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Genetic clues to the origin of the apple.

Molecular genetic markers complement archaeological, breeding and geographical investigations of the origins, history and domestication of plants. With increasing access to wild apples from Central Asia, along with the use of molecular genetic markers capable of distinguishing between species, and explicit methods of phylogeny reconstruction, it is now possible to test hypotheses about the origin of the domesticated apple. Analyses of nuclear rDNA and chloroplast DNA (cpDNA) sequences indicate that the domesticated apple is most closely related to series Malus species. Moreover, the occurrence of a shared 18-bp duplication in the cpDNAs of wild and cultivated apple supports the close relationship between them. Hypotheses about the hybridization and the origin of the domesticated apple cannot be rejected completely until more variable, phylogenetically informative markers are found.

DNA, Ribosomal Spacer↗

The embryologic development of the human lateral pterygoid muscle and its relationships with the temporomandibular joint disc and Meckel's cartilage.

The morphology of the developing lateral pterygoid muscle and its relationships with the temporomandibular joint disc and Meckel's cartilage were studied in 16 human embryos and fetuses ranging in age from 5 weeks to 14 weeks. All the temporomandibular joint structures and the lateral pterygoid muscle assumed their adult shapes by the 14th week of fetal life. At this stage, the lateral pterygoid muscle is a complex structure with several aponeuroses dividing the muscle into three main parts: superior, inferomedial, and inferoanterior. The superior part is attached to the disc superiorly and medially. The inferomedial part inserts into the anteromedial aspect of the condyle and disc. The inferoanterior portion is attached to the anterior aspect of the condyle. Anteriorly, the buccal nerve and associating blood vessels traverse the muscle in a mediolateral direction, dividing it into superior (small) and inferior (large) compartments. Posteriorly, the muscle remains intact with no separation. The lateral pterygoid muscle fibers show no direct attachment to Meckel's cartilage at any stage of development.

Cartilage↗

A critical look at transition ratings.

Patient ratings of the extent to which they have improved or deteriorated-transition ratings-are extremely common in clinical practice and clinical research. However, some have raised concerns about transition rating validity. We examined data from three studies, each of which explored the relation between a disease-specific health-related quality of life (HRQL) instrument and transition ratings corresponding to instrument domains. For instance, we looked at the relation between differences in score on the dyspnea domain of the Chronic Respiratory Questionnaire at Times 1 (pre score) and 2 (post score), and the patients' global rating of change in dyspnea at time 2. We restricted ourselves to comparisons in which the correlation between the HRQL instrument domain and the corresponding global rating of change was at least 0.5. A perfectly valid transition rating would show correlations with the pre and post scores of equal magnitude and opposite sign, and regression coefficients of similar magnitude. Of 14 comparisons, correlations between pre and post scores and transition ratings were similar in three instances, and regression coefficients similar in eight. After considering the post score in a regression in which the transition score was the dependent variable, the pre score explained a statistically significant portion of the variance at the 0.01 level in all but four instances. Although transition scores seldom show the ideal pattern of association with pre and post scores, pre scores usually show appreciable correlation and highly significant regression coefficients with transition scores. Investigators using transition scores should ensure their validity by exploring relationships with pre and post scores of corresponding domain scores.

Asthma↗

Clinical impact versus factor analysis for quality of life questionnaire construction.

OBJECTIVE: We have compared two philosophically different methods for selecting items for a disease-specific quality of life questionnaire. The impact method selects items that are most frequently perceived as important by patients whereas the psychometric method (factor analysis) selects items primarily according to their relationships with one another. PATIENTS: 150 adults with symptomatic asthma and a wide range of disease severity were enrolled from asthma clinics and notices in the local media. STUDY DESIGN: From a list of 152 items that are potentially troublesome to patients with asthma, the patients identified those items they had experienced in the previous year and scored the importance of each on a five-point scale. For the impact method, items that were identified most frequently and that scored the highest were included in the final instrument. For the psychometric method, factor analysis was performed after highly skewed items had been removed. Items with high factor loading were included in the final instrument. RESULTS: The impact method resulted in a 32-item instrument and psychometric analysis in one with 36 items. Twenty items were common to both instruments. The psychometric approach discarded the highest impact emotional function and environmental items and included in their place lower impact items mainly associated with fatigue. CONCLUSIONS: Although some items were the same for both methods, there were also some important differences. Different approaches to item reduction led to appreciably different instruments.

Adolescent↗

Peripheral streptomycin/lidocaine injections versus lidocaine alone in the treatment of idiopathic trigeminal neuralgia. A double blind controlled trial.

Seventeen patients with long-lasting idiopathic trigeminal neuralgia (ITN) were treated with either five, weekly peripheral streptomycin/lidocaine (S/L) or lidocaine alone injections, in a double blind controlled study. Eight patients responded initially to the treatment in the S/L group and three patients in the lidocaine group. Pain recurred in four patients from the S/L group within two weeks and six months following the last injection. One patient from the lidocaine group remained pain-free for eight months. At the final assessment, three patients from the S/L group and two patients from the lidocaine group remained pain-free up to 30 months. Neither treatment affected sensory functions of the injected nerves. It is concluded that S/L injections are initially effective in the treatment of ITN. In the long term, however, their effects are similar to the effects of lidocaine alone.

Aged↗

Audiological evaluation of the aural symptoms in temporomandibular joint dysfunction.

In this study, audiological assessments of the 57 patients with temporomandibular joint dysfunction and 57 controls were made. The analyses of audiograms, tympanograms and Eustachian tube functions showed no significant differences statistically. A slight increase in compliance peak in 48 female patients suggests that the sound conducting structures of the middle ear could be influenced by the reflex spasm of the tensor tympani muscle to a minor degree. This change does not seem to cause a major dysfunction either in the middle ear or in the Eustachian tube.

Acoustic Impedance Tests↗

Morphometric analysis of the insertion of the upper head of the lateral pterygoid muscle.

OBJECTIVE: This article reports on the morphometric characteristics of the upper head of the lateral pterygoid muscle. STUDY DESIGN: Several morphologic characteristics were initially examined in 40 postmortem specimens. The length of the upper head of the lateral pterygoid muscle was determined in 34 specimens. Of the 26 specimens in which the upper head of the lateral pterygoid muscle was found to be inserted into the meniscus and condyle, 22 specimens were examined microscopically to morphometrically quantify the proportion of muscle fibers to their respective insertions. RESULTS: The upper head of the lateral pterygoid muscle was approximately 33.3 mm in length and was significantly longer in males. There were no age-related differences. Approximately 29.5% of the fibers of this muscle were inserted into the meniscus of the temporomandibular joint. CONCLUSION: This study demonstrated that the insertion of the upper head of the lateral pterygoid muscle to the meniscus ranged from a fleshy mass to a few fibers. The number of fibers entering both the meniscus and the condyle decreased correspondingly as they approached the joint and could be interpreted as this muscle having a tendon of insertion into the meniscus.

Adult↗

Olopatadine ophthalmic solution adjunctive to loratadine compared with loratadine alone in patients with active seasonal allergic conjunctivitis symptoms.

BACKGROUND: Olopatadine ophthalmic solution 0.1% (Patanol, Alcon Laboratories, Fort Woth, TX) is approved for the treatment of the signs and symptoms of allergic conjunctivitis. Loratadine 10 mg (Claritin, Schering-Plough, Madison, NJ) is a nonsedating oral antihistamine approved for the treatment of the signs and symptoms of allergic rhinitis. OBJECTIVE: To compare the efficacy of olopatadine used adjunctively with loratadine versus loratadine alone in patients with seasonal allergic conjunctivitis. METHODS: This three-center, observer-masked, treatment-controlled, randomized, parallel-group study involved patients aged 7 to 74 years with seasonal allergic conjunctivitis. Patients were treated for 7 days with either olopatadine twice daily adjunctive to loratadine once daily or only loratadine once daily. Efficacy variables (ocular itching and redness, physician's impression, patient's impression, patient diary ratings of ocular redness and itching), and safety parameters were evaluated during the screening visit and on days 0, 3, and 7. Patients completed the rhinoconjunctivitis quality of life questionnaire on days 0 and 7. RESULTS: Ninety-four patients received study drug. Patients receiving olopatadine twice daily in addition to loratadine once daily exhibited less ocular itching (P = 0.0436) and rated their ocular condition as more improved compared with those receiving loratadine alone (P < 0.0022). Twenty minutes after initial dosing, olopatadine plus loratadine relieved ocular itching and redness significantly better than loratadine alone (P = 0.001). Both treatment groups showed clinically meaningful improvements in overall quality of life in all but one of the rhinoconjunctivitis quality of life questionnaire domains. Overall, and in most domains, olopatadine plus loratadine also provided significantly better (P < 0.05) quality of life than loratadine alone at day 7. CONCLUSIONS: Compared with loratadine alone, olopatadine adjunctive to loratadine provides greater relief of ocular itching and redness, a better quality of life, and is well tolerated in patients with seasonal allergic conjunctivitis.

Adolescent↗

Quality of life in patients with allergic rhinitis.

LEARNING OBJECTIVES: Reading this article will familiarize the practitioner with ongoing efforts to measure the effects of allergic rhinitis symptoms and its treatments on the health-related quality of life (HRQOL) of patients. The reader will learn about instruments used to collect HRQOL data, results of studies showing the burden of illness and the effects of treatments on HRQOL, and efforts to interpret the clinical relevance of changes in HRQOL status. DATA SOURCES: Information was gleaned from articles listed in MEDLINE regarding HRQOL in allergic rhinitis between 1966 and 2000 (English language only), and from the personal experiences of the authors. STUDY SELECTION: Questionnaire validation studies and representative controlled trials employing measures to assess the effects of allergic rhinitis symptoms and its treatments on HRQOL are described. RESULTS FROM THIS REVIEW: Allergic rhinitis symptoms can have detrimental effects on the physical, psychologic, and social aspects of patients' lives. Clinical trial data suggest a variety of pharmacologic therapies can significantly improve HRQOL in patients with allergic rhinitis. Validated questionnaires are now available that can easily be used in clinical practice to measure the effects of interventions on HRQOL for individual patients. CONCLUSIONS: Evaluating the effects of interventions on HRQOL may be particularly important in a non-life-threatening condition such as rhinitis. Health-related quality of life measures can be used to indicate the risk/benefit and the cost/benefit ratios of competing treatment options. Clinicians and policy makers are already using HRQOL data to evaluate results of medical interventions to guide patient management and reimbursement decisions.

Humans↗

Health-related quality of life in asthma studies. Can we combine data from different countries?

The aim was to compare health-related quality of life (HRQL) in patients with asthma from 4 countries, and to investigate the correlations between HRQL and clinical indices.341 patients; 140 (Sweden), 54 (Norway), 65 (the Netherlands) and 82 (Greece) were treated with formoterol fumarate 4.5 microg or with terbutaline sulphate 0.5mg for 12 weeks inhaled 'on demand' via Turbuhaler. The Asthma Quality of Life Questionnaire (AQLQ) and clinical indices were assessed. The mean baseline AQLQ overall scores in Sweden (4.97), in the Netherlands (5.04), in Norway (4.68) and in Greece (4.68) were in the same range, however, with a significant difference between the four countries (p=0.038). When comparing AQLQ, activity limitation and symptoms domains, the differences between the countries were not statistically significant. The cross-sectional correlations between AQLQ overall score and the clinical indices were similar in all four countries. The magnitude of change in AQLQ was consistent with the other clinical variables. The correlations between change in AQLQ overall score and change in clinical indices were low to medium in all countries. In conclusion, the consistency of cross-sectional correlations between the AQLQ overall and clinical indices across countries supports the validity of translations of the AQLQ used in this study. There were differences in baseline values between the countries. The treatment response in AQLQ differed to the same extent as other clinical indices. When combining HRQL data from different countries, there might be cultural, gender and socio-economic differences, explaining different responses to treatment.

Adult↗

Isoform specific differences in binding of a dual-specificity A-kinase anchoring protein to type I and type II regulatory subunits of PKA.

Dual-specificity AKAPs bind to type I (RI) and type II (RII) regulatory subunits of cAMP-dependent protein kinase A (PKA), potentially recruiting distinct cAMP responsive holoenzymes to a given intracellular location. To understand the molecular basis for this "dual" functionality, we have examined the pH-dependence, the salt-dependence, and the kinetics of binding of the A-kinase binding (AKB) domain of D-AKAP2 to the regulatory subunit isoforms of PKA. Using fluorescence anisotropy, we have found that a 27-residue peptide corresponding to the AKB domain of D-AKAP2 bound 25-fold more tightly to RIIalpha than to RIalpha. The higher affinity for RIIalpha was the result of a slower off-rate as determined by surface plasmon resonance. The high-affinity interaction for RIalpha and RIIalpha was pH-independent from pH 7.4 to 5.0. At pH 4.0, both isoforms had a reduction in binding affinity. Additionally, binding of the AKB domain to RIalpha was independent of solution ionic strength, whereas RIIalpha had an increased binding affinity at higher ionic strength. This suggests that the relative energetic contribution of the charge stabilization is different for the two isoforms. This prediction was confirmed by mutagenesis in which acidic mutations, primarily of E10 and D23, in the AKB domain affected binding to RIalpha but not to RIIalpha. These isoform-specific differences provide a foundation for developing isoform-specific peptide inhibitors of PKA anchoring by dual-specificity AKAPs, which can be used to evaluate the physiological significance of dual-specificity modes of PKA anchoring.

A Kinase Anchor Proteins↗

Does electronic implementation of questionnaires used in asthma alter responses compared to paper implementation?

BACKGROUND: Electronic implementation of questionnaires has many advantages, but there may be concerns that it alters versions that were validated on paper. OBJECTIVE: To determine whether electronic implementation alters responses to the SF-36 and asthma quality of life questionnaire (AQLQ), compared to paper implementation. METHODS: Patients with asthma presenting to a pneumologist were asked for consent to participate. Each patient completed both forms of each questionnaire. The order of presentation was alternated sequentially, with the first patient completing the electronic version first. Each patient waited at least 2 hours between completions to minimize recollection of answers. For both the SF-36 and AQLQ, intraclass correlations coefficients were calculated to compare patients' scores, for each scale and overall, on the electronic and paper versions. RESULTS: Sixty-eight patients (mean age: 48 years, 50 females) of 311 contacted were enrolled. Overall intraclass correlation coefficients for the SF-36 and AQLQ were excellent (0.965 and 0.991 respectively). For paper versions, eight questions (AQLQ) and 24 (SF-36) were left blank and nine questions (SF-36) were answered incorrectly by patients selecting more than one answer. Electronic data for one patient could not be retrieved. CONCLUSION: Collecting SF-36 and AQLQ data electronically can decrease the number of spoiled responses without altering the results. Successful implementation depends on proper instruction of the respondent in the handling of the electronic instrument.

Adolescent↗

Can the standard gamble and rating scale be used to measure quality of life in rhinoconjunctivitis? Comparison with the RQLQ and SF-36.

BACKGROUND: With interest in health economics growing, it is important to know whether utilities may be used to measure health-related quality of life in patients with rhinoconjunctivitis. The objective was to compare the validity and measurement properties of disease-specific versions of the standard gamble and rating scale with those of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the Short-Form 36 (SF-36). METHODS: One hundred adults with symptomatic rhinoconjunctivitis participated in a 5 week observational study, completing the standard gamble, rating scale, RQLQ and SF-36 at baseline and after 1 and 5 weeks. Symptom diaries were completed for 1 week before each follow-up visit. RESULTS: Reliability was highest for the RQLQ (intraclass correlation coefficient = 0.97), followed by the rating scale (0.75), the SF-36 physical (0.75), the SF-36 mental (0.74) and the standard gamble (0.12). The responsiveness index was highest for the RQLQ (0.76), followed by the rating scale (0.56) and the SF-36 mental (0.28). Both cross-sectional and longitudinal validity were strongest for the RQLQ and the rating scale. CONCLUSIONS: Both the rating scale and the RQLQ have strong evaluative and discriminative properties. The SF-36 has acceptable discriminative properties but its evaluative properties are poor. All measurement properties for the standard gamble are inadequate. Poor correlation between the standard gamble and the rating scale indicates that utilities cannot be derived from rating scale data.

Adolescent↗

Development and validation of the Mini Asthma Quality of Life Questionnaire.

The 32-item Asthma Quality of Life Questionnaire (AQLQ) has shown good responsiveness, reliability and construct validity; properties that are essential for use in clinical trials, clinical practice and surveys. However, to meet the needs of large clinical trials and long-term monitoring, where efficiency may take precedent over precision of measurement, the 15-item self-administered MiniAQLQ has been developed. The MiniAQLQ was tested in a 9-week observational study of 40 adults with symptomatic asthma. Patients completed the MiniAQLQ, the AQLQ, the Short Form (SF)-36, the Asthma Control Questionnaire and spirometry at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability was very acceptable for the MiniAQLQ (intraclass correlation coefficient (ICC)=0.83), but not quite as good as for the AQLQ (ICC=0.95). Similarly, responsiveness in the MiniAQLQ (p=0.0007) was good but not quite so good as for the AQLQ (p<0.0001). Construct validity (correlation with other indices of health status) was strong for both the MiniAQLQ and the AQLQ. Criterion validity showed that there was no bias between the instruments (p=0.61) and the correlation between them was high (r=0.90). The Mini Asthma Quality of Life Questionnaire has good measurement properties but they are not quite as strong as those of the original Asthma Quality of Life Questionnaire. The choice of questionnaire should depend on the task at hand.

Adolescent↗