Halofantrine in acute malaria.
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Biomedical subjects
Publications and source records attributed to S Wadhwa.
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Early development of retinal ganglion cell morphology has been studied in human fetuses of gestational age ranging from 7-8 weeks to 19-20 weeks by retrograde labelling with a lipophilic fluorescent dye, DiI. The retinal ganglion cells with simple and relatively uniform appearance having few dendritic processes between 7 to 11 weeks of gestation show progressive growth and elaboration of dendrites at 17-18 weeks revealing some morphological variation in shapes. It is by 19-20 weeks of gestation that the three major ganglion cell types resembling the alpha, beta and gamma classes of cat ganglion cells are identifiable in the developing human retina. The dendrites of some ganglion cells exhibit varicosities, filiform processes and spines even as early as 10-11 weeks indicating a possibility of involvement in synaptic connectivity.
The expression of substance P (SP) was examined in dentate nucleus (DN) of human cerebellum. A spatial and temporal sequence was observed in the innervation of the DN. SP appeared at 9-10 weeks and was dense in the dorsomedial region of DN. The SP immunoreactivity continued to increase until 19-21 weeks and showed a decline in the dorsomedial region by 24 weeks. By now, however, the ventrolateral region had a denser innervation. There is thus seemingly a relation between SP innervation and gyri formation in DN. SP-positive fibers were also localized in the neuroepithelium of the IV ventricle at all the ages studied. SP-positive fibers, however, reached the cerebellar cortex only by 24 weeks.
The aim of the investigation was to find out the role of noradrenergic (NE) terminals of the medial preoptic area (mPOA), in the regulation of sleep-wakefulness. Studies were conducted on free-moving adult male rats with chronically implanted cannulae in the mPOA. Sleep-wakefulness was assessed on the basis of EEG, EMG, and EOG recordings along with behavioral observations. Lesioning of catecholamine terminals (with 6-hydroxydopamine) in the mPOA produced an increase in quiet wakefulness. Prevention of NE fiber destruction, by pretreating the rats with imipramine, prevented this effect. This demonstrated that the increased quiet wakefulness produced by 6-OHDA was the result of NE fiber destruction. Changes in sleep-wakefulness were also assessed after microinjection of NE into the mPOA, in normal and ventral noradrenergic bundle (VNA)-lesioned rats. NE administration induced sleep in VNA-lesioned rats, and arousal in normal rats. The findings suggest that the NE terminals in the mPOA, projecting via VNA, play a role in the induction of sleep.
The temporal pattern of development and distribution of gamma aminobutyric acid, serotonin, substance P and neuropeptide Y immunoreactive profiles was studied in the human visual cortex from 16 to 26 weeks of gestation, using an immunohistochemical technique. The immunoreactive profiles showed an increase in number and a change in their morphology and distribution pattern over the time period studied. A large number of neurons, fibers and terminals were stained with GABA antibody at 17-18 weeks and were distributed throughout the five zones of the developing visual cortex. GABA neurons were non-pyramidal and bipolar in form at 17-18 weeks while at 18-19 and 20-21 weeks the cells of subplate and intermediate zones were multipolar. Substance P and serotonin immunopositive fibers were present mainly in the intermediate zone at 16 and 17-18 weeks, where they were oriented in a horizontal manner. At subsequent ages they invaded the other zones also. Substance P positive neurons could be visualized only at 26 weeks of gestation in the intermediate, subventricular and ventricular zones; no cell bodies, however, stained with serotonin antibody. Neuropeptide Y immunoreactive cells and fibers were first seen in the intermediate zone but later were found to be distributed in other zones too. The observations indicate that the intermediate zone of the visual cortex in which the transmitters and peptides appear earlier assumes importance in the normal development as also noted in other mammals.
Using morphometric methods, a quantitative study has been carried out on the lateral geniculate nucleus (LGN) of human fetuses ranging in gestational age from 13 to 38 weeks. The volume of the nucleus as well as the neuronal, glial and dead cell populations have been studied in Nissl preparations. While the volume of the LGN shows a progressive increase throughout the period of study, the age period of 15-20 weeks is identified as a period of spurt in volumetric growth. Neuronal density and total neuronal number fall continuously while glial density and total glial population show a steady increase with advancing gestational age. Pyknotic dead cells are seen throughout the period of study with a peak die off between 14 and 18 weeks. The study, for the first time, outlines the critical period for volumetric spurt and neuronal death in the developing human LGN.
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Histological and quantitative studies were carried out in dentate nucleus (DN) of 14 human fetuses of gestational ages ranging from 10 weeks to 28 weeks in Nissl stained sections. The dentate nucleus was already well delineated at 11 weeks, but the adult profile was attained only by 27-28 weeks. The magnocellular dorsomedial region and the parvocellular ventrolateral region became apparent at 17-18 weeks. The numerical density of neurons showed a steady decline with advancing gestational age. However, the absolute neuronal count until 19-20 weeks was 367.1 x 10(3) followed by a count of 249.5 x 10(3) at 22-23 weeks. The reduction in the count between the two periods was significant and coincided with cell death which was striking between 19 and 23 weeks. The glial cell population continued to increase with advancing gestational age. The occurrence of significant neuronal cell death and its probable role in the developing human DN is reported for the first time.
Golgi-stained sections of the human cerebellar dentate nucleus (DN) at various gestational ages were examined to study the dendritic proliferation and maturation of the DN neurons. Bipolar cells were seen at 14-15 weeks. By 19-20 weeks, three cell types were identifiable: bipolar, hemispheric and pyriform. The cells of the dorsomedial region matured earlier than those of the ventrolateral region. In addition to the above cell types, multipolar and nuclear boundary cells were observable at 24-25 weeks. The five cell types persisted during subsequent development. At no stage of development was any neuronal organizational pattern apparent. A remarkable dendritic proliferation occurred at 27-28 weeks. Spines and filiform processes were seen at 34 weeks of intrauterine life.
OBJECTIVE: To assess the cost effectiveness of a periodic program of colorectal cancer screening in the elderly. DESIGN: A model was constructed of four strategies for the periodic screening of persons 65 to 85 years of age. The effect of each strategy on life expectancy and health care costs was estimated under assumptions that were uniformly unfavorable to screening. Cost and added years of life were discounted at 5% per year. Cost per year of life gained from screening was calculated for each screening strategy. DATA SOURCES: Assumptions used in the model were based on a review of pertinent studies; those studies with results more unfavorable to screening were given more weight. Strengths and weaknesses of studies are discussed. MAIN RESULTS: A program of annual fecal occult blood testing (FOBT) in the elderly would detect at least 17% of the expected cases of cancer and could cost $35,000 per year of life saved. Screening schedules that include periodic sigmoidoscopy would prevent more cases of cancer but could cost between $43,000 and $47,000 per year of life gained. These estimates are based on uncertain assumptions, but results were not extremely sensitive to further relaxation of the values of the most uncertain assumptions. In no case did the cost per year of life gained from annual FOBT exceed $55,000 or did the cost per year of life gained from FOBT with sigmoidoscopy every 5 years exceed $61,000. CONCLUSIONS: Although colorectal cancer screening is costly in the aggregate, its potential medical benefits make it a reasonably cost-effective preventive intervention for the elderly.
The three-dimensional configurational and volumetric changes of the human dentate nucleus (DN) during intrauterine life were examined in 11 fetuses (11 to 27-28 weeks of gestation). During intrauterine life, the dentate nuclear profile successively passes through the pongid, cercopithecus and prosimian phases of configuration. The smooth, elongated, crescent-shaped DN of 11 weeks lies along a dorsal-ventral axis. A 45 degrees clockwise shift in the position of the nucleus changes the axis to dorsomedial-ventrolateral at 14-15 weeks, which is maintained in subsequent ages. The formation of gyri is preceded by a thinning of the substantia grisea. This begins at 17-18 weeks in the dorso-medial region of the DN. Gyri first make their appearance at 24-25 weeks. The DN of 27-28 weeks resembles the adult human DN. Two regions are discernible at this stage--a microgyric, magnocellular region and a macrogyric, parvocellular region. The DN volume increases with increasing gestational age. Between 14-15, 19-20 and 24-25 weeks the volumetric increase is statistically significant. This is simultaneously accompanied by a modification of the configuration of the DN.
Immunohistochemical studies for analysing the development of the profile of two peptides--substance P (SP) and Leu-enkephalin (Leu-ENK), and serotonin (SER)--have been conducted on the lateral geniculate nuclear (LGN) complex of albino rats at gestation day 18 and various postnatal age periods. SP immunoreactivity is found to increase from 1 day postnatal (DPN) up to 20 DPN and decrease thereafter, whereas the SER and Leu-ENK-immunoreactive fibres and terminals seen as occasional fibres at 1, 5, and 10 DPN are better visualized from 20 DPN and gradually increase up to 40 DPN. The possible role and significance of the changes seen in these putative neurotransmitters/neuromodulators with development are discussed.
Substance P has been immunohistochemically localized in the human optic nerves and lateral geniculate nuclei during the prenatal period from 13-14 to 37 weeks of gestation. Substance P-immunoreactive fibres were present in the optic nerves and lateral geniculate nuclei in all these ages thereby providing direct evidence of this undecapeptide being associated with the retinogeniculate pathway. At 16-17 weeks, greater numbers of fibres were observed than in the later ages. It is likely that the reduction in number of optic nerve fibres seen quantitatively during prenatal life may partly be due to the loss of substance P fibres.
The developing neural substrate in dorsal lateral geniculate nucleus of human fetuses and premature, full-term and postnatal infants, has been analysed using rapid Golgi impregnation, computerized image analysis, electronmicroscopy, and immunocytochemical method for localization of gamma-aminobutyric acid. Nuclear and cytoplasmic neuronal maturation is observed to extend over the entire period studied. Axodendritic synapses, presumably of retinal origin, are occasionally seen at 13-14 fetal weeks. They become increasingly apparent at 18-19 weeks. Dendrodendritic contacts are visualized at 15 weeks. Cortical terminals and occasional triadic contacts are evident around 21 weeks. The inhibitory interneurons containing gamma-aminobutyric acid are present in small numbers at 15-16 weeks; their numerical density increases considerably at 17 weeks but decreases thereafter. The presence of gamma-aminobutyric acid containing nerve cells and synaptic triads is indicative of the formation of inhibitory circuitry. At 15-16 weeks neurons are mostly bipolar although different forms of multipolar cells may be seen. By 24 weeks the radiated and bitufted multipolar neurons, neurons with beaded dendrites and neurons with axon-like dendritic processes are identifiable. There are no apparent differences in differentiation of neurons between the cranial and caudal parts of dorsal lateral geniculate nucleus. At 15-16 weeks, however, the cells of prospective magnocellular zone appear to be more mature than do the cells in the parvocellular zone. The neuronal soma increases continuously in size. Dendrite development starts at 15-16 weeks of gestation, thereafter the increase in number of their branches and their length is observed. Between 15-16 and 24 weeks, spines and filiform processes appear first on the proximal shafts of the dendrites and subsequently on their distal portion. There is increase in the number of filiform processes and hair-like appendages on geniculate neurons of premature infants born at 32 and 37 weeks of gestation and of a 4-day postnatal infant. Computerized quantitative data substantiate the progressive increase in growth parameters. The significance of comparative and functional aspect of the data is discussed.