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Biomedical subjects

S Thompson

Publications and source records attributed to S Thompson.

At least 91 records · Page 5Linked to original sources

The effect of importance level, delay, and rate of forgetting on prose recall in multiple sclerosis.

Memory deficits are frequently seen in patients with multiple sclerosis (MS). The focus of this study was to examine semantic encoding and the rate of forgetting in MS patients. The prose passages of the Wechsler Memory Scale Logical Memory subtest were used to examine MS patients' semantic sensitivity to the idea units of a story. The stories were divided into high, medium, and low idea units, reflecting their overall importance to the meaning of the story. MS patients recalled fewer idea units than controls, but both groups favored the main ideas relative to the nonessential details at both the immediate and delayed recall of the passages. Likewise, MS patients forgot information at a much faster rate than controls. Implications of this faster forgetting rate in MS patients are discussed from an applied setting.

Adult↗

Infectious mononucleosis in an outpatient population: diagnostic utility of 2 automated hematology analyzers and the sensitivity and specificity of Hoagland's criteria in heterophile-positive patients.

OBJECTIVES: To determine the sensitivity and specificity of 2 modern hematology analyzers in flagging heterophile-positive patients; to determine if heterophile-positive, instrument-flagged specimens contain a larger number or a different spectrum of atypical lymphocytes; to document the overall sensitivity and specificity of Hoagland's morphologic criteria in identifying heterophile-positive patients in an outpatient population with a clinical diagnosis of mononucleosis; and to examine whether individual morphologic features might aid in the diagnosis of suspected infectious mononucleosis. DESIGN: A prospective study of patients referred with a clinical diagnosis of infectious mononucleosis who subsequently tested positive for the heterophile antibody. The control group consisted of a similar population of patients who tested negative for the heterophile antibody. INTERVENTION: Hematology profiles of peripheral blood samples were determined with Coulter STKS and Sysmex NE-8000 analyzers. A corresponding Wright-Giemsa-stained blood smear was subsequently examined by a single skilled technologist, who performed a 200-cell white blood cell differential and a 200-cell lymphocyte differential. A specific morphologic search was made for the presence of smudge cells or lymphocytes with cloverleaf nuclei. RESULTS: Using a combination of all flagging criteria, the 2 analyzers identified 156 (86.2%) of 181 heterophile-positive patients as meriting further review. The sensitivity and specificity values of the Coulter analyzer in predicting positive heterophile status for the blast flag were 41% and 97.1%, respectively; for the variant lymphocyte flags, 72.4% and 79.1%, respectively; and for both flags, 40% and 98.1%, respectively. For the Sysmex analyzer, the sensitivity and specificity values in predicting positive heterophile status for the blast flag were 43.4% and 88.6%, respectively; for the variant lymphocyte flag, 15.8% and 90.8%, respectively; and for both flags, 10.5% and 96%, respectively. Considering the classic criteria developed by Hoagland, a lymphocytosis of at least 50% was present in 120 (66.3%) heterophile-positive patients, while an atypical lymphocytosis of at least 10% of the total WBC count was noted in 135 patients (74.6%). The sensitivity and specificity values of a lymphocytosis > or =50% for diagnosing heterophile-positive status were 66.3% and 84.5%, respectively, while the sensitivity and specificity of an atypical lymphocytosis > or =10% were 74.6% and 92.3%, respectively. The presence of smudge cells or cloverleaf lymphocyte nuclei was verified as having high specificity but low sensitivity for suggesting a diagnosis of infectious mononucleosis. CONCLUSION: Although a number of patients did not meet Hoagland's criteria for the diagnosis of infectious mononucleosis, the flagging systems of modern hematology analyzers successfully identified most cases as requiring further review.

Adolescent↗

The pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast.

Exposure of Saccharomyces cerevisiae to sorbic acid strongly induces two plasma membrane proteins, one of which is identified in this study as the ATP-binding cassette (ABC) transporter Pdr12. In the absence of weak acid stress, yeast cells grown at pH 7.0 express extremely low Pdr12 levels. However, sorbate treatment causes a dramatic induction of Pdr12 in the plasma membrane. Pdr12 is essential for the adaptation of yeast to growth under weak acid stress, since Deltapdr12 mutants are hypersensitive at low pH to the food preservatives sorbic, benzoic and propionic acids, as well as high acetate levels. Moreover, active benzoate efflux is severely impaired in Deltapdr12 cells. Hence, Pdr12 confers weak acid resistance by mediating energy-dependent extrusion of water-soluble carboxylate anions. The normal physiological function of Pdr12 is perhaps to protect against the potential toxicity of weak organic acids secreted by competitor organisms, acids that will accumulate to inhibitory levels in cells at low pH. This is the first demonstration that regulated expression of a eukaryotic ABC transporter mediates weak organic acid resistance development, the cause of widespread food spoilage by yeasts. The data also have important biotechnological implications, as they suggest that the inhibition of this transporter could be a strategy for preventing food spoilage.

ATP-Binding Cassette Transporters↗

Nonlinearities in 2-acetylaminofluorene exposure responses for genotoxic and epigenetic effects leading to initiation of carcinogenesis in rat liver.

The dose responses for several effects of low-level limited exposures to 2-acetylaminofluorene (AAF) in the livers of male Fischer 344 rats were measured and a subsequent phenobarbital tumor promotion regimen was used to manifest initiation of carcinogenesis. Three doses over a 10-fold range yielding cumulative total exposures of 0.126, 0.42, and 1.26 mmol AAF/kg body weight were achieved by daily intragastric instillation for up to 12 weeks with interim terminations. This was followed by 24 weeks administration of 500 ppm phenobarbital (PB) in the diet to promote liver tumor development. At 12 weeks at the end of AAF administration, all exposures produced adducts in liver DNA, measured by 32P postlabeling, and the level of adducts increased with exposure, except that the high exposure did not produce a dose proportional increase. Measurement of arylsulfotransferase activity, a key enzyme in the metabolic activation of AAF, revealed that in livers from the high exposure animals, the enzyme was inhibited. To assess for toxicity, the centrilobular zone of glutamine synthetase-positive hepatocytes was quantified immunohistochemically at 12 weeks. The area of the zone was reduced in the high exposure group and there was a trend to reduction in relationship to exposure. The two lower exposures to AAF produced no increase in cell proliferation, whereas the high exposure resulted in a marked increase, about 8-fold over controls. Initiation was assessed by induction of hepatocellular altered foci (HAF) that expressed the placental form of glutathione S-transferase. AAF induced HAF in the high exposure group, 9-fold at 8 weeks and 170-fold at 12 weeks compared to controls. In rats maintained on PB for 24 weeks after exposure, the multiplicity of HAF increased in controls and comparably in the low and mid exposure groups, but remained at the about the same high level in the high exposure group. The high exposure produced a substantial incidence of benign neoplasms by 12 weeks, and with promotion by 36 weeks, all rats developed hepatocellular neoplasia. In the mid exposure group, only one adenoma occurred at 36 weeks in 17 rats, while in the low exposure group, no liver tumor occurred in 23 rats. Thus, these findings document nonlinearities for some of the effects of AAF, with supralinear effects at the high exposure for cell proliferation and induction of HAF, and a no-observed-effect level for induction of promotable liver neoplasms at the lowest cumulative exposure of 0.126 mmol/kg, in spite of the formation of DNA adducts. We conclude that the effects of this DNA-reactive hepatocarcinogen leading to initiation exhibit nonlinearities and possible thresholds.

2-Acetylaminofluorene↗

The role of Gulf Coast oysters harvested in warmer months in Vibrio vulnificus infections in the United States, 1988-1996. Vibrio Working Group.

Vibrio vulnificus infections are highly lethal and associated with consumption of raw shellfish and exposure of wounds to seawater. V. vulnificus infections were reported to the Centers for Disease Control and Prevention from 23 states. For primary septicemia infections, oyster trace-backs were performed and water temperature data obtained at harvesting sites. Between 1988 and 1996, 422 infections were reported; 45% were wound infections, 43% primary septicemia, 5% gastroenteritis, and 7% from undetermined exposure. Eighty-six percent of patients were male, and 96% with primary septicemia consumed raw oysters. Sixty-one percent with primary septicemia died; underlying liver disease was associated with fatal outcome. All trace-backs with complete information implicated oysters harvested in the Gulf of Mexico; 89% were harvested in water >22 degrees C, the mean annual temperature at the harvesting sites (P < .0001). Control measures should focus on the increased risk from oysters harvested from the Gulf of Mexico during warm months as well as education about host susceptibility factors.

Adolescent↗

Obstacles to timely neonatal screening in North Thames.

OBJECTIVE: To assess the timeliness of neonatal (Guthrie card) screening in North Thames, and to identify the most effective ways of improving it. DESIGN: Analysis of information routinely collected in the course of neonatal screening; reanalysis of published data on blood phenylalanine concentration in phenylketonuria (PKU) over the first two weeks; simulation studies on the impact of different interventions. SUBJECTS: 100,690 infants born over one year and screened at Great Ormond Street Hospital NHS Trust. OUTCOME MEASURE: Interval between birth and reading PKU screen results. RESULTS: Although 75% of samples (district range 55-91%) were collected by day 7, only 81% had arrived in the laboratory seven days later (range 57-96%). The average interval between birth and reading results was 14.5 days, with only 9.7% read by day 10. Samples could be collected from day 4 without significant impact on false negative rates for PKU. If samples were collected from day 4 and posted promptly (second class), the average interval between birth and reading results could be reduced to 9.3 days. If first class mail were used and the laboratory operated on Saturdays, and used assays that could be read the same day rather than bacterial inhibition assays, the average would be 7.8 days, with 96% read by day 10. CONCLUSION: Timeliness of neonatal screening shows unacceptable variation between districts, and delays in dispatch of specimens to the laboratory. Same day, first class posting should be introduced, and samples could be collected between days 4 and 8.

Blood Specimen Collection↗

Risk of squamous cell carcinoma and adenocarcinoma of the lung in relation to lifetime filter cigarette smoking.

BACKGROUND: Over the past few decades, the incidence of adenocarcinoma (AC) of the lung increased much more rapidly than that of squamous cell carcinoma (SCC) in men and women. During this time period, filter cigarettes with substantially reduced "tar" and nicotine yields in the smoke came to dominate the market. METHODS: The risk of SCC and AC in lifelong smokers of filter cigarettes relative to lifelong nonfilter cigarette smokers was assessed in a case-control study performed between 1977 and 1995 with 2292 lung carcinoma patients and 1343 hospital controls who were current smokers. RESULTS: Odds ratios (OR) for SCC in male and female subjects who had smoked filter cigarettes exclusively during their lives were slightly reduced relative to lifetime nonfilter cigarette smokers in men (OR = 0.8; 95% confidence interval [CI], 0.5-1.2), and significantly reduced in women (OR = 0.4; 95% CI, 0.2-0.8). No reduction in risk was observed for AC of the lung in men or women. CONCLUSIONS: Evidence that the increasing predominance of AC over SCC may be due in part to the reduced risk of SCC (but not AC) associated with lifelong filter cigarette smoking is strongest in women; for men, further studies that include larger numbers of lifetime filter smokers are needed to confirm this finding. A lack of protection against AC from low yield filter cigarettes may result from smokers' "compensating" with deeper and more frequent inhalation, thereby increasing delivery of carcinogens to the peripheral lung. The smoke of modern cigarettes also contains higher concentrations of nitrosamines that primarily produce AC.

Adenocarcinoma↗

Nissen and Toupet fundoplications effectively inhibit gastroesophageal reflux irrespective of natural anatomy and function.

BACKGROUND: The physiology of Nissen fundoplication (NF) and Toupet fundoplication (TF) is controversial. The aim of this study was to determine the contribution of elevated intragastric pressure to the antireflux mechanism after surgically created fundoplication in explanted porcine stomachs. METHODS: The stomachs and 6-8 cm of distal esophagus were removed from 15 pigs and placed in anatomic position. Five NF, 2 cm in length with three interrupted sutures, were performed, taking full-thickness bites of stomach and partial-thickness bites of esophagus around a 60 French dilator. Five 270 degree TF 2 cm in length with six interrupted sutures were performed taking full-thickness bites of stomach and partial-thickness bites of esophagus around a 60 French dilator. Each stomach served as its own control. The pylorus was tied off and the stomach was inflated with Ringer's lactate while the pressure was monitored. RESULTS: Before NF, reflux could be easily induced with a mean intragastric pressure of 5.5 +/- 3.7 mmHg. After NF reflux could not be induced but the sutures pulled out of the stomach at a mean pressure of 36.8 +/- 11.7 mmHg (p<0.01 vs control). Before TF, reflux could easily be induced with a mean intragastric pressure of 3.0 +/- 3.0 mmHg. After TF, reflux could not be induced and the sutures pulled out of the esophagus or stomach with a mean pressure of 30.8 +/- 9.0 mmHg (p<0.01 vs control). Porcine stomachs in vivo are resistant to reflux, but when explanted they reflux easily. NF and TF are so effective at interrupting reflux that the sutures tear out instead of allowing reflux. CONCLUSIONS: While not yet statistically significant, it appears that sutures tear out of the esophagus (TF) more readily than they tear out of the stomach (NF). TF and NF prevent reflux in the absence of anatomic or functional components of the lower esophageal sphincter.

Animals↗

A new intraluminal antigastroesophageal reflux procedure in baboons.

BACKGROUND: A new endoscopic intraluminal procedure (valvuloplasty) was designed to provide a simple, easy approach to the cardia and to correct and augment any mechanical deficiencies present. The feasibility, durability, and efficacy of this procedure was tested in 13 baboons. METHODS: The valvuloplasty consisted of an intussusception of the gastroesophageal junction into the stomach to create a nipple-type valve. The configuration of the valve was maintained with eight staples and stability was aided by an intramural injection of sodium morrhuate. Gastrointestinal endoscopy and esophageal manometry were performed before and after the procedure. Competency was determined as the intragastric pressure (yield pressure) and volume (yield volume) needed to result in equalization of gastric and esophageal pressure while distending the stomach with water. Comparisons were made with a group of normal baboons (n = 10). RESULTS: All baboons had a normal eating pattern with none showing any evidence of vomiting or regurgitation. Endoscopic circumferential integrity of the valves was 86% at 6 months. The median lower esophageal sphincter length in the valvuloplasty group was significantly (p < 0.01) increased after the procedure from 21 mm to 30 mm. The median yield pressure (22.1 mm Hg) and yield volume (1,525 ml) of the valvuloplasty group was significantly (p < 0.01) greater than the controls (14 mm Hg and 859 ml). CONCLUSIONS: The valvuloplasty is simple, safe, and durable. It augments mechanical function of the cardia and improves competency.

Animals↗

Vibrio vulnificus infection reporting on death certificates: the invisible impact of an often fatal infection.

This study assessed accuracy of (a) recording Vibrio vulnificus infection on death certificates and (b) International Classification of Disease (ICD)-9 codes for V. vulnificus. Patients with microbiologically confirmed V. vulnificus infection were identified as part of co-ordinated surveillance in four USA Gulf Coast states between 1989 and 1993. Of 60 deaths, 51 death certificates were reviewed and V. vulnificus was recorded as the immediate cause of death on 11 (22%). There was no ICD-9 code for V. vulnificus infection, thus no patients had an ICD-9 code indicating V. vulnificus infection. Of 23 certificates where V. vulnificus was recorded on the death certificate, only 5 (22%) were coded for Gram-negative, septicaemia. This study highlights the importance of teaching physicians how to provide epidemiologically meaningful data on death certificates and the need for accurate ICD mortality codes.

Centers for Disease Control and Prevention, U.S.↗

Parents of adults with mental retardation living in-home and out-of-home: caregiving burdens and gratifications.

Interviews with parents of adult children with mental retardation were conducted to identify differences in caregiver burdens and gratifications, based on in-home and out-of-home placement. Parental responses indicate that caretakers of adult children with mental retardation are worried and feel responsibility for their care regardless of residential placement of the adult child.

Activities of Daily Living↗

Alterations in dopamine clearance and catechol-O-methyltransferase activity by dopamine infusions in children.

OBJECTIVE: To determine the role of catechol-O-methyltransferase (COMT) in the biodisposition of pharmacologic concentrations of dopamine. DESIGN: The study was an open-label dose escalation trial in which dopamine was employed as the sole exogenous catecholamine. The dosage was adjusted to achieve improvements in cardiac output or to augment renal function. SETTING: A 16-bed pediatric intensive care unit serving both medical and surgical patients. PATIENTS: The study was performed using 14 dopamine-treated and five untreated control patients. Children ranged in age from 16 days to 12 yrs; five of the treated patients and two of the untreated controls were female. All but one of the study patients were enrolled within 24 hrs of palliative or corrective surgery for congenital heart disease. Control patients had noncardiac surgical procedures. Both treated and control groups were similar with respect to severity of illness, as judged by Therapeutic Intervention Scoring System score. INTERVENTIONS: All treated patients received dopamine as a continuous intravenous infusion. Infusion rates were determined by caregivers and ranged from 3.0 to 20 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Serial, timed blood samples were obtained from patients and control subjects for the determination of plasma dopamine concentrations and for the determination of mononuclear cell COMT activity. Measured rates of dopamine infusion (3.0 to 18.3 micrograms/kg/min) were consistently less than the nominal rates (3.0 to 20.0 micrograms/kg/min) of infusion (p < .0001) due in part to calculations based on the hydrochloride salt rather than dopamine base. At similar steady-state infusion rates, plasma dopamine concentrations varied over a four-fold range, with steady-state concentrations at even the lowest infusion rate exceeding endogenous concentrations by at least ten-fold. Variations in steady-state plasma dopamine concentration reflected large age-associated variations in dopamine clearance, which was found to be saturable at concentrations of > 200 ng/mL. Mononuclear cell COMT activity was assessed simultaneously in these patients. Baseline COMT activity varied over a six-fold range and was unrelated to dopamine clearance or patient age. COMT activity increased two- to six-fold in dopamine-treated patients with plasma steady-state dopamine concentrations of > 100 ng/mL. CONCLUSIONS: These data demonstrate marked age and concentration-dependent differences in dopamine clearance that account for large interindividual differences in the steady-state plasma dopamine concentrations in patients receiving similar infusion rates. While concomitant variability in COMT activity is observed, the lack of correlation between dopamine clearance and COMT activity suggests that COMT is not rate-limiting for the clearance of exogenously administered dopamine.

Catechol O-Methyltransferase↗