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Biomedical subjects

M Horn

Publications and source records attributed to M Horn.

At least 19 recordsLinked to original sources

[Therapy-resistant depression with fatigue. A case of presumed streptococcal-associated autoimmune disorder].

After a tick bite and erythema chronicum migrans, a 31-year-old patient developed headaches, fatigue, multilocular pain and therapy-resistant depression with cognitive disturbances. Antibodies against Borrelia and Borna disease virus, high antibody titers against streptococci at the point of most severe depression and blood-CSF barrier dysfunction were found. Streptococcal antibody titers were normal 2 years before and 4 years after. With penicillin treatment and tonsillectomy, therapy-resistant depression improved. We suggest that the whole syndrome was streptococcal-associated autoimmune disease.

Adult↗

The use of confocal laser-scanning microscopy in microsurgery for invasive squamous cell carcinoma.

BACKGROUND: Ex-vivo confocal laser-scanning microscopy offers rapid imaging of excised tissue specimens without conventional histotechnical procedures. As vertical sections are prepared, morphological features can be assessed according to standard criteria used in conventional histopathology. OBJECTIVES: To validate the diagnostic confocal examination of squamous cell carcinoma (SCC) in microscopy-guided surgery. METHODS: Four independent observers received standardized instructions about diagnostic confocal microscopy features of SCC. Subsequently, 120 confocal images of fresh excisions from SCC or normal skin, imaged using a commercially available, near-infrared, reflectance confocal laser-scanning microscope, were evaluated by each observer. RESULTS: General morphology, such as location, size and shape of the cancer area could be visualized by the imaging system. Furthermore, densely packed and irregularly organized nuclei and nuclear atypia could be delineated. Overall, a sensitivity of 95% and a specificity of 96.25% were achieved by the four observers (positive predictive value 96.25%, negative predictive value 95.23%). CONCLUSIONS: This study provides a set of well-described morphological criteria with obvious diagnostic impact which should be used in further investigations. In the future, confocal laser-scanning microscopy may guide microsurgery of any skin cancer.

Carcinoma, Squamous Cell↗

The use of telemedicine in combination with a new stroke-code-box significantly increases t-PA use in rural communities.

BACKGROUND: The benefit of tissue plasminogen activator (t-PA) is strongly associated with the time to treatment. In Bavaria, Germany, only half of the population has the opportunity to be transferred to 1 of the 19 stroke units within the critical time window of less than 3 hours. The aim of this study was to investigate the benefit of a new stroke-code-box for t-PA thrombolysis combined with a telemedicine network system to increase the use of acute stroke thrombolysis. METHODS: Two specialized stroke centers in Germany established a 24-hour telemedicine network (Telemedicine Pilot Project of an Integrated Stroke Care [TEMPiS]) to advise 12 community hospitals in eastern Bavaria. These clinics are linked via telemedicine in a 24-hour/7-day service network that allows patients to be examined by experts via a videoconference system Additionally, a special stroke-code-box for acute t-PA thrombolysis was designed to reduce time in the application and documentation process. RESULTS: In the 12-month period before implementation of the TEMPiS network system, 10 patients had received systemic thrombolysis. In our 6-month study period (from July to December 2003) and after implementation of a stroke-code-box for t-PA thrombolysis within the telestroke network, 164 patients with acute stroke were presented with t-PA treatment indications. Of this patient population, 27.4% (45 of 164) received t-PA. CONCLUSIONS: Stroke care, including t-PA thrombolysis in non-urban areas, is feasible using a modern stroke unit concept within a telestroke network. With the expertise of specialized stroke centers accessed via telemedicine and the design of a stroke-code-box for t-PA thrombolysis, nearly one-third of patients presented with a possible indication for systemic thrombolysis can be treated with t-PA, thereby increasing the options for a successful stroke treatment.

Aged↗

Quality of life after decompressive craniectomy in patients suffering from supratentorial brain ischemia.

BACKGROUND: Decompressive craniectomy in patients suffering from severe ischemic stroke in the middle cerebral artery territory (MCA) decreases mortality to near 30%. Additionally functional outcome in patients after early craniectomy seems to be better than in patients without surgery. The aim of this study was to investigate the quality of life of patients who were treated with a decompressive craniectomy for severe ischemic stroke. METHODS: We retrospectively investigated the patient records of 48 patients (26 men, mean age 48 years) suffering from ischemic strokes who underwent craniectomy since 1993. We registrated the preoperative neurological status, the diagnostic data as well as the operative procedure. The outcome was assessed using the Barthel Index, the Glasgow outcome score and a questionnaire to assess the quality of life according to Blau consisting of eleven items at follow-up. FINDINGS: The mortality rate was 26%, age correlated to mortality (44.5 versus 60.3 years GOS 1, mean, p<0.0006). Craniectomy without dura patch correlated to mortality (58% versus 14% GOS 1 with dura patch, p<0.005). The quality of life index was 6 points mean. The quality of life index did neither differ significantly between patients with left or right sided lesions nor in patients with and without aphasia. 83% of the surviving patients and/or dependents would agree to surgery in the future. CONCLUSION: Despite the fact that some patients remain in a poor neurological condition, quality of life after decompressive surgery for ischemic stroke seems to be acceptable to the patients.

Adult↗

[Telemedicine stroke department network. Introduction of a telemedicine pilot project for integrated stroke management in South Bavaria and analysis of its efficiency].

More than 100 stroke units have been established in Germany. In rural areas, however, acute stroke care needs to be improved. In order to advance clinical stroke therapy, two specialized stroke centers founded a telemedicine network (TEMPiS) among 12 community hospitals in eastern Bavaria. Each network hospital established specialized stroke wards where qualified teams manage acute stroke patients. Twenty-four hours daily, physicians in local hospitals are able to contact the stroke centers via videoconferencing including transmission of digital DICOM data. To study the efficacy of this network, a controlled trial will be performed. Five TEMPiS-network hospitals will be matched with five other hospitals equal in size, catchment area, and diagnostic techniques. For about 1 year, all consecutive stroke cases in the matched study hospitals will be prospectively recorded in a database. Neurological deficits will be quantified on the National Institute of Health Stroke Scale within 24 h after stroke onset. Mortality and institutional care as a combined primary endpoint will be assessed after 3 and 12 months. Furthermore, functional outcome according to the modified Rankin scale, Barthel score, and quality of life will be assessed using a standard telephone interview. Data acquisition started in July 2003, and final results are expected in 2005.

Centralized Hospital Services↗

Surgery for unruptured intracranial aneurysms in a low-volume neurosurgical unit.

OBJECTIVES: To evaluate outcomes after surgical treatment for unruptured intracranial aneurysms in a low-volume neurosurgical unit. MATERIAL AND METHODS: Consecutive patients operated during the years 1988-98 at the Department of Neurosurgery, University Hospital of North Norway, were studied retrospectively. Procedure-related complications were registered. The modified Rankin Scale and the Glasgow Outcome Scale, Extended version (GOS-E), were used for assessment of outcome. RESULTS: Thirty-six aneurysms were repaired in 32 patients during 34 surgical procedures. Surgery-related central nervous system complications occurred in eight (25%) patients. The complication rate was 35% for the first 17 procedures, and 12% for the last 17. The latter group of procedures were performed during a period of 3 years, whereas the former group was spread over a period of 8 years. A favourable outcome (GOS-E score 6-8) was reached in 27 (84%) patients. CONCLUSION: Decision-making in patients with unruptured intracranial aneurysms must be based on knowledge about institution-specific complication rates, preferably followed on a prospective basis.

Adult↗

Microbial diversity of marine sponges.

The recent application of molecular microbial ecology tools to sponge-microbe associations has revealed a glimpse into the biodiversity of these microbial communities, that is considered just 'the tip of the iceberg'. This chapter provides an overview over these new findings with regard to identity, diversity and distribution patterns of sponge-associated microbial consortia. The sponges Aplysina aerophoba (Verongida), Rhopaloeides odorabile (Dicytoceratida) and Theonella swinhoei (Lithistida) were chosen as model systems for this review because they have been subject to both, cultivation-dependent and cultivation-independent approaches. A discussion of the microbial assemblages of Halichondriapanicea is presented in the accompanying chapter by Imhoff and Stöhr. Considering that a large fraction of sponge-associated microbes is not yet amenable to cultivation, an emphasis has been placed on the techniques centering around the 16S rRNA gene. A section has been included that covers the potential of sponge microbial communities for drug discovery. Finally, a 'sponge-microbe interaction model' is presented that summarizes our current understanding of the processes that might have shaped the community structure of the microbial assemblages within sponges.

Animals↗

Local recurrence in melanoma in situ: influence of sex, age, site of involvement and therapeutic modalities.

BACKGROUND: Melanoma in situ (MIS) occurs on various body sites, in various age groups, and is managed by a variety of treatment modalities. Despite early treatment, recurrences may be encountered. OBJECTIVES: To evaluate the influence of sex, age, body site and treatment modalities on recurrence rate in MIS. Methods Histologically confirmed cases of MIS from our dermatopathological database (n = 1351) from 1990 to 2000 were statistically analysed with respect to epidemiological characteristics, treatment modalities and outcome. Treatment modalities of the included MIS were evaluated by searching for data in the medical records and histopathological data sheets. RESULTS: There was a predominance of female patients (60.8%), and of involvement of the head and neck (53.4%). Total excision was performed in 95.9% of all patients; the remainder received cryotherapy, laser therapy or radiotherapy. In 265 patients, no data on definitive treatment were available. Alternatives to total excision were particularly performed in patients with advanced age and with lesions localized on the face. The mean +/- SD 5-year recurrence rate was 6.8 +/- 1.3% for surgically removed lesions, but was 31.3 +/- 8.5% for lesions treated by other modalities (log rank test: P < 0.0001). In a multivariate approach, mode of therapy and site of involvement, but not age, were significant prognostic variables (Cox proportional hazard model: P < 0.01). CONCLUSIONS: In MIS, treatment modalities other than surgical excision may be used in certain situations, but carry a significantly increased risk of local recurrence.

Adolescent↗

Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment.

BACKGROUND: Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid-face) and size of the lesion. OBJECTIVES: Following reports that such difficult-to-treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL-PDT. METHODS: An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL-PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24-month follow-up is reported here. Ninety-four patients with 123 lesions were enrolled and treated with MAL-PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult-to-treat BCC according to the protocol. RESULTS: The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and 94% at 24 months follow-up. CONCLUSIONS: Topical MAL-PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL-PDT preserves the skin and shows favourable cosmetic results.

Administration, Topical↗

Evidence for additional genus-level diversity of Chlamydiales in the environment.

The medically important order Chlamydiales has long been considered to contain a few closely related bacteria which occur exclusively in animals and humans. This perception of diversity and habitat had to be revised with the recent identification of the genera Simkania, Waddlia, Parachlamydia, and Neochlamydia with the latter two comprising endosymbionts of amoebae. Application of a newly developed PCR assay for the specific amplification of a near full length 16S rDNA fragment of these novel Chlamydia-related bacteria on activated sludge samples revealed the existence of at least four additional, previously unknown evolutionary lineages of Chlamydiales (each showing less than 92% 16S rRNA sequence similarity with all recognized members of this order). These findings suggest that some waste water treatment plants represent reservoirs for a diverse assemblage of environmental chlamydiae, a discovery which might also be of relevance from the viewpoint of human public health.

Chlamydiales↗

Chronic phosphocreatine depletion by the creatine analogue beta-guanidinopropionate is associated with increased mortality and loss of ATP in rats after myocardial infarction.

BACKGROUND: The failing myocardium is characterized by reductions of phosphocreatine (PCr) and free creatine content and by decreases of energy reserve via creatine kinase (CK), ie, CK reaction velocity (Flux(CK)). It has remained unclear whether these changes contribute directly to contractile dysfunction. In the present study, myocardial PCr stores in a heart failure model were further depleted by feeding of the PCr analogue beta-guanidinopropionate (GP). Functional and metabolic consequences were studied. METHODS AND RESULTS: Rats were subjected to sham operation or left coronary artery ligation (MI). Surviving rats were assigned to 4 groups and fed with 0% (n=7, Sham; n=5, MI) or 1% (n=7 Sham+GP, n=8 MI+GP) GP. Two additional groups were fed GP for 2 or 4 weeks before MI. After 8 weeks, hearts were isolated and perfused, and left ventricular pressure-volume curves were obtained. High-energy phosphate metabolism was determined with (31)P NMR spectroscopy. After GP feeding or MI, left ventricular pressure-volume curves were depressed by 33% and 32%, respectively, but GP feeding in MI hearts did not further impair mechanical function. Both MI and GP feeding reduced PCr content and Flux(CK), but here, effects were additive. In MI+GP rats, PCr levels and Flux(CK) were reduced by 87% and 94%, respectively. Although ATP levels were maintained in the GP and MI groups, ATP content was reduced by 18% in MI+GP hearts. Furthermore, 24-hour mortality in GP-prefed rats was 100%. CONCLUSIONS: Rats with an 87% predepletion of myocardial PCr content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.

Adenosine Triphosphate↗

Development of a technology for automation and miniaturization of protein crystallization.

The usage of standard 96 well microplates for the screening of crystallization conditions of recombinant proteins offers several advantages when compared to commonly used crystallization plate formats. The adoption of robotic technology for plate and glass slide preparation within a "hanging drop" vapour diffusion crystallization experiment enables to work with an increased throughput at reduced costs. In addition to commercial pipetting devices with a 96-channel aspirator/dispenser, solenoid ink-jet technology was applied to form 250 nl droplets with a diameter of approximately 1 mm. This allows miniaturization of crystallization screening set-ups with an estimated ten-fold cost reduction when compared to commonly used 24 well plates.

Concanavalin A↗

Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts.

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.

Antigens, CD↗

Large-gel two-dimensional electrophoresis-matrix assisted laser desorption/ionization-time of flight-mass spectrometry: an analytical challenge for studying complex protein mixtures.

The large-gel two-dimensional electrophoresis (2-DE) technique, developed by Klose and co-workers over the past 25 years, provides the resolving power necessary to separate crude proteome extracts of higher eukaryotes. Matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) provides the sample throughput necessary to identify thousands of different protein species in an adequate time period. Spot excision, in situ proteolysis, and extraction of the cleavage products from the gel matrix, peptide purification and concentration as well as the mass spectrometric sample preparation are the crucial steps that interface the two analytical techniques. Today, these routines and not the mass spectrometric instrumentation determine how many protein digests can be analyzed per day per instrument. The present paper focuses on this analytical interface and reports on an integrated protocol and technology developed in our laboratory. Automated identification of proteins in sequence databases by mass spectrometric peptide mapping requires a powerful search engine that makes full use of the information contained in the experimental data, and scores the search results accordingly. This challenge is heading a second part of the paper.

Animals↗

Detection of myocardial viability based on measurement of sodium content: A (23)Na-NMR study.

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content post-myocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in buffer-perfused rat hearts, infarct scar can be differentiated from intact myocardium by (23)Na-MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post-MI (N = 6-8 each), Na content was determined by (23)Na-NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083 vs. control). In Protocol 2, (23)Na-MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, (23)Na-MRI revealed a mean increase in signal intensity, to 142 +/- 6% of control values, in scar tissue. A threshold of 2 standard deviations of the image intensity allowed determination of infarct size, correlating with histologically determined infarct size (r = 0.91, P < 0.0001).

Animals↗

Simulated limnological effects of the Shasta Lake temperature control device.

We estimated the effects of a temperature control device (TCD) on a suite of thermodynamic and limnological attributes for a large storage reservoir, Shasta Lake, in northern California. Shasta Dam was constructed in 1945 with a fixed-elevation penstock. The TCD was installed in 1997 to improve downstream temperatures for endangered salmonids by releasing epilimnetic waters in the winter/spring and hypolimnetic waters in the summer/fall. We calibrated a two-dimensional hydrodynamic reservoir water quality model, CE-QUAL-W2, and applied a structured design-of-experiment simulation procedure to predict the principal limnological effects of the TCD under a variety of environmental scenarios. Calibration goodness-of-fit ranged from good to poor depending on the constituent simulated, with an R2 of 0.9 for water temperature but 0.3 for phytoplankton. Although the chemical and thermal characteristics of the discharge changed markedly, the reservoir's characteristics remained relatively unchanged. Simulations showed the TCD causing an earlier onset and shorter duration of summer stratification, but no dramatic affect on Shasta's nutrient composition. Peak inreservoir phytoplankton production may begin earlier and be stronger in the fall with the TCD, while outfall phytoplankton concentrations may be much greater in the spring. Many model predictions differed from our a priori expectations that had been shaped by an intensive, but limited-duration, data collection effort. Hydrologic and meteorological variables, most notably reservoir carryover storage at the beginning of the calendar year, influenced model predictions much more strongly than the TCD. Model results indicate that greater control over reservoir limnology and release quality may be gained by carefully managing reservoir volume through the year than with the TCD alone.

Climate↗

Temporal fluctuations of myocardia high-energy phosphate metabolite with the cardiac cycle.

This review describes the temporal changes of high-energy phosphate metabolites during the cardiac cycle. Under baseline condition, the extent of cyclical changes ("cycling") of ATP, phosphocreatine and inorganic phosphate varies between 10-15%. Such energy oscillations are not augmented under various forms of metabolic stress including 1) inotropic stimulation, 2) acute hypoxia and 3) failing, chronically infarcted hearts. Thus, the concentrations of high-energy phosphates over the cardiac cycle are a tightly regulated entity, even when energetic needs are substantially augmented.

Adenosine Triphosphate↗

Alterations in myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme-distribution in a model of left ventricular dysfunction.

The purpose of the current study was to evaluate myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) systems in a model of epinephrine-induced cardiomyopathy in rabbits. Eight rabbits received four repetitive epinephrine infusions (300 mg/kg/60 min, i.v.) in 12-day intervals and eight untreated rabbits served as controls (CTRL). Echocardiography demonstrated a significant deterioration of LV function as well as increased LV-diameter and -mass index in catecholamine-induced cardiomyopathy. Histological examination revealed that repetitive catecholamine infusion resulted in LV fibrous areas with collagenous content and an increase in myocyte width (16.9+/-0.8 microm vs. CTRL 12.9+/-0.9; P<0.05). LV dysfunction was associated with a decreased total LV lactate dehydrogenase activity (LDH; 0.43+/-0.03 IU/mg protein vs. CTRL 0.52+/-0.04; P<0.05) whereas total creatinine kinase activity was unchanged (CK; 7.30+/-0.63 IU/mg protein vs. CTRL 9.20+/-0.49, n.s.). Furthermore, myocardial LDH isoenzymes were shifted with a decrease in LDH(1) and an increase in LDH2 and LDH3 (LDH(1): 84.90+/-2.60% vs. CTRL 94.50+/-0.40; LDH2: 7.30+/-1.20% vs. 1.50+/-0.13; LDH3: 5.40+/-0.90% vs. 3.20+/-0.25; all P<0.05). Foetal B-CK isoenzymes were significantly increased (CK-MB 5.30+/-0.66 vs. 2.20+/-0.35%; P<0.05). The current study demonstrates changes in cardiac energy metabolism including an impaired LDH activity with a shift towards anaerobic isoenzymes as well as a more efficient CK system in a model of catecholamine-induced LV dysfunction.

Animals↗