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New discriminatory level for glucosidase activity to diagnose epididymal obstruction or dysfunction.

Neutral alpha-glucosidase activity was measured in seminal plasma of 30 patients consulting for infertility with a variety of disorders, and compared with 25 normal controls. Significantly more of the study populations (asthenozoospermia, 4/6; oligozoospermia, 3/5; azoospermia 8/15) had a neutral alpha-glucosidase activity less than 10 mIU/mL as compared with control samples (3/25). Also the mean (+/- SD) neutral alpha-glucosidase activity in patients with asthenozoospermia (11.7 +/- 9.2) oligozoospermia (11.3 +/- 7.2), and post vasectomy azoospermia (5.3 +/- 3.4) was significantly (p < .05) less than ejaculate from controls (21.2 +/- 14). A seminal alpha-glucosidase level of 10 mIU/mL appears to be a useful discriminatory marker in the diagnosis of epididymal obstruction or dysfunction.

Biomarkers↗

Alzheimer's disease: diagnosis and treatment.

This review describes and evaluates developments in the early diagnosis and the treatment of Alzheimer's disease. It is hoped that early diagnosis of the disorder will enable treatment that will reduce or arrest the associated cognitive loss so that affected individuals can retain significant function and institutionalization can be delayed or averted. Diagnostic techniques, including use of neuropsychological measures, functional imaging measures, and biological markers, are reviewed; such techniques are useful for confirming diagnosis but do not replace a comprehensive clinical evaluation. Potential treatment modalities, such as techniques to enhance neurotransmission, replace estrogen effects, reduce the effects of free radicals, and combat inflammation, are explored. Cholinesterase inhibitors are the only modality thus far shown in large-scale studies to be effective, but their effect is small.

Alzheimer Disease↗

Hemostasis activation in patients undergoing brain tumor surgery.

Patients undergoing brain tumor surgery are at high risk for the occurrence of a thromboembolic event. To identify a laboratory marker suitable for risk estimation the authors studied the perioperative time pattern of routine coagulation parameters and the specific hemostasis activation marker D-dimer in 28 consecutive patients at high risk (11 patients with glioma and eight patients with meningioma) and low risk (nine patients with metastases) for thromboembolism, as previously reported. As is typical during major surgery, most of the routine parameters declined, probably because of hemodilution, and recovered postoperatively to values higher than baseline, probably because of an acute-phase reaction. On Days 2 and 7 after surgery no difference in the routine parameters was recorded between patients at high (meningioma and glioma) and low risk (metastasis). The level of D-dimer was elevated at baseline in patients with metastasis, indicating a hemostatic hyperactivity that is usual in cancer patients. During surgery a marked increase in D-dimer levels occurred in patients with meningioma and glioma (pre- and postoperative median 90/2000 and 100/1020 ng/ml, respectively), but the increase was less pronounced in patients with metastasis (320/660 ng/ml). Postoperatively, D-dimer declined in patients with metastases to lower than preoperative levels (Day 7, 270 ng/ml); in patients with meningioma or glioma, however, D-dimer levels remained elevated until Day 7 (450 and 200 ng/ml, respectively). These results indicate that levels of D-dimer correlate with the reported high risk for thromboembolism in patients with meningioma and glioma, and D-dimer should be evaluated for its use in estimating individual risk and the efficiency of its use in the control of prophylactic treatment.

Acute-Phase Reaction↗

Cytokines and Inflammatory Gene Polymorphisms Associated With Nosocomial Pulmonary Infection After Spontaneous Intracerebral Hemorrhage.

Nosocomial pulmonary infection is a frequent complication after spontaneous intracerebral hemorrhage and may worsen neurological recovery, prolong hospitalization, and increase clinical burden. This retrospective clinical-laboratory study presents a reproducible workflow for evaluating inflammatory biomarker and host immune-genetic profiles associated with nosocomial pulmonary infection after primary spontaneous intracerebral hemorrhage. Patients are classified according to whether nosocomial pulmonary infection occurs after admission. Peripheral venous blood is collected in the early post-admission period under standardized pre-analytical conditions. Serum is separated, aliquoted, and stored for enzyme-linked immunosorbent assay measurement of IL-1&#x3b2;, IL-6, IL-10, IL-17, IFN-&#x3b3;, TNF-&#x3b1;, TLR2, TLR4, and TLR9. In parallel, genomic DNA is extracted from anticoagulated whole blood and used for polymerase chain reaction-restriction fragment length polymorphism genotyping of selected cytokine- and Toll-like receptor-related loci. The workflow also includes quality-control procedures for sample handling, duplicate ELISA measurements, DNA purity assessment, genotype calling, and repeat genotyping. Statistical analysis includes between-group comparison of clinical characteristics and biomarker levels, Hardy-Weinberg equilibrium testing, logistic regression analysis for genotype and allele associations, adjustment for relevant clinical covariates, and false-discovery-rate correction for multiple genetic comparisons. This combined clinical, inflammatory, and immune-genetic workflow may help characterize infection-risk profiles after spontaneous intracerebral hemorrhage, although prospective multicenter validation is still required before routine clinical application.

Humans↗

[Markers of thrombophilia in patients with retinal vein thrombosis].

BACKGROUND: Thrombophilia is an alteration of hemostasis that increases the risk to venous or arterial thrombosis. This condition may be the underlying cause of retinal vein thrombosis. AIM: To study the presence of thrombophilia in patients with retinal vein thrombosis. PATIENTS AND METHODS: Prospective study of 55 patients aged 22 to 86 years, with retinal vein thrombosis (central or branch). Antithrombin III, coagulant protein C, functional protein S, resistance to activated C protein, homocysteine, prothrombin G20210A gene, lupus anticoagulant and anticardiolipin antibodies were measured in all. RESULTS: Seventeen patients had thrombophilic markers (antiphospholipid syndrome in seven, hyperhomocysteinemia in six and resistance to protein C in three). Of these 17 patients, 53% had high blood pressure, 35% an abnormal serum lipid profile and 23% a personal history of thrombosis. The thrombosis was central in 12 (ischemic in four) and of a branch in five (ischemic in two). CONCLUSIONS: Thrombophilic markers must be assessed in patients with retinal vein thrombosis.

Activated Protein C Resistance↗

Fibrinolytic markers and neurologic outcome in traumatic brain injury.

AIMS: To determine the usefulness of fibrinolytic markers as early prognostic indicators in patients with isolated head trauma. MATERIALS AND METHODS: Sixty-two consecutive patients (26 women and 36 men; mean age 61 years, range 2-76 years) with isolated head trauma seen within the first three hours of the trauma were included in the study. The Glasgow Coma score (GCS), platelet counts (Plt), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin degradation products (FDP) and D-dimer levels were measured. Head computerized tomography (CT) findings were categorized as brain edema, linear fracture, depressed fracture, contusion and bleeding. Plt counts, PT, PTT, fibrinogen, FDP, D-dimer levels and CT findings were compared with both GCS and mortality in the first week. Statistical significance was accepted at P <or=0.05. RESULTS: A marked negative relationship was found between GCS and PT, PTT, FDP and D-dimer levels (P < 0.001). Plt levels did not correlate with GCS. Mortality was most strongly related to GCS, PT, FDP and D-dimer levels (P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively). We found no relationship between mortality and CT findings, nor was there any significant relationship between Plt, PTT and fibrinogen levels. CONCLUSION: GCS and fibrinolytic markers measured within the first three hours were useful in determining the prognosis of patients with isolated head trauma.

Adolescent↗

Some implications of genetic biomarkers in occupational epidemiology and practice.

This paper addresses the use of genetic biomarkers in occupational epidemiology and some of the scientific, ethical, and social implications for epidemiologists and practitioners to consider, including issues involving individual risk estimation, the communication of epidemiologic results, and the translation of epidemiologic data into clinical or occupational health practice. Three scenarios from the occupational setting illustrate some of these issues and implications. The scenarios involve glutathione-S-transferase theta 1 (GSTT1) and hematopoietic cancer in hospital workers, human leukocyte antigen coding for glutamic acid in the 69th position (HLA DPB1(E69)) and chronic beryllium disease in beryllium workers, and peripheral myelin protein 22 (PMP22) deletion and carpal tunnel syndrome in railroad track workers. Epidemiologic research involving genetic biomarkers requires the application of genetic tests and can be considered on a continuum between basic sciences and clinical and occupational and public health practice for which questions of test relevance, validity, and utility become important.

Environmental Monitoring↗

[TAME]-esterase--a new cardiovascular risk factor in smokers.

A mathematical model has been proposed to study the effect of [TAME] esterase on blood clotting time. Using this model, clotting time was found to decrease by 30% with increasing plasma [TAME] esterase activity in a group of smokers. It is hypothesized that [TAME] esterase through its effect on Hageman factor could affect clotting time. However mechanism of clotting by [TAME] esterase remains to be elucidated. It is concluded that [TAME] esterase is involved in the cascade of reactions leading to blood coagulation and increased [TAME] esterase activity could be an additional risk factor for possible cerebro-vascular accidents in smokers.

Adult↗

[Anti-TPO antibodies and screening of thyroid dysfunction in type 1 diabetic patients].

The diagnosis of thyroid dysfunction is often late in type 1 diabetic population. So, the aims of this study were 1) to evaluate the prevalences of thyroperoxydase (TPO) and thyroglobulin (Tg) autoantibodies detected by highly sensitive radioimmunological method in a cohort of 258 adult type 1 diabetic patients without evidence of clinical thyroid disease; 2) to determine whether or not measurement of TPO and/or Tg antibodies can identify subjects at risk of clinical or infraclinical thyroid dysfunction by measuring TSH in the entire group. TPO antibodies were found in 45 of the 258 diabetic patients (17%). The prevalence of TPO antibodies was not influenced by the following factors: gender, duration of disease, age at screening and at diabetes diagnosis, positivity of familial history. Tg antibodies were found in 19 patients (7%), including 13 cases with TPO antibodies. All patients without TPO antibody (n=213), including Tg-positive patients displayed TSH values in normal range. Among the 45 TPO-positive patients, 11 patients displayed infraclinical thyroid dysfunction. At the end of the 5-year follow-up, only 2/45 patients became anti-TPO negative. Thirteen of the 45 patients developed subclinical or clinical thyroid diseases (4 Graves'disease and 9 thyroiditis with hypothyroidism). By contrast, none of 45 TPO negative patients, sex and age matched with the TPO-positive patients, developed during follow-up anti-TPO positivity and/or infraclinical thyroid dysfunction. In conclusion, the determination of TPO antibodies by a highly sensitive method allows identifying diabetic patients with thyroid autoimmunity and at risk of subsequent impaired thyroid function, whatever age at diagnosis and diabetes duration. By contrast, anti-Tg determination did not give further information about subsequent thyroid dysfunction. In TPO antibody positive patients repeated thyroid clinical examination and TSH determination could be recommended to detect infraclinical thyroid dysfunction.

Adolescent↗

Establishment and characterization of a cell line (T201) derived from a human larynx squamous cell carcinoma.

The purpose of this report was the initiation and further maintenance of tumor cells from a primary larynx squamous cell carcinoma. A tumor fragment was mechanically dissociated, the cells were grown in RPMI medium, being the primary culture dependent on the presence of epidermal growth factor and insulin; during subsequent passages the adaptation to conventional growth conditions was obtained. Cells grew in monolayer with an epitheliod shape, showing a pavement-like arrangement; at confluence, cells piled up without contact inhibition maintaining the same morphology. Population doubling time was about 48 h with a colony-forming efficiency of 10%. Immunocytochemical characterization was performed with a panel of monoclonal antibodies reactive against tumor associated antigens, including mucin glycoproteins and related carbohydrate antigens, carcinoembryonic antigen (CEA), p53 as well as cytokeratins, vimentin and desmin. T201 expressed CEA, sialyl Lewis x, Lewis x, Lewis y, MUC1 mucin, Tn hapten, p53, vimentin and cytokeratins. On the other hand, a modal chromosome diploid number of 46 occurring in 74% of cells was detected. Present data confirmed that the methodology employed was adequate for the establishment and characterization of a new cell line which can provide a useful model to study biological and immunological aspects of larynx squamous cell carcinoma.

Animals↗