Imaging of disorders of the spine

Although many papers were published during the past year on disorders of the spine, in this review, papers were chosen and grouped under five broad headings: 1) spinal trauma, 2) disk disease, 3) neoplastic disease, 4) spinal arthritis, and 5) other studies of interest. Although some of the articles chosen for review dealt with conventional radiography, the majority were on applications of CT and MR imaging to conditions affecting the spine.     

Observer variation in quantitative assessment of rheumatoid arthritis. Part I. Scoring erosions and joint space narrowing

Six observers, including two bone and joint radiologists, two general radiologists, and two senior radiology residents, compared scores to quantitate radiographic findings in the hands and wrists of patients with rheumatoid arthritis. In the scoring system used, erosions and joint-space narrowing are graded separately. This scoring system differs from other methods in that equivocal findings are not scored, while ankylosis, subluxation, and dislocation are scored, and data from postoperative joints are included. Total radiographic scores were highly significantly correlated for all observers (R = .908-.958, P less than .001), as were subtotal scores for erosions (R = .723-.931, P less than .001) and joint-space narrowing (R = 0.843-0.966, P less than .001). Analysis of proximal interphalangeal, metacarpophalangeal, and wrist-joint scores showed highly significant correlations for all observers in each location. Highly significant correlations were found among three separate readings of two bone and joint radiologists (R = .950-.961, P less than .001). This scoring system provides highly consistent and reproducible results, even in the hands of less experienced observers.     

A negative phase II trial methylene dimethane sulphonate in advanced ovarian cancer (Cancer Research Campaign Phase I/II Trials Committee)

Methylene dimethane sulphonate (MDMS), the first member of the homologous series of dimethane sulphonic acid esters, was administered to 19 patients with advanced epithelial ovarian cancer. All patients had received prior chemotherapy and in addition 3 had received prior radiotherapy. MDMS was given as an i.v. bolus injection at a dose of 125mg m-2 and repeated in a q35 day schedule. Ten patients received only one course, six two courses, two three courses and one four courses. The major toxicity was thrombocytopenia which was cumulative. Serious neutropenia did not occur and no infective episodes requiring i.v. antibiotics were seen. Seven patients experience hair loss and four nausea and vomiting. Sixteen patients were evaluable for response but no objective remissions were seen although three patients had stable disease lasting at least 8 weeks. MDMS is therefore not recommended for further trial in epithelial ovarian carcinoma.     

Rheumatoid arthritis: explanatory power of specific radiographic findings for patient clinical status

Radiographs of the hands and wrists of 201 patients with rheumatoid arthritis (RA) were scored for erosion, joint space narrowing, and malalignment. The explanatory power of these findings for measures of clinical status was studied with stepwise multiple linear regression analyses. Radiographic scores explained 59.2% of variation in physical joint count deformity scores, 58.5% of variation in limited motion scores, 22.5% of variation in grip strength scores, 20.5% of variation in button test scores, and 13.5% of variation for the American Rheumatism Association (ARA) Functional Class. Malalignment scores best explained variation in physical deformity, limited motion, and button test scores; joint-space-narrowing scores best explained variation in grip strength; erosion scores best explained variation in ARA Functional Class. When age, duration of disease, erythrocyte sedimentation rate, and rheumatoid factor titer were included in the regression analyses, results were similar to those without these variables. Therefore quantitative scores of specific radiographic findings are in themselves explanatory for measures of clinical status.     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}     

Protein kinase C inhibitors

Protein kinase C (PKC) is a family of serine-threonine protein kinases that are involved in signal transduction pathways that regulate growth factor response, proliferation, and apoptosis. Its central role in these processes, which are closely involved in tumor initiation, progression, and response to antitumor agents, makes it an attractive therapeutic target in cancer. Despite initial activity seen in melanoma (bryostatin and UCN-01), non-Hodgkin’s lymphoma (ISIS 3521, bryostatin, and UCN-01), and ovarian carcinoma (ISIS 3521 and bryostatin) in phase I studies, single-agent activity in those phase II studies reported to date has been limited. Preclinical data highlight a role for PKC in modulation of drug resistance and synergy with conventional cytotoxic drugs. A randomized phase III study of ISIS 3521 in combination with carboplatin and paclitaxel, compared with chemotherapy alone, in advanced non-small-cell lung cancer is underway. This paper reviews the rationale for using PKC inhibitors in cancer therapy, the challenges for clinical trial design, and the recent clinical experience with modulators of PKC activity.     

Multidrug resistance: clinical relevance in haematological malignancies.

Multidrug resistance describes an experimental observation which appears to explain cross-resistance to certain structurally unrelated cytotoxic agents, including anthracyclines, vinca alkaloids and podophyllotoxins. It is now clear that a major factor responsible for its development is increased expression of a membrane glycoprotein--P-glycoprotein, which functions as an energy-dependent efflux pump. Recent data, particularly in haematological malignancies such as acute non-lymphocytic leukaemia, myeloma and non-Hodgkin's lymphoma, indicate that P-glycoprotein may be involved in the development of clinical drug resistance. The potential therefore exists for new therapeutic studies aimed at circumventing resistance which develops through this mechanism, by using modulators, such as verapamil, quinidine and several others, which prevent cellular drug efflux by competitive binding to P-glycoprotein.     

A phase II study of Gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck

BACKGROUND: Gemcitabine is a new pyrimidine antimetabolite with novel metabolicproperties and mechanism of action. Phase I clinical trialshave demonstrated acceptable toxicity and promising antitumoractivity. The objectives of this open multicenter phase II trialwere to determine the efficacy and toxicity of this agent inpatients with advanced head and neck cancer. PATIENTS AND METHODS: Sixty-one patients with advanced and/or recurrent squamous cellcarcinoma of the head and neck were treated with Gemcitabineas a weekly 30 minutes i.v. administration for 3 consecutiveweeks followed by one week rest. The Gemcitabine starting dosewas 800 mg/m²/week in 47 patients (a majority being pre-treatedwith chemotherapy) and was later increased to 1250 mg/m² in14 chemotherapy-naive patients. Dose adjustements were basedon hematologic and non-hematologic toxicities. RESULTS: Seven partial responses were observed among 54 evaluable patients,yielding a response rate of 13% (95% confidence interval: 4%–22%).The incidence of hematologic toxicity was low, with grade 3–4neutropenia in less than 10% of the courses. Fifty-three percentof the patients experienced an increase in liver enzymes, mainlygrade 1 or 2. Fatigue was reported by 39% of the patients, frequentlyassociated with flu-like symptoms. CONCLUSION: Gemcitabine is a drug with documented antitumor activity inpatients with advanced squamous cell carcinoma of the head andneck. head and neck cancer, gemcitabine, phase II study