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W Weber

Publications and source records attributed to W Weber.

At least 145 records · Page 8Linked to original sources
PubMed1997

Predicting desipramine levels in children and adolescents: a naturalistic clinical study.

OBJECTIVE: To determine the predictability and stability of desipramine (DMI) concentrations in a clinically treated sample of children, estimating the risk of developing potentially toxic DMI levels at a higher dose after a most recent level in a clinically acceptable range. METHOD: Subjects were 90 consecutive psychiatrically referred children and adolescents treated with DMI with at least two assays of serum DMI concentrations (462 pairs). Assay data were analyzed after log transformation and linear regression. RESULTS: Despite wide between-patient variability in serum DMI levels at the same dose, future within-subject DMI blood levels were highly predictable from knowledge of current levels, current dose, and the future dose. When the DMI serum level was 200 to 300 ng/ml, there was a 7.0% risk for subsequent levels at the same dose to exceed 300 ng/mL, but potentially toxic levels above 500 ng/mL were very infrequent (1.7%). CONCLUSIONS: Although the results of this naturalistic clinical study may not generalize to other situations, the results indicate a reasonable stability, predictability, and safety of DMI levels in individual psychiatrically treated children that result from clinically chosen dose changes.

Adolescent↗
PubMed1997

Correspondence between DSM-III-R and DSM-IV attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the correspondence between DSM-III-R and DSM-IV definitions of attention-deficit/hyperactivity disorder (ADHD) in clinically referred children. Results of the field trials led to the hypothesis that there would be a strong correspondence between DSM-III-R and DSM-IV subtypes. METHOD: The sample consisted of all children and adolescents consecutively referred to a pediatric psychopharmacology clinic (N = 405). Children were comprehensively evaluated with structured diagnostic interviews assessing both DSM-III-R and DSM-IV ADHD. DSM-III-R symptoms were used to approximate DSM-IV subtypes. Kappa statistics and conditional probabilities were used to examine the correspondence between DSM-III-R and DSM-IV ADHD. RESULTS: Ninety-three percent of children who received a DSM-III-R diagnosis of ADHD also received a DSM-IV ADHD diagnosis. The kappa coefficient assessing the agreement between DSM-III-R and DSM-IV ADHD was .73 (z = 14.6, p < .0001). The kappa coefficient assessing the agreement between the DSM-III-R-approximated subtypes and the actual DSM-IV subtypes was .71 (z = 15, p < .0001). CONCLUSION: These results confirm previous findings and indicate that the change from DSM-III-R to DSM-IV results in minimal changes in case identification and provides support for diagnostic continuity between the two classification systems.

Adolescent↗
PubMed1997

Fluorine-18-FDG PET and iodine-123-IMT SPECT in the evaluation of brain tumors.

UNLABELLED: The high glucose utilization of normal gray matter limits the detection of brain tumor tissue by PET using 18F-fluorodeoxyglucose (FDG). The aim of this study was to evaluate whether the examination of amino acid transport with the SPECT tracer 123l-alpha-methyl-L-tyrosine (IMT) allows better identification of tumor tissue than FDG-PET. METHODS: Nineteen patients (16 with gliomas, 3 with nontumorous lesions) were included in the study. Two independent observers classified PET and SPECT images as positive or negative for tumor tissue and defined the extent of tumor with regions of interest. Tracer uptake of FDG and IMT was quantified by calculating the tumor uptake relative to contralateral gray and white matter. RESULTS: SPECT studies were interpreted concordantly in 18 patients (kappa = 0.77) and all tumors were identified by both observers. PET studies were interpreted discordantly in 4 patients (kappa = 0.52) and only 10 tumors were identified by both observers, interobserver variability in definition of tumor extent was significantly lower in the IMT-SPECT than in the FDG-PET studies (p = 0.03). Mean tumor uptake relative to gray and white matter was 1.93 +/- 0.42 and 2.25 +/- 0.46 for IMT and 0.93 +/- 0.32 and 1.61 +/- 0.52 for FDG. All tumor uptake ratios were significantly (p < 0.01) higher for IMT than FDG, even when only glioblastomas were analyzed. No significant correlation was observed between the various uptake ratios of FDG and IMT. CONCLUSION: Despite the lower resolution and lower sensitivity of SPECT compared with PET, IMT-SPECT was clearly superior to FDG-PET in the detection and delineation of tumor tissue.

Astrocytoma↗
PubMed1997

[Immunohistochemical evidence of immuno-reactive hCG in the secretory endometrium in women].

The endometrium is a highly differentiated hormone dependent tissue. Its function is to make an implantation and pregnancy possible. The present study was carried out to investigate whether human endometrial cells are able to produce immune reactivity like hCG (ir-hCG). Immunohistochemical examinations of the endometrium were performed in 15 patients in the proliferative phase, 2 patients in the peri-ovulatory phase and 13 patients in the secretory phase. Immunohistochemical investigations of placenta from women who had an artificial abortion were used as controls. No immunohistochemical reaction in the endometrium could be recognized during the proliferative phase. In contrast a clear reaction was observed in the cells of the epithelium of the endometrium during the secretory phase. At the beginning of the secretory phase the ir-hCG was detected to be in the basal subnuclear region. In the middle of the secretory phase ir-hCG was found in the apical supranuclear region and later on in the glands. In the stroma of the endometrium single immunohistochemical positive cells could be seen. The function of the ir-hCG of the endometrium should be elucidated.

Adult↗
PubMed1997

Breast imaging with fluorine-18-FDG PET: quantitative image analysis.

UNLABELLED: This study evaluated various quantitative criteria for analysis of breast imaging with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG). METHODS: In a prospective study, 73 patients with abnormal mammography or palpable breast masses scheduled for biopsy were investigated with PET. A total of 97 breast tumors were evaluated by histology, including 46 benign and 51 malignant tumors. Using a whole-body PET scanner, attenuation-corrected images were acquired between 40 and 60 min after tracer injection. For Patlak analysis, dynamic data acquisition was obtained in 24 patients. To differentiate between benign and malignant breast tumors, receiver operating characteristic curves were calculated using incrementally increasing threshold values for tumor/ nontumor ratios based on average and maximum activity values per region of interest, standardized uptake values (corrected for partial volume effect, normalized to blood glucose, partial volume effect and blood glucose, using the lean body mass as well as the body surface area) and calculating the FDG influx rate (K) assessed by Patlak analysis. RESULTS: Quantification of FDG uptake in breast tumors provided objective criteria for differentiation between benign and malignant tissue with similar diagnostic accuracy as compared with visual analysis. Applying correction for partial volume effect and normalization by blood glucose yielded the highest diagnostic accuracy. CONCLUSIONS: These quantitative methods provided accurate evaluation of PET data for differentiating benign from malignant breast tumors. Quantitative assessment is recommended to complement visual image interpretation with the potential benefit of reduced interobserver variability.

Breast Diseases↗
PubMed1996

Therapeutic effect of m-[131I]- and m-[125I]iodobenzylguanidine on neuroblastoma multicellular tumor spheroids of different sizes.

m-[l25I]iodobenzylguanidine (m-[125I]MIBG) has been suggested as an alternative to m-[131I]MIBG for the treatment of metastatic neuroblastoma to achieve a higher radiation dose in micrometastases. To compare these two radiopharmaceuticals, a mathematical model was developed in the present study that allows for the calculation of radiation dose rates within small spherical tumors for different distributions of 131I and 125I. Furthermore, the relationship between tumor size and the therapeutic effects of m-[131I]- and m-[125I]MIBG was studied in vitro using multicellular tumor spheroids of the neuroblastoma cell line SK-N-SH. According to the calculations, higher mean dose rates can be achieved by m-[125I]MIBG than by m-[131I]MIBG up to a tumor diameter of 100 microm when both substances are homogeneously distributed within the tumor. In larger tumors, however, mean dose rates achieved by 131I are up to 8-fold higher. Evaluation of various activity distributions demonstrated that even in tumors of less than 100 microm in diameter, marked heterogeneities of the dose rate can occur when m-[125I]MIBG is not distributed homogeneously. By treatment with m-[131I]MIBG, the growth of tumor spheroids ranging from 100 to 250 microm in diameter was inhibited more effectively in the larger than in the smaller spheroids. The growth inhibition of spheroids treated with m-[125I]MIBG was independent of the spheroid size. In consistency with the calculations, the therapeutic effect of m-[125I]- and m-[131I]MIBG was equal in spheroids with diameters of about 100 microm. In larger spheroids, m-[131I]MIBG induced a more pronounced delay in spheroid growth than m-[125I]MIBG. According to these calculations and in vitro data, m-[125I]MIBG as a single agent does not seem to be a promising alternative to m-[131I]MIBG for treatment of metastatic neuroblastoma. However, the combined use of m-[131I]- and m-[125I]MIBG may be more effective than treatment with m-[131I]MIBG alone.

3-Iodobenzylguanidine↗
PubMed1996

Crystallization and preliminary diffraction data of a major pollen allergen. Crystal growth separates a low molecular weight form with elevated biological activity.

Group V major allergen Phl p 5b of timothy grass pollen induces allergic rhinitis and bronchial asthma in 90% of grass pollen-allergic patients. In addition to its allergenicity ribonuclease activity has recently been attributed to this 29-kDa protein. The allergen was expressed in Escherichia coli and subsequently purified. Spontaneous conversion of these preparations to a mixture of various forms with molecular sizes between 10 and 29 kDa was consistently observed. Surprisingly, crystals could be grown from this heterogenous preparation. Single crystals, redissolved and analyzed by SDS-polyacrylamide gel electrophoresis and immunoblot, yielded one distinct low molecular weight protein, which was identified by amino acid sequencing as the C-terminal 13-kDa portion of the allergen. Histamine release assays with single crystal solutions using basophils of an allergic patient demonstrated allergenicity comparable with that of the holo-allergen. By contrast, RNase activity of the crystallized C-terminal form was 23 times higher than that of the full-length parent allergen. Crystals were used to collect preliminary diffraction data; the space group was evaluated to I4122 with cell dimensions of a = 87.7 A, b = 87.7 A, and c = 59.6 A. We conclude that preferential crystal growth of the 13-kDa form is indicative of a compact conformation of this particular C-terminal portion of the allergen. Thus, we show here that protein crystallization is not only a prerequisite for structural analyses, but it also can provide a unique separation technique to localize the functional domain of a major allergen.

Allergens↗
PubMed1996

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.

Adult↗
PubMed1996

cAMP-activation of amiloride-sensitive Na+ channels from guinea-pig colon expressed in Xenopus oocytes.

Guinea-pig distal colonic mRNA injection into Xenopus laevis oocytes resulted in expression of functional active epithelial Na+ channels in the oocyte plasma membrane. Poly(A)+ RNA was extracted from distal colonic mucosa of animals fed either a high-salt (HS) or a low-salt (LS) diet. The electrophysiological properties of the expressed amiloride-sensitive Na+ conductances were investigated by conventional two-electrode voltage-clamp and patch-clamp measurements. Injection of poly(A)+ RNA from HS-fed animals [from hereon referred to as HS-poly(A)+ RNA] into oocytes induced the expression of amiloride-sensitive Na+ conductances. On the other hand, oocytes injected with poly(A)+ RNA from LS-fed animals [LS-poly(A)+ RNA] expressed a markedly larger amount of amiloride-blockable Na+ conductances. LS-poly(A)+ RNA-induced conductances were completely inhibitable by amiloride with a Ki of 77 nM, and were also blocked by benzamil with a Ki of 1.8 nM. 5-(N-Ethyl-N-isopropyl)-amiloride (EIPA), even in high doses (25 "mu"M), had no detectable effect on the Na+ conductances. Expressed amiloride-sensitive Na+ channels could be further activated by cAMP leading to nearly doubled clamp currents. When Na+ was replaced by K+, amiloride (1 "mu"M) showed no effect on the clamp current. Single-channel analysis revealed slow gating behaviour, open probabilities (Po) between 0.4 and 0.9, and slope conductances of 3. 8 pS for Na+ and 5.6 pS for Li+. The expressed channels showed to be highly selective for Na+ over K+ with a permeability ratio PNa/PK > 20. Amiloride (500 nM) reduced channel Po to values < 0.05. All these features make the guinea-pig distal colon of LS-fed animals an interesting mRNA source for the expression of highly amiloride-sensitive Na+ channels in Xenopus oocytes, which could provide new insights in the regulatory mechanism of these channels.

Amiloride↗
PubMed1996

Patient controlled analgesia for shock wave lithotripsy: the effect of self-administered alfentanil on pain intensity and drug requirement.

PURPOSE: Second generation lithotriptors offer immersion-free treatment and a decrease in shock wave induced pain. Pain sensations caused by advanced lithotriptors vary widely and have a significant impact on clinical management. We tested patient controlled analgesia during extracorporeal shock wave lithotripsy (ESWL) and quantified analgesic requirements by means of patient controlled analgesia during ESWL of renal stones. MATERIALS AND METHODS: Patients with renal stone disease undergoing ESWL were randomized prospectively to receive an alfentanil infusion titrated by 4 different anesthesiologists not otherwise involved in the study (22 controls) or to self-administer alfentanil via a patient controlled infusion pump (22 patients). As a measure of individual pain sensitivity the detection, pain and tolerance thresholds of electrocutaneous sensitivity were determined in all patients. RESULTS: Alfentanil was used more often in the patient controlled analgesia group than in the control patients (12 versus 8 required the narcotic, respectively, p = 0.226). Patients using patient controlled analgesia needed less drug (0.5 versus 2.15 mg., p = 0.005, median values), tolerated higher discharge voltages and pain intensities, needed significantly fewer shock waves to complete stone fragmentation (1,612 versus 2,105, p = 0.014) and had shorter treatment times (36.9 versus 46.2 minutes, p = 0.069). There was a significant correlation between the duration of shock wave exposure tolerated without analgesia, and pain (p = 0.0009) and tolerance (p = 0.0020) thresholds but not with regard to detection thresholds (p = 0.1400). Male patients showed significantly higher tolerance thresholds to electrocutaneous stimulation (10.2 versus 6.9 mA., p = 0.0238), which corresponded to longer analgesia-free treatment times in male versus female patients (31.7 versus 19.4 minutes, p = 0.0510). CONCLUSIONS: Patient controlled analgesia increases pain tolerance, decreases narcotic requirements, simplifies ESWL as an outpatient procedure and can be used to quantify analgesic requirements during lithotripsy. Pain and tolerance thresholds of electrocutaneous sensitivity are sensitive markers of pain tolerance during lithotripsy, which may be more pronounced in male patients.

Alfentanil↗
PubMed1996

Immunosuppressive activity of sera from patients with colorectal and gynecological carcinomas as evaluated by impaired IFN-gamma, IL-1 alpha and TNF-alpha production of human peripheral mononuclear cells.

The sera from patients with preoperative colorectal and gynecological carcinomas (ovarian and breast cancer) were investigated for their putative immunosuppressive activity (ISA). ISA was measured by determining the changes in the production of IFN-gamma, IL-1 alpha and TNF-alpha by human peripheral mononuclear cells (PBMC) from six normal donors. Phytohemagglutinin-stimulated PBMC were incubated with sera from patients with colorectal and gynecological carcinomas and healthy controls and in the 4-day post-inductional supernatants the cytokines were measured by an enzymoimmunological assay (ELISA). Sera from patients with carcinomas significantly decreased the IFN-gamma production as compared to the controls. In the cultures containing sera from patients with colorectal and ovarian but not breast carcinoma, significantly lower levels of IL-1 alpha and TNF-alpha were measured compared to the cultures with sera from healthy controls.

Adult↗
PubMed1996

Characterization of the C-terminal domain of ras-GTPase-activating protein (ras-GAP) as substrate for epidermal growth factor receptor and p60c-src kinase.

We describe in vitro tyrosine phosphorylation of the C-terminal 334 amino acids of ras-GTPase-activating protein (ras-GAP)1 that contains the activity domain for ras interaction. To date, there have been no other phosphorylation sites determined than the reported in N-terminal domain of ras-GAP Tyr-460, which is considered to be the major phosphorylation site of ras-GAP. In our assays some differences of the kinetic parameters were observed when the reaction was catalyzed by EGF-R compared to p60c-src. Enzyme specific regulation of activity is associated with autophosphorylation which leads to reduced (in case of EGF-R) or increased (in case of p60c-src) phosphorylation of the C-terminal 334 amino acids of ras-GAP (GAP334). Because of the characteristics of these investigated reactions the phosphorylation of GAP334 seems to be-independent from the presence of SH2 or SH3 domains-triggered off by complex mechanisms different from those regulating the phosphorylation at Tyr-460.

Electrophoresis, Polyacrylamide Gel↗