Search PubMed⌕ Search

Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

At least 73 records · Page 4Linked to original sources

Bilateral linear scleroderma "en coup de sabre" associated with facial atrophy and neurological complications.

BACKGROUND: Linear scleroderma "en coup de sabre" (LSCS) usually affects one side of the face and head in the frontoparietal area with band-like indurated skin lesions. The disease may be associated with facial hemiatrophy. Various ophthalmological and neurological abnormalities have been observed in patients with LSCS. We describe an unusual case of LSC. CASE PRESENTATION: A 23 year old woman presented bilateral LSCS and facial atrophy. The patient had epileptic seizures as well as oculomotor and facial nerve palsy on the left side which also had pronounced skin involvement. Clinical features of different stages of the disease are presented. CONCLUSIONS: The findings of the presented patient with bilateral LSCS and facial atrophy provide further evidence for a neurological etiology of the disease and may also indicate that classic progressive facial hemiatrophy (Parry-Romberg syndrome) and LSCS actually represent different spectra of the same disease.

Adult↗

Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial.

BACKGROUND: Photodegradation of certain vitamins such as riboflavins, carotinoids, tocopherol, and folate has been well-documented. Previous observations suggest that ultraviolet (UV) radiation may cause folate deficiency. This is of great importance since folate deficiency is also known to be linked with the development of neural tube defects. To investigate the influence of UVA radiation on serum folate levels in vivo, we conducted a two-group randomised controlled trial on healthy subjects. MATERIAL AND METHODS: Twenty-four healthy volunteers with skin type II were enrolled into the study. Eight volunteers of the study population were randomly assigned to the control group. UVA irradiation was administered with an air-conditioned sunbed. Blood samples were taken from all volunteers at baseline (T1), 30 min after the first UVA exposure (T2), and at the end of the study 24 h after the sixth UV exposure (T3). The volunteers had two UVA exposures weekly within three weeks (cumulative UVA dose: 96 J/cm2). Volunteers of the control group had no UVA exposures. Serum folate was analysed with an automated immunoassay system. RESULTS: At all times of blood collection the differences between serum folate levels were insignificant (P > 0.05), except of the non-exposed controls at T2 (P < 0.05). We did not observed significant differences of folate levels between UVA exposed and non-exposed volunteers (P > 0.05). CONCLUSIONS: Our data suggest that both single and serial UVA exposures do not significantly influence serum folate levels of healthy subjects. Therefore, neural tube defects claimed to occur after periconceptual UVA exposure are probably not due to UVA induced folate deficiency.

Adult↗

Assignment to menopausal status and estimation of age at menopause for women with missing or invalid data--a probabilistic approach with weighting factors in a large-scale epidemiological study.

OBJECTIVE: Gynaecologic surgeries and hormone medication increasingly interfere with the concept of determining menopausal status based on self-reported data about the last menstrual period-an approach frequently applied in epidemiological studies. This analysis compared different approaches of menopausal status determination, including a probabilistic approach that was developed to reduce misclassification of menopausal status. METHODS: Interview and questionnaire data relating to hormone status from about 16,000 German women were used to determine menopausal status using different approaches: menses based, age based, self-assessment based, and a probabilistic approach. RESULTS: Applying strict menses-based criteria, 29.1% of the women were found to be with undetermined menopausal status. The probabilistic approach was applied to determine menopausal status and age at menopause for these women. The proposed approach uses the current age of the women with undetermined menopausal status, and the relative age-dependent frequencies of pre- or postmenopausal status among those with natural menopausal status to calculate weighting factors, which represent the probabilities of being pre- and postmenopausal of each woman previously undetermined. Correspondingly, the missing age at menopause was estimated with the same probabilistic approach. Applying various approaches to determine menopausal status, the ratio of pre- to postmenopausal women differed considerably, ranging from 1.03 to 1.61. In addition, considerable differences were observed with respect to the number of missing values for both menopausal status and age at menopause. CONCLUSION: The probabilistic approach allowed to estimate menopausal status and age at menopause with the advantage that all available information from the entire study population and from the individual is used.

Adult↗

Protection against ultraviolet radiation by commercial summer clothing: need for standardised testing and labelling.

BACKGROUND: The use of clothing as a means of sun protection has been recommended in recent education campaigns. Contrary to popular opinion, however, some fabrics provide insufficient ultraviolet (UV) protection. MATERIAL AND METHODS: We investigated 236 apparel textiles of the spring/summer collections 2000 and 2001. In accordance with the forthcoming European standard the UV protection factor (UPF) of the fabrics was determined spectrophotometrically. RESULTS: Seventy-eight (33%) fabrics had UPF < 15, 45 (19%) had UPF = or > 15 and < 30, and 113 (48%) had UPF = or > 30 (30+). More than 70% of the wool, polyester, and fabric blends, and only less than 30% of the cotton, linen, and viscose fabrics had UPF values of 30+. Fabrics with black, navy-blue, white, green, or beige colours provided most frequently UPF values of 30+. CONCLUSIONS: It is difficult for the sun-aware consumer to choose the 'right' garment, with a third of summer clothing providing insufficient UV protection and only half of the fabrics having UPF 30+, the UPF recommended by the European standard. Therefore, apparel summer fabrics should be measured and labelled in accordance with a standard document.

Adult↗

The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects.

UNLABELLED: Suboptimal gastrointestinal absorption is a problem for many direct thrombin inhibitors. The studies presented herein describe the new oral direct thrombin inhibitor H 376/95, a prodrug with two protecting residues added to the direct thrombin inhibitor melagatran. Absorption properties in vitro: H 376/95 is uncharged at intestinal pH while melagatran is charged. H 376/95 is 170 times more lipophilic (octanol water partition coefficient) than melagatran. As a result, the permeability coefficient across cultured epithelial Caco-2 cells is 80 times higher for H 376/95 than for melagtran. Pharmacokinetic studies in healthy volunteers: H 376/95 is converted to melagatran in man. Oral bioavailability, measured as melagatran in plasma, is about 20% after oral administration of H 376/95, which is 2.7-5.5 times higher than after oral administration of melagatran. The variability in the area under the drug plasma concentration vs. time curve (AUC) is much smaller with oral H 376/95 (coefficient of variation 20%) than with oral melagatran (coefficient of variation 38%). Pharmacodynamic properties: H 376/95 is inactive towards human alpha-thrombin compared with melagatran [inhibition constant (K(i)) ratio, 185 times], a potential advantage for patients with silent gastrointestinal bleeding. In an experimental thrombosis model in the rat, oral H 376/95 was more effective than the subcutaneous low molecular weight heparin dalteparin in preventing thrombosis. CONCLUSION: By the use of the prodrug principle, H 376/95 endows the direct thrombin inhibitor melagatran with pharmacokinetic properties required for oral administration without compromising the promising pharmacodynamic properties of melagatran.

Administration, Oral↗

Improvement and validation of the fluorescence-based histone deacetylase assay using an internal standard.

The determination of the activity of histone deacetylase (HDAC) and the potency of its inhibitors has become an important goal in medicinal chemistry. This is due both to the involvement of HDAC in gene regulation and the ability of its inhibitors to modulate transcription and induce differentiation and/or apoptosis in cancer cells. We have previously reported the development of a non-isotopic assay for HDAC using a fluorescent derivative of epsilon-acetyl lysine. It can replace existing methods that rely on radioactively labeled histones or oligopeptides as substrates. Here we report validation and improvement of the procedure using an internal standard for the quantitation of the fluorescent substrate by HPLC.

Animals↗

[Correlation between histopathology and epiluminescent microscopy in nonmelanocytic skin lesions].

Epiluminescence microscopy techniques make surface and subsurface structures accessible to visual examination in vivo. The visualization of a multitude of special morphological features, such as blood vessels, adnexa and deposits of pigments in normal and pathologically changed skin allows a reproducible and topographical stratification. There is a chance of identifying the architecture of the stratum corneum, the epidermis and the papillary bodies. Changes in the amount of melanin can be individually assessed in the stratum corneum and the deeper layers extending into the upper dermis. It is possible to differentiate the orientation, size and color of the blood vessels of the cutaneous vascular plexus, involving the capillaries of the stratum papillare and the subpapillary plexus.

Equipment Design↗

Mechanical transmission of poleroviruses.

Previously, transmission of poleroviruses has relied solely on the use of their aphid vectors. Biolistic inoculation allowed for the first time the mechanical transmission of Beet western yellows virus (BWYV) and Potato leafroll virus (PLRV) to several host plants. Inoculation with purified preparations and viral RNA extracts of PLRV resulted in 30-50% systemically infected Nicotiana occidentalis P1 plants and 15-30% infected Nicotiana clevelandii plants. Particle bombardment was also used successfully to infect N. clevelandii plants with in vitro RNA transcripts of full-length cDNA of BWYV.

Animals↗

Polymodal motion processing in posterior parietal and premotor cortex: a human fMRI study strongly implies equivalencies between humans and monkeys.

In monkeys, posterior parietal and premotor cortex play an important integrative role in polymodal motion processing. In contrast, our understanding of the convergence of senses in humans is only at its beginning. To test for equivalencies between macaque and human polymodal motion processing, we used functional MRI in normals while presenting moving visual, tactile, or auditory stimuli. Increased neural activity evoked by all three stimulus modalities was found in the depth of the intraparietal sulcus (IPS), ventral premotor, and lateral inferior postcentral cortex. The observed activations strongly suggest that polymodal motion processing in humans and monkeys is supported by equivalent areas. The activations in the depth of IPS imply that this area constitutes the human equivalent of macaque area VIP.

Acoustic Stimulation↗

Identification of the stimulated hemiretina in primary school children and adults based on left and right hemifield pattern reversal visual evoked potentials--a comparative study.

OBJECTIVES: The analysis of left and right hemifield pattern-reversal visual evoked potentials (PVEPs) in children and the identification of the stimulated hemiretina testing different identification procedures previously applied to adults. METHODS: Lateral hemifield PVEPs were recorded in 40 children (6-11 years) and 27 adults (25-40 years) from, at least, 19 standard electrodes. Two procedures were tested for the determination of the stimulated hemifield: firstly, the evaluation of the values of instantaneous frequency at the occipital electrodes at P100 latency (determined by the global field power), and secondly, the application of a generalised dynamic neural network (GDNN) using the PVEP time course at selected electrode positions as the external input. RESULTS: P100 latency as well as P100 amplitude over the contralateral occiput in children were significantly greater than in adults. Contrary to the behaviour in adults, instantaneous frequency is not a robust identifier of left and right hemiretina stimulation in children. The best identification performances were achieved when using group trained GDNNs with the bipolar difference signals of electrodes P3/P4 or T5/T6 as the external input. CONCLUSIONS: The PVEPs at electrodes P3/P4 and T5/T6 contain essential information for the determination of the stimulated hemifield. This should be further considered during the development of on-line procedures for automatic PVEP detection in future studies.

Adult↗

Balneophototherapy of psoriasis: highly concentrated salt water versus tap water--a randomized, one-blind, right/left comparative study.

BACKGROUND/PURPOSE: Apart from climatotherapy and spa therapy, combined treatment with salt water baths and artificial UV radiation (balneophototherapy) has been advocated for the treatment of psoriasis. As there is a lack of controlled studies on balneophototherapy (BPT), we conducted a randomized, one-blind, right/left comparison with salt water versus tap water in order to investigate the significance of the salt concentration in the efficacy of BPT. METHODS: Ten psoriasis patients with chronic plaques on the elbows were included in the study. One elbow was soaked in 24% NaCl solution and the other in tap water. Subsequently, broadband UVB irradiation was administered. BPT was performed 4 times weekly with a total of 30 treatments. RESULTS: A highly significant (P<0.001) decrease of the clinical baseline score was observed after 30 treatments; however, there was no significant (P>0.5) difference in clearance of the psoriatic lesions between the sites soaked in salt water and tap water. CONCLUSION: Our results suggest that any additional benefit of soaking in salt water and tap water in BPT are unlikely to be due to the salinity of the liquids.

Adult↗

Determination of the ultraviolet protection factor of textile materials:measurement precision.

BACKGROUND: There is much interest in the use of textiles for sun protection. In vitro test methods are frequently used to assess the degree of protection to solar ultraviolet radiation of textile materials. It is, however, of paramount importance that methods are clearly described and that the precision of these methods is determined such that comparison between laboratories can be performed. An in vitro method for the determination of the Ultraviolet Protection Factor (UPF) is described in a new European Standard and is referred to as prEN 13758. Thirty experts from 11 European member states, forming a working group of the European Standardization Commission (CEN), have developed this method in consensus. In this paper the reliability of this test method for the determination of the UPF of textiles worn in close proximity to the skin and in a relaxed and dry state is studied. METHODS: For the determination of the precision of the test method, eight laboratories, using nine different measuring devices located in five different countries, have measured 14 textile materials of various types of construction and levels of UVR protection. Statistical analysis of the results has been performed according to ISO 5725. RESULTS: The repeatability standard deviation of the described method is independent of the UPF in the range 1-70 and is 1.36. The reproducibility standard deviation, however, clearly increases with the level of UPF. CONCLUSIONS: For high UPF values, differences between laboratories, due to factors such as different operators, equipment and calibration, can become important. This makes classification of high UPF materials questionable.

Humans↗

Repeatability of in vitro measurements of the ultraviolet protection factor (UPF) by spectrophotometry with automatic sampling.

BACKGROUND/AIMS: Spectrophotometric assessment (in vitro) is the most established method for determining the ultraviolet protection factor (UPF) of textiles. Apart from stringent requirements for measurement precision, practical methods are required for the routine determination of the UPF. We report here spectrophotometric measurements of textiles using a newly developed autosampler. Measurement precision was evaluated under repeatable conditions. METHODS: Fifteen different textiles were spectrophotometrically assessed for the determination of the UPF. Sample handling inside the spectrophotometer was performed with a computer-controlled sampling device, capable of loading and unloading a textile sample from a magazine as well as rotating the sample perpendicular to the spectrometer beam. In order to evaluate the repeatability of measurements, one sample of each textile was assessed eight times under the same conditions in the same laboratory. RESULTS: A mean percentage of the standard error of 1% [E(UPF)] was calculated for the UPF measurements. For UPFs >30, a significantly higher E(UPF) was found (r=0.78; P<0.001). E(UV) (3.9%) of ultraviolet A (UVA) transmission differed significantly from E(UV) (1.1 %) of ultraviolet B (UVB) transmission (P<0.05). CONCLUSIONS: Though a slight decrease of repeatability was observed for UVA transmission measurements and UPFs higher than 30, our data indicate a high measurement precision under repeatable conditions. In conclusion, spectrophotometric measurements of textiles with the aid of the autosampler presented have been shown to be highly practical, time saving and precise.

Automation↗

Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1.

Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of SMN1. Its product is involved in various cellular processes, including cytoplasmic assembly of spliceosomal small nuclear ribonucleoproteins, pre-mRNA processing and activation of transcription. Spinal muscular atrophy with respiratory distress (SMARD) is clinically and genetically distinct from SMA. Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2; on chromosome 11q13.2-q13.4). In six SMARD1 families, we detected three recessive missense mutations (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift deletion (exon 5) and one splice donor-site mutation (intron 13). Mutations in mouse Ighmbp2 (ref. 14) have been shown to be responsible for spinal muscular atrophy in the neuromuscular degeneration (nmd) mouse, whose phenotype resembles the SMARD1 phenotype. Like the SMN1 product, IGHMBP2 colocalizes with the RNA-processing machinery in both the cytoplasm and the nucleus. Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals.

Amino Acid Sequence↗

Ultraviolet protection by summer textiles. Ultraviolet transmission measurements verified by determination of the minimal erythema dose with solar-simulated radiation.

BACKGROUND: Apart from sunscreen lotions, clothing provides protection from acute and chronic sun damage. Therefore, it is very important to know the ultraviolet (UV) protection factor (UPF) of textiles, in particular of lightweight summer clothing. Usually, the UPF of a textile is determined by spectrophotometric assessment of the UV transmission (in vitro method). OBJECTIVES: To compare the relationship between in vitro tests and in vivo tests of UPF using solar simulators for determination of the minimal erythema dose (MED), applied to 30 different summer textiles. METHODS: Thirty summer textiles were spectrophotometrically assessed, and UPFs were calculated with respect to the International Commission on Illumination (CIE) erythemal action spectrum.1 Based on the in vitro UPFs 'on skin' and 'off skin', in vivo testing was performed using a solar simulator for the determination of the MEDunprotected and MEDprotected. RESULTS: The UPFs obtained from in vivo 'on skin' testing were significantly (r = 0.95; P < 0.001) lower than the predicted in vitro UPFs. This disparity was also confirmed by chromometric assessment of the MED testing; the erythemal responses measured after textile protection were significantly (P < 0.001) higher than those obtained without protection. However, the in vivo 'off skin' UPFs did not significantly (r = 0.98; P > 0.05) differ from the in vitro UPFs; comparison of the chromometrically assessed erythemal responses was also insignificant (P > 0.05). CONCLUSIONS: The different correlation between in vitro and in vivo measurements of the UPF may be due to the optical-geometrical properties of textiles and the different amount of direct and diffuse radiation passing through the spaces between the yarns. As spectrophotometric measurements of a textile may generally yield lower UPFs than those obtained under average field conditions, the in vitro test method provides 'safe' UPF values representing a 'worst-case scenario'. In contrast to in vitro testing, in vivo methods are much more expensive and time-consuming. Thus, with respect to practicality, spectrophotometric measurements seem to be most suitable for the evaluation of UV protection of textiles.

Adult↗

Low-dose ultraviolet-A1 phototherapy for lichen sclerosus et atrophicus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin disease characterized by white porcelain-like sclerotic skin lesions. It is most commonly seen in adult females and usually affects the genitoanal area. Extragenital LSA appears in 15-20% of cases. We report a 9-year-old Caucasian girl suffering from extragenital LSA that was resistant to conventional treatment. After 40 treatment sessions with low-dose UVA1 phototherapy, all skin lesions were resolved completely. Moreover, the improvement of skin status has been sustained during 6-months of follow-up. Long-wave UVA irradiation has been shown to induce intensively collagenase activity in human dermal fibroblasts. We suggest that UVA1 irradiation could be an effective treatment in patients suffering from extragenital LSA.

Child↗