Ethics and the student dentist.
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Biomedical subjects
Publications and source records attributed to J M Long.
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A method is described for the determination of fenticonazole in human female plasma. The method utilizes high performance liquid chromatography coupled to atmospheric pressure positive-ion chemical ionization triple quadrupole mass spectrometry. Multiple reaction monitoring is employed for selectivity and sensitivity which enables quantification over the range 0.5-20 ng mL-1 with acceptable precision and accuracy. A comparison is made with an existing HPLC-UV assay and the utility of the technology of combined liquid chromatography and tandem mass spectometry for subnanogram per mL assays is discussed.
The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias (POSCH) that was stratified by cigarette smoking status at the time of randomization. The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied. POSCH was a randomized, controlled, clinical trial designed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infarction subjects with hypercholesterolemia. Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease (ACHD) mortality rates and recurrent confirmed nonfatal myocardial infarction rates. In current cigarette smokers at baseline (n = 90) with a mean follow-up of 8.3 years, the overall mortality rate was 45.2% in patients with no aspirin use and 10.4% in patients who reported even infrequent aspirin use (relative risk = 4.3, 95% confidence interval (CI) = 2.4 to 10.6, p < 0.001). For ACHD mortality in this cohort, the relative risk was 17.1 (35.7% vs 2.1%, 95% CI = 1.4 to 125.0, p < 0.001); for the combined end-point of ACHD mortality and nonfatal myocardial infarction, the relative risk was 2.4 (40.5% vs 16.7%, 95% CI = 1.2 to 5.1, p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of phencyclidine (PCP), an NMDA antagonist, was assessed on a complex task that has been shown to be dependent on hippocampal function. This task required memory for the temporal order of spatial locations. Rats were given IP injections of saline or PCP (3-4 mg/kg) on a double alternation schedule. With PCP injections rats were severely impaired relative to saline injections. Furthermore, PCP was shown to have no effects on the ability of rats to discriminate three-dimensional objects (a task that is not dependent on hippocampal function). The present data, in conjunction with previous results, suggest that the involvement of NMDA receptors in the hippocampus might be a function of the complexity of the task.
The pattern of frontal activation as measured by the ongoing electroencephalogram (EEG) may be a marker for individual differences in infant and adult disposition to respond with either positive or negative affect. We studied 48 4-year-old children who were first observed in same-sex quartets during free-play sessions, while making speeches, and during a ticket-sorting task. Social and interactive behaviors were coded from these sessions. Each child was subsequently seen 2 weeks later when EEG was recorded while the child attended to a visual stimulus. The pattern of EEG activation computed from the session was significantly related to the child's behavior in the quartet session. Children who displayed social competence (high degree of social initiations and positive affect) exhibited greater relative left frontal activation, while children who displayed social withdrawal (isolated, onlooking, and unoccupied behavior) during the play session exhibited greater relative right frontal activation. Differences among children in frontal asymmetry were a function of power in the left frontal region. These EEG/behavior findings suggest that resting frontal asymmetry may be a marker for certain temperamental dispositions.
Septohippocampal cholinergic system involvement in acquisition of an aversively motivated 14-unit T-maze was evaluated in 4-month-old male Fischer-344 rats. Each rat was assigned to one of two groups that received either a bilateral electrolytic lesion to the medial septal area (MSA) or a sham operation. One week after surgery, each rat began pretraining in one-way active avoidance (footshock = 0.8 mA) consisting of 10 trials per day on each of 3 consecutive days. Criterion for successful completion of pretraining was 8/10 avoidances on the third day. On the day following completion of pretraining, each rat received 10 trials in a shock-motivated 14-unit T-maze. The performance requirement was to move through each of five maze segments within 10 s to avoid footshock (0.8 mA). A second 10-trial session was provided 24 h later. Performance measures included errors, alternation errors, runtime, shock frequency, and duration. Following maze training, each rat was sacrificed, and formalin-fixed brains were frozen for histology, which included procedures for thionin Nissl and acetylcholinesterase (AChE) staining. MSA-lesioned rats were observed to be significantly impaired on all measures of maze performance compared to sham-operated controls. Densitometric analysis of hippocampal AChE staining revealed a 30% reduction in relative AChE staining of MSA-lesioned rats compared to sham-operated controls. Lesion size was observed to be highly positively correlated with maze errors. A negative correlation of mean error score with density of AChE staining was observed for MSA-lesioned rats, but not for sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Probe tests provide an important additional converging operation to identify the characteristics of cognitive processes being assessed by other behavioral measures. We introduce a new procedure using a variable-interval (VI) probe test to assess spatial memory in the water maze. Three groups of rats were trained in spatial discrimination with traditional platform trials. For the probe trials, 2 groups had no-platform (NP) probe trials in which the escape platform was unavailable for the entire trial. The 3rd group had variable interval (VI) probe trials, in which the escape platform was available only after a VI. The VI probe trial was a more sensitive measure of spatial memory than was the NP probe trial and was useful for repeated measurements of spatial memory, a characteristic not readily attainable with the NP probe trial.
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In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24-25 month) and young (6-7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant (ps less than 0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4-6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations (ps less than 0.05) were observed between maze errors and baseline glucose levels, r(21) = -.62, and peak glucose response, r(19) = .49. However; within the aged group, significant correlations (ps less than 0.01) with maze errors emerged only for baseline glucose, r(13) = -.69, and peak insulin response, r(13) = -.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)
The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.
We studied 114 neonates by pneumocardiogram recordings in order to examine the effects of cocaine with and without opiate exposure on neonatal respiration, heart rate, apparent life threatening events (ALTE), and sudden infant death syndrome (SIDS). In full-term infants exposed to cocaine without opiates we found increased longest apnea duration and more episodes of bradycardia, but decreased periodic breathing and average heart rate than in control full-term infants. Term infants prenatally exposed to cocaine with opiates also had less periodic breathing. Preterm infants exposed to cocaine with and without opiates had decreased apnea density and periodic breathing compared with preterm controls. Discriminant analysis to determine whether perinatal asphyxia or exposure to other drugs could predict cardiorespiratory abnormalities showed no consistent relationship. In 72 of 114 infants available for follow-up, no ALTE occurred but two were lost to SIDS. Our data support the hypothesis that prenatal cocaine exposure may perturb, albeit subtly, the maturation of respiratory control, resulting in disruption of postnatal respiration.
BACKGROUND AND METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS: When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS: Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression.
K(+) content and concentration within the apoplast of mesophyll tissue of pea (Pisum sativum L., cv Argenteum) leaflets were determined using an elution procedure. Following removal of the epidermis, a 1 centimeter (inside diameter) glass cylinder was attached to the exposed mesophyll tissue and filled with 5 millimolar CaCl(2) solution (1 degrees C). From time-course curves of cumulative K(+) diffusion from the tissue, the amount of K(+) of extracellular origin was estimated. Apoplastic K(+) contents for leaves from plants cultured in nutrient solution containing 2 or 10 millimolar K(+) were found to range from 1 to 4.5 micromoles per gram fresh weight, comprising less than 3% of the total K(+) content within the lamina tissue. Assuming an apoplastic solution volume of 0.04 to 0.1 milliliters per gram fresh weight and a Donnan cation exchange capacity of 2.63 micromoles per gram fresh weight (experimentally determined), the K(+) concentration within apoplastic solution was estimated at 2.4 to 11.8 millimolar. Net movement of Rb(+) label from the extracellular compartment within mesophyll tissue into the symplast was demonstrated by pulse-chase experiments. It was concluded that the mesophyll apoplast in pea has a relatively low capacitance as an ion reservoir. Apoplastic K(+) content was found to be highly sensitive to changes in xylem solution concentration.
Detection of Chlamydia trachomatis infection was evaluated by culture and a new Syva enzyme immunoassay (EIA) in 1,012 patients at two Baltimore, Md., sexually transmitted disease clinics. The overall chlamydia prevalence determined by culture was 12%. For 506 fresh cervical and urethral specimens, the sensitivity of Syva EIA was 90% and its specificity was 94% compared with culture. Discordant Syva EIA results were further evaluated by staining the sediment in centrifuged culture transport media and Syva EIA transport tubes with a fluorescent monoclonal antibody to C. trachomatis to detect elementary bodies. Reanalysis of the data after use of this technique to resolve discordant results increased sensitivity and specificity to 92 and 96%, respectively. A subsample of 307 fresh cervical specimens was also tested in a three-way comparison using Abbott Chlamydiazyme, Syva EIA, and culture. In this sample, compared with culture, the sensitivity and specificity of Syva EIA were 87 and 95%, respectively, and for Chlamydiazyme they were 77 and 98%, respectively. Syva EIA is a 4-h, easy-to-perform enzyme-linked immunosorbent assay which has a high sensitivity with fresh genital specimens and offers an excellent alternative to culture.
Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.
The safety and efficacy of ofloxacin, 400 mg orally, were compared with those of amoxicillin, 3.0 g, plus probenecid, 1.0 g orally, as single-dose therapy in 201 heterosexual patients (101 men and 100 women) with uncomplicated gonococcal infection. Treatment groups were comparable in age, duration of symptoms, number of sexual partners within the previous month, and number of previous episodes of sexually transmitted diseases. The cure rate for men treated with ofloxacin was 98% (47 of 48), and that for women was 100% (52 of 52). Cure rates for both men and women treated with amoxicillin-probenecid were 96% (51 of 53 men; 46 of 48 women). All 13 patients with positive rectal cultures and 7 of 8 patients with positive pharyngeal cultures treated with ofloxacin were cured. Neither regimen reliably eradicated coexistent infection with Chlamydia trachomatis. The MIC of ofloxacin for all but two of 198 pretreatment isolates was 0.3 microgram/ml or less. The MIC of amoxicillin for 90% of isolates tested was 1.0 microgram/ml. Single oral doses of ofloxacin and of amoxicillin plus probenecid were equally effective for treatment of urethral and cervical gonorrhea. Ofloxacin appears promising as treatment for rectal and pharyngeal infection, but studies with larger numbers of patients with rectal or pharyngeal infection or both are required for confirmation. Relative contraindications in children and possibly pregnant women plus the potential for single-step, high-level resistance may limit the usefulness of quinolone therapy for gonorrhea.
Some candidate medical expert system applications have a significant visual component. Knowledge engineers usually dismiss such task domains as potential expert systems applications. Our success in developing ESCA, a system for evaluating serial coronary angiograms, shows that such task domains should not be dismissed so quickly. We used a symbiotic approach between man and machine, where technologists provide the visual skills with an expert system imitating the conceptual skills of the expert, to produce a partially automated system that is more consistent and cost effective than one that is fully manual. The agreement between the system's conclusions and that of a panel of experts is good. The expert system actually has a slightly higher agreement rate with the expert panel than the agreement rate between two expert panel teams evaluating the same film pair.