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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 109 records · Page 6Linked to original sources

Mirtazapine versus selective serotonin reuptake inhibitors.

The results of 3 completed comparative studies of mirtazapine versus selective serotonin reuptake inhibitors (SSRIs; fluoxetine, paroxetine, and citalopram) are reviewed. The studies aimed to compare efficacy and tolerability in acute treatment of inpatients and outpatients with major depressive disorder. In comparative trials with fluoxetine, patients who had high baseline total 17-item Hamilton Rating Scale for Depression (HAM-D) and depressed mood item scores were included (scores > or = 21 and > or = 2, respectively). In the comparative trials with citalopram and paroxetine, the inclusion criteria were total Montgomery-Asberg Depression Rating Scale (MADRS) score > or = 22 and 17-item HAM-D score > or = 18. In all 3 studies, statistically significant and clinically relevant differences in favor of mirtazapine were evident on several outcome variables. Against citalopram and paroxetine, the differences in antidepressant efficacy were registered early in treatment but not later, thus suggesting potentially faster onset of efficacy of mirtazapine. These differences were demonstrated on both the 17-item HAM-D and MADRS scales. In addition, mirtazapine demonstrated an accelerated anxiolytic effect as shown by changes from baseline on the Hamilton Rating Scale for Anxiety. Tolerability of all studied compounds was very good, as reflected in a low percentage of premature terminations due to adverse events. On the other hand, differences in pharmacologic profiles between mirtazapine and SSRIs were reflected in their adverse events profiles. The results of these studies confirm that mirtazapine displays good efficacy--leading to an early relief of symptoms--in combination with good tolerability.

Antidepressive Agents, Tricyclic↗

Interleukin 2-mediated uncoupling of T cell receptor alpha/beta from CD3 signaling.

T cell activation and clonal expansion is the result of the coordinated functions of the receptors for antigen and interleukin (IL)-2. The protein tyrosine kinase p56(lck) is critical for the generation of signals emanating from the T cell antigen receptor (TCR) and has also been demonstrated to play a role in IL-2 receptor signaling. We demonstrate that an IL-2-dependent, antigen-specific CD4(+) T cell clone is not responsive to anti-TCR induced growth when propagated in IL-2, but remains responsive to both antigen and CD3epsilon-specific monoclonal antibody. Survival of this IL-2-dependent clone in the absence of IL-2 was supported by overexpression of exogenous Bcl-xL. Culture of this clonal variant in the absence of IL-2 rendered it susceptible to anti-TCR-induced signaling, and correlated with the presence of kinase-active Lck associated with the plasma membrane. The same phenotype is observed in primary, resting CD4(+) T cells. Furthermore, the presence of kinase active Lck associated with the plasma membrane correlates with the presence of ZAP 70-pp21zeta complexes in both primary T cells and T cell clones in circumstances of responsive anti-TCR signaling. The results presented demonstrate that IL-2 signal transduction results in the functional uncoupling of the TCR complex through altering the subcellular distribution of kinase-active Lck.

Animals↗

Characterization of an HPV-negative cell line (FR-CAR) derived from a cervical squamous intraepithelial lesion.

A new cell line, FR-car, has been established from a biopsy of a low-grade human cervical squamous intraepithelial lesion (SIL). We confirmed the epithelial origin of the cells by keratin staining using polykeratin, AE1/AE3 and CAM 5.2 antibodies. Sixty percent to 80% of the cultured cells stained positive for proliferative cell nuclear antigen (PCNA) and Ki-67. There was no overexpression of p53. Karyotyping revealed that the cell line was hypodiploid with clonal abnormalities on chromosome 6 and 16. Sections of a biopsy adjacent to the lesion from which the culture was initiated tested positive for human papillomavirus (HPV) 18 DNA by the polymerase chain reaction, but cultured cells tested at several passages were HPV-negative by either type-specific or consensus PCRs. This HPV-negative SIL line may be useful in studies into the cell biology of dysplastic epithelium.

Adult↗

Parental smoking and risk factors for cardiovascular disease in 10- to 12-year-old children.

OBJECTIVE: Smokers have multiple adverse health-related behaviors and an increased risk of cardiovascular disease. We examined whether health behaviors in parents who smoke may influence children's health behaviors. STUDY DESIGN: Cross-sectional data from 10- to 12-year-olds (n = 800) entering a trial of health promotion programs. RESULTS: Smoking in children was independently associated with maternal (odds ratio 2.1, confidence interval 1.2, 3.8) and paternal smoking (odds ratio 2.1, confidence interval 1.2, 3.7) and was less likely in girls (odds ratio 0.4, confidence interval 0.2, 0.6). Maternal smoking and paternal smoking were additive predictors in children of lower physical activity (P = .0013 for mothers; P = .0476 for fathers) and more television watching (P = .0335 for mothers; P = .0241 for fathers). Children's fat intake was significantly greater if either parent smoked. Children's body mass index (P = .0183) and waist-to-hip ratio (P = .0009) were significantly greater if mothers smoked. CONCLUSIONS: Poor health behaviors associated with smoking in parents, particularly mothers, are likely to influence children's long-term risk of having lifestyle diseases. The results may also explain some of the apparent effects attributed to passive smoking in families.

Adult↗

A controlled trial of health promotion programs in 11-year-olds using physical activity "enrichment" for higher risk children.

OBJECTIVE: To evaluate the short and long term benefits of a school and home based physical activity "enrichment" program for children at higher risk of cardiovascular disease as identified by cluster analysis. STUDY DESIGN: During two 10-week school terms, 800 11-year-olds took part in a randomized controlled trial with the standard physical activity and nutrition program in six schools, the standard program in a further seven schools but with the addition of physical activity enrichment for higher risk children in those schools, and no program in five control schools. Cluster analysis identifying the 29% or so highest risk children used systolic blood pressure, percent body fat, physical fitness, and blood cholesterol. RESULTS: Fitness improved significantly in program schools, particularly with enrichment in higher risk boys. Substantial improvements persisted 6 months later in girls from program schools. At "Enrichment" schools, cholesterol showed significant benefits in higher risk girls and, 6 months later, in both boys and higher risk girls. Sodium intake and, in girls, subscapular skinfolds were lower in "Enrichment" schools when the program ended, but not 6 months later. CONCLUSION: Two-semester health programs with physical activity enrichment for higher risk children can produce benefits sustained for at least 6 months. Improvements extend to lower risk children exposed indirectly to the enrichment. Attenuation of effects on diet and body composition in the longer-term suggest the need for on-going programs.

Anthropometry↗

Eye movements, prematurity and developmental co-ordination disorder.

Horizontal pursuit eye movements were investigated in two separate groups of children: One group exhibited developmental co-ordination disorder (n = 8) whilst another group of children were born prematurely (n = 8). Both studies found a reduced gain in pursuit eye movements when the respective populations were compared with control groups (n = 32). A difference was also found in the ability of some children to temporally synchronize their tracking response to the stimulus, which was indicative of poor predictive control rather than lags in the control system. We suggest that horizontal eye movements may be a sensitive indicator of more general motor deficits during childhood development.

Adult↗

Seasonal Affective Disorder and response to light in two patients with learning disability.

BACKGROUND: Seasonal Affective Disorder is now a well recognised variant of recurrent depressive disorder. No previous description of its occurrence in people with a learning disability has appeared. METHODS: Two patients are described who manifested seasonal cycles in mood related behaviour. RESULTS: Both patients were treated with bright artificial light and showed adequate clinical responses. CONCLUSION: Patients with a learning disability and recurrent behavioural changes indicative of a mood disorder should be assessed for the seasonal pattern of the illness and, if appropriate, given a trial of treatment with bright artificial light. LIMITATION: The data relates to two case reports without structured assessments. Further studies in this population should use standardised diagnostic criteria and systematic severity of depression scores. CLINICAL RELEVANCE: Patients with poor verbal skills may not be able to express their seasonal changes adequately but careful observation of the timing of behavioural abnormalities may aid the diagnosis of SAD leading to new therapeutic possibilities in phototherapy.

Adult↗

Development and preliminary validation of the multiattribute Rhinitis Symptom Utility Index.

The Rhinitis Symptom Utility Index (RSUI) was developed as a preference-based measure of rhinitis symptoms. The RSUI consist of ten questions on the severity and frequency of stuffy or blocked nose, runny nose, sneezing, itching, watery eyes and itching nose or throat over a 14 day period. A cross-sectional survey of 100 adults with allergic rhinitis was completed, with data collected on rhinitis history and severity, physician-rated rhinitis severity, the Rhinitis Quality of Life Questionnaire (RQLQ) and the Health Utilities Index Mark 2 (HUI2). The mean age of the patients was 37 +/- 11 years and 60% were female and 38% had a diagnosis of asthma. A multiplicative multiattribute utility function was developed from patient-derived preferences for different rhinitis-related symptom states. The mean RSUI score for this sample was 0.72 +/- 0.23, with a range of 0.15-1.0. Two week reproducibility of the RSUI was weak (ICC = 0.40). The index differentiated patients by physician-rated severity (p < 0.05) and was correlated 0.35 (p < 0.001) with the HUI2 and -0.67 (p < 0.001) with the RQLQ total score. The RSUI is brief and easy to administer and the results of this study support its reliability and validity. The modest reproducibility reflects the day to day variability of rhinitis. The RSUI may be a useful patient outcome for clinical trials and for cost-effectiveness studies comparing medical treatments for rhinitis.

Adult↗

A method to compare costs of drugs and supplies among anesthesia providers: a simple statistical method to reduce variations in cost due to variations in casemix.

BACKGROUND: Comparison of costs among anesthesia providers using "cost per case" does not adjust for variations in casemix (such as the type of procedure and patient condition). The authors propose an alternative method for comparing costs using the American Society of Anesthesiologists' Relative Value Scale (ASARVS) system, which incorporates basic units (for the procedure), modifier units (for the patient's physical condition), "other" units (such as for the placement of invasive monitors), and time units (proportional to the case duration). METHODS: Data were obtained from a series of 3,340 anesthetics performed at a tertiary hospital. Administered and discarded drug, supply, and fluid costs were used. RESULTS: Costs expressed as dollars per ASARVS unit had 54% less variability than costs expressed as dollars per case (P < 0.0001). Pearson correlations between demographic variables and cost per ASARVS unit ranged from -0.10 to 0.13. Total (e.g., quarterly) costs for simulated sets of cases were predicted within 0.0 +/- 2.3% by multiplying (1) their sum of units and (2) a like set of case's sum of costs divided by sum of units. CONCLUSIONS: Costs of anesthetic supplies and drugs of a case were more accurately reported as "cost per unit" than as "cost per case." This method of calculating the cost of anesthetic drugs and supplies has several applications, including (1) comparison of costs among anesthesia providers and (2) benchmarking costs among hospitals and anesthesia groups. By design, anesthesia providers' time is quantified by their ASARVS units. Together anesthesia costs (personnel, supplies, and drugs) are better reported as "cost per unit" than as "cost per case."

Adult↗

Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits.

To evaluate the effects of activated protein C therapy in a rabbit model of meningococcal endotoxin-induced shock, we performed a prospective, blinded, placebo-controlled animal trial. Forty New Zealand White rabbits were challenged with intravenous meningococcal endotoxin (lipooligosaccharide) 100 microg/kg. Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 microg/mL (n = 20) or an equal volume of saline (n = 20) as an initial bolus. After endotoxin challenge, activated protein C treated animals were administered a continuous infusion of activated protein C 160 microg/kg/h and saline-treated animals were administered an equal volume infusion of saline. Both activated protein C treated and saline control animals demonstrated evidence of shock after endotoxin challenge; mean arterial pressure and serum bicarbonate significantly (p < .01) declined, and heart rate significantly (p < .01) increased from baseline. In activated protein C treated animals, mean plasma activated protein C activity was 5.69 microg/mL (+/- 3.2) 1 h after challenge, whereas plasma protein C activity was not detected in controls. Mean prothrombin and activated partial thromboplastin times were significantly (p < or = .01) prolonged compared with saline-treated controls. Other hematologic and chemical measurements did not differ between groups. Fifteen of 20 (75%) animals treated with activated protein C concentrate survived to 24 h, while 9 of 20 (45%) control animals survived to 24 h (p = .05). Those animals treated with activated protein C had improved survival, which corroborates the findings of early clinical studies in which replacement of protein C improved outcome.

Animals↗

Point mutations in SP1 motifs in the upstream regulatory region of human papillomavirus type 18 isolates from cervical cancers increase promoter activity.

Evidence of the functional significance of two naturally occurring mutations at nt 40 or 41 in the Sp1 motif in the promoter proximal segment of the upstream regulatory region (URR) of human papillomavirus (HPV) type 18 is presented. In electrophoretic mobility shift assays, Sp1 protein bound more efficiently to the Sp1 mutant motifs than to the prototype; while in both HeLa and HT3 cells, luciferase activity controlled by the mutant URRs was upregulated 2- and 3-fold, or 4- and 6-fold, in comparison with the prototype URR or HeLa cell-derived URR respectively. The HeLa URR represents a more appropriate baseline for promoter activity, containing a series of point mutations representative of most HPV-18 cancer isolates, including one in the Yin Yang 1 (YY1) site at the P105 promoter. The effect of the Sp1 mutations was found to be largely maintained in the context of the HeLa URR containing the prototype YY1 site.

Alanine↗

Bacterial SOS checkpoint protein SulA inhibits polymerization of purified FtsZ cell division protein.

Cell division of Escherichia coli is inhibited when the SulA protein is induced in response to DNA damage as part of the SOS checkpoint control system. The SulA protein interacts with the tubulin-like FtsZ division protein. We investigated the effects of purified SulA upon FtsZ. SulA protein inhibits the polymerization and the GTPase activity of FtsZ, while point mutant SulA proteins show little effect on either of these FtsZ activities. SulA did not inhibit the polymerization of purified FtsZ2 mutant protein, which was originally isolated as insensitive to SulA. These studies define polymerization assays for FtsZ which respond to an authentic cellular regulator. The observations presented here support the notion that polymerization of FtsZ is central to its cellular role and that direct, reversible inhibition of FtsZ polymerization by SulA may account for division inhibition.

Bacterial Proteins↗