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To investigate the incidence, risk factors, and outcomes of barotrauma (pneumomediastinum and subcutaneous emphysema) in mechanically ventilated COVID-19 patients. To describe the chest radiography patterns of barotrauma and understand the development in relation to mechanical ventilation and patient mortality.We performed a retrospective study of 363 patients with COVID-19 from March 1 to April 8, 2020. Primary outcomes were pneumomediastinum or subcutaneous emphysema with or without pneumothorax, pneumoperitoneum, or pneumoretroperitoneum. The secondary outcomes were length of intubation and death. In patients with pneumomediastinum and/or subcutaneous emphysema, we conducted an imaging review to determine the timeline of barotrauma development.Forty three out of 363 (12%) patients developed barotrauma radiographically. The median time to development of either pneumomediastinum or subcutaneous emphysema was 2 days (IQR 1.0-4.5) after intubation and the median time to pneumothorax was 7 days (IQR 2.0-10.0). The overall incidence of pneumothorax was 28/363 (8%) with an incidence of 17/43 (40%) in the barotrauma cohort and 11/320 (3%) in those without barotrauma (p ≤ 0.001). In total, 257/363 (71%) patients died with an increase in mortality in those with barotrauma 33/43 (77%) vs. 224/320 (70%). When adjusting for covariates, barotrauma was associated with increased odds of death (OR 2.99, 95% CI 1.25-7.17).Barotrauma is a frequent complication of mechanically ventilated COVID-19 patients. In comparison to intubated COVID-19 patients without barotrauma, there is a higher rate of pneumothorax and an increased risk of death.

Allergic respiratory disease represents a significant and expanding health problem worldwide. Allergic symptoms, such as asthma and hay fever, cause sleep impairment and reduce school and work performance. The cost to society is substantial. Allergen avoidance and pharmacotherapy cannot control the disease. Only allergy immunotherapy has disease-modifying potential and should be included in optimal treatment strategies. Allergy immunotherapy was first administered as subcutaneous injections and has been practiced for the past 100 years or so. Recently, tablet-based sublingual allergy immunotherapy (SLIT) was introduced with comprehensive clinical documentation. SLIT tablets represent a more patient-friendly concept because they can be used for self-treatment at home.

A cytotoxicity assay to determine growth inhibition after a 1-hr treatment with xenobiotics in serum-free medium and subsequent re-incubation in serum-containing medium without test chemicals was characterized and optimized for cytotoxicity screening. Our results indicated that after treatment of human fibroblasts with the test chemicals a 44-hr re-incubation period is most suitable for measuring the growth inhibitory effects of a broad spectrum of chemicals. Applying the assay, the activity to inhibit growth by 10% (log IC 10 ) correlated with the lipophilicity (specified as octanol-water partition coefficient = log K ow ) of 19 xenobiotics. The linear regression coefficient was r = 0.91. This close correlation between toxicity and lipophilicity shows that the test, which avoids long-term incubation in serum-containing medium, is suitable for cytotoxicity screening and structure-activity analysis.

The sensitivity of three methods measuring basal cytotoxicity in human fibroblasts was compared. Cell survival, inhibition of growth and colony-forming ability were measured after 1 hr of incubation with nine environmental chemicals from different substance classes. The sensitivity of the method of determining inhibition of growth was similar to that of the test of colony-forming ability and was double that of a commonly used method to determine cell survival. Linear regression analysis showed that the three methods correlated well with each other, the strongest correlation being between colony-forming ability and growth.

Rationale Exposure and sensitization to domestic cat (Felis domesticus) is a significant risk factor for developing allergic rhinitis and asthma. Earlier studies have shown that majority of the cat allergic patients develop allergic responses against major cat allergen Fel d 1. Several attempts have been made to produce of recombinant (r) Fel d 1 as heterodimer. We have recently shown that baculovirus expression system is able to produce rFel d 1 that has compatible characteristics to nFel d 1. Methods In the present study an immunological characterization of rFel d 1 in comparison to the purified nFel d 1 and cat allergen extract (IMP Fel d, ALK-Abello') was performed by use of IgE inhibition, lymphocyte proliferation and basophile histamine release assay(s). Results In inhibition assay against cat allergen extract, natural and rFel d 1 were able to inhibit 87% of the binding of cat allergen specific serum IgE antibodies. The basophile histamine release responses with rFel d 1 and nFel d 1 showed to be in line with the responses given by the cat allergen extract. Comparable T-cell responses towards natural and rFel d 1 was obtained in lymphocyte proliferation assay and when the response of Fel d 1-specific T-cell lines was investigated even though nFel d 1 seemed to be recognized more frequently. Conclusions These results show that heterodimeric rFel d 1 elicits immunological responses that are comparable to nFel d 1. The present study demonstrates that recombinant allergen(s) with well defined biochemical and immunological characteristics are feasible for development of therapeutic vaccines.

Rationale The next generation allergy vaccines have been suggested to be recombinant major allergens. Since naturally occurring major allergens are composed of many isoforms, it is necessary to investigate if all allergic patients will benefit from treatment with a single recombinant isoform or a genetically modified hypoallergenic variant. Methods Naturally occurring isoforms, recombinant allergens and genetically modified forms of the recombinant allergens were used in assays to stimulate T-cell lines from atopic patients raised against natural purified allergens. Samples were tested for proliferation (3H-thymidine) and cytokine production (IFN-gamma, IL-10, IL-5, IL-4). Results Eight nBet v 1 T-cell lines were established and all except one responded equally well to both nBet v 1 and rBet v 1. Different IFN-gamma/IL-5 ratios were found, but were not affected by the different stimulants. Five nPhl p 5 T-cell lines responded equally well to natural and recombinant and even to extensively substituted rPhl p 5 proteins, except for one mutant, which did not react in one line. Four nDer p 1 T-cell lines varied in stimulation to nDer p 1, rDer p 1 and mutated rDer p 1 allergens. One line did not respond to some mutant rDer p 1. nPhl p 5 and nDer p 1 lines produced Th2 cytokines to all allergen preparations. Conclusions T-cell lines responding to natural purified allergens were also stimulated by recombinant allergens. These data suggests that for T-cell stimulation, one carefully selected isoform of the natural purified allergen can in most allergen systems substitute for the mixture of isoforms.

In an attempt to solve the problem of chemosensitivity testing of renal cell carcinoma in vitro, a modified short-term culture technique was developed. The kinetic study of hypernephroma cells and normal renal cells showed that the uptake of H3-uridine and H3-thymidine is at its maximum after eighty hours. The effect of doxorubicin, cisplatinum, vinblastine, and mitomycin C in different concentrations was tested. Tumors generally showed more resistance than sensitivity. Some tumors showed sensitivity to one or more drugs, but no one drug was persistently effective in all tumors. Our short-term culture technique solved the discrepancy between cell kinetics and test duration found in the Volm test and the problem of nongrowth in the clonogenic assay.

Regulation of protein synthesis in BHK21/13 cells has been examined as a function of cell growth rate and density, both in vivo by pulse-labeling of cells with [3H]valine and in an in vitro cell-free protein-synthesizing system. The specific activity of [3H]valyl-tRNA in the pulse-labeled cells was determined and the true in vivo rate of [3H]valine incorporation into protein was measured. Unlike the reported behavior of many other cell lines, BHK21/13 cells did not shut off their protein synthesis at all while their growth rate declined 10-fold or more during density-dependent inhibition of growth or during arrest of growth by serum deprivation. In vitro assays of the cells' protein synthetic activity with both synthetic and natural messenger RNA confirmed that all of the components needed for protein synthesis were equally active in rapidly growing and in density-inhibited or serum-deprived cells. Hence, in these cells the protein synthesis rate and the cell division rate are not coupled, and the amount of protein in the cell is not regulated at the level of synthesis, but rather at the level of protein degradation or export.

The effects of 31 different steroids on the formation of 3α-androstanediol from [1,2- 3 H]-dihydrotestosterone were assessed in both microsomal and cytosolic fractions of dog prostate. Several features of the substrate specificity of the reaction were deduced from these studies. First, 4-ene-3-keto steroids and 5β-reduced steroids were weak or inactive inhibitors of the reaction. Second, oxo substitution at C 6 or C 11 abolished the inhibitory ability of 5α-reduced steroids. Third, 2α-halogenated androstanes were good inhibitors, and, in particular, the 2α-bromo steroids (2α-bromo-androstanedione and -dihydrotestosterone) were at least five fold more inhibitory than the parent androstane. Fourth, the 3-keto function of the steroid nucleus is critical whereas a 17-oxo-group (hydroxyl or keto) is not essential. Fifth, the relative inhibition of the microsomal and cytosolic enzyme correlated closely, a finding compatible with enzymic identity of the two intracellular fractions.

After a short explanation of the memory contention problem a queueing network of a multiprocessor system is derived. Some known results of closed queueing networks are given, which are then applied to compute the throughput of the MPS.

On the basis of results obtained with other malignancies, the usefulness of serum ferritin as a tumor marker in the diagnosis of testicular tumors was studied. In 68 patients with malignant testicular tumors and 22 patients with benign testicular processes, serial determinations of beta-human chorionic gonadotropin (beta-HCG), alpha-fetoprotein (AFP) and serum ferritin were performed. The serum ferritin values showed no relationship to tumor stage, and no difference in nonseminomatous and seminomatous tumors. In particular, no diagnostic improvement was achieved in those cases in which the conventional markers AFP and beta-HCG were unsuccessful (falsely negative results). Furthermore, serum ferritin values were influenced by hepatic factors and anemia, so that serum ferritin - on the basis of the present material-could not be considered a useful tumor marker in testicular malignancies. Further studies on the determination of carcinofetal isoferritin and other new tumor markers are warranted.

After ligation of ureters and urethra, male Sprague-Dawley rats were treated over 3 h with either 2 mg mitomycin C (MMC) intravesically (group I), or in conjunction with pre-instillation bladder electrocoagulation (group II) or iatrogenic Escherichia coli/xylene-induced severe cystitis (group III). Vesical absorption of MMC was investigated by measuring serum MMC up to 180 min postinstillation on the basis of a thin agar plate method. There was no statistically significant different with regard to the total amount of MMC absorbed between groups I and II. However, when groups I and III or II and III were compared, a significant differing transvesical absorption was calculated, being higher for the electrocoagulation than for the cystitis group. The possible clinical implication of this finding is discussed in connection with the most recent literature.

Gonadotropin-releasing hormone (Gn-RH), a hypothalamic decapeptide, mediates the synthesis and release of pituitary luteinizing hormone (LH). Synthetic Gn-RH analogues with prolonged duration of action are therapeutically administered with 'pro-fertility' intention to overcome endogenous Gn-RH deficiency, i.e. hypogonadotropic hypogonadism and related disorders. When Gn-RH analogues are chronically administered in high supraphysiological dosages, however, a paradoxical effect of pituitary overstimulation becomes evident: gonadotropin release is reduced, Leydig cell responsiveness is impaired, and testosterone secretion is blocked to castrate levels. Metabolic mechanisms involved include desensitization of the pituitary to Gn-RH, down-regulation of Gn-RH receptors, the depletion of the releasable LH pool, the breakdown of physiological feedback mechanisms, as well as direct interactions of the Gn-RH analogue with the Leydig cell. It is tempting to assume that, on the basis of this untoward side effect, high dose Gn-RH analogues will acquire a therapeutical dimension in the palliative treatment of prostate cancer. The therapeutical effect of castrate levels of testosterone is achieved without orchiectomy, cardiovascular side effects of estrogen are avoided, and the drug is conveniently applicable via the pernasal route. From the data available today Gn-RH analogues in overstimulatory dosage can be expected to be safe and effective in the palliative treatment of prostate cancer and would thus prove a true alternative to conventional contrasexual measures.

From 1967 to 1985, 246 cystectomies for treatment of transitional cell carcinoma of the urinary bladder were performed. Perioperative mortality decreased from 15% in the early years to 0% in 1985. Preoperative radiotherapy was not given. Patients who underwent cystectomy immediately following the diagnosis of invasive bladder carcinoma had a significantly better prognosis than those having cystectomy after recurrence of a transurethrally resected invasive carcinoma in spite of identical G and T criteria. A total of 26 patients who were cystectomized because of tumor recurrence after definitive radiotherapy (salvage cystectomy) represented the group with the worst prognosis: they had a 5-year survival rate of less than 10%. It is concluded from these results that recurrence of an infiltrating bladder tumor is an indication of poor prognosis. Early cystectomy after diagnosis of tumor infiltration can improve survival rates. Transurethral resection without adjuvant therapy cannot be regarded as reliable curative treatment of bladder cancer infiltrating the lamina propria (pT1). Modern surgical techniques of continent urinary diversion or total bladder replacement combined with sparing of the pelvic nerves (and thus preservation of potency) reinforce our view that radical cystoprostatectomy need no longer be regarded as mutilating surgery.

The variation of the electrical resistivity of the intermetallic compound β-NiAl at 77° and 298°K is characterized by a sharp minimum at the stoichiometric composition and can be explained by electron scattering from constitutional point defects. The Hall coefficient shows proportionality to the electrical conductivity and changes the sign twice within the homogeneity range. Positive and negative contributions to the Hall coefficient are interpreted by the shape of the Fermi surface relative to the Brillouin zones. Room temperature values of the absolute thermoelectric power and of the high frequency conductivity measured by optical methods indicate that the Fermi surface overlaps into higher Brillouin zones in 〈110〉 direction, when the Al-concentration approaches 50 at.%. From the low energy part of the conductivity spectra effective electron masses were computed. Absorption maxima found at 1·5, 2·5, 4 and 5 eV are attributed to interband transitions of electrons. The compositional dependence of the hydrogen solubility suggests that hydrogen dissociates into proton and electron, the solubility being primarily controlled by the electron potential. Thus the rapid rise in Fermi energy between 46 and 50 at.% Al simultaneously causes the solubility to decrease.

The defect structure of β NiAl is investigated, with copper substituted for nickel in fixed concentration ratios x Ni Cu and in Ni1−yCuyAl. The number of nickel vacancies is increased due to the addition of copper to the alloy, as is shown by lattice spacing and density measurements. Vacancy formation does not originate from a critical valence electron concentration but from repulsion between neighboring positively charged ions AlAl-AlNi3+ or AlAl-CuNi+. A disorder model for calculation of the concentration of defects and normally occupied lattice sites is based on two intrinsic disorder reactions: the dissociation of the ideal ordered lattice into vacancies VNi and antistructure atoms CuAl and NiAl, and the distribution of copper atoms on nickel sites and aluminum sites. The corresponding disorder parameters are determined from the experimental vacancy concentration and are estimated from the measured electrical resistivity. The state of order is characterized by integral and partial molar configurational entropies, which are computed on the basis of the disorder model assuming a random distribution of point defects.

Optical constants of several ternary β Hume-Rothery phases have been investigated as a function of the valence electron concentration and defect structure. The composition of the alloys was based on the β phase NiAl, the absorption spectrum of which is dominated by two maxima at 2·5 and 4 eV. The intensity of the 2·5 eV-e 2 peak is considerably increased with increasing valence-electron concentration, whereas that of the other peak is decreased. The valence electron concentration is varied by substituting Cu for Ni in Ni 1− y Cu y Al or Si for Al in NiAl 1− y Si y . The 2·5 eV absorption peak disappears when Co is substituted for Ni in Ni 1− y Co y Al. The absorption peaks are attributed to interband transitions of electrons and are discussed according to the rigid band model. The absorption in the infrared is explained by the scattering of electrons from lattice defects and phonons. The position of the d -band relative to the Fermi level is discussed in connection with s-d band scattering.

The effect of three lectins, Ricinus communis agglutinin (RCA II), concanavalin agglutinin (ConA), and wheat germ agglutinin (WGA), on KK-47 bladder cancer cell line was studied, RCA 11 showed effective inhibition of H 3 -uridine and H 3 -thymidine uptake by KK-47. ConA showed a stimulatory effect in all three concentrations used. WGA also showed stimulatory effect, but it was less pronounced than ConA.

In 30 nephrectomy specimens, fine needle aspiration biopsies (FNAB) were performed both in the tumor and in the macroscopically normal part of the kidney: 18 were well differentiated renal cell carcinoma (RCC), 6 were moderately differentiated RCC, 4 were poorly differentiated RCC, and 2 were oncocytomas. FNAB was also performed in a bone metastasis of RCC. FNAB materials were stained using the immunoperoxidase method with RCC-specific monoclonal antibody and were compared with the staining of frozen sections. In all cases where tumor-antigen expression could be demonstrated in the frozen sections, a FNAB had already proven positive. There were only 2 false-negative cases where sufficient cellular material could not be obtained due to extensive tumor necrosis. There was no false-positive case. Oncocytomas showed no expression of antigen. The use of immunoperoxidase staining of FNAB with tumor-specific monoclonal antibody is discussed.