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PubMed1993

[Multiple personality disorder: old concepts presented as new].

The rapid increase in numbers of MPD patients in the Anglo-American literature requires discussion of the diagnostic concept. The classification of MPD as Dissociative Disorders by DSM-III-R and ICD-10 follows the traditional conceptualization of hysteria and hypnosis. In the view of the majority of modern authors child abuse appears as a new etiological issue. This theme highly sensitive is critically discussed against the background of older psychopathological concepts of forgetting. A careful analysis of personality traits and motivation in the individual case help to avoid overuse of the new diagnostic label.

Child↗

PubMed1997

[Clinical and biological markers of secondary uveitis: results of a discriminant analysis].

BACKGROUND: The association of uveitis and systemic disease is well known. Patients suffering from uveitis often undergo a extensive battery of tests in order to detect underlying disease, but the efficiency of such screening is uncertain. The aim of this study was to investigate useful clinical data for recognizing secondary uveitis. PATIENTS AND METHODS: We conducted a prospective analysis of 115 patients with uveitis of unknown etiology. All of them were included in an extensive protocol study. Four groups were considered: specific ocular disease (SOD), idiopathic uveitis, HLA-B27 associated uveitis without arthritis (HLA-B27-AU) and secondary uveitis. Groups were compared by analysis of variance for continuous variables, and chi 2 test or Student's t-test for discrete variables. A stepwise multiple discriminant analysis was performed for ranking the variables in order of their usefulness for distinguishing idiopathic and secondary uveitis. RESULTS: We diagnosed 11 SOD (9.6%), 54 idiopathic uveitis (47%), 6 HLA-B27-AU (5.2%) and 41 secondary uveitis (35.7%). The discriminant analysis showed that age, an elevated erythrocyte sedimentation rate, presence of cutaneous lesion, joint pain and genital ulcers are the strongest predictors of secondary uveitis. This model classification functions detected 92.5% of idiopathic uveitis and 72% of secondary uveitis. The global percentage of patients with a correct diagnosis was 84.6%. CONCLUSIONS: Anamnesis, physical examination and basic laboratory tests are sufficient tools for the diagnostic approach of the majority of patients with uveitis. Subsequent diagnostic procedures must be planned in each patient to confirm a specific disease.

Adolescent↗

PubMed1998

Prediction of cirrhosis in patients with chronic hepatitis C infection by artificial neural network analysis of virus and clinical factors.

The diagnosis of cirrhosis in patients with hepatitis C virus (HCV) infection is currently made using a liver biopsy. In this study we have trained and validated artificial neural networks (ANN) with routine clinical host and viral parameters to predict the presence or absence of cirrhosis in patients with chronic HCV infection and assessed and interpreted the role of the different inputs on the ANN classification. Fifteen routine clinical and virological factors were collated from 112 patients who were HCV RNA positive by reverse transcriptase-polymerase chain reaction (RT-PCR). Standard and Ward-type feed-forward fully-connected ANN analyses were carried out both by training the networks with data from 82 patients and subsequently testing with data from 30 patients plus performing leave-one-out tests for the whole patient data set. The ANN results were also compared with those from multiple logistic regression. The performance of both ANN methods was superior compared with the logistic regression. The best performance was obtained with the Ward-type ANNs resulting in a sensitivity of 92% and a specificity of 98.9% together with a predictive value of a positive test of 95% and a predictive value of a negative test of 97% in the leave-one-out test. Hence, further validation of the ANN analysis is likely to provide a non-invasive test for diagnosing cirrhosis in HCV-infected patients.

Adult↗

PubMed2004

Detection of differentially expressed proteins in early-stage melanoma patients using SELDI-TOF mass spectrometry.

Tumor progression is a dynamic sequence of events that involves specific protein changes. We hypothesized that Surface Enhanced Laser Desorption/Ionization (SELDI) mass spectrometric analysis of sera from patients with AJCC stage I and II melanoma with negative loco-regional lymph nodes could identify potential melanoma-associated protein biomarkers of disease recurrence. Serum specimens were collected from 49 patients who developed recurrence (n = 25) or remained free of recurrence (n = 24) without evidence of disease following complete resection (AJCC stage I and II). Follow-up was longer than 5 years. Serum proteins were denatured and applied onto two protein chip chemistry surfaces (weak cationic WCX2; metal-binding, IMAC3-Cu). SELDI ProteinChip mass spectrometry was then performed. SELDI data were analyzed, protein peak clustering and classification were performed, and a supervised classification algorithm was employed to classify the dataset. Multiple protein peaks ranging from 3.3 to 30 kDa were identified between patients with recurrence and those without recurrence, and the expression pattern differences of three proteins were used to generate the discriminating classification tree. The biomarkers were expressed with a high degree of reproducibility. In this early characterization study, melanoma recurrence was predicted with a sensitivity of 72% (18/25) and a specificity of 75% (18/24). This novel pilot study revealed three proteins that accurately identified patients who developed recurrence after curative resection of primary melanoma.

Adult↗

PubMed1996

The empirical identification of insomnia subtypes: a cluster analytic approach.

Over the past 15 years, there has been considerable debate concerning the extent to which insomnia patients can be classified into diagnostic subtypes. Despite this debate, relatively little research has been conducted to empirically determine whether naturally occurring insomnia subtypes might be identified within populations of sleep clinic patients. In the current study we used a hierarchical cluster analysis to empirically identify subtypes among a mixed group of normal sleepers and the insomnia outpatients who presented to our sleep center over the past decade. Using factor-analytically derived composite variables that summarized data obtained from sleep history questionnaires and polysomnographic monitoring, this clustering procedure resulted in the identification of 14 subgroups that varied between four and 34 patients/subjects in size. Subsequently, subgroup mean scores for the composite variables used in the clustering procedure were used to construct profiles for each of the 14 clusters. A multivariate profile analysis, employed to elucidate subgroup differences, showed that these cluster profiles differed in terms of their configural shapes, average elevations, and degrees of interscale differences. Furthermore, both DSM-III-R (American Psychiatric Association) and International Classification of Sleep Disorders (ICSD) insomnia diagnoses, assigned independent of cluster findings, suggested that these subtypes differed significantly in regard to their diagnostic compositions. Nevertheless, a far-from-perfect concordance was observed between such clinically assigned diagnoses and cluster group membership. In fact, many of the empirically identified groups were composed of various DSM-III-R and/or ICSD diagnostic subtypes. These results provided only partial support for current DSM and ICSD insomnia categories. However, our results support the existence of multiple, clinically discrete insomnia subtypes and provide information that may be useful in future revisions of current insomnia nosologies.

Adult↗

PubMed2006

The molecular phylogeny of the genus Rhizopus based on rDNA sequences.

In order to establish the molecular phylogeny of the genus Rhizopus, three molecules of the ribosomal RNA-encoding DNA (rDNA), complete 18S, internal transcribed spacer (ITS)1-5.8S-ITS2, and 28S D1/D2 regions of all the species of the genus were sequenced. Phylogenetic trees showed three major clusters corresponding to the three groups in the current morphological taxonomy, microsporus-group, stolonifer-group, and R. oryzae. R. stolonifer var. lyococcos was clustered independently from the major clusters. R. schipperae clustered differently in all trees. Strains of R. sexualis had multiple ITS sequences. A. rouxii clustered with R. oryzae. These results indicate the possibility of molecular identification of species groups using rDNA sequencing. Reclassification of the genus might be appropriate.

Base Sequence↗

PubMed2005

Mosaics of convergences and noise in morphological phylogenies: what's in a viverrid-like carnivoran?

Adaptive convergence in morphological characters has not been thoroughly investigated, and the processes by which phylogenetic relationships may be misled by morphological convergence remains unclear. We undertook a case study on the morphological evolution of viverrid-like feliformians (Nandinia, Cryptoprocta, Fossa, Eupleres, Prionodon) and built the largest morphological matrix concerning the suborder Feliformia to date. A total of 349 characters grouped into four anatomical partitions were used for all species of Viverridae and viverrid-like taxa plus representatives of the Felidae, Hyaenidae, Herpestidae, and one Malagasy mongoose. Recent molecular phylogenetic analyses suggest that viverrid-like morphotypes appeared independently at least three times during feliformian evolution. We thus used a synthetic molecular tree to assess morphological evolutionary patterns characterizing the viverrid-like taxa. We examined phylogenetic signal, convergence and noise in morphological characters using (a) tree-length distribution (g1), (b) partitioned Bremer support, (c) RI values and their distribution, (d) respective contributions of diagnostic synapomorphies at the nodes for each partition, (e) patterns of shared convergences among viverrid-like taxa and other feliformian lineages, (f) tree-length differences among alternative hypotheses, and (g) the successive removal of convergent character states from the original matrix. In addition, the lability of complex morphological structures was assessed by mapping them onto the synthetic molecular tree. The unconstrained morphological analysis yielded phylogenetic groupings that closely reflected traditional classification. The use of a synthetic molecular tree (constraint) combined with our thorough morphological investigations revealed the mosaics of convergences likely to have contributed to part of the historical uncertainty over viverrid classification. It also showed that complex morphological structures could be subjected to reversible evolutionary trends. The morphological matrix proved useful in characterizing several feliformian clades with diagnostic synapomorphies. These results support the removal from the traditionally held Viverridae of several viverrid-like taxa into three distinct families: Nandiniidae (Nandinia), Prionodontidae (Prionodon), and the newly defined Eupleridae (including Cryptoprocta, Fossa, Eupleres plus all "mongoose-like" Malagasy taxa). No clearly "phylogenetically misleading" data subsets could be identified, and the great majority of morphological convergences appeared to be nonadaptive. The multiple approaches used in this study revealed that the most disruptive element with regards to morphological phylogenetic reconstruction was noise, which blured the expression of phylogenetic signal. This study demonstrates the crucial need to consider independent (molecular) phylogenies in order to produce reliable evolutionary hypotheses and should promote a new approach to the definition of morphological characters in mammals. [Constrained analysis; convergence; evolutionary scenario; Feliformia; morphology; noise; phylogenetic signal; phylogeny; Viverridae.].

Anatomy, Comparative↗

PubMed2006

Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).

OBJECTIVES: To establish the cost-effectiveness of surgery and sclerotherapy for the treatment of varicose veins. DESIGN: Randomised controlled trials (RCTs) were carried out for conservative treatment, sclerotherapy and surgery for varicose veins. An economic analysis was carried out alongside the randomised trial. Economic modelling was undertaken based on the primary data collection and a literature review (database searches undertaken in April 2000 and updated in March 2001). SETTING: Primary data collection was from a large district general hospital and a teaching hospital both in England over a 2-year period from January 1999. Cost-effectiveness analysis and economic modelling were carried out using an NHS perspective. PARTICIPANTS: A total of 1009 patients were recruited. INTERVENTIONS: Thirty-four patents were randomised in Group 1 (minor varicose veins with no reflux, randomised between conservative treatment and sclerotherapy), 77 in Group 2 (moderate varicose veins with reflux, randomised between surgery and sclerotherapy) and 246 in Group 3 (severe varicose veins with reflux, randomised between conservative treatment and surgery). The remaining 652 patients formed the observational part of the study. MAIN OUTCOME MEASURES: The cost-effectiveness analysis was based on NHS treatment costs for the 2002--3 financial year, and utilities based on the Short Form 6D (SF-6D) preference-based health measure. For the clinical trial, the outcome measures were health-related quality of life (HRQoL) [Short Form with 36 Items (SF-36), EuroQol quality of life questionnaire (EQ-5D), visual analogue scale (VAS) and standard gamble], symptomatic relief, anatomical extent (for which a new classification was developed and validated), patient satisfaction and the incidence of complications. RESULTS: Of the RCTs, only the Group 3 trial was large enough to provide clear results. This showed that surgical treatment produced better results than conservative treatment in terms of HRQoL, symptomatic relief, anatomical extent and patient satisfaction. Clinical outcomes of surgery and sclerotherapy showed significant improvement in the extent of varicose veins, symptomatic and HRQoL parameters. Cost-effectiveness analysis based on the Group 3 trial showed that the surgery produced an estimated discounted benefit of 0.054 quality-adjusted life-year (QALY) over a 2-year period, with an additional discounted cost of pound 387.45, giving an incremental cost-effectiveness ratio (ICER) of pound 7175 per QALY. Economic modelling suggested that surgery produced a still greater benefit when considered with a 10-year time horizon, with an ICER of pound 1936 per QALY. Injection sclerotherapy produced an incremental benefit of approximately 0.044 QALY at a cost of pound 155 when compared with conservative treatment, giving an ICER of pound 3500 per QALY. When surgery was compared with sclerotherapy, surgery produced greater benefit with a lower ICER (showing extended dominance). CONCLUSIONS: Standard surgical treatment of varicose veins by saphenofemoral ligation, stripping and multiple phlebectomies is a clinically effective and cost-effective treatment for varicose veins, with an ICER well below the threshold normally considered appropriate for the funding of treatments within the NHS. Injection sclerotherapy also appears to be cost-effective, but produces less overall benefit, with a higher ICER than surgery for patients with superficial venous reflux. In minor varicose veins without reflux, sclerotherapy is likely to provide a small average benefit with acceptable cost-effectiveness. Research is needed into methods for accurate and acceptable utility evaluations for conditions with relatively minor effect on HRQoL and also for a validated and standardised method of classification for varicose veins.

Adolescent↗

PubMed2006

Differentiation of faecal Escherichia coli from humans and animals by multiple antibiotic resistance analysis.

AIMS: Multiple antibiotic resistance (MAR) was performed on 128 Escherichia coli isolates, recovered from faecal samples of humans and animals (cattle, goat, sheep) to determine and compare their antibiotic resistance patterns and to evaluate them statistically in order to specify the source of the faecal material. METHODS AND RESULTS: Disk diffusion method was applied with a selection of antibiotics. Statistical approach was performed with hierarchical cluster analysis (CA), discriminant analysis (DA) and principal component analysis. Comparing human and animal isolates there was significant difference in levels of resistance to all antibiotics tested (P<0.05) with 46 and 24 distinct resistance patterns for human and animal isolates respectively. CA and DA separated human and animal isolates with a high average rate of correct classification (99.2%), when all animal isolates were pooled together. CONCLUSIONS: MAR analysis compared with appropriate statistical evaluation may provide a useful tool for differentiating the human or animal origin of E. coli isolates derived from environmental samples. Subsequently, determination of the source of faecal pollution becomes possible. SIGNIFICANCE AND IMPACT OF THE STUDY: Determining the source of faecal pollution enables the prediction of possible risk for public health and the application of appropriate management plans for prevention of further contamination.

Animals↗

PubMed1991

Evaluation of aortic regurgitation by cardiac cine magnetic resonance imaging: planar analysis and comparison to Doppler echocardiography.

Cine magnetic resonance imaging (MRI) displays cardiac flow in cine loop fashion on multiple tomographic sections. Since laminar flow is easily distinguished from turbulent flow, cine MRI may be uniquely suited to the study of valvular regurgitation: the entire cardiac volume can be sampled and the regurgitant jet at the valve plane can be depicted. We therefore assessed aortic regurgitation (AR) by cine MRI in 35 patients and 11 normal volunteers and compared results to pulsed (n = 32) or color flow Doppler (n = 14). The extent of the flow disturbance was estimated for both cine MRI and Doppler by indexing the size of the maximal, single plane regurgitant jet area (JA) to the left ventricular (LV) area. Cine MRI JA/LV ratio compared well with pulsed (r = 0.81) and color flow (r = 0.88) Doppler; classification as mild (less than 20%), moderate (20-40%), and severe (greater than 40%) AR by both methods was identical in 43 of 46 cases with no differences of more than one grade. Overall sensitivity and specificity of cine MRI, compared to Doppler, were 94 and 95%, respectively. Cine MRI also depicted the regurgitant jet at the valve plane in 11 patients. Thus planar analysis of cine MRI images in patients with AR provides a semiquantitative assessment of the AR flow disturbance which is similar to Doppler but, in addition, can image the entire cardiac volume and the regurgitant jet at the valve plane.

Adult↗

PubMed1986

Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics.

Quantitative morphometric determinations of neuronal and glial density, neuron-glia ratios, and neuronal size were performed in the prefrontal, anterior cingulate, and primary motor cortex of ten controls and ten schizophrenics diagnosed by Feighner criteria under blind conditions to assess whether neuronal degeneration had occurred. Stepwise multiple regression and multiple classification analyses were used to evaluate the effect of potential confounding variables such as age, postmortem interval, fixation, hypoxia, and neuroleptic exposure on the measures studied. The neuronal density was significantly lower in layer VI of the prefrontal, layer V of the cingulate, and layer III of motor cortex. There was also a trend toward fewer neurons in most layers of both prefrontal and motor cortex, although by discriminant analysis this generalized pattern was significant only for the prefrontal area. The glial density also tended to be lower throughout most layers of all three cortical regions. There were no differences in the neuron-glia ratios or neuronal size between the two groups. The data do not support the presence of neuronal degeneration in schizophrenic cortex as it is conventionally described by neuropathologists, but do suggest the possibility that cytoarchitectural variations in cortical structure might exist in this group of schizophrenics.

Aged↗

PubMed2003

Laparoscopic vs open colectomy: outcomes comparison based on large nationwide databases.

HYPOTHESIS: Laparoscopic colectomy has significant advantages over open colectomy in the treatment of diverticular disease with respect to the length of hospital stay, routine hospital discharge, and postoperative morbidity and mortality. DESIGN: Retrospective secondary data analysis. PATIENTS AND SETTING: Patients with primary International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes for laparoscopic (709 patients [3.8%]) and open sigmoid resection (17 735 patients [96.2%]) were selected from the 1998, 1999, and 2000 Nationwide Inpatient Samples. These databases represent 20% stratified probability samples of all US community hospital discharges. Sampling weights were used to allow generalization of the study findings to the overall US population. Multiple linear and logistic regression analyses were performed to assess the risk-adjusted association between the surgery type and patient outcomes. MAIN OUTCOME MEASURES: Length of hospital stay, in-hospital complications, in-hospital mortality, and the rate of routine discharge. RESULTS: The patients had a mean age of 59.8 years; they were preponderantly white (89.1%) and female (54.0%). After adjusting for other covariates, laparoscopic sigmoidectomy was associated with a shorter mean hospital stay (laparoscopic sigmoidectomy vs open sigmoidectomy, 7.47 vs 9.37 days; P<.001), fewer gastrointestinal tract complications (odds ratio, 0.57; 95% confidence interval, 0.35-0.93; P =.03), a lower overall complication rate (odds ratio, 0.64; 95% confidence interval, 0.47-0.88; P =.007), and a higher routine hospital discharge rate (odds ratio, 2.21; 95% confidence interval, 1.51-3.21; P<.001). CONCLUSION: Laparoscopic sigmoid resection in patients with diverticular disease has statistically and clinically significant advantages over open sigmoid resection with respect to the length of hospital stay, rate of routine hospital discharge, and postoperative in-hospital morbidity.

Age Distribution↗

PubMed1998

Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3-, CD3epsilon+, CD56+ phenotype and associated with the Epstein-Barr virus.

A novel interleukin-2 (IL-2)-dependent cell line, HANK1, was established from a patient with CD56+ NK/T-cell lymphoma arising in the retroperitoneum. Morphologically, HANK1 is a pleomorphic large cell line with irregular nuclei, which contains azurophilic granules in the cytoplasm. Immunophenotypic analysis showed that HANK1 expressed CD2, CD3epsilon, CD56, TIA-1, granzyme B, and HLA-DR, but no other T-lineage markers. These features were the same as seen in the original tumour, and are highly characteristic of nasal and 'nasal-type' NK/T-cell lymphoma as described in the proposed W.H.O. classification. Genotypically, this cell line also demonstrated the germline configuration of the T-cell receptor beta, gamma and the immunoglobulin heavy chain genes and clonal integration of the Epstein-Barr virus (EBV) together with antigen expression with a type II latency pattern (LMP-1+ and EBNA2-). Furthermore, Southern blot analysis using the EBV termini as probes confirmed its derivation from the original lymphoma, and revealed that it contained multiple copies of the EBV genome. Dose-dependent growth on IL-2 was observed in an in vitro study with a doubling time of 3 d at maximal stimulation. These data indicate that HANK1 seemed to preserve the biological characteristics of the original tumour and therefore may serve as a good model for the further analysis of unusual 'nasal-type' NK/T-cell lymphoma.

Blotting, Southern↗

PubMed2006

Work routinization and implications for ergonomic exposure assessment.

Jobs in many modern settings, including manufacturing, service, agriculture and construction, are variable in their content and timing. This prompts the need for exposure assessment methods that do not assume regular work cycles. A scheme is presented for classifying levels of routinization to inform development of an appropriate exposure assessment strategy for a given occupational setting. Five levels of routinization have been defined based on the tasks of which the job is composed: 1) a single scheduled task with a regular work cycle; 2) multiple cyclical tasks; 3) a mix of cyclical and non-cyclical tasks; 4) one non-cyclical task; 5) multiple non-cyclical tasks. This classification, based primarily on job observation, is illustrated through data from a study of automobile manufacturing workers (n = 1200), from which self-assessed exposures to physical and psychosocial stressors were also obtained. In this cohort, decision latitude was greater with higher routinization level (p < 0.0001), and the least routinized jobs showed the lowest self-reported exposure to physical ergonomic stressors. The job analysis checklist developed for non-routinized jobs is presented, and limitations of the task analysis method utilized in the study are discussed. A work sampling approach to job analysis is recommended as the most efficient way to obtain a comparable unbiased exposure estimate across all routinization levels.

Arm↗

PubMed1987

[Virus carriers: analysis of states of equilibrium between the virus and its host].

The various mechanisms of virus persistence are described. Four kinds of virus persistence are presented, depending on their epidemiological significance, persistence associated with continuous multiplication and transmission (feline calicivirus, calf rotavirus); persistence associated with continuous multiplication but discontinuous transmission (equine infectious anemia retrovirus); persistence with continuous multiplication associated with immunotolerance (feline leukaemia retrovirus; mucosal disease pestivirus); latent carrier state with discontinuous transmission (feline and pigeon herpesvirus; infectious bovine rhinotracheitis herpesvirus). The classification of these kinds of virus persistence is based upon their epidemiological significance, even if the mechanisms allowing the persistence are completely different.

Animals↗

PubMed1995

Analysis of Bacteroides species by pyrolysis mass spectrometry.

Two methods for the classification of isolates of the Bacteroides fragilis group were compared in a study of 133 clinical isolates and 10 reference strains. There was broad similarity between the pattern of clusters in pyrolysis mass spectrometry (PyMS), which reflects whole-cell composition, and that in conventional tests, which reflect nutritional interactions with the environment. A single large cluster was resolved by both approaches; this cluster comprised mainly strains identified as B. fragilis and was surrounded by a multiplicity of small clusters (42 in PyMS and 24 in conventional tests). Individual clusters corresponding to strains identified as Bacteroides thetaiotaomicron and Bacteroides vulgatus, respectively, were found by both techniques. However, for the remainder of strains, little correlation was evident between clustering in PyMS and that in conventional tests. Further comparison with data obtained by sodium dodecyl sulfate- polyacrylamide gel electrophoresis for this collection of strains showed equal levels of disagreement between classification based on whole-cell protein and each of the classifications described here. In previous studies of other genera, PyMS-based and conventional test-based classifications showed good agreement. It appears that the B. fragilis group presents intractable problems in phenotypic characterization.

Bacterial Typing Techniques↗

PubMed1978

A multivariate analysis of the likelihood and volume of preventive visit demand in a prepaid group practice.

An economic framework for the investigation of the demand for preventive medical care services is suggested and empirical models for the likelihood and volume of preventive physician visits are specified. These are tested using data on 3,892 individuals enrolled in the Kaiser Foundation Prepaid Health Plan of Portland, Oregon. Preventive visits, delineated by the Kaiser Clinical Behavioral Classification System, included general medical examinations, eye examinations, well-child care and immunization services. Multiple regression is used to estimate the likelihood of preventive visits for all persons and the volume of preventive visits for users. Income and coinsurance were the most significant economic variables in the likelihood equation, possessing the expected positive and negative signs, respectively. The usual findings of a positive education effect and negative family size effect were supported by the results. The economic variables were less significant in the volume equations than in the likelihood equations, suggesting that system and physician effects may neutralize these factors. Females were more likely to make a preventive visit than were males and the relatively young and old were the heaviest age-group users of preventive care. Perceived helath status did not appear to significantly affect preventive care demand.

Adult↗

PubMed2000

[Analysis of causes for anemia in patients with multiple myeloma].

UNLABELLED: Pathogenetic mechanism of myeloma (MM) associated anaemia may involve: decreased level of erythropoietin (Epo) production, insufficient response to this hormone, bone marrow replacement by tumour cells, and cytokine mediated suppressive effect on erythropoiesis (ACD type of anaemia). We evaluated some possible causes of MM associated anaemia in a group of MM patients before treatment, using tests of in vitro culture of erythroid precursors and determination of the level of selected cytokines and evaluation of patient sera and media conditioned by patient cells for haematopoietic growth in vitro inhibitory/stimulatory activity. The study group included 15 patients with advanced MM at III clinical stage (according Durie and Salmon classification) prior treatment with a median age 61.8 women and 7 men. Diagnostic work-up included cytogenetics and serum Epo level as well as routine tests. We determined number of CFU-E, BFU-E and CFU-GM in the bone marrow of patients and healthy donors after mononuclear and T cell depletion in serum free culture under different conditions: 1) with conditioned medium (CM) by patients T cells, 2) CM by T cells of healthy donors and 3) without CM. IL-6, IL-1 alpha and TNF-alpha level in the serum and CM was determined. All patients were slightly anaemic--mean Hb 6 mmol/l (9.6 g/dl), transferrin level was increased--mean 1612 pmol/l (732 ng/ml) whereas iron level was normal. The average frequency of erythropoietic cells in myelogram was decreased (12%), however, the frequency of plasmocytes was increased (32%). Epo serum level was decreased in comparison with degree of anaemia (mean 22.2 U/ml). The average number of CFU-E/10(5) was slightly lower--212 and in the cultures containing CM by patient T cell and CM-by T cells of healthy donor decreased significantly to 138 and 183, accordingly. This phenomenon was not observed in cultures containing normal bone marrow cells. IL-6 level was increased in patients' serum and CM by patients T cells (27 ng/ml and 51 ng/ml, respectively). CONCLUSIONS: The results of this study support the notion on the multifactorial origin of anaemia in myeloma patients. The factors specified in this study include 1. defective response of Epo to the degree of anaemia 2. decreased number of committed erythroid cells in the marrow 3. suppression of erythropoiesis by IL-6.

Adult↗