Biomedical subjects
Publications and source records attributed to C Johnson.
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A series of rotationally restricted phenolic analogs of the neurotransmitter serotonin has been synthesized with the 5-hydroxyindole portion of serotonin replaced by a dihydropyrano[3,2-e]-indole (1, 3, 4, and 5) and a dihydropyrano[2,3-f]indole (2). The receptor binding profile of these compounds has been studied and compared to the natural substrate serotonin. The dihydropyrano[3,2-e]indole derivatives (1, 3, 4, and 5) possess lower affinity for 5-HT1 receptors but equal or greater affinity for 5-HT2 receptors. Like serotonin, these compounds dose-dependently stimulated phosphatidylinositol turnover in rat brain slices. Moreover, the response to 1-(2-aminoethyl)-3-methyl-8,9-dihydropyrano[3,2-]indole (5, CP-132,484) and 1-(2-aminoethyl)-8,9-dihydropyrano[3,2-e]indole (4) is selectively antagonized by 5-HT2 receptor antagonists establishing these tryptamines as selective 5-HT2 receptor agonists. The high affinity and potency of 5 for 5-HT2 receptors suggests that the C5-hydroxy group in serotonin can function as a hydrogen bond acceptor in a 5-HT2 receptor with a directionality of interaction which is down and away from C6 in serotonin (Figure 5). Furthermore, the potent affinity of these compounds for 5-HT2 receptors coupled with their poor affinity for 5-HT1 receptors indicates that the aminoethyl side chain of serotonin adopts significantly different conformations in 5-HT1 versus 5-HT2 receptors.
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OBJECTIVES: To investigate the demographic characteristics and circumstances surrounding fatal snowmobile accidents in Ontario, to examine the risk factors and to observe any fatality trends over the study period. DESIGN: Case series. PATIENTS: All 131 people who died accidentally while operating a snowmobile in Ontario from 1985-86 to 1989-90. Records were obtained from the chief coroner's office; registration data were obtained from the Ministry of Transportation. RESULTS: Although the absolute number of deaths increased each year, owing to a rapid increase in the number of registered snowmobiles, the risk of death from snowmobile accidents remained relatively constant. Deaths occurred most frequently in northeastern Ontario. Youths and men predominated among the victims. Fatal accidents occurred more often on lakes (in 66% of the cases in which this information was known) than on roads (in 26%) or trails (in 8%). Weekend fatalities predominated, and deaths occurred most often during times of suboptimal lighting (from 4 pm to 8 am). The driver was killed in 84% of the cases in which the person's role was known. Alcohol use before death was implicated in 69% of the cases, the level exceeding the Ontario legal limit in 59%. CONCLUSION: Snowmobile-related deaths result from factors that are generally avoidable. Strategies need to be instituted to reduce the rate of these events.
Annual age-specific incidence rates of Streptococcus pneumoniae or Haemophilus influenzae bacterial septicemia in sickle cell anemia (SS) were determined for the years of 1957 through 1989. Forty-nine patients had 64 episodes of septicemia among a population of 786 SS patients observed for 8,138 person-years. Peak frequency of infection occurred between 1968-1971 and 1975-1981 with a conspicuous absence of episodes in 1972, 1973, 1982-1984, and 1986-1987, thus demonstrating cycles of high and low attack rates. The annual age-specific incidence rate of septicemia varied from 64.5 (1965) to 421.1 (1980) per 1,000 person-years for those under 2 years of age and never exceeded 10.2 per 1,000 in those over 4 years of age. Following the introduction of pneumococcal polyvalent vaccine in 1978, incidence of infection decreased in SS children greater than 2 years of age. No modification of the risk of infection was observed in immunized children less than 2 years of age. During these three decades, there has been a ten-fold increase in the number of SS adults over 20 years of age. The relative risk of chronic sickle complications comparing the survivors of septicemia to the non-infected patients was: subsequent death 1.76, retinopathy 4.06, avascular necrosis 1.95, symptomatic cholelithiasis 1.33, stroke 1.30, and priapism 1.26. These data suggest that prognosis for lifetime severe SS is initially manifested as an increased risk of septicemia during childhood.
We report a family in which three members presented with minimal phenotypic abnormalities, normal intelligence to mild mental retardation, and a cytogenetically terminal chromosome deletion at band 8p23.1 Whole chromosomal painting with a chromosome 8-specific DNA library confirmed this familial chromosome abnormality as a deletion, while fluorescence in situ hybridization with telomeric probes demonstrated the presence of telomeres at the deletion site. Coagulation studies were additionally performed to evaluate the purported location of the coagulation factor VII regulator gene at 8p23.1. A review of the clinical findings of seven cases of del(8)(p23.1) is presented.
OBJECTIVE: The purpose of this study is to determine whether routine urine drug screening at the first prenatal visit will identify and permit early intervention for those at risk for poor outcome. STUDY DESIGN: Comparisons of maternal and neonatal outcomes between 166 randomly chosen patients with positive and 150 randomly chosen patients with negative drug screens identified by the enzyme multiplied immunoassay test were made by unpaired t test, chi 2 test, probit analysis, and tests of independent Poisson distributions. RESULTS: Forty percent of those identified denied drug use. Antepartum (p less than 0.01) and postpartum (p less than 0.05) complications were increased among drug users. Birth weight (p less than 0.001), gestational age (p less than 0.03), and head circumference (p less than 0.05) were decreased among neonates. CONCLUSION: Because of difficulty in identifying illicit substance--using patients, consideration should be given to the implementation of routine urine drug screening at the first prenatal visit in populations with a high rate of illicit substance use.
Agonist induced increases in intracellular free calcium, [Ca2+]i, were measured in single Fura-2 loaded bovine aortic endothelial (BAE) cells by dual wavelength microspectrofluorimetry. Low doses of ATP (less than 10 microM) induced complex changes in [Ca2+]i. These changes usually consisted of a large initial transient peak with subsequent fluctuations superimposed upon a maintained rise in [Ca2+]i. Higher doses of ATP (greater than 50 microM) produced much simpler biphasic increases in [Ca2+]i in individual cells. Acetylcholine and bradykinin also elicited increases in [Ca2+]i in single cells in confluent monolayers of endothelial cells. However, only acetylcholine produced complex fluctuations. High doses of acetylcholine evoked simple rises in [Ca2+]i similar to those seen with high doses of ATP. In contrast, bradykinin evoked relatively simple rises in [Ca2+]i at all doses used. These results indicate that the mechanisms responsible for generating agonist induced increases in [Ca2+]i in BAE cells are not homogeneous. ATP and acetylcholine produced more complex Ca2+ changes or 'signatures' in single confluent bovine aortic endothelial cells than bradykinin. All three agonists appeared to release Ca2+ from intracellular stores as well as stimulating Ca2+ influx. The possible mechanisms underlying these phenomena are discussed.
Twelve ASA class I patients scheduled for removal of third molars under intravenous sedation were included in the study. Samples for venous blood gas analysis were drawn every 5 minutes and the venous partial pressure of carbon dioxide was compared to the end-tidal CO2 recorded from a modified nasal cannula at the same time the samples were drawn. Correlation analysis was performed using the Pearson correlation coefficient. The overall correlation between end-tidal CO2 and PVCO2 was .54 (P = .0001). The results of the investigation indicate that through simple modifications of the end-tidal CO2 monitoring device, the correlation between end-tidal CO2 and serum PCO2 in a nonintubated patient can be improved.
This paper suggests ways in which the nurse in charge of a brainstem dead patient can help in the management of the patient's family so that they can more easily and effectively come to terms with his or her death and consider the possibility of organ donation. Many nurses, in spite of their basic training, are unprepared to assume such a role successfully, and three areas are preliminarily identified for closer study, i.e. 1) the preparation of the family for brainstem death, 2) the approach to the family for possible organ donation, and 3) the care of the family throughout the process of organ donation. Certain recommendations are suggested which might help to promote the necessary caring approach to the problem. Review of literature on the nurse's role in such a situation shows how important that role is thought to be. Guidelines are tentatively laid down for explaining brainstem death and preparing the family for it; and the importance of their acceptance of the finality of death is stressed, so that they can begin the essential grieving process. Emphasis is also laid on the need for the nurse to adopt a sensitive, caring and supportive attitude which will help the family in their bereavement and encourage them to accept the possibility of organ donation. In conclusion, it is recommended that nurses be provided with more detailed advice and guidance on managing the family in the many aspects of such a situation.
In this study, we investigated the relationships among gender, academic achievement, and student preferences for cooperative, competitive, and individualistic learning in a sample of 136 African-American adolescents enrolled in sixth and seventh grades in a school in Georgia. We used the Learning Preference Scale for Students (LPSS; Barnes, Owens, & Straton, 1978) to measure cooperative, competitive, and individualistic preferences. Three two-way ANOVAs (Gender x Academic Achievement) were conducted, in which the three learning preferences were the dependent variables. Gender had a significant effect on the preference for cooperative learning, with girls reporting a higher preference for this method than boys did. For the other two learning preferences, no significant gender differences were found. Academic achievement did not correlate significantly with any of the three learning preferences. A two-way interaction between gender and academic achievement was observed for competitive learning preferences. Girls' preferences for competition increased as academic achievement increased; boys' preferences for competition decreased as academic achievement increased.
Forty-eight healthy male students ate an average American diet (AAD) with 37% of calories from fat and 16% from saturated fatty acids for 3 wk. During the next 7 wk, one-third of the students continued to eat the AAD, one-third switched to a 30%-fat diet with 9% saturated fatty acids (Step 1 diet), and one-third switched to a 30%-fat diet with 14% saturated fatty acids (Sat diet). The Step 1 group had a significant reduction in plasma total cholesterol (TC) (0.36 +/- 0.37 mmol/L) compared with the AAD group (0.07 +/- 0.39 mmol/L) and the Sat group (0.08 +/- 0.25 mmol/L). The Sat group did not differ from the AAD group. Changes in low-density-lipoprotein (LDL) cholesterol paralleled changes in total cholesterol. High-density-lipoprotein cholesterol fell significantly in the Step 1 group (0.11 +/- 0.08 mmol/L) compared with the AAD group. Plasma triglycerides did not differ between groups at the end of the randomized periods. In summary, reduction of dietary fat intake from 37% to 30% of calories did not lower plasma total and LDL cholesterol concentrations unless the reduction in total fat was achieved by decreasing saturated fatty acids.
PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC.
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When bovine aortic endothelial (BAE) cells are superfused with a solution containing low calcium (approximately 10 nM) and subsequently exposed to a solution containing normal Ca2+ (2 mM) a large transient increase in intracellular calcium is seen. This elevation in [Ca2+]i is similar to that described as the calcium paradox in cardiac cells. If the cells are exposed to the agonist, ATP, during the period in low-Ca2+ solution the paradoxical rise in [Ca2+]i is increased. Removal of external Na+ from the low-Ca2+ solution reduces the rise in [Ca2+]i on returning to 2mM-Ca2+ solution. These data are consistent with the presence of a calcium paradox in these cells and with the hypothesis that the underlying mechanism involves the loading of the cell with Na+ during the period in low Ca2+. This process may occur as a result of the altered selectivity of the ATP-activated Ca2+ influx mechanism.
Agonist-evoked rises in [Ca2+]i were recorded from single bovine aortic endothelial cells in the middle of confluent monolayers by dual-wavelength microspectrofluorimetry. Low doses of ATP (1-5 microM) induced a transient rise in [Ca2+]i followed by a maintained plateau phase upon which were superimposed irregular fluctuations in [Ca2+]i. The mechanism underlying these fluctuations is not known. Addition of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), to single cells displaying ATP-induced fluctuations reduced the amplitude and frequency of these fluctuations but the maintained plateau phase was unaffected. Elevation of intracellular cAMP by activation of adenylate cyclase with forskolin, or application of dibutyryl cAMP did not affect the ATP-induced fluctuations. These results suggest a possible role for the diacylglycerol limb of the phosphoinositide hydrolysis pathway, via activation of protein kinase C, but not cAMP, in the mechanism responsible for generating ATP-induced fluctuations in [Ca2+]i.
Although the Gram stain and culture of expectorated sputum are considered standard methods for the diagnosis of presumptive pneumococcal pneumonia, these methods remain relatively insensitive and nonspecific. We developed an enzyme immunoassay (EIA) for the quantitation of pneumococcal C polysaccharide (PnC) in the sputum of patients with presumptive pneumococcal pneumonia. Of 34 patient sputum samples collected within 24 h of the first radiographic report of pneumonia, 12 grew Streptococcus pneumoniae on culture. By using a cutoff point of 0.5 micrograms of PnC per ml of sputum, all 12 specimens were positive (sensitivity, 100%) by EIA. PnC levels ranged from 1.43 to 57.53 micrograms/ml. Blood samples from 18 of the 34 patients were cultured. S. pneumoniae grew in the culture of a blood sample from one patient, whose sputum also had the highest PnC level. Of 22 sputum samples from patients with pneumonia that did not grow S. pneumonia, two were positive by EIA (specificity, 90.1%). Sputa from both patients had low levels of PnC (2.7 and 4.5 micrograms/ml), and both patients had received antibiotics before sputum collection. The positive predictive value of the quantitative EIA was 85.7%. Quantitation of PnC has the potential for improving the accuracy of sputum examination for S. pneumoniae, monitoring disease severity and the effectiveness of antibiotic therapy, and differentiating between those patients with invasive pneumococcal disease and those who are carriers of S. pneumoniae.
The degree to which the physical illness of a parent affects adolescents is unknown. This study examines this issue through a cross-sectional survey of patients referred consecutively to an adolescent outpatient psychiatry clinic. Demographic and clinical data concerning symptoms, diagnosis of major depression, peer isolation, and family functioning were collected on all subjects from both the adolescent and a parent (usually the mother). No significant differences were found between the groups on measures of family functioning, peer isolation and major depression. According to both youth and parent report, adolescents with physically ill parents had more somatic symptoms than controls. These findings are discussed in the light of the existing literature and the methodological shortcomings of the study.