Biomedical subjects

J Hoffmann

Publications and source records attributed to J Hoffmann.

At least 19 recordsLinked to original sources

PubMed2007

Complete extirpation of benign breast lesions with an ultrasound-guided vacuum biopsy system.

OBJECTIVES: To investigate whether ultrasound-guided vacuum biopsy (VB) with curative intent is suitable for the complete extirpation of selected sonographically detectable benign lesions of the breast, and to establish the limitations of the method with regard to lesion size and complications, the extent of scar formation and the prognostic value. METHODS: One hundred and nine patients underwent hand-held, ultrasound-guided VB (8G or 11G needle) between June 2000 and September 2003. Of these, 45 (41%) women underwent ultrasound-guided extirpation of 46 lesions, and 42 women with 43 lesions were followed up clinically and sonographically for an average of 5.9 months. The complete extirpation rate, residual lesions, and patient satisfaction with the intervention were evaluated. RESULTS: Removal of all sonographic evidence of lesions (median diameter, 13 mm) was achieved in 86% of cases (8G needle, 80%; 11G needle, 89%). 19% of the patients had suspected scar formation at the biopsy site. A palpable lesion in the breast could be removed by VB in 90% of cases. None of the patients developed infections and there were no hemorrhages requiring intervention, or damage to the skin or chest wall. A total of 95% of the patients stated that they would prefer this approach to open excision for possible future intervention. CONCLUSIONS: VB is an ambulatory procedure associated with a low degree of pain. It has a high degree of patient acceptance and, as a minimally invasive biopsy technique for benign lesions, is a good alternative to open excision. The rate of complications is low and is similar to that observed with conventional microbiopsy.

Adolescent↗

PubMed2006

Effects of molecular rotation in low-energy electron collisions of H3+.

Measurements on the energetic structure of the dissociative recombination rate coefficient in the millielectronvolt range are described for H3+ ions produced in the lowest rotational levels by collisional cooling and stored as a fast beam in the magnetic storage ring TSR (Test Storage Ring). The observed resonant structure is consistent with that found previously at the storage ring facility CRYRING in Stockholm, Sweden; theoretical predictions yield good agreement on the overall size of the rate coefficient, but do not reproduce the detailed structure. First studies on the nuclear spin symmetry influencing the lowest level populations show a small effect different from the theoretical predictions. Heating processes in the residual gas and by collisions with energetic electrons, as well as cooling owing to interaction with cold electrons, were observed in long-time storage experiments, using the low-energy dissociative recombination rate coefficient as a probe, and their consistency with the recent cold H3+ measurements is discussed.

Journal Article↗

PubMed2006

Assessment of clinical palpation of the axilla as a criterion for performing the sentinel node procedure in breast cancer.

AIMS: Clinically palpable lymph nodes (LNs) are regarded as a contraindication for performing the sentinel node (SN) procedure. Many studies have shown, however, that clinical assessment of axillary LNs is inaccurate. This study evaluated the reliability of clinical axillary LN assessment by experts and assessed whether inaccuracy can be related to LN size. METHODS: Three hundred and one consecutive breast cancer patients undergoing either axillary dissection or SN were studied prospectively. RESULTS: The risk of having metastasis to the LN was 40.4% if the preoperative clinical assessment was "non-palpable LN", 61.5% if the assessment was "palpable but benign LN" and 84.4% if it was "suspicious LN". There were no clinically significant differences in mean size either when the LN was palpable versus non-palpable, or when the LN had metastasis or not. CONCLUSIONS: The clinical assessment of axillary LNs as a criterion for offering the SN procedure is of little value.

Adult↗

PubMed2006

Dielectric relaxation in chevron surface stabilized ferroelectric liquid crystals.

The dielectric response of surface stabilized ferroelectric liquid crystals with chevron layer structure is studied within low and intermediate frequency ranges, characteristic for collective molecular excitations. By analytically solving the dynamic equation for collective molecular fluctuations under a weak alternating electric field, it is demonstrated that chevron cells stabilized by both nonpolar and polar surface interactions undergo at medium frequencies two Debye relaxation processes, connected with two chevron slabs, on opposite sides of the interface plane. This result is confirmed, experimentally, making use of the electro-optic technique. Based on qualitative arguments supported by microscopic observations of zigzag defects at different frequencies and amplitudes of the external electric field, it is shown that, at low frequencies, the electro-optic response of chevron samples is determined by three kinds of motions of zigzag walls. The first two dynamic categories are related to collective relaxation processes at weak fields, within smectic A layers forming zigzag walls, and drift or creep motions of thick walls occurring at stronger field amplitudes. Dynamic processes of the third kind correspond to sliding of zigzag walls, which appear at yet stronger field amplitudes, but below the switching threshold.

Journal Article↗

PubMed2006

[Mental neuropathy and pathologic fracture of the mandible as initial symptoms of metastatic prostate carcinoma].

BACKGROUND: Distant metastases of solid tumors account for about 1% of all malign neoplasms. In about 30% of all patients who present with an oral metastasis, the distant primary tumour has not been diagnosed yet. CASE REPORT: We report the case of a 71-year-old man who clinically demonstrated unilateral mental neuropathy as well as pathologic fracture of the mandible. Prostate carcinoma was identified as a primary tumor. Clinically, there was significant hypesthesia of the skin area innervated by the left inferior alveolar nerve. X-ray examination revealed an osteolytic lesion of the ascending ramus of the mandible as well as a pathologic fracture of the mandible. Further imaging showed an extensive neoplasm of the mandible and adjacent soft tissues and significant supraclavicular lymph node enlargement. The diagnosis of metastatic carcinoma of the prostate was histopathologically confirmed. CONCLUSION: Mental neuropathy without a dental focus indicates screening for an osseous metastasis. In cases of left-sided supraclavicular lymph node enlargement in men over 45 years, metastatic prostate carcinoma must be excluded.

Aged↗

PubMed2006

[Volumetry of the human tongue by MRI].

AIM: The purpose of this study was to determine the volume of the tongue using MRI. The correlation of the individual volume of the tongue and the size of the oral cavity was to be investigated. MATERIAL AND METHODS: To analyze the tongue volume we combined coronal and sagittal data acquisition, which divided the tongue virtually into two lateral and one medial part. This procedure helped to decrease artefacts by partial volume effect. In 20 probands (m/f 7/13, average age of 36.3 years) the volume of the tongue was determined. Imaging protocol: Magnetom 63 SP (Siemens, Erlangen), T1-weighted sequences (TR/TE 500 ms/10 ms), slice thickness 5 mm, matrix 256 x 256, FOV 250 mm. RESULTS: There was a significant linear regression between the tongue volume and height of the mouth cavity. This correlation can be used to calculate the normal volume of a patient's tongue. DISCUSSION: Volumetry of the tongue can be carried out by means of MRI without application of injurious X-rays. It can be employed before as well as after tongue reduction surgeries for therapy control. The individual ideal tongue volume can be determined easily by determination of the height of the oral cavity.

Adult↗

PubMed2006

Differences in platelet growth factor release and leucocyte kinetics during autologous platelet gel formation.

Three commercial systems for whole blood separation were compared to obtain the buffy coat composed of platelet-rich plasma (BC-PRP) and leucocytes . These samples of the buffy coat were used to make a platelet gel (PG), which was used to measure platelet growth factor (PGF) release, to perform a white blood cell (WBC) count and to measure myeloperoxidase (MPO) release from WBCs. Aliquots of whole blood obtained from ten volunteers were distributed either to a blood cell separator (The Electa Cell-Separator, E-CS) or to a tabletop centrifuge (Gravitational Platelet Sequestration System, GPS) to prepare the BC-PRP. The third system combines the BC-PRP production by E-CS with a micro porous filter (Autologous Growth Factor filter, AGF) to enrich for the BC-PRP. Autologous thrombin was used to activate the BC-PRP and to prepare the PG and subsequently to degranulate the platelet concentrate. Platelet-derived growth factor-AB and transforming growth factor-beta1 were present in high levels after thrombin activation of the E-CS or GPS prepared samples. However, the AGF prepared samples released their growth factors before thrombin activation. The WBCs were significantly increased with each of the three systems. Contrary to the AGF, no leucocyte degranulation occurred with the E-CS or GPS prepared samples, based upon the low MPO concentrations in the BC-PRP. The three types of apparatus had different harvesting capacities for collecting the enriched platelets and the release of high concentrations of PGF. When the E-CS and GPS, but not the AGF, were used, low levels of MPO were maintained in the PG, which potentially contributes to antimicrobial properties of platelet gel at the site of application.

Adult↗

PubMed2005

High-resolution dissociative recombination of cold H3+and first evidence for nuclear spin effects.

The energy-resolved rate coefficient for the dissociative recombination (DR) of H(3)(+) with slow electrons has been measured by the storage-ring method using an ion beam produced from a radiofrequency multipole ion trap, employing buffer-gas cooling at 13 K. The electron energy spread of the merged-beams measurement is reduced to 500 microeV by using a cryogenic GaAs photocathode. This and a previous cold- measurement jointly confirm the capability of ion storage rings, with suitable ion sources, to store and investigate H(3)(+) in the two lowest, (J,G) = (1,1) and (1,0) rotational states prevailing also in cold interstellar matter. The use of para-H(2) in the ion source, expected to enhance para-H(3)(+) in the stored ion beam, is found to increase the DR rate coefficient at meV electron energies.

Journal Article↗

PubMed2005

Analysis of surgical and diagnostic quality at a specialist breast unit.

The quality of a specialist breast unit was analysed prospectively, comparing data from 1998, with data from 2003. The analysis is based on 5451 new referrals and 632 major breast cancer operations. The period was characterized by an increasing number of surgical specialists and improvements in diagnostic resources. There was statistically significant improvement in the following parameters: frequency of excision biopsies fell from 17.3% to 10.4%; preoperative cancer diagnosis without excision biopsy rose from 67.4% to 95.1%; percentage of women receiving breast conserving surgery rose from 24.4% to 44.7%. Cases where less than 10 lymph nodes were removed at axillary dissection fell from 5.8% to 0.5%. Severe postoperative bleeding fell from 4.1% to 0.8%, severe wound infection from 4.7% to 1.1% and severe skin necrosis from 3.7% to 0.2%. It is concluded that centralization of surgical and diagnostic expertise at a high volume institution contributes positively to the quality of care.

Adult↗

PubMed2005

Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity.

Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.

Angiopoietin-1↗

PubMed2005

Determination of piezoelectric and flexoelectric polarization in ferroelectric liquid crystals.

A method of determining the local polarization in chiral smectic liquid crystals is proposed. The method consists of simultaneous measurement of the electric permittivity and depth of electro-optic modulation in a helical liquid crystal using weak ac electric field. The spontaneous polarization of a single smectic layer determined in this way contains both the flexoelectric and piezoelectric component. On the other hand, the polarization measured using strong electric fields in a switching experiment contains the piezoelectric component only. The comparison of polarization obtained using strong and weak fields makes it possible to determine the value of flexoelectric polarization. This kind of measurement has been performed for two ferroelectric liquid crystals having quite small absolute values of the spontaneous polarization (few nC/cm2). It turned out that in both cases, the flexoelectric polarization is of the same order of magnitude as the piezoelectric one.

Journal Article↗

PubMed2005

The ototoxicity of styrene: a review of occupational investigations.

OBJECTIVES: The objective of this study was to review critically a number of occupational investigations of the exposure and effect relation between inhaled styrene vapour and hearing loss. There is concern that workers' hearing may be impaired by exposure to styrene, as used in industries making plastics and fibreglass-reinforced products. METHODS: Seven occupational studies, each dealing with the ototoxicity of styrene, were examined. Factors assessed included the experimental design and number of subjects within exposure groups, measurement of the styrene-in-air concentration, confirmation of the styrene exposure by blood or urine analysis, determination of the hearing threshold levels for the exposure and control groups, and measurement of any occupational noise in the subjects' workplaces. Consideration was also given to statistical relations between high-frequency hearing loss and lifetime exposure indices for styrene and noise. RESULTS: The results are equivocal. Four investigations failed to find any effect of styrene on hearing thresholds. In contrast, other investigations claimed to have demonstrated styrene-induced hearing loss in industrial populations, with synergism between styrene and noise. However, these reports exhibited shortcomings of experimental design and data analysis. CONCLUSIONS: Considering the body of evidence as a whole, hearing deficits due to occupational exposure to styrene at low concentrations have not been demonstrated by scientifically reliable argument. There is some suggestion of an association between styrene exposure, occupational noise, and hearing dysfunction. Further studies in humans are necessary to clarify this question.

Denmark↗

PubMed2005

Epidermal-skin-test 1,000 (EST-1,000)--a new reconstructed epidermis for in vitro skin corrosivity testing.

The determination of a possible corrosive or irritative potential of certain products and ingredients is necessary for their classification and labeling requirements. Reconstructed skin as a model system provides fundamental advantages to single cell culture testing and leads to promising results as shown by different validation studies (for review: Fentem, J.H., Botham, P.A., 2002. ECVAM's activities in validating alternative tests for skin corrosion and irritation. ATLA 30(Suppl. 2), 61-67). In this study we introduce our new reconstructed epidermis "Epidermal-Skin-Test" (EST-1,000). This fully grown epidermis consists of proliferating as well as differentiating keratinocytes. EST-1,000 shows a high comparability to normal human skin as shown by histological and immunohistochemical data. Characteristic markers (KI-67, CK 1/10/5/14, transglutaminase, collagen IV, involucrin, beta 1 integrin) can be identified easily. The main focus of this work was to characterize EST-1,000 especially with respect to its barrier function by testing several substances of known corrosive potential. Skin corrosion was detected by the cytotoxic effect of the substances on a reconstructed epidermis after short-term application to the stratum corneum. The effect was determined by standard MTT assay and accompanying histological analysis. Hence EST-1,000 shows a very high predictive potential and closes the gap between animal testing and the established full-thickness model Advanced-Skin-Test 2,000 (AST-2,000) (Noll, M., Merkle, M.-L., Kandsberger, M., Matthes, T., Fuchs, H., Graeve, T., 1999. Reconstructed human skin (AST-2,000) as a tool for pharmaco-toxicology. ATLA 27, 302).

Acrylates↗

PubMed2005

Decreased levels of interleukin-12p40 in the serum of patients with Whipple's disease.

BACKGROUND: An impaired production of interleukin (IL)-12 and T cell interferon-gamma (IFN-gamma) of in vitro stimulated monocytes has been discussed as a pathogenic factor in Whipple's disease (WD). It is unclear whether this defect of cellular immunity is translated to the humoral immune system and to serum correlates. METHODS: We analyzed the serum of 40 patients with Whipple's disease in various degrees of disease activity by sandwich enzyme-linked immunosorbent assay for differences in cytokine and cell adhesion molecule concentrations compared with age- and sex-matched controls. RESULTS: We observed a highly significant reduction of IL-12p40 levels (patients, 0.18+/-0.05 ng/ml (mean+/-SEM); controls, 3.19+/-0.39 ng/ml; p<0.01) in all stages of disease activity, whereas the concentration of IL-12p70 was comparable with controls. Furthermore, we observed a slight decrease in tumour necrosis factor alpha (TNF-alpha) concentrations in the serum of patients (patients, 6.36+/-0.90 pg/ml; controls, 10.5+/-1.23 pg/ml; p<0,05). The levels of other cytokines such as IFN-gamma, IL-2, IL-13 and transforming growth factor beta, as well as soluble cell adhesion molecules lymphocyte function-associated antigen 3 and intercellular adhesion molecule 1, were not significantly different compared with controls. Levels of immunoglobulin G2 (IgG2) measured in the serum of WD patients were below normal in 24 of 29 patients and were even below the 95% confidence interval in 10 patients. CONCLUSION: Our data demonstrate a persistent defect of the cellular immune response with decreased serum concentrations of IL-12p40 and TNF-alpha and decreased IgG2 levels in a large group of WD patients. These data support as in vivo finding the results obtained in previous investigations with stimulated monocytes/lymphocytes. The isolated decrease in IL-12p40 may hint at possible defects in the IL-12/IFN-gamma promoter system.

Biomarkers↗

PubMed2005

Steroid hormone receptors as targets for the therapy of breast and prostate cancer--recent advances, mechanisms of resistance, and new approaches.

Surgical ovariectomy and orchiectomy, first proposed over a century ago, are effective in breast and prostate cancer therapy, respectively. Later, the discovery of steroid hormones and their nuclear receptors led to the concept that inhibition of steroid receptor function by an antagonist prevents tumour growth. While the first anti-hormones, cyproteroneacetate (CPA) and tamoxifen were found accidentally, deeper understanding of nuclear receptors as transcription factors enabled more rational, structure-activity based drug discovery. Results from a drug-finding program on pure anti-estrogens will be reported. These new steroidal anti-estrogens are highly active, pure ER-antagonists that lead to an efficient degradation of the estrogen receptor alpha (ERalpha) protein without any agonistic activity. Data obtained in preclinical tumour models in mice and rats showed a high potency in growth inhibition of ERalpha-positive breast cancer. In parallel, by comparing three independently generated anti-estrogen-resistant breast cancer cell lines, it was our intention to gain insight into the mechanisms of endocrine resistance which will allow to define new approaches for the treatment of endocrine-resistant breast cancer. Candidate proteins potentially involved in mechanisms of anti-estrogen-resistant growth of breast cancer cell lines were analyzed. ERalpha and progesterone receptor (PR) expressions were lost on the protein level in all three anti-estrogen-resistant cell lines, whereas binding of epidermal growth factor (EGF) and protein expression of epidermal growth factor receptor (EGFR) were increased. Loss of ERalpha expression may be linked to the acquisition of anti-estrogen resistance and enhanced expression of the EGFR and of members of the S100 family of Ca2+-binding proteins may contribute to the outgrowth of resistant cells. Furthermore, we describe the pharmacological development of a novel, highly potent progesterone receptor antagonist. In rat mammary tumour models, treatment with the PR antagonist completely suppressed the growth of established tumours and prevented the development of breast tumours. Advanced prostate cancer is effectively treated by androgen ablation. However, this therapy becomes inefficient although the androgen receptor (AR) is still functionally expressed. One novel strategy for the treatment of advanced prostate cancer could be the selective inhibition of AR protein expression by anti-sense oligonucleotides or small interfering RNA (siRNA) molecules. Down-regulation of the human AR caused significant inhibition of LNCaP prostate cancer growth in vivo. Taken together, many promising alternatives for endocrine therapy of breast and prostate cancer are arising.

Androgen Receptor Antagonists↗

PubMed2005

[Oral manifestation of miliary tuberculosis].

CASE REPORT: We report on the clinical course of a 40-year-old patient with an oral manifestation of miliary tuberculosis. In addition to oral mucosa and lung, the colon and ileum were also infested. The oral lesions may resemble malignant tumors and are difficult to diagnose, especially because tuberculosis has become a rare disease in industrialized countries. DISCUSSION: Oral lesions and concomitant pulmonary complaints can be a sign for existing tuberculosis. Patients with these problems should undergo a chest X-ray and a biopsy from the oral mucosa. In addition, tests should be conducted to determine if mycobacteria are present in the sputum, gastric fluid, and urine and cultures grown. In cases with negative results PCR may detect DNA of Mycobacterium tuberculosis.

Adult↗

PubMed2005

Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy.

OBJECTIVE: Whereas the efficacy of the newer antiepileptic drugs (AEDs) is well established, there remain questions regarding their cognitive side effects. Therefore, we performed a comparative open randomized trial with TPM and TGB as add-on therapy, with particular consideration of cognition, mood, and health-related quality of life (HRQOL). METHODS: Forty-one patients with refractory epilepsy were randomly assigned to one of the two treatment groups (TPM vs TGB) and received neuropsychological testing at baseline (T1), after titration (3 months, T2), and during the maintenance phase (another 3 months, T3). Tests included measures of intelligence, attention, working memory, episodic memory, language, and self-report questionnaires regarding mood and HRQOL. Twenty patients (8 TPM, 12 TGB) discontinued the trial for different reasons (no group difference). RESULTS: Seizure outcome (intention-to-treat analysis) was comparably good in both groups (8.1% seizure free, 29.7% seizure reduction>50%). From baseline to after the titration paired sample t tests revealed significant deterioration in verbal fluency, language comprehension, working memory, and visual block tapping under TPM and a deterioration in verbal memory (delayed free recall) in the TGB group. These functions remained stable in the maintenance phase. Self-report measures initially indicated concerns about AED side effects in both groups and concerns about worse cognitive functioning and depression under TPM. In the maintenance phase the TGB group reported feeling a lack of energy, whereas patients on TPM demonstrated improvement on all QOLIE scales on a descriptive level. CONCLUSION: This study demonstrates the comparable efficacy of TPM and TGB. Consistent with previous reports, TPM but not TGB appears to be associated with persistent negative cognitive side effects on frontal lobe-associated functions, the degree of which may be estimated by the fact that this effect was observed with a very small sample size. In contrast, in patients taking TPM, initially negatively affected HRQOL returns to baseline in the long run on a descriptive level. The latter finding may be interpreted in accordance with the observation that objective performance and subjective self-report under TPM can be dissociated.

Adolescent↗

PubMed2005

Microcystic adnexal carcinoma: an often misdiagnosed, locally aggressive growing skin tumor.

Microcystic adnexal carcinoma (MAC) belongs to the spectrum of locally aggressive adnexal carcinomas and most commonly occurs in the head and neck region. Recently it has been proposed that MAC is an apocrine tumor. It is characterized by slow, but locally aggressive growth with infiltration of subcutaneous fat tissue, muscles, perichondrium, periosteum, or perineurium. As a result, surgical treatment often leads to ablation defects, which are many times the size of the clinical lesion. In 1982, Goldstein and colleagues first reported MAC to be a distinct histologic entity characterized by a combination of keratinous cysts in the upper dermis, islands and strands of small basaloid, benign-appearing keratinocytes or squamous cells in the deeper dermis within a dense desmoplastic stroma, and areas of ductular differentiation. The authors report the case of a 78-year-old woman in whom a diagnosis of MAC was made when a tumor on the right cheek recurred for the second time. Previous histopathologic diagnoses were squamous cell carcinoma and desmoplastic trichoepithelioma. Local recurrences of the tumor occurred, despite histographic surgery because in hematoxylin and eosin stains, small islands of the deceptively benign-appearing small basaloid cells of MAC were not recognized as tumor cells. The reported case demonstrates the difficulties in diagnosing MAC and indicates that MAC should always be considered in the differential diagnosis of slowly growing tumors in the head and neck region. If MAC is diagnosed too late, it can be inoperable because of its infiltrative growth.

Aged↗