九寨沟景区急诊病例疾病谱调查

目的探讨九寨沟景区急诊患者疾病谱流行病学特点,提高九寨沟景区急诊患者的诊治水平。方法对2013年1~12月四川省九寨沟县人民医院14 196例急诊病例资料进行回顾性分析。结果院前急诊病种排序在前4位的是呼吸系统疾病、高原反应、损伤、心脑血管疾病,呼吸系统疾病患病比例最高,达60.44%;呼吸系统疾病、高原反应、损伤发生率女性高于男性,心脑血管疾病发生率男性明显高于女性;高原反应、损伤、心脑血管疾病以60岁以上人群为主。结论在类似九寨沟这种高寒景区,老年旅游者需要特别重视对呼吸系统疾病、高原反应、损伤、心脑血管疾病的预防。     

T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7-1 and B7-2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7-1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7-1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7-1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7-1 expression on lymphocytes, B7-3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7-1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.     

Surgery and anesthesia in sickle cell disease. Cooperative Study of Sickle Cell Diseases

From 1978 to 1988, The Cooperative Study of Sickle Cell Disease observed 3,765 patients with a mean follow-up of 5.3 +/- 2.0 years. One thousand seventy-nine surgical procedures were conducted on 717 patients (77% sickle cell anemia [SS], 14% sickle hemoglobin C disease [SC], 5.7% S beta zero thalassemia, 3% S beta zero + thalassemia). Sixty-nine percent had a single procedure, 21% had two procedures, and the remaining 11% had more than two procedures during the study follow- up. The most frequent procedure was abdominal surgery for cholecystectomy or splenectomy (24% of all surgical procedures, N = 258). Of these, 93% received blood transfusion, and there was no association between preoperative hemoglobin A level and complication rates (except reduction in pain crisis). Overall mortality within 30 days of a surgical procedure was 1.1% (12 deaths after 1,079 surgical procedures). Three deaths were considered to be related to the surgical procedure and/or anesthesia (0.3%). No deaths were reported in patients younger than 14 years of age. Sickle cell diseases (SCD)-related complications after surgery were more frequent in SS patients who received regional compared with general anesthesia (adjusted for risk level of the surgical procedure, patient age, and preoperative transfusion status, P = .058). Non-SCD-related postoperative complications were higher in both SS and SC patients who received regional compared with those who received general anesthesia (P =.095). Perioperative transfusion was associated with a lower rate of SCD- related postoperative complications for SS patients undergoing low-risk procedures (P = .006, adjusted for age and type of anesthesia), with crude rated of 12.9% without transfusion compared with 4.8% with transfusion. In SC patients, preoperative transfusion was beneficial for all surgical risk levels (P = .009). Thus, surgical procedures can be performed safely in patients with SCD.     

Favorable prognosis of hyperdiploid common acute lymphoblastic leukemia may be explained by sensitivity to antimetabolites and other drugs: results of an in vitro study

DNA hyperdiploidy is a favorable prognostic factor in childhood acute lymphoblastic leukemia (ALL). The explanation for this prognostic significance is largely unknown. We have studied whether DNA ploidy was related to cellular resistance to 12 drugs, assessed with the methyl- thiazol-tetrazolium assay, in samples of 74 children with common (CD10+ precursor B-cell) ALL. Sixteen patients had hyperdiploid ALL cells and 58 patients had nonhyperdiploid ALL cells. Hyperdiploid ALL cells were more sensitive to mercaptopurine (median, 9.0-fold; P = .000003), to thioguanine (1.4-fold; P = .023), to cytarabine (1.8-fold; P = .016), and to I-asparaginase (19.5-fold; P = .022) than were nonhyperdiploid ALL cells. In contrast, these two ploidy groups did not differ significantly in resistance to prednisolone, dexamethasone, vincristine, vindesine, daunorubicin, doxorubicin, mitoxantrone, and teniposide. The percentage of S-phase cells was higher (P = .05) in the hyperdiploid ALL samples (median, 8.5%) than in the nonhyperdiploid ALL samples (median, 5.7%). However, the percentage of cells in S-phase was not significantly related to in vitro drug resistance. We conclude that the favorable prognosis associated with DNA hyperdiploidy in childhood common ALL may be explained by a relative sensitivity of hyperdiploid common ALL cells to antimetabolites, especially to mercaptopurine and to I-asparaginase.     

Expression studies of missense mutations p.D141Y, p.C275S located in the propeptide of von Willebrand factor in patients with type 3 von Willebrand disease

Summary Missense mutations are not considered a common cause of type 3 von Willebrand’s disease (VWD), the most severe defect of von Willebrand factor (VWF) characterized by undetectable levels of this protein in plasma and platelets. Nevertheless, several missense mutations have been identified in these patients. In this study, we report the cases of two Italian patients with type 3 VWD, both compound heterozygotes for different missense mutations and null alleles, p.D141Y/c.2016_2019del and p.C275S/p.W222X. We performed in vitro expression studies of the candidate missense mutations, both located in the D1 domain of VWF propeptide, to confirm their link with the disease and to understand the mechanisms of type 3 VWD responsible in these patients. Mutant and wild‐type (WT) expression vectors were used for transient transfection and co‐transfection studies in COS‐7 cells. Single construct transfections of both missense mutations showed a strongly reduced but detectable secretion of recombinant (r)VWFs (approximately 15% of WT), with essentially only dimers being visualized on multimeric analysis. As expected, expression of a single construct of either mutation with the WT, showed mildly reduced secretion (approximately 40% of WT) and a full set of multimers. These expression studies indicate that the two amino acids D141 and C275 are key residues in the tertiary structure of the VWF propeptide. Their replacement with a tyrosine and a serine, respectively, might compromise propeptide folding, affecting both its intracellular survival and its capacity to mediate multimerization. Co‐expression of hybrid rVWFs confirmed the recessive inheritance pattern of these missense mutations.     

The effects of tumor-promoting phorbol esters on human granulopoiesis in vitro

In order to determine whether the tumor-promoting phorbol esters are capable of inducing normal human committed granulocytic-monocytic progenitor cells (CFUc) to proliferate and differentiate in the absence of granulocyte-monocyte colony-stimulating activity (CSA), we studied the effects of these compounds on human granulopoiesis in vitro. We found that when light-density human marrow cells or peripheral blood leukocytes were depleted of adherent cells and then incubated in semisolid tissue culture medium under conditions optimal for CFUc growth, phorbol myristate acetate (PMA) and its congeners produced no measurable stimulatory effect on the proliferation of CFUc in the absence of added CSA. Likewise, when light-density marrow cells that had not been depleted of adherent cells were plated in the cultures, no stimulation of CFUc colony growth resulted from the addition of PMA. However, when light-density peripheral blood leukocytes were used as a target source of CFUc without first subjecting them to adherence separation, enhanced proliferation and differentiation of CFUc were noted in cultures that contained PMA. To investigate the possibility that CSA production by monocytes in these cultures in response to activation by PMA might account for the enhanced colony formation that we observed, we incubated isolated peripheral blood monocytes in short- term liquid suspension cultures and found that in the presence of PMA, large quantities of CSA were secreted into the surrounding medium. Finally, we noted that when marrow cell suspensions were suboptimally stimulated by low concentrations of CSA added to the cultures, the effects of PMA on CFUc proliferation were unpredictable, enhancing colony formation in some cases and inhibiting it in others. Our data indicate that although the tumor-promoting phorbol esters do not appear capable of directly stimulating the proliferation or differentiation of human CFUc in the absence of CSA, they may do so indirectly by causing auxiliary cells such as monocytes to secrete CSA.     

Therapeutic efficacy of recombinant interleukin-6 (IL-6) alone and combined with recombinant human IL-3 in a nonhuman primate model of high-dose, sublethal radiation-induced marrow aplasia

Using a nonhuman-primate model of radiation-induced bone marrow aplasia, we examined whether the single, concomitant, or sequential administration of recombinant human interleukin-3 (IL-3) and IL-6 would promote bone marrow regeneration measured by an increase in circulating platelets (PLT) and neutrophils (PMN). Rhesus monkeys were irradiated at 450 cGy and were randomly assigned to one of five treatment protocols, receiving IL-6; IL-3; combined IL-6 and IL-3; sequential IL- 3 and IL-6; or human serum albumin (HSA) as a control. Cytokines or HSA were administered at total dosages of 15 micrograms/kg/day. Complete blood counts and white blood cell differentials were monitored for 60 days postirradiation. Both IL-3 and IL-6 significantly enhanced the regeneration of PLTs and decreased the duration of thrombocytopenia (P = .005) without affecting PMN recovery. The radiation-induced anemia that was observed in the HSA-treated controls was less severe and resolved more quickly in the IL-6 treated animals. Sequential IL-3/IL-6 significantly increased the production of PLTs when compared with the HSA-treated controls (P = .003) and monkeys receiving concomitant IL- 3/IL-6 (P = .041) but did not alter PMN levels significantly (P = .80). Coadministration of IL-6 and IL-3 did not enhance PLT but improved PMN recovery over IL-6 alone. In this primate model of marrow aplasia, IL-6 significantly enhanced the regeneration of PLTs but had no significant effect on PMN production, and did not exacerbate radiation-induced anemia. Furthermore, the use of sequentially administered IL-3 and IL-6 may improve PLT recovery as compared with concurrent IL-3/IL-6 administration, although this protocol is not significantly different in effect than either cytokine alone.     

COMPARISON OF THE EFFECT OF APOMORPHINE AND l-DOPA ON SERUM GROWTH HORMONE LEVELS IN NORMAL MEN

Apomorphine hydrochloride (0.75 mg s.c.) has been compared with L-dopa (500 mg p.o.) in their effects on growth hormone secretion in a double blind cross-over study involving nine healthy men. Apomorphine increased serum GH levels above 10 ng/ml in all nine subjects 30-60 min after injection. In contrast, only six of these subjects showed a similar elevation with L-DOPA and in only three had the level increased above 6 ng/ml by 60 min. One subject failed to respond to L-dopa and in two others the peak was less than 6 ng/ml. GH levels were significantly higher at 30, 45 and 60 min following apomorphine than following L-dopa. Apomorphine-induced GH release was not related to changes in serum cortisol or blood sugar. Benztropine mesylate (1 mg i.m.) had no effect on apomorphine-induced GH release. These results suggest: (a) apomorphine may have advantages over L-dopa as a provocative agent to assess GH secretory capacity; (b) a dopaminergic mechanism subserves GH secretion; (c) cholinergic mechanisms do not antagonize dopaminergic-related GH release.     

The role of calcium in the age-related decline of neutrophil function

Upon activation by formyl-methionyl-leucyl-phenylalanine (FMLP), either in the presence of absence of cytochalasin B, neutrophils from old subjects generated significantly less superoxide than did neutrophils from the young. This reduction in activity was associated with a significant decrease in the basal cytosolic calcium concentration and a diminished flux of calcium to the cytosol after activation. At all concentrations of FMLP tested, cytosolic calcium remained significantly lower in neutrophils from the old as compared with the young, whereas permeability to extracellular calcium and efflux of calcium from the cell were also significantly diminished. Pretreatment of the cell with the ionophore ionomycin elevated the cytosolic calcium concentration and significantly improved function in old neutrophils. These findings demonstrate that aging results in alterations in neutrophil calcium homeostasis that may play a role in the age-related decline in neutrophil function.