Alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase activity in the sera of patients with esophageal cancer

Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the human esophageal mucosa. In our last experiments we have shown that ADH and ALDH are present also in the esophageal cancer cells. Moreover, the activities of total ADH and class IV isoenzymes were significantly higher in cancer tissue than in healthy mucosa, which suggests that these changes may be reflected by enzyme activity in the serum. Therefore, we measured the activity of total alcohol dehydrogenase, and classes I–IV of this enzyme and aldehyde dehydrogenase in the sera of patients with this cancer. Serum samples were taken for routine biochemical investigation from 67 patients with esophageal cancer before treatment. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes, we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was measured by the photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. A statistically significant increase of class IV alcohol dehydrogenase isoenzymes was found in the sera of cancer patients. The median activity of this class isoenzyme in the total cancer group increased by about 26.5% (7.42 mU/l) in comparison to the control level (5.46 mU/l). The total alcohol dehydrogenase activity was significantly higher (30%) among patients with cancer. The activities of other tested ADH isoenzymes and total ALDH were unchanged. The activity of the class I ADH isoenzyme was significantly higher in the sera of drinkers with esophageal cancer than non-drinking patients. The increased total activity of alcohol dehydrogenase and class IV isoenzyme in the sera of patients with esophageal cancer probably can be caused by release of this isoenzyme from cancer cells or might be stimulated by alcohol drinking.     

A phase II trial of Triapine® (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Study 1503

Background: The objective of ECOG 1503 was to determine the response rate of this combination in the second-line treatment of advanced NSCLC. Methods: Triapine 105 mg/m² IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m² on days 1, 8, and 15, of a 28 day cycle. Results: Eighteen patients enrolled. Three patients were not eligible due to protocol violations. No objective antitumor responses were seen. Three patients (20%) experienced stable disease (90% CI 5.7–44%). Median overall survival: 5.4 months (95% CI 4.2–11.6 months); median time to progression: 1.8 months (95% CI 1.7–3.5 months). Five patients developed acute infusion reactions to Triapine? related to elevated methemoglobinemia. Patients with MDR1 variant genotypes of C3435T experienced superior overall survival compared to non-variants (13.3 vs. 4.3 months, respectively, p = 0.023). Conclusion: This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating.     

Early detection of Alzheimer's disease using neuroimaging

Neuroimaging is being increasingly used to complement clinical assessments in the early detection of Alzheimer's disease (AD). Structural magnetic resonance imaging (MRI) and metabolic positron emission tomography (FDG-PET) are the most clinically used and promising modalities to detect brain abnormalities in individuals who might be at risk for AD but who have not yet developed symptoms. The knowledge of established risk factors for AD enabled investigators to develop enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study duration. The present review focuses on the results obtained by MRI and FDG-PET studies that examined the preclinical AD stages in several at risk populations: (1) individuals from families with autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI), particularly in memory, who are at very high risk for declining to AD with an estimated decline rate of 10-30% per year, (3) normal young and middle-age subjects carriers of known susceptibility genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these studies show that the use of imaging for the early detection of AD is successful even in the earlier stages of disease when clinical symptoms are not fully expressed and the regional brain damage may be limited.     

Cardioverter-defibrillator lead-related thrombus treated with prolonged anticoagulation in patient with prothrombotic disorder.

Following an accidental finding of a large atrial lead-related thrombus in a 33-year-old woman with suspected prothrombotic disorder, a conservative treatment with low molecular weight heparin injections and close transthoracic and transesophageal echocardiographic monitoring was used. It led to a complete resolution of the thrombus in 4 weeks without the need for a high-risk operation in this patient.     

Epithelioid Sarcoma of the Bartholin's Gland Primarily Diagnosed as Vulvar Carcinoma

A case of vulvar epithelioid sarcoma (VES) in a 49-year-old female is described. The disease originated from Bartholin's gland and was originally diagnosed as vulvar squamous cell carcinoma. The patient was treated by radical vulvectomy and bilateral inguinal lymphadenectomy. Multidrug chemotherapy using doxorubicin, cyclophosphamide, vincristine, and dacarbazin was started, but had to be abandoned because of cardiac toxicity. Despite intensive treatment, the patient developed pulmonary metastatic disease and died after 8 months. The course of epithelioid sarcoma in this site seems to be more aggressive than in typical extremity locations and was consistent with other cases described in the literature.     

Multidrug-resistant bacteria isolated from patients hospitalised in Intensive Care Units

Surveys of the prevalence and susceptibility patterns of bacterial isolates are important in determining optimum empirical therapy for infections in critically ill patients. The aim of this study was to determine possible differences in the patterns of bacterial resistance in two Intensive Care Units (ICUs) depending on the patient profile. There was a high percentage of non-fermenting Gram-negative rods (NFGNR) among the bacterial isolates from both wards. NFGNR comprised 43.8% of all isolates from ICU-B and 38.9% from ICU-A. Extended-spectrum beta-lactamase production was detected in 40.0% of Gram-negative rods cultured from ICU-A compared with 26.7% from ICU-B; whilst imipenem-resistant strains of Acinetobacter baumannii constituted 17.1% of isolates from ICU-A and 9.6% from ICU-B. Emergence of A. baumannii strains resistant to imipenem was recorded, particularly among blood isolates. In both wards, multidrug-resistant (MDR) strains of Gram-negative bacilli were more prevalent among blood isolates than among strains cultured from other specimens. Longer stay in ICU-A promoted selection of MDR Gram-negative rods.     

Protective effect of local temporary ischemia depends on applied dose of radiation

The aim of this study was to verify hypothesis that protective effect of local temporary ischemia depends on dose of radiation. 56 male WAG-strain rats were used. Total body irradiation with 3 x 3 and 3 x 5 Gy was performed. Local temporary ischemia was induced by clamping the tail base. The biochemical parameters were the thiobarbituric acid-reactive substances (TBA-RS). In bone marrow smears the polychromatic erythrocyte (PCE) numbers were counted and the numbers of micronucleated PCEs were analyzed. In small intestines the numbers of crypts were calculated. The levels of TBA-RS in the serum of the animals irradiated with a 3 x 3 Gy dose were significantly different (P < 0.002). Also in animals irradiated with a dose of 3 x 3 Gy the numbers of intestinal crypts were different (P < 0.05). In animals irradiated with dose 3 x 5 Gy, for analyzed parameters differences did not achieve statistical significance. Local temporary ischaemia provides general protection against radiation damage for lower dose. This protective effect disappeared after applications of a higher dose of radiation.     

The role of quantitative structural imaging in the early diagnosis of Alzheimer's disease

The goal of this article is to review the role of structural neuroimaging in the diagnosis of Alzheimer's disease (AD). We present relevant neuroanatomy, highlight progress in the domain of AD imaging, and review the clinical characteristics of the prodromal phase of AD. We describe the history of the diagnostic issue by examining at cross-section and longitudinally the differences between patients who have AD and normal controls. We also present how subsequent works applied these characteristic traits to the early detection of the prodromal disease and to prediction of future decline. The article delineates the differences between subjects who have mild cognitive impairment and AD, which illustrate the spreading of the pathology with disease progression. The last section describes problems encountered in the differential diagnosis.     

Comparison of the efficacy of ICSI using either spermatozoa aspired microsurgically from the epididymis (MESA-ICSI) or obtained from the ejaculation

OBJECTIVE: Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection (MESA-ICSI) is a viable alternative to the treatment of couple sterility caused by obstructive azoospermia. Because there are structural differences between epididymal and ejaculated spermatozoa and it is not univocally stated, if this fact influences positively or negatively the results of ICSI, it was decided to compare the efficacies of ICSI using both the kinds of spermatozoa at the same setting. DESIGN: Retrospective comparative analysis. MATERIALS AND METHODS: The MESA group consisted of 27 couples and the control ICSI group of 154 couples--both matched in age, duration of sterility, health status, stimulation protocols and luteal supplementation. The trial was performed at the same period in one center, keeping the same laboratory and personal conditions in both the groups. RESULTS: In the MESA group the fertilization rate was 53.9%, the cleavage rate 87.6% and pregnancy rates 37.0% per microinjection and 43.5% per embryotransfer. In the control group the corresponding values were 50.1%, 90.0%, 28.0% and 31.7%. The differences between the groups were insignificant. CONCLUSIONS: It may be concluded, that the structural differences between epididymal and ejaculated spermatozoa do not significantly influence the efficacy of ICSI, however further investigations are still needed.