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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 91 records · Page 5Linked to original sources

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↗

Contraceptive needs of women attending a genitourinary medicine clinic for the first time.

OBJECTIVE: To assess the need for, and potential uptake of, a contraceptive service within a genitourinary medicine (GUM) clinic. METHODS: 544 women, median age 17 years (range 13-54) including 142 teenagers, attending the Fife GUM clinics serving a semirural population of 350,000 for the first time in the 12 month period from 1 September 1995 to 31 August 1996 were interviewed. RESULTS: Contraception was required by 353, of whom only 5% (29) were at risk of unplanned pregnancy, although half (15) of these were teenagers. 23 of 29 (79%) stated that they would access contraception at a GUM clinic if it were available. Of women using contraception, 67% (217/324) were taking the oral contraceptive pill (OCP), of whom 177 obtained supplies from their general practitioners and were happy with this. However, 92/177 (52%) stated that they would access the OCP at GUM clinics if it were available. Overall, of the 243 women who stated that they would access contraception at the GUM clinic, 23 of whom were currently at risk of an unplanned pregnancy, the demand was principally for condoms and the OCP. CONCLUSION: The majority of women attending GUM clinics for the first time are using contraception, or have deliberately chosen not to do so. Only 5% were at risk of unplanned pregnancy. In general, the women using contraception were happy with their current source of contraception, but about two thirds would use a contraceptive service at GUM clinics if it were available at the time they were attending the clinic. It was found that teenagers accounted for half of those women at risk of unwanted pregnancy. However, the majority of teenagers requiring contraception would consider obtaining it from GUM clinics.

Adolescent↗

Audit of diagnostic criteria for Trichomonas vaginalis in a genitourinary medicine clinic.

A comparison between high vaginal swab (HVS) wet prep examination within the genitourinary medicine (GUM) clinic and that made from an HVS transported in Amies charcoal medium to the laboratory for the diagnosis of Trichomonas vaginalis was made in a prospective study. Clinic wet prep compared with Amies had a sensitivity of 68% and specificity of nearly 100%. Using the clinic wet prep alone, 9/30 (30%) cases would have been missed.

Animals↗

Osmoregulation in clinical disorders of thirst appreciation.

Thirst and drinking are essential components of normal osmoregulation in healthy man. Abnormalities of thirst appreciation, in particular hypodipsia, have profound implications for water homeostasis. The combination of cranial diabetes insipidus and hypodipsia can have particularly serious consequences, with the potential for life-threatening hyponatraemia. Although the tools for measuring thirst are subjective and lack true specificity, their use in clinical research has contributed greatly to our understanding of the physiology of thirst appreciation and the abnormal control of thirst in osmoregulatory disorders. The precise neural control of thirst appreciation remains unknown, and perhaps as a result of this, satisfactory therapies for the treatment of disorders of thirst have not yet been developed; behavioural modification and retraining of drinking habits remain the rather limited cornerstones of management.

Adult↗

Polyvalent binding to carbohydrates immobilized on an insoluble resin.

Numerous studies have established that polyvalency is a critical feature of cell surface carbohydrate recognition. Nevertheless, carbohydrate-protein interactions are typically evaluated by using assays that focus on the behavior of monovalent carbohydrate ligands in solution. It has generally been assumed that the relative affinities of monovalent carbohydrate ligands in solution correlate with their polyvalent avidities. In this paper we show that carbohydrate ligands synthesized directly on TentaGel beads interact with carbohydrate-binding proteins in a polyvalent manner. The carbohydrate-derivatized beads can, therefore, be used as model systems for cell surfaces to evaluate polyvalent carbohydrate-protein interactions. By using a combinatorial approach to synthesize solid-phase libraries of polyvalent carbohydrates, one can rapidly address key issues in the area of cell surface carbohydrate recognition. For example, studies reported herein demonstrate that there is an unanticipated degree of specificity in recognition processes involving polyvalent carbohydrates. However, the correlation between polyvalent avidities and solution affinities is poor. Apparently, the presentation of carbohydrates on the polymer surface has a profound influence on the interaction of the ligand with the protein receptor. These findings have implications for how carbohydrates function as recognition signals in nature, as well as for how polyvalent carbohydrate-protein interactions should be studied.

Carbohydrate Metabolism↗

Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial.

OBJECTIVE: To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects. DESIGN: Randomized, double-blind, placebo-controlled intervention study. SETTING AND PARTICIPANTS: A total of 88 free-living, healthy subjects at least 65 years of age. INTERVENTION: Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. RESULTS: Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum alpha-tocopherol (vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed. CONCLUSIONS: Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.

Aged↗

CD28/B7 costimulation regulates autoimmune diabetes induced with multiple low doses of streptozotocin.

Insulin-dependent diabetes mellitus is believed to occur as a result of a T cell-mediated destruction of the islets of Langerhans. The factors that regulate the T cell responses, in particular the costimulatory signals required for the T cell activation, which result in islet cell destruction, are still unclear. CD28/B7 interactions have been shown to be important in the regulation of T cell immune responses. We, therefore, have examined the role of CD28/B7 interactions in a model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis and hyperglycemia occur over a brief period, following multiple low doses of streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus). Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA following STZ, unlike CD28 +/- C57BL/KsJ mice. The expression of B7-1 (CD80) and B7-2 (CD86) molecules was closely regulated during development of the disease. Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in STZ-treated C57BL/KsJ mice. Expression of only CD86 increased on islet cells in diabetic mice. In wild-type animals, treatment with mAb against CD86 prevented, whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia, indicating that mAbs against these molecules differentially affect development of disease. We conclude that CD28 signal transduction is required for development of diabetes in multidose STZ-induced diabetes mellitus. CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes.

Animals↗

Seasonality prevalence and incidence of depressive disorder in a general practice sample: identifying differences in timing by caseness.

A total of 2225 consecutive consulting general practice patients attending a North London Health Centre over the course of a year were screened and interviewed for the presence of psychiatric disorder using the GHQ and SADS; 196 patients suffering from RDC depressive disorders were identified and followed up for a further 12 months. A difference in prevalence incidence and recovery time was identified between major and minor depression. Various associations between season of onset and a range of variables were observed. Logistic modelling identified interactions between some of these variables some of which have not been explored in previous studies.

Bipolar Disorder↗

Polymorphism at codons 114, 116, 145, and 163 muddle the typing of HLA-B*1304.

Genetic exchanges often muddle the typing of HLA class I molecules, this is also the case for HLA-B*1304. Serologic and molecular DNA class I typing report a B15/B55 type for cell 847, whereas DNA sequencing finds B*5501/B*1304. HLA-B*1304 differs by no more than four amino acids from other HLA-B13 molecules, a comparative analysis of the B13 and B15 families was therefore performed to determine why serologic and molecular DNA approaches report a B15 type for B*1304. Comparisons demonstrate that limited differences individuate the B15 and B13 molecules such that the genetic recombination of codons 145 and 163 in the class I heavy chain's alpha 2 alpha helix prompt B*1304 to exhibit a B15X21 pattern of serologic cross-reactivity. Molecular DNA class I typing approaches are also swayed by genetic recombinations to type B*1304 as a B15 molecule: B15-like nucleotide sequences encoding residues 114, 116, and 145, lead B*1304 to exhibit a B15 PCR amplification pattern. Thus, genetic exchanges encoding key amino acids in the class I heavy chain lead molecular and serologic typing approaches to categorize HLA-B*1304 as a member of the B15 family.

Alleles↗