Inter-observer variability in APACHE II scoring: effect of strict guidelines and training.

Objective: To assess the effect of strict guidelines and a rigorous training program on variability in scoring the revised Acute Physiology and Chronic Health Evaluation (APACHE II).

Design And Setting: Prospective survey and intervention in the surgical ICU of a university teaching hospital.

Measurements: Seven experienced intensivists and nine residents determined APACHE II scores in one set of patients before and in another set 4 months after a rigorous training program, following strict guidelines for using the APACHE II.

Metabolism and growth inhibition of four retinoids in head and neck squamous normal and malignant cells.

Isotretinoin (13-cis-retinoic acid, 13cRA) has proven to be active in chemoprevention of head and neck squamous cell carcinoma (HNSCC). Moreover, both all-trans-retinoic acid (ATRA) and 13cRA induce objective responses in oral premalignant lesions. After binding of retinoids to retinoic acid receptors (RARs and RXRs) dimers are formed that are able to regulate the expression of genes involved in growth and differentiation.

Do Fanconi anemia genes control cell response to cross-linking agents by modulating cytochrome P-450 reductase activity?

The Fanconi anemia (FA) genes play an important role in maintaining chromosomal stability and the defense of mammalian cells against cross-linking agents, such as cisplatin and mitomycin C (MMC). Cells derived from FA patients display a characteristic hypersensitivity toward cross-linking agents. Despite great progression in our understanding of the mechanisms that protect cells against these potent anti-cancer drugs, the specific roles of FA gene products in these processes have not been delineated.

HPV presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears.

In a retrospective case-control study, we investigated high-risk HPV DNA presence by general primer GP5+/6+ PCR in the last normal cervical smear in the patient archives (i.e. baseline smear) of 57 women who later developed cervical cancer.

Rb, mcl-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer.

Background: Thymidylate synthase (TS) has been associated with clinical outcome in disseminated colorectal cancer. However, many patients with low TS expression still fail to respond to treatment. Therefore, we studied the cell cycle proteins, Rb, E2F2, Ki67, p21 and p53 and the apoptotic proteins, mcl-1, hax, bcl-xl, bcl-2, Fas receptor, Fas ligand, caspase-3, M30 and PARP as potential predictive factors.

Serial evaluation of perfusion defects in patients with a first acute myocardial infarction referred for primary PTCA using intravenous myocardial contrast echocardiography.

Aims: To investigate whether myocardial contrast echocardiography using Sonazoid could be used for the serial evaluation of the presence and extent of myocardial perfusion defects in patients with a first acute myocardial infarction treated with primary PTCA, and specifically, (1) to evaluate safety and efficacy of myocardial contrast echocardiography to detect TIMI flow grade 0--2, (2) to evaluate the success of reperfusion and (3) to predict left ventricular recovery after 4 weeks follow-up.

Methods And Results: Fifty-nine patients underwent serial myocardial contrast echocardiography, immediately before primary PTCA (MCE1), 1 h (MCE2) and 12--24 h after PTCA (MCE3). A perfusion defect was observed in 21 of 24 patients (88%) with anterior acute myocardial infarction.

The responsiveness of the Action Research Arm test and the Fugl-Meyer Assessment scale in chronic stroke patients.

The responsiveness of the Action Research Arm (ARA) test and the upper extremity motor section of the Fugl-Meyer Assessment (FMA) scale were compared in a cohort of 22 chronic stroke patients undergoing intensive forced use treatment aimed at improvement of upper extremity function. The cohort consisted of 13 men and 9 women, median age 58.5 years, median time since stroke 3.

Selective gene delivery toward gastric and esophageal adenocarcinoma cells via EpCAM-targeted adenoviral vectors.

Application of recombinant adenoviral vectors for cancer gene therapy is currently limited due to lack of specificity for tumor cells. For gastric and esophageal adenocarcinoma, we present here that the relative abundant expression of the primary adenovirus receptor, coxsackie/adenovirus receptor (CAR), on normal epithelium compared to carcinoma favors the transduction of the epithelium. As such, to achieve specific transduction of cancer cells, targeting approaches are required that ablate the binding of the virus to CAR and redirect the virus to tumor-specific receptors.

Circulating V(alpha24+) Vbeta11+ NKT cell numbers are decreased in a wide variety of diseases that are characterized by autoreactive tissue damage.

Natural killer T (NKT) cells have been implicated as playing an important role in regulating immune responses. Defects in the NKT cell population were reported in animal autoimmune disease models and in distinct human autoimmune diseases. Here, we report that circulating V(alpha24+) Vbeta11+ NKT cell numbers are decreased in a broad variety of disorders with (auto)immune-mediated pathology, affecting the skin, bowel, central nervous system, and joints, regardless of disease duration or activity.

Bronchial intraepithelial neoplastic lesions in head and neck cancer patients: results of autofluorescence bronchoscopy.

To determine the efficacy of autofluorescence bronchoscopy for detection of bronchial intraepithelial neoplastic lesions in head and neck cancer patients, we analyzed data from head and neck cancer patients who underwent both white light bronchoscopy and autofluorescence bronchoscopy for the rates of detection of intraepithelial neoplastic lesions. The results of the histopathologic examination were compared with the bronchoscopic findings. The sensitivity for detection of intraepithelial neoplastic lesions was calculated.

Combination treatment in autoimmune diseases. Methodology of combination trials.

Even with the limited number of antirheumatic agents available, theoretical considerations lead to an almost infinite number of combination strategies. This article outlines possible strategies based on the primary choice between maximization of efficacy or minimization of toxicity. Strategies are illustrated with examples from trial experience in the field of rheumatoid arthritis.

The Human Achaete Scute Homolog 2 gene contains two promotors, generating overlapping transcripts and encoding two proteins with different nuclear localization.

Placental development involves control by the basic helix-loop-helix transcription factor Mash2. Transcript analysis of the Human Achaete Scute Homolog 2 (HASH2) mRNA revealed the presence of two overlapping transcripts in first trimester placentae. The two transcripts (2.

Differences in sulfation patterns of heparan sulfate derived from human bone marrow and umbilical vein endothelial cells.

Objective: Heparan sulfates (HS), the polysaccharide side chains of HS proteoglycans, differ in structure and composition of sulfated domains among various tissue types, resulting in selective protein binding. HS proteoglycans on bone marrow endothelial cells (BMEC) could contribute to tissue specificity of the bone marrow endothelium and play a role in the presentation of chemokines such as stromal cell-derived factor-1 (SDF-1) and adhesion of hematopoietic progenitor cells after stem cell transplantations. We characterized differences in HS structure and SDF-1 binding between BMEC and human umbilical vein endothelial cells (HUVEC).

High-dose melphalan with G-CSF-stimulated whole blood rescue followed by stem cell harvesting and busulphan/cyclophosphamide with autologous stem cell transplantation in multiple myeloma.

In 90 consecutive patients with multiple myeloma, we investigated the feasibility of administering a tandem high-dose therapy regimen, using whole blood for rescue after the first and leucapheresis harvested between the two high doses, for rescue after the second high dose. After 5 days of G-CSF 1 litre of whole blood (WB) was obtained, left undisturbed at 4 degrees C and reinfused 24 h after HDM (140 mg/m(2)). Patients not in progression after 3-6 months were again mobilised, leucapheresed and treated with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg (Bu/Cy) and reinfusion.

New synthetic flavonoids as potent protectors against doxorubicin-induced cardiotoxicity.

A series of 3,7-disubstituted-2(3',4'-dihydroxyphenyl) flavones has been studied as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 position of the flavone nucleus on antioxidant activity cytotoxicity and cardioprotective properties was explored to improve the activity of our lead compound 7-monohydroxyethylrutoside. In the protection against Fe(2+)/vitamin C-induced microsomal lipid peroxidation (LPO assay), IC(50) values ranged from 0.

The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells.

Background: The effectiveness of systemic treatment of psoriasis with fumaric acid esters has been proven, but their mode of action at the cellular and molecular level has not yet been fully elucidated.

Objectives: To study the effect of dimethylfumarate (DMF) on the production of the chemokines CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11, formerly known as GROalpha, interleukin-8, Mig, IP-10 and IP-9/I-TAC, respectively, in human keratinocytes and peripheral blood mononuclear cells (PBMC).

Methods: Cultured keratinocytes were stimulated with interferon (IFN) -gamma to produce CXCL9, CXCL10 and CXCL11 and with phorbol myristate acetate to produce CXCL1 and CXCL8 in the absence and presence of DMF (5, 15 and 45 micromol L(-1)).

Differences in the induction of DNA damage, cell cycle arrest, and cell death by 5-fluorouracil and antifolates.

Thymidylate synthase (TS) is an important target for chemotherapy and can be inhibited by 5-fluorouracil (5-FU) and the antifolates, AG337 (Nolatrexed) and multitargeted antifolate (MTA or Pemetrexed). In addition, 5-FU can be incorporated into RNA and DNA, and MTA can inhibit two other enzymes. It is, however, unclear to what extent these differences in drug action will influence activation of downstream mechanisms mediated via TS inhibition.

Is disease severity in ankylosing spondylitis genetically determined?

Objective: To assess the role of genes and the environment in determining the severity of ankylosing spondylitis.

Methods: One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI).

Radioimmunotherapy in patients with head and neck squamous cell carcinoma: initial experience.

Background: Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells.

Impaired left ventricular filling due to right ventricular pressure overload in primary pulmonary hypertension: noninvasive monitoring using MRI.

Objective: To analyze the effect of primary pulmonary hypertension (PPH) on cardiac function using MRI.

Methods: In 12 patients (9 women; age range, 30 to 56 years), the diagnosis of PPH had been established by catheterization (mean +/- SD pulmonary artery pressure [PAP] was 56 +/- 8 mm Hg). With breath-hold cine MRI, a series of short-axis images was acquired covering the whole left ventricle (LV) and right ventricle (RV).

Continuing expansion of internal iliac artery aneurysms after surgical exclusion of the inflow. A report of two cases.

Two patients with continuing expansion of an internal iliac artery aneurysm following earlier repair of an aortoiliac aneurysm are described. At the primary operation, inflow to small internal iliac aneurysms had been interrupted by simple proximal ligation only. During follow-up, however, increasing diameter of the by CT-angiography completely thrombosed internal iliac aneurysms required re-operation.

Treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomized clinical trials.

A blinded meta analysis was performed on randomized clinical trials (RCT) on the medicinal treatment of reflex sympathetic dystrophy (complex regional pain syndrome type I) to assess the methodological quality and quantify the analgesic effect of treatments by calculating individual and summary effect sizes. The internal validity of 21 RCTs was investigated and the quality weighted summary effect size was calculated using a fixed effect model (Glass Delta). The methodological quality ranged from moderate to good (average 46%).

Telomerase suppression by chromosome 6 in a human papillomavirus type 16-immortalized keratinocyte cell line and in a cervical cancer cell line.

Background: High-risk human papillomavirus (HPV) types play a major role in the development of cervical cancer in vivo and can induce immortalization of primary human keratinocytes in vitro. Activation of the telomere-lengthening enzyme telomerase constitutes a key event in both processes. Because losses of alleles from chromosome 6 and increased telomerase activity have been observed in high-grade premalignant cervical lesions, we analyzed whether human chromosome 6 harbors a putative telomerase repressor locus that may be involved in HPV-mediated immortalization.

Cloning and characterization of human liver cytosolic beta-glycosidase.

Cytosolic beta-glucosidase (EC 3.2.1.