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Development of neuroventricular cells into ocular pigment cells in embryonic chick eyes: morphometrical and electrophysiological observations.

The development of neuro-ventricular cells into pigment cells (outer layer of the optic cup) was studied morphometrically and electrophysiologically in eye primordia of chick embryos. The prospective pigment cells are homogeneous until days 4 to 5 1/2 of embryonic development. During this period, all cells are devoid of pigment and display a basic neuroventricular profile of both inward (probably sodium) and outward (potassium) currents evoked by depolarization. Pigment cell differentiation occurs rapidly between days 5 and 6. On day 6 most cells are pigmented and respond to depolarization with outward currents only. Inward currents were elicted only in a few pigmented cells. By contrast, the minority of unpigmented cells (or cells with faintly dark cytoplasmic inclusions, probably premelanosomes) still present on day six displayed the "immature" pattern of mixed inward and outward currents. We conclude, that the differentiation of neuroepithelial cells into pigment cells involves both the synthesis of pigment granula and the down-regulation of the expression of inward current-mediating ion channels in their membrane.

Animals↗

Coexpression of two visual pigments in a photoreceptor causes an abnormally broad spectral sensitivity in the eye of the butterfly Papilio xuthus.

The compound eye of the butterfly Papilio xuthus consists of three different types of ommatidia, each containing nine photoreceptor cells (R1-R9). We have found previously that the R5-R8 photoreceptors of type II ommatidia coexpress two different mRNAs, encoding opsins of green- and orange-red-absorbing visual pigments (Kitamoto et al., 1998). Do these cells contain two functionally distinct visual pigments? First, we identified the sensitivity spectrum of these photoreceptors by using combined intracellular recording and dye injection. We thus found that the R5-R8 of type II ommatidia have a characteristic sensitivity spectrum extending over an excessively broad spectral range, from the violet to the red region; the photoreceptors are therefore termed broadband photoreceptors. The spectral shape was interpreted with a computational model for type II ommatidia, containing a UV visual pigment in cells R1 and R2, two green visual pigments in cells R3 and R4, a far-UV-absorbing screening pigment (3-hydroxyretinol) in the distal part of the ommatidium, and a red-screening pigment that surrounds the rhabdom. The modeling suggests that both visual pigments in the R5-R8 photoreceptors participate in phototransduction. This work provides the first compelling evidence that multiple visual pigments participate in phototransduction in single invertebrate photoreceptors.

Animals↗

Thickness, medullation and growth rate of female scalp hair are subject to significant variation according to pigmentation and scalp location during ageing.

The biological importance and/or significance of human hair colour is unknown even though greying is obviously associated with ageing. In order to further characterise hair pigmentation in relation with hair growth variables we evaluated 3 scalp sites (top of the head (T): left and right and occipital(O)) in 12 untreated menopausal women (age range: 49-66 years: average 59.63 +/- 5.66) who presented complaining of hair loss and/or diffuse alopecia. Controls were 12 non menopausal sexually mature woman (7 age range 15-21 and 5 age range 38-48) not complaining of hair loss. One hair sample (whenever possible n = 60) was taken one month after clipping from T and O on each person; menopausal women were sampled twice. The following measures were performed with a light microscope: diameter (average min-max., microm), medulla (0% = absent to 100% = fully developed) and linear hair growth rate (mm/day). The hairs were categorised as pigmented (P) or non-pigmented (white, W) as compared with a black and white reference card. A total of 3343 hairs were analysed with 2-factor analysis of variance (ANOVA). A global comparison (all hairs) showed that the average diameter of W hair (67.68 microm) exceeded that of P hair (57.41 microm) (p = 0.0001) and this was maintained on all 3 scalp sites. In addition, the medulla of W hair (23.91%) appeared more developed than the medulla of P hair (12.21%) (p = 0.0001) and was more expressed in W T hairs as compared with W O hairs (p = 0.0325). There was also a significant interaction between site and pigmentation (p = 0.0074). Growth rate of W hairs (0.38 mm/d) was higher than that of P hairs (0.35 mm/d) (p = 0.0001) and there was a significant variation according to scalp sites (p = 0.0001). There was also a significant interaction between site and pigmentation (p = 0.0062) with the following rank order: O W (0.40 mm/d), T W (0.37 mm/d), O P (0.37 mm/d) and T P (0.34 mm/d). Subgroups of W and P of paired thickness in the range of 50 to 80 pm consistently showed a 10% faster growth rate of W. Previous studies have shown that growth rate and diameter declines in age and alopecia i.e. in hair thinning. Our data shows that the reduced growth rate of terminal hairs is in fact limited to the pigmented hairs. The mechanisms by which white hairs are spared these ageing changes are not yet understood. Less pigmented hairs are usually undetected by photo- graphic techniques used for drug trials. The potential role of drug induced modifications of hair pigmentation should be taken into account during the interpretation of efficacy except if contrast-enhancement has been applied.

Aged↗

Role of intestinal barrier in pathogenesis of pigment gallstone in a guinea pig model.

BACKGROUND: The function of the intestinal barrier has drawn more and more attention from researchers in recent years for its important role in many diseases such as burns, wounds, and pancreatitis. In our experimental studies on pigment gallstone, we found potential relationships between the function of the intestinal barrier and pigment gallstone formation. This study was undertaken to investigate the possible action and mechanism of the function of the intestinal barrier in the pathogenesis of pigment gallstone. METHODS: Eighty guinea pigs were divided into a normal group (CON), a pigment gallstone group (PS) and an intestinal mucosa protection group (GLN). Normal forage, pigment gallstone-forming forage and pigment gallstone-forming forage with supplemental intestinal mucosa protector (glutamine) were given to each group. In the gallstone-forming rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin and biliary beta-glucuronidase were assessed after 8 weeks. RESULTS: The rate of gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa, endotoxemia (from 77+/-43 X 10(-6) EU/L to 1,367+/-525 X 10(-6) EU/L, P<0.01) and increased activity of biliary beta-glucuronidase (endogenous beta-glucuronidase from 122.1+/-39.5 to 209.8+/-47.5 Fishman Unit, P<0.01, and exogenous beta-glucuronidase from 573.5+/-476.9 to 2,206.6+/-983.9 Fishman Unit, P<0.01) were observed in the PS group compared with the CON group. The rate gallstone-formation decreased significantly to 44.4% and the other indices except beta-glucuronidase were lower in the GLN group than in the PS group. CONCLUSIONS: The function of the intestinal barrier is correlated with pigment gallstone formation. Dysfunction of the intestinal barrier function may promote pigment gallstone formation through bacterial translocation, endotoxemia, and biliary beta-glucuronidase.

Animals↗

[Morphology of live retinal pigment epithelial cells].

We attempted to observe, by means of fluorescein angiography, the retinal pigment epithelial cells in pigmented rabbits. Fluorescein angiography was performed in 31 pigmented rabbits, after intravenous injection of 14mg/kg fluorescein sodium. The angiograms were evaluated as prints and as negative film under a light microscope. Animals were sacrificed and submitted to studies by scanning electron microscopy and fluorescein light microscopy. On fluorescein angiograms, we observed mosaic pattern which consisted of numerous polygonal spots overlying choroidal vasculature. Each polygonal spot showed central hypofluorescent area surrounded by hyperfluorescent rim. They were seen in all the eyes except 4 lightly pigmented eyes. They seemed to correspond, in size, to each retinal pigment epithelial cell. This pattern appeared from the early choroidal phase on, to become more distinct 5 to 15 minutes after dye injection. A hexagonal pattern was regularly seen away from the medullary rays by 3 or more disc diameters. The pattern became larger in the periphery than in the posterior pole. These angiographic findings closely matched those of retinal pigment epithelial cells as seen by scanning electron microscopy and fluorescein light microscopy in sizes and shapes. The findings indicate that it is possible to identify retinal pigment epithelial cells in pigmented rabbits by conventional fluorescein angiography.

Animals↗

The development of the larval pigment patterns in Triturus alpestris and Ambystoma mexicanum.

1. Melanophores and xanthophores are pigment cell derivatives of the NC. In amphibian embryos they migrate from their original position on the neural tube dorsally (into the dorsal fin) as well as laterally (between somites and epidermis) and arrange themselves into typical pigment patterns of the skin. We investigated pigment pattern formation in two species of tailed amphibians, Triturus alpestris (alpine newt) and Ambystoma mexicanum (Mexican axolotl). In larvae of T. alpestris alternating longitudinal stripes or bands of melanophores and xanthophores develop, whereas in larvae of A. mexicanum a barred pattern with alternating transverse bands of melanophores and xanthophores is formed. Iridophores, a third type of pigment cell, are present later in both species and therefore play no role during early larval pigment pattern development. Visibly differentiated melanophores and xanthophores can be distinguished from each other under the light microscope by their contents of black melanins and yellow pterins respectively. With the dopa reaction (indicates tyrosinase in melanophores), and ammonia treatment (stimulates pterin fluorescence in xanthophores), the pigment cell phenotypes can be visualized even before their normal visible differentiation. In the TEM, melanophores and xanthophores can be distinguished from each other by their morphologically distinct pigment organelles and in the SEM by their different surface structure. 2. Because of the NC origin of melanophores and xanthophores and the ease with which these cells can be demonstrated even before they are visible from outside, their different arrangements in Triturus and axolotl embryos offer suitable model systems for studying the migration, interaction and localization of NC derivatives in relation to specific environmental influences. The environment of NC cells are the neural tube, epidermis, somites and lateral plate mesoderm, and the subepidermal ECM, a network of collagen fibrils associated with glycosaminoglycans, proteoglycans and glycoproteins. 3. Development of the pigment pattern in T. alpestris: Melanophores and xanthophores start to leave the NC at stage 28, melanophores slightly earlier than xanthophores. Both cell types become scattered in the dorsolateral trunk. In contrast to melanophores in the axolotl, melanophores in T. alpestris cannot be demonstrated with the dopa reaction before they become visibly black. From stage 29+ onwards, melanophores start to accumulate in zones alongside the dorsal and lateral somite edges, where they form compact stripes later. Xanthophores can be demonstrated from stage 28+ onwards only with the SEM (by means of their specific surface structures) or with the fluorescence microscope (by means of their fluorescing pterins). At state 34, xanthophores become visible externally as yellow cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Ambystoma↗

Structure and ultrastructure of the pigmented cells in the adult dog pineal gland.

The light and electron microscopic features of pigmented cells in the adult dog pineal gland have been described. The presence of pigmented cells was a constant characteristic of the dog pineal gland, though wide variations in the amount of pigment could be found among different animals. Conversely, the localisation of pigmented cells was very constant on the basal surface of the proximal region of the pineal gland. Frequently, clusters of pigmented cells were seen in the posterior commissure and the neighbour meningeal spaces, near the pigmented pineal zone. The pineal pigment has been identified as melanin according to its morphological features and histochemical properties. Several types of granules were identified ultrastructurally, apparently corresponding to different stages of a maturation process. The pigmented cells were identified as a special type of pinealocyte according to their ultrastructural features.

Animals↗

Pathology of the pigment epithelium and retina in rabbits poisoned with lead.

Multifocal lesions of the retinal pigment epithelium were observed in rabbits fed a diet contaning 0.5% lead subacetate for periods of up to 2 years. Groups of pigment epithelial cells became congested with a lipofuscin pigment which was apparently derived from phagosomes of rod outer segments. Lipofuscin granules displaced melanin granules from the apical surface of the retinal pigment epithelial cells and resulted in conspicuous brown pigmentation of these cells in albino animals. Migration of macrophages and pigment epithelial cells into the subretinal space was common in affected areas. This pathology was not observed in the pigment epithelium of the ora serrata, or ciliary body. At the latest time periods, the abnormal lipofuscin pigmentation subsided, and degeneration of photoreceptors occurred. The pathogenesis of the lesions is discussed.

Animals↗

The effect of colchicine on the pigmentation of the enamel surface in rat incisors.

The effect of colchicine and lumicolchicine on the secretion of an iron-containing pigment vesicle onto the enamel surface in the rat maxillary incisors has been studied histologically and by line scan analysis of the iron with an X-ray microanalyzer. Rats were killed at intervals of 12 and 24 hours and 3, 6 and 10 days after the subcutaneous injection of colchicine or lumicolchicine at a dose of 1.3 mg/kg. At 10 days after the colchicine injection, two pigmentation-free bands were observed on the enamel surface in each pair of incisors. By the line scan analysis of the iron with an X-ray microanalyzer, the pigmentation-free bands corresponded to the decrease of the iron concentration profile. By the histological observation at 12 and 24 hours after the injection, no remarkable changes were observed from the late pigmentation stage to the regression stage. However, at 3 and 6 days after the injection, the pigmentation-free bands appeared on the enamel surface. A large number of pigment vesicles was observed in the ameloblasts and in the papillary cells facing the pigmentation-free bands. These phenomena were not observed in the rats injected with lumicolchicine. The present study suggests that the secretion of an iron-containing pigment vesicle in the ameloblasts onto the enamel surface is mediated by the microtubules.

Animals↗

Pigments and antibiogram of transconjugants from nonpigmented mutants of Serratia marcescens.

Serratia marcescens produces a characteristic red pigment, prodigiosin, which is formed by the enzymatic coupling of 4-methoxy-2,2'-bipyrrole-5-bipyrrole-5-carboxaldehyde (MBC) and 2-methyl-3-amylpyrrole (MAP). Many clinical isolates which are resistant to multiple antibiotics are nonpigmented. However, the relationship of pigmentation (or nonpigmentation) to drug resistance of the strains has not yet been established. In this study we demonstrated the pigment synthesizing capability in the transconjugants obtained from nonpigmented mutants WF and 9-3-3 of S. marcescens under the condition of cell-to-cell contact. Mutant WF produces MAP while mutant 9-3-3 synthesized only MBC. After genetic transfer, the color of the recombinant colonies was red indicating the successful transfer of the pigment synthesizing capability. The antibiogram of the transconjugants indicated that they inherited the resistance characteristics to polymyxin B and chloramphenicol from their parent strains. further supportive evidence was obtained by spectroscopic and high performance liquid chromatographic analysis of the resulting pigments extracted from the pigmented transconjugants. The pigments produced by the transconjugants were similar, if not identical, to those produced by the wild type strain 08 and those synthesizes syntrophically. The possibility of simultaneous transfer of pigment synthesizing capability and drug resistance remains to be explored .

Conjugation, Genetic↗

Pigmented pulmonary carcinoid tumor. An immunohistochemical and ultrastructural study.

We evaluated three cases of pigmented pulmonary carcinoid tumors that were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Clinical follow-up showed no indication of tumor recurrence or metastases, nor was there evidence of malignant melanoma. All three cases exhibited histologic features of typical carcinoid tumor; there were focal oncocytic changes in two cases. Finely dispersed, brown pigment, believed to be melanin, was distributed in two different patterns: in sustentacular cells (case 1) or within the tumor cells (cases 2 and 3). Fontana-Masson stain was positive in areas of this pigment in all cases. The tumor cells showed immunoreactivity for chromogranin, synaptophysin, keratin (AE1/AE3 and CAM-5.2), and S100 protein in all cases. Focal staining for vimentin and corticotropin was seen within neoplastic cells in two cases. The pigmented sustentacular cells in case 1 showed focal immunoreactivity for S100 protein and HMB-45. Ultrastructural studies of paraffin-embedded tissues were performed in two cases. They showed well-developed melanosomes in the pigmented sustentacular cells in case 1. In both cases, cytoplasmic neurosecretory-type granules were identified in neoplastic cells. These findings demonstrate that pigmented pulmonary carcinoid tumor has an immunohistochemical profile similar to that of typical pulmonary carcinoid tumor. In some instances, pigmented pulmonary carcinoid tumors may show ultrastructural evidence of melanocytic and neuroendocrine differentiation. These immunohistologic and ultrastructural findings distinguish pigmented pulmonary carcinoid tumor from malignant melanoma and support the concept of "multidirectional cellular differentiation."

Adult↗

Drug-related pigmentation of the thyroid associated with papillary carcinoma.

Black pigmentation of the thyroid attributed to minocycline hydrochloride is known, but to our knowledge, pigmentation associated with antidepressants has not been reported. We studied four patients with papillary carcinoma associated with thyroid pigmentation; two had received minocycline therapy, and two had received long-term treatment with antidepressants. The thyroids of patients who had been treated with minocycline were black, with pigment primarily in nontumorous tissue. The thyroids associated with antidepressant therapy were dark red, with pigment in both tumorous and nontumorous tissue. All four cases were positive for periodic acid-Schiff, periodic acid-Schiff with diastase predigestion, and Schmorl's stains and negative for Prussian blue; the results differed from those found with Fontana's technique. Minocycline-related pigmentation appears to imply a role for the iodide peroxidase system in the accumulation of pigment, whereas pigmentation attributed to intake of antidepressants appears to result from lysosomal accumulation of the drug itself.

Adult↗

Pigment dispersion in frog melanophores can be induced by a phorbol ester or stimulation of a recombinant receptor that activates phospholipase C.

Pigment dispersion in frog melanophores is classically mediated by receptors that activate protein kinase A via an elevation of intracellular cyclic AMP. Here, 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, is found to induce pigment dispersion. To demonstrate that an increase in cAMP is not required for the melanosome movement, a murine bombesin receptor was expressed in the melanophores. When these cells were treated with bombesin, they accumulated intracellular inositol phosphates but not cAMP and dispersed their pigment. Four agonists, one partial agonist, and two antagonists for the bombesin receptor were compared for their ability to induce or block bombesin-induced pigment dispersion. In all cases, the degree of pigment dispersion followed simple equilibrium reactions. The resulting dose-response curves allowed for the determination of the effective concentration for half-maximal pigment dispersion (EC50) or half-maximal inhibition of bombesin-stimulated pigment dispersion (IC50) for the peptides. As the pigment dispersion assay can rapidly evaluate chemicals for their effects on receptors that activate phospholipase C via a functional assay, it has potential utility for investigations of ligand-receptor interactions and for massive drug screening.

Animals↗

Metallothionein shows an age-related decrease in human macular retinal pigment epithelium.

PURPOSE: To investigate the possible role of zinc-metallothionein in human retinal pigment epithelium with regard to age-related changes. METHODS: A cadmium/heme assay was used to quantitate metallothionein in isolated macular and peripheral retinal pigment epithelium from donors ranging in age from 28 to 91 yr (n = 16, mean age = 68.6 yr). RESULTS: It was found that peripheral retinal pigment epithelium contained significantly more metallothionein and zinc than macular retinal pigment epithelium. Macular retinal pigment epithelium cells contained 17.6 +/- 2.2 micrograms metallothionein/mg cytosolic protein in donors younger than 70 yr, compared to 5.6 +/- 0.9 in macular retinal pigment epithelium from donors older than 70 yr, a 68% decline (P = 0.0007). In cultured retinal pigment epithelium, when we lowered the zinc concentration in the medium, metallothionein was reduced by 72% after 1 wk of incubation. CONCLUSIONS: It is suggested that lower levels of metallothionein in retinal pigment epithelium are caused by reduced metallothionein gene activity or a faster rate of protein degradation, both of which are known to be regulated, at least partly, by bioavailable zinc.

Adult↗

Fundus pigmentation in retinopathy of prematurity.

OBJECTIVE: A prospective study design was used to investigate the association between different degrees of fundus pigmentation and the indicence of retinopathy of prematurity (ROP) among very low birth weight infants in a large neonatal intensive care unit. METHODS: The study group consisted of 161 infants weighing 1500 g or less at birth and included all infants born from 1988 to 1990 who survived at least 10 weeks. Presence or lack of any acute stage ROP was determined by weekly ophthalmological examination from the age of 4 weeks. The degree of fundus pigmentation was recorded for each infant during the first examination. RESULTS: Infants with dark fundus pigmentation were found to be at half the risk of developing ROP as compared with infants having light/medium fundus pigmentation (relative risk = 0.5; 95% confidence interval = 0.2-1.1). When controlled for birth weight, gestational age, length of oxygen therapy, and ethnic group in multivariate analysis, dark pigmentation was an independent and statistically significant protective factor (odds ration = 0.09, 95% confidence interval = 0.02-0.06). None of the infants with Stage III ROP or higher had dark pigmentation. CONCLUSION: We speculate that large amounts of melanin in the retinal pigment epithelium or choroid may protect the dark-pigmented very low birth weight infant from developing ROP.

Female↗

Neural crest cell migration and pigment pattern formation in urodele amphibians.

This review deals with research on the development and differentiation of the neural crest (NC) in amphibians carried out during the past twenty years. First, earlier studies on the migration and differentiation of NC cells in vitro are summarized. These studies include the modes of NC cell migration and their differentiation into chondroblasts, perichondral cells, neurons, Schwann cells and pigment cells (melanophores and xanthophores). Then a summary is given on the development of cranial sensory ganglia and enteric ganglia in Xenopus laevis. In the subsequent sections, mechanisms of NC cell migration are investigated in Ambystoma mexicanum, the Mexican axolotl (wild-type and white mutant) using ultrastructural, immunohistochemical and biochemical methods. In wild-type or dark axolotl embryos, pigment cells leave the NC and migrate out under the epidermis, whereas in the white mutant, pigment cells remain closely confined to the original position of the NC. This system provides an excellent model for analyzing NC cell migration in vertebrate embryos. Further sections deal with the development of larval pigment patterns in Triturus alpestris, (horizontal melanophore stripes) and Ambystoma mexicanum (vertical melanophore bars). Comparing the formation of these patterns shows that two different principles exist in the distribution of pigment derivatives of the NC: patterns following environmental cues (Triturus) and those ignoring these cues, relying solely on cell-cell interactions (Ambystoma). Other studies relate to evolutionary perspectives in pigment pattern formation. They are based on phylogenetic analyses of North American ambystomatids, combined with data on pigment patterns and their formation where such data are available. These studies have shown that vertical bars which develop from aggregates in the NC string are an evolutionary innovation, compared to the more primitive horizontal stripes lacking aggregates in the NC. Thus, in this review we show that the NC of amphibians (T. alpestris, Xenopus laevis, dark and white axolotls and other ambystomatids) may be used for various analyses concerning the migration and differentiation of its derivatives, as well as for studies on the formation and evolution of pigment patterns.

Animals↗

Accuracy of pulse oximetry in pigmented patients.

OBJECTIVE: Prospective assessment of the accuracy of three pulse oximeters and two probe sites in darkly pigmented critically ill patients under clinical conditions. PATIENTS AND METHODS: One hundred consecutive, darkly pigmented critically ill adult patients with arterial lines in situ were studied. Patients were excluded if the haemoglobin concentration was less than 7 g/dl and carboxyhaemoglobin or methaemoglobin levels exceeded 2%. Pigmentation was objectively quantified with a portable EEL reflectance spectrophotometer (Evans Electroselenium Company, Diffusion Systems Limited, London). Reflectance was measured at nine wavelengths. RESULTS: The degree of pigmentation as measured by percentage reflectance closely matched that of a control group of black Africans from a pigmentation study. The limits of agreement (2.6% to 5.8%), precision and bias values between pulse oximeter and co-oximeter readings fell within a narrow range. The 95% confidence intervals of the limits of agreement reflected a small variation in the difference between pulse oximeter and co-oximeter readings. These small differences were not clinically significant in the pigmented patients who were enrolled in the study. CONCLUSION: The accuracy of pulse oximetry is not adversely affected by skin pigmentation, and it remains a useful oxygenation monitoring device in darkly pigmented patients.

Humans↗

Clearance kinetics of parasites and pigment-containing leukocytes in severe malaria.

In tropical areas, where unsupervised use of antimalarial drugs is common, patients with an illness consistent clinically with severe malaria but with negative blood smears pose a management dilemma. Malaria pigment is evident in peripheral blood leukocytes in greater than 90% of patients with severe malaria. To characterize the clearance kinetics of parasitized erythrocytes and malaria pigment-containing leukocytes, sequential peripheral blood and intradermal smears were assessed in 27 adult Vietnamese patients with severe falciparum malaria. The clearance of parasitized erythrocytes and pigment-containing monocytes (PCMs) followed first order kinetics. The elimination of pigment-containing neutrophils (PCNs) was first order initially, but deviated from this when counts were low. Clearance of peripheral blood PCMs (median clearance time, 216 hours; range, 84 to 492 hours) was significantly slower than that of parasitized erythrocytes (median, 96 hours; range, 36 to 168 hours) or PCNs (median, 72 hours; range, 0 to 168 hours; P < .0001). Intradermal PCM clearance times were the longest of all (median, 12 days; range, 6 to 23 days; significantly longer than peripheral blood PCM clearance, P < .001). Twenty-one (88%) patients still had signs, symptoms, or laboratory features of severe malaria after parasite clearance but before phagocyte pigment clearance. Sixteen of the 23 surviving patients (70%; 95% confidence interval, 50% to 87%) still had intraleukocytic malaria pigment on peripheral blood films 72 hours after parasite clearance. Thus, by determining the distribution of malaria pigment in peripheral blood and intradermal phagocytes, the time since effective antimalarial treatment started can be estimated. Microscopy for intraleukocytic pigment is valuable in the differential diagnosis of severe febrile illnesses in malarious areas where uncontrolled use of antimalarial drugs is widespread.

Adult↗