Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: a retrospective evaluation of a 12-year single-center experience.

Delayed cerebral infarction (DCI) is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). The benefits of magnesium sulfate as an alternative treatment are controversial, and most previous studies examined its benefits only as adjunctive treatment to traditional nimodipine. We retrospectively analyzed aSAH patients records with magnesium sulfate between 2010 and 2021. We aimed for a serum magnesium concentration of 2-2.5 mmol/l between post-hemorrhage days 3 and 12. The patients were separated in three groups based on average serum magnesium concentration (magnesium >2 mmol/l, reduced magnesium 1.1-1.9 mmol/l, and no magnesium). Additionally, we assessed delayed cerebral infarction (DCI) and clinical outcome at follow-up, using the modified Rankin Scale (mRS), categorized in favorable (0-3) and unfavorable outcome (4-5). In this analysis, 548 patients were included. Hereof, radiological evidence of DCI could be found in 23.0% (n = 126) of patients. DCI rates were lower if patients' average serum magnesium was higher than 2 mmol/l (magnesium 18.8%, n = 85; reduced magnesium 38.3%, n = 23; no magnesium 51.4%, n = 18; p < 0.001). Also, at the last follow-up, patients in the group with a higher serum magnesium concentration had better outcome (favorable outcome: magnesium 64.7%, n = 293; reduced magnesium 50.0%, n = 30; no magnesium 34.3%, n = 12; p < 0.001). This 12-year study reveals the value of serum concentration-guided magnesium administration in aSAH patients. Our findings demonstrate the safety and efficacy when titrated to a serum concentration of 2-2.5 mmol/l. We observed higher rates of delayed cerebral infarction and unfavorable outcomes in patients with serum concentrations below 2 mmol/l.

Mixing Efficiency in the Ocean.

Mixing efficiency is the ratio of the net change in potential energy to the energy expended in producing the mixing. Parameterizations of efficiency and of related mixing coefficients are needed to estimate diapycnal diffusivity from measurements of the turbulent dissipation rate. Comparing diffusivities from microstructure profiling with those inferred from the thickening rate of four simultaneous tracer releases has verified, within observational accuracy, 0.2 as the mixing coefficient over a 30-fold range of diapycnal diffusivities. Although some mixing coefficients can be estimated from pycnocline measurements, at present mixing efficiency must be obtained from channel flows, laboratory experiments, and numerical simulations. Reviewing the different approaches demonstrates that estimates and parameterizations for mixing efficiency and coefficients are not converging beyond the at-sea comparisons with tracer releases, leading to recommendations for a community approach to address this important issue.

How do long-term development and periodical changes of river-floodplain systems affect the fate of contaminants? Results from European rivers.

In many densely populated areas, riverine floodplains have been strongly impacted and degraded by river channelization and flood protection dikes. Floodplains act as buffers for flood water and as filters for nutrients and pollutants carried with river water and sediment from upstream source areas. Based on results of the EU-funded "AquaTerra" project (2004-2009), we analyze changes in the dynamics of European river-floodplain systems over different temporal scales and assess their effects on contaminant behaviour and ecosystem functioning. We find that human-induced changes in the hydrologic regime of rivers have direct and severe consequences on nutrient cycling and contaminant retention in adjacent floodplains. We point out the complex interactions of contaminants with nutrient availability and other physico-chemical characteristics (pH, organic matter) in determining ecotoxicity and habitat quality, and draw conclusions for improved floodplain management.

Tumor-associated neoexpression of the pS2 peptide and MUC5AC mucin in primary adenocarcinomas and signet ring cell carcinomas of the urinary bladder.

To gain more detailed insight into the histogenesis of primary nonurachal adenocarcinomas and signet ring cell carcinomas of the urinary bladder, we analyzed by immunohistochemistry the expression of a broad panel of proteins, associated with cell differentiation (pS2 peptide, MUC5AC, MUC6, spasmolytic polypeptide, cyclooxygenases-1 and -2, caveolin-1), and of various novel known or candidate tumor suppressors (14-3-3 sigma, SYK, PTEN, maspin). Included were 12 adenocarcinomas admixed to urothelial carcinomas, 10 pure adenocarcinomas and 5 signet ring cell carcinomas. As the most important finding, the majority of signet ring cell carcinomas and three quarters of the adenocarcinomas (72.7%) expressed the pS2 peptide, and nearly half of the adenocarcinomas (45.5%) as well as most of the signet ring cell carcinomas were observed to secrete the MUC5AC apomucin. Since expression of both proteins was absent in the normal nonneoplastic urothelium, their tumor-associated appearance is regarded as a neoexpression or reexpression, respectively, of normally cryptic antigenic determinants, and is assumed to be involved in the phenotypical formation of vesical adenocarcinomas, including signet ring cell carcinomas. The expression of both pS2 and MUC5AC in variants of urothelial carcinomas with a glandular differentiation and an extracellular mucus production support the concept that adenocarcinomas may histogenetically develop from preexistent TCC. Adenocarcinomas which secrete the pS2 peptide and the MUC5AC glycoprotein are proposed to be subclassified as adenocarcinomas of the intestinal type, as distinguished from those of the common type lacking an expression. The tumor suppressor genes showed a loss of protein expression in adenocarcinomas, ranging from 54.5% (14-3-3 sigma), to 31.8 (PTEN), 27.3% (SYK) and 18.2% (maspin). Similar expression profiles in the coexistent urothelial carcinomas argue against a specific involvement of these genes during the morphogenesis of adenocarcinomas.

[Recurrent familial cardiac myxomas and lentiginosis. Second recurrence in a 41-year-old female patient]. / Rezidivierende familiäre kardiale Myxome und Lentiginose. Zweites Myxomrezidiv bei einer 41-jährigen Patientin.

The case of a 41-year-old woman with recurrent cardiac myxomas and widespread lentiginosis is reported. The diagnosis of a Carney complex was established 7 and 25 years, respectively, after first manifestation of the cardiac myxomas in both the patient and her brother. This peculiar hereditary disease is commonly associated with multiple neoplasms and an endocrine overactivity, requiring a thorough examination of the patients and their relatives to detect additional typical manifestations.

[Epithelioma cuniculatum plantare in the region of a skin scar due to mechanical trauma. Insurance law aspects of scar carcinomas]. / Carcinoma cuniculatum plantare im Bereich einer mechanisch-traumatisch verursachten Hautnarbe. Versicherungsrechtliche Aspekte des Narbenkarzinoms.

We herein report a case of a highly differentiated verrucous squamous cell carcinoma of the sole of the left forefoot ("epithelioma" or "carcinoma cuniculatum plantare") that had--as a specific feature--developed within a preexisting long-standing skin scar due to an earlier occupational crush injury. Because of expansive tumor growth extending to the metatarsal bones and penetrating the tissue between the tendons, an ultrashort amputation of the hindfoot was performed according to the method of Chopart. The pathogenetic mechanisms possibly underlying the formation of scar carcinomas are discussed. For judgement of legal liability insurance questions, the criteria indicating a causal relationship between traumatic scars and cancer development are presented.

[Solitary intraparotid neurofibroma of the facial nerve. Symptomatology, biology and management]. / Das solitäre intraparotideale Neurofibrom des N. facialis. Symptomatik, Biologie und Management.

Neurogenic neoplasms of the parotid gland are extremely uncommon. We present the case of a solitary intraparotid neurofibroma of the N. facialis occurring in a 55-year-old female who noted a painless left-side enlargement in the region of the parotid gland over a period of 2 years. Facial function was normal. Magnetic resonance imaging revealed a well-demarcated round mass within the left parotid. At surgery, a tumor was found involving the main trunk of the facial nerve, histopathologically representing a neurofibroma. Since solitary intraparotid neurofibromas are characterized by a very slow growth lacking the propensity for malignant transformation, the tumor was left to preserve facial nerve function. The clinical course over months or even years and the non-specific symptomatology are characteristic of intraparotid facial neurofibromas. Surgical management depends on the clinical setting in the individual case. Conservative treatment based on facial nerve preservation and leaving the tumor in situ is recommended, rather than radical tumor removal with resection of the segment of the N. facialis involved.

[Erdheim-Chester disease]. / Erdheim-Chester-Krankheit.

HISTORY AND CLINICAL FINDINGS: A 55-year-old female was admitted complaining of musculoskeletal pain and weakness of both lower extremities for a number of years. Due to a hypothalamic mass of unknown aetiology a diabetes insipidus, a gonadotrophic, somatotrophic and a partially corticotrophic insufficiency had developed. INVESTIGATIONS: Laboratory investigations yielded elevated levels of several inflammatory parameters (C-reactive protein, blood sedimentation rate, fibrinogen and thrombocytes). Serological parameters indicating a systemic rheumatic disorder were absent. X-ray examination revealed combined osteolytic and osteoblastic lesions within the distal parts of both femora and within the proximal portions of both tibiae. MRI showed signal alterations and (99m)Technetium bone scan exhibited a considerably increased uptake. Histopathologically, a biopsy of the left tibia showed multifocal small infiltrates of foamy histiocytes indicating Erdheim-Chester disease (ECD). TREATMENT AND COURSE: Under treatment with glucocorticosteroids musculoskeletal complaints improved, but re-appeared following dose reduction. A therapeutic trial using methotrexat did not affect the complaints. CONCLUSION: The Erdheim-Chester syndrome is considered to belong to diseases with a proliferation of the monocytic-histiocytic and dendritic cellular system. In the presence of symmetric musculoskeletal symptoms associated with osteosclerotic and osteolytic lesions particularly occurring in the long bones of the lower extremities and concomitant with elevated serum markers of inflammation, the Erdheim-Chester disease should be taken into account. To date, no validated therapy exists.

Brain tissue oxygen guided treatment supplementing ICP/CPP therapy after traumatic brain injury.

OBJECTIVE: To evaluate the effects of a brain tissue oxygen (P(ti)O(2)) guided treatment in patients with traumatic brain injury. METHODS: P(ti)O(2) was monitored in 93 patients with severe traumatic brain injury. Forty patients admitted from 1993 to 1996 were treated with intracranial pressure/cerebral perfusion pressure (ICP/CPP) management alone (ICP < 20 mm Hg, CPP > 70 mm Hg). Fifty three patients admitted from 1997 to 2000 were treated using ICP/CPP management, but in this second group CPP was also increased as individually required to raise the P(ti)O(2) above 1.33 kPa (10 mm Hg) (P(ti)O(2) guided group). RESULTS: Cerebral hypoxic phases with P(ti)O(2) values below 1.33 kPa occurred significantly less often in the P(ti)O(2) guided group. P(ti)O(2) values were higher over the whole monitoring period. No statistical differences could be observed in outcome at six months, despite a positive trend in the P(ti)O(2) guided group. CONCLUSIONS: Cerebral hypoxic events can be reduced significantly by increasing cerebral perfusion pressure as required. To show a clear beneficial effect of P(ti)O(2) guided cerebral perfusion pressure management on outcome, a multicentre randomised trial needs to be undertaken.

Fluid flow-induced prostaglandin E2 response of osteoblastic ROS 17/2.8 cells is gap junction-mediated and independent of cytosolic calcium.

It has been well demonstrated that bone adapts to mechanical loading. To accomplish this at the cellular level, bone cells must be responsive to mechanical loading (mechanoresponsive). This can occur via such mechanisms as direct cell deformation or signal transduction via complex pathways involving chemotransport, hormone response, and/or gene expression, to name a few. Mechanotransduction is the process by which a bone cell senses a biophysical signal and elicits a response. While it has been demonstrated that bone cells can respond to a wide variety of biophysical signals including fluid flow, stretch, and magnetic fields, the exact pathways and mechanisms involved are not clearly understood. We postulated that gap junctions may play an important role in bone cell responsiveness. Gap junctions (GJ) are membrane-spanning channels that physically link cells and support the transport of small molecules and ions in the process of gap junctional intercellular communication (GJIC). In this study we examined the role of GJ and GJIC in mechanically stimulated osteoblastic cells. Following fluid flow stimulation, we quantified prostaglandin E(2) (PGE(2)) (oscillatory flow) and cytosolic calcium (Ca(2+)) (oscillatory and steady flow) responses in ROS 17/2.8 cells and a derivative of these cells expressing antisense cDNA for the gap junction protein connexin 43 (RCx16) possessing significantly different levels of GJIC. We found that the ROS17/2.8 cells possessing increased GJIC also exhibited increased PGE(2) release to the supernatant following oscillatory fluid flow stimulation in comparison to coupling-decreased RCx16 cells. Interestingly, we found that neither osteoblastic cell line responded to oscillatory or steady fluid flow stimulation with an increase in Ca(2+). Thus, our results suggest that GJ and GJIC may be important in the mechanotransduction mechanisms by which PGE(2) is mechanically induced in osteoblastic cells independent of Ca(2+).

Therapeutic aspects of brain tissue pO2 monitoring after subarachnoid hemorrhage.

Prolonged phases of brain tissue hypoxia (ptiO2 < 10 mmHg) lead to cerebral infarction. Therefore, the present study investigates the role of ptiO2--monitoring to guide hypervolemic hypertensive therapy in patients suffering from severe subarachnoid hemorrhage (SAH). Besides transcranial doppler, neuromonitoring of ICP/CPP was supplemented by ptiO2 monitoring. The ptiO2 catheter was inserted into viable tissue in the vascular territory with the highest risk for vasospasm. Patients were divided in an infarction (n = 21) and a non-infarction group (n = 11). Critical CPP (< 70 mmHg) as well as hypoxic ptiO2 (< 10 mmHg) was significantly more frequent in the infarction group (CPP: 25 vs 13%, p < 0.001; ptiO2: 16 vs 7%, p < 0.001). In both groups, over 25% of the critical ptiO2 values occurred at a CPP > 90 mmHg. In the infarction group, 13 patients showed transient phases of hypoxia which normalized under induced hypervolemic hypertension and 5 patients developed persistent hypoxia. In the non-infarction group 6 patients showed transient hypoxia and in 5 patients no hypoxic values could be found. In conclusion, monitoring of ptiO2 provides an additional independent parameter to detect hypoxic events and to guide therapy.

Histogenesis of nonurothelial carcinomas of the urinary bladder from pre-existent transitional cell carcinomas. A histopathological and immunohistochemical study.

The histogenesis of nonurothelial carcinomas of the urinary bladder is difficult to understand, since the bladder is normally lined exclusively by transitional cell epithelium. To gain more insights into the pathogenesis of nonurothelial carcinomas, the morphology and immunohistochemistry of transitional cell carcinomas (TCC), mixed transitional cell and nonurothelial carcinomas, and pure nonurothelial carcinomas were comparatively studied. Of papillary and of nonpapillary (solid) TCC (overall incidence 6.8%), 4.8% and 15.4%, respectively, disclosed foci of altered celllular and architectural phenotypes, consisting of squamous epithelium, pseudoglandular formations, and true glands with or without mucus production. The diverse phenotypic variants develop obviously by a metaplastic process as a result of the well-known inherent potential of the urothelium to undergo several pathways of cellular differentiation. There is strong evidence that squamous cell carcinomas arise secondarily from a squamous metaplasia and adenocarcinomas from metaplastic glandular epithelium within pre-existing TCC following complete carcinogenic transformation of the initially bland-looking metaplastic tumor cells. The metaplastic origin of nonurothelial bladder carcinomas is supported by immunohistochemical findings. The high molecular weight cytokeratin 34betaE12 identifies tumor cells with squamous characteristics, helping to explain the development of squamous cell carcinomas. Secretion of MUC5AC apomucin is assumed to play a central role in the histogenesis of nonurachal mucus-producing adenocarcinomas, including signet ring cell carcinomas. Metaplastic phenotypic variants of TCC should be recognized as distinct tumor entities with the potential to transform into nonurothelial carcinomas and thus possibly implying a poorer clinical outcome than typical, uniform TCC.

(99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model.

INTRODUCTION: In the present study, (99m)Tc-radiolabelled E-selectin binding peptide ((99m)Tc-IMP-178) was investigated for its potential to image acute pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were performed using an irrelevant peptide ((99m)Tc-IMP-100) to demonstrate specificity. METHODS: An acute pyogenic osteomyelitis was induced by injecting 0.05 ml of 5% sodium morrhuate and 5x10(8) CFU of Staphylococcus aureus into the medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as untreated controls. Whole-body imaging of pyogenic (n=4) and untreated (n=4) animals was performed continuously during the first 8 h (12 MBq i.v. of (99m)Tc-IMP-178 and (99m)Tc-IMP-100 for control), and one further single image was acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after injection. Data of the histological/radiological and haematological investigations were obtained in all animals. RESULTS: Histopathologically, 15 of 16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major infiltration of the bone marrow by polymorphonuclear leukocytes as well as the formation of sequestra. Haematologically, the number of leukocytes increased by 100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v. injection, (99m)Tc-IMP-178 rapidly cleared from the body resulting in good scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer in the pyogenic bone was observed at 60 min p.i. (0.43+/-0.02% ID.g-1 for (99m)Tc-IMP-178 and 0.30+/-0.02% ID.g-1 for (99m)Tc-IMP-100), resulting in a higher osteomyelitis-to-healthy collateral ratio with T/B of 2.40+/-0.65 ((99m)Tc-IMP-178) compared with 1.85+/-0.48 ((99m)Tc-IMP-100). No adverse reactions were seen after injection of (99m)Tc-IMP-178. CONCLUSIONS: (99m)Tc-IMP-178 allows imaging of an acute osteomyelitic lesions, presumably by interaction of (99m)Tc-IMP-178 with activated upregulated vascular endothelium.

Clear cell adenocarcinoma of the male urethra in association with so-called nephrogenic metaplasia.

A clear cell adenocarcinoma of the urethra associated with so-called nephrogenic metaplasia occurring in a 57-year-old male patient is presented. Ten months following total urethrectomy, multiple pulmonary metastases had developed. The patient died 2.5 years after surgery. The possible histogenesis of clear cell adenocarcinoma of the lower urinary tract - reported to develop in the male urethra only in a very few cases - is reviewed briefly. We favor an origin from preexisting nephrogenic metaplasia as one of the possible histogenetic pathways.

Application of differential inflammatory cell count as a tool to monitor udder health.

A flow cytometric technique called differential inflammatory cell count was standardized by staining bovine peripheral blood leukocytes with a combination of DNA binding dyes SYBR green 1 and propidium iodide in water. Leukocytes were also stained with propidium iodide in detergent to determine total cell count. Differential inflammatory cell count assay was evaluated with individual quarter milk samples from 13 cows. Cows were sampled at weekly intervals for 3 wk and assayed for total cell count, mononuclear leukocyte count, and polymorphonuclear leukocyte count. Simultaneously, milk samples were evaluated by the conventional electronic somatic cell count (SCC) technique. Somatic cell count positively correlated with total cell count (r = 0.9), mononuclear leukocyte count (r = 0.8), and polymorphonuclear leukocyte count (r = 0.89). Quarters with SCC > log10 5.4 had a higher total cell count, mononuclear leukocyte count, and polymorphonuclear leukocyte count and were more often culture positive compared with quarters with SCC < log10 5.4. Quarters that were culture positive on all three test occasions had a higher proportion of polymorphonuclear leukocytes (33 to 49%) compared with quarters that were culture negative on all three test occasions (17 to 25%). The findings of this study suggest that differential inflammatory cell count assay has the potential to evolve as a new technique for evaluation of udder health status.

Expression of MUC5AC apomucin in transitional cell carcinomas of the urinary bladder and its possible role in the development of mucus-secreting adenocarcinomas.

The histogenesis of primary nonurachal mucus-producing adenocarcinomas of the urinary bladder including signet ring cell carcinomas remains to be elucidated, since the normal bladder contains neither columnar nor mucus-secreting glandular epithelium. Based upon the assumption that adenocarcinomas may develop secondarily from pre-existent transitional cell carcinomas (TCC) by a metaplastic process, it was the purpose of the current immunohistochemical study to analyze whether urothelial carcinomas are capable of secreting MUC5AC apomucin, using the monoclonal antibody 45MI. This antibody has been initially demonstrated to strongly react with the mucus-producing columnar cells of the surface gastric epithelium, recognizing a specific epitope located on the peptide core of glycoproteins as major components of mucins. Nine of 64 uniformly differentiated papillary (14.1%) and 5 of 66 nonpapillary (solid) TCC with a uniform urothelial differentiation (7.6%) expressed the MUC5AC antigen, yielding an overall incidence of 10.8%. Transitional cell carcinomas with a focally altered cellular and structural differentiation (squamous cell, pseudoglandular, true glandular and mixed differentiation) stained positively in a substantially higher percentage of 43.8% (21 of 48 cases). A positive immunoreactivity was also observed in 3 of 19 mixed transitional cell and nonurothelial carcinomas. The tumor-associated resurgence of normally cryptic MUC5AC antigenic determinants in transitional cell carcinomas is considered as a re-expression of oncofetal antigenicity, probably as a result of the embryologic origin of the urinary bladder from the pluripotent tissues of the cloacal endoderm and the mesodermal wolffian ducts. Our findings may help to better understand the histogenetic development of mucus-secreting vesical adenocarcinomas from pre-existent urothelial carcinomas.

Clinical cerebral microdialysis: brain metabolism and brain tissue oxygenation after acute brain injury.

While continuous monitoring of brain tissue oxygenation (P(ti)O2) is known as a practicable, safe and reliable monitoring technology supplementing traditional ICP-CPP-monitoring, the impact of cerebral microdialysis, now available bedside, is not proven extensively. Therefore our studies focused on the practicability, complications and clinical impact of microdialysis during long term monitoring after acute brain injury, especially the analysis of the correlation between changes of local brain oxygenation and metabolism. Advanced neuromonitoring including ICP-CPP-p(ti)O2 was performed in 20 patients suffering from acute brain injury. Analysis of the extracellular fluid metabolites (glucose, lactate, pyruvate, glutamate) were performed bedside hourly. No catheter associated complications, like infection and bleeding, occurred. However, longterm monitoring was limited in 5 out of 20 patients caused by obliteration of the microdialysis catheter after 3-4 days. In the individual patients partly a correlation between increased lactate levels as well as lactate pyruvate ratios and hypoxic brain tissue oxygenation could be found. Analysing the data sets of all patients only a low correlation was detected indicating physiological and increased lactate and lactate/pyruvate ratio during sufficient brain oxygenation. Additionally, concentrations of excitatory amino acid glutamate were found in normal and elevated range during periods of hypoxic oxygenation (P(ti)O2 < 10 mmHg) and intracranial hypertension. Our data strongly suggest partly evidence of correlation between hypoxic oxygenation and metabolic disturbances after brain injury. On the other hand brain metabolism is altered without changes of cerebral oxygenation. Further studies are indicated to improve our pathophysiological knowledge before microdialysis is routinely useful in neurointensive care.