The ultrastructural organization of the mature gametocytes of Plasmodium falciparum isolated from the peripheral circulation of naturally infected Gambians is examined and compared with immature forms obtained from the peripheral circulation of a chloroquine treated patient. The latter are recognized as the stage 2 and 3 developmental forms (Hawking, Wilson & Gammage 1971 Trans. R. Soc. trop. Med. Hyg . 65, 549-559) observed by light microscopy and are distinguished in the electron microscope by three characters; (i) they do not fill the host cell, (ii) they contain few, if any, osmiophilic bodies, (iii) they possess an extensive subpellicular tubule system. Maturation (capacitation) of these immature parasites takes many days and is followed by an extended period of maturity during which the gametocytes will exflagellate. Mature macro- and microgametocytes have numerous characters in common with the gametocytes of avian and reptilian Plasmodiidae, namely a tripartite pellicle, cristate mitochondria, a comparatively high density of osmiophilic bodies in the macrogametocyte, cytostomal feeding, Golgi body, and persistent nucleolus in the female gametocyte. These similarities together with the unexpected nuclear changes detected in macrogametogenesis suggest that P. falciparum is best considered as pre-dating the ‘malariae’ and ‘vivax’ groups and not as having evolved from them. Light microscopy, scanning and transmission electron microscopy and videotape analyses of gamete formation were undertaken. Nuclei in the mature gametocytes are Feulgen negative but upon activation rapidly become Feulgen positive. The gametes also are Feulgen positive. The crescentic parasites swell to become large spherical cells and escape from the host cell by osmotic or enzymic activity. The microgametocyte undergoes three mitotic divisions during which the chromosomes are sequentially reduced in number such that ca . 7 are incorporated into each gametic nucleus. The microtubule organizing centre (m. t. o. c.), which in the mature gametocyte is associated with the intranuclear body, is attached to the centriolar plaque of the first division spindle. There it differentiates into kinetosomes which act as foci for the polymerization of axonemes. The kinetosomes and axonemes remain attached to the centriolar plaques during division and are segregated synchronously with the genome at each division. Subsequently one axoneme enters each haploid gamete at exflagellation. Exflagellation is accompanied by a significant reduction in microgametocyte volume which is associated with an increase in density of the cytoplasm. The female gametocyte does not decrease in volume but undergoes nuclear changes in which a single pole of an intranuclear spindle is detected. Comparisons are made with macrogametogenesis in avian malarial parasites from which it is suggested that this spindle, if not half of a normal mitotic spindle, is an atavistic trait. The possibility of a meiotic gametic division is discussed but discounted. The activity pattern of the microgamete was found to be similar to that of other malarial parasites, with states of high and low activity or immobility. High activity, which results in rapid movement through the medium, is produced by long wavelength (12 μm), low amplitude (1.1μm) waves generated at ca . 12 waves per second; low activity, which results in contorted gyrating on the spot, is produced by long wavelength (14.1), high amplitude (2.3) waves produced at ca 1 wave per second. Following an initial period of continuous activity the gamete usually alternates between high and low activity states. Subsequent low activity and immobility is in turn followed by death. Microgamete activity was profoundly affected by the plasma of some patients, presumably as a result of the antigametocyte antibodies present. The microgamete contains a single axoneme, at one end of which lies the kinetosome with the juxtakinetosomal sphere and granule. It is this end which emerges first from the parental gametocyte. A single nucleus is centrally located in many microgametes although 23% are anucleate.
Intracranial compliance, as estimated from a computerized frequency analysis of the intracranial pressure (ICP) waveform, was continuously monitored during the acute postinjury phase in 55 head-injured patients. In previous studies, the high-frequency centroid (HFC), which was defined as the power-weighted average frequency within the 4- to 15-Hz band of the ICP power density spectrum, was found to inversely correlate with the pressure-volume index (PVI). An HFC of 6.5 to 7.0 Hz was normal, while an increase in the HFC to 9.0 Hz coincided with a reduction in the PVI to 13 ml and indicated exhaustion of intracranial volume-buffering capacity. The mean HFC for individual patients in the present study ranged from 6.8 to 9.0 Hz, and the length of time that the HFC was greater than 9.0 Hz ranged from 0 to 104.8 hours. The mortality rate increased concomitantly with the mean HFC, from 7% when the mean HFC was less than 7.5 Hz to 46% when the mean HFC was 8.5 Hz or greater. The length of time that the HFC was 9.0 Hz or greater was also associated with an increased mortality rate, which ranged from 16% if the HFC was never above 9.0 Hz to 60% if the HFC was 9.0 Hz or greater for more than 12 hours. In 12 patients who developed uncontrollable intracranial hypertension or clinical signs of tentorial herniation during the monitoring period, 75% were observed to have had an increase in the HFC to 9.0 Hz or more 1 to 36 hours prior to the clinical decompensation. The more rapid the increase in the HFC, the more likely the deterioration was to be caused by an intracranial hematoma. Continuous monitoring of intracranial compliance by computerized analysis of the ICP waveform may provide an earlier warning of neurological decompensation than ICP per se and, unlike PVI, does not require volumetric manipulation of intracranial volume.
Histological and ultrastructural studies of four placentae heavily infectd with Plasmodium falciparum revealed large intervillous accumulations of erythrocytes containing parasites together with monocytes which had ingested pigment. These appearances were associated with focal syncytial necrosis, loss of syncytial microvilli and proliferation of cytotrophoblastic cells. In addition, marked irregular thickening of trophoblastic basement membranes and protrusion of tongue-like projections of syncytiotrophoblast into the basement membrane were observed. In six other placentae which contained scanty amounts of pigment but no parasites, representing past or inactive infection, no large collections of monocytes or abnormalities of trophoblast were apparent but basement membrane thickening was evident. Immunohistological studies revealed no significant differences between placentae positive for parasites and those containing pigment only, although the amount of certain immunoproteins and clotting factors was clearly increased above normal. These findings establish that P. falciparum infection in the placenta may result in substantial damage although lesions within the villus are rare. Furthermore, previous infection, although adequately controlled, may leave a heritage of pigment deposition, basement membrane thickening and immunopathological lesions. These results may thus account for both the high frequency of intra-uterine growth retardation and the rarity of congenital malaria in the presence of P. falciparum malaria.
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