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The neurogenic vasodilator response to endothelin-1: a study in human skin in vivo.

We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 microM ET-1 (1.43 +/- 0.64 microM, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 +/- 0.38 microM) whilst that in the flare increased to reach a peak value of 2.28 +/- 0.61 microM at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ET(A)/ET(B) antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo.

Adult↗

Malaria diagnosis and treatment under the strategy of the integrated management of childhood illness (IMCI): relevance of laboratory support from the rapid immunochromatographic tests of ICT Malaria P.f/P.v and OptiMal.

The algorithm developed for the integrated management of childhood illness (IMCI) provides guidelines for the treatment of paediatric malaria. In areas where malaria is endemic, for example, the IMCI strategy may indicate that children who present with fever, a recent history of fever and/or pallor should receive antimalarial chemotherapy. In many holo-endemic areas, it is unclear whether laboratory tests to confirm that such signs are the result of malaria would be very relevant or useful. Children from a holo-endemic region of Tanzania were therefore checked for malarial parasites by microscopy and by using two rapid immunochromatographic tests (RIT) for the diagnosis of malaria (ICT Malaria P.f/P.v and OptiMal. At the time they were tested, each of these children had been targeted for antimalarial treatment (following the IMCI strategy) because of fever and/or pallor. Only 70% of the 395 children classified to receive antimalarial drugs by the IMCI algorithm had malarial parasitaemias (68.4% had Plasmodium falciparum trophozoites, 1.3% only P. falciparum gametocytes, 0.3% P. ovale and 0.3% P. malariae). As indicators of P. falciparum trophozoites in the peripheral blood, fever had a sensitivity of 93.0% and a specificity of 15.5% whereas pallor had a sensitivity of 72.2% and a specificity of 50.8%. The RIT both had very high corresponding sensitivities (of 100.0% for the ICT and 94.0% for OptiMal) but the specificity of the ICT (74.0%) was significantly lower than that for OptiMal (100.0%). Fever and pallor were significantly associated with the P. falciparum asexual parasitaemias that equalled or exceeded the threshold intensity (2000/microl) that has the optimum sensitivity and specificity for the definition of a malarial episode. Diagnostic likelihood ratios (DLR) showed that a positive result in the OptiMal test (DLR = infinity) was a better indication of malaria than a positive result in the ICT (DLR = 3.85). In fact, OptiMal had diagnostic reliability (0.93) which approached that of an ideal test and, since it only detects live parasites, OptiMal is superior to the ICT in monitoring therapeutic responses. Although the RIT may seem attractive for use in primary health facilities because relatively inexperienced staff can perform them, the high cost of these tests is prohibitive. In holo-endemic areas, use of RIT or microscopical examination of bloodsmears may only be relevant when malaria needs to be excluded as a cause of illness (e.g. prior to treatment with toxic or expensive drugs, or during malaria epidemics). Wherever the effective drugs for the first-line treatment of malaria are cheap (e.g. chloroquine and Fansidar), treatment based on clinical diagnosis alone should prove cost-saving in health facilities without microscopy.

Algorithms↗

Effects of intradermal lignocaine and mepivacaine on human cutaneous circulation in areas with histamine-induced neurogenic inflammation.

The vasoconstrictive potencies of lignocaine and mepivacaine were studied in human skin. Lignocaine 0.5%, 0.25% mepivacaine (both plain and mixed with adrenaline or ornipressin), and saline (control) were injected intradermally into skin areas with enhanced perfusion (1% histamine prick). Flux was determined by scanning laser Doppler flowmetry and the size of any eventual pallor was measured. The artificially enhanced flux was increased further by saline, but not altered by the local anaesthetics. Mepivacaine produced a small pallor. Both vasoconstrictors reduced flux significantly and produced a larger pallor. We conclude that both local anaesthetics have only a mild constrictive effect on precapillary vessels. Mepivacaine has, additionally, a constrictor effect on the postcapillary vascular bed, causing pallor. An effective precapillary constriction which reduces the capillary clearance of both local anaesthetics can be achieved only by addition of a vasoconstrictor.

Adult↗

Neuropathologic correlates of leuko-araiosis.

We describe the pathologic findings in 17 persons with dementia, 12 of whom exhibited leuko-araiosis on computed tomographic scan. The presence of white matter pallor was confirmed on autopsy in 11 of these 12 cases, 9 with Alzheimer's disease and 2 with multi-infarct dementia. Two further patients, 1 with Alzheimer's disease and 1 with multi-infarct dementia, proved to have white matter changes on pathologic examination. White matter pallor coexisted with cerebral amyloid angiopathy in the brains of the patients with Alzheimer's disease. The presence of severe white matter pallor in patients with Alzheimer's disease correlated with early death, while the presence of cortical scars was associated with prolonged survival. Because early death in patients with Alzheimer's disease has been linked with severe pathologic and chemical changes, the presence of white matter pallor may be further evidence of a particularly severe process in patients with early onset of Alzheimer's disease.

Aged↗

Further observations on the pathology of subcortical lesions identified on magnetic resonance imaging.

We performed postmortem magnetic resonance imaging and pathologic examinations on the brains of seven consecutive patients older than 50 years of age who died of non-neurologic causes. Multiple hyperintense subcortical lesions were identified in each patient, and a total of 29 lesions were examined histologically (eight rims, six caps, six punctate lesions, and nine patches). Rims were characterized by subependymal gliosis and loss of the ependymal lining; caps were associated with myelin pallor, gliosis, and arteriosclerosis; punctate lesions were characterized by dilated perivascular spaces and perivascular gliosis; and patches were associated with myelin pallor and dilated perivascular spaces. The pattern of myelin pallor defined the size and shape of caps and patches. Arteriosclerosis was identified in six of six caps, three of six punctate lesions, and in three of nine patches. These data indicate that (1) each type of hyperintense subcortical lesion has a distinct pathologic correlate; (2) arteriosclerosis is not invariably associated with all types of hyperintense subcortical lesions on magnetic resonance imaging; and (3) myelin pallor appears to contribute to the magnetic resonance imaging signal at 1.5 tesla.

Aged↗

Cyclooxygenase products mediate the cutaneous vasodilation induced by endothelin-1 in humans.

Intradermal injection of endothelin-1 (ET-1) causes vasoconstriction (pallor) at the injection site, surrounded by a larger area of vasodilation (flare) in humans. Some of the vasomotor responses to ET-1 are thought to be mediated by prostaglandins. In the present study, we investigated the involvement of cyclooxygenase-derived products of arachidonic acid metabolism on the cutaneous vasomotor responses to ET-1. Ten normal subjects (25-44 years) were studied after treatment with either indomethacin (50 mg t.i.d.) or placebo according to a double blind cross-over design. Five doses of ET-1 (5 x 10(-5) to 5 x 10(-1) pmol) were injected intradermally 2 h after the last dose of indomethacin or placebo. Pallor and flare areas measured by planimetry 15 min after the injection were analyzed to evaluate cutaneous vasomotor responses to ET-1. ET-1 induced dose-dependent pallor and flare responses that were significant at the dose of 5 x 10(-3) pmol or greater. Indomethacin did not affect the ET-1-induced pallor but significantly shifted to the right the flare dose-response curve to ET-1. The inhibition of the flare response to 5 x 10(-1) pmol ET-1 was 58.9 +/- 8.5%. These results indicate that the cutaneous vasodilation induced by intradermal injection of ET-1 is mediated by the release of vasodilating cyclooxygenase products.

Adult↗

Correlation between optic disc atrophy and aetiology: anterior ischaemic optic neuropathy vs optic neuritis.

BACKGROUND: The morphologic features of swollen disc in the acute stage of optic neuritis and anterior ischaemic optic neuropathy (AION) have been extensively investigated in contrast to the morphologic features of optic disc atrophy after these events. OBJECTIVE: : A prospective study to evaluate the morphologic features of optic disc atrophy 6 months or more after optic neuritis and nonarteritic AION. PATIENTS AND METHODS: A total of 35 optic discs after nonarteritic AION (n=27) and 24 after optic neuritis (n=19) in otherwise healthy subjects have been evaluated by direct fundoscopic examination with a +90 diopters lens and optic disc photography. The average age of patients at the onset of AION was 57.8 years (range: 38-80) and at the onset of optic neuritis was 32.6 (range: 19-46). The female:male ratio was 18 : 17 in the former and 15 : 9 in the latter. The evaluated parameters included: degree of rim pallor (0 to +3), location of rim pallor, height of rim above the retina, depth and width of cup, peripapillary retinal artery to vein (A : V) ratio, and peripapillary pigment epithelial atrophy. A comparison was made also with 17 age-matched normal discs of 17 patients. Statistical significance was calculated with chi(2) and Fisher's exact test. RESULTS: Most of the discs after AION were paler (+2: 70%, +3: 26%) than after optic neuritis (normal colour: 8%, +1: 58%, P< or =0.007). Rim segmental involvement after AION was usually either superior 'altitudinal' (53%) or inferior 'altitudinal' (29%), whereas after optic neuritis, it was usually either temporal-central (papillomacular) (42%) or diffuse temporal (42%, P<0.0001). Discs had lower A : V ratio (1 : 3, 40%) after AION compared with optic neuritis (1 : 3, 8%) (P=0.007). There were no significant differences between the two groups in height of the rim, cupping, and peripapillary atrophy. CONCLUSIONS: : A combination of the degree of rim pallor, location of rim pallor, and A : V ratio may be of value in assessing the aetiology of optic disc atrophy when no previous clinical data are available and a compressive lesion has been ruled out.

Acute Disease↗

Neuropathological investigation of cerebral white matter lesions caused by closed head injury.

In order to ascertain whether there is widespread axonal disruption of cerebral white matter in the so-called 'diffuse axonal injury' (DAI), a type of closed head injury, proposed by Adams et al. the author investigated his own cases clinicopathologically. Twenty-six male autopsied cases of head injury, aged between 19 and 84, 15 of which had sustained road traffic accidents, were examined; the others were due to falling from heights and so on. The study group all belonged to non-missile head injuries and included 12 cases of diffuse brain injury, as well as 14 cases of focal brain injury, according to the classification of Gennarelli et al. The survival time ranged from 2 h to 21 years. Formalin-fixed brains were cut coronally so as to make paraffin-embedded hemispheric sections. Then these sections were stained conventionally (HE, Bodian, Kluver-Barrera and Holzer) and immunohistochemically (GFAP) to assess axonal decrease, myelin pallor and gliosis by the use of light microscopy. In the 13 chronic cases that died more than 1 month after the accidents, the intensities of gliosis, myelin pallor and axonal decrease tended to correlate with each other. In the 13 acute cases who died less than 1 month after their accident, the degree of axonal decrease in white matter seemed to correlate with the severity of myelin pallor. Regardless of types of trauma, however, axonal retraction balls, the so-called hallmark of DAI, were found only with myelin pallor suggesting the presence of brain swelling after the injury. Therefore these findings indicate that it may be difficult to accept the notion of DAI, that is, the presence of axonal retraction balls without brain swelling. In addition, diffuse vascular injury (2 cases) as well as rarefaction of subcortical white matter (6 cases) were presented and their pathogenesis individually discussed based on a literature review.

Adult↗

Inhibitors of nitric oxide synthase in human skin.

The aim of this study was to investigate in human skin in vivo the role of nitric oxide in maintaining resting vascular tone, in the vasodilatation caused by local warming and by ultraviolet B light exposure, and in the response to exogenous calcitonin gene-related peptide (CGRP). Cutaneous blood flow was assessed by planimetry of the visible erythema or pallor and by laser Doppler flowmetry. Intradermal injection of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol), into forearm skin produced a visible pallor and a reduction of blood flow at a controlled ambient temperature of 21 degrees C. The control, NG-nitro-D-arginine methyl ester (D-NAME; 25 nmol) or NG-monomethyl-L-arginine (L-NMMA; 25 nmol) did not cause pallor or reduce blood flow. L-NAME and L-NMMA caused dose- and time-dependent increases in pallor, and reductions in cutaneous blood flow in skin that had been locally warmed by immersion in water at 45 degrees C and in skin that had been exposed to ultraviolet B light. D-NAME and D-NMMA at comparable concentrations did not have the effects on skin blood flow observed with the L forms. L-NAME and L-NMMA both inhibited the increased blood flow in human skin caused by the intradermal injection of CGRP (12.5 or 25 pmol). The reduction of CGRP-induced increase of blood flow by L-NAME was reversed by L-arginine. Neither D-NAME nor D-NMMA inhibited the increase in blood flow caused by CGRP. Neither L-NAME nor L-NMMA inhibited the increase in blood flow in human skin caused by the intradermal injection of prostaglandin E2 (63 pmol). The data show that nitric oxide is involved in the maintenance of resting blood flow in human skin and also in the cutaneous vasodilator responses to local warming, ultraviolet B irradiation, or injection of CGRP.

Adolescent↗

Optic disc morphology of patients with OPA1 autosomal dominant optic atrophy.

BACKGROUND/AIMS: Patients with autosomal dominant optic atrophy (ADOA) are genetically heterogeneous, but all have disc pallor. A degree of cupping in ADOA can make the distinction from normal tension glaucoma (NTG) clinically difficult. This study aimed to clarify the features of the optic nerve of patients with ADOA at the OPA1 locus. METHODS: 29 patients (58 eyes), from 12 families, were identified in a prospective observational study of patients with ADOA examined by a single observer between 1995 and 1998, in whom genetic analysis showed either evidence for linkage to chromosome 3q28 or mutations in the ADOA gene, OPA1. All of the patients had disc and fundal photographs available for retrospective analysis. Clinical data collected included disc appearance, intraocular pressure, Snellen visual acuity, Hardy-Rand-Rittler colour vision plates, and Humphrey 30-2 visual fields. RESULTS: Mean age at time of examination was 37 years and mean visual acuity was 6/24. Disc morphology showed temporal disc pallor in 30 eyes (52%) and total disc pallor in 28 eyes (48%). At least one disc showed a cup to disc ratio of more than 0.5 in 18 patients (28 discs, 48%). The temporal neuroretinal rim always showed pallor and shallow shelving (or saucerisation) was seen in 46 eyes (79%). Only 12 discs (21%) had deep excavation and baring of blood vessels. All of the patients had normal intraocular pressure and no family history of glaucoma. There was a temporal grey, pigmentary crescent in 12 patients (18 eyes, 31%) and peripapillary atrophy in 20 patients (40 eyes, 69%), but disc margin haemorrhages were not seen. There was no maculopathy or retinopathy. CONCLUSION: The optic disc morphology, described for the first time in this genetically homogeneous population of patients with OPA1 ADOA, shows a distinctive absence of a healthy neuroretinal rim and shallow saucerisation of the optic disc cup, with frequent peripapillary atrophy.

Adolescent↗

Evaluation of the circulation in the retina, peripapillary choroid and optic disk in normal-tension glaucoma.

Computerized image analysis, including fluorescein angiography, was used to evaluate the retinal, choroidal and optic disk blood flow in 16 patients with normal-tension glaucoma (NTG) and to correlate this measurement with visual fields, retinal vessel width, optic disk pallor and blood pressure (BP). The angle of the ascending slope of the fluorescein dye curve was measured as an index of blood flow from the densitometric and time curves of the fluorescein angiograms in the optic disk, peripapillary choroid, retinal artery and vein for each quadrant. While the ascending slope as well as the retinal vessel width were most reduced in the inferior and nasal regions, the mean threshold was lowest in the superior and nasal quadrants. There were positive significant correlations between artery width and threshold value, between angles of slopes and pallor. In addition, systolic BP had a negative correlation with pallor, and diastolic BP had a positive one with slope in the choroid. These results indicated the probable association of a decrease in retinal, choroidal and optic disk blood flow in the inferior and nasal quadrants as well as vessel width in the inferior nasal quadrant with visual field loss in the superior quadrant, and also demonstrated an increasing blood flow for enlargement of pallor. A decrease in BP was found to be related to reduced blood flow in choroid and optic disk impairment.

Blood Circulation↗

White matter changes in elderly people: MR-pathologic correlations.

Magnetic resonance (MR) imaging features of white matter lesions, often seen in the elderly, are correlated with histologic findings. Dilatation of perivascular spaces is seen, especially in the frontal and/or parietal subcortical white matter; the spaces are less than 3 mm in diameter and have sharp margins with no perifocal abnormality. Old lacunar infarcts are larger than 3 mm in diameter and are irregularly shaped and accompanied by perifocal myelin pallor and gliosis. Periventricular hyperintensity, including cap and rim, histologically shows myelin pallor, dilatation of perivascular spaces, discontinuity of the ependymal lining, and subependymal gliosis. Deep and subcortical white matter hyperintensity reflects myelin pallor and dilatation of perivascular spaces. Diffuse white matter lesion, seen in Binswanger's disease, shows myelin pallor and tissue rarefaction associated with loss of myelin and axons. U-fibers are usually well preserved. Severe arteriosclerosis and arteriolosclerosis are usually seen in the white matter. Knowledge of the pathologic features of incidental changes in white matter helps in understanding MR imaging findings.

Aged↗

An experience with sixty cases of haematological malignancies; a clinico haematological correlation.

BACKGROUND: Haematological malignancies are not uncommon in our area. Due to inadequate diagnostic facilities and lack of health education they are diagnosed at an advanced stage when treatment is either impossible or very difficult. In our study, sixty patients with haematological malignancies were studied from 1-1-1999 to 1-1-2001, at Ayub Teaching Hospital. Abbottabad. METHODS: Patients were interviewed in detail, a thorough physical examination and blood tests including haemoglobin estimation, total and differential leukocyte count, platelets count, reticulocyte count and blood film examination was done on each patient. Bone marrow examination for routine giemsa staining and cytochemistry was also done in each case. Trephine biopsy was done in selected cases. RESULTS: About 35.9% patients had acute myeloid leukemia, while 19.15% patients had acute lymphoblastic leukemia. Non Hodgkin's lymphoma was seen in 15.39% cases. Among chronic leukemias, chronic lymphocytic leukemia outnumbered chronic myeloid leukemia (13.91% against 10.76%). Multiple myeloma was seen in 4.61% patients while a single patient had Hodgkin's disease. Male to female ratio in haematological malignancies was 1.4:1 and majority of the patients (66.66) belonged to two districts (i.e. Mansehra and Abbottabad). Low grade fever, progressive pallor, weakness and body aches were the commonest symptoms (70% cases) while pallor was the frequently observed sign. Medium age for acute myeloid and acute lymphoblastic leukemia was 26 years and 7 years respectively. For chronic myeloid and chronic lymphocytic leukemia it was 22 years and 56 years respectively. In case of non Hodgkin's lymphoma it was 22.5 years. CONCLUSION: In our study acute myeloid leukemia was the commonest type of haematological malignancy. Males were affected more than the females. Majority of the patients belonged to districts Mansehra and Abbottabad. Non specific symptoms like low grade fever, progressive pallor and bodyaches were the commonest symptoms while pallor was the most frequently observed sign.

Adolescent↗

Variability of expert observers in evaluating the optic disc.

A significant amount of variability exists between observers in designating cup/diac (C/D) ratios. Further, different methods are used for evaluating the size of the cup. On method uses a combination of contour and color, the other specifically measures contour and pallor separately. This study confirms that these methods yeild different numerical results. Interestingly, the "cupping/pallor" observers show no significant difference among one another in C/D determination which may support the notion that cupping observations are more consistent than "standard" C/D ratios. Though both groups feel the cup is larger on stereo compared to monocular viewing, the "cupping/pallor" group demonstrated much greater differences in this regard. However, the evaluation of pallor by the latter group corresponded closely to the C/D ratios of the "standard" group both for nonstereo and stereo. An individual observer is reasonably consistent on repeat evaluation, but at times, inconsistency is quite substantial. These inconsistencies lead to the conclusion that C/D ratios are an inexact method of recording the status of a disc. Except for considerable changes over time, this numerical method is probably not reliable in checking for small disc changes. However, the disc alone can provide clues as to whether it is physiologic or pathologic. Nevertheless, even with expert observers, significant variability exists in interpretation of an optic disc in this regard. Individuals who evaluate the disc cup by cupping and pallor tend to call discs more pathologic than other observers. The clinical implications of this study suggest that certain observers are more accurate than others and certain discs are more easily evaluated than others. Yet, no one method seems foolproof and no specific criteria can as yet distinguish a normal from an abnormal disc. Stereo color transparencies are evaluated more accurately than are nonstereo color prints. Vessel detail and pallor patterns are probably the most useful disc characteristics to observe. In this regard, a C/D ratio does nothing to indicate whether a disc is normal or not. A statement as to the observer's opinion should be made for each disc evaluation in addition to recording the appearance of the disc.

Fundus Oculi↗

Cutaneous responses to endothelin-1 and histamine in patients with vibration white finger.

Vibration white finger (VWF) is the episodic blanching of the fingers that occurs in response to cold in those who work with hand-held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent pain and paresthesia are common in the hands and arms and occur independently of the "white attacks." We have previously reported a decrease in protein gene product 9.5 and calcitonin gene-related peptide-immunoreactive nerve fibers in the digital skin of individuals with VWF. In this study, we have sought to determine whether this deficit of immunoreactive sensory-motor nerves has a functional counterpart in vivo. Histamine produces a rapid wheal and flare response following intradermal injection, whereas endothelin-1 (ET-1) produces a central area of pallor with a surrounding neurogenic flare. In contrast, calcitonin gene-related peptide produces a non-neurogenic erythema. In this study, histamine and ET-1 were injected into the dorsum of the middle phalanx and the local neurovascular response was assessed by measuring the area of the visible flare or pallor. Basal finger blood flow was also measured by laser Doppler flowmetry in each of the digits prior to intradermal injection. The experiments were performed at 21 degrees C and 4 degrees C. Patients with VWF and asymptomatic vibration-exposed workers had significantly lower resting skin blood flow at both 21 degrees C and 4 degrees C than heavy manual workers with no vibration exposure. The size of the histamine- and ET-1-induced flares at both 21 degrees C and 4 degrees C was significantly smaller in patients with VWF when compared with the asymptomatic vibration-exposed workers and heavy manual workers. The size of the ET-1-induced pallor was smaller in patients with VWF when compared with the heavy manual workers at both 21 degrees C and 4 degrees C. In contrast, the area of erythema induced by intradermal injection of calcitonin gene-related peptide at both 21 degrees C and 4 degrees C was of a similar size in patients with VWF and in heavy manual workers. These results indicate that the neuroneal deficit identified by immunohistochemistry in the digital skin of patients with VWF has a functional counterpart in vivo and is evident as a reduced ability to propagate an axon-reflex vasodilator response when challenged with histamine and ET-1. Furthermore, these results enable patients with VWF to be differentiated from both asymptomatic vibration-exposed workers, in whom the histamine- and ET-1-induced flares are normal, and those with primary Raynaud's disease, in whom the ET-1 flare is reduced and the histamine-induced flare is normal.

Adult↗

Clinical algorithm for malaria during low and high transmission seasons.

OBJECTIVES: To assess the proportion of children with febrile disease who suffer from malaria and to identify clinical signs and symptoms that predict malaria during low and high transmission seasons. STUDY DESIGN: 2490 children aged 2 to 59 months presenting to a health centre in rural Ethiopia with fever had their history documented and the following investigations: clinical examination, diagnosis, haemoglobin measurement, and a blood smear for malaria parasites. Clinical findings were related to the presence of malaria parasitaemia. RESULTS: Malaria contributed to 5.9% of all febrile cases from January to April and to 30.3% during the rest of the year. Prediction of malaria was improved by simple combinations of a few signs and symptoms. Fever with a history of previous malarial attack or absence of cough or a finding of pallor gave a sensitivity of 83% in the high risk season and 75% in the low risk season, with corresponding specificities of 51% and 60%; fever with a previous malaria attack or pallor or splenomegaly had sensitivities of 80% and 69% and specificities of 65% and 81% in high and low risk settings, respectively. CONCLUSION: Better clinical definitions are possible for low malaria settings when microscopic examination cannot be done. Health workers should be trained to detect pallor and splenomegaly because these two signs improve the specificity for malaria.

Algorithms↗

[Assessing severe maternal anemia and its consequences: the value of a simple examination of the coloration of palpebral conjunctiva].

The aims of this study were: (1) to investigate the relationship between pre-delivery hemoglobin (Hb) concentration and the outcome of the pregnancy for the mother and child and (2) to assess the extent to which the pallor of the conjunctiva indicates severe anemia in pregnancy (Hb < 7 g/dl). We carried out a prospective study in 1995, in the maternity department of the National Sourô Sanou Hospital (Bobo-Dioulasso, Burkina Faso). Women arriving to give birth at the maternity unit gave verbal consent and underwent a physical examination including the assessment of conjunctiva coloration. Finger-prick blood samples were taken from all the women selected and Hb was determined with a portable hemoglobin meter (HemoCue AB, Sweden). For each woman, information about age, obstetric history, the condition of mother and child at admission and delivery and any post-delivery complications in the first 48 hours was collected before discharge from the maternity unit, 3 to 5 days after the delivery. Women with multiple pregnancies were excluded from the study and 247 women were included overall. Endometriosis was observed in only three cases. Three women died, two due to septic shock. The third woman died from hypovolemic shock. The Hb concentrations of these women were 8 g/dl, 10.2 g/dl and 2.6 g/dl respectively. The mean Hb concentration for our population was 10.1 g/dl (SD = 2.08), with 165 women (67%) having less than 11 g Hb/dl. Forty-one women (17%) had less than 9 g Hb/dl and 16 (6%) had less than 7 g Hb/dl. Severe maternal anemia and pallor of the conjunctiva were significantly associated with pre-term delivery and perinatal death, but not with low birth weight. The sensitivity of the pallor of the conjunctiva for detection of severe maternal anemia was 87%, and its specificity was 88%. We found no evidence that maternal Hb levels of 9 to 10.9 g/dl were associated with a high risk of poor pregnancy outcome for either the mother or the child, although women with such levels of Hb are classed as anemic by the World Health Organization criteria. These results show that poor pregnancy outcome is associated with severe maternal anemia. Examination of the coloration of the conjunctiva is a suitable and affordable screening method for the detection of severe anemia. Mothers with severe anemia present with signs and symptoms of anemia and could therefore be given iron treatment to improve their health. This demonstrates the importance of nutritional intervention during pregnancy.

Adult↗

Passive malaria surveillance in a low endemic area of India: validation of a clinical case definition.

BACKGROUND: In India, 2.55 million cases of malaria were reported during 1997; roughly one-third were due to Plasmodium falciparum. Malaria cases are identified by passive and active surveillance and all patients with fever are treated with chloroquine (10 mg/kg body weight). Since all fevers are not malaria, this results in overtreatment and has a bearing in terms of the parasites developing resistance. We aimed to test the validity of a clinical algorithm for passive malaria surveillance by primary care doctors (fever with pallor or splenomegaly) in a low endemic, Plasmodium vivax-predominant area of Ballabgarh block in Faridabad District, Haryana. METHODS: Passive surveillance was carried out at the general and paediatric outpatient departments (OPDs) of Ballabgarh hospital. All persons with fever attending the OPD were examined for the presence of fever, pallor and splenomegaly by the treating doctor. A blood smear was prepared and examined in all these cases. RESULTS: A total of 3119 slides for malaria were made at Ballabgarh hospital but clinical details in the requisition form were available for only 2616 patients who form the subjects of this analysis. A total of 59 malaria cases (30 P. vivax cases and 29 P. falciparum) were diagnosed. The presence of fever with pallor or splenomegaly had a sensitivity of 28.8% (95% CI: 18.1-42.3); specificity of 88.6% (95% CI: 87.3-89.8), positive predictive value of 5.5% (95% CI: 3.3-8.8) and negative predictive value of 98.2% (95% CI: 97.5-98.7). CONCLUSION: The algorithm did not have sufficient sensitivity to detect malaria cases by passive surveillance.

Algorithms↗