Biomedical subjects

H Hoffmann

Publications and source records attributed to H Hoffmann.

At least 55 records · Page 3Linked to original sources

PubMed2000

Phase Behavior, Structure, and Physical Properties of the Quaternary System Tetradecyldimethylamine Oxide, HCl, 1-Hexanol, and Water.

The phase diagram of the ternary surfactant system tetradecyldimethylamine oxide (TDMAO)/HCl/1-hexanol/water shows with increasing cosurfactant concentration an L(1) phase, two L(alpha) phases (a vesicle phase L(alpha1) and a stacked bilayer phase L(alphah)), and an L(3) phase, which are separated by the corresponding two-phase regions L(1)/L(alpha) and L(alpha)/L(3). In this investigation, the system was studied where some of the TDMAO was substituted by the protonated TDMAO. Under these conditions, one finds for constant surfactant concentration of 100 mM TDMAO a micellar L(1) phase, an L(alpha1) phase (consisting of multilamellar vesicles), and an interesting isotropic L(1)(*) phase in the middle of the L(1)/L(alpha) two-phase region. The L(1)(*) phase exists at intermediate degrees of charging of 30-60% and for 40-120 mM TDMAO and 70-140 mM hexanol concentration. At surfactant concentrations less than 80 mM the L(1)(*)-phase borders directly on the L(1) phase. The phase transition between the L(1) phase and the L(1)(*) phase was detected by electric conductivity and rheological measurements. The conductivity values show a sharp drop at the L(1)/L(1)(*) transition, and the zero shear viscosity of the L(1)(*) phase is much lower than in L(1) phase. The form and size of the aggregates in L(1)(*) were detected with FF-TEM and SANS. This phase contains small unilamellar vesicles (SUV) of about 10 nm and some large multilamellar vesicles with diameters up to 500 nm. The system exhibits another peculiarity. For 100 mM surfactant, the clear L(alpha1)-phase exists only at chargings below 30%. With oscillating rheological measurements a parallel development of the storage modulus G' and the loss modulus G" was observed. Both moduli are frequency independent and the system possesses a yield stress. The storage modulus is a magnitude larger than the loss modulus. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Hypersusceptibility of A/J mice to tuberculosis is in part due to a deficiency of the fifth complement component (C5).

Mycobacterium tuberculosis (MTB) causes tuberculosis in man, which occurs as an acute, chronic or dormant disease reactivating over several years. The mechanisms of persistence and reactivation are not well understood and there is a need for animal models. Moderate-dose, aerosol infection killed A/J mice earlier than partially resistant C57Bl/6 mice, whereas a low-dose, aerosol-induced chronic infection exacerbated earlier in A/J mice. A/J mice lethally infected with MTB but drug cured of disease underwent reactivation of tuberculosis at least 100 days before similarly infected C57Bl/6 mice. Because A/J mice were C5 deficient, congenic B10 mice sufficient and deficient for C5 were infected intravenously with MTB to define the role of C5. C5-deficient mice again showed enhanced growth of MTB in the lungs. MTB-infected macrophages from C5-deficient mice showed enhanced growth of MTB coinciding with a reduced secretion of both cytokines (TNF-alpha, IL-1beta, IL-6, IL-12) and chemokines (KC, MIP-2 and MIP-1alpha) in A/J and TNF-alpha and chemokines in C5-deficient mice. Because C5-deficient macrophages could be activated from extraneous C5 and TNF-alpha we suggest that both play a role in the macrophage-mediated killing as well as containment mechanisms in tuberculosis.

Animals↗

PubMed2000

Synaptic activity-dependent developmental regulation of NMDA receptor subunit expression in cultured neocortical neurons.

The biophysical properties of NMDA receptors are thought to be critical determinants involved in the regulation of long-term synaptic plasticity during neocortical development. NMDA receptor channel properties are strongly dependent on the subunit composition of heteromeric NMDA receptors. During neocortical development in vivo, the expression of the NMDA receptor 2A (NR2A) subunit is up-regulated at the mRNA and protein level correlating with changes in the kinetic and pharmacological properties of functional NMDA receptors. To investigate the developmental regulation of NMDA receptor subunit expression, we studied NR2 mRNA expression in cultured neocortical neurons. With increasing time in culture, they showed a similar up-regulation of NR2A mRNA expression as described in vivo. As demonstrated by chronic blockade of postsynaptic glutamate receptors in vitro, the regulation of NR2A mRNA was strongly dependent on synaptic activity. In contrast, NR2B mRNA expression was not influenced by activity blockade. Moreover, as shown pharmacologically, the regulation of NR2A mRNA expression was mediated by postsynaptic Ca(2+) influx through both NMDA receptors and L-type Ca(2+) channels. It is interesting that even relatively weak expression of NR2A mRNA was correlated with clearly reduced sensitivity of NMDA receptor-mediated whole-cell currents against the NR2B subunit-specific antagonist ifenprodil. Developmental changes in the expression of NR1 mRNA splice variants were also strongly dependent on synaptic activity and thus might, in addition to regulation of NR2 subunit expression, contribute to developmental changes in the properties of functional NMDA receptors. In summary, our results demonstrate that synaptic activity is a key factor in the regulation of NMDA receptor subunit expression during neocortical development.

Alternative Splicing↗

PubMed2000

[Vocational rehabilitation in chronic mental illness. The current position].

Vocational rehabilitation has long been of central importance in the comprehensive treatment of the psychiatrically disabled. This is reflected by the creation of a broad spectrum of vocational rehabilitation programs, ranging from inpatient and outpatient work therapy and sheltered employment to supported employment programs within the competitive labour market. Evaluation studies have shown that although sheltered vocational rehabilitation programs effect a significant rise in the work activity, rate of employment, job tenure and income of people with chronic mental illness in the alternative labour market, these programmes do not substantially increase job placement in the competitive labour market. By contrast, supported employment programs have proven more successful in achieving a higher integration rate in the competitive labour market for the chronically mentally ill. As opposed to the well-developed alternative labour market, supported employment programs are not broadly disseminated in German-speaking countries. Furthermore, vocational rehabilitation in general suffers from a lack of systematic evaluation and thus from inadequate scientific foundation.

Humans↗

PubMed2000

Course patterns of psychosocial functioning in schizophrenia patients attending a vocational rehabilitation program.

Although considerable research has been undertaken on psychosocial treatment and rehabilitation of patients with chronic schizophrenia, few studies have examined individual courses by means of repeated and frequent observation. A more dynamic view of rehabilitation might disclose patterns of response useful for both understanding and treating symptoms and disabilities associated with chronic schizophrenia. In an exploratory study, time series of 35 schizophrenia outpatients participating in a vocational rehabilitation program were examined by a relatively original quantitative approach to the identification of dynamical patterns. By using time series regression on weekly behavioral ratings, dynamical properties of mean, trend, and variability were calculated. Cluster analysis revealed five subgroups of courses: (1) stable at a high level, (2) fluctuating at a middle level, (3) at a middle level, tending toward a slight descent, (4) showing a steep descent, and (5) unstable at a low level of functioning. The subgroups varied at intake in psychopathology; in cognitive dysfunction; and in measures of self-concept, locus of control, and coping. At program end, pronounced differences were found among the subgroups in vocational reintegration. These different dynamical patterns can be understood as typical pathways linking patient characteristics to rehabilitation outcome. A broader use of dynamical designs could substantially clarify the variety of reactions of patients to psychosocial interventions.

Adaptation, Psychological↗

PubMed2000

Calcifying fibrous pseudotumor of the neck.

Calcifying fibrous pseudotumor is a rare lesion of uncertain histogenesis that has a unique histologic appearance. We report herein a case of a 24-year-old woman with a mass on the right posterior side of the neck. Magnetic resonance imaging with contrast showed a well-circumscribed mass between the right splenius and semispinalis cervicis muscles; the study suggested high collagen content. Simple excision was performed. The histologic findings were diagnostic of calcifying fibrous pseudotumor. Our review of 19 previously reported cases suggests that a good outcome is expected when a diagnosis of calcifying fibrous pseudotumor is made.

Adult↗

PubMed2000

Development and validation of an indirect enzyme-linked immunosorbent assay (ELISA) for the nonsteroidal anti-inflammatory drug S-ibuprofen.

An indirect enzyme-linked immunosorbent assay (ELISA) was developed for the nonsteroidal anti-inflammatory drug (NSAID) S-ibuprofen. Conjugates for immunization were prepared by linking S-ibuprofen via the spacer 4-aminobutyric acid to bovine serum albumin as well as to a novel synthetic lipopeptide using the N-hydroxysuccinimide/dicyclohexylcarbodiimide method. Immunization with these immunogens was carried out in New Zealand rabbits. A poly-L-lysine-S-ibuprofen conjugate was used as a hapten-carrier for coating the surface of the microtiter plates with the hapten. Horse-radish peroxidase labeled anti-rabbit IgG served as secondary antibody using hydrogen peroxide and ABTS as substrates. The characterization of the polyclonal antiserum with compounds of analogous structure demonstrated that the antiserum possesses a very high specificity for S-ibuprofen (cross-reactivity < 0.14-1.4%). Additional cross-reactivity experiments using R-ibuprofen (cross-reactivity 50.5%), ibufenac (58%) and isopropylphenylacetic acid (6.4%) were carried out to obtain more detailed information about the antigenic recognition concerning the chiral center. The results indicated that the polyclonal antiserum possesses an additional antibody population, whose antigenic recognition did not contain the chiral center. The upper and lower limits of quantification of the developed ELISA were defined as 362 and 3.62 ng S-ibuprofen/ml, respectively, based on a 90% confidence interval.

Animals↗

PubMed1999

The CCAAT displacement protein/cut homeodomain protein represses osteocalcin gene transcription and forms complexes with the retinoblastoma protein-related protein p107 and cyclin A.

Developmental control of bone tissue-specific genes requires positive and negative regulatory factors to accommodate physiological requirements for the expression or suppression of the encoded proteins. Osteocalcin (OC) gene transcription is restricted to the late stages of osteoblast differentiation. OC gene expression is suppressed in nonosseous cells and osteoprogenitor cells and during the early proliferative stages of bone cell differentiation. The rat OC promoter contains a homeodomain recognition motif within a highly conserved multipartite promoter element (OC box I) that contributes to tissue-specific transcription. In this study, we demonstrate that the CCAAT displacement protein (CDP), a transcription factor related to the cut homeodomain protein in Drosophila melanogaster, may regulate bone-specific gene transcription in immature proliferating osteoblasts. Using gel shift competition assays and DNase I footprinting, we show that CDP/cut recognizes two promoter elements (TATA and OC box I) of the bone-related rat OC gene. Overexpression of CDP/cut in ROS 17/2.8 osteosarcoma cells results in repression of OC promoter activity; this repression is abrogated by mutating OC box I. Gel shift immunoassays show that CDP/cut forms a proliferation-specific protein/DNA complex in conjunction with cyclin A and p107, a member of the retinoblastoma protein family of tumor suppressors. Our findings suggest that CDP/cut may represent an important component of a cell signaling mechanism that provides cross-talk between developmental and cell cycle-related transcriptional regulators to suppress bone tissue-specific genes during proliferative stages of osteoblast differentiation.

Animals↗

PubMed1999

Electrorheological Effects in Lecithin Organogels with Water and Glycerol.

The effect of an external electric field on ternary mixtures consisting of lecithin, n-decane, and small amounts of polar additives (water or glycerol) has been studied by oscillating rheology, polarizing microscopy, and electric birefringence. It is shown that an electric field that is applied induces a so-called electrorheological (ER) effect, i.e., an increase in the viscosity and dynamic shear moduli of all the examined mixtures. The ER effect is absent in solutions of nonoverlapping micelles. The electric field causes the formation of fiber-like structures in the interelectrode gap. The ER effect becomes evident at a critical field of about 40 and 100 V/mm for water- and glycerol-containing organogels, respectively. In the latter case, a region of the reproducible and stable ER effect is extended up to 1700 V/mm, which is 3-4 times greater than that observed in the jelly-like phases with water. The buildup, as followed from birefringent measurements, includes fast and slow processes. Those correspond to both the local motions of parts of micellar chains and the restructuring of the whole network under the action of an external electric field. The ER response depends on the molar ratio of the polar additives to lecithin. Diagrams describing the behavior of ternary mixtures under the electric field have been constructed. They differ for water- and glycerol-containing organogels. The dependence of the stable ER effects on the molar ratio of glycerol to lecithin has a maximum in the vicinity of the phase separation of the homogeneous organogel, whereas for water-containing systems there is a gradual increase up to and including mixtures with the solid precipitate. A new rheological regime has been first established for solutions of polymer-like micelles. This feature is the square-root scaling of the dynamic moduli with the frequency. Such a scaling is inherent in polymers. A possible mechanism is considered, basing on the ordering of cylindrical micelles under the action of an external electric field. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Formation of Ultrathin Films at the Solid-Liquid Interface Studied by In Situ Ellipsometry.

Ellipsometric investigations of self-assembled monolayers (SAMs) of alkylsiloxanes on native silicon substrates and of organothiols on gold substrates were performed under in situ conditions with the substrate in direct contact with the adsorbate solution. Specially designed liquid cells matched for different incidence angles were used to carry out measurements in a range of organic solvents with different refractive indices as the ambient medium. The observed shifts in the ellipsometric phase angles Delta upon monolayer formation were found to depend very sensitively on the incidence angle and the refractive indices of the adsorbate film and the ambient solvent, from which a rather simple method for determining the refractive index of the adsorbate film, based on a variation of the ambient refractive index, was derived. Time-resolved in situ measurements of SAM formation in different solvents and onto different substrates yielded accurate kinetic information on the monolayer growth process and revealed hitherto unknown strong solvent effects on the growth rate. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

The Branching of Reversed Polymer-like Micelles of Lecithin by Sugar-Containing Surfactants.

The effects of n-dodecyl-beta-D-glucopyranoside and n-dodecyl-beta-D-lactobionamide on the formation and rheological behavior of lecithin organogels consisting of reverse long cylindrical (polymer-like) micelles were studied by oscillating rheology. The alkylglucoside addition results in a decrease of the zero shear viscosity and plateau modulus of the organogel, whereas the lactobionamide derivative causes an increase of these parameters. Despite their different effects, both the sugar-containing surfactants change the scaling exponents of the zero shear viscosity, plateau modulus, and terminal relaxation time in a similar way. Before their addition, the scaling behavior is in a satisfactory agreement with that expected from a model by Cates who considered polymer-like micelles as linear and flexible. In mixtures of lecithin with n-dodecyl-beta-D-glucopyranoside or n-dodecyl-beta-D-lactobionamide, the power law exponents are close to the theoretical predictions that follow from a model for branched (connected) cylindrical micelles. It was concluded that both the sugar-containing surfactants bring about a change in the growing mechanism of the lecithin micelles in nonpolar media. A molecular model is considered. This takes into account the formation of hydrogen bonds between amphiphile molecules, occurrence of packing constraints, and a change of excess free energy of the micellar endings. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

[Distribution pattern and involvement of regional lymph nodes in non-small-cell bronchial carcinoma].

Despite the important role of lymph node infiltration for the classification and prognosis of non-small-cell lung cancer (NSCLC), no standards exist to evaluate the quality of mediastinal lymphadenectomy. Researches at several centers are not convinced that complete ipsilateral lymphadenectomy is necessary. We investigated 270 consecutive patients undergoing a potential curative operation for NSCLC including complete ipsilateral lymph node dissection in order to ascertain whether or not there is a correlation between tumor localization and lymph node infiltration. Patients were classified into the UICC (1987) stages I (n = 115), II (n = 42), and IIIa (n = 113). In patients with N1-positive lymph nodes (n = 61) we found higher 5-year survival for patients with only intrapulmonary lymph node infiltration (39%) than for patients with hilar infiltration (21%). Patients with N2 disease showed skip metastases in up to 81% of cases. We found that no tumor location predicted the lymph node infiltration. Due to the variability of lymph node infiltration and the frequently occurring skip metastases, complete ipsilateral lymphadenectomy should be the standard for curative operations for NSCLC.

Aged↗

PubMed1999

Effects of lung preservation solutions on PMN activation in vitro.

Polymorphonuclear leukocyte (PMN) activation and PMN-endothelial cell interactions may cause graft failure due to ischemia-reperfusion injury after lung transplantation. We investigated the effects of Euro-Collins solution (EC), low-potassium dextran solution (LPD), and EC plus pentoxifylline (EC-PTXF) on adhesion molecule (CD11b/CD18 and L-selectin) expression, chemotaxis, and oxidative burst of PMN. PMN from healthy human volunteers were incubated with EC, LPD, and EC-PTXF, and, in controls, without preservation solution. LPD exerted a suppressive effect on PMN chemotaxis as compared to EC (P < 0.05), but had no attenuating effect on the increase of CD11b/CD18, the shedding of L-selectin, and intracellular oxidant generation. EC-PTXF attenuated the expression of CD11b/CD18 and the oxidative burst as compared to EC alone (P < 0.05). These effects of LPD and PTXF on PMN function may contribute to successful organ preservation in transplantation.

CD18 Antigens↗

PubMed1999

Mediastinal lymph node infiltration in non-small cell lung cancer and its role in curative surgery.

Despite the importance of lymph node infiltration for the classification and prognosis of non-small cell lung cancer (NSCLC), there are no accepted standards for quality of mediastinal lymphadenectomy. In 270 consecutive patients undergoing potentially curative surgery for NSCLC, including complete ipsilateral lymph node dissection, we investigated the possibility of a correlation between tumour location and lymph node infiltration. The tumours were classified as UICC stage I (n = 115), II (n = 42) or IIIa (n = 113). Patients with N2-disease (n = 68) showed up to 81% skip metastasis. Because of the observed dissemination of lymph node metastasis, tumour location could not predict nodal infiltration. The variability of nodal involvement and the frequent occurrence of skip metastasis thus make complete ipsilateral lymphadenectomy mandatory for curative management of NSCLC.

Adenocarcinoma↗

PubMed1999

[Lymph node dissection during surgery for lung cancer. Solely staging or therapy?].

The accuracy of staging of lung cancer is reflected by the extent of mediastinal lymph node sampling. The more extensively a patient is tested, the more likely there will be the accurate N-stage diagnosed. Adequate lymph node dissection during surgery for lung cancer therefore requires complete dissection of all three ipsilateral mediastinal compartments including the infracarinal region. Additional contralateral mediastinal lymph node exploration may not be justified. A direct therapeutic effect of mediastinal lymph node removal may be attributed to the prevention of local tumor growth. However, its overall prognostic significance remains unclear because it must be assumed that proven tumor within the mediastinal lymph nodes reflects the state of tumor generalization that may not be cured by localized therapeutic means. New systemic interventions are clearly warranted to significantly improve prognosis in stage II and III lung cancer patients.

Humans↗

PubMed1999

[Pulmonary nodule. The surgeon's approach].

Malignancy must be suspected with any pulmonary nodule detected on radiologic examination of the chest until its benign origin has been proven. This requires further evaluation of the patient. The non invasive diagnostic steps include patient's history, clinical examination, lung function testing, and standard radiographs and a computed tomography (CT) of the chest. Based on these findings the presumed diagnosis claims the next appropriate diagnostic steps. If lung cancer is the most likely diagnosis and lung function testing revealed that the patient is a candidate for lung resection than surgery may be the next step. Preoperative proof of the histologic diagnosis is not mandatory. It is the less required the more surgery may be curative. If curative resectability is indoubt or the patient is not candidate for lung resection than histologic diagnosis should be confirmed prior to introduction of radiotherapy or chemotherapy by the least invasive procedure (bronchoscopy < lymph node biopsy < needle biopsy < mediastinoscopy/-tomy < VATS). If metastatic disease must be suspected, staging should be completed as required for the primary malignancy. With local recurrence and other metastases excluded the number of pulmonary nodules detected on CT scan points to the appropriate surgical approach. In case of a solitary nodule or multiple but resectable nodules, complete (wedge) resection with lymph node dissection through a lateral thoracotomy will be the procedure of choice. With multiple and unresectable nodules, surgery allows definitive diagnosis and videothoracoscopy affords the opportunity to accomplish wedge resection of the lung along with low morbidity. When lesions are deemed indeterminate, definitive diagnosis should nevertheless be attempted. If there is no history of malignancy routine evaluation for such in asymptomatic patients is not indicated. With small nodules (less than 3 cm in diameter) located in the periphery of the lung, videothoracoscopic wedge resection is indicated without preoperative sputum cytology, bronchoscopy or transthoracic needle biopsy. The histologic diagnosis obtained by intraoperative frozen sections than determines the further surgical approach. Benign lesion: completion of surgery; lung cancer: proceed to thoracotomy with anatomic lung resection and mediastinal lymph node resection; metastatic disease: completion of surgery and further search for primary malignancy.

Diagnostic Techniques and Procedures↗

PubMed1999

[Is vocational integration in the competitive labor market a realistic goal for the chronically mentally ill?].

A wide range of sheltered jobs has been created in the second or special labour market with the aim of enabling the chronically mentally ill to participate in working life. However, having a job in the special labour market often precludes the chance of obtain-ing employment in the competitive labour market. To date, vocational integration programs enable only a small number of persons with psychiatric disabilities to attain reintegration into competitive employment. The predictors of successful vocational integration are subsequently discussed. A substantial increase in both sheltered and competitive jobs on the common labour market could be achieved for mentally ill and disabled people by adapting the "supported employment" model, as widely practised in the USA, to European labour market standards and appropriately funding its implementation. The utilisation of this model could serve to reduce the necessity of further expansion in the special labour market.

Employment↗

PubMed1999

The efficacy and tolerability of Valette: a postmarketing surveillance study.

OBJECTIVES AND METHODS: A postmarketing survey was carried out to determine the efficacy and tolerability of Valette (dienogest 2.0 mg and ethinylestradiol 0.03 mg) in routine gynecological practice. RESULTS: Valette had excellent contraceptive efficacy (unadjusted Pearl index 0.14), with 11 unplanned pregnancies from a total of 92 146 cycles of exposure, of which at least four were attributable to user failure. Cycle control was good, with spotting and breakthrough bleeding, which affected 5.0% and 3.4% of women, respectively, during the first cycle, becoming less frequent thereafter. Silent menstruation, i.e. the absence of withdrawal bleeding, affected on average 2.0% of women per cycle and 5.9% within the observation period. Valette was well tolerated. The most common adverse drug reactions were mastalgia (1.46% of all users), weight gain (1.11%), headache (0.98%), nausea/vomiting (0.96%), dysmenorrhea (0.35%), decreased libido (0.31%) and depressive moods (0.28%). The dropout rate due to adverse drug reactions was only 3.2%. Only six of the 16 267 women reported events which were considered to be serious adverse drug reactions; all recovered with appropriate treatment. CONCLUSIONS: These results confirm those from previous clinical trials, and demonstrate that Valette is highly effective, very well tolerated and produces excellent cycle control in routine practice.

Adolescent↗