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Biomedical subjects

R C Collins

Publications and source records attributed to R C Collins.

At least 37 records · Page 2Linked to original sources
PubMed1988

Seasonality of adult black flies and Onchocerca volvulus transmission in Guatemala.

Transmission of Onchocerca volvulus, principally by Simulium ochraceum, was studied over a 14-month period in the Atitlán region of Guatemala. Semimonthly catches of black flies were made on human volunteers at 4 localities with different prevalences of human onchocerciasis. Host-seeking activity of S. ochraceum reached its greatest magnitude in the early dry season (October-January) but then declined rapidly and was lowest during the late dry season (February-May). The frequency of O. volvulus larvae in parous host-seeking S. ochraceum also varied seasonally, and this variation was most pronounced for third stage larvae. At a hyperendemic locality, the highest frequency of this larval stage occurred during the February-March period (0.0142 in 1979 and 0.0095 in 1980). From June-January, the frequency of third stage larvae in S. ochraceum was less than 0.003. The frequency of early first stage larvae exhibited the least seasonal variation, ranging from 0.0354 in August-September to 0.0628 in April-May. The transmission rate of O. volvulus by S. ochraceum also varied seasonally. At the same hyperendemic locality, infective biting density of S. ochraceum attained its greatest magnitude in February-March. The survival rate of female S. ochraceum from one gonotrophic cycle to the next was estimated from the ratio of flies with early first stage larvae to those with infective stage larvae. These rates varied seasonally and ranged from 0.2132 to 0.3974, with the highest rates occurring in the late dry season.

Animals↗
PubMed1988

Transmission of Onchocerca volvulus by secondary vectors in Guatemala.

A comprehensive study of the transmission of Onchocerca volvulus at 4 locations in Guatemala with different prevalence rates of onchocerciasis included observations on potential secondary vectors, the most prevalent of which were Simulium metallicum, S. callidum, and S. gonzalezi. Filariae encountered in S. metallicum were primarily of a Dipetalonema-like species, but third-stage larvae indistinguishable from O. volvulus were found in 4 flies of this species. Our findings suggest that O. volvulus may occasionally be transmitted by S. metallicum, but such transmission is likely limited to areas having both a high parasite prevalence maintained by S. ochraceum and a relatively high host-seeking density of S. metallicum. Two third-stage larvae that could not be differentiated from O. volvulus were found once in S. gonzalezi; however, transmission by this species appears to be inconsequential.

Animals↗
PubMed1988

Vector density, parasite prevalence, and transmission of Onchocerca volvulus in Guatemala.

Transmission of Onchocerca volvulus at 4 locations with different prevalences of human onchocerciasis in the Atitlán region of Guatemala is described in relation to vector density and infection rates. The percentages of residents with skin biopsies positive for microfilariae of O. volvulus at these locations were 13.8%, 33.3%, 65.4%, and 89.6%. The following variables associated with transmission were calculated from our observations (the values are presented in an order that corresponds with the above prevalence rates): frequency of third-stage larvae (calculated on an annual basis) in parous Simulium ochraceum, 0, 0.004, 0.005, and 0.004; estimated daily biting density of S. ochraceum, 23, 24, 254, and 1,509 flies per day; and estimated annual infective biting density (based on S. ochraceum), 0, 18, 185, and 1,101 potentially infective bites per year. The frequencies of third-stage larvae are very small compared with those observed in Africa, and suggest that transmission of O. volvulus in Guatemala depends on high vector density. Locations with low, and perhaps tolerable, levels of onchocerciasis (less than 15% of female residents with skin biopsies positive for microfilariae) have mean daily biting densities for S. ochraceum of less than or equal to 24 flies, and infected residents normally have mean microfilarial densities of less than or equal to 3 microfilariae per mg of skin. Stratification of prevalence rates by age group proved useful for assessing current transmission within a village.

Adolescent↗
PubMed1988

Prefrontal-limbic epilepsy: experimental functional anatomy.

Nonconvulsive seizures from prefrontal cortex in humans cause complex behavioral, motor, and autonomic manifestations. In order to gain insight into the possible anatomical basis of these phenomena, we have studied experimental seizures from medial and lateral prefrontal-limbic cortex and the amygdaloid complex in rat. Small injections of penicillin or electrical stimulation were used to induce seizures, and the [14C]deoxyglucose technique was employed to map pathways of seizure spread. Analysis of results indicates that prefrontal-limbic cortex and amygdala exhibit strong bilateral reciprocal interaction. Mild seizures from these different areas activated both unique and similar pathways and targets. With increasing strength of discharge from these areas, there was a convergence of the subcortical pattern of activation in medial and midline thalamic nuclei and bilateral substantia nigra. These studies suggest that complex epileptic phenomena in humans evoked from a prefrontal seizure focus relate to activation of cortical and subcortical functional limbic anatomy.

Amygdala↗
PubMed1987

The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures.

Subcutaneous treatment of rats with low doses of lithium and pilocarpine or a high dose of pilocarpine results in a severe seizure--brain damage syndrome. Rats thus treated were studied with multiple-depth electrodes, quantitative [14C]2-deoxyglucose autoradiography, and light and electron microscopy. Rats receiving lithium-pilocarpine did not differ from high-dose pilocarpine rats in behavioral, electrographic, metabolic or histopathological findings, but lithium-pilocarpine reproduced the syndrome more reliably and with a lower acute mortality rate. Organized electrographic seizure activity developed just prior to the onset of behavioral forelimb clonus and appeared to originate from ventral forebrain in the vicinity of the ventral pallidum and/or nucleus accumbens. From these sites activity spread rapidly to involve other regions. Once initiated, electrographic seizures persisted for hours. Increased glucose utilization was found in most brain regions during the period of continuous seizure activity. The greatest increases were found in the ventral pallidum, globus pallidus, hippocampus, entorhinal cortex, amygdala, lateral septum, substantia nigra, ventrobasal and mediodorsal thalamus and frontal motor cortex. Animals sustaining seizures displayed a disseminated pattern of neural degeneration not involving globus pallidus or ventral pallidum but otherwise coinciding with the above pattern of enhanced glucose utilization. No consistent correlation was observed between the pattern of brain damage and known regions of high muscarinic cholinergic receptor density. Ultrastructurally, the cytopathological changes, like those associated with various other sustained seizure syndromes, resemble the excitotoxic type of damage glutamate is known to cause. This seizure-brain damage syndrome and that induced by systemic kainic acid appear to be similar in behavioral but not in electrophysiological or metabolic manifestations. During kainic acid seizures, electrographic changes are first recorded in the hippocampus while they are first detected in the ventral forebrain region in pilocarpine seizures. Pilocarpine also induced metabolic activation of ventral forebrain sites not activated by kainic acid. The cytopathology associated with the two syndromes is identical in type but not in pattern, the cholinergic model being characterized by much greater neocortical and slightly less hippocampal damage. Further study of these cholinergic models may provide new insights into the roles of the major excitatory neurotransmitter systems (cholinergic and glutamergic) in limbic epilepsy.

Animals↗
PubMed1987

Cerebral glucose utilization: comparison of [14C]deoxyglucose and [6-14C]glucose quantitative autoradiography.

The [14C]deoxyglucose [Sokoloff et al., J. Neurochem. 28, 897-916 (1977)] and [6-14C]glucose [Hawkins et al., Am. J. Physiol. 248, C170-C176 (1985)] quantitative autoradiographic methods were used to measure regional brain glucose utilization in awake rats. The spatial resolution and qualitative appearance of the autoradiograms were similar. In resting animals, there was no significant difference between the two methods among 18 gray and three white matter structures over a fourfold range in glucose utilization rates (coefficient of correlation = 0.97). In rats given increasing frequencies of photoflash visual stimulation, the two methods gave different results for glucose utilization within visual pathways. The linearity of the metabolic response was studied in the superior colliculus using an on-off checkerboard stimulus between 0 and 33 Hz. The greatest increment in activity occurred between 0 and 4 Hz stimulation with both methods, probably representing recruitment of neuronal elements into activity. Above 4 Hz, there was a progressive increase in labeling with [14C]deoxyglucose up to 1.7 times control at 33 Hz. With [6-14C]-glucose, there was no further increment in change above a 30% increase seen at 4 Hz. Measurement of tissue glucose revealed no drop in the visually stimulated structures compared to control. We interpret these results to indicate that, with increasing rates of physiological activity, the products of deoxyglucose metabolism accumulate progressively, but the products of glucose metabolism are removed from brain in 10 min.

Animals↗
PubMed1986

Penicillin-induced epileptiform activity does not prevent ocular dominance shifts in monocularly deprived kittens.

Epileptiform activity was induced in the visual cortex with penicillin to test whether it would prevent the ocular dominance shift that normally occurs in monocularly deprived kittens. The eyelids of one eye of 5-week-old kittens were sutured shut for several days. During this period, whenever the kittens were in the light, aqueous penicillin in artificial cerebrospinal fluid (CSF) or just CSF was applied in a cylinder mounted over the visual cortex. Electroencephalograms monitored during the period of deprivation indicated nearly continuous interictal spiking in the visual cortex. Extracellular recordings were made of cells in the region directly under the position of the cylinder. 14C-labeled 2-deoxyglucose autoradiography in a control kitten showed that this area had considerably increased metabolism during epileptiform activity. The majority of cortical cells were dominated by the non-deprived eye in both epileptic and control kittens, with no noticeable difference between them. These preliminary observations indicate that the disruption of cortical activity that occurs during interictal epileptiform activity does not prevent the ocular dominance shift in monocularly deprived kittens.

Animals↗
PubMed1986

The effects of ivermectin on transmission of Onchocerca volvulus.

Ivermectin, given to onchocerciasis patients as a single oral dose of 200 micrograms per kilogram of body weight, substantially reduced the uptake of Onchocerca volvulus microfilariae by Simulium yahense, an efficient black fly vector of the parasite in the tropical rain forests of West Africa. Three months after treatment, patients given ivermectin infected flies at a significantly lower rate than those who had received diethylcarbamazine or placebo, thereby reducing the number of developing larvae in the vector population. This diminished rate of infectiousness was also evident 6 months after treatment. These results strongly suggest that ivermectin could be effective in interrupting transmission of Onchocerca volvulus for epidemiologically important periods of time.

Humans↗
PubMed1986

Distribution of cytochrome oxidase in rat brain: studies with diaminobenzidine histochemistry in vitro and [14C]cyanide tissue labeling in vivo.

Studies in experimental animals and post-mortem studies in humans have indicated that the level of the mitochondrial enzyme cytochrome oxidase within brain anatomical pathways is regulated by the long-term functional use of those pathways. To study this relationship, we have measured cytochrome oxidase spectrophotometrically in punch biopsies from different brain regions of rat. We compared these assays against results from the diaminobenzidine histochemical technique. We found a high degree of correlation (r = 0.90) between the density of diaminobenzidine reaction product and enzyme activity. This validates the usefulness of the diaminobenzidine technique for anatomical localization and measurement of this enzyme. To study the feasibility of using radioactive cyanide as an in vivo ligand of cytochrome oxidase, we performed quantitative autoradiographic analysis of rat brains of animals given an intravenous bolus injection of [14C]cyanide. Analysis of the arterial blood curve indicated a complex redistribution of cyanide between red blood cells, plasma, and tissues. Brain labeling reached peak levels at 1 min and then fell despite rising concentrations of free plasma cyanide. Analysis of autoradiographic images revealed good anatomical resolution. The density of labeling in individual structures over time failed to show a strong correlation with cytochrome oxidase activity or diaminobenzidine reaction product.

3,3'-Diaminobenzidine↗
PubMed1986

Angiotensin II inhibition on blood pressure and renal hemodynamics in pregnant rats.

Late-pregnant (18-20 days) and virgin rats were studied under anesthesia or while awake to investigate the effect of acute angiotensin II (ANG II) inhibition (with saralasin or captopril) on mean arterial blood pressure (AP) and renal hemodynamics. ANG II inhibition had no effect on AP in either anesthetized or awake virgin rats. Saralasin produced no effect on renal hemodynamics although with captopril small increases in renal plasma flow rate (RPF) and decreases in renal vascular resistance (RVR) occurred in virgins. In anesthetized pregnant rats, ANG II inhibition evoked marked decreases in AP. In some rats receiving saralasin, AP was only mildly depressed and RVR fell, leading to increases in glomerular filtration rate and RPF. In others, saralasin produced large decreases in AP, and indices of renal function became unmeasurable because of near cessation of urine flow. All late-pregnant anesthetized rats receiving captopril showed increased RPF irrespective of the magnitude of the fall in AP. In awake pregnant rats no effect on AP was seen with ANG II inhibition. Saralasin had no effect on renal hemodynamics although with captopril a small increase in RPF was observed. These data indicate that the stress of acute surgery and anesthesia produces a dependence of AP on ANG II in the pregnant but not the virgin rat. Under normal pregnant (awake) conditions, however, ANG II inhibition has no net effect on AP.

Angiotensin II↗
PubMed1986

Excitotoxic mechanisms of epileptic brain damage.

It is well established that the putative excitatory neurotransmitters, glutamate (Glu) and aspartate (Asp), are neurotoxins that have the potential of destroying central neurons by an excitatory mechanism. Kainic acid (KA), a rigid structural analog of Glu, powerfully reproduces the excitatory neurotoxic (excitotoxic) action of Glu on central neurons and, in addition, causes sustained limbic seizures and a pattern of seizure-linked brain damage in rats that closely resembles that observed in human epilepsy. In the course of studying the seizure-related brain damage syndrome induced by KA, we observed that a similar type of brain damage occurs as a consequence of sustained seizure activity induced by any of a variety of methods. These included intraamygdaloid or supradural administration of known convulsants such as bicuculline, picrotoxin and folic acid, or systemic administration of lithium and cholinergic agonists or cholinesterase inhibitors that have not commonly been viewed as convulsants. We have further observed that this type of brain damage can be reproduced in the hippocampus by persistent electrical stimulation of the perforant path, a major excitatory input to the hippocampus that is thought to use Glu as transmitter. It is a common feature of all such neurotoxic processes that the acute cytopathology resembles the excitotoxic type of damage induced by Glu or Asp, which is acute swelling of dendrites and vacuolar degeneration of neuronal soma, without acute changes in axons or axon terminals. We have found that the seizure-brain damage syndrome induced by cholinergic agents can be prevented by pretreatment with atropine and that the syndrome induced by any of the above methods, cholinergic or noncholinergic, can be either prevented or aborted respectively by either pre-or posttreatment with diazepam. Our findings in experimental animals may be summarized in terms of their potential relevance to human epilepsy as follows. Sustained complex partial seizure activity consistently results in cellular damage if allowed to continue for longer than 1 hr. Hippocampal, or Ammon's horn, sclerosis is the primary pathological result. It may be a priority goal, therefore, in the management of human epilepsy to control such seizure activity within very narrow limits. This proposal is discussed in terms of three major transmitter systems that may be involved; cholinergic, GABAergic, and glutamergic/aspartergic. The cholinergic system may play a role in generating or maintaining this type of seizure activity, and anticholinergics may protect against it provided they are given prior to commencement of behavioral seizures.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Topical↗
PubMed1986

Functional metabolic mapping during forelimb movement in rat. I. Stimulation of motor cortex.

The quantitative 14C-deoxyglucose (DG) autoradiographic technique has been used to study changes in cerebral metabolism during forelimb movements induced by graded stimulation of motor cortex. Experiments were directed at studying basic physiologic and anatomic aspects of the metabolic changes. Single shocks caused movement without metabolic change, whereas low-frequency trains caused seizures. Repetitive high-frequency train stimuli of short duration (500 Hz for 20 msec) caused jerk movements coupled with DG uptake in pathways. With stimulation of the forelimb motor zone at frequencies of 15-30/min there was prominent activation of cortical columns and strips in ipsilateral SI, SII, and MII, and contralateral MI and SI. Higher frequencies (120/min) were required to cause significant changes in DG in subcortical circuits. The most prominent changes occurred within a longitudinal corridor in dorsal thalamus and a ventral corridor in second-order sites in basal ganglia. Metabolic activation also occurred in contralateral cerebellum, the cuneate nucleus, and dorsal horn of the cervical spinal cord. Changes in these latter two sites were largely eliminated by removing feedback sensory activity. Stimulation of the forelimb sensory zone activated different sites in caudatoputamen and thalamus but similar zones in midbrain and cerebellum. The magnitude of the metabolic response in distant sites depended on the frequency of cortical stimulation. Different frequency-response relationships in different sites seemed to reflect the nature of the cortical input as well as differential effects of anesthesia. The pattern of the metabolic response was studied by comparing sites of activation with sites of the anatomic projections from motor and sensory cortical zones. 3H- and 14C-labeled amino acids were used to map the site and relative strength of pathways. Results revealed good correlation between the site of anatomic projection and the site of DG uptake but no consistent relationship between the relative strength of a projection and the magnitude of metabolic change within its field. Changes in glucose utilization with metabolic mapping experiments depend on the nature, strength, and frequency of stimulation; the site and nature of anatomic projection; the effects of anesthesia; and the strength of sensory feedback associated with the induced behavior.

Animals↗
PubMed1986

Functional metabolic mapping during forelimb movement in rat. II. Stimulation of forelimb muscles.

Repetitive electrical stimulation of wrist extensor muscles in rat was combined with quantitative 14C-deoxyglucose autoradiography to study sensory systems functionally activated during forelimb movement. Metabolism increased ipsilaterally in the wrist extensors, the dorsal horn of the cervical spinal cord, the cuneate nucleus and cerebellar hemisphere. The metabolic activation in cerebellum occurred in cortex surrounding the primary fissure anteriorly (lobules simplex and V), and the prepyramidal fissure posteriorly (lobules paramedian and copula pyramis). Metabolism was increased in both granule cell and molecular layers and was uniform throughout the zone of activation. Hindlimb stimulation primarily activated the medial aspect of copula pyramis, demonstrating the somatotopic specificity of changes. Forelimb stimulation also activated contralateral sites in the dorsal accessory nucleus of the inferior olive, ventrobasal thalamus, and SI and SII in cortex. Studies of the relationship between the magnitude of the response and the frequency of the stimulation revealed a positive correlation in muscle, dorsal horn and cuneate nucleus. Other activated sites only showed a significant change at the highest rates of stimulation. Comparison of the pattern of metabolic activation during forelimb movements induced centrally (Collins et al., 1986) with the pattern induced peripherally revealed overlap primarily in the paramedian zone of anterior and posterior cerebellum, and the granular cortex of SI and SII. These studies suggest that forelimb movement initiated centrally would have considerable influence on feedback sensation from the moving limb in these sites.

Animals↗
PubMed1985

[1-14C]Octanoate: a fast functional marker of brain activity.

[1-14C]Octanoate (OCTO) is rapidly extracted from blood and metabolized by brain. Up to 6 min following an intravenous pulse injection the autoradiographic pattern of brain labeling reflects differences in blood flow and energy metabolism. When animals are given OCTO during visual or somatosensory stimulation the autoradiograms reveal differential labeling of activated pathways. Studies can be performed in 7-20 s allowing fast labeling of functional brain anatomy.

Afferent Pathways↗
PubMed1985

The gonotrophic cycle of wild Simulium ochraceum and the associated development of Onchocerca volvulus.

A total of 1,700 host-seeking Simulium ochraceum were allowed to feed to repletion on human volunteers heavily infected with Onchocerca volvulus and then were marked and released. Seventy-three (4.3%) of the flies were recaptured. The gonotrophic cycle of S. ochraceum, including the host seeking and oviposition phases, was approximately 74-97 hr in duration; however, for a few flies the cycle was up to an additional 24 hr in length. The frequency distribution of recaptured flies indicated that 2 gonotrophic cycles may be completed in 7-8 days. The large proportion of flies recaptured with sac-stage follicular dilatations indicates that S. ochraceum may begin to search for and can rapidly locate a new host almost immediately after oviposition. Larvae of O. volvulus were found in 15 (20.6%) of the recaptured flies. Early first stage larvae were present in host-seeking flies that had completed 1 gonotrophic cycle: 12 of 13 infected flies recaptured between 74 and 97 hr had early first stage larvae. Development of O. volvulus larvae to the infective stage was estimated to require approximately 11 days at the study site. During this time, S. ochraceum would normally have completed 3 gonotrophic cycles and be in the host seeking phase of a fourth at approximately 11 days after ingesting microfilariae.

Animals↗
PubMed1984

The functional anatomy of frontal lobe neglect in the monkey: behavioral and quantitative 2-deoxyglucose studies.

A syndrome of hemisensory neglect follows damage to frontal association areas in monkeys and humans. To study the syndrome we removed frontal association cortex from the right hemisphere of macaque monkeys. After operation, behavioral testing showed conditional deficits in visual, somatosensory, and motor responses contralateral to the lesion. Brains of animals were studied with [14C]2-deoxyglucose autoradiography to evaluate functional neuroanatomical changes. Ipsilateral striatal and selected thalamic and midbrain nuclei exhibited depression of glucose utilization (10 to 60%). No consistent glucose utilization changes appeared in cortex or in primary motor or sensory pathways. Brains from unoperated control animals did not exhibit these changes, nor did brains from operated animals with behavioral recovery from neglect. We conclude that the symptoms of frontal lobe neglect in the monkey are the result of dysfunction within a widely distributed system of subcortical centers. The distribution of the dysfunction provides an explanation for some of the clinical features of neglect.

Animals↗
PubMed1984

Descriptive statistics for the larval stages of Onchocerca volvulus in host-seeking Simulium ochraceum.

In four localities of Guatemala with dissimilar intensities of onchocerciasis, filarial larvae were recovered by dissection from host-seeking Simulium ochraceum. Measurements made on over 600 Onchocerca volvulus larvae were used to characterize the early first, late first, second, and third developmental stages. The numerical attributes used to characterize the third larval stage and the associated means were body length (657.3 microns); anterior body width (18.9 microns); posterior body width (20.2 microns); distance from anterior end to nerve ring (87.9 microns), to junction of muscular and glandular esophagus (137.6 microns), and to junction of esophagus and intestine (419.6 microns); and distance from anus to tip of tail (36.8 microns). Ratios to total body length were as follows: distance from anterior end to nerve ring, mean = 0.133, to junction of esophagus and intestine, mean = 0.634, and to anus, mean = 0.945. Differences between these phenotypic features and those reported for African O. volvulus appeared to be insufficient to distinguish the two forms. With very few exceptions, the filarial larvae found in host-seeking S. ochraceum were considered to be O. volvulus.

Anal Canal↗