Isomorphic versus isotopic response: data and hypotheses.
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Dermatology↗
Biomedical subjects
R Wolf
Publications and source records attributed to R Wolf.
Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data.
OBJECTIVE: Therapeutic drug monitoring (TDM) of the atypical antipsychotic drug clozapine is recommended. Clinical studies have indicated a therapeutic window for clozapine serum levels in schizophrenic and schizo-affective patients during acute treatment, i.e. for patients who do not respond to treatment with typical antipsychotics. However, despite the frequent use of clozapine also in maintenance treatment, very few data are available showing the relationship between serum levels of clozapine and the prevention of relapse. Thus, the primary objective of the study was to investigate the relationship between serum levels ofclozapine and relapse during maintenance treatment. METHODS: A retrospective study of routine TDM-data was conducted. Samples obtained on an acute treatment ward from patients with < 4 days hospitalization (recent admissions) were regarded as samples associated with relapse. Samples which can be attributed to an intoxication were identified as described in the TDM-form. The serum level of clozapine, as well as age, gender, smoking habits, concurrent drugs, psychiatric diagnosis and dose of clozapine were evaluated. Data analysis was performed on individual samples and, alternatively, on multiple samples from a single patient which are summarized according to a typical clinical situation. RESULTS: 404 serum levels were measured in 86 patients. After exclusion of patients receiving acute treatment, 65 relevant clinical situations were identified in 50 patients: 12 relapses, 8 intoxications (a total of 20 situations with poor outcome) and 45 situations involving patients with good maintenance outcome. Samples involving relapse had serum levels of 198 +/- 211 ng/ml (10-624), intoxications had serum levels of 1,969 +/- 705 ng/ml (900-2,900) and those with good outcome had serum levels of 384 +/- 255 ng/ml (56-1,028) (mean +/- SD (range)). By means of sensitivity of receiver operating characteristic curves (ROC) a lower limit of the therapeutic window can be estimated at about 50-250 ng/ml and an upper limit at about 745-1,050 ng/ml. The frequencies of good and poor outcome were significantly different within and outside these ranges, e.g. chi2 = 11.8 and p < 0.001 for 250 to 745 ng/ml. Comparison of only good outcome and relapse provided a significant difference in the serum level of clozapine (Student's t-test p = 0.024). However, 67% of relapses were predicted in a model of logistic regression only if the variables serum level and concurrent treatment with other psychotropic drugs were included simultaneously as independent variables. Neither variable was able to predict relapse if used as a single variable in separate models. Finally, it was found that serum levels of clozapine were increased in women, in aged patients and in nonsmokers. CONCLUSIONS: It is tentatively concluded that serum levels of clozapine < 50 ng/ml are related to relapse irrespective of concurrent psychotropic drugs. In cases where there are no concurrent psychotropic drugs, serum levels of clozapine < 250 ng/ml are associated with relapse. The risk of relapse is low for serum levels of clozapine > 250 ng/ml irrespective of concurrent psychotropic drugs. The risk of intoxication is increased with serum levels > 750 ng/ml. The TDM of clozapine is recommended during maintenance treatment.
Adult↗
Successful treatment of reboxetine-induced urinary hesitancy with tamsulosin.
Urinary hesitancy can be an uncomfortable side effect during antidepressant treatment. Clinicians often use the selective alpha(1A)-adrenoceptor antagonist, tamsulosin, to treat urinary hesitancy associated with prostate enlargement. We report here a series of case studies in which tamsulosin has been successfully used in the management of urinary hesitancy during therapy with the selective noradrenaline reuptake inhibitor reboxetine for major depressive disorder (MDD). Eight male adults (aged 43-64 years; DSM-IV diagnosis of MDD) who were receiving treatment with reboxetine (4-8 mg/day) were considered candidates for concomitant tamsulosin (0.4 mg/day) therapy. Tamsulosin was administered either as prophylaxis (n=4) or as treatment (n=4) for emergent urinary hesitancy. All patients experienced relief of urinary hesitancy within 20 min of tamsulosin therapy and this effect was sustained. Concomitant treatment with tamsulosin should be considered for those patients in whom urinary hesitancy may lead to withdrawal from reboxetine therapy.
Adrenergic alpha-Antagonists↗
Second-generation microstimulator.
The first-generation injectable microstimulator was glass encased with an external tantalum capacitor electrode. This second-generation device uses a hermetically sealed ceramic case with platinum electrodes. Zener diodes protect the electronics from defibrillation shocks and from electrostatic discharge. The capacitor is sealed inside the case so that it cannot be inadvertently damaged by surgical instruments. This microstimulator, referred to as BION, is the main component of a 255-channel wireless stimulating system. BION devices have been implanted in rats for periods of up to 5 months. Results show benign tissue reactions resulting in identical encapsulation around BION and controls. Stimulation threshold levels did not change significantly over time and ranged between 0.81 to 1.35 mA for all the animals at a 60 micros pulse width. All of the tests performed to date indicate that the BION is safe and effective for long-term human implant. We have elected to develop BION applications by seeking collaboration with the research community through our BION Technology Partnership.
Animals↗
Traumatic lumbar puncture at diagnosis and outcome in childhood acute lymphoblastic leukemia.
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Child↗
Activation or detoxification of mutagenic and carcinogenic compounds in transgenic Drosophila expressing human glutathione S-transferase.
Sensitivity of transgenic Drosophila melanogaster with expression of a human gene encoding the glutathione S-transferase alpha subunit (GSTA1-1) to 1,2:5,6-dibenzanthracene (DBA) and 1,2-dichloroethane (DCE) was investigated in the somatic mutation and recombination test (SMART). We performed the same assay in control transgenic flies expressing the bacterial lacZ gene. Three types of transgenic Drosophila strains carrying GSTA1-1 were used: two transgenic strains homozygous for the second chromosome with a single-copy transgene insertion and one strain with two transgene insertions. Larvae carrying the lacZ gene were significantly more sensitive to genotoxic effects of DBA than those carrying three copies of the GSTA1-1 gene. The larvae with lacZ expression showed significantly lower sensitivity to DCE compared with those expressing GSTA1-1. Finally, a pretreatment with buthionine-sulphoximine (BSO) in experiment with DCE significantly decreased the frequency of mutation events in larvae with three GSTA1-1 copies in comparison with others.
Animals↗
[Diagnostic imaging in acute pancreatitis].
Acute pancreatitis is a potentially severe disease with a high morbidity and mortality rate. The natural history of acute pancreatitis is characterised by a variable clinical picture ranging from a mild and self-limiting disease to a necrotising form with various severe and potentially lethal complications. The use of early and reliable diagnostics in the detection of (infected) pancreatic necrotic tissue in the treatment of acute pancreatitis allows adequate supportive treatment to be initiated before the onset of complications, such as infection of the pancreatic necrotic tissue or multiple organ failure. Contrast-enhanced CT is currently the gold standard in the detection of necrosis. Because of some diagnostic shortcomings and disadvantages associated with this technique, such as the use of ionising radiation and the potential nephrotoxicity of the contrast agents, reliable alternative (imaging) techniques are being sought. In particular, contrast-enhanced MRI may play an increasingly important role in the future diagnostics of acute pancreatitis.
Contrast Media↗
Immunoprecipitation and liquid chromatographic-mass spectrometric determination of the peptide glucose-dependent insulinotropic polypeptides GIP1-42 and GIP3-42 from human plasma samples. New sensitive method to analyze physiological concentrations of peptide hormones.
The gastrointestinal peptide glucose-dependent insulinotropic polypeptide (GIP1-42) is one of the incretin hormones regulating glucose-induced insulin secretion from the endocrine pancreas. GIP1-42 is a substrate of the circulating enzyme dipeptidyl peptidase IV, which removes the N-terminal peptide Tyr-Ala resulting in the inactive polypeptide GIP3-42. Hither to existing immunoassays do not enable a separate quantification of active and inactive forms, respectively. Therefore, we developed a highly specific and sensitive LC-MS assay for the identification and quantification of GIP1-42 and GIP3-42. Total GIP was immunoprecipitated from crude plasma samples using a C-terminally directed antibody. Thus, peptides were purified and concentrated prior to LC-MS analysis. The present immunoprecipitation-LC-MS assay enables the quantification of active and inactive GIP over a concentration range from 5 to 350 pmol/l in human plasma samples. Since this range covers the basal and postprandial levels of GIP the method is applicable to the determination of concentration changes and changes in the ratio of active and inactive forms of GIP in human plasma.
Chromatography, Liquid↗
Street crime as a treatment for migraine.
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Female↗
Development of intrahepatic arterial shunts in a transplanted liver: a potential pitfall for Doppler sonography.
We describe the hemodynamic features and anatomic basis of false-negative Doppler sonographic findings compared with angiographic findings in a 42-year-old woman after orthotopic liver transplantation complicated by hepatic artery thrombosis. Complete common hepatic artery thrombosis was demonstrated by Doppler sonography and digital subtraction angiography (DSA) on the first postoperative day. A thrombectomy was performed. DSA on the third day after transplantation again showed occlusion of the left hepatic artery. No perfusion was observed in the left hepatic lobe. Liver function remained normal. Doppler sonography on days 8, 10, and 16 after transplantation demonstrated arterial blood flow in both the right and left lobes of the liver, suggesting patent left and right hepatic arteries. Repeat DSA revealed that the arterial flow in the left lobe depended on large, intrahepatic shunts originating from the right hepatic artery. Apparently, shunts can develop within a few days in a transplanted liver from radiologically undetectable structures into vessel-like channels capable of supplying the entire left hepatic lobe.
Adult↗
Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE).
Diffusion-weighted single-shot EPI (sshEPI) is one of the most important tools for the diagnostic assessment of stroke patients, but it suffers from well known artifacts. Therefore, sshEPI was combined with SENSitivity Encoding (SENSE) to further increase EPI's potential for stroke imaging. Eight healthy volunteers and a consecutive series of patients (N = 8) with suspected stroke were examined with diffusion-weighted SENSE-sshEPI using different reduction factors (1.0 < or = R < or = 3.0). Additionally, a high-resolution diffusion-weighted SENSE-sshEPI scan was included. All examinations were diagnostic and of better quality than conventional sshEPI. No ghostings or aliasing artifacts were discernible, and EPI-related image distortions were markedly diminished. Chemical shift artifacts and eddy current-induced image warping were still present, although to a markedly smaller extent. Measured direction-dependent diffusion-coefficients and isotropic diffusion values were comparable to previous findings but showed less fluctuation. We have demonstrated the technical feasibility and clinical applicability of diffusion-weighted SENSE-sshEPI in patients with subacute stroke. Because of the faster k-space traversal, this novel technique is able to reduce typical EPI artifacts and increase spatial resolution while simultaneously remaining insensitive to bulk motion.
Adult↗
[Coronary risk profile in women with angiographically normal coronary arteries or initial coronary arteriosclerosis].
The pathophysiology and prognosis of coronary heart disease in women are the subject of intensive epidemiological and clinical investigations due to sex specific considerations. We have estimated the prevalence of modifiable coronary risk factors in 36 consecutive women (mean age 59.7 years) with suspected coronary heart disease in whom coronary angiography was performed due to unclear chest pain. Seventeen women revealed angiographically normal coronary arteries (gr. I) and 19 women showed coronary vessels with initial arteriosclerosis (luminal diameter reduction < 35%) (gr. II). Mean age was 59.1 years in gr. I and 60.3 years in gr. II (p = ns). No woman received lipid lowering drugs within the last 6 months. A hormone replacement therapy was not performed in any case. Women in gr. I showed significantly higher total and LDL cholesterol levels (271.6 +/- 34.3 vs 243.5 +/- 44.8 mg/dl; p < 0.005 and 190.5 +/- 36.8 vs 149.7 +/- 45.1 mg/dl; p < 0.025, respectively) and significantly lower HDL cholesterol values (57.8 +/- 16.5 vs 72.8 +/- 19.1 mg/dl; p < 0.0125) compared to women in gr. II. The total/HDL cholesterol ratio was 3.6 +/- 1.2 in gr. I and 5.1 +/- 1.7 in gr. II (p < 0.005). The positive predictive value for the existence of initial coronary atherosclerosis and a total cholesterol/HDL ratio > 4 was 76.5%. The negative predictive value and a ratio < 4 was 81.3%. Women in gr. I revealed 1.2 +/- 0.9 and in gr. II 1.6 +/- 0.8 risk factors (smoking, hypertension, body mass index > 30 kg/m2, diabetes mellitus, hyperlipidemia) (p < 0.10). The 10-year risk for the occurrence of a coronary event was 9.1 +/- 3.7% in gr. I and 14.2 +/- 5.8% in gr. II (p < 0.005). The positive predictive value for the existence of initial coronary atherosclerosis and a 10-year risk > 10% was 90%. The negative predictive value and a 10-year risk < 10% was 64.0%. Our investigation indicates that women with a mean age of 60 years, unclear chest pain and without exercise induced ischemia are highly suspected to have initial coronary arteriosclerosis, when a distinct risk factor profile and a 10-year cardiac event risk > 10% are present. For this high risk group of women, intensive secondary prevention measures are necessary.
Aged↗
Familial erythromelanosis follicularis and chromosomal instability.
We report a 17-year-old male patient with erythromelanosis follicularis faciei et colli (EFFC), oral leucokeratosis and diabetes mellitus without islet cell antibody. His sister also had minimal findings of EFFC and minimal follicular papules on her shoulders and extensor surfaces of the arms. The father had only fine follicular papules, but no erythromelanosis. Skin and mucous membrane lesions of the proband were investigated histopathologically. Interestingly, in peripheral lymphocyte cultures of the family members, chromosomal breakage was not observed spontaneously, but it was seen with nitrogen mustard, although this disease may be of autosomal recessive inheritance. Thus, we suggest that EFFC may be a polyaetiological disorder (i.e. familial and environmental) and might be considered one of the chromosomal instability syndromes.
Adolescent↗
Differential effects of trimipramine and fluoxetine on sleep in geriatric depression.
The effects of trimipramine, a tricyclic antidepressant (TCA) with atypical pharmacological properties, and fluoxetine, a selective serotonine reuptake inhibitor (SSRI), were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients. In sleep EEG measures, trimipramine demonstrated clear-cut effects on sleep measures resulting in higher values for sleep efficiency, total sleep time, stage 2 sleep, and shorter wake time. Under fluoxetine treatment, the proportion of REM sleep was decreased and REM latency was lengthened, whereas no change in REM sleep parameters was observed in the trimipramine group. The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep, i.e. suppression of REM sleep.
Affect↗
Topiramate as a mood stabilizer.
Topiramate is a novel anticonvulsant agent with a broad spectrum mechanism of action, and recent clinical reports indicate that it may have mood stabilizing properties in bipolar disorder. Therefore, we treated a 41-year-old woman who had 12 previous hospitalizations for acute mania during a 10-year history of bipolar I disorder with this compound. Since 1991, the patient had been treated with carbamazepine, valproate and lamotrigine with limited success. At the beginning of a new manic episode, topiramate was started in the outpatient clinic. Eight weeks after initiation of treatment, the patient was hospitalized. This inpatient treatment lasted less than 3 weeks. Subsequently, the patient has not been hospitalized again. Topiramate was well tolerated. Even though, during subsequent topiramate treatment, a serious life event (suicide attempt of brother) induced re-occurence of the patient's psychopathology, which did not require hospitalization. Fortunately, inpatient treatment was not necessary due to an increase of topiramate dosage and addition of risperidone and clonazepam. The patient, now on 200 mg/day, is mostly asymptomatic and has functioned well for over 17 months, in contrast to 13 hospitalizations during the previous 10 years.
Acute Disease↗
Identifying a cohort of patients with early-stage breast cancer: a comparison of hospital discharge and primary data.
BACKGROUND: Hospital discharge data are a potential source of information for quality of care; however, they lack detailed clinical data. OBJECTIVES: To assess the usefulness of hospital discharge data for describing patterns of care. RESEARCH DESIGN: Cohort study comparing hospital discharge data with data collected from medical records and patients. PATIENTS: Women diagnosed with early-stage breast cancer in Massachusetts and Minnesota (1993-1995). MEASURES: The percentage of patients in the primary data set who did not match a record in the discharge data set, and the percentage of patients in the discharge data set who did not match a record in the primary data set. Odds ratios for appearing in one data set, but not the other according to patient and hospital characteristics. RESULTS: For patients in the primary data set, 26.9% from Massachusetts and 13.2% from Minnesota did not match a record in the discharge data set. In both states, factors associated with failure to match to the discharge data included receipt of breast conserving surgery, shorter length of stay, and treatment hospital. For patients in the discharge data set, 43.4% in Massachusetts and 30.3% in Minnesota did not match a patient in the primary data set. In both states, factors associated with failure to match to the primary data included treatment hospital and the presence of positive lymph nodes. CONCLUSIONS: Hospital discharge data were fairly sensitive when linked to patients with early-stage breast cancer who were identified through hospital records. The discharge data lacked specificity, however. If discharge data are used to characterize patterns care for inpatients with early stage disease, estimates are likely to be inaccurate due to the inclusion of unsuitable patients in the denominator used to calculate procedure rates.
Adult↗
The treating physician as active gatekeeper in the recruitment of research subjects.
BACKGROUND: Institutional Review Boards vary in regard to the conditions imposed on investigators concerning contacting potential subjects to participate in health-services research studies. OBJECTIVE: The impact of more active involvement of the treating physician was examined in the approval process for recruiting study subjects. DESIGN: In recruiting subjects for a Massachusetts-based, multihospital (n = 17), health-services research study of treatment patterns for early stage breast cancer that required patient interviews, four hospitals stipulated that the treating surgeon provide written permission to the investigators to allow any contact with a potential study subject for the purpose of recruitment (active physician involvement group); the remaining 13 hospitals stipulated that the treating surgeon need only respond to the investigators if contact with a potential subject was forbidden (passive physician involvement group). SUBJECTS: Of the 1401 potential subjects treated for early stage breast cancer, 697 were in the active physician involvement group and 704 were in the passive physician involvement group. MEASURES: The percentages of patients for whom contact was allowed for recruitment purposes and who enrolled in the study were determined for the active physician involvement group and the passive physician involvement group, respectively. Logistic regression models were used to assess the independent effect of physician involvement on study enrollment. RESULTS: Of the 697 patients in the active physician involvement group, contact was approved by the treating surgeon for 72% (n = 505), compared with 91% (n = 638) of the passive physician involvement group (P <0.001). After adjustment for a variety of patient, physician, and hospital-level variables, patients in the passive physician involvement group were found to be significantly more likely to be enrolled in the study (adjusted OR 2.61; 95% CI, 1.53-4.45). However, among those patients approved for investigator contact, there were no significant differences between patients who were enrolled and patients who were not enrolled in the study with regard to physician involvement in the recruitment process (adjusted OR 1.13; 95% CI, 0.70-1.81). CONCLUSION: Our findings demonstrate that more stringent IRB requirements on health services researchers to verify permission from the treating physician to access patients for recruitment purposes adversely impact on the enrollment of patients even in noninterventional research studies. Current procedures for involving the treating physician as a gatekeeper in the recruitment of research subjects may limit access to patient participation in research studies from the perspectives of both researchers and potential subjects.
Adult↗
Validation of the Crisis in Family Systems-Revised, a contemporary measure of life stressors.
The objectives of this study were to establish the validity of the Crisis in Family Systems-Revised, a recently developed measure of contemporary life stressors, using the same validation technique as in the original validation and to provide further evidence of construct validity by assessing its relationship to socioeconomic status and residential location. We conducted 124 in-person interviews with parents in three outpatient pediatric asthma clinics affiliated with an academic medical center. The design was cross-sectional and correlational. Total count of life stressors accounted for 19% of the variance in scores on the Center for Epidemiologic Studies-Depression. Respondents using Medicaid and living in the city experienced more objective stressors, but the proportions of stressors rated as negative or positive (Valence), and ongoing (Chronicity) were fairly constant across subsamples, as was the Difficulty rating. Psychologists and health and mental health services researchers are in need of constructs relevant to contemporary society and its issues and tools to measure these constructs. Life stressors appears to be such a construct and the Crisis in Family Systems-Revised a measure with considerable utility.
Adult↗