Vasculitides are rare diseases characterized by inflammation of blood vessels. According to diameter of the blood vessels involved in the inflammatory process, the clinical presentation and the histological appearance, different vasculitic syndromes may be distinguished. Primary vasculitides are of unknown origin while secondary vasculitides may be caused by drugs, malignancy or infection. Panarteriitis nodosa caused by chronic Hepatitis B and mixed cryoglobulinemia secondary to chronic Hepatitis C are classical examples of vasculitides triggered by infections. However, these are rare complications of chronic viral hepatitis. Patients infected by HIV frequently suffer from vasculitis, which may be caused by opportunistic infections and by defects in immune regulation. In numerous case reports, various other infectious particles have been reported to cause different forms of vasculitis, either by direct infection of endothelial cells or by induction of an immunologic process leading to blood vessel destruction. Immunologically mediated vasculitis secondary to infection may be due to a predisposing reactivity of the patient's immune system. After successful treatment of the infection, the vasculitis usually subsides. Therefore, all patients with vasculitis should be evaluated for underlying infection.

Antigen-Antibody Reactions↗

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Pneumocystis carinii pneumonia as a complication of immunosuppressive therapy.

BACKGROUND: Patients receiving immunosuppressive therapy with corticosteroids and cytotoxic agents may develop opportunistic infections such as Pneumocystis carinii pneumonia (PCP). This indicates a severe T-cell defect, but so far there are no established criteria for identifying patients at risk. PATIENTS AND METHODS: CD4+ and CD8+ T-lymphocyte counts were determined by flow cytometry in seven HIV-negative patients who developed PCP as a complication of immunosuppressive treatment. RESULTS: CD4+ T-lymphocyte counts (T-helper phenotype) were less than 200/microl in all seven patients (mean 90.6/microl). The markedly reduced CD4 counts measured in these patients are similar to those observed in organ transplant recipients who developed PCP during immunosuppressive therapy for prevention of graft rejection and in HIV-positive patients with PCP as an AIDS-defining illness. CONCLUSION: Measuring CD4+ T-lymphocyte counts may be helpful in determining the risk of PCP not only in HIV-positive patients, but also in patients receiving immunosuppressive therapy. The risk of acquiring PCP seems to increase when CD4+ lymphocyte counts drop below 200/microl, regardless of the underlying disease.

CD4 Lymphocyte Count↗

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Peroxidative activation of 3,3'-dichlorobenzidine to mutagenic products in the Salmonella typhimurium test.

The direct and H2O2-dependent mutagenicity of 3,3'-dichlorobenzidine (DCB) were compared in Salmonella tester strains TA98, TA98/1,8-DNP6, TA100 and TA102 using the Ames test. DCB exhibited both direct and H2O2-dependent mutagenicity to both tester strains TA98 and TA98/1,8-DNP6. This H2O2-dependent mutagenicity of DCB was prevented by horseradish peroxidase. DCB, in contrast to its effects in tester strains TA98, was not mutagenic to TA100 and TA102 either directly or in the presence of H2O2. These results suggest that mechanisms, perhaps enzymes endogenous to tester strains TA98, may play a role in the activation of DCB.

3,3'-Dichlorobenzidine↗

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Estimation of the cut-off value in cardiovascular autonomic nervous function tests: not-age-related criteria or the age-related 5th percentile.

The aim of the study was to estimate the cut-off value of cardiovascular tests using not-age-related criteria or the age-related 5th percentile in 165 diabetic patients. The cANP, pANP, and smNP were assessed using previously recommended standardized test procedures. Prevalence of overall definite (borderline) cANP was 35.2% (23.0%) when using the 5th percentile or 16.4% (27.9%) when using not age-related criteria (p for the difference < 0.0001) (p = 0.3205). Prevalence of pANP was 54.0% and of smNP 37.0%. Concerning cANP, the number of test results below the 5th percentile (N5) correlated significantly with the number of abnormal test results using not age-related criteria (Nnar) (p < 0.000001) but the slope of the regression line differed substantially from 1. Using the 5th percentile as the cut-off value for cANP testing, sensitivity and specificity were calculated for not age-related criteria for respiratory sinus arrhythmia (90.5%, 80.2%), Valsalva test (30.4%, 98.0%), lying-to-standing test (46.3%, 98.7%), orthostatic systolic blood pressure fall (69.0%, 78.3%), and overall definite cANP (44.8%, 92.8%). The statistical analysis revealed that the age-related 5th percentile is superior to the not-age-related cut-off values in diabetic patients. We therefore suggest that age-related normal values (percentiles) have to be applied when cANP is estimated.

Adolescent↗

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Peptide neurotoxins, small-cell lung carcinoma andneurological paraneoplastic syndromes.

Peptide neurotoxins isolated from the venom of snakes, spiders and snails have represented invaluable tools for the identification and characterisation of membrane ion channels and receptors in vertebrate cells, including human neurons. We here report on the use of these toxins for the characterisation of membrane ion channels and receptors expressed by one of the most aggressive human cancers, small-cell lung carcinoma. This tumour shares many properties with other neuro-endocrine cell types, including the ability of firing action potentials and release hormones in a calcium-dependent manner. Toxins such as alpha-bungarotoxin and omega-conotoxins, among others, have been successfully used to characterise neuronal nicotinic receptors and voltage-dependent calcium channels, respectively, in human small-cell lung carcinoma cells. These receptors and ion channels are not only crucial for the growth of this specific tumour, but also represent autoantigens against which cancer patients build an autoimmune response. Although the aim of this autoimmune response is eventually the destruction of the cancer cells, the circulating antibodies cross-react with similar ion channels and receptors present in normal neurons or other cells, causing a number of different paraneoplastic diseases, the best characterised of which is the Lambert-Eaton myasthenic syndrome. Conotoxin-based radioimmunoassays have become an invaluable tool for the diagnosis and follow up of these paraneoplastic disorders and could represent a step forward in the early diagnosis of small-cell lung carcinoma itself.

Binding Sites↗

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Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line.

Certain cancers exert unexplained remote effects on the nervous system. Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis and which is of possible neural crest origin, is present in approximately 70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by fatigable muscle weakness. Patients with this syndrome have a defect in the (Ca2+-dependent) quantal release of acetylcholine from motor nerve terminals evoked by a nerve impulse or by high K+ (ref.5), and a decreased number of presynaptic active zone particles. The physiological and morphological features of the syndrome can be transferred to mice by the patients' IgG, consistent with an autoantibody interfering with the function of voltage-dependent Ca2+ channels. Here we demonstrate that K+-induced 45Ca2+ flux in a cultured human SCC line is significantly reduced by LEMS IgG, suggesting that in SCC-LEMS an autoantibody to tumour Ca2+-channel determinants is triggered; its cross-reaction with similar determinants at the motor nerve terminal could lead to the remote neurological syndrome.

Antibody Specificity↗

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Assessment of indoor fine aerosol contributions from environmental tobacco smoke and cooking with a portable nephelometer.

Personal monitoring studies have indicated that environmental tobacco smoke (ETS) and cooking are major indoor particulate sources in residential and nonindustrial environments. Continuous monitoring of fine particles improves exposure assessment by characterizing the effect of time-varying indoor sources. We evaluated a portable nephelometer as a continuous monitor of indoor particulate levels. Simultaneous sampling with the nephelometer and PM2.5 impactors was undertaken to determine the relationship between particle light scattering extinction coefficient (sigma(sp)) and particle mass concentration in field and environmental chamber settings. Chamber studies evaluated nephelometer measurements of ETS and particles produced from toasting bread and frying foods. Field measurements were conducted in 20 restaurants and bars with different smoking restrictions, and in five residential kitchens. Additional measurements compared the nephelometer to a different mass measurement method, a piezobalance, in a well-characterized residence where various foods were cooked and ETS was produced. Since the piezobalance provides 2-min average mass concentration measurements, these comparisons tested the ability of the nephelometer to measure transient particle concentration peaks and decay rate curves. We found that sigma(sp) and particle mass were highly correlated (R2 values of 0.63-0.98) over a large concentration range (5-1600 microg/m3) and for different particle sources. Piezobalance and gravimetric comparisons with the nephelometer indicated similar sigma(sp) vs. mass slopes (5.6 and 4.7 m2/g for piezobalance and gravimetric comparisons of ETS, respectively). Somewhat different sigma(sp) vs. particle mass slopes (1.9-5.6 m2/g) were observed for the different particle sources, reflecting the influence of particle composition on light scattering. However, in similar indoor environments, the relationship between particle light scattering and mass concentration was consistent enough to use independent nephelometer measurements as estimates of short-term mass concentrations. A method to use nephelometer measurements to determine particulate source strengths is derived and an example application is described.

Aerosols↗

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Recognition of adverse and nonadverse effects in toxicity studies.

One of the most important quantitative outputs from toxicity studies is identification of the highest exposure level (dose or concentration) that does not cause treatment related effects that could be considered relevant to human health risk assessment. A review of regulatory and other scientific literature and of current practices has revealed a lack of consistency in definition and application of frequently used terms such as No Observed Effect Level (NOEL), No Observed Adverse Effect Level (NOAEL), adverse effect, biologically significant effect, or toxicologically significant effect. Moreover, no coherent criteria were found that could be used to guide consistent interpretation of toxicity studies, including the recognition and differentiation between adverse and nonadverse effects. This presentation will address these issues identified first by proposing a standard set of definitions for key terms such as NOEL and NOAEL that are frequently used to describe the overall outcome of a toxicity study. Second, a coherent framework is outlined that can assist the toxicologist in arriving at consistent study interpretation. This structured process involves two main steps. In the first, the toxicologist must decide whether differences from control values are treatment related or if they are chance deviations. In the second step, only those differences judged to be effects are further evaluated in order to discriminate between those that are adverse and those that are not. For each step, criteria are described that can be used to make consistent judgments. In differentiating an effect from a chance finding, consideration is given inter alia to dose response, spurious measurements in individual parameters, the precision of the measurement under evaluation, ranges of natural variation and the overall biological plausibility of the observation. In discriminating between the adverse and the non-adverse effect consideration is given to: whether the effect is an adaptive response, whether it is transient, the magnitude of the effect, its association with effects in other related endpoints, whether it is a precursor to a more significant effect, whether it has an effect on the overall function of the organism. whether it is a specific effect on an organ or organ system or secondary to general toxicity or whether the effect is a predictable consequence of the experimental model. In interpreting complex studies it is recognised that a weight of the evidence approach, combining the criteria outlined here to reach an overall judgment, is the optimal way of applying the process. It is believed that the use of such a scheme will help to improve the consistency of study interpretation that is the foundation of hazard and risk assessment.

Animals↗

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The edentulous patient: attitudes toward oral health status.

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Adult↗

PubMedDate not supplied

Efficacy of tissue brushing as measured by the prosthodontic tissue index.

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Adult↗

PubMedDate not supplied

Prognostic factors in childhood ependymomas.

Between 1975 and 1989, 45 children with newly diagnosed intracranial ependymomas were treated at the authors' institution. Patients were managed with aggressive surgical resection, followed by postoperative CT or MRI scans to evaluate the extent of resection. Most patients received involved-field radiation therapy, however 10 were treated with craniospinal axis irradiation for disseminated disease, or malignant histology. Beginning in 1983, all patients were also treated with adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vincristine, and cisplatinum. Four patients died in the immediate postoperative period for an operative mortality of 8.8%. The 5-year progression-free survival for the remaining 41 patients was 36%. Tumor location had little effect on survival, as the 5-year PFS for supratentorial tumors was 26%, compared with 40% for the posterior fossa lesions (ns). Neither histologic degree of malignancy, nor use of adjuvant chemotherapy impacted on survival. The extent of surgical resection, as determined by operative reports and postoperative imaging studies, was a major determinant of outcome, as patients with total or near-total resections experienced a 5-year PFS of 60%, compared with 21% for children with partial resection or biopsy (p less than 0.01). It is concluded that the use of adjuvant chemotherapy with CCNU, vincristine, and cisplatinum does not improve progression-free survival in childhood ependymoma, and that the extent of surgical resection is a major determinant of outcome in this disease.

Adolescent↗

PubMedDate not supplied

[Kidney function in therapy with non-steroidal antiphlogistic drugs. A double-blind cross-over study with diclofenac, indomethacin and piroxicam].

The effect of piroxicam (1 x 20 mg daily), diclofenac (2 x 50 mg daily) and indomethacin (3 x 25 mg daily) on renal function was compared in a double-blind cross-over study of 33 patients with various rheumatologic diseases. Individuals with preexisting renal impairment were excluded. In 16 patients piroxicam was compared with diclofenac. In another group of 17 patients piroxicam was compared with indomethacin. Each drug was given for 28 days. The mean inhibition of renal prostaglandin E2 by the three drugs was comparable. There was no significant alteration of the renal function parameters in any of the drugs. These results confirm that nonsteroidal antiinflammatory drugs with short (diclofenac, indomethacin) but also with long half life (piroxicam) do not decrease renal function in individuals without renal impairment.

Arthritis, Rheumatoid↗

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[Role of hormonal receptors in the regulation of the corpus luteum (author's transl)].

Recent publications dealing with the hormonal regulation of the corpus luteum function have been reviewed. Hormones involved in this regulation are: LH and placental analogue hCG, FSH, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction in the luteal cells and the role of each hormone in the modulation of the cell responsiveness has been reviewed.

Animals↗