Detection of DNA of Chlamydophila psittaci in subjects with psoriasis: a casual or a causal link?

BACKGROUND: Recent evidence indicates that subclinical infection by Chlamydophila psittaci occurs in a significant percentage of patients with chronic inflammatory polyarthritis, including psoriatic arthritis. OBJECTIVE: To assess the prevalence of Chlamydiae infection in a large cohort of well-characterized patients with psoriasis. METHODS: The presence of a subclinical C. psittaci infection was investigated in 64 patients with psoriasis, including 12 patients with psoriatic arthritis. Two hundred and twenty-five healthy controls were also investigated. The presence of infection was assessed in peripheral blood mononuclear cells using several polymerase chain reaction protocols, targeting different regions of the bacterial genome. The DNA of other species (Chlamydophila pneumoniae and Chlamydia trachomatis) was also investigated. RESULTS: Chlamydophila psittaci infection was observed in a significantly higher percentage of patients with psoriasis (11/64, 17%) compared with healthy controls (1/225, 0.4%) (odds ratio 46.49, 95% confidence interval 5.87-368.03; P < 0.0001). No differences in age, sex or disease duration were noticed between positive and negative patients, but the majority of the positive patients were on immunomodulatory treatments. CONCLUSION: Chlamydophila psittaci may be an infectious trigger possibly involved in the pathogenesis of psoriasis.

Fractional Fokker-Planck subdiffusion in alternating force fields.

The fractional Fokker-Planck equation for subdiffusion in time-dependent force fields is derived from the underlying continuous time random walk. Its limitations are discussed and it is then applied to the study of subdiffusion under the influence of a time-periodic rectangular force. As a main result, we show that such a force does not affect the universal scaling relation between the anomalous current and diffusion when applied to the biased dynamics: in the long-time limit, subdiffusion current and anomalous diffusion are immune to the driving. This is in sharp contrast with the unbiased case when the subdiffusion coefficient can be strongly enhanced, i.e., a zero-frequency response to a periodic driving is present.

Dimer diffusion in a washboard potential.

The transport of a dimer, consisting of two Brownian particles bounded by a harmonic potential, moving on a periodic substrate is investigated both numerically and analytically. The mobility and diffusion of the dimer center of mass present distinct properties when compared with those of a monomer under the same transport conditions. Both the average current and the diffusion coefficient are found to be complicated nonmonotonic functions of the driving force. The influence of dimer equilibrium length, coupling strength, and damping constant on the dimer transport properties are also examined in detail.

Use and abuse of a fractional Fokker-Planck dynamics for time-dependent driving.

We investigate a subdiffusive, fractional Fokker-Planck dynamics occurring in time-varying potential landscapes and thereby disclose the failure of the fractional Fokker-Planck equation (FFPE) in its commonly used form when generalized in an ad hoc manner to time-dependent forces. A modified FFPE (MFFPE) is rigorously derived, being valid for a family of dichotomously alternating force fields. This MFFPE is numerically validated for a rectangular time-dependent force with zero average bias. For this case, subdiffusion is shown to become enhanced as compared to the force free case. We question, however, the existence of any physically valid FFPE for arbitrary varying time-dependent fields that differ from this dichotomous varying family.

Fractional Fokker-Planck dynamics: Numerical algorithm and simulations.

Anomalous transport in a tilted periodic potential is investigated numerically within the framework of the fractional Fokker-Planck dynamics via the underlying continuous-time random walk. An efficient numerical algorithm is developed which is applicable for an arbitrary potential. This algorithm is then applied to investigate the fractional current and the corresponding nonlinear mobility in different washboard potentials. Normal and fractional diffusion are compared through their time evolution of the probability density in state space. Moreover, we discuss the stationary probability density of the fractional current values.

Current and universal scaling in anomalous transport.

Anomalous transport in tilted periodic potentials is investigated within the framework of the fractional Fokker-Planck dynamics and the underlying continuous time random walk. The analytical solution for the stationary, anomalous current is obtained in closed form. We derive a universal scaling law for anomalous diffusion occurring in tilted periodic potentials. This scaling relation is corroborated with precise numerical studies covering wide parameter regimes and different shapes for the periodic potential, being either symmetric or ratchetlike.

Lysosomal evaluation of endometrioma capsule epithelium and endometrium of patients with or without endometriosis.

OBJECTIVE: To evaluate the number of lysosomes in glandular epithelia of the endometrioma capsule and endometrium from patients with or without endometriosis using a histochemical method (acidic phosphate determination) under light microscopy. METHOD: We studied 31 selected patients with similar clinical features, except for the occurrence of menorrhagia enhanced in patients with endometriosis. All patients were submitted to video laparoscopic procedures and endometrial biopsies through hysteroscopy during the secretory phase. After surgery, the patients were divided into two groups for hysteroscopic data: GI--without endometriosis (control, n = 16) and GII--with endometriosis (n = 15). In GII, the lysosomes of the endometrioma were also counted (GIIa). RESULTS: The GI sample was comprised only of endometrial biopsies. We found that the number of lysosomes in the topic endometrial tissue of patients with endometriosis was significantly larger than the number in endometrioma. Also, there were more lysosomes in the endometrium of patients with endometriosis than in endometrioma-bearing patients. CONCLUSION: Our data suggest that variations in the number of lysosomes may underlie the pathogenesis of endometriosis.

[Estimate of uncertainty of measurements in clinical laboratories and in environmental, occupational, and preventive medicine]. / Stima dell'incertezza di misura nel laboratorio clinico e in medicina ambientale, occupazionale e preventiva.

According to recently issued (UNI CEI EN ISO/IEC 17025, UNI CEI ENV 13005 and prEN ISO 15189) standards, to assure the quality of analytical results and their comparability in time and in different places, testing and clinical laboratories must demonstrate to use validated methods, guarantee the traceability of their measurements and state the measurement uncertainty associated with each result. For some SI quantities, such as the mass, the traceability to SI and the estimate of measurement uncertainty are warranted by established methods. In the clinical laboratory and especially in preventive, environmental and occupational laboratory medicine, specific difficulties arise to warrant the traceability to the mole. On one hand, the whole concept of measurement uncertainty is new in laboratory medicine, on the other hand, its application faces practical difficulties, because of the wideness and the complexity of the analytical repertory, the lack of officially validated methods and matrix-specific reference materials traceable to SI. In this paper we discuss briefly the concept of measurement uncertainty and its meaning in comparison with other parameters used to define the performance of analytical methods. In addition, we describe the procedures recommended by international organisations for estimating measurement uncertainty and interpreting analytical results with an associated measurement uncertainty in comparison with limit values.

Ultrasonographic and morphological studies of the postmenopausal endometrium using unopposed estrogen replacement therapy with regular pause: a prospective preliminary study.

UNLABELLED: Hormone replacement therapy with progestogen is known to have severe side effects or complications in certain patients. OBJECTIVE: The goal of this study is to evaluate the safety and efficacy of an alternative treatment regimen with a mensal pause using both transvaginal sonography (TVS) and endometrial biopsy to follow patients. METHODS: A total of 30 postmenopausal women were treated with unopposed estrogen for 21 days each month followed by a regular pause of 9-10 days, and were studied prospectively for 18 months. The TVS measurements of endometrial thickness and biopsy of the endometrium were done on the 21st day of treatment and the 7th day of the pause at 6-month intervals throughout the study. RESULTS: There was a significant decrease of proliferative activity at all three time points during the study (6, 12 and 18 months) when tested on the 7th pause day (PD7). The percentage of patients with hyperplasia without nuclear atypia and endometrial thickness > or =8mm was 32% at 6 months, but decreased to 22 and 19% at 12 and 18 months, respectively. All cases of hyperplasia regressed after the hormonal pause throughout the treatment period. CONCLUSIONS: This study presents an alternative treatment regimen for select patients having side effects or complications from progestogen administration; however, studies evaluating the safety and efficacy of this regimen over longer time periods are necessary.

A Novel Dinuclear Diaminoplatinum(II) Glutathione Macrochelate.

Both oxidized and reduced glutathione (gamma-L-Glu-L-Cys-Gly) react with the anticancer complex [Pt(en)Cl(2)] to form the bicyclic complex illustrated (en=ethylenediamine). This unprecedented structure, which was determined from extensive NMR experiments, contains a ten-membered macrochelate ring.

[The role of biological monitoring in the evaluation of the risk of from chemical compounds]. / Il ruolo del monitoraggio biologico nella valutazione del rischio da composti chimici.

Over the years, the assessment of the risk to human health from occupational and environmental exposure to chemicals has become increasingly important. Exposure to chemicals, their biochemical effects and individual susceptibility can be estimated by biological monitoring carried out on potentially exposed subjects. Valid markers are needed to be effectively used within the framework of biological monitoring programs. Quality assurance, which includes all those activities necessary to provide adequate confidence that the results of laboratory test are reliable, is of the utmost importance. Among these activities the participation in external quality assessment schemes is strongly recommended. Biological monitoring has a key role also in the field of human reproduction since the level of exposure to many chemicals which are known or suspected to be reproductive toxicants can be assessed by specialized laboratories.

Determination of low concentrations of potentially toxic elements in human liver from newborns and infants.

One hundred and fifty-seven liver samples from newborns and infants who had died from sudden infant death syndrome (SIDS) or other known causes have been analysed by ICP-MS for Ag, Cd, Co, Pb and Sb. The median concentrations found were: 15.4 (Ag), 2.9 (Cd), 15.9 (Co), 65.2 (Pb) and 1.8 (Sb) ng g-1 wet mass. There was no measurable difference in the concentrations of any of these elements between the SIDS and non-SIDS groups. The validity of the results was assessed by analysis of appropriate reference materials, interlaboratory comparison and isotope dilution analysis. The instrumental limits of detection were 0.25 (Ag), 0.14 (Cd), 0.21 (Co), 3.8 (Pb) and 0.38 (Sb) ng g-1 wet mass. The limits of detection of the method depend on the reagent blank and the extent of background contamination.

Use of the stable isotope 65Cu test for the screening of Wilson's disease in a family with two affected members.

BACKGROUND/AIMS: An improved method for the study of copper metabolism in Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu) has recently been described. We report on the use of this method for the study of a family with two members affected by Wilson's disease. SUBJECTS: The family comprised parents and four siblings: one 20-year-old male and three females, aged 22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated liver copper content and/or low caeruloplasmin levels and Kayser-Fleischer ring. METHODS: All family members were given an oral dose of 3 mg of 65Cu. Blood samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu in serum was determined in all samples by means of Inductively Coupled Plasma Mass Spectrometry. RESULTS: The diagnosis of Wilson's disease was confirmed in the two symptomatic members by the unequivocal decrease observed in the 65Cu percent enrichment, which approached zero by 72 hours. In contrast, Wilson's disease could be definitely excluded in both siblings, one of whom only 5 years old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu into caeruloplasmin. These findings were later confirmed by genetic analysis. Parents, who carried defective genes with different mutations, also showed different abnormalities of copper metabolism. CONCLUSIONS: The oral test with the stable copper isotope 65Cu is a safe, non invasive option able to exclude Wilson's disease in patients with a difficult diagnosis or in a presymptomatic stage. However, positive tests must still be confirmed by copper dosage in liver biopsies, as heterozygotes can present with severe alterations of copper metabolism, without developing symptoms of the disease. The use of this test in conjunction with genetic analysis on a larger number of heterozygous subjects may add to the understanding of the Wilson's disease defect.

[Quality control of data produced in biological population surveillance studies on the risk of environmental lead poisoning]. / Il controllo di qualità dei dati prodotti nelle indagini per la sorveglianza biologica della popolazione contro il rischio dell'inquinamento ambientale da piombo.

The biological surveys of the general population against the risk of lead intoxication carried out in Italy--in accomplishment both of the EEC directive EEC 77/312 and the Presidential Decree 496/1982--have been always conceived as multicentric activities. Therefore, starting from the first campaign carried out in 1979, strict quality control procedures have been adopted. In brief, each participant laboratory used internal quality control samples and took part in external quality assessment exercises. In addition, ten percent of the blood samples collected during the campaign were analyzed as blind duplicate by both participating laboratories and a reference laboratory. In this paper the quality control procedures adopted will be presented and discussed in detail together with the quality of results obtained in each campaign.

[Lead exposure: risk evaluation for the general Italian population in 1990]. / Esposizione al piombo: valutazione del rischio per la popolazione generale italiana negli anni '90.

The second Italian campaign for the biological surveillance of the general population against the risk of lead intoxication has been carried out according to the regulations contained in the Presidential Decree DPR 496/82. The investigations of the second campaign--based on the measurement of blood lead levels (PbB)--have been carried out mainly between 1992 and 1996 by various operating centers in some Italian regions. A work group from the Istituto Superiore di Sanità (Italian National Institute of Health) coordinated the activity of the various centers and organised an appropriate quality control program to guarantee the quality of the analytical data collected. A total of 7749 non exposed subjects (4346 females and 3403 males) has been examined, 1170 of which (559 females and 611 males) were under 15 years of age. The median PbB was, for adults, 86 micrograms/l in males and 53.5 micrograms/l in females. As for subjects under the age of 15, PbB levels were 50 micrograms/l and 43 micrograms/l in males and females, respectively. Our investigation confirms the correlation between blood lead levels, wine, and cigarette smoking. The comparison with the results of previous investigations shows a reduction between 40% and 50% of PbB in the general Italian population during the 1985-96 period. It should be pointed out that in certain areas more than 5% of subjects under 15 years of age had PbB exceeding the level (100 micrograms/l) considered safe for avoiding irreversible injury to the central nervous system.

Nickel metabolism in humans investigated with an oral stable isotope.

We report the results of the first complete study of nickel metabolism in human subjects using a stable nickel isotope (62Ni) as tracer. Four healthy adult subjects (two women and two men) fasted overnight before ingesting 10 microg 62Ni/kg body wt. Blood samples were drawn after fixed intervals of time and the total daily output of urine and feces was collected for the first 5 d after dose ingestion. 62Ni in plasma, urine, and feces was determined by isotope-dilution inductively coupled plasma-mass spectrometry with 61Ni. The direct measurement of the fecal excretion of the tracer allowed a reliable assessment of nickel absorption from the gastrointestinal tract and we found no evidence of the excretion of absorbed nickel via the gut. The percentage absorption calculated from the amount of 62Ni excreted in the feces ranged from 29% to 40%. Urinary excretion over 5 d ranged from 51% to 82% of the absorbed dose. Plasma 62Ni peaked between 1.5 and 2.5 h after ingestion and decreased by a factor of > 10 over the next few days. We observed low between-subject variability of nickel absorption and excretion. Confounding factors such as contamination and dietary intake of nickel, which hampered earlier measurements in subjects dosed with naturally abundant nickel, were eliminated by using the tracer isotope 62Ni.

Morphological action of tamoxifen in the endometrium of persistent estrous rats.

BACKGROUND: The aim of this study was to evaluate the action of tamoxifen on the endometrium in states of chronic anovulation. METHODS: Thirty-eight rats inducted to persistent estrous (testosterone propionate) confirmed by hormonal colpocytology were divided into a control and an experimental group; the latter received tamoxifen and had fragments of the uterine horns processed for morphological and morphometrical analysis. Data were analysed statistically by the Mann-Whitney and Student's t tests. RESULTS: Our findings revealed minor uterine weight, epithelial thickness; number of endometrial glands and low eosinophil counts in the group that received tamoxifen. These results were statistically significant. We often observed areas of metaplasic stratified squamous epithelium between cylindrical epithelial cells in both groups. CONCLUSIONS: Our results indicate that antiestrogenic effect of tamoxifen was only partial in persistent estrous, since there was no blocking against the squamous metaplasia of the endometrium.

First steps toward harmonisation of European EQAS in occupational and environmental laboratory medicine: from Dublin to Rome.

Laboratories performing analyses in the field of occupational and environmental medicine (OELM) must provide reliable results for an increasing number of analytes related to exposure to chemicals. Participation in external quality assessment schemes (EQAS) allows laboratories to assess their performance and is regarded as a pre-requisite for accreditation from appropriate national and supranational bodies. Within the framework of the European Union, harmonisation of procedures for evaluation of laboratory performance in EQAS is desirable, in order to achieve a similar degree of excellence within Europe. Collaboration among different countries would also be profitable to compare experiences, develop new schemes, covering a wider range of analytes, and to devise common research on specific problems. We report on initiatives developed to meet this objective, in collaboration with the Standards, Measurements & Testing (SM&T) programme of the European Commission (EC), Directorate General XII. Meetings were held in Dublin and Rome which allowed experience among European EQAS organisers in OELM to be shared. Discussion focused on the identification of common needs and areas where collaborative work could be carried out.

The Italian external quality assessment scheme for trace element analysis in body fluids.

We describe the operative procedures of the Italian external quality assessment scheme (EQAS) for the determination of trace elements in body fluids. The aims of the scheme are both the education of participants and the continuous development and optimization of procedures for collaborative EQA trials. Participation is free of charge. Interlaboratory exercises for EQA are organised every three or four months for the determination of cadmium and lead in blood; aluminium, copper, selenium and zinc in serum; chromium and nickel in urine. Freeze-dried control materials are prepared in the laboratory from animal blood or human urine. In each trial, each participant receives from six to eight samples, chosen from among the pools selected for that occasion using a randomised strategy and including unknown duplicate specimens. Laboratory performances are evaluated on the basis of proximity to target values, differences in results for duplicate samples and comparison with established acceptability limits. The development of dedicated software for the bidirectional transmission of data between the organising centre and the peripheral laboratory gives the participants the chance to verify immediately the quality of their results and take action without delay, if needed.

Prospects of harmonisation of European external quality assessment schemes in occupational and environmental laboratory medicine.

Since 1979, twelve external quality assessment schemes (EQAS) in occupational and environmental laboratory medicine (OELM) have been developed in nine European countries. These schemes cover a broad range of analytes and matrices and have developed differing procedures for the evaluation of laboratories' performances. Collaboration among EQAS in OELM and harmonisation of methods for evaluation of laboratory performance would be advantageous to cope with the demand for assessment of quality of analytical results for an increasing number of analytes and the need to guarantee comparability and consistency of conclusions on health and regulatory issues in different countries and at an international level. This paper compares the different features of the existing EQAS, to highlight critical points for further discussions, and to make some suggestions for possible further collaboration.