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Biomedical subjects

A Donner

Publications and source records attributed to A Donner.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Whipple disease and non-Hodgkin lymphoma].

6 years ago a 60-year-old man had been suffering from chronic diarrhea, weight loss and epigastric pain. Some years before he had developed joint pain, symmetric at both hands and feet. Duodenal biopsy and PCR reaction revealed Whipple's disease. Treatment with Co-trimoxazole for more than 21 months achieved remission. 6 years after diagnosis of Whipple's disease the patient presented with multilocal lymphadenopathy. Malignant Non-Hodgkin-Lymphoma (Centrocytom) stage PS IV b was diagnosed. COP-chemotherapy (Vincristine, Cyclophosphamide, Prednisone) achieved partial remission up to now. Whether the appearance of the malignant lymphoma is a consequence of Whipple's disease or a second neoplastic disease remains to be answered by further epidemiological studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Efficiency considerations in the analysis of inter-observer agreement.

The reliability of binary assessments is often measured by the proportion of agreement above chance, as estimated by the kappa statistic. In this paper, we develop a model to estimate inter-rater and intra-rater reliability when each of the two observers has the opportunity to obtain a pair of replicate measurements on each subject. The model is analogous to the nested beta-binomial model proposed by Rosner (1989, 1992). We show that the gain in precision obtained from increasing the number of measurements per rater from one to two may allow fewer subjects to be included in the study with no net loss in efficiency for estimating the inter-rater reliability.

Journal Article↗
PubMed2001

Inference procedures for assessing interobserver agreement among multiple raters.

We propose a new procedure for constructing inferences about a measure of interobserver agreement in studies involving a binary outcome and multiple raters. The proposed procedure, based on a chi-square goodness-of-fit test as applied to the correlated binomial model (Bahadur, 1961, in Studies in Item Analysis and Prediction, 158-176), is an extension of the goodness-of-fit procedure developed by Donner and Eliasziw (1992, Statistics in Medicine 11, 1511-1519) for the case of two raters. The new procedure is shown to provide confidence-interval coverage levels that are close to nominal over a wide range of parameter combinations. The procedure also provides a sample-size formula that may be used to determine the required number of subjects and raters for such studies.

Binomial Distribution↗
PubMed2001

Statistical methods for the meta-analysis of cluster randomization trials.

Cluster randomization trials have become a very attractive research strategy, particularly for the evaluation of health service interventions. The need to conduct meta-analyses of such trials is also becoming more common. However, as with cluster randomization trials in general, such analyses raise special methodologic challenges. In this paper, we discuss and illustrate several statistical approaches that might be applied to a meta-analysis of cluster randomization trials, each of which has a binary endpoint. Statistical methods for constructing inferences for a summary intervention odds ratio include those based on Mantel-Haenszel procedures, the ratio estimator approach, Woolf procedures and generalized estimating equations using robust variance estimation. The advantages and disadvantages of each method are discussed in the context of an example.

Cluster Analysis↗
PubMed2000

Testing the equality of two dependent kappa statistics.

Procedures are developed and compared for testing the equality of two dependent kappa statistics in the case of two raters and a dichotomous outcome variable. Such problems may arise when each of a sample of subjects are rated under two distinct settings, and it is of interest to compare the observed levels of inter-observer and intra-observer agreement. The procedures compared are extensions of previously developed procedures for comparing kappa statistics computed from independent samples. The results of a Monte Carlo simulation show that adjusting for the dependency between samples tends to be worthwhile only if the between-setting correlation is comparable in magnitude to the within-setting correlations. In this case, a goodness-of-fit procedure that takes into account the dependency between samples is recommended.

Analysis of Variance↗
PubMed2000

Superimposed high-frequency jet ventilation for laryngeal and tracheal surgery.

OBJECTIVE: To describe our experience with superimposed high-frequency jet ventilation (SHFJV), which does not require any endotracheal tubes or catheters, for performing laryngeal and tracheal surgery. DESIGN: A case series of 500 patients. SETTING: A university medical center. PATIENTS: Four hundred sixty adult patients and 40 children in a consecutive sample who required laryngeal or tracheal surgery under SHFJV. INTERVENTIONS: The SHFJV uses 2 jet streams with different frequencies simultaneously and is applied using a jet laryngoscope. Ventilation was performed with an air-oxygen mixture, and intravenous agents were used for anesthesia. Arterial blood gas values were analyzed. MAIN OUTCOME MEASURES: Reported values of oxygenation and ventilation during the application of SHFJV and laryngotracheal surgery. RESULTS: In 497 patients, adequate oxygenation with a mean +/- SD PaO2 of 91.8 +/- 22.9 mm Hg and ventilation with a PaCO2 of 29.7 +/- 5.5 mm Hg were achieved using SHFJV. The average duration of the application of ventilation was 27 minutes, and the longest duration was 118 minutes. No complications due to the ventilation technique were observed. Laser surgery was performed in 150 patients. CONCLUSIONS: The use of SHFJV in combination with the jet laryngoscope provides patients with sufficient ventilation during laryngotracheal surgery. Even in patients at high risk because of pulmonary or cardiac disease, this technique can be applied safely. In patients with stenosis, the ventilation is applied from above the stenosis, reducing the risk of barotrauma. The SHFJV can be used for tracheobronchial stent insertion, and laser can be used without any additional protective measures.

Adolescent↗
PubMed2000

Responsiveness of the short form-36, disability of the arm, shoulder, and hand questionnaire, patient-rated wrist evaluation, and physical impairment measurements in evaluating recovery after a distal radius fracture.

We evaluated the responsiveness of patient questionnaires and physical testing in the assessment of recovery after distal radius fracture. Patients (n = 59) were assessed at their baseline clinic visit and again 3 and 6 months after injury. At each visit patients completed a short form-36, Disability of the Arm, Shoulder, and Hand questionnaire, and patient-rated wrist evaluation (PRWE). At 3 and 6 months grip strength, range of motion, and dexterity were analyzed. Standardized response means (SRM) and effects sizes were calculated to indicate responsiveness. The PRWE was the most responsive. Both the PRWE (SRM = 2.27) and the Disability of the Arm, Shoulder, and Hand (SRM = 2.01) questionnaire were more responsive than the short form-36 (SRM = 0.92). The physical component summary score of the short form-36 was similar to that of the physical component subscales. Questionnaires were highly responsive during the 0- to 3-month time period when physical testing could not be performed. Of the physical tests, grip strength was most responsive, followed by range of motion. Responsive patient-rating scales and physical performance evaluations can assist with outcome evaluation of patients with distal radius fracture.

Adolescent↗
PubMed2000

The effect of collapsing multinomial data when assessing agreement.

BACKGROUND: In epidemiological studies researchers often depend on proxies to obtain information when primary subjects are unavailable. However, relatively few studies have performed formal statistical inference to assess agreement among proxy informants and primary study subjects. In this paper, we consider inference procedures for studies of interobserver agreement characterized by two raters and three or more outcome categories. Of particular interest is the consequence of dichotomizing such data on the expected confidence interval width for the kappa coefficient. The effect of dichotomization on sample size requirements for testing hypotheses concerning kappa is also evaluated. METHODS: Simulation studies were used to compare coverage levels and widths for constructing confidence intervals. Sample size requirements were compared for multinomial and dichotomous data. We illustrate our results using a published data set on drinking habits that assesses agreement among primary and proxy respondents. RESULTS: Our results show that when multinomial data are treated as dichotomous, not only do the expected confidence interval widths become greater, but the penalty in terms of larger sample size requirements for hypothesis testing can be severe. CONCLUSION: We conclude that there are clear advantages in preserving multinomial data on the original scale rather than collapsing the data into a binary trait.

Alcohol Drinking↗
PubMed2000

Propofol without muscle relaxants for conventional or fiberoptic nasotracheal intubation: a dose-finding study.

UNLABELLED: Endotracheal intubation has been performed during the administration of propofol anesthesia without neuromuscular blockade. In this study, we determined the propofol dose required for conventional nasotracheal or for fiberoptic nasotracheal intubation of all patients. Thirty-two patients undergoing maxillofacial surgery were randomly assigned to the conventional (n = 16) or to the fiberoptic (n = 16) intubation group. In both groups, anesthesia was induced by using IV fentanyl and IV titrated propofol according to clinical need (spontaneous respiration rate, verbal response). An endotracheal tube was placed nasally in the pharynx and the vocal cords visualized by using a fiberscope inserted via the tube. In the conventional group, the larynx was visualized additionally with a laryngoscope blade (Miller). In both groups propofol was titrated until the vocal cords opened. Patients were tracheally intubated, and the propofol dose was recorded. In all patients, the trachea could be intubated without the use of muscle relaxants. Considerable interindividual differences of dose requirements were observed. The amount of propofol required in the conventional group was significantly (P < 0.0001) larger (median +/- SD: 2.74 +/- 1.59 mg/kg; range 1.95-7.07 mg/kg) than in the fiberoptic group (1.37 +/- 0.59 mg/kg; 0.72-2.86 mg/kg). Hemodynamics remained stable in all patients. Postintubational hoarseness occurred in three patients of each group. Fiberoptic nasal intubation without a muscle relaxant can be facilitated with significantly smaller and more predictable dosages of propofol than conventional nasal endotracheal intubation. The possibility of titrating the propofol dose under assisted ventilation until the vocal cords open during fiberoptic nasotracheal intubation and the better predictability of the required dose favors the fiberoptic approach. IMPLICATIONS: In this study, contrary to all preceding studies using predefined doses of propofol and opioids, we determined the minimal required propofol dose in combination with fentanyl for conventional or fiberoptic nasotracheal intubation without muscle relaxants.

Adult↗
PubMed2000

Ventricular cerebrospinal fluid and serum concentrations of sTNFR-I, IL-1ra, and IL-6 after aneurysmal subarachnoid hemorrhage.

Postsubarachnoid hemorrhage, systemic inflammatory response syndrome and associated organ system failure are more frequently found in patients in poor neurologic condition. Since subarachnoid hemorrhage causes a profound intrathecal inflammatory response with production of proinflammatory cytokines TNFalpha, IL-1beta, and IL-6, a possible explanation for this association is that brain-derived cytokines may enter the systemic circulation in the presence of postsubarachnoid hemorrhage blood brain barrier disruption to systemically activate inflammatory cascades and thereby contribute to the development of postsubarachnoid hemorrhage systemic inflammatory response syndrome and extracerebral organ system failures. In 44 patients with aneurysmal subarachnoid hemorrhage admitted within 3 days of the initial bleed, extracerebral organ system functions were assessed individually and in aggregate using the modified Multiple Organ Dysfunction Score. Serum and cerebrospinal fluid concentrations of soluble tumor necrosis factor-alpha receptor-I, interleukin-1beta receptor antagonist, and IL-6 were determined during the first 2 weeks after subarachnoid hemorrhage and tested for correlation with (1) admission Hunt-Hess grade, (2) development of systemic inflammatory response syndrome and extracerebral organ system failures, and (3) neurologic outcome. The development of postsubarachnoid hemorrhage systemic inflammatory response syndrome and extracerebral organ system failures was paralleled by a significant increase in serum but not in cerebrospinal fluid levels of soluble tumor necrosis factor-alpha receptor-I and IL-1ra, that is, patients with and without extracerebral organ system failures did not differ in pattern and time course of cerebrospinal fluid cytokine concentrations. In contrast, increasing soluble tumor necrosis factor-alpha receptor-I and interleukin-1beta receptor antagonist serum levels correlated with a higher Multiple Organ Dysfunction score and with individual organ system dysfunctions. Postsubarachnoid hemorrhage, systemic inflammatory response syndrome and extracerebral organ system failures could therefore not be linked to changes in cerebrospinal fluid cytokine concentration profiles.

Adult↗
PubMed2000

Allelic loss involving the tumor suppressor genes APC and MCC and expression of the APC protein in the development of dysplasia and carcinoma in Barrett esophagus.

Samples of Barrett metaplastic specialized epithelium (SE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) derived from 36 esophagectomy specimens were studied for loss of heterozygosity (LOH) in APC and MCC and for expression of APC protein. Of 18 cases that were heterozygous (informative) for APC, LOH was found in none of 14 SE samples, 2 of 8 LGD samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immunohistochemically, markedly reduced expression of APC protein (< 50% positive cells) was found in 3 of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17 cases informative for the MCC gene, LOH was detectable in 1 of 14 SE samples, none of 7 LGD samples, none of 9 HGD samples, and 4 of 16 CA samples. Allelic loss of APC and/or loss of APC protein expression occurs earlier in the metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC gene. The determination of alterations at APC or MCC would be of limited importance for the surveillance of patients with Barrett esophagus.

Adenocarcinoma↗
PubMed2000

The impact of patient-centered care on outcomes.

BACKGROUND: We designed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization. METHODS: We selected 39 family physicians at random, and 315 of their patients participated. Office visits were audiotaped and scored for patient-centered communication. In addition, patients were asked for their perceptions of the patient-centeredness of the visit. The outcomes were: (1) patients' health, assessed by a visual analogue scale on symptom discomfort and concern; (2) self-report of health, using the Medical Outcomes Study Short Form-36; and (3) medical care utilization variables of diagnostic tests, referrals, and visits to the family physician, assessed by chart review. The 2 measures of patient-centeredness were correlated with the outcomes of visits, adjusting for the clustering of patients by physician and controlling for confounding variables. RESULTS: Patient-centered communication was correlated with the patients' perceptions of finding common ground. In addition, positive perceptions (both the total score and the subscore on finding common ground) were associated with better recovery from their discomfort and concern, better emotional health 2 months later, and fewer diagnostic tests and referrals. CONCLUSIONS: Patient-centered communication influences patients' health through perceptions that their visit was patient centered, and especially through perceptions that common ground was achieved with the physician. Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals.

Adult↗
PubMed1999

SELEX and missing phosphate contact analyses reveal flexibility within the AP-2[alpha] protein: DNA binding complex.

The AP-2 family of transcription factors are defined by the presence of a novel DNA binding domain, termed a 'basic helix-span-helix' motif. The AP-2 genes regulate important aspects of vertebrate embryogenesis and have also been linked to the control of cell proliferation and tumorigenesis, but the cellular targets that the AP-2 proteins control are largely undefined. In particular, since only a limited number of sequences have previously been utilized to define the nature of the AP-2 binding site, the range of DNA sequences recognized by the AP-2 proteins remains unknown. We have therefore utilized a SELEX analysis to identify multiple new AP-2[alpha] binding sites. Moreover, we have devised a novel missing phosphate and nucleotide competition analysis to characterize the residues in the binding site required for AP-2[alpha] protein:DNA contact. These studies suggest that the AP-2[alpha] protein:DNA complex is flexible and indicate that AP-2[alpha] can bind three related sequence motifs: GCC N3 GGC, GCC N4 GGC and GCC N3/4 GGG. The availability of these more refined consensus sequences should assist in the identification of target genes for this critical transcription factor.

Base Sequence↗
PubMed1999

In vitro invasiveness of human epithelioid-sarcoma cell lines: association with cell motility and inverse correlation with the expression of tissue inhibitor of metalloproteinases.

Epithelioid sarcoma (ES) is a very aggressive soft-tissue tumor in vivo, but no experimental data on its invasive and metastatic behavior have been reported. In the present study, 3 different clonal sub-populations (GRU-1A, GRU-1B and GRU-1C), derived from the same human ES cell line, GRU-1, were investigated for in vitro invasiveness in relation to migration, adhesion and the expression of different invasion- and metastasis-related genes. Tumor spheroids of GRU-1A were markedly more invasive in the chick-heart invasion assay (CHIA) than spheroids of GRU-1B and GRU-1C. These results were paralleled by a significantly higher cell motility of GRU-1A than GRU-1B and GRU-1C (p < 0.05) on distinct substrates, suggesting that the observed differences in invasion result at least in part from differences in motility. When invasion was assayed with suspended tumor cells in the Matrigel assay, differences between the 3 cell lines were much more pronounced than in the CHIA, where cell-cell contacts are established. These results indicate that interclonal differences in ES invasion result mainly from differences in motility, but also partly depend on differences in cell-cell adhesion. On the molecular level, low invasive potential was associated with over-expression of distinct tissue inhibitor of metalloproteinases (TIMPs) relative to matrix metalloproteinase-2 and -9. However, no association was found between invasion and the expression of CD44 splicing variants or nm23 isoforms. Our results suggest that differences in invasion between GRU-1A, GRU-1B and GRU-1C are caused mainly by interclonal differences in migration, and might result from differences in the expression of distinct TIMPs.

Cell Adhesion↗
PubMed1999

Testing the equality of twin correlations with multinomial outcomes.

Twin studies are widely used to study genetic and environmental influences on human measurements. Correlations are often used in such studies to compare the levels of similarity between monozygotic and dizygotic twins with respect to a specified trait. In this paper, we compare three procedures for testing the equality of twin correlations when the outcome variable of interest is multinominal. One method is a likelihood ratio test based on an underlying Dirichlet-multinomial distribution. The second method is based on the estimated large sample variance of the estimated correlation, and the third method is based on a chi 2 goodness-of-fit test. The results of a Monte Carlo simulation show that the three methods have similar properties if the number of twin pairs is large (> 100), and the prevalence of the underlying trait is not extreme. Otherwise, the goodness-of-fit approach is to be preferred. We illustrate the methods by analyzing data from a previously published smoking study.

Analysis of Variance↗
PubMed1999

Characteristic growth of human choriocarcinoma xenografts in nude mice.

In order to investigate the mechanisms and regulation of trophoblast vessel invasion, we established a model using malignant trophoblast cells grown in nude mice. The human choriocarcinoma cell line Jeg-3 established fast-growing tumours within 2 weeks after subcutaneous injection into nude mice. Interestingly, instead of neoangiogenesis the tumours were characterized by large blood-filled lacunae. Staining for hCG-beta and for mouse panendothelial antigen revealed that the majority of the lacunae were lined by trophoblast cells. The blood supply of the lacunae resulted from invasion of the choriocarcinoma cells into the host vessels at the junctional zone between tumour and mouse tissue. These large blood-filled lacunae led to a much faster expansion of tumours with less necrotic areas compared to tumours of non-trophoblastic origin (Hec-1A and HeLa), which revealed neovascularization. Jeg-3 choriocarcinoma cells eroded host vessels and replaced the endothelial lining in a similar way to trophoblast cells during the establishment of a haemochorial placenta. This model can be useful in investigating the cell biological mechanisms of trophoblast vessel invasion and replacement of the endothelium by trophoblast cells.

Animals↗
PubMed1999

Shivering and shivering-like tremor during labor with and without epidural analgesia.

BACKGROUND: Effective treatment and prevention of hyperthermia and shivering-like tremor during labor is hindered by a poor understanding of their causes. The authors sought to identify the incidence of nonthermoregulatory shivering-like tremor and the factors associated with this activity. METHODS: The authors studied women in spontaneous full-term labor who chose epidural analgesia (n = 21) or opioid sedation (n = 31). Shivering-like tremor and sweating were evaluated by observation. Core temperature was recorded in the external auditory canal using a compensated infrared thermometer. Arteriovenous shunt tone was evaluated with forearm minus fingertip skin temperature gradients; gradients less than 0 were considered evidence of vasodilation. Tremor was considered nonthermoregulatory when core temperature exceeded 37 degrees C and the arms were vasodilated. Pain was evaluated using a visual analog scale. RESULTS: Shivering-like tremor was observed in 18% of 290, 30-min data-acquisition epochs before delivery. The patients were both normothermic and vasodilated during 15% of these epochs. Shivering was observed in 16% of 116 postdelivery epochs and was nonthermoregulatory in 28%. Sweating was observed in 30% of predelivery epochs, and the patients were both hypothermic and vasoconstricted during 12%. The mean core temperature in patients given epidural analgesia was approximately 0.2 degrees C greater than in those given sedation. Hyperthermia was observed during 10 epochs (38.4+/-0.3 degrees C) during epidural analgesia and during 10 epochs (38.4+/-0.3 degrees C) with sedation. The patients were vasoconstricted in more than 50% of these epochs in each group. Multivariate mixed-effects modeling identified high pain scores and vasoconstriction as significant predictors of shivering. There were no predictors for shivering epochs in patients who were simultaneously normothermic and vasodilated. Significant predictors of sweating were time before delivery, high pain scores, hypothermia with vasoconstriction, high thermal comfort, and low mean skin temperature. There were no predictors for sweating epochs in patients who were simultaneously hypothermic and vasoconstricted. CONCLUSIONS: This study confirms the clinical impression that some peripartum shivering-like tremor is nonthermoregulatory. The authors also identified nonthermoregulatory sweating. These data indicate that shivering-like tremor and sweating in the peripartum period is multifactorial.

Adult↗