Biomedical subjects

D Marx

Publications and source records attributed to D Marx.

At least 19 recordsLinked to original sources

PubMed2006

[Stability of the "amok runner syndrome"].

BACKGROUND: Running amok is considered a rare but dangerous act of violence which has been investigated predominantly on a case by case basis. German-wide data on amok cases covering the decades 1980 - 1989 and 1991 - 2000 were used to perform the first epidemiological study world-wide on the stability of socio-demographic, criminological and psychiatric variables of amok behaviour. METHODS: A content analysis study on nation-wide press reports of amok cases included a total of 104 subjects who were identified by combined homicidal-suicidal acts of violence and fulfilled structured criteria originally defined according to former Malayan amok events. RESULTS: Amok cases in both decades were comparable except for the significant increase of weapon use, especially of firearms. Total prevalence showed a tendency to decline from 1 : 5.5 million to 1 : 8.5 million men per year, females were involved in rare single cases only. The male offenders showed a bimodal age distribution with a mean of 35 years. They were professionally well qualified, but had a 5 - 7fold higher risk of unemployment than the normal population. Motives and reasons for running amok were serious but not unusual, they varied widely and addressed all areas of daily life. Most offenders were characterized by abnormal personality patterns such as passive, aggressive, impulsive and paranoid and were in possession of firearms and previously convicted. Psychiatric diseases such as psychosis, paranoia, depression or personality disorders were present in more than 50 % of cases; further 20 % were intoxicated. The presence of psychiatric disorders influenced patterns of violent behaviour in individual subjects. Victims were predominantly unknown to the offenders. Close to one third of the amok runners committed suicide or were killed by legal authorities. CONCLUSION: Amok represents a temporarily stable syndrome of extreme violent behaviour even in modern industrialized societies. Subjects exhibit a complex combination of serious causative motives, social burden and psychiatric diseases which do not explain common causes of amok rather than the origin of amok behaviour in individual cases. Amok joins the wide spectrum of human homicidal-suicidal acts which show similarities in many aspects.

Adult↗

PubMed2006

Effect of bird cage space and dietary metabolizable energy level on production parameters in laying hens.

A study was conducted to assess the effects of varying cage spaces on a commercial laying hen strain fed differing levels of dietary metabolizable energy (ME) for 15 wk. Four cage space allowances (342, 413, 516, and 690 cm2/hen) were combined with 3 levels of dietary ME (2,800, 2,850, and 2,900 kcal of ME/kg) in a 4 x 3 factorial arrangement. Each treatment was assigned to 6 replicate cages for a total of 72 cages in randomized complete block design. Feed intake and metabolizable energy intake were significantly (P < 0.01) greater for hens housed at 690 cm2/hen compared with those housed at 413 and 342 cm2/hen, but not those housed at 516 cm2/hen, across all dietary ME levels. Egg production and egg mass were significantly (P < 0.001) improved for hens housed at 690 cm2/ hen in contrast to other cage spaces and across all energy levels. There were no interaction effects of ME levels on laying hen performance at varying cage space except for body weight change. Hens housed at 516 cm2/ hen and fed 2,800 kcal of ME/kg exhibited the greatest weight change, which was significantly (P < 0.05) greater than those fed other levels of ME at the same cage space. Hens housed at 690 cm2/hen had significantly (P < 0.05) greater ME efficiency of egg production than hens housed at other cage spaces. Hens fed the diet with 2,900 kcal of ME/kg had significantly (P < 0.001) greater ME digestibility compared with those fed 2,800 or 2,580 kcal of ME/ kg with differences of 107 and 118 kcal of ME/kg, respectively. There were no significant effects of ME levels observed except ME digestibility, and no significant effects of cage space allowance on egg weight, hen weight, bone ash, or maintenance energy intake. It is evident that decreasing the number of birds per cage and increasing cage space allowance per hen had an overall positive effect on performance.

Animal Nutritional Physiological Phenomena↗

PubMed2005

Inhibition of airway hyperresponsiveness and pulmonary inflammation by roflumilast and other PDE4 inhibitors.

Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity. We compared the anti-inflammatory effects of roflumilast with those of PDE4 inhibitors rolipram, piclamilast, and cilomilast in ovalbumin (OVA)-sensitized and challenged Brown-Norway rats. Animals were treated orally 1h before OVA challenge with roflumilast (0.3, 1.0, and 3.0mg/kg), rolipram (0.8, 2.8, and 8.3mg/kg), piclamilast (10.0, 20.0, and 30.0mg/kg), or cilomilast (10.3, 34.3, and 103.0mg/kg). Airway hyperresponsiveness (AHR) against adenosine was investigated by measuring airway resistance 200min after OVA challenge. Subsequently, neutrophil influx and tumor necrosis factor-alpha (TNF-alpha) release in the lungs were determined by bronchoalveolar lavage. Direct bronchodilation at the time point of AHR assessment by PDE4 inhibitors was examined in serotonin-challenged animals. Evaluation of neutropenic animals or treatment with anti-TNF-alpha antibody revealed that AHR was independent of neutrophil accumulation or TNF-alpha release. Roflumilast (50% inhibitory dose [ID(50)]=1.5mg/kg) inhibited AHR 3-, 16-, and 27-fold more potently than rolipram, piclamilast, and cilomilast, respectively. Likewise, roflumilast was a more potent inhibitor of neutrophil influx (ID(50)=0.9mg/kg) than rolipram (ID(50)=6.9mg/kg), piclamilast (ID(50)=28.1mg/kg), or cilomilast (ID(50)=37.7mg/kg). Roflumilast, rolipram, and piclamilast-but not cilomilast-suppressed OVA-induced TNF-alpha release in a dose-dependent manner. Roflumilast (ID(50)=0.9mg/kg) exhibited 9- and 23-fold more potent inhibition of TNF-alpha release than rolipram and piclamilast, respectively. Roflumilast did not inhibit serotonin-induced bronchoconstriction 4.5h after administration, suggesting that inhibition of AHR by roflumilast results from anti-inflammatory, not bronchodilatory, effects. This study suggests that roflumilast has anti-inflammatory action and provides rationale for the investigation of roflumilast in asthmatic patients.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2004

Percentage of canals filled in apical cross sections - an in vitro study of seven obturation techniques.

AIM: To compare the apical density of several obturation techniques when used in palatal roots of extracted maxillary molars. METHODOLOGY: Seventy extracted molars were randomly divided into seven groups with 10 teeth each. The palatal root canals were instrumented to size 60 MAF, coated with Kerr's Pulp Canal Sealer, and obturated using one of seven techniques. The palatal roots were separated from the crowns, decalcified, and sectioned horizontally at 2 and 4 mm from the apex. The cross-sections were photographed through a microscope, the photos were analysed, and the amount of area in the canal that was obturated with gutta-percha was measured. The means for the 20 sections per group were calculated and the means were compared using mixed analysis of variance test. RESULTS: Simplifill used in accordance with the manufacturer's directions and Thermafil had the greatest mean obturated area, but neither were statistically better than mechanical lateral or warm vertical compaction (WVC; Schilder Technique). Simplifill as recommended and Thermafil were statistically better than cold lateral (P = 0.0210 and 0.0433, respectively), WVC (continuous wave) (P = 0.0006 and 0.0015), and the modified Simplifill group (P = 0.0010 and 0.0012). In addition, mechanical lateral and WVC (Schilder) had statistically more obturated area than WVC (continuous wave) (P = 0.0054 and 0.0073) and modified Simplifill (P = 0.0015 and 0.0016). Cold lateral and WVC (continuous wave) had significantly more obturated area than modified Simplifill (P = 0.0040 and 0.0087). CONCLUSIONS: Simplifill as recommended, Thermafil, mechanical lateral and WVC (Schilder) obturation techniques created more complete obturation using gutta-percha at the 2 and 4 mm levels than cold lateral, WVC (continuous wave), and Simplifill not used as directed.

Analysis of Variance↗

PubMed2003

Stabilization of polar ZnO surfaces: validating microscopic models by using CO as a probe molecule.

The determination of the structure of inhomogeneous metal-oxide surfaces represents a formidable task. With the present study, we demonstrate that using the binding energy of a probe molecule, CO, is a reliable tool to validate structural models for such complex surfaces. Combining several types of first-principles calculations with advanced molecular beam methods, we are able to provide conclusive evidence that the polar O-terminated surface of ZnO is either reconstructed or hydrogen covered. This finding has important consequences for the ongoing discussion regarding the stabilization mechanism of the electrostatically unstable ("Tasker type 3") polar ZnO surfaces.

Journal Article↗

PubMed2003

Neuromuscular objectives of the human masticatory apparatus during static biting.

OBJECTIVE: The central nervous system controls the muscles of mastication and may dictate muscle outputs according to a biologically important objective. This study tested the hypotheses that (a) the effective sagittal TMJ eminence morphology, and (b) the outputs of the masticatory muscles during static biting, are consistent with minimisation of joint loads or minimisation of muscle effort. DESIGN: Numerical modelling predicted effective eminence morphology (from sagittal plane directions of TMJ force for centred loading over a range from molar to incisor biting) and TMJ and muscle forces during static unilateral biting in seven subjects. In vivo effective eminence morphology was measured from jaw tracking recorded from each subject. Muscle activities during biting tasks on first molar and incisor teeth were measured by electromyography using surface or indwelling electrodes. RESULTS: Subject-specific predicted effective eminence morphology correlated with in vivo data (0.85< or =R2< or =0.99). Mixed and random coefficient analysis of covariance indicated good agreement between predicted and measured muscle outputs for all muscles of mastication investigated. Individual linear regression analysis showed that modelled muscle outputs accurately predicted EMG data, with average errors of 8% for molar and 15% for incisor biting. CONCLUSIONS: Effective sagittal eminence morphology was consistent with minimisation of joint loads for all subjects. Masticatory muscle outputs during unilateral biting were consistent with minimisation of joint loads or minimisation of muscle effort, or both, depending on the subject. These results are believed to be the first to test model predictions of muscle output during biting for all muscles of mastication.

Adult↗

PubMed2003

[Helicobacter pylori infection in a group of symptomatic and asymptomatic children and adolescents in the Czech Republic].

BACKGROUND: There exist only inconsistent results of studies on the relationship between Helicobacter pylori (H. pylori) infection and functional dyspepsia and/or recurrent abdominal pain in children and adolescents. The answer could bring a comparison of the epidemiological features of H. pylori infection between children and adolescents with dyspepsia and/or recurrent abdominal pain (symptomatic) and without these symptoms (asymptomatic), living in the Czech republic. METHODS AND RESULTS: Study includes children and adolescents (2-18 years) with upper gastrointestinal symptoms visiting paediatric gastroenterology department between 1994 and 1999. Age, sex, socioeconomic level matched control (asymptomatic) group consisted of children and adolescents visiting the general paediatric service with symptoms not related to the upper gastrointestinal tract. Demographic and socioeconomic factors, including parent(s) educational level, place of residence, living conditions, type of drinking water and pets in their household were evaluated. Serum of the children and adolescents was tested for H. pylori IgG by enzyme linked immunosorbent assay. In addition, the symptomatic children and adolescents underwent endoscopic examination and biopsies from gastric antrum and corpus were taken for the quick urease test, histology/histoscopy, and H. pylori cultivation. H. pylori infection in this group was stated when at least two tests were positive. Altogether 829 children and adolescents were examined, 624 cases were symptomatic and 205 represented controls (asymptomatic). The prevalence of infection was 33% among symptomatic children vs. 7.5% among controls (OR = 6.2, p.001) and was similar among boys and girls (32% vs. 34.5%, respectively). H. pylori prevalence increased with age among symptomatic children (10% for children below 6 years and 37% between 11 to 16 years) (p.001). In contrary, prevalence tended to fall with age among asymptomatic children (11% in children below 6 years vs. 6% in children over 10 years (OR = 2.0, 95% CI = 0.7-6.2). In both groups, an inverse correlation between H. pylori occurrence and mother's educational level was observed. The H. pylori incidence was 10% among asymptomatic children who drank water from municipal water supply or from a well vs. 3% among those who drank bottled water (OR = 4, 95% CI = 1.1 to 18, p.05). CONCLUSIONS: H. pylori infection was more prevalent among symptomatic children and adolescents vs. asymptomatic children and adolescents within the same population. H. pylori incidence increased with age among symptomatic children and adolescents and tended to fall among controls, showing deep differences between the two groups. With exception of the bottled water drinking, presence of any other factor studied represented significant risk for acquiring the H. pylori infection.

Adolescent↗

PubMed2001

Heavy-atom skeleton quantization and proton tunneling in "intermediate-barrier" hydrogen bonds.

Quantum effects on proton transfer through barriers of several kcal/mol in hydrogen bonds are investigated theoretically in malonaldehyde. Such "intermediate-barrier" proton transfer processes play a key role in the catalytic activity of some enzymes. Tunneling is shown to be significant in this reaction even at room temperature. More importantly, the quantum nature of the heavy molecular frame atoms is found to substantially enhance proton tunneling. These findings have far-reaching implications for common modeling strategies of proton transfer in complex systems such as biomolecules.

Journal Article↗

PubMed2001

Systemic delivery of cetrorelix to rats by a new aerosol delivery system.

PURPOSE: To study the pulmonary absorption and tolerability of various formulations of the decapeptide cetrorelix acetate in rats by a new aerosol delivery system (ASTA-ADS) for intratracheal application. METHODS: Using the ASTA-ADS, cetrorelix liquid formulations (aqueous solutions for ultrasonic nebulization) were firstly selected and subsequently delivered as nebulized aerosol to orotracheally cannulated rats. The pharmacologic effect (decrease of testosterone serum level) of four cetrorelix formulations was determined in rats by enzyme linked immunosorbant assay, and pharmacokinetic data were determined after measurement of cetrorelix serum level by radioimmunoassay. Histological examination of the lung was performed at the end of the experiments, and in a supplementary experiment the respiratory parameters (resistance and compliance) of rats were monitored by a validated pulmonary monitoring system during the aerosol application of the same formulations. RESULTS: After an exposure time of 5 min, the applied formulations reduced the testosterone concentration in serum to subnormal levels (< or =1 ng/ml) over a period of 24 h. Comparing the plasma concentration after intratracheal aerosolization with data of intravenous administration, the mean calculated bioavailabilities for the four formulations using the corrected dose (delivered--exhaled amount) were between 48.4 +/- 27.0% and 77.4 +/- 44.0%. The histologic examination of the lungs revealed different tolerability of the various tested formulations ranging from locally intolerable to well tolerated. The measurement of the lung function parameters did not reveal any compound or formulation related changes. CONCLUSIONS: Our studies show that cetrorelix can be effectively administered as aerosol and that intratracheal aerosolization via the ASTA-ADS provides results that are well comparable to other application routes, as demonstrated by statistical comparison of the newly obtained data with previous results from intratracheal instillation of cetrorelix solutions in rats.

Administration, Inhalation↗

PubMed2001

Animal models of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), which encompasses both chronic bronchitis and emphysema, is one of the most common respiratory conditions of adults in the developed world. Despite the high prevalence and enormous cost to healthcare and society, COPD has received scant attention in comparison to other respiratory conditions such as asthma and lung cancer. It is often thought of as a self-inflicted disease. But not all people who smoke develop COPD and not all patients with COPD are smokers. The causes of COPD are different. Its pathogenesis is complex. There are very few effective treatments. Therefore, there is an urgent need to improve present therapy by drugs with new modes of actions. In contrast to many human diseases, chronic bronchitis and emphysema occur seldom in the animal world. Therefore, we have to mimic some characteristic features of these diseases in animals. For this reason, a wide variety of animal models have been developed and are employed in the search for new chemical entities for the treatment of COPD. In the present paper, the experimental models of COPD are critically reviewed.

Animals↗

PubMed2001

Development of a new aerosol delivery system for systemic pulmonary delivery in anaesthetized and orotracheal intubated rats.

Over the last decade, the systemic absorption of a broad range of therapeutics after pulmonary application has been demonstrated in animals as well as in humans. The most common method used in the laboratory is the intratracheal instillation of drugs in solution. This method is, however, unsatisfactory, because of discrepancies in particle distribution, clearance, kind of injury and bioavailability between instillation and inhalative application. On the other hand, a precise determination of the amount of drug applied by aerosol, and of the aerosol volume retained within the lungs is rather difficult, and is not possible for use with small animals such as mice or rats. We describe a system which allows the delivery of aerosols directly into the animal's lungs, and calculation of the amount of drug retained in the lungs. Our system was tested in vitro and in vivo and was shown to allow precise and efficient pharmacokinetic and toxicological studies to be carried out.

Absorption↗

PubMed2001

Detection of serum autoantibodies to tumor suppressor gene p53 with a new enzyme-linked immunosorbent assay in patients with ovarian cancer.

Sera from 99 ovarian cancer patients were assayed for serum autoantibodies to p53 using a newly developed enzyme-linked immunosorbent assay (ELISA). Results were compared to the investigation using the former ELISA. The incidence of autoantibodies (25%) was lower using the newly developed ELISA as compared to the previous results (41%). The results were consistent in 79% of patients (P < .001). The incidence of autoantibodies was lower in patients with complete remission (19%) as compared to that of patients with recurrence (30%) and before primary surgery (26%). No statistically significant correlation was found among p53 serum autoantibody status and tumor stage, degree of malignancy, histologic subtype, and residual tumor after primary surgery. Use of the newly developed ELISA resulted in a higher consensus between immunohistochemically negative and autoantibody negative cases. Owing to further purifying of the prepared human recombinant p53. the newly developed ELISA seems to be of higher specificity as compared to the former ELISA.

Adenocarcinoma, Clear Cell↗

PubMed2001

[Acute hemorrhage in Crohn's disease].

The authors present a case of profuse haemorrhage into the lower part of the digestive tract in a 17-year-old patient where Crohn's disease of the terminal ileum and right colon up to the hepatal flexure was diagnosed by sonographic examination. The haemorrhage occurred after preparation for coloscopic examination with Fortrans only 2 months after the onset of the first symptoms of the disease. Because of developing signs of haemorrhagic shock emergency surgery was necessary. Resection of the terminal ileum and dextrolateral hemicolectomy was performed and during operation coloscopy to eliminate further sources of haemorrhage. The patient recovered p.p.i. and was discharged on the 10th day after surgery. The authors discuss diagnostic and therapeutic pitfalls of this rare complication of Crohn's disease and compare their findings with data from the literature.

Acute Disease↗

PubMed2001

Therapy of bronchial asthma with adenosine receptor agonists or antagonists.

Adenosine is an endogenous nucleoside that is released under pathological conditions and interacts with four G-protein-coupled receptor subtypes. These receptors are widely distributed throughout the body. They are involved in many central and peripheral processes, including immunological and inflammatory responses. In inflammatory and asthmatic conditions, the extracellular concentration of adenosine increases in the airway tissue. It enhances mast cell degranulation and bronchoconstriction, but may also inhibit eosinophil or lymphocyte function or modulate reactive oxygen species generation in neutrophils. Despite a large number of studies clearly indicating the effects of adenosine in vitro, many aspects of the mechanisms involved in the adenosine-mediated responses are still unclear, and our knowledge is limited in understanding the complex multifactorial interactions occurring in the whole body. The discovery of adenosine receptor compounds acting with increasing selectivity will bring new approaches to the use of adenosine receptor agonists and antagonists and may clarify some of the current uncertainties. On the basis of our present knowledge, the development of adenosine A(2A)- or (A3)-receptor agonists as antiinflammatory agents or A(2B)-receptor antagonists as inhibitors of mast cell degranulation for the treatment of asthma holds promise.

Journal Article↗

PubMed2000

Solvation of radical cations in water--reactive or unreactive solvation?

The solvation and reaction of ethylene radical cation in aqueous solution has been studied with Car-Parrinello molecular dynamics simulations. All ab initio simulations were performed using a system of 56 water and one ethylene molecule. Using a favorable symmetrically solvated radical cation as the starting point of the simulation a fast addition of water (within 90 fs) to the radical cation is observed. The primary addition product is rapidly deprotonated (within 100 fs) to yield the ethanol-2-yl radical. A second simulation was initiated through vertical ionization of neutral hydrated ethylene, representing a significantly less favorable situation for the addition process. No addition of water can be observed in this second simulation over a time span of 1.7 ps. Taken together the two simulations are indicative of a rearrangement of the solvent shell which represents the major part of the overall reaction barrier. Under these circumstances, the reaction rate of an otherwise spontaneous reaction is limited by the intrinsic solvent relaxation time. This interpretation of the reactivity of hydrated radical cations reconciles previously conflicting experimental condensed phase and theoretical gas phase studies.

Journal Article↗

PubMed2000

Exploring the electronic structure of elemental lithium: from small molecules to nanoclusters, bulk metal, and surfaces

Clusters of lithium atoms ranging in size from Li4 to Li40 and bulk metallic solids, including surfaces, are investigated through first principles electronic structure calculations, which are based upon density functional theory and the electron localization function (ELF). It is found that large lithium ppi-type contributions in the electronic wavefunction cause the electrons to localize in interstitial regions, which leads to multicenter bonding for both the clusters and the solids, including their surfaces. For the smaller clusters these stabilizing ppi interactions also lead to short Li-Li interatomic distances, which in conjunction with the longer bonds induces "distance alternation" in the range from 2.45 A to 3.15 A. This consequence of the additional ppi interactions is absent in simple solids due to symmetry. The electronic structure of the clusters is topologically insensitive to deformations that do not affect their general shape, but changes significantly upon isomerization. The ramifications upon dynamic properties is that the clusters are quasi-rigid at low temperatures and retain their shape though the distance alternation pattern is suppressed. The picture which emerges for bonding in the bulk solid is that the metallic state arises from the presence of a large number of partially occupied multicenter bonds. For nanoscale clusters only the surface of these clusters exhibits strong localization, whereas their interiors display localization properties similar to the bulk metallic solid. On the other hand, localized states similar to those of the clusters ("dangling bonds") are found on the (001) surface of body-centered cubic (bcc) and face-centered cubic (fcc) lithium solids.

Journal Article↗

PubMed2000

Glucose uptake increases relative to oxygen consumption during short-term hibernation.

BACKGROUND: Although glucose uptake is increased in chronically hypoperfused, viable myocardium, the dynamic changes in glucose uptake relative to oxygen consumption in "short-term" models of hibernation have not been fully explored. METHODS: 14 anesthetized swine were instrumented with an hydraulic occluder and flow probe on the proximal LAD artery. Blood flow was reduced approximately 30% for 1 hour. Myocardial blood flow and uptake of oxygen, free fatty acids, glucose and lactate were determined in the LAD region at baseline and at 10, 30, and 60 minutes of ischemia. Transmural biopsies for ATP and creatine phosphate (CP) were obtained in the LAD region prior to and at 15 and 45 minutes of ischemia. In 5 animals, glycogen was assayed at baseline and at the end of 60 minutes of ischemia. RESULTS: In the LAD region, myocardial oxygen consumption was reduced from 2.06 +/- 0.16 micromol/min/gram to 1.46 +/- 0.13 micromol/min/gram (P < 0.05). By 15 minutes of ischemia, transmural creatine phosphate fell from 7.48 +/- 0.76 micromol/g-wet weight at baseline to 6.19 +/- 0.32 micromol/g-wet weight (P < 0.05) but normalized by 45 minutes of ischemia (7.39 +/- 0.56 micromol/g-wet weight; NS). Between 10 and 60 minutes of constant flow reduction, glucose uptake as a percentage of MVO2 increased from 3 +/- 2% to 10 +/- 2% (P < 0.05) while lactate uptake increased from -9 +/- 9% to -1 +/- 2% (P < 0.05). Glycogen decreased from 27.8 +/- 3.7 at baseline to 16.9 +/- 1.2 micromol/g-wet weight at end-ischemia. CONCLUSIONS: In this model of short-term hibernation, glucose and lactate uptake increase relative to oxygen consumption during sustained ischemia, and temporally coincide with the recovery of bioenergetics. The findings are consistent with the notion that glycolytically derived ATP is important for the maintainance of energy supply during sustained ischemia.

Animals↗

PubMed2000

nm23-H1 expression defines a high-risk subpopulation of patients with early-stage epithelial ovarian carcinoma.

The role of the nm23 gene in human ovarian cancer is still controversial. We studied the expression of the nm23-H1 gene in 247 human epithelial ovarian carcinomas. The patients were followed-up until their death, or for a minimum of 5 years if they survived. The expression of the gene was studied by means of immunohistochemistry and a semiquantitative scoring system considering the staining intensity and the number of reactive tumour cells. Patients carrying tumours with higher expression scores (4-6 on a scale from 0 to 6) had a significantly lower survival (P = 0.01) than the rest. Further stratified statistical analysis revealed that this effect was mainly attributable to the subgroup of patients with early-stage (I and II), well- and moderately differentiated tumours. In fact, a multivariate analysis carried out for this subset of patients showed nm23-overexpression to be the only significant independent predictor of an ominous prognosis. The association of nm23-overexpression with a worse prognosis was most probably not due to mutation of the nm23 gene, since mutational analysis in 60 tumours by means of single-strand conformational polymorphism and direct sequencing disclosed only one mutation, which was located outside the open reading frame. Our results seem to indicate that nm23 expression is associated with a significantly worse prognosis in early-stage, well-differentiated epithelial ovarian carcinoma, a finding with important clinical implications, considering that many patients with ovarian cancers showing these features do not undergo any further treatment beyond surgical staging. If confirmed, they could help in tailoring the treatment of these patients in the future.

Aged↗