Decision analysis.
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Decision Support Techniques↗
Biomedical subjects
A Lee
Publications and source records attributed to A Lee.
Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid.
OBJECTIVES: To determine and compare the gastrointestinal (GI) responses of young adults following consumption of 45 g sucrose, 20, 35 and 50 g xylitol or erythritol given as a single oral, bolus dose in a liquid. DESIGN: The study was a randomized, double-blind, placebo-controlled study. SUBJECTS: Seventy healthy adult volunteers aged 18-24 years were recruited from the student population of the University of Salford. Sixty-four subjects completed the study. INTERVENTIONS: Subjects consumed at home without supervision and in random order, either 45 g sucrose or 20, 35 and 50 g erythritol or xylitol in water on individual test days, while maintaining their normal diet. Test days were separated by 7-day washout periods. Subjects reported the prevalence and magnitude of flatulence, borborygmi, bloating, colic, bowel movements and the passage of faeces of an abnormally watery consistency. RESULTS: Compared with 45 g sucrose, consumption of a single oral, bolus dose of 50 g xylitol in water significantly increased the number of subjects reporting nausea (P<0.01), bloating (P<0.05), borborygmi (P<0.005), colic (P<0.05), watery faeces (P<0.05) and total bowel movement frequency (P<0.01). Also 35 g of xylitol increased significantly bowel movement frequency to pass watery faeces (P<0.05). In contrast, 50 g erythritol only significantly increased the number of subjects reporting nausea (P<0.01) and borborygmi (P<0.05). Lower doses of 20 and 35 g erythritol did not provoke a significant increase in GI symptoms. At all levels of intake, xylitol produced significantly more watery faeces than erythritol: resp. 50 g xylitol vs 35 g erythritol (P<0.001), 50 g xylitol vs 20 g erythritol (P<0.001) and 35 g xylitol vs 20 g erythritol (P<0.05). CONCLUSIONS: When consumed in water, 35 and 50 g xylitol was associated with significant intestinal symptom scores and watery faeces, compared to the sucrose control, whereas at all levels studied erythritol scored significantly less symptoms. Consumption of 20 and 35 g erythritol by healthy volunteers, in a liquid, is tolerated well, without any symptoms. At the highest level of erythritol intake (50 g), only a significant increase in borborygmi and nausea was observed, whereas xylitol intake at this level induced a significant increase in watery faeces.
Adolescent↗
Endotoxin levels in rural Thai and urban Singaporean homes.
BACKGROUND: Exposure to dust endotoxin and allergens in early childhood may influence the development of allergic diseases. AIMS: This study aimed to evaluate dust endotoxin and dust mite allergens in urban Singapore and rural Thai homes of young children and study potential environmental influences. METHODS: Mattress dust endotoxin and Der p 1, Der f 1, group 2 (Der f 2 and Der p 2) and Blo t 5 allergen levels were quantified in 101 infant mattress dust samples, 51 from urban Singapore and 50 from rural Thailand. Comprehensive questionnaires on the home environment and cleaning practices were completed. RESULTS: Endotoxin levels in rural Thailand were significantly higher than in urban Singapore (geometric mean 26,334.12 +/- 4.60 and 18,377.85 +/- 2.52 endotoxin units/g, respectively; p = 0.032). In contrast, higher levels of Der f 1 (p = 0.02), group 2 (p < 0.01) and Blo t 5 (p < 0.01) allergens were found in Singapore homes compared with rural Thai homes. Multiple logistic regression analysis showed that the use of detergents (p = 0.001) and disinfectants (p = 0.024) to clean floors and mattress protectors (p = 0.021) were independently associated with lower endotoxin levels. CONCLUSION: Endotoxin levels are higher in rural compared with urban homes in South East Asia. The reverse was true for dust mite allergen levels. Certain identifiable home environmental conditions and practices accounted for the differences in endotoxin levels.
Air Pollution, Indoor↗
Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations with rheumatoid arthritis.
The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1*09 and DRB1*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility.
Alleles↗
Long-term antibiotics for preventing recurrent urinary tract infection in children.
BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms include fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment consists of a course of antibiotics. Due to acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. OBJECTIVES: To determine the efficacy and harms of long-term antibiotics to prevent recurrent UTI in children. SEARCH STRATEGY: We searched without language restriction MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, the Cochrane Renal Group's Specialised Register, reference lists of review articles and contacted content experts. Date of most recent search: January 2006 SELECTION CRITERIA: Randomised comparisons of antibiotics with other antibiotics, placebo or no treatment to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. A random-effects model was used to estimate relative risk (RR) and risk difference (RD) for recurrent UTI with 95% confidence intervals (CI). MAIN RESULTS: Eight studies (618 children) were identified, five (406) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied from 10 weeks to 12 months. Compared to placebo/no treatment, antibiotics reduced the risk of repeat positive urine culture (RR 0.44, 95% CI 0.19 to 1.00; RD -30%, 95% CI -56% to -4%) No side effects were reported. One study reported that nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). The other study found cefixime was more effective in preventing recurrent UTI than nitrofurantoin (RR 0.74, 95% CI 0.13 to 4.10; RD -3%, 95% CI -17% to -12%). However, 62% of patients receiving cefixime experienced an adverse reaction during the first six months of treatment (18/29) while only 26% (8/31) of patients receiving nitrofurantoin reported an adverse reaction. AUTHORS' CONCLUSIONS: Large, properly randomised, double blinded studies are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.
Acute Disease↗
Effectiveness of a Chinese herbal medicine preparation in the treatment of cough in uncomplicated upper respiratory tract infection: a randomised double-blinded placebo-control trial.
BACKGROUND: Rigorous scientific and well-designed clinical trials to evaluate the effect of traditional Chinese medicine (TCM) is lacking. We, therefore, designed this study to evaluate the effectiveness of a commonly used TCM preparation in treating acute cough of uncomplicated URTI in adults and to search for a safe, effective and affordable alternative treatment for this common condition. METHODS: A randomised, double-blinded, placebo-control study comparing this TCM preparation with a placebo was conducted in 82 patients who attended the Family Medicine Training Centre, Prince of Wales Hospital, Hong Kong between November and December, 2003. The TCM herbal preparation includes nine commonly used TCM herbs for cough such as chuanbei, fangfeng, jiegeng, gancao and baibu (see Table 1). The treatment lasted for 5 days and patients were followed-up for another 6 days. Patients were asked to fill in a cough score and validated Leicester cough questionnaire (LCQ). RESULTS: 62 patients (75.6%) had completed the trial and no adverse effects were reported. Both intervened and control groups had improved in cough score and LCQ in the follow-up period, despite no overall statistical significance was observed in the differences of scores between the two groups. Women taking TCM had significantly fewer problems with sputum production (p = 0.03) and older subjects (>35 years of age) reported a significant improvement in hoarseness (p = 0.05) when compared to those using placebo. CONCLUSION: TCM was well-tolerated and received among the Hong Kong Chinese population. This TCM preparation appeared to have some benefits in the treatment of cough. Future research on TCM should concentrate more on commonly encountered conditions such as UTRI and cough. Our experience on the sensitivity of assessment tools used in detecting subtle differences in an otherwise self-limiting illness and clinical trial methodology when applying the underlying theory of how TCM works in disease management was invaluable.
Journal Article↗
High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33.
We have completed a genome wide linkage scan using >5700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD>16), regions with LOD>2.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.
Arthritis, Rheumatoid↗
Epithelial and connective tissue cell CTGF/CCN2 expression in gingival fibrosis.
Gingival overgrowth is a side effect of certain medications and occurs in non-drug-induced forms either as inherited (human gingival fibromatosis) or idiopathic gingival overgrowth. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin; the least fibrotic lesions are caused by cyclosporin A; and intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Connective tissue growth factor (CTGF/CCN2) expression is positively related to the degree of fibrosis in these tissues. The present study has investigated the hypothesis that CTGF/CCN2 is expressed in human gingival fibromatosis tissues and contributes to this form of non-drug-induced gingival overgrowth. Histopathology/immunohistochemistry studies showed that human gingival fibromatosis lesions are highly fibrotic, similar to phenytoin-induced lesions. Connective tissue CTGF/CCN2 levels were equivalent to the expression in phenytoin-induced gingival overgrowth. The additional novel observation was made that CTGF/CCN2 is highly expressed in the epithelium of fibrotic gingival tissues. This finding was confirmed by in situ hybridization. Real-time polymerase chain reaction (PCR) analyses of RNA extracted from drug-induced gingival overgrowth tissues for CTGF/CCN2 were fully consistent with these findings. Finally, normal primary gingival epithelial cell cultures were analysed for basal and transforming growth factor beta1 (TGF-beta1) or lysophosphatidic acid-stimulated CTGF/CCN2 expression at protein and RNA levels. These data indicate that fibrotic human gingival tissues express CTGF/CCN2 in both the epithelium and connective tissues; that cultured gingival epithelial cells express CTGF/CCN2; and that lysophosphatidic acid further stimulates CTGF/CCN2 expression. These findings suggest that interactions between epithelial and connective tissues could contribute to gingival fibrosis.
Adult↗
The effects on maternal anxiety of two-dimensional versus two- plus three-/four-dimensional ultrasound in pregnancies at risk of fetal abnormalities: A randomized study.
OBJECTIVE: To test the hypothesis that the use of two-dimensional (2D) ultrasonography with three-dimensional/four-dimensional (3D/4D) ultrasonography can reduce anxiety to a greater extent in women at risk of having a fetus with congenital abnormalities than the use of 2D ultrasonography alone. METHODS: A total of 124 women attending the prenatal diagnostic clinic of a teaching hospital were randomized into the intervention group (2D ultrasonography followed by 3D/4D ultrasonography) or control group (2D ultrasonography alone). The primary outcome was maternal anxiety levels, which were assessed by the Spielberger state-trait anxiety inventory. We measured the anxiety levels in all women at the first visit, at around 18 weeks' gestation (immediately after ultrasound examinations) and at 28 weeks' gestation. RESULTS: A short-term reduction of the state-anxiety score (by around 2 points) from the first visit to after ultrasound examinations was observed in both the intervention group and the control group. Unexpectedly, a small increase in the state-anxiety score from the first visit to 28 weeks' gestation was observed in the intervention group but not in the control group, though there was no significant difference in the changes between the two groups. Repeated measures ANOVA (analysis of variance) also showed that there was no significant interaction effect between groups and time of assessment on the state-anxiety scores (F = 1.072 and P = 0.344). About 80% of women reported a better understanding that their baby was normal after viewing 3D rather than 2D images. CONCLUSION: This randomized study indicates that the addition of 3D/4D ultrasound does not cause a significant reduction in maternal anxiety in pregnancies at risk of fetal abnormalities compared with conventional 2D ultrasound alone.
Adult↗
What are the barriers faced by general practitioners in treating depression and anxiety in Hong Kong?
Barriers faced by general practitioners in Hong Kong to manage patients with depression and anxiety disorders and their association with postgraduate qualification in family medicine were studied. Postal questionnaires were sent to 179 family medicine tutors affiliated with a university in Hong Kong with a response rate of 64.2%. 'Too time consuming' was the largest barrier for these physicians in treating patients with depression and anxiety. General practitioners without higher qualifications in family medicine were significantly more likely to report 'lack of confidence', 'lack of experience' and 'lack of supporting service' as being the barriers in treating patients with depression and anxiety. Our results showed that time constraint is an important barrier for general practitioners in managing patients with depression and anxiety in Hong Kong. Having a higher qualification in family medicine may reduce the barriers of having lack of confidence and experience in these physicians.
Adult↗
The detection of human herpesvirus-8 DNA in plasma and peripheral blood mononuclear cells in adult patients with pityriasis rosea by polymerase chain reaction.
BACKGROUND: Herpesvirus-like particles have been reported to be detectable by electron microscopy in lesional biopsy of patients with pityriasis rosea (PR). We report a study investigating the association of PR with human herpesvirus-8 (HHV-8) infection. METHODS: Our setting is a teaching clinic affiliated to a university. We recruited eight patients aged 28-47 years (mean: 34.5 years) diagnosed with PR during a one-year period. We collected acute blood specimens at presentation and convalescent blood specimens three to four weeks later. We also collected skin scrapings from the herald patch where present and from truncal secondary lesions. RESULTS: We detected HHV-8 DNA by a nested PCR (polymerase chain reaction) targeting, respectively, a 233-bp and a 160-bp fragment of ORF 26. PCR for HHV-8 DNA was negative in the peripheral blood mononuclear cells and plasma of acute and convalescent specimens of all patients, and negative in all skin scrapings. We detected anti-HHV-8 IgG and IgM antibodies by the indirect immunofluorescence. Four patients had IgG antibodies against HHV-8, but with no significant rise of titre. None were positive for anti-HHV-8 IgM antibody. CONCLUSION: We conclude that PR is not associated with HHV-8 infection.
Adult↗
Ventilatory and intensive care requirements following oesophageal resection.
INTRODUCTION: The aim of this study was to analyse the results of early postoperative extubation following oesophagectomy. PATIENTS AND METHODS: All patients who had undergone oesophageal resection between 1994 and 2001 were identified from a prospectively collected database. Their records were then reviewed in order to analyse morbidity and mortality along with intensive care unit (ICU) and ventilatory requirements. All patients were extubated immediately following surgery and monitored on a surgical high dependency unit (HDU). RESULTS: A total of 98 resections were undertaken (76 men; mean age, 64.3 years; range, 40-80 years). Surgical procedures were Ivor-Lewis (71), left thoraco-abdominal (15) and transhiatal (12) oesophagectomies. Overall, 8 patients died and 13 patients had anastomotic leaks. Sixteen patients required ventilation and admission to ICU, of whom 5 died. Three patients died on HDU following an elective decision not to transfer to ICU. Reasons for ventilation and ICU admission were anastomotic leaks (6), respiratory problems (6), left ventricular failure (1), cardiac arrest (1), small bowel herniation through the hiatus (1) and ischaemic stomach requiring revision of anastomosis (1). No patient required ventilation and admission to ICU within 48 h of original surgery. CONCLUSIONS: Patients undergoing oesophageal resection can be safely managed on a surgical HDU without routine postoperative ventilation. Although ventilation and ICU will be required in a significant number due to postoperative complications, this is unlikely to occur in the first 48 h. The requirement for an ICU bed to be available on the day of surgery should, therefore, no longer be considered necessary. This has important implications for the scheduling of elective oesophageal surgery.
Adenocarcinoma↗
Open Rives-Stoppa ventral hernia repair made simple and successful but not for everyone.
BACKGROUND: The Rives-Stoppa (RS) repair of ventral incisional hernias (VIHR) is technically difficult. It involves the retromuscular placement of mesh anterior to the posterior fascia and the primary closure of the anterior fascia. Recurrence rates are 0-8%. We proposed that the operation could be done with equal success by placing the mesh in an intraperitoneal position and primarily closing the fascia anterior to the mesh. METHODS: 81 patients who had undergone an open RS-VIHR with intraperitoneal mesh were evaluated for hernia recurrence and factors associated with recurrence. RESULTS: 55 women and 26 men (mean BMI 38+/-9) underwent RS-VIHR (mean age 49+/-11 years). Of these patients, 44 (54%) had a prior VIHR, 30 (37%) had an incarcerated hernia and 34 (42%) had multiple fascial defects. PTFE was used in 83% and Prolene in 12%. Average LOS was 5.8+/-12 days. All received perioperative intravenous antibiotics and 28% were discharged on oral antibiotics. Follow-up averaged 30+/-24 months. Recurrent VIH developed in 12/81 (15%), with three occurring after removal of infected mesh and one after a laparotomy. Excluding these four, the recurrence rate was 10%. There was no correlation between hernia recurrence and age, BMI, hernia size, number of prior repairs, or LOS (t-test p>0.05). Hernia recurrence did not correlate with gender, prior peritoneal contamination, incarceration, multiple defects, adhesions, mesh type, oral antibiotics, cardiac disease, diabetes, tobacco use, or seroma (X(2) p>0.05). Those with a wound infection and/or abscess formation had a significantly higher recurrent hernia rate (60% vs. 8%, X(2) p<0.001). Patients with pulmonary disease had a significantly higher recurrence rate (50% vs. 12%, X(2) p=0.01). CONCLUSIONS: RS-VIHR with intraperitoneal mesh is a successful and less technically challenging method of repair than prior modifications. Aggressive efforts to identify infection and treat early may prevent abscess formation and subsequent recurrent hernia. Patients with chronic pulmonary disease have an unacceptably high recurrence rate and should not be considered as candidates for elective RS-VIHR.
Adult↗
Force level independent representations of predictive grip force-load force coupling: a PET activation study.
The existence of forward internal models is a fundamental principle in theories of predictive motor control. There are indications that internal models are represented in the cerebellum. So far, no conclusive data exist on automated procedures involving predictive motor behavior. In particular, it is unknown whether single or multiple task-specific internal models handle the broad range of behavioral situations in which they occur. Using H2(15)O PET in eight subjects, we examined predictive motor control in an automated grip force-load force coupling task at three differing load force levels. In the experimental condition, subjects pulled a grasped object against an isometric resistance while simultaneously producing anticipatory grip forces. There were three control conditions (pull force isolated; grip force isolated; motor rest). A 2 x 2 factorial design was chosen to reveal the interaction effect of grip force-pull force coupling. The factors were pull force (with/without) and grip force (with/without). Grip and load forces were well matched between experimental and control conditions. Conjunction inference and interaction analyses identified force coupling related activity in the ipsilateral posterior cerebellum that was independent of force levels. Interaction effects were also identified in the anterior cingulate and frontal association regions, the right caudate nucleus, and the left lingual gyrus. These data demonstrate the existence of modular representations for predictive force coupling, with the ipsilateral cerebellum playing a major role. Moreover, the data implicate that the representations for predictive force control are applicable to a range of different environmental affordances.
Brain↗
Prenatal magnetic resonance imaging as a useful adjunctive to ultrasound-enhanced diagnosis in case of a giant foetal tumour of the neck.
Large cervical masses in the prenatal period are rare and can cause life threatening situations after birth. All available diagnostic techniques should therefore be used to determine the best mode of delivery in the case of such malformation. A large cervical mass was detected by ultrasound in a 41-year-old women, gravida 4, para 3, at 29 + 5 weeks of gestation. US imaging was most consistent with the diagnosis of a large cervical teratoma, but it was not possible to sufficiently evaluate the cervical anatomy of the oropharynx and trachea. An MRI scan demonstrated a distorted oropharynx and a trachea displaced to the right and posteriorly, but not detectable from the middle of the neck up to the larynx. Based on these facts, an EXIT procedure was planned and performed at 30 + 5 weeks of gestation. Foetal MRI provided valuable anatomical information for all specialists deciding on the indication and the pre-therapeutic planning of the EXIT procedure.
Adult↗
Does pulmonary rehabilitation give additional benefit over tiotropium therapy in primary care management of chronic obstructive pulmonary disease? Randomized controlled clinical trial in Hong Kong Chinese.
OBJECTIVE: To evaluate whether multidisciplinary pulmonary rehabilitation programme (PRP) provides additional benefit over tiotropium therapy in managing chronic obstructive pulmonary disease (COPD) in primary care. DESIGN: A randomized controlled trial to analyse the difference in outcomes of COPD patients receiving tiotropium plus PRP vs. tiotropium treatment alone. SETTING: Two primary care teaching clinics affiliated with a university which serves a population of 600,000. PARTICIPANTS: Fifty primary care COPD patients. METHODS: Fifty subjects underwent spirometry and their status of COPD was confirmed by using the Vitalograph Gold Standard. They were then assessed by the 6-min walking distance (6MWD), Peak Visual Analogue Scale (Peak VAS) and Chronic Respiratory Disease Questionnaire (CRQ). All subjects were given tiotropium to optimize their treatment. After a 6-week period, half were randomized to the intervention group (i.e. receiving PRP), whereas the rest were randomized to control group which received only medication. Spirometry, 6MWD, Peak VAS and CRQ were performed in both groups at 6 weeks, 12 weeks and 3 months. OUTCOMES: Spirometry, 6MWD, Peak VAS and CRQ. RESULTS: Significant improvement (P < 0.05) was seen in 6MWD, symptoms of dyspnoea measured by Peak VAS and CRQ. The improvement was sustained at 3-month follow-up. However, no additional significant improvement was seen in the intervention group when compared with control. CONCLUSION: Tiotropium therapy has improved health outcomes in COPD patients in primary care settings. A 6 weekly PRP did not give any additional benefits in patients already given tiotropium.
Aged↗
Atypical presentations of pityriasis rosea: case presentations.
Atypical cases of pityriasis rosea (PR) are fairly common and less readily recognized than typical eruptions. We present four patients for whom we believe atypical PR is the most likely diagnosis. A 33-year-old man had purpuric lesions bilaterally on the legs with classical rash on the trunk. A 28-year-old woman had intensely pruritic and urticarial lesions. A 10-year-old girl had hundreds of small papular lesions 1-3 mm in size. A pregnant woman aged 26 had oral haemorrhagic ulcers with classical PR eruption on her trunk. The oral ulcers erupted and remitted at the same time as the generalized eruption. We reviewed the literature and proposed a classification based on rash morphology, rash size, rash distribution, number of lesions, site of lesions, severity of symptoms and course of the eruption. We believe that it is difficult to make a clear division to define typical and atypical PR, and that it is important not to ascribe any unusual or atypical skin eruption with PR unless other dermatoses have been excluded.
Adult↗
The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development.
The docking protein FRS2alpha is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2alpha in vivo remains unknown. In this report, we show that Frs2alpha-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8. We demonstrate that FRS2alpha is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2alpha also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2alpha-null embryos. These experiments underscore the critical role of FRS2alpha in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis.
Animals↗