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Biomedical subjects

D Ko

Publications and source records attributed to D Ko.

At least 37 records · Page 2Linked to original sources
PubMed1996

Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging.

OBJECTIVE: To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS: We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS: The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS: VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Adult↗
PubMed1996

A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia.

This report presents the initial analysis of a prospective, population-based study of status epilepticus (SE) in the city of Richmond, Virginia. The incidence of SE was 41 patients per year per 100,000 population. The frequency of total SE episodes was 50 per year per 100,000 population. The mortality rate for the population was 22%, 3% for children and 26% for adults. Evaluation of the seizure types for adult and pediatric patients demonstrated that both partial and generalized SE occur with a high frequency in these populations. Based on the incidence of SE actually determined in Richmond, Virginia, we project 126,000 to 195,000 SE events with 22,200 to 42,000 deaths per year in the United States. The majority of SE patients had no history of epilepsy. These results indicate that SE is a common neurologic emergency.

Adolescent↗
PubMed1995

Felbamate monotherapy: implications for antiepileptic drug development.

We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 +/- 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 hd an episode of panic. There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy.

Adolescent↗
PubMed1993

Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation.

BACKGROUND: Accelerated coronary atherosclerosis has become a critical problem in cardiac transplantation. Although the pathogenesis of this disease is unknown, hypercholesterolemia has been shown to be a major risk factor. METHODS AND RESULTS: To study this problem, a hypercholesterolemic rabbit model of heterotopic cardiac transplantation was developed to study accelerated graft atherosclerosis. Based on suggestions in the literature, it was hypothesized that dehydroepiandrosterone (DHEA) may retard the progression of the disease. Using semiquantitative light microscopy, a predilection for the development of small vessel occlusive disease in the transplanted hearts was found. Chronic DHEA administration produced a 45% reduction in the number of significantly stenosed vessels in the transplanted hearts (p < 0.05) compared with controls and a 62% reduction in the nontransplanted hearts (p < 0.05), yielding an overall 50% reduction in the number of significantly stenosed vessels in both the transplanted and nontransplanted hearts. This reduction in luminal stenosis was observed in the absence of any significant alterations in lipid profiles. CONCLUSIONS: It is concluded that chronic DHEA administration in a hypercholesterolemic rabbit model of heterotopic cardiac transplantation significantly retards the progression of accelerated atherosclerosis in both the transplanted heart and in the native heart.

Animals↗
PubMed1992

In situ hybridization of corticotropin-releasing factor-encoding messenger RNA in the hypothalamus of the white sucker, Catostomus commersoni.

In situ hybridization procedure with a 32P-labelled synthetic oligonucleotide probe was used to detect corticotropin-releasing factor-encoding messenger RNA (CRF mRNA) in the hypothalamus of the white sucker, Catostomus commersoni. Adjacent sections were immunostained by a sucker CRF-specific antiserum. CRF mRNA-containing neurons were identified by autoradiography in the magnocellular and parvocellular subdivisions of the preoptic nucleus (PON). Many of these neurons were also immunostained by sucker antiserum, showing the same distribution patterns. These results confirm the presence of CRF mRNA and CRF peptide in the white sucker hypothalamus and support the view that the magnocellular and parvocellular neurons of the PON may be involved in the control of adrenocorticotropic hormone secretion from the pituitary in the white sucker.

Animals↗
PubMed1992

Status epilepticus in children, adults, and the elderly.

Status epilepticus (SE) is a major neurological and medical emergency associated with a high morbidity and mortality. Retrospective and prospective studies from the Medical College of Virginia Epilepsy Research Center have been utilized to investigate several clinical and epidemiological factors associated with SE. Univariate and multivariate logistic regression analysis of predictive indicators in patients with SE indicated that seizure duration, certain specific etiologies, and age were predictors of mortality. Sex, race, and certain other etiologies were not found to be factors that significantly affect mortality. These findings demonstrate that specific indicators are important in predicting mortality in SE. Preliminary prospective epidemiological data from Richmond, Virginia suggested that more than 250,000 cases of SE may occur annually in the United States with a mortality greater than 55,000 individuals. Studies comparing community and university hospitals in Richmond indicate that the mortality and clinical variables associated with SE in these two hospital populations are essentially identical. Further investigations employing prospective population-based studies are essential in evaluating the epidemiology and mortality of SE.

Adolescent↗
PubMed1986

Radioimmunoassays for fish tail neuropeptides: II. Development of a specific and sensitive assay for and the occurrence of immunoreactive urotensin II in the central nervous system and blood of Catostomus commersoni.

A sensitive radioimmunoassay (RIA) based on an antiserum to synthetic Gillichthys mirabilis urotensin II (UII) generated in rabbits, reacting with all known forms of the UII peptides, was developed. The UII was iodinated by either the chloramine-T or the lodogen method and was purified by high-pressure liquid chromatography. The antiserum, at a final dilution of 1:125,000, gave 50% binding of the iodinated UII. The sensitivity of the RIA was 1.8 +/- 0.2 pg/assay tube (1.2 +/- 0.2 fmol/tube; n = 7). Crossreactivity studies with various UII peptides, modified UII peptides, and fragments indicated that the immunoreactive recognition site of this antiserum is directed to the disulfide ring region (positions 6-11) of the UII peptides. Somatostatin 14, which has the part sequence 7-9 in common with UII peptides, did not crossreact. No detectable crossreactivity with urotensin I, urophysin B or D from Catostomus commersoni, arginine vasopressin, or arginine vasotocin could be shown. Displacement curves obtained with standard extracts of G. mirabilus urophyses were similar to those of synthetic G. mirabilus UII. comparison of RIA and bioassay of G. mirabilis urophysial extracts showed good correlation. Immunoreactive UII was detected in different parts of the brain, spinal cord, and blood of C. commersoni.

Animals↗
PubMed1986

Radioimmunoassays for fish tail neuropeptides: I. Development of assay and measurement of immunoreactive urotensin I in Catostomus commersoni brain, pituitary, and plasma.

Antisera were raised in rabbits using highly purified urotensin I (UI) or UI (4-41) conjugated with high-molecular-weight proteins. Antiserum 2U4, at a final dilution of 1:300,000, gave 50% binding to iodinated UI (specific activity 40-120 microCi/micrograms). Carp (Cyprinus carpio) and sucker (Catostomus commersoni) UI peptides cross-reacted completely with the antiserum. Results from cross-reactivity tests using various tryptic and Staphylococcus aureus protease fragments of UI indicated that the antigenic sites of the main antibody(ies) are directed against a part sequence in the C-terminal region of the peptide although antibodies with lower concentration or affinity, recognizing N-terminal region(s) of the peptide, are also present. No cross-reactivity was seen with insulin, secretin, vasoactive intestinal peptide or a structural UI-homolog, the ovine hypothalamic corticotropin-releasing factor, up to molar concentrations. Sauvagine, another structurally homologous peptide from frog skin, showed only 0.1% cross-reactivity. The urophysis-specific proteins, urophysins B and D, showed a low degree of cross-reactivity. Assays of serial dilutions of urophysis extracts from teleostean species yielded parallel displacement curves, except in the case of the pacific goby, Gillichthys mirabilis. Varying concentrations of immunoreactive UI were present in different regions of C. commersoni brain, spinal cord, and pituitary, and also in plasma. The measurement of 17.5 +/- 2.1 fmol UI/ml of plasma indicates that this assay may be used for the study of circulating UI peptide(s).

Amino Acid Sequence↗
PubMed1986

A multinomial model for estimating the size of a whale population from incomplete census data.

This paper adapts the removal method of population size estimation to the problem of estimating the size of the western Arctic stock of bowhead whales. The whales are counted during their spring migration as they pass two census camps located near Point Barrow, Alaska. Whales seen at the first camp are "removed" from the population of concern to the second camp, where only whales missed by the first camp are counted. If both camps were in operation throughout the migration and if the probability of missing a whale were constant, the removal method would provide a population size estimate based on a trinomial model in which the size of the population would be the number of trials, whales counted by each camp would provide the observed cell totals, and whales missed by both camps would represent an unobserved cell total. Since the probability of missing a whale depends on visibility, we model the population size as the sum of the number of trials of several independent trinomial distributions, each of which represents a particular visibility condition occurring during the census. To account for the fact that watch cannot be maintained at both camps throughout the migration, we derive a confidence interval estimate of the number of trials under a more general model allowing for incomplete observation of totals within particular cells as well as for completely unobserved cells.

Alaska↗
PubMed1982

Vasopressin concentration in cord blood: correlation with method of delivery and cord pH.

Cord plasma vasopressin concentration, determined by radioimmunoassay, was higher in arterial than in venous blood in 122 (84%) infants; the highest vasopressin values were recorded in 21 acidotic infants (mean cord pH, 7.13) delivered per vaginam and the lowest values in 50 infants delivered by cesarean section. Cord vasopressin levels were not elevated in infants delivered by cesarean section because of obstructed labor. There was a lack of correlation between vasopressin levels and the length of labor or cervical dilatation; a significant correlation was found between cord arterial vasopressin values and pH. Low vasopressin values were recorded in a group of 22 healthy infants (mean cord pH, 7.29) delivered by low forceps operation.

Abruptio Placentae↗
PubMed1980

Circulating antidiuretic hormone during labour and in the newborn.

Using a high specificity radioimmunoassay, antidiuretic hormone (ADH) concentrations were measured in the plasma of 33 expectant mothers during labour, in cord arterial and venous plasma of their infants at the time of delivery (19 delivered vaginally; 14 delivered by Cesarean section) and in the plasma of the same infants in the first few days of life. Extremely high concentrations of ADH (about 50 times higher than adult basal concentrations) were present in cord arterial blood indicating active fetal production of ADH. Plasma ADH decreased rapidly within an hour after birth and usually fell to adult basal levels during the first day of life. Stressed babies and babies subjected to difficult deliveries had higher plasma levels of ADH.

Adolescent↗
PubMed1979

Synthesis of angiotensin II antagonists containing sarcosine in position 7.

Analogues of the type [1-sarcosine,7-sarcosine, 8-X]angiotensin II, where X = isoleucine, leucine, alanine, methionine, O-methylthreonine, or DL-alloisoleucine, were synthesized by the solid-phase method and purified by partition chromatography, cation-exchange chromatography, and high-pressure liquid chromatography. In the isolated rat uterus, these analogues had activities of less than 0.1, less than 0.1, less than 0.1, less than 0.1, less than 0.1, and 0.7%, respectively, of the hyotropic activity of angiotensin II and inhibited the contractile response to angiotensin II with pA2 values of 8.1, 7.2, 6.7, 7.7, 7.4, and 8.4, respectively. In the vagotomized ganglion blocked rat, the analogues had 0.7, 0.21, 0.06, 0.72, 0.13, and 12.5%, respectively, of the pressor activity of angiotensin II.

Angiotensin II↗
PubMedDate not supplied

Urotensin I-like immunoreactivity in the central nervous system of Aplysia californica.

In the present study the occurrence and localization of urotensin I (UI, a corticotropin releasing factor-like peptide) in the CNS of Aplysia californica were investigated by immunocytochemistry and radioimmunoassay. The RIA cross-reactivity pattern indicated that the UI antiserum used recognized an epitope in the C-terminal region of the UI, but it did not cross-react with mammalian corticotropin-releasing factor (CRF) and partially recognized sauvagine (SVG, a frog CRF-like peptide). The use of CRF-specific and sauvagine-specific antisera failed to give positive immunostaining. The application of UI antiserum (which does not cross-react with CRF in RIA) gave a positive staining, which was blocked by synthetic sucker (Catostomus commersoni) UI, but not by rat/human CRF (10 microM). On the basis of immunostaining and RIA parallel to fish UI displacement curves of cerebral ganglia extracts, the unknown UI/CRF-like substance in the Aplysia ganglia is likely to have greater homology with sucker UI than with the known CRF peptides. Urotensin I-immunoreactive (UI-ir) neurons were seen mainly in the F neuron clusters, located in the midline and rostrodorsal portion of the cerebral ganglia. Few UI-ir neurons were also found in the C and D neuron clusters of the cerebral ganglia, as well as in the left pleural and abdominal ganglia. In addition, numerous fine and coarse, and beaded UI-ir fibers were found in the cerebral commissure. UI-ir fibers were also seen in the neuropile of the buccal, pedal and pleural ganglia, and abdominal ganglion. A cuff-like arrangement of UI-ir fibers was seen in the supralabial nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗