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K Neufeld

Publications and source records attributed to K Neufeld.

9 recordsLinked to original sources

A comparison of self-report and clinical diagnostic interviews for depression: diagnostic interview schedule and schedules for clinical assessment in neuropsychiatry in the Baltimore epidemiologic catchment area follow-up.

BACKGROUND: The field of psychiatric epidemiology continues to employ self-report instruments, but the low degree of agreement between diagnoses achieved using these instruments vs. that achieved by psychiatrists in the clinical modality threatens the credibility of the results. METHODS: In the Baltimore Epidemiologic Catchment Area follow-up, 349 individuals who had a Diagnostic Interview Schedule (DIS) interview were blindly examined by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Comparisons were made at the level of diagnosis, syndrome, and DSM-IV symptom group. Indexes of agreement were computed and characteristics of discrepant cases were identified. RESULTS: Agreement on diagnosis of major depressive disorder was only fair (kappa = 0.20), with the DIS missing many cases judged to meet criteria for diagnosis using the SCAN (29% sensitivity). A major source of discrepancy was respondents with false-negative diagnoses who repeatedly failed to report DIS symptoms attributed to life crises or medical conditions. Older age, male sex, and lower impairment were associated with underdetection by the DIS, using logistic regression analysis. In spite of the diagnostic discrepancy, there was substantial correlation in numbers of symptom groups in the 2 modalities (r = 0.49). Agreement was highest (about 55% sensitivity and 90% specificity) when both the SCAN and DIS thresholds were set at the level of depression syndrome instead of diagnosis. CONCLUSIONS: Weak agreement at the level of diagnosis continues to threaten the credibility of estimates of prevalence of specific disorders. A bias toward underreporting, as well as stronger agreement at the level of the depression syndrome and on ordinal measures of depressive symptoms, suggests that associations with risk factors are conservative.

Adolescent↗

Apc1638T: a mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development.

The adenomatous polyposis coli (APC) gene is considered as the true gatekeeper of colonic epithelial proliferation: It is mutated in the majority of colorectal tumors, and mutations occur at early stages of tumor development in mouse and man. These mutant proteins lack most of the seven 20-amino-acid repeats and all SAMP motifs that have been associated with down-regulation of intracellular beta-catenin levels. In addition, they lack the carboxy-terminal domains that bind to DLG, EB1, and microtubulin. APC also appears to be essential in development because homozygosity for mouse Apc mutations invariably results in early embryonic lethality. Here, we describe the generation of a mouse model carrying a targeted mutation at codon 1638 of the mouse Apc gene, Apc1638T, resulting in a truncated Apc protein encompassing three of the seven 20 amino acid repeats and one SAMP motif, but missing all of the carboxy-terminal domains thought to be associated with tumorigenesis. Surprisingly, homozygosity for the Apc1638T mutation is compatible with postnatal life. However, homozygous mutant animals are characterized by growth retardation, a reduced postnatal viability on the B6 genetic background, the absence of preputial glands, and the formation of nipple-associated cysts. Most importantly, Apc1638T/1638T animals that survive to adulthood are tumor free. Although the full complement of Apc1638T is sufficient for proper beta-catenin signaling, dosage reductions of the truncated protein result in increasingly severe defects in beta-catenin regulation. The SAMP motif retained in Apc1638T also appears to be important for this function as shown by analysis of the Apc1572T protein in which its targeted deletion results in a further reduction in the ability of properly controlling beta-catenin/Tcf signaling. These results indicate that the association with DLG, EB1, and microtubulin is less critical for the maintenance of homeostasis by APC than has been suggested previously, and that proper beta-catenin regulation by APC appears to be required for normal embryonic development and tumor suppression.

Adenomatous Polyposis Coli Protein↗

Sensitive determination of erythromycin in human plasma by LC-MS/MS.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of erythromycin in human plasma (EDTA as anticoagulant) was developed and validated. The concentration ranges were 0.5-50 and 50-5000 ng ml-1. The procedure involved alkalization of 0.5 ml of plasma, one step liquid-liquid extraction, dryness of the extract and reconstitution in 80:20 water:acetonitrile. An Inertsil ODS-2 5 microns, 3.0 x 50 mm column (Metachem) with a C8 guard column and isocratic mobile phase were used for liquid chromatography. The mobile phase consisted of 1:1 acetonitrile:water with 2 mM NH4OAc and 0.1% HOAc. A flow rate of 0.7 ml min-1 was used. The analysis time on LC-MS/MS for one sample was approximately 2 min. A Turbo-Ionspray source was interfaced between the HPLC and triple quadrupole mass spectrometer (Sciex API III Plus). MS/MS analysis used Multi-Reaction Monitoring (MRM) mode. The lowest limit of quantitation (LOQ) was 0.5 ng ml-1 with all Quality Control (QC) sample recoveries varying between 88 and 105%. Nine intraday and interday calibration curves were generated yielding correlation coefficients ranging from 0.995 to 1.000. Average recovery for erythromycin at 1 ng ml-1 was 105% (+/- 4.5%). Average recovery for the internal standard was 83-103%. Short-term and long-term stability in the freezer (-20 degrees C), bench stability, and stability after 3 freeze/thaw cycles at -20 and -80 degrees C were conducted. The samples were found to be stable under all conditions. The method developed and validated proved useful for clinical pharmacokinetic study sample analysis with high throughput due to its high sensitivity and very short analysis time.

Anti-Bacterial Agents↗

Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).

Adult↗

Onset and recovery from panic disorder in the Baltimore Epidemiologic Catchment Area follow-up.

BACKGROUND: The objective is to estimate parameters of the natural history of panic disorder, including its prodrome, incidence, recovery and recurrence. METHOD: In 1981 the Baltimore Epidemiologic Catchment Area Study interviewed 3481 individuals probabilistically selected from the household population. During 1993-1996, 1920 of these individuals (73% of survivors) were interviewed again. Baseline and follow-up interviews included the National Institute of Mental Health Diagnostic Interview Schedule. During the follow-up, a subsample was assessed by psychiatrists using the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry (SCAN). RESULTS: There were 35 new cases of panic disorder in 24,475 person years of exposure, yielding an annual incidence of 1.43 per 1000 per year. Data from the SCAN assessments suggest the incidence estimate is conservative. Incidence is greater in females and declines with age. About one-third of the new cases arise without agoraphobia, but about half have anxiety of some sort present for many years prior to meeting criteria for diagnosis. People with agoraphobia have less intense onsets but slower recoveries than those without agoraphobia. CONCLUSIONS: Panic is heterogeneous in its pattern of onset and recovery. Some of the heterogeneity is associated with the presence of other anxiety over a long period of the life.

Adolescent↗

Description and evaluation of the vallecula sign: a new radiologic sign in the diagnosis of adult epiglottitis.

STUDY OBJECTIVE: To describe and prospectively evaluate a new radiologic sign with the potential to increase the diagnostic accuracy of soft-tissue radiography of the neck in the identification of adult epiglottitis. METHODS: We conducted a prospective, before-and-after blinded study at two tertiary care institutions. A convenience sample of four staff emergency physicians, three otolaryngology residents, four radiology residents, and four senior medical students volunteered to participate. We assembled 26 soft-tissue radiographs of the neck from consecutive patients ED with the diagnosis of epiglottitis made on the basic of direct visualization. Twenty-six control radiographs were identified from ED patients who were being evaluated for the presence of foreign bodies or minor cervical trauma. We then randomly mixed the two sets of radiographs. Participants were asked to identify epiglottis among the 52 randomly sequenced radiographs. A standardized 5-minute tutorial on the vallecula sign was presented to all participants after the first interpretation. We then asked the participants to make a second interpretation of the 52 radiographs without knowledge of correct answers from the initial evaluation. RESULTS: The participants accurately classified 80.5% of all radiographs reviewed before the tutorial and 98.8% after the tutorial (P < .0001). Similarly, sensitivity improved from 78.5% to 98.2% (P < .0001) and specificity improved from 82.8% to 99.5% (P < .0001). We found no significant differences in performance characteristics among the different types of participants. CONCLUSION: We have described a new radiographic sign that improves the diagnostic accuracy of soft-tissue radiography of the neck. If reproduced in prospective studies, the absence of the vallecula sign on radiography might obviate the need for routine use of direct visualization as an initial screen.

Acute Disease↗

Our journey.

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Canada↗

Management of anxiety and panic attacks in immediate care facilities.

The records of all patients entering the Emergency Department of a large general hospital and an adjacent walk-in medical clinic were reviewed for a 4-week period. Information was gathered on the assessment and treatment of patients given a final diagnosis of anxiety or panic disorder. The majority of patients receiving these diagnoses in both settings presented with physical complaints. In the Emergency Department, where psychiatric consultation services were available, psychiatric appointments were arranged for 80% of patients with anxiety as an entrance complaint and none of those with physical entrance complaints.

Anxiety Disorders↗