股骨干骨折扩髓腔髓内钉固定对凝血机能和肺换气功能的影响

【目的】探讨股骨干骨折扩髓与不扩髓髓内钉固定对凝血机能和肺换气功能的影响。【方法】 38例股骨干骨折分别采用扩髓 (RFN)和不扩髓 (UFN)髓内钉固定 ,在手术开始前至术后 4 8h内 7个不同时间段监测血小板、纤维蛋白原、凝血酶原时间 (PT)和部分凝血活酶激活时间 (APTT)的变化 ,并动脉血气分析 ,计算肺泡 动脉血氧分压递差 [P(A aDO2 ) ]。【结果】RFN组 ,扩髓后血小板开始减少 ,P(A aDO2 )升高 (P<0 0 5 ) ;髓钉插入后 30min纤维蛋白原减少 ,PT、APTT延长 (P <0 0 5 ) ;UFN组表现出同样的趋势 ;两组中各项指标均在 2 4～ 4 8h内恢复正常 ;动脉血气分析各时间段和组间差异无显著性 (P >0 0 5 )。【结论】扩大髓腔的髓内钉固定 ,和不扩髓相比 ,并不影响肺换气功能 ,对凝血机能的影响是一个自限过程 ,单纯股骨干骨折 ,可耐受扩髓固定手术。     

The pharmaco-economics of peri-operative beta-blocker and statin therapy in South Africa.

We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost saving through a reduction in major perioperative cardiovascular complications in patients with an expected peri-operative major cardiovascular complication rate exceeding 10% following elective major non-cardiac surgery. The validity of these findings is dependent on whether the incidence of cardiovascular complications following major noncardiac surgery reported in the international literature is found to be similar in South Africa.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Analysis of CDKN1A polymorphisms: markers of cancer susceptibility?

The CDKN1A (TP21) gene encodes a 21-kD protein that is a critical downstream mediator of wild-type TP53 and an important regulator of the cell cycle. Failure in the function of this gene would be expected to result in abnormal cell proliferation and transformation. Tumor-associated mutations of the coding region of the TP21 are rare. On the other hand, some TP21 polymorphisms have been identified and characterized by single base substitutions. In the present study, we investigated the potential role of TP21 gene polymorphisms in skin, head, and neck tumorigenesis. A total of 261 samples were examined by polymerase chain reaction single-strand conformational analysis, and one mutation at codon 31 and four polymorphisms in exons 2 (codon 55) and 3 [nucleotide (nt)590] and in promoter region (nt2298) were identified. In conclusion, this investigation confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers. Also, our results show significant differences in nt2298 allele frequencies between normal individuals and skin malignant tumors (P < 0.05). The results suggest that this polymorphism affects TP21 transactivator binding and may be important during the pathogenesis of skin cancer.     

Bacteremia caused by an undescribed species of Janibacter

A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Lineage relationship of chronic lymphocytic leukemia and hairy cell leukemia: studies with TPA

The tumor promoting agent TPA (phorbol ester; 1.6 X 10(-8)M) was used to induce the differentiation in vitro of B-chronic lymphocytic leukemia (B-CLL) cells from 14 untreated patients. The uninduced phenotype was SIg+, Mrbc+, RFT-1+, RFA-4-, FMC7-. After 72 h incubation with TPA, B-CLL cells became RFA-4+, FMC7+ and lost the capability of Mrbc rosetting. Large proportions of the "induced" cells also showed morphological and ultrastructural changes, such as undulating membranes and bleblike protusions and became strongly positive for tartrate resistant acid phosphatase (TRAP+) and also contained cytoplasmic immunoglobulins. These features are very similar to the features of hairy cell leukemia (HCL). These observations confirm previous clinical findings that B-CLL and HCL are related disorders of the B lineage. The development of "hairy" features in induced B-CLL and in HCL seems to be a malignancy-associated feature because the Mrbc+ normal B cells (B-CLL-equivalent cells) isolated from tonsil also develop TRAP positivity but no membrane aberrations.     

The preparation and characterization of fine dusts carried out in the Clinica del Lavoro di Milano in support of experimental studies

This paper aims to illustrate the conditions selected at the Clinica del Lavoro of the University of Milan to prepare and analyze a large number of fine dust samples produced over a period of about 50 years, that were initially used for studies within the Clinic performed in its own facilities, and since 1956 were sent to other Italian and overseas laboratories (Luxembourg, UK, Germany, Norway, Sweden, South Korea, USA). The total quantity of material distributed (with maximum size 7-10 microns) was about 2 kg and consisted of the following mineral and artificial compounds: quartz, HF-treated quartz, tridymite, HF-treated tridymite, cristobalite, chromite, anthracite, quartz sand for foundry moulds, sand from the Lybian desert, vitreous silica, pumice, cement, as well small quantities of metallic oxides, organic resins, chrysotile, crocidolite, fibres (vitreous, cotton and polyamidic). About half of the entire quantity of dusts produced consisted of partially HF-treated tridymite. Initially, research on the etiology of silicosis used quartz dust samples, simply sieved or ventilated (consisting of classes finer than 0.04 mm, containing a 15-20% respirable fraction). From 1956 to 1960 the dusts were produced by manual grinding in an agate mortar, below about 10 microns, starting from quartz from Quincinetto (near Ivrea, Province of Turin), containing about 99.5% quartz: particle size and composition were checked using an optical-petrographic technique, with identification of the free and total silica content. Subsequently, the dusts used for biological research were obtained by grinding coarse material with a cast iron pestle and planetary mills, agate and corundum jars. The grinding products were sized by means of centrifugal classification, using the selector developed by N. Zurlo, ensuring control of dust size both optically and by means of wet levigators and hydraulic classifiers (in cooperation with the Institute of Mines of Turin Polytechnic School). After 1990 pestles and rotating drum mills with autogenic grinding load were used for grinding: the size of the treated samples was reduced to 0.05 mm and an extremely fine fraction was extracted, smaller than 7-10 microns, which was used for pneumoconioses research. The characterization of the dust produced was in any case achieved by means of preliminary examination under the optical microscope (polarized light, sometimes supplemented with phase contrast), followed by quantitative analysis using chemical/petrographic, chemical diffraction or, more commonly, petrographic/diffraction techniques. Microscopic examination, if necessary supplemented with photo-micrography, was also used for particle size control, for numerical counting and subsequent reference to weight proportion. For all operational procedures the essential data on instruments and methods are reported. During studies on production, separation of fine dusts and their characterization, partly performed with support from the European Community (EEC/European Coal and Steel Commission), the following topics in particular were addressed: connections between particle size and free silica content in the measurable dust size fraction of the grinding products and in airborne dusts; characteristics of the dusts and risk indices in Italian iron and pyrite mines; possibility of abatement of the ultrafine classes of airborne dusts in pneumatically filled stopes by the addition of salts; comparison of the latest dust selectors used within the European Community; influence of the grinding methods on the results of fibrous and soft mineral measurement using X-ray diffraction analysis.