Biomedical subjects
K Hartmann
Publications and source records attributed to K Hartmann.
Mast cells enhance contraction of three-dimensional collagen lattices by fibroblasts by cell-cell interaction: role of stem cell factor/c-kit.
Reorganization of the extracellular matrix is important in many biological and pathophysiological processes, including tissue remodelling, wound healing, or cancer metastasis. The ability of cultured fibroblasts to reorganize and contract three-dimensional type I collagen gels is regarded as an in vitro model for this process. In tissue fibrosis, complex interactions among fibroblasts, inflammatory cells and the extracellular matrix are taking place. Mast cells have often been discussed to play a role in several fibrotic conditions including scleroderma, scar formation, or wound healing. In this study, we examined the effects of mast cells on contraction of collagen lattices. The results demonstrate that co-culture of dermal fibroblasts with a human mast cell line (HMC-1) significantly enhanced contraction of the three-dimensional collagen lattices, whereas mast cells alone failed to contract the gel. Addition of culture supernatants of mast cells did not enhance the speed of gel contraction, indicating the importance of cell-cell contact. Morphological analysis showed that mast cells were incorporated into the lattices. Histological examination also demonstrated that within the lattices, mast cells were localized in close contact to, or attached to, fibroblasts. As fibroblasts and mast cells are known to attach via stem cell factor (SCF)/c-kit interaction when co-cultured in monolayers, we also examined the effect of antibodies against SCF and c-kit in this system. Addition of both antibodies inhibited gel contraction up to 70%. In contrast, antibodies against interleukin-4 (IL-4) and IL-4 receptor did not affect gel contraction. These results indicate that mast cells enhance fibroblast-mediated contraction of collagen lattices via direct cell-cell contact, mediated in part by SCF/c-kit interactions.
Improvement of cold urticaria by treatment with the leukotriene receptor antagonist montelukast.
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Metabolite monitoring in plants with double-quantum filtered chemical shift imaging.
1H spectroscopic imaging in combination with double-quantum filtering with magnetic field gradients is used for in vivo applications in humans and animals. Because of its high selectivity and strong reduction of water signal it is also a useful tool for monitoring the distribution of specific metabolites in plants. The development and application of a double-quantum selective spectroscopic imaging sequence for detecting the sucrose distribution in the stem of sugar cane (Saccharum officinarum L.) is described. The results show that local differences in sucrose distribution can be detected non-invasively with a resolution of 0.4x0.4x6 mm(3) to 0.645x0.645x6 mm(3).
Cervical neoplasia originating from the vagus nerve in a dog.
An eight-year-old intact male Bernese mountain dog was referred with a history of chronic vomiting, coughing and signs of respiratory distress. Other historical findings included lethargy, weight loss and choking. On presentation, clinical findings were Horner's syndrome, ipsilateral laryngeal hemiplegia, coughing, gagging, respiratory distress and vomiting. Lateral cervical radiographs showed ill-defined mineralisation in the soft tissue ventral to the third cervical vertebra, while ultrasonography of the neck revealed a well marginated heterogeneous mass with focal hyperechogenic lesions and acoustic shadowing. Results of an ultrasound-guided fine needle aspirate suggested neoplasia. At necropsy, a large tumour was detected in the ventral cervical region, originating from the right vagosympathetic trunk. In view of the infiltrating pattern, the cellular pleomorphism and the numerous mitoses on histopathological examination, the tumour was classified as a malignant peripheral nerve sheath tumour.
Iron-Mediated Diastereoselective Spiroannelations with Vinylogous Urethanes - A Novel Access to Spiroannelated Carbo- and Heterocycles.
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Measurement of venous outflow pressure in the central retinal vein to evaluate intraorbital pressure in Graves' ophthalmopathy: a preliminary report.
PURPOSE: To evaluate the intraorbital pressure in patients with Graves' ophthalmopathy (GO) in relation to the intraocular pressure (IOP) and proptosis and to find out whether optic nerve compression is predictable. METHODS: The venous outflow pressure (VOP) in the central retinal vein was measured by the perviously described technique of oculodynamometry.1 Since the central retinal vein passes through the orbit, the VOP cannot be lower than the intraorbital pressure if outflow is to be guaranteed. The IOP was measured either in primary position or with slight chin elevation to avoid restriction of the globe. Fifty-seven patients underwent a complete ophthalmologic examination, including VOP measurements, Hertel exophthalmometry and visual fields. RESULTS: The IOP in primary position ranged between 10 and 29 mmHg and in most (n=54) cases the VOP was 0-4 mmHg higher than the IOP. These patients had neither scotomas nor visual deterioration during an observation period of up to 2 years. In those cases (n=3) where the difference between IOP and VOP was 35 mmHg, the patients developed scotomas and visual deterioration and had to be treated (high-dose steroids or orbital decompression). The elevation in VOP did not correlate with the degree of proptosis. In one unilateral case, treatment of high IOP (32 mmHg) with dorzolamide drops led to a decrease in visual acuity of two lines, inferior field depression and relative afferent pupillary defect. The difference between IOP and VOP was 10 mmHg. Stopping treatment normalized visual function, the IOP rose to its original level and the difference between IOP and VOP was 4 mmHg. CONCLUSION: The increased IOP in GO is not caused by primary glaucoma but by elevated intraorbital pressure. The difference between IOP and VOP must be <5 mmHg to guarantee normal perfusion. We interpret these findings to suggest that loss of visual acuity and visual field defects may not only be caused by optic nerve compression at the apex but also by deterioration of optic nerve head perfusion.
Behavioral and pharmacological treatment methods for pregnant smokers: issues for clinical practice.
Active and passive exposure to tobacco smoke are the most serious and preventable causes of poor maternal, fetal, and infant outcomes in the United States. Unfortunately, the majority of pregnant smokers do not quit smoking before or during pregnancy or after childbirth. We describe a standardized behavioral counseling model and discuss issues to consider in recommending the use of pharmacotherapy during pregnancy. Although the Food and Drug Administration no longer classifies nicotine replacement therapy (NRT) as contraindicated during pregnancy, precautions should be carefully considered for use in this population. This paper provides a synopsis of the risks of exposure to tobacco smoke during pregnancy and the postpartum; estimates the population at risk and the potential for increased cessation if effective health education methods during pregnancy were routinely provided; presents a meta-analysis of "best practice" patient education methods for pregnant smokers; and estimates the number of pregnant heavy smokers who might be eligible for NRT. We suggest five issues for the physician to consider before recommending NRT medications to pregnant patients who are heavy smokers. The judicious use of NRT medications may significantly reduce harm to the infants of heavy smokers. More evidence derived from large population-based research, however, is needed to provide guidance to the physician about NRT eligibility, dose, scheduling, and effectiveness in clinical practice.
Biochemical and molecular characterization of corn (Zea mays L.) root elongases.
Root surfaces are protected against the soil environment by the deposition of lignin and suberin. In order to obtain more insight into the regulation of root suberin biosynthesis, elongases from primary roots of corn (Zea mays L.) seedlings were characterized. Elongase activities (acyl-CoA and ATP-dependent) were located in the microsomal fraction of the root cells. C(20), C(22) and C(24) fatty acids were detected as primary products of elongases. Preferred substrates of the acyl-CoA elongases were C(18:0)-CoA and C(20:0)-CoA. Applying a molecular approach, using PCR and degenerate primers derived from the sequences of known leaf and seed 3-ketoacyl-CoA synthases (KCSs), catalysing the first step of very-long-chain fatty acid synthesis, the cDNA of a putative root KCS was obtained showing high homology to known leaf and seed KCSs at the DNA and amino acid levels. Thus, our approach provides the first direct evidence for the presence and the activity of root elongases in Z. mays. Ongoing research is focusing on the molecular analysis and the regulation of KCS expression in roots in reaction to different environmental stimuli.
Treatment of feline leukemia virus (FeLV) infection.
FeLV infection is still considered to account for most disease-related deaths in pet cats. Different treatment attempts with various drugs were performed in the past but none resulted in healing or complete virus elimination. Therefore, it caused a sensation when Horber and Mayr [Horber, D., Mayr, B., 1991. Prax. 19, 311-314; Horber, D., Schnabl, W., Mayr, B., 1992. Tierarztl. Umschau 47, 556-560; Mayr, B., Horber, D., 1992. Kleintierprax. 37, 515-518] published that they were able to cure 80 to 100% FeLV-infected cats from viremia by using an immunomodulating compound. Articles in cat breeder and cat owner journals appeared assuming that obviously there is a rescue for FeLV-infected cats suffering from this deadly infection. The immunomodulator [Buttner, M., 1993. Comp. Immun. Microbiol. Infect. Dis. 18, 1-10] used in those studies was the so-called 'paramunity inducer' PIND-ORF (Baypamun, Bayer, Leverkusen, Germany) consisting of inactivated parapox ovis virus. Since that time, Baypamun is the most commonly used drug for treatment of FeLV infection in Germany and other European countries. Four placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of Baypamun and other compounds in naturally FeLV-infected cats under controlled conditions.
[Extensive eosinophilic pulmonary infiltrates in a depressive patient treated with maprotiline].
A 74 year old man developed progressive dyspnea under treatment with the tetracyclic antidepressant maprotiline for three months. A chest x-ray revealed extended pulmonary infiltrates. Marked eosinophilia of the periperal blood was found (up to 2300/microliter). Rapid clinical and radiological improvement was observed solely by withholding the drug. The eosinophil count retourned to normal within a few weeks. The possible pathogenesis is discussed and the literature reviewed.
Reactivation of herpesvirus infections after vaccinations?
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[Angioedema induced by ACE inhibitors and angiotensin II-receptor antagonists: analysis of 98 cases].
Angiooedema has been reported as a rare but in most cases serious adverse effect of ACE inhibitors. Recent reports have indicated that angiotensin II-receptor antagonists may also induce angiooedema. As part of the spontaneous reporting scheme in Switzerland the Swiss Drug Monitoring Centre (SANZ) has received reports on 94 cases of ACE inhibitor-induced and 4 cases of angiotension II-receptor antagonist-induced angiooedema. These 98 spontaneously reported cases were analysed in detail. 28 cases were classified as serious and in three patients intubation was even required. In 35% of cases angiooedema was induced within the first week of therapy and in 64% within the first year. In one case the angio-oedema displayed latency of 8 years. Latency of this duration shows that this adverse drug reaction (ADR) may be hard to detect. In 45 of the 98 cases the oedema persisted for more than one day (maximum 2 months), although in some instances the patients continued ACE-inhibitor therapy. In 25 cases the oedema recurred, in one instance as many as 20 times. In rare cases angiooedema may also be induced by angiotensin II-receptor antagonists, although in such instances the course of the oedema was usually milder. In two of the four reported cases angiooedema recurred after switching from an ACE inhibitor to an angiotensin II-receptor antagonists. The four reported cases from Switzerland showed a similar profile when compared with 25 internationally documented cases. Our data indicate that angiooedema is a specific ACE inhibitor ADR. A protracted latency period may be observed and recurrence of oedema is frequent. Angiotensin II-receptor antagonist-induced angiooedema may also occur in rare instances.
Postmarketing safety information: how useful are spontaneous reports?
UNLABELLED: From 1995 until June 1998 123 new chemical entities (NCEs) were launched in Switzerland. In this time period 250 reports of adverse reactions (ADRs) involving 56 different NCEs were reported to the Swiss Drug Monitoring Center SANZ directly by physicians within the voluntary spontaneous reporting scheme (SRS). No cases from observational or clinical postmarketing studies were included. Of the reports 88% were suspected to be drug-related and 20% of them were serious. In 64% the ADRs were unlabelled and not notified to the health professionals. Disorders of the central nervous system (CNS) were reported in 32% and cardiovascular disorders in 26% of the unlabelled and serious cases. The non-serious cases accounted for 80% of the reported NCE-ADRs and 60% of them were unlabelled. Skin reactions were reported most frequently (18%), followed by psychic (15%), gastrointestinal (10%), cardiovascular and CNS disorders (8% each). In the labelled non-serious cases gastrointestinal and skin reactions were reported in 25% and 24% respectively. The other system organ classes were involved to a much smaller extent (<8%). CONCLUSIONS: (1) Spontaneous reports are of great value in optimizing postmarketing safety information. (2) Early reports give rise to a different ADR profile than expected from premarketing safety information. (3) Spontaneous reports have a strong signalling function especially for drugs used by general practitioners. (4) Sensitive signal detection systems are of great value in detecting non-labelled and serious ADRs in an early phase.
Cervical dimensions and risk of preterm birth: a prospective cohort study.
OBJECTIVE: To examine the relation between cervical dilatation and length and the risk of spontaneous preterm birth, including its subtypes preterm labor and preterm premature rupture of membranes (PROM). METHODS: Cervical dimensions assessed by clinical examination were recorded prospectively at 24-29 weeks' gestation in 871 subjects with singleton pregnancies who were followed to delivery. Relative risks (RRs) of preterm birth, preterm labor, and preterm PROM were calculated for clinically distinguishable categories of cervical dilatation and length and for cervical score (length minus dilatation). Regression analysis was used to adjust for confounding. Time to delivery from baseline examination was summarized using survival analysis. RESULTS: There were 73 spontaneous preterm births (8.3%), 46 preterm labors and 27 cases of preterm PROM. All cervical measurements were associated with increased risks of preterm birth, with increasing abnormality more strongly predictive of risk. The adjusted RR for preterm birth with dilatation of at least 0.5 cm was 2.9 (95% confidence interval [CI] 1.2, 7.3); for length of 1.5 cm or less, the RR was 2.1 (95% CI 1.0, 4.5), and for cervical score less than 2.0, the RR was 2.8 (95% CI 1.4, 5.6). The association with cervical measurements was stronger for preterm PROM than for preterm labor, although precision was limited. These measurements had high specificity (93-99%) and low sensitivity (8-20%) for predicting preterm birth. CONCLUSION: In asymptomatic women at 24-29 weeks' gestation, greater cervical dilatation and shorter length were associated with increased risk of spontaneous preterm delivery, particularly preterm PROM.
Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device.
Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is especially a problem in long-term treatment of non-life threatening diseases, such as growth retardation in children. Until recently, all human growth hormone (hGH) products required a reconstitution process. Norditropin((R)) SimpleXx(TM) is a liquid formulation of the biosynthetic hGH product Norditropin((R)), and, together with an improved NovoPen((R)) 1.5, NordiPen(TM), and an auto-insertion device, PenMate(TM)/NordiPenMate(TM), it has been developed in order to ease the injection process for patients. A randomized, open, multicentre, crossover trial compared Norditropin((R)) SimpleXx(TM)/improved NovoPen((R)) 1.5 with freeze-dried Norditropin((R)) PenSet((R))/Nordiject((R)). A total of 67 children with GH deficiency, aged 5-18 years, were treated with either Norditropin((R)) SimpleXx(TM) for 6 weeks followed by Norditropin((R)) for 6 weeks or the opposite (sequences I and II, respectively). Acceptability/convenience and pain perception were evaluated by questionnaire after each period. The function and handling of the PenMate(TM) were evaluated in a Dutch trial by 27 GH-treated children with intrauterine growth retardation, aged 4-16 years, and their parents. All children were accustomed to using the Nordiject((R)) pen. The evaluation of the PenMate(TM) was based on a questionnaire. A similar trial was conducted in England, in which the NordiPen(TM) and the NordiPenMate(TM) were evaluated by 25 GH-treated children and their parents. Norditropin((R)) SimpleXx(TM) was found to be easier to inject by 64% of the children, and 98% of the children found the system easier to use overall. There was no difference in pain perception between the two administration systems, as judged by questionnaires and visual analogue scale score. Three out of four patients preferred to continue treatment with Norditropin((R)) SimpleXx(TM). The safety profiles of the two systems were similar. In the Dutch trial, the PenMate(TM) was found to be easy and safe to handle, even for very young children (aged 4-5 years). Of patients who took a long time to get used to the injections, 73% found that the new pen would help. A total of 88% of the children would prefer to use the PenMate(TM) in the future. Positive results of the handling tests were also reported in the British trial. The use of Norditropin((R)) SimpleXx(TM) and the auto-insertion device may improve patient compliance.
Treatment of feline leukemia virus-infected cats with paramunity inducer.
Two placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of the paramunity inducer, Baypamun in feline leukemia virus (FeLV)-infected cats under controlled conditions. In the first study, 120 cats were involved; 60 cats were treated with Baypamun and 60 with a placebo preparation of virus-free cell culture medium. Dosage and administration of the drug over a 7-week period were performed according to the instructions given by the company. Remission of viremia occurred in 12% and 7% of the cats treated with Baypamun and placebo, respectively. This difference was not statistically significant. In the second study, 30 naturally infected cats were treated in a placebo-controlled double-blind trial. In total, 20 immunological, clinical, laboratory, and virological parameters were examined. No statistically significant differences could be demonstrated between Baypamun and placebo application. Therefore, FeLV infection was not influenced by Baypamun treatment.
Expression and functional activity of the IL-8 receptor type CXCR1 and CXCR2 on human mast cells.
To further elucidate mechanisms involved in mast cell accumulation at sites of cutaneous inflammation, we have studied the ability of human leukemic mast cells (HMC-1 cells) to express functionally active IL-8 receptors. Expression of mRNA for both types of IL-8 receptors (CXCR1 and CXCR2) was demonstrated by PCR and of both proteins by flow cytometry. Binding and competition studies with 125I-labeled IL-8 and its homologue melanoma growth stimulating activity (125I-labeled MGSA) revealed two specific binding sites for IL-8, K1 = 1.1 x 10(11) M(-1) and K2 = 5 x 10(7) M(-1); and for MGSA, K1 = 2.8 x 10(10) M(-1) and K2 = 5 x 10(7) M(-1). This finding was supported by a dose-dependent rise of cytosolic free calcium concentration ([Ca2+]i) induced by both chemokines and to a lesser extent by the homologue neutrophil-activating peptide-2 (NAP-2). A significant migratory response of human leukemic mast cells (HMC-1) was observed with all three chemokines at a range from 10(-8) M to 10(-9) M. Moreover, the formation of cellular F-actin was induced in a rapid, dose-dependent fashion, with a maximally 1.7-fold increase at 10(-7) M. Using postembedding immunoelectron microscopy, we could show the expression of CXCRI on the cytoplasmatic membrane of isolated human skin mast cells whereas CXCR2 was located in mast cell-specific granules. These findings demonstrate for the first time the functional expression of both types of IL-8 receptors on human mast cells, suggesting a role for their ligands during mast cell activation and recruitment.