Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

[Expression of alpha-acetolactate decarboxylase gene from Bacillus subtilis in Brewer's yeast].

Yeast YIp-type expression recombinant plasmid(pCMA2-1) was constructed. The expression of alpha-acetolactate decarboxylase gene from Bacillus subtilis was controled by CUP1 promoter and its own terminator. The recombinant plasmid pCMA2-1 was introduced into the brewer's yeast PJ3-5. Transformants were selected using copper resistance as selected marker. The results of activity assay showed that PJ3-5 didn't produce alpha-acetolactate decarboxylase(ALDC), where as the activity of alpha-ALDC in transformants were induced by copper sulfate. The laboratory scale fermentation test confirmed that the total diacetyl concentration was reduced effectively by alpha-ALDC in transformant.

Construction of high ergosterol-producing yeast strains and study on the optimal conditions for culture.

High ergosterol-producing yeast strains were constructed by primary screening isolation of haploid mutagenesis and protoplasts fusion. The fermentation conditions of fused strain YEF-21 were studied. Under the optimal conditions, i.e., the medium for fermentation consisted of 8% glucose 1% polypeptone 1% yeast extract; initial pH nature; 60 mL broth/250 mL flask; inoculum volume 10%; fermentation time 30 hours at 28 degrees C and 200 r/min; the comprehensive value of biomass and ergosterol content of YEF-21 is 1.54 and 1.55 times that of the parent strains YE227 and YE180, respectively. The fused strain YEF-21 is stable enough genetically according to the analysis of genetic stability, and it is a high ergosterol-producing strain that has prospect for application.

[Distinction of yeast flocculent phenotypes and studies of the physiological and biochemical characteristics of yeast flocculation].

More than 400 yeast strains were examined for their flocculation, and five of them displayed strong flocculation. The 5 strains were divided into two groups which are Flo 1 and NewFlo phenotypes on the basis of their response to sugar inhibition. Related physiological and biochemical characteristics of the two phenotypes' strains were studied. The results showed that the flocculation of Flo 1 phenotype was only inhibited by mannose; it was sensitive to high temperature (70 degrees C), pronase E, trypsin, whereas tolerant to pronase K, chymotrypsin, Ca2+, pH; the flocculation of NewFlo was inhibited by many sugars, such as glucose, maltose, sucrose, mannose; it was sensitive to high temperature (70 degrees C), pronase, Ca2+, pH. The Calcium concentration and pH value of the optimum flocculaton of the Flo1 and NewFlo phenotypes strains were respectively 10 mmol/L-1 mol/L; 3.0-4.5.

Prolonged survival in a nasopharyngeal carcinoma patient with multiple metastases: a case report and review of the literature.

Nasopharyngeal carcinoma is a common cancer in South East Asia. In the early stages, radiotherapy alone may achieve sustained control, but once metastasis occurs, it becomes an incurable disease with limited survival time. We report a case of nasopharyngeal carcinoma, initial stage T4N0M0, diagnosed in 1985 in a patient aged 36 years who received 70 Gy radiotherapy to the head and neck region. In 1988, relapse occurred with multiple lung metastases. The patient received many chemotherapy regimens with a very good response, including near complete remission with the first treatment regimen of cisplatin, 5-fluorouracil and leucovorin for lung metastases, and with the fifth chemotherapy regimen of ifosfamide as a single agent. After ifosfamide treatment, there was residual fibrotic change in the lung and complete disappearance, lasting for almost a year, of the liver and bone lesions. The patient eventually died in July 1995 due to progressive disease. Prolonged survival after mainly thoracic metastasis is possible in patients with nasopharyngeal carcinoma, especially if the tumor is chemo-responsive.

Topical treatment of psoriasis with fludarabine.

Fludarabine is not used as a topical medication for the treatment of psoriasis. In this study we evaluated the efficacy of fludarabine for this purpose. Four male patients with two bilaterally symmetrical psoriatic plaques were treated with 0.2 percent topical fludarabine in aquaphor (fludarabine site) or aquaphor alone (control site). The fludarabine and control sites were compared before and during the study on a weekly basis for three weeks by degree of redness, scaliness, and thickness on a scale of 0 to 4 (0, not apparent; 4, very apparent). The results of our study showed no significant difference between topical fludarabine and aquaphor in the treatment of psoriatic plaques.

A high SPF sunscreen's effects on UVB-induced immunosuppression of DNCB contact hypersensitivity.

Several studies in mice of the protection afforded by sunscreens from UVB-induced suppression of contact hypersensitivity have yielded conflicting reports ranging from complete protection to no protection. Firstly, we sought to determine the effects of sunscreen and UVB on Langerhans cells; secondly we sought to determine whether the effect of preapplication of sunscreen with a sun protection factor of 30 could prevent local UVB-induced suppression of contact hypersensitivity to dinitrochlorobenzene in humans. In the first part of the study we compared a control group with a sunscreen plus UVB group and enumerated the number of Langerhans cells in each group. In the second part of the study we had four groups: a control group, a UVB group, a sunscreen group, and a sunscreen plus UVB group. Our results show that application of a sunscreen prior to UVB can prevent the decrease in number of Langerhans cells in an irradiated site. In the second part of the study, our results indicate that sunscreen, in itself, does not interfere with contact hypersensitivity, and that a high SPF sunscreen applied prior to UVB irradiation partially prevents suppression of contact hypersensitivity.

Suppressive and enhancing effects of ultraviolet B radiation on expression of contact hypersensitivity in man.

Ultraviolet B (UVB) radiation has multiple effects on the immune system, and these effects contribute to the development of UVB-induced skin cancers in mice, and probably man. Depending upon dose and duration of UVB exposure, the resultant immune aberrations may be strictly local (at the irradiated skin site) or systemic. One important local effect of acute, low-dose UVB regimens is impaired induction of contact hypersensitivity (CH). Because a significant proportion of humans who develop CH when hapten is painted on UVB-exposed skin fall to display a primary allergic reaction at that site, we inquired into the effects of UVB radiation on the expression of CH in man. A high proportion of individuals who were first exposed to a sensitizing dose of hapten via UVB-exposed skin displayed CH when challenged on unirradiated (normal) skin 11 d later. However, only 50% of these subjects developed CH when challenged simultaneously on skin that had been exposed to UVB radiation 11 d previously. Because the density of epidermal antigen-presenting cells was comparable in both responders and non-responders, we interpret these findings to mean that UVB radiation can create a sustained immunosuppressive microenvironment that inhibits the expression of CH. In separate experiments, when normal volunteers were sensitized with hapten via unirradiated (normal) skin, expression of CH at UVB-exposed challenge sites 11 d later was found to be enhanced, at least in some individuals, compared to expression of CH at unirradiated challenge sites. Thus, the local effects of UVB radiation on expression of CH in man may be enhancing or inhibitory, depending upon whether initial sensitization occurred through normal or through UVB-exposed skin.

Interrelationship between ultraviolet light and recurrent herpes simplex infections in man.

In humans, epicutaneous application of a universally sensitizing dose (2000 micrograms) of dinitrochlorobenzene (DNCB) to skin exposed to 4 consecutive daily doses (144 mJ/cm2) of ultraviolet-B radiation (UVB) induces contact hypersensitivity (CH) in approximately 56% of normal, adult individuals (UVB-resistant--UVB-R), but not in the remaining 44% (UVB-susceptible--UVB-S). In patients with biopsy proven basal/squamous cell cancer, the frequency of the UVB-S trait exceeds 90%, indicating that this phenotype may be a risk factor for sunlight-induced skin cancer. Since many patients with recurrent herpes labialis complain that lip lesions are precipitated by acute sun exposure, we wondered whether the UVB-S trait might be associated with this recurrent disease. A group of 31 volunteers was selected, each with a history of numerous episodes of labialis secondary to reactivated herpes simplex virus-1 infection. Subjects were questioned carefully concerning factors, including sun exposure, thought to be important in precipitating lip lesions. Each individual was then subjected to the UVB plus DNCB protocol. When forearm skin of these individuals was assayed for CH after 30 days, 20 (65%) proved to be UVB-S (approximately 1.5 times the expected frequency), while the remainder displayed vigorous DNCB-specific CH. A strong history of sun-induced recurrent herpes simplex labialis did not predict the UVB phenotype. A subset of these subjects was exposed to 2 MEDs of UVB to their faces. None of the UVB-R subjects developed recurrent herpes labialis while 6 of 8 UVB-S subjects developed recurrent lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between ultraviolet radiation-induced immunosuppression and carcinogenesis.

The capacity of ultraviolet B (UVB) radiation to damage the cutaneous immune system has been extensively documented, and there is good reason to believe that UVB-induced damage is a critical, albeit permissive, factor in the development of sunlight-induced skin cancers. A summary of the evidence shows that acute, low-dose UVB protocols, which resemble quantitatively and qualitatively the manner in which human beings typically experience sun exposure, alter the cutaneous immune system in at least two important ways: they impair the induction of contact hypersensitivity to cutaneous antigens, and induce antigen-specific tolerance. In mice there is compelling evidence that immunogenetic factors dictate whether UVB radiation will impair contact hypersensitivity induction or not. The genetic loci that contain the relevant polymorphic alleles include tumor necrosis factor-alpha and lipopolysaccharide. Because the effects of UVB radiation on contact hypersensitivity induction are mimicked by intracutaneous injections of subinflammatory doses of tumor necrosis factor-alpha or cis-urocanic acid, the favored hypothesis to explain the mechanism of action of UVB radiation in UVB-susceptible individuals is that UVB-dependent transformation of trans- to cis-urocanic acid in the epidermis triggers the intracutaneous release of excess amounts of tumor necrosis factor-alpha. By transiently immobilizing Langerhans cells and other local antigen-presenting cells within the skin, the requirement that hapten be brought to the draining lymph node to sensitive naive hapten-specific T cells is not met, and contact hypersensitivity fails to develop. Because the UVB-susceptibility and UVB-resistance traits have also been demonstrated in human beings, the hypothesis is advanced that these traits are similarly under control of immunogenetic factors, and that a constellation of immune susceptibility genes contributes to the risk of developing sunlight-induced skin cancer. The cellular and molecular basis of UVB-induced tolerance is not as well described, but current evidence suggests that different mechanisms, and presumably different polymorphic genes, dictate whether tolerance will emerge after UVB exposure in mice. Because acute, low-dose UVB also induces tolerance in human beings, the immunogenetic factors that dictate tolerance of this type may also contribute to the risk of developing sunlight-induced skin cancer.

Immune surveillance and sunlight-induced skin cancer.

Immune surveillance poses the existence of a recirculating pool of lymphocytes that migrate randomly through somatic tissues. Upon recognition of neoantigens on malignantly transformed cells, lymphocytes proceed to attack and destroy degenerate cells before a tumor emerges. Here, J. Wayne Streilein and colleagues review the effects of ultraviolet B irradiation on the induction of cutaneous immunity in the skin of mice and humans. Furthermore, they discuss the possibility of a genetic predisposition to skin cancer, mediated by a defect in the normal process by which contact hypersensitivity, and therefore immunogenicity, is elicited.