction was an additional marker of a poor prognosis, but, in contrast to severe malaria in adults, none of these children with severe malaria had acute renal failure.
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PMID:Clinical features and outcome of severe malaria in Gambian children. 852 47


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