Natural interferon-alpha versus its combination with 6-methyl- prednisolone in the therapy of type II mixed cryoglobulinemia: a long- term, randomized, controlled study

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6- methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemoattractant-induced changes in surface expression and redistribution of a functional ligand for P-selectin on neutrophils

Adhesion between platelets and neutrophils is mediated through the interaction of P-selectin on activated platelets with a carbohydrate- containing structure on neutrophils, and occurs under both static and shear conditions. Recent studies using flow chambers have shown that neutrophils become activated after binding to surface-adherent platelets expressing P-selectin. The objective of the present study was to investigate the effect of such activation on the interactions of platelet P-selectin with its ligand on neutrophils. Flow cytometric analyses using P-selectin chimeras revealed that activation induced a rapid and marked reduction in chimera binding, with levels of binding decreased by 71% after 15 minutes of stimulation with the chemotactic agent, FMLP. Using a visual assay of platelet-neutrophil rosetting, we showed that the P-selectin ligand was translocated and clustered at the uropod of neutrophils following the shape changes and polarization induced by chemotactic stimulation. Activated neutrophils bound to surface-adherent platelets also displayed the clustering of P-selectin ligand at the uropod, and these neutrophils detached from the platelets when a shear stress (2 dynes/cm2) was applied through the adhesion chamber. These results indicate that chemotactic stimulation of neutrophils induces changes in the surface expression and distribution of a biologically relevant ligand for P-selectin, and that these changes might influence the adhesive interactions occurring between neutrophils and activated platelets.     

In vitro interactions of PGE and cAMP with murine and human erythroid precursors

Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells.     

A canine model of hemophilic (factor VIII:C deficiency) bleeding

A model of bleeding due to clotting factor deficiency has been developed in dogs. Normal and hemophilic (factor VIII:C deficient) animals were used. Bleeding was induced in lightly anesthetized animals by severing the apex of the nail cuticle using a guillotine device. In normal animals, bleeding usually ceased spontaneously after 2-8 min. In contrast, in hemophilic animals, bleeding continued for up to 20 min and necessitated either cauterization or the application of topical thrombin to achieve hemostasis. Pretreatment of the hemophilic animals with canine cryoprecipitate corrected the cuticle bleeding time to within the range noted for normal animals. The method is simple and reproducible and has the advantage that a number of observations can be made sequentially on the same animal. Rebleeding of the cauterized cuticle of the hemophilic animals did not usually occur. This model has considerable potential for the preclinical testing of products considered to bypass or replace factor VIII:C in patients with acquired inhibitors of factor VIII:C and may be adapted to the study of other mechanisms involved in normal and abnormal hemostasis.     

World Workshop on Oral Medicine VI: a systematic review of medication‐induced salivary gland dysfunction

The aim of this paper was to perform a systematic review of the pathogenesis of medication‐induced salivary gland dysfunction (MISGD). Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers were retained for the final analysis. MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, α‐and β‐adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting on the nervous, cardiovascular, genitourinary, musculoskeletal, respiratory, and alimentary systems. Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology.     

Microaggregate counts in frozen-preserved erythrocytes: effects of washing in three blood processors and filtration

Since microaggregates have been implicated in posttransfusion pulmonary insufficiency, their elimination has become an active concern in blood transfusion. Various types of filters, as well as frozen-preserved erythrocytes, have been used to provide blood relatively low in microaggregates. We have counted particles in frozen-stored blood before deglycerolization, after washing in each of three cell processing systems, and after filtration through a 40-micrometer filter. Washing frozen erythrocytes reduced the total particle counts by an average of 89%. Slight differences were found among the three blood processors with respect to particle removal. Passing washed blood through a 40-micrometer filter did not result in significant further reduction in particle counts. Hence, the use of such filters in a frozen-preserved blood system is not warranted.     

Use of healthcare a long time after severe burn injury; relation to perceived health and personality characteristics

Purpose.?The aim of the study was to evaluate which factors are associated with the use of healthcare a long time after severe burn injury.

Method.?After a review process based on clinical reasoning, 69 former burn patients out of a consecutive group treated at the Uppsala Burn Unit from 1980?–?1995 were visited in their homes and their use of care and support was assessed in a semi-structured interview. Post-burn health was assessed with the Burn-Specific Health Scale-Brief (BSHS-B) and personality was assessed with the Swedish universities Scales of Personality (SSP).

Results.?The participants were injured on average eight years previously. Thirty-four had current contact with healthcare due to their burn injury and had significantly lower scores on three BSHS-B-domains: Simple Abilities, Work and Hand function, and significantly higher scores for the SSP-domain Neuroticism and the SSP-scales Stress Susceptibility, Lack of Assertiveness, and lower scores for Social Desirability. There was no relation to age, gender, time since injury, length of stay, or to the surface area burned.

Conclusions.?A routine screening of personality traits as a supplement to long-term follow-ups may help in identifying the patient's need for care.     

薄层扫描法测定熊胆引流物中胆汁酸含量

熊胆向以贵重药材闻名,被称之为稀有药品,为开发熊胆资源,解决熊胆奇缺问题,我校解剖教研室已成功地完成了人工引流熊胆汁技术,可随时进行人工引流获取熊胆汁。为了确定胆汁的质量指标,了解其主要成分,我们进行了引流胆汁与天然熊胆的分析。文献报道,熊胆中主要含熊去氧胆酸(ursodesoxycholic acid,UDCA)、鹅去氧胆酸(cheno desoxycholic acid,CDCA)、胆酸(cholic acid,CA)、去氧胆酸(deoxycholic,acid DCA)等。