Biomedical subjects
Publications and source records attributed to R C Collins.
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.
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.
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.
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.
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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.
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Simulium ochraceum females collected after feeding on subjects harboring Onchocerca volvulus were maintained and transported from Guatemala to California in small plastic tubes. Each tube had a perforated cap for entry of air, a wick as a reservoir for the nutrient solution (30% sucrose), a strip of filter paper for anchorage, and contained one fly. The tubes were kept in plastic boxes which, in turn, were maintained in portable coolers. Direct sunlight, heat and mechanical trauma easily killed the flies; moreover, loss of flies was also due to oversaturated wicks, high humidity in the plastic boxes, and loose tube caps. Approximately 70% of the captured flies could survive an 8-day period of captivity, and approximately 40% were still alive 11 days after capture.
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The effectiveness of a mass separation technique, previously used for the extraction of larvae of lymphatic-dwelling filarial worms from batches of vector mosquitoes, was tested as a means of recovering infective-stage larvae of Onchocerca volvulus from Simulium ochraceum in Guatemala. Blood-engorged flies, collected from 10 infected human attractants, were maintained for 9 days to allow ingested microfilariae to develop to the infective stage. The numbers of Onchocerca larvae recovered after groups of these flies were crushed and washed into tissue culture fluid in Baermann funnels was compared with the numbers obtained by individual dissections of flies fed on the same subjects. The mass separation procedure gave a mean recovery rate of 0.03 larva/fly and detected larvae only in flies which had fed on those subjects with the highest microfilarial skin densities. Dissections yielded 0.50 larva/fly (a 16.7-fold increase) and detected larvae in flies collected from all test subjects. The explanation for the ineffectiveness of the mass separation technique may lie in the observed sluggishness of infective-stage Onchocerca larvae and a consequent inability to free themselves from the fly fragments in the Baermann funnel.
Contralateral focal seizures occurred in rats following the intracortical injection of penicillin into the anterior motor cortex. The anatomic dimensions of the metabolic response in the focus as well as the spread of increased activity through the brain were studied by autoradiography following intravenous injection of carbon 14-labeled 2-deoxyglucose. Injections of 25 to 200 units of penicillin resulted in mild to severe contralateral motor jerks coincident with repetitive single spike discharges on the electroencephalogram. Concurrent autoradiography revealed a 1.3- to 2.5-fold increase in metabolic activity in discrete areas in ipsilateral cortex, basal ganglia, thalamus, and contralateral cerebellum. Intracortical injections of over 300 units resulted in the development of recurrent contralateral tonic-clonic seizures, with 20% becoming bilateral. In brains of these animals there was activation of bilateral medial frontal cortex, bilateral extrapyramidal system, thalamus, cerebellum, and limbic structures.
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Among 1,459 autopsied patients with cancer, 12 had multifocal infarcts of the brain that appeared to be caused by intravascular coagulation. Most of these patients were women with leukemia or lymphoma, and all had a clinical course in which neurologic signs and symptoms were prominent. All had evidence of generalized brain disease (delirium and stupor or coma), and several also had focal brain disease (focal seizures, hemiparesis). All patients had laboratory evidence of coagulation abnormalities, although these were often not severe when neurologic symptoms began. Pathologically, there were multifocal hemorrhagic or ischemic infarcts in the distribution of several cerebral vessels, without a systemic source for cerebral emboli. Fibrin thrombi were identified in cerebral vessels and in vessels of several other organs. The clinical findings fit the pathologic picture, and in most instances the correct diagnosis might have been made earlier had it been considered.