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Biomedical subjects

R C Collins

Publications and source records attributed to R C Collins.

At least 19 recordsLinked to original sources

Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats.

Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Microepidemiology of onchocerciasis in Guatemala: dispersal and survival of Simulium ochraceum.

Wild Simulium ochraceum females, both blood engorged and non-blood engorged, were collected from human volunteers infected with Onchocerca volvulus, marked with fluorescent dyes, and released from the same locality as they were collected during February and March 1989. A small hyperendemic village located within 0.5 km of streams supporting large populations of S. ochraceum larvae served as the site for both collection and release of adult females. Fifteen sites for the recapture of flies were located within this same village, within two other villages located 1.0 and 3.7 km from it, and at other places spaced approximately 0.25-3.5 km within a coffee agroecosystem. Flies from both groups were recaptured at distances ranging to 3.5 km from the point of release. Non-blood-engorged flies, however, exhibited a greater tendency to disperse away from the release site. Of the total number of blood-engorged flies recaptured, 51.9% were collected at the release point, 25.7% at 1.0 km, and 1.6% at 3.3-3.5 km. The corresponding percentages for non-blood-engorged flies were 26.9%, 40.4%, and 4.4%, respectively. No flies from either group were recaptured at the most distant site, a large village that was 3.7 km away. Marked flies from both groups were recaptured 12-14 days after release, which was sufficient time for the development of infective O. volvulus larvae. A survival rate (4.7%) of marked, blood-engorged flies over the second and third gonotrophic cycles was estimated from the slope of the regression line of the log number of flies recaptured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities.

Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given.

Adolescent

The effects of repetitive community-wide ivermectin treatment on transmission of Onchocerca volvulus in Guatemala.

The effects of biannual ivermectin treatment at the community level on transmission of Onchocerca volvulus during the dry season were measured over a 30-month period in Guatemala. In the Los Tarrales Transmission Zone, an area encompassing three villages, significant changes occurred in both the prevalence and quantity of infection in the Simulium ochraceum vector population. These included a 76% reduction in females with infective stage larvae (L3S) and an 80% reduction in number of L3S per 1,000 parous flies. Significant reductions in both the mean infective biting density (IBD) and mean transmission potential (TP) also occurred. In Santa Emilia, the prevalence of infection with L3S in S. ochraceum was significantly reduced by 77% from the baseline value. The number of O. volvulus L3S per 1,000 parous flies was also reduced by 92%. Changes in both the IBD and TP were substantial but not significant due to the high degree of variance in the occurrence of O. volvulus L3S in the vector population. This was due, in part, to the movement of infected migrant workers into the finca (coffee farm). In Los Andes, four recurrent treatments successfully blocked transmission of infective stage larvae. Prevalence (flies with all stages of developing larvae) in the vector population was reduced by 89% over the two-year period; yearly reductions in both the IBD and TP were also highly significant, ultimately ending in zero values. This finding is particularly striking since prior to treatment, Los Andes exhibited the highest IBD of the three study locations and the second highest TP.

Animals

Basic aspects of functional brain metabolism.

Brain energy metabolism and blood flow are greatest in neuropil where there is a high density of oxidative enzymes and capillaries. Here fluctuations in synaptic potentials cause the greatest demand on metabolism through the continuous need to pump ions to maintain membrane charge. A transient increase in functional activity within a pathway causes an increase in energy metabolism followed by an increase in blood flow. The vascular response is biphasic, with an initial increase followed by a plateau phase. The site and magnitude of the response reflect the quality and intensity of the stimulus. Prolonged changes in functional activity within a pathway cause a reorganization of energy metabolizing enzymes and vascular architecture.

Animals

Functional anatomy of occipital lobe seizures: an experimental study in rats.

Small amounts of penicillin were used to create a seizure focus in the primary visual cortex (area 17), extrastriate cortex (area 18 and 18a), and neighboring somatosensory and temporal areas in rats. Autoradiography with 14C-deoxyglucose was used to map the focus and the local cortical and long subcortical circuits. Mild seizures from area 17 were associated with focal spiking without behavioral manifestations. There was restricted utilization of local U-fiber circuits and ipsilateral subcortical visual system nuclei. Stronger seizures filled up the visual cortex and projected into adjacent neocortex and limbic cortex, the contralateral 17-18a border, and additional subcortical nuclei. Seizures originating in the posterior visual cortex were associated with prolonged afterdischarges and stereotyped behavioral manifestations, with spread into the posterior cingulum, the subicular complex, and the bilateral hippocampus. After analyzing the electrographic discharges, behavior, and seizure pathways in each animal, we conclude that ictal symptoms associated with seizures would not be the expression of the function of a cortical focus, but rather of the dysfunction of excessive discharges through many local and long circuits.

Animals

The gonotrophic cycle in Simulium ochraceum.

Oogenesis in Simulium ochraceum is characterized in terms of distinct stages of follicular development following emergence, sugar feeding, and completion of a blood meal. Changes in the ovary following the first oviposition are also described. This black fly species was found to be anautogenous and exhibited gonotrophic concordance. The formation of follicular dilatations after oviposition followed a distinct pattern with traces of cellular debris evident up to 144 hours. The presence of fructose, as detected by the cold Anthrone test, indicated that both parous and nulliparous flies routinely imbibe nectars as part of their foraging behavior. The availability and frequent use of nectar may contribute significantly to longevity of parous flies, hence increasing their vector potential.

Animals

Development of Onchocerca volvulus in Simulium ochraceum and Simulium metallicum.

The development of Onchocerca volvulus was compared in Simulium ochraceum and S. metallicum by maintaining infected flies under uniform conditions. Larval development in S. ochraceum was synchronous and orderly so that nearly all larvae reaching the thoracic muscles from a single blood meal matured to third-stage infective larvae within 192 hours. In contrast, development in S. metallicum was asynchronous, slower, and retarded. In this species many first-larvae were malformed and stunted after the 5th day of development; and microfilariae and first- and second-stage larvae were still present 8--10 days after a single infecting blood meal when third-stage larvae had developed. The development of O. volvulus in S. ochraceum is more compatible with the intense transmission associated with human disease.

Animals

Onchocerciasis transmission potentials of four species of Guatemalan simuliidae.

Two complete days of collections and dissections of all black fly species landing on two persons infected with Onchocerca volvulus were made at monthly intervals for 13 months within a single endemic area of Guatemala. A comparison of the infective biting densities and transmission potentials showed that Simulium ochraceum was the only significant vector.

Adult

Effect of amino-oxyacetic acid (AOAA) on focal penicillin seizures.

The biochemical and behavioral effects of the anticonvulsant amino-oxyacetic acid (AOAA) have been studied in a model of focal penicillin seizures in rats. At 20 mg/Kg AOAA treatment results in a progressive 11 fold increase in GABA levels in cortex over three hours. There is a decrease in aspartate, ketoglutarate, alanine and glutamine, and an initial decrease followed by an increase in pyruvate and glutamate. These results reflect a functional inhibition of several B-6 dependent aminotransferase enzymes. When rats are pretreated 30 min before the onset of focal penicillin seizures there is a 60% reduction in the number of discharges and a 34% reduction in seizure duration. Pretreatment beyond 75 min results in progressively less anticonvulsant effect, such that seizures eventually become more severe than control. There is an increase in the number and duration of discharges, seizure spikes become complex, and tonic-clonic events develop. Penicillin seizures do not cause a change in levels of GABA, but result in a decrease in glutamate within the focus. AOAA pretreatment initially prevents this decrease in glutamate but later accentuates it. The biochemical effects of AOAA are complex, but biphasic anticonvulsant properties coincide in time with a change in the balance of excitatory and inhibitory amino acids in the seizure focus.

Acetates

Use of cortical circuits during focal penicillin seizures: an autoradiographic study with [14C]deoxyglucose.

Autoradiography with [14C]deoxyglucose was used to study the architectural pattern of glucose utilization in the motor cortex of rats during focal penicillin seizures. The seizure focus was characterized by a well circumscribed area whose metabolic activity was increased 2-3 times normal. This was tightly surrounded by cortex that was normal or slightly depressed. The posterior third of the focus showed an increase in glucose utilization in a columnar pattern with particular accentuation of activity in lamina V. There was a loss of normal activity in lamina IV within the focus and in somatosensory and occipital cortex far behind the focus. This depression was particularly prominent in the ipsilateral barrel field. Increased metabolic activity was found in a small area in contralateral homotopic cortex, in lamina Vb with columns extending above this from lamina IV to the surface. Glucose utilization was accentuated 1.2-1.8 fold in the ipsilateral secondary somatosensory area, but was normal in the contralateral cortex. The intensity of focal seizures was increased by the intracortical injection of more penicillin or by giving intravenous metrazol. Both of these methods resulted in an increase in the size of the focus as determined with [14C]deoxyglucose. This was most prominent on the lateral border in lamina I-II and V. In addition, there was an accentuation of the columnar pattern in the posterior part of the focus, ipsilateral somatosensory cortex, and contralateral motor cortex. The architectural pattern of glucose utilization in the cortex during focal seizures is discussed with reference to corticocortical, commissural, and corticothalamic circuits that have been identified by others in anatomical studies. Superimposed on this structure are physiological principles of recurrent excitation, lateral spread, and surround inhibition that characterize basic electrophysiological mechanisms of epilepsy, and influence the intensity of activity within the architectural design.

Animals

Kindling of neuroanatomic pathways during recurrent focal penicillin seizures.

Sequential changes in convulsive phenomena have been studied using intracortical injections of penicillin as a kindling agent. Rats given 25 units of penicillin every 4 days had a progressive increase in the frequency of contralateral muscle jerks. Unilateral tonic-clinic events began after the third injection, and bilateral jerks of both upper extremities began subsequent to that. No generalized convulsions occurred, and further changes in focal convulsions stopped after 7 injections. The seizure events occurring in this kindled state could be seen in rats given a single injection of 100 units of penicillin. Rats subjected to daily injections at this dosage did not develop more intense seizures, and afterdischarges essentially stopped after the first injection. Animals studied with deoxyglucose autoradiography during kindling with 25 units showed an increase in the size and intensity of metabolic activity in the seizure focus. In addition there was an increase in size and intensity of most transynaptic sites, with new activity appearing in contralateral basal ganglia. A comparison of these findings with the autoradiographic results of animals receiving 100 units of penicillin suggests that the major change during kindling takes place in the focus itself. The appearance of new activity in contralateral basal ganglia is probably an expression of activity in crossed corticostriate pathways from the focus as well as pathways descending from the homotopic cortex in an obligatory input-output response. Use of these pathways is not dependent on kindling, but is available on a first come basis if the intensity of discharges from the seizure focus is strong enough.

Animals

A double-blind trial of transfer factor vs placebo in multiple sclerosis patients.

A double-blind trial of the effect of transfer factor on multiple sclerosis patients was carried out. In a series of fifty-six multiple sclerosis patients treated with monthly injections of either transfer factor or placebo for 1 year, no beneficial effect of transfer factor was noted. In addition, none of the immunological and serological parameters studied (measles migration inhibition, measles HI titre or CSF immunoglobulin) changed as a result of transfer factor therapy. Histocompatibility typing and CSF IgG/TP ratios were correlated with the disease activity. Of interest was the finding that the presence of the DW2 antigen, when unassociated with HLA-B7 antigen, appeared to correlate with the mildest form of disease activity.

Adult