OBJECTIVE: To establish whether there is a role for advertising in the promotion of the Breast Screening Programme and what the role of advertising might be. DESIGN: Four hundred and sixty questionnaires were completed by women attending their breast screening appointment. Quantitative and qualitative data were collected from the static unit at Calder Street and the mobile unit in Govan. SETTING: The advertising (budget 30,000 Pounds) campaign ran over an eight week period in the Govan, Paisley Road West and Cardonald areas of Glasgow. Media used included press advertising, The Glasgow Underground, adshells, bus advertising (interiors) and poster distribution via local outlets. RESULTS: Forty-two per cent of the sample were aware of the campaign. Ninety-seven per cent liked the campaign images. Eighty eight per cent felt that breast screening should be advertised more. Screening uptake increased in the areas covered by the advertising campaign. Govan -58%-71% and Ibrox (Paisley Road West and Cardonald) -59%-61%. CONCLUSION: Women were very supportive of the role of advertising for the Breast Screening Programme. In particular they found the campaign images and messages reassuring, supportive and credible. Their views suggest that the role of advertising should be: To raise awareness of the service To make women more conscious of the benefits of screening To change public perceptions of the screening process However, it is recognised that a fully integrated approach is required for the promotion of the service to account for the improvement in uptake, as advertising cannot be expected to work in isolation.

Advertising↗

PubMed1999

Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates.

Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we determined the effect of different Bps on incorporation of [(14)C]mevalonate (MVA), [(14)C]IPP, and [(14)C]dimethylallyl pyrophosphate (DMAPP) into polyisoprenyl pyrophosphates in a homogenate of bovine brain. HPLC analysis revealed that the three intermediates were incorporated into FPP and geranylgeranyl pyrophosphate (GGPP). In contrast to clodronate, the nitrogen-containing Bps (NBps), alendronate, risedronate, olpadronate, and ibandronate, completely blocked FPP and GGPP formation and induced in incubations with [(14)C]MVA a 3- to 5-fold increase in incorporation of label into IPP and/or DMAPP. Using a method that could distinguish DMAPP from IPP on basis of their difference in stability in acid, we found that none of the NBps affected the conversion of [(14)C]IPP into DMAPP, catalyzed by IPP isomerase, excluding this enzyme as target of NBp action. On the basis of these and our previous findings, we conclude that none of the enzymes up- or downstream of FPP synthase are affected by NBps, and FPP synthase is, therefore, the exclusive molecular target of NBp action.

Animals↗

PubMed1999

Expression of the T cell antigen receptor zeta chain following activation is controlled at distinct checkpoints. Implications for cell surface receptor down-modulation and re-expression.

The multisubunit T cell antigen receptor (TCR) is involved in antigen recognition and signal transduction, leading to T cell activation and rapid down-modulation of the cell surface expressed TCRs. Although the levels of TCR cell surface expression are pivotal to the efficiency and duration of the immune response, the molecular mechanisms controlling TCR down-modulation and re-expression upon activation, remain obscure. Here, we provide a biochemical characterization of the regulatory mechanisms governing TCR expression following long-term T cell activation. We focused primarily on the TCR zeta chain, as this is considered the limiting factor in TCR complex formation and transport to the cell surface. We found that following TCR-mediated activation zeta mRNA is up-regulated by a transcription-dependent mechanism. Concomitantly, zeta protein levels are modified according to a biphasic pattern: rapid degradation coinciding with TCR cell surface down-regulation, followed by a rebound to normal levels 24 h subsequent to T cell activation. Even though there are adequate levels of all the TCR subunits within the cell following 24 h of activation, TCR cell surface expression remained very low, provided the activating antibody is continuously present. Correlative with the latter, we detected a previously undescribed monomeric form of the zeta chain. This form could be indicative of adverse endoplasmic reticulum conditions affecting correct protein folding, dimerization, and TCR assembly, all critical for optimal receptor surface re-expression. Cumulatively, our results indicate that the levels of TCR expression following activation, are tightly controlled at several checkpoints.

Animals↗

PubMed1999

[Many faces of parvovirus].

2 women, aged 31 and 37 years, respectively, suffered from acute febrile illness due to acute infection with human parvovirus B19. 1 also had a maculopapular rash and articular symptoms after her fever stopped, a clinical picture typical of erythema infections. The other had leukopenia and thrombocytopenia and had received dipyrone. Although acute infection with human parvovirus usually occurs in childhood, it may also occur in adults, with protean manifestations.

Adult↗

PubMed1999

A physician's struggle to close Pandora's box.

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Adult↗

PubMed1999

[Distal Miyoshi muscular dystrophy in a Moroccan patient].

BACKGROUND: Muscular dystrophy usually involves a deficiency in the proximal muscles. We report a case of distal muscular dystrophy in a Moroccan patient. CASE REPORT: A 21-year-old Moroccan complained of progressive onset weakness of the lower limbs and frequent falls. The neurological examination demonstrated amyotrophy involving both legs and almost complete regression of the posterior muscle compartment. Clinical findings were confirmed by muscle scans. The electromyogram showed a progressive myogenic process. Creatine kinase was elevated. The severe dystrophic aspect was evidenced at muscle biopsy and led to the diagnosis of distal Miyoshi muscular dystrophy. DISCUSSION: Miyoshi muscular dystrophy, a distal myopathy transmitted by autosomal recessive inheritance, is usually observed in young adults who present characteristic amyotrophy of the posterior leg muscles. The proximal muscles of the lower and upper limbs may become involved during the disease course. Approximately one-third of the patients require wheel chair assistance after 10 years. Creatine kinase levels are constantly elevated. The differential diagnosis with other muscular dystrophies predominating in the distal muscles, particularly Steinert's myotonic dystrophy and inclusion body myositis, is discussed.

Adult↗

PubMed1999

Medical simulation is wave of the future, U of O doctors say.

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Curriculum↗

PubMed1999

Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo.

Bisphosphonates, synthetic compounds which suppress bone resorption, are used in the treatment of skeletal disorders. Their mode of action and intracellular targets have not yet been identified. Recent evidence suggested that enzymes of the mevalonate pathway are the potential targets. In this study, we examined the effect of four potent nitrogen (N)-containing bisphosphonates, clodronate and NH2-olpadronate, an inactive analogue of olpadronate, on isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase, geranylgeranyl pyrophosphate synthase, and protein geranylgeranyl transferase I activity. We found that all N-containing bisphosphonates inhibited isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity dose dependently with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo, whereas clodronate and NH2-olpadronate had no effect. Furthermore, none of the bisphosphonates tested affected geranylgeranyl pyrophosphate synthase or geranylgeranyl transferase I activity. Our study reveals for the first time the intracellular target of N-containing bisphosphonates and supports the view that all bisphosphonates do not share the same molecular mechanism of action.

Animals↗

PubMed1999

A man who borrowed cars.

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Aneurysm, Ruptured↗

PubMed1999

Exploring differences between subgroups of multiple sclerosis patients in health-related quality of life.

Health-related quality of life (HRQoL) questionnaires finding increasing use in medicine, but still only few publications have reported on HRQoL in patients with multiple sclerosis (MS). Because of its progressive and disabling nature, the disease has a considerable effect on HRQoL. To facilitate the interpretation of scores for the heterogeneous MS population, we explored differences between subgroups of MS out-patients (n = 90) on two HRQoL instruments: the Medical Outcome Study Short Form-36 and the Disability and Impact Profile. Three disease-related characteristics were studied: severity of MS, time since diagnosis, and MS progression in the past 6 months. The results show that each of these have an effect on one or more aspects of HRQoL. Thus, the longer the disease duration and the more severe and progressive the MS, the lower is the patient's experienced HRQoL.

Adult↗

PubMed1999

Surgical resection alone is effective treatment for ovarian immature teratoma in children and adolescents: a report of the pediatric oncology group and the children's cancer group.

OBJECTIVE: In both adult women and children the potential for malignant recurrence from ovarian immature teratoma has prompted the standard use of chemotherapy after complete resection of the primary tumor. The efficacy of postoperative chemotherapy in children and adolescents with ovarian immature teratoma, however, has not been established. A pediatric intergroup trial (INT 0106) was designed to determine the need for postoperative chemotherapy in patients with ovarian immature teratoma after management with surgical resection only. STUDY DESIGN: Between 1990 and 1995, 44 patients with completely resected ovarian immature tumor and without postoperative chemotherapy, who were able to undergo assessment, were accrued. Tumor tissue was evaluated by central pathology review to confirm diagnosis and determine tumor grading of immature neural elements. Patients were followed carefully for recurrence of disease with appropriate diagnostic imaging and serum marker studies. RESULTS: Thirty-one patients had pure ovarian immature teratoma with a tumor grade of 1 (n = 17), 2 (n = 12), or 3 (n = 2). Age at diagnosis ranged between 1.5 and 15 years (median, 10). Of the 29 patients studied, the serum alpha-fetoprotein level was elevated in 10 (34%); the median level was 25 ng/ml. Thirteen patients had ovarian immature teratoma plus microscopic foci of yolk sac tumor. Tumor grade was 1, 2, or 3 in 1, 6, and 6 patients, respectively. Age ranged between 6 and 20 years (median, 12). In the 12 patients evaluated for serum alpha-fetoprotein, 10 (83%) had elevated levels; the median level was 262 ng/ml. The 4-year event-free and overall survival for the ovarian immature teratoma group and for the ovarian immature teratoma plus yolk sac tumor group was 97.7% (95% confidence interval, 84.9%-99.7%) and 100%, respectively. The only yolk sac tumor relapse occurred in a child with ovarian immature teratoma and yolk sac tumor who was then treated with chemotherapy and is alive and free of disease 57 months after recurrence. CONCLUSION: The results of this study suggest that surgery alone is curative for most children and adolescents with resected ovarian immature teratoma of any grade, even when elevated levels of serum alpha-fetoprotein or microscopic foci of yolk sac tumor are present. This experience strongly supports avoiding the long-term effects of chemotherapy in most children with ovarian immature teratoma by reserving postoperative therapy for cases with relapse.

Adolescent↗

PubMed1999

Preoperative ultrasound assessment of adnexal masses in premenopausal women.

OBJECTIVES: This study was undertaken to determine the accuracy of preoperative transvaginal ultrasound in predicting ovarian histopathology in premenopausal women. METHODS: A retrospective cohort study was performed from reproductive-age women that underwent removal of an ovarian cyst between May 1990 and April 1998. RESULTS: Of the 120 consecutive patients identified, 19 did not meet inclusion criteria. Pathologic diagnosis confirmed endometriomas (n = 55), mature teratoma (n = 25), serous cystadenoma (n = 18), persistent corpus luteum (n = 7) and other (n = 5). The primary preoperative transvaginal ultrasound impression was accurate in most cases (endometrioma: 85%, mature teratoma: 86%, serous cystadenoma: 80%). CONCLUSION: Endometriomas and mature cystic teratomas can be predicted with a moderate degree of accuracy by preoperative ultrasound.

Adnexal Diseases↗

PubMed1999

Pharmacokinetics of doxepin in subjects with pruritic atopic dermatitis.

BACKGROUND: Doxepin applied topically by itself or in combination with triamcinolone acetonide is a safe and effective treatment for atopic dermatitis. OBJECTIVE: We evaluated the pharmacokinetic profile of doxepin and desmethyldoxepin after topical application of doxepin hydrochloride 5% cream alone or in combination with 0.025% triamcinolone acetonide (doxepin/TAC). METHODS: Twenty-four subjects with atopic dermatitis received either doxepin or doxepin/TAC cream 4 times daily for 7 days in a randomized, double-blind, controlled trial. Serum samples were obtained and pharmacokinetic parameters estimated from the dose-normalized serum concentrations of doxepin and desmethyldoxepin. Efficacy and adverse experiences were determined by physician and subject evaluations. RESULTS: Pharmacokinetic parameters (K(e ), t(1/2 ) and AUC) calculated in 9 subjects (doxepin/TAC = 4 subjects, doxepin = 5 subjects) with detectable serum concentrations were similar for both groups. Pruritus relief and lessening of pruritus severity were significantly greater with doxepin/TAC than doxepin alone. CONCLUSION: Topically applied doxepin is safe and effective therapy for pruritus.

Administration, Topical↗

PubMed1999

Comparison of 2 myocardial velocity gradient assessment methods during dobutamine infusion with Doppler myocardial imaging.

Myocardial velocity gradient (MVG) has been shown to be the best quantitative parameter for the detection of ischemic myocardium during dobutamine infusion with the use of Doppler myocardial imaging. MVG has been previously assessed by velocity measurements across the thickness of the myocardium at the time of visually selected maximal color brightness (thickness-velocity plot method). We hypothesized that MVG could be assessed by velocity measurements throughout the cardiac cycle in the subendocardium parallel to the endocardial boundary to the left ventricular cavity and in the subepicardium parallel to the epicardial boundary (time-velocity plot method). This study was designed to compare MVG obtained from the thickness-velocity plot method and from the time-velocity plot method in quantifying dobutamine-induced changes in myocardial wall motion in 8 phases of the cardiac cycle on color M-mode Doppler myocardial imaging recordings of the left ventricular posterior wall performed in 8 conscious dogs at baseline and at steady state during dobutamine infusion (10 microg/kg per minute). For both methods, MVG was considered present if its mean value was significantly different from zero and if endocardial and epicardial velocities were significantly different. There was close agreement between the 2 methods. MVG was present during the preejection period, systole, rapid ventricular filling, and atrial contraction. Dobutamine induced a significant increase in MVG during the preejection period (from 2.64 +/- 0.83 to 4.05 +/- 0.81 seconds-1 ), systole (from 2.14 +/- 0.59 to 6.08 +/- 2.20 seconds-1 in early systole, from 1.90 +/- 1.06 to 5.31 +/- 2.95 seconds-1 in mid systole, from 1.37 +/- 0.57 to 2.44 +/- 0.53 seconds-1 in end systole), and rapid ventricular filling (from 3.06 +/- 1.12 to 7.82 +/- 2.58 seconds-1 ), related to a greater rise in endocardial than in epicardial velocities. The time-velocity plot method showed that ejection and diastole were 11% and 28% decreased during dobutamine infusion, respectively, as heart rate was 31% increased. Thus according to our quantitative criteria, both MVG assessment procedures enabled objective interpretation of dobutamine effects on left ventricular wall motion. In addition, the time-velocity plot method provided automatic detection of peak velocity, timing, and duration of wall velocity changes over time.

Animals↗