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Biomedical subjects

M Coleman

Publications and source records attributed to M Coleman.

At least 37 records · Page 2Linked to original sources

Cancer prevalence in European registry areas.

BACKGROUND: Information on cancer prevalence is of major importance for health planning and resource allocation. However, systematic information on cancer prevalence is largely unavailable. MATERIALS AND METHODS: Thirty-eight population-based cancer registries from 17 European countries, participating in EUROPREVAL, provided data on almost 3 million cancer patients diagnosed from 1970 to 1992. Standardised data collection and validation procedures were used and the whole data set was analysed using proven methodology. The prevalence of stomach, colon, rectum, lung, breast, cervix uteri, corpus uteri and prostate cancer, as well as of melanoma of skin, Hodgkin's disease, leukaemia and all malignant neoplasms combined, were estimated for the end of 1992. RESULTS: There were large differences between countries in the prevalence of all cancers combined; estimates ranged from 1170 per 100000 in the Polish cancer registration areas to 3050 per 100000 in southern Sweden. For most cancers, the Swedish, Swiss, German and Italian areas had high prevalence, and the Polish, Estonian, Slovakian and Slovenian areas had low prevalence. Of the total prevalent cases, 61% were women and 57% were 65 years of age or older. Cases diagnosed within 2 years of the reference date formed 22% of all prevalent cases. Breast cancer accounted for 34% of all prevalent cancers in females and colorectal cancer for 15% in males. Prevalence tended to be high where cancer incidence was high, but the prevalence was highest in countries where survival was also high. Prevalence was low where general mortality was high (correlation between general mortality and the prevalence of all cancers = -0.64) and high where gross domestic product was high (correlation = +0.79). Thus, the richer areas of Europe had higher prevalence, suggesting that prevalence will increase with economic development. CONCLUSIONS: EUROPREVAL is the largest project on prevalence conducted to date. It has provided complete and accurate estimates of cancer prevalence in Europe, constituting essential information for cancer management. The expected increases in prevalence with economic development will require more resources; allocation to primary prevention should therefore be prioritised.

Adolescent↗

Development of symptoms of tobacco dependence in youths: 30 month follow up data from the DANDY study.

OBJECTIVE: To determine if there is a minimum duration, frequency or quantity of tobacco use required to develop symptoms of dependence. DESIGN AND SETTING: A retrospective/prospective longitudinal study of the natural history of tobacco dependence employing individual interviews conducted three times annually in two urban school systems over 30 months. Detailed histories of tobacco use were obtained including dates, duration, frequency, quantity, patterns of use, types of tobacco, and symptoms of dependence. PARTICIPANTS: A cohort of 679 seventh grade students (age 12-13 years). MAIN OUTCOME MEASURES: The report of any of 11 symptoms of dependence. RESULTS: Among 332 subjects who had used tobacco, 40% reported symptoms, with a median latency from the onset of monthly smoking of 21 days for girls and 183 days for boys. The median frequency of use at the onset of symptoms was two cigarettes, one day per week. The report of one or more symptoms predicted continued smoking through the end of follow up (odds ratio (OR) 44, 95% confidence interval (CI) 17 to 114, p < 0.001). CONCLUSIONS: Symptoms of tobacco dependence commonly develop rapidly after the onset of intermittent smoking, although individuals differ widely in this regard. Girls tend to develop symptoms faster. There does not appear to be a minimum nicotine dose or duration of use as a prerequisite for symptoms to appear. The development of a single symptom strongly predicted continued use, supporting the theory that the loss of autonomy over tobacco use begins with the first symptom of dependence.

Adolescent↗

Safety toxicity study of plasmid-based IL-12 therapy in Cynomolgus monkeys.

We have investigated the potential toxicity of hlL-12 DNA plasmid formulated with 5% polyvinylpyrrolidone (PVP) administered twice weekly via subcutaneous injections to Cynomolgus monkeys for four weeks, and have evaluated recovery from any effects of the test article over a four-week treatment-free period. Doses of the formulated hIL-12 plasmid were selected based on anti-tumour efficacy studies previously conducted in mice. The duration of the study and the frequency of dosing were designed to support clinical trials. No clinical signs indicative of an adverse effect of administration of formulated hIL-12 plasmid were observed. There were no apparent effects of the formulated hIL-12 plasmid on body weights or on serum chemistry, haematology, coagulation or urinalysis parameters. No treatment-elated ocular abnormalities were evident. In addition, examination of the electrocardiograms from all monkeys at the pre-study, week-4, and week-8 time points did not reveal any treatment-related effects. No treatment-related gross lesions were noted at days 28 or 57. Slight histopathological changes associated with high doses of PVP vehicle were observed at both time points. These results suggested that the administration of formulated hIL-12 plasmid at a dose level up to 18 mg kg(-1) dose twice per week for four weeks to experimentally naïve Cynomolgus monkeys did not result in significant toxicity. These results support further testing of this gene therapy in clinical trials.

Animals↗

Broad-spectrum mildew resistance in Arabidopsis thaliana mediated by RPW8.

Plant disease resistance (R) genes control the recognition of specific pathogens and activate subsequent defense responses. We show that the Arabidopsis thaliana locus RESISTANCE TO POWDERY MILDEW8 (RPW8) contains two naturally polymorphic, dominant R genes, RPW8.1 and RPW8.2, which individually control resistance to a broad range of powdery mildew pathogens. Although the predicted RPW8.1 and RPW8.2 proteins are different from the previously characterized R proteins, they induce localized, salicylic acid-dependent defenses similar to those induced by R genes that control specific resistance. Apparently, broad-spectrum resistance mediated by RPW8 uses the same mechanisms as specific resistance.

Alleles↗

The relationship between support and stress in forensic community mental health nursing.

UNLABELLED: AIMS OF THE STUDY/PAPER: This paper reports the results of a survey of forensic community mental health nurses (FCMHNs) in England and Wales which aimed to ascertain the level of stress and burnout experienced by this group. BACKGROUND/RATIONALE: Several studies have identified that mental health nursing is a stressful activity and the relationship between factors such as age, experience, support, caseload size and perceived stress have been explored. However, until recently, no studies have examined the situation of FCMHNs and this paper extends the analysis of studies completed by the main author, considering issues related to coping abilities and support systems. DESIGN/METHODS: The survey involved respondents completing a demographic questionnaire and a range of standardized validated measures (Maslach Burnout Inventory, General Health Questionnaire and Community Psychiatric Nurse Stress Questionnaire). The population for the study was all identified FCMHNs attached to the 26 National Health Service (NHS) Medium Secure Units in England and Wales (n=104). RESULTS/FINDINGS: A high response rate of 77% (n=80) was achieved. The results identified that a number of respondents were experiencing burnout. Statistically significant associations were found between caseload size and level of stress. The results also suggest that support from managers and colleagues were an important factor in ameliorating the experience of stress and show that individuals in this study experiencing high levels of stress adopted palliative behaviours such as use of alcohol. CONCLUSIONS: The paper concludes by suggesting that such findings should be considered when delivering stress management programmes and reinforce the potential benefit of effective clinical supervision as a means of staff support.

Adaptation, Psychological↗

Multimeric hemoglobin of the Australian brine shrimp Parartemia.

The hemoglobin molecule of the commercially important brine shrimp Artemia sp. has been used extensively as a model for the study of molecular evolution. It consists of nine globin domains joined by short linker sequences, and these domains are believed to have originated through a series of duplications from an original globin gene. In addition, in Artemia, two different polymers of hemoglobin, called C and T, are found which differ by 11.7% at the amino acid level and are believed to have diverged about 60 MYA. This provides a set of data of 18 globin domain sequences that have evolved in the same organism. The pattern of amino acid substitution between these two polymers is unusual, with pairs of equivalent domains displaying differences of up to 2.7-fold in total amino acid substitution. Such differences would reflect a similar range of molecular-clock rates in what appear to be duplicate, structurally equivalent domains. In order to provide a reference outgroup, we sequenced the cDNA for a nine-domain hemoglobin (P) from another genus of brine shrimp, Parartemia zietziana, which differs morphologically and ecologically from Artemia and is endemic to Australia. Parartemia produces only one hundredth the amount of hemoglobin that Artemia produces and does not upregulate production in response to low oxygen partial pressure. Comparison of the globin domains at the amino acid and DNA levels suggests that the Artemia globin T gene has accumulated substitutions differently from the Parartemia P and Artemia C globin genes. We discuss the questions of accelerated evolution after duplication and possible functions for the Parartemia globin.

Amino Acid Substitution↗

Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies.

OBJECTIVES: To document the change in synovial membrane macrophage and T-lymphocyte content in rheumatoid arthritis (RA) patients who achieve remission induced by disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Arthroscopic synovial biopsies were taken from four to seven sites around a knee joint in 13 patients with RA before and at regular intervals after commencing treatment with a DMARD. The cellular content of synovial membrane biopsies taken at regular intervals for a period of up to 3 yr after commencing treatment was quantitated by routine histopathology and immunohistochemical labelling with anti-macrophage (CD68) and anti-T lymphocyte (UCHL-1) antibodies. Synovial biopsies were quantitated with a validated semiquantitative scoring system and video image analysis. RESULTS: Nine patients obtained clinical remission, as defined by American College of Rheumatology (ACR) criteria. The changes that occurred in the synovial biopsies included a reduction in lining layer thickness, reduced vascularity and cellular infiltrate. The most significant reduction in cellular infiltrate was in the lining layer macrophages, with less dramatic change in the subintimal macrophage infiltrate. Although there was a reduction in CD45 Ro-positive T lymphocytes in the synovial membranes of patients who attained ACR-defined disease remission, it was less significant than the reduction in macrophage content of the synovial membranes and tended to plateau at a reduced level of T-cell infiltration. CONCLUSIONS: Remission in RA patients is characterized by a predominant reduction in macrophage content of the synovial membrane, suggesting that current DMARDs may target this cell and its inflammatory mediators.

Aged↗

Successful treatment of rheumatoid arthritis is associated with a reduction in synovial membrane cytokines and cell adhesion molecule expression.

OBJECTIVE: To investigate the change in synovial membrane cytokine content and cell adhesion molecule expression in sequential biopsies from the same knee joint of patients with rheumatoid arthritis, before and following anti-rheumatic drug treatment and to assess the relationship of these changes with clinical responses to the drug treatment. METHODS: A selected group of patients with rheumatoid arthritis, some of whom had achieved a disease remission based on American College of Rheumatology (ACR) criteria, were included in this study. Sequential synovial biopsies obtained before and throughout the treatment period were studied by immunohistochemical labelling techniques for the cellular content, production of a range of pro- and anti-inflammatory cytokines and the expression of cell adhesion molecules. The staining was quantitated using computer-assisted digital image analysis. RESULTS: There was a decrease in tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) production in the synovial membrane lining and sublining of all patients who responded to treatment. The changes in IL-1 receptor antagonist production were variable. Paradoxically, there was a trend to decreased synovial membrane production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGFbeta), while IL-4 was not detectable in any of the synovial membrane biopsies. A significant reduction in the density and total amount of E-selectin expression in the synovial membrane was seen. Similarly, intercellular adhesion molecule-1 (ICAM-1) expression in the lining and sublining was decreased in those patients who had a significant clinical response to drug treatment or attained disease remission. There were no consistent or significant changes seen in the expression of other cell adhesion molecules in the synovial membranes of these patients. CONCLUSIONS: Successful drug treatment of rheumatoid arthritis patients is characterized at the synovial membrane level by a decrease in TNFalpha, IL-10 and TGFbeta production. Some (E-selectin and ICAM-1) but not all (P-selectin, VCAM-1, PECAM-1) cell adhesion molecules are modulated in patients who respond clinically to drug treatment. E-selectin and ICAM-1 may be important targets for the development of future drug treatments for rheumatoid arthritis.

Aged↗

Biology and management of mantle cell lymphoma.

Mantle cell lymphoma is a distinct subtype and accounts for approximately 5 to 10% of non-Hodgkin lymphomas. The malignant cells express pan B-cell markers, including CD19, CD20 and CD22, and the T-cell marker CD5, whereas CD10 and CD23 expression are usually absent. By cytogenetic analysis, the t(11;14)(q13;q32) translocation is commonly observed, resulting in overexpression of cyclin D1. This entity often combines some unfavorable clinical features of the indolent and aggressive lymphoma subtypes, as it is generally incurable and relatively aggressive. It is most commonly observed in men 50 to 70 years of age and is characterized by disseminated disease, usually involving lymph nodes, bone marrow, and spleen. Frequently, there is extranodal involvement including the gastrointestinal tract. These tumors are incurable with the currently available therapeutic options, with usual time to progression after chemotherapy of approximately 1 year. Newer chemotherapy regimens (including stem cell transplantation) and monoclonal antibody-based therapies have shown limited evidence of additional benefit. Overall, the prognosis for patients with mantle cell lymphoma remains poor, and novel strategies are needed.

Age of Onset↗

Beyond sexual assessment: lessons learned from couples post radical prostatectomy.

PURPOSE: To share selected experiences of advanced practice nurses (APNs) who implemented a home-based nursing protocol related to psychosexual function for couples following radical surgery for prostate cancer. DATA SOURCES: Selected research-based articles, the PLISSIT Model for sexual rehabilitation counseling, and the authors' experiences. CONCLUSIONS: Five lessons related to communicating about sexuality and intimacy were synthesized from the experience, including examining knowledge and self-awareness regularly, using a structured interview guide to facilitate the process, developing a trusting relationship with the couple, attending to verbal and nonverbal cues, and providing information about the full range of sexual expression. IMPLICATIONS FOR PRACTICE: Include an assessment of sexual health as an integral part of a general health assessment. Patients do not generally volunteer information about their sexual concerns unless the subject is introduced by the APN.

Clinical Protocols↗

Sources of tobacco for youths in communities with strong enforcement of youth access laws.

AIM: To determine how youths obtain tobacco in communities with strong enforcement of tobacco sales laws. SETTING: Ten communities in Massachusetts with merchant compliance rates at or above 90%. METHODS: Paper surveys and focus group discussions with 68 adolescent smokers. RESULTS: Parents and friends are the primary sources of tobacco for new smokers. When stealing from parents can no longer satisfy the need for cigarettes, young adolescents ask strangers to buy them tobacco. For high school age smokers, teenage store clerks are a major source. Teenage clerks sell to other teenagers, steal tobacco, and help their friends steal from their employers. Friends who are 18 years of age or over are a second major source for older adolescents. Parents often purchase tobacco for older adolescents. CONCLUSION: Recommended actions include raising the minimum age for the purchase of tobacco to 21 years, and prohibiting individuals less than 21 years of age from selling tobacco.

Adolescent↗

DICE (dexamethasone, ifosfamide, cisplatin, etoposide) infusional chemotherapy for refractory or relapsed non-Hodgkin's lymphoma (NHL).

Continuous exposure to naturally-derived chemotherapy agents such as etoposide may theoretically override drug resistance due to overexpression of the multidrug resistance gene product, p-glycoprotein. Dexamethasone in high dose may have a similar overriding effect. Data also suggest that ifosfamide both by continuous infusion and when combined with a platinum compound may be more effective. Forty-four chemotherapy-refractory/relapsed lymphoma patients received the DICE infusional regimen. The programme consisted of dexamethasone 40 mg i.v. daily for 4 days, ifosfamide 1500 mg mixed with equal dosing of mesna continuously infused i.v. daily for 4 days, cisplatin 25 mg i.v. each day for 4 days and etoposide 150 mg continuously infused i.v. daily for 4 days, all administered every 3 weeks. Doses of ifosfamide and etoposide were escalated by 250 mg and 25 mg, respectively, based on patient tolerance, usually lack of myelosuppression. Special hydration was not required. G-CSF support was provided to patients as required. All patients had disease that had relapsed from or was resistant to CHOP or a similar anthracycline-containing combination regimen. A majority had previously received at least two regimens and 27% had received three or more. Of 44 patients, 32 (73%) achieved a significant response consisting of 18 complete remissions (CR) (41%) and 14 (32%) partial remissions (PR). There were 81% objective responses in large cell lymphoma comprised of 50% CR and 31% PR. Previous response to chemotherapy predicted response to DICE: 83% (25/30) of prior responders vs 50% (7/14) of non-responders had a response to the treatment regimen (p = 0.031, Fisher's exact test). Patients not undergoing transplantation had a median time of 8 months on therapy and a mean of 10 months. Toxicity was haematological (36% developing grade III-IV toxicity) and neurological (9%). There were only three episodes of clinical cystitis or gross haematuria. Infusional DICE is an easily administered and well tolerated programme with significant activity in refractory or relapsed NHL and may be useful as a tumour-reductive therapy prior to high-dose chemotherapy and autologous stem cell transplantation.

Age Factors↗

The Noh mask effect: vertical viewpoint dependence of facial expression perception.

Full-face masks, worn by skilled actors in the Noh tradition, can induce a variety of perceived expressions with changes in head orientation. Out-of-plane rotation of the head changes the two-dimensional image characteristics of the face which viewers may misinterpret as non-rigid changes due to muscle action. Three experiments with Japanese and British viewers explored this effect. Experiment 1 confirmed a systematic relationship between vertical angle of view of a Noh mask and judged affect. A forward tilted mask was more often judged happy, and one backward tilted more often judged sad. This effect was moderated by culture. Japanese viewers ascribed happiness to the mask at greater degrees of backward tilt with a reversal towards sadness at extreme forward angles. Cropping the facial image of chin and upper head contour reduced the forward-tilt reversal. Finally, the relationship between head tilt and affect was replicated with a laser-scanned human face image, but with no cultural effect. Vertical orientation of the head changes the apparent disposition of facial features and viewers respond systematically to these changes. Culture moderates this effect, and we discuss how perceptual strategies for ascribing expression to familiar and unfamiliar images may account for the differences.

Adolescent↗

Purine metabolism abnormalities in a hyperuricosuric subclass of autism.

A subclass of patients with classic infantile autism have uric acid excretion which is >2 S.D.s above the normal mean. These hyperuricosuric autistic individuals may comprise approx. 20% of the autistic population. In order to determine the metabolic basis for urate overexcretion in these patients, de novo purine synthesis was measured in the cultured skin fibroblasts of these patients by quantification of the radiolabeled purine compounds produced by incubation with radiolabeled sodium formate. For comparison, de novo purine synthesis in normal controls, in normouricosuric autistic patients, and cells from patients with other disorders in which excessive uric acid excretion is seen was also measured. These experiments showed that de novo purine synthesis is increased approx. 4-fold in the hyperuricosuric autistic patients. This increase was less than that found in other hyperuricosuric disorders. No unusual radiolabeled compounds (such as adenylosuccinate) were detected in these experiments, and no gross deficiencies of radiolabeled nucleotides were seen. However, the ratio of adenine to guanine nucleotides produced by de novo synthesis was found to be lower in the cells of the hyperuricosuric autistic patients than in the normal controls or the cells from patients with other disorders. These results indicate that the hyperuricosuric subclass of autistic patients have increased de novo purine synthesis, and that the increase is approximately that expected for the degree of urate overexcretion when compared to other hyperuricosuric disorders. No particular enzyme defect was suggested by either gross deficiency of a radiolabeled compound or the appearance of an unusual radiolabeled compound, and no potentially neurotoxic metabolites were seen. Although an enzyme defect responsible for the accelerated purine synthesis was not identified, the abnormal ratio of adenine to guanine nucleotides suggests a defect in purine nucleotide interconversion.

Autistic Disorder↗