ADHD-KG: a knowledge graph of attention deficit hyperactivity disorder.

Purpose: Attention Deficit Hyperactivity Disorder (ADHD) is a widespread condition that affects human behaviour and can interfere with daily activities and relationships. Medication or medical information about ADHD can be found in several data sources on the Web. Such distribution of knowledge raises notable obstacles since researchers and clinicians must manually combine various sources to deeply explore aspects of ADHD. Knowledge graphs have been widely used in medical applications due to their data integration capabilities, offering rich data stores of information built from heterogeneous sources; however, general purpose knowledge graphs cannot represent knowledge in sufficient detail, thus there is an increasing interest in domain-specific knowledge graphs. Methods: In this work we propose a Knowledge Graph of ADHD. In particular, we introduce an automated procedure enabling the construction of a knowledge graph that covers knowledge from a wide range of data sources primarily focusing on adult ADHD. These include relevant literature and clinical trials, prescribed medication and their known side-effects. Data integration between these data sources is accomplished by employing a suite of information linking procedures, which aim to connect resources by relating them to common concepts found in medical thesauri. Results: The usability and appropriateness of the developed knowledge graph is evaluated through a series of use cases that illustrate its ability to enhance and accelerate information retrieval. Conclusion: The Knowledge Graph of ADHD can provide valuable assistance to researchers and clinicians in the research, training, diagnostic and treatment processes for ADHD.

Diagnosing attention-deficit hyperactivity disorder (ADHD) using artificial intelligence: a clinical study in the UK.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting a large percentage of the adult population. A series of ongoing efforts has led to the development of a hybrid AI algorithm (a combination of a machine learning model and a knowledge-based model) for assisting adult ADHD diagnosis, and its clinical trial currently operating in the largest National Health Service (NHS) for adults with ADHD in the UK. Most recently, more data was made available that has lead to a total collection of 501 anonymized records as of 2022 July. This prompted the ongoing research to carefully examine the model by retraining and optimizing the machine learning algorithm in order to update the model with better generalization capability. Based on the large data collection so far, this paper also pilots a study to examine the effectiveness of variables other than the Diagnostic Interview for ADHD in adults (DIVA) assessment, which adds considerable cost in the screenining process as it relies on specially trained senior clinicians. Results reported in this paper demonstrate that the newly trained machine learning model reaches an accuracy of 75.03% when all features are used; the hybrid model obtains an accuracy of 93.61%. Exceeding what clinical experts expected in the absence of DIVA, achieving an accuracy of 65.27% using a rule-based machine learning model alone encourages the development of a cost effective model in the future.

Composition of place: towards a compositional view of functional space.

A long-standing question in GIScience is whether geographic information systems (GIS) facilitates an adequate quantifiable representation of the concept of place. Considering the difficulties of quantifying elusive concepts related to place, several researchers focus on more tangible dimensions of the human understanding of place. The most common approaches are semantic enrichment of spatial information and holistic conceptualization of the notion of place. However, these approaches give emphasis on either space or human meaning, or they mainly exist as concepts without practically proven usable artifacts. A partial answer to this problem was proposed by the function-based model that treats place as functional space. This paper focuses primarily on the level of composition, describing and formalizing it as a rule-based framework with the following objectives: (a) contribute to the formalization efforts of the notion of place and its integration within GIS and (b) maintain tangible properties intertwined with the human understanding of place. The operationalization potential of the proposed framework is illustrated with an example of identifying the shopping areas in an urban region. The results show that the proposed model is able to capture all shopping malls as well as other areas that are not explicitly labeled as such but still function similarly to a shopping mall.

The spectrum of myocardial homeostasis mechanisms in the settings of cardiac surgery procedures (Review).

Classic cardiac surgery, determined through the function of cardiopulmonary bypass machine and myocardial cardioplegic arrest, represents the most controlled scenario for cardiomyocyte homeostatic disturbances due to systemic inflammatory response and myocardial reperfusion injury. An increasing number of studies have demonstrated that myocardial cell homeostasis in cardiac surgery procedures is a sequence of molecularly interrelated and overlapping mechanisms in the form of apoptosis, autophagy and necrosis, which are activated by a plethora of induced inflammatory mediators and gene­related signaling pathways. In this study, we outline the molecular mechanisms of the cardiomyocyte adaptive homeostatic process and the associated clinical implications, in the settings of classic cardiac surgery procedures.

Carotene production from waste cooking oil by Blakeslea trispora in a bubble column reactor: The role of oxidative stress.

The oxidative stress induced by hydroperoxides and reactive oxygen species (ROS) during carotene production from waste cooking oil (WCO) and corn steep liquor (CSL) by the fungus Blakeslea trispora in a bubble column reactor was investigated. The specific activities of the intracellular enzymes superoxide dismutase (SOD) and catalase (CAT) as well as the micromorphology of the fungus were measured in order to study the response of the fungus to oxidative stress. The changes of the morphology of microorganism leaded to pellets formation and documented using a computerized image analysis system. As a consequence of the mild oxidative stress induced by hydroperoxides of WCO and ROS a significant increase in carotene production was obtained. The highest carotene concentration (980.0 mg/l or 51.5 mg/g dry biomass) was achieved in a medium consisted of CSL (80.0 g/L) and WCO (50.0 g/L) at an aeration rate of 5 vvm after 6 days of fermentation. In this case the carotenes produced consisted of ß-carotene (71%), γ-carotene (26%), and lycopene (3%). The strong oxidative stress in the fungus caused a significant increase of γ-carotene concentration. Bubble column reactor is a useful fermentation system for carotene production in industrial scale.

Thromboelastographic phenotypes of fibrinogen and its variants: clinical and non-clinical implications.

INTRODUCTION: Thromboelastography (TEG), a widely used clinical point of care coagulation test, is poorly understood. To investigate its fibrin determinants we used normal and variant fibrinogen isolates. MATERIALS AND METHODS: We focused mainly on the TEG maximum signal amplitude (MA), a shear modulus and clot stiffness indicator. Isolates included normal des-αC, cord, and abnormal congenital variants with amino acid substitutions or deletions that impaired fibrin polymerization. Heterophenotypic congenital isolates were from cryoprecipitate-depleted plasma owing to their more diminished clot MA than their cryoprecipitate counterparts. By colorimetric assay, the amount of fibrinogen adsorbed by untreated TEG cups was 83.5±12.4 pM/cm(2), n=18. Thrombin-induced clots were obtained at pH6.4 or 7.4, the latter containing 8mM CaCl2, and 14% afibrinogenemic plasma with and without gel-sieved platelets. RESULTS AND CONCLUSIONS: Measured by the water droplet contact angle, >90% reduction of surface hydrophobicity by exposure of TEG cup and pin to ozone plasma decreased MA by 74%. Increasing normal fibrinogen or thrombin concentrations progressively increased MA. Platelets increased MA further ~2 fold, except for ≥10 fold for des-αC clots. Examined in the absence of platelets, MA of heterophenotypic fibrin variants averaged 21%, n=15. The results imply that essential MA determinants include hydrophobic fibrinogen/fibrin adsorption and each polymerization contact site, with substantial enhancement by platelets. Also, cryoprecipitate-harvested soluble fibrinogen/fibrin complexes contained mostly normal molecules, while cryoprecipitate-depleted plasma contained mostly variant molecules. Moreover, significantly decreased MA by fibrinogen anomalies and/or low level thrombin generation can potentially impact clinical interpretation of MA.

Occurrence of pesticides in transboundary aquifers of North-eastern Greece.

A five-year groundwater monitoring program undertaken in Evros (north-east Greece), showed a diversification in the levels of pesticide residues detected in adjacent transboundary aquifers. During the first two years 37 wells, including irrigation, drinking water and artesian wells were monitored while the next three years the survey was focused on the 11 most contaminated wells. The presence of pesticide residues was also monitored in the phreatic horizon (shallow groundwater) of four experimental boreholes drilled in the respective margins of four fields. Among the compounds found alachlor, metolachlor, atrazine, desethylatrazine (DEA), desisopropylatrazine (DIA) and caffeine were constantly detected. Pesticide concentrations were much lower (up to 1.54 µg/L) in the water of the monitored drinking water wells (deep groundwater aquifers) compared to those found in the phreatic horizon (experimental boreholes) of the respective areas (up to 5.20 µg/L). DEA to atrazine concentration ratios (DAR) determined for the phreatic horizon of the three boreholes and respective wells were lower than 1, indicating that preferential flow was the cause of the fast downward movement of atrazine to the phreatic horizon. In contrast the DAR for the fourth borehole and the adjacent well were greater than 1 indicating the absence of preferential flow of atrazine. Catabolic processes of the soil converted atrazine to DEA which is more mobile than atrazine itself through chromatographic (darcian) flow. This differential behavior of pesticides in adjacent aquifers (3 km) was further investigated by determining the apparent age of water in the two wells. The apparent age of the water present in the first aquifer was 21.7 years whereas the apparent age of that in the second aquifer was approximately 1.2 years. The faster replenishing rate of the latter is an indication that this aquifer is very vulnerable to contamination with pollutants present in the infiltrated soil water.

Leaching of Br-, metolachlor, alachlor, atrazine, deethylatrazine and deisopropylatrazine in clayey vadoze zone: a field scale experiment in north-east Greece.

An extensive four-year research program has been carried out to explore and acquire knowledge about the fundamental agricultural practices and processes affecting the mobility and bioavailability of pesticides in soils under semi-arid Mediterranean conditions. Pesticide leaching was studied under field conditions at five different depths using suction cups. Monitoring of metolachlor, alachlor, atrazine, deethylatrazine (DEA), deisopropylatrazine (DIA), and bromide ions in soil water, as well as dye patterns made apparent the significant role of preferential flow to the mobility of the studied compounds. Irrespective to their adsorption capacities and degradation rates, atrazine, metolachlor and bromide ions were simultaneously detected to 160 cm depth. Following 40 mm irrigation, just after their application, both alachlor and atrazine were leached to 160 cm depth within 18 h, giving maximum concentrations of 211 and 199 µg L(-1), respectively. Metolachlor was also detected in all depth when its application was followed by a rainfall event (50 mm) two weeks after its application. The greatest concentrations of atrazine, alachlor and metolachlor in soil water were 1795, 1166 and 845 µg L(-1), respectively. The greatest concentrations of atrazine's degradation products (both DEA and DIA) appeared later in the season compared to the parent compound. Metolachlor exhibited the greatest persistence with concentrations up to 10 µg L(-1) appearing in soil water 18 months after its application. Brilliant blue application followed by 40 mm irrigation clearly depict multi-branching network of preferential flow paths allowing the fast flow of the dye down to 150 cm within 24 h. This network was created by soil cracks caused by shrinking of dry soils, earthworms and plant roots. Chromatographic flow of the stained soil solution was evident only in the upper 10-15 cm of soil.

Intraventricular hemorrhage in preterm infants: coagulation perspectives.

It has long been considered that a severe coagulation deficiency in premature newborns could be a major contributing factor in the occurrence of intraventricular hemorrhage (IVH). High-grade IVH has also been shown to coincide with severe derangement of coagulation in extremely low birth weight infants. This review focuses on the relevance of the physiologically developing immature hemostatic system to IVH, and the potential benefit of agents affecting hemostasis for IVH therapy or prevention in preterm infants. The findings of small, open-label interventional studies on the effect of ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII, and prothrombin complex concentrate on the premature coagulation system will be reviewed.

Epidemiologic, clinical characteristics, and risk factors for adverse outcome in multiresistant gram-negative primary bacteremia of critically ill patients.

BACKGROUND: Characteristics and burden of primary bacteremia because of multidrug-resistant (MDR) gram-negative bacteria (GNB) in intensive care unit (ICU) patients remain understudied. METHODS: A cohort study of patients with primary MDR GNB-related bacteremia from the ICU of a tertiary Greek hospital during a 3-year period was conducted for recognition of clinical characteristics and risk factors for adverse outcome. A case-control study was further performed to evaluate risk factors for development of MDR GNB-related primary bacteremia. RESULTS: Fifty monomicrobial episodes of primary bacteremia because of Klebsiella pneumoniae (n = 20), Acinetobacter baumannii (n = 18), and Pseudomonas aeruginosa (n = 12) were recorded. The presence of diabetes mellitus was the only significant risk factor for development of MDR GNB-related primary bacteremia. Most episodes (78%) were ICU acquired in patients with prolonged mechanical ventilation and previous hospitalization in the ward. Mortality was 47.6% vs 19% of controls, P = .01. Mortality was higher in recurrent bacteremia (62.5%). Mortality was statistically associated with age (P = .002) and degree of multiorgan dysfunction expressed by sequential organ failure assessment score on day of bacteremia documentation (P = .001). CONCLUSION: Critically ill patients with MDR GNB-related primary bacteremia present significant mortality mainly associated with age and multiorgan failure. A baumanii bacteremia confers significant mortality compared with the benign course of K pneumoniae in such settings. Diabetes mellitus is a risk factor for development of such episodes, which may, in part, be general ward acquired, underlining the need for expanded vigilance.

Leptospirosis in a European intensive care unit.

We report the first series of indigenous European patients with severe leptospirosis in need of intensive care because of acute respiratory distress syndrome, coma and shock. The all-cause hospital mortality was 16.7%, and may have been influenced by relatively early diagnosis, indicating the need for heightened clinical suspicion in Europe.

Platelet GP IIIA polymorphism HPA-1 (PLA1/2) is associated with hypertension as the primary cause for end-stage renal disease in hemodialysis patients from Greece.

Human platelets carry membrane glycoproteins that control platelet aggregation and activation. A number of clinical studies have suggested that certain polymorphisms of genes encoding these proteins increase the risk for cardiovascular disease. The frequency of gene polymorphisms for the four most common platelet glycoproteins (HPA 1, 2, 3 and 5) was examined and correlated with the primary cause of end-stage renal disease (ESRD) in Greek patients on HD. Fifty-five (55) patients on chronic maintenance haemodialysis (HD) (22 female, 33 male), aged from 23- to 87-years-old, (mean age 66 years), being on dialysis for 53 +/- 34 months, were included in the study. HPA-1, -2, -3, and -5 genotyping was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP). Calculated relative frequencies of the alleles were as follows: HPA-1a/b 0.81/0.19, HPA-2a/b 0.92/0.08, HPA-3a/b 0.62/0.38 and HPA-5a/b 0.93/0.07. There was a statistically significant association between the HPA-1b allele and hypertension as the primary cause of ESRD (65% of patients with hypertension vs 23% of all other patients carried the HPA-1b allele, p=0.02, Fisher's exact test). The results suggest that Greek carriers of the HPA-1b allele with hypertension may be at increased risk for developing end-stage renal disease.

P53Arg72 homozygosity and its increased incidence in left-sided sporadic colorectal adenocarcinomas, in a Greek-Caucasian population.

BACKGROUND: The current case-control study was conducted in order to elucidate any possible association of the single nucleotide polymorphism (SNP) of codon 72 of the p53 gene (Arg72Pro) and sporadic colorectal adenocarcinoma development in a Caucasian population in Greece. The distribution of its alleles, in relation to many clinical parameters of the cancer group, was also investigated. MATERIALS AND METHODS: Genomic DNA samples from 93 sporadic colorectal adenocarcinoma cases and 95 healthy controls (age and ethnicity matched) were used to genotype the p53 codon 72 polymorphism. RESULTS: A strong association of the homozygous 72Arg allele with the development of colorectal cancer was observed (Chi-Square = 11,212, p = 0.001, O.R = 2.902, 95% (CI) = 1.540-5.469, for Arg/Arg vs. Arg/Pro and Pro/Pro). When tumor location was accounted for, the Arg/Arg carrier genotypes were associated with an increased incidence of left colon cancer (Chi-Square = 5.256, p = 0.026, OR = 2.975, 95% (CI) = 1.150-7.699). CONCLUSION: p53Arg homozygosity is associated with the development of sporadic colorectal adenocarcinoma, in the Greek-Caucasian population studied and this polymorphism may have a significant prognostic value, where tumor location is concerned.

Incidence and risk factors of coronary heart disease in elderly patients on chronic hemodialysis.

AIM: To determine the incidence of coronary heart disease (CHD) in patients (pts) over 65 years (y) and its relation to common risk factors. METHODS: We retrospectively studied 128 hemodialysis (HD) pts (80 M and 48 F), mean age 73+/-6.5 years, mean time on HD 44.4+/-26.4 months and BMI 25.4+/-3 kg/m2. They were evaluated for: age, sex, smoking, diabetes, hypertension, left ventricular hypertrophy, secondary hyperparathyroidism (SHP), inflammation, as evidence by elevated level of hsCRP, hyperhomocysteinemia (HOC), time on HD, fluid overload and adequacy of HD. Forty-eight pts (37%) had CAD diagnosed by coronary angiography in 22 (46%) and (201)TL-chloride dipyridamole stress test in 26 (54%). RESULTS: There was a statistically significant correlation between CAD and increasing age (p<0.0001). The relative risk was significantly increased concerning: (1) male over female pts (RR: 1.95, p<0.01), (2) diabetic vs. non diabetic pts (RR: 2.09, p<0.001), (3) patients with SHP over pts with iPTH values<250 pg/ml (RR: 2.16, p<0.001), (4) hypertensive vs. non hypertensive pts (RR: 2.26, p=0.002), (5) smokers vs. non smokers (RR: 1.69, p<0.05), (6) pts with HOC over pts with normal homocysteine values (RR: 2.09, p<0.05), (7) pts with increased CRP levels over pts with normal CRP levels (RR: 1.8, p<0.01), (8) pts undergoing HD for 36 vs. 12 months (RR: 1.71, p=0.03), (9) between pts with inadequate or adequate HD (RR: 1.73, p=0.02). No significant correlation existed between CAD incidence and the other risk factors. CONCLUSIONS: Coronary heart disease incidence in elderly HD patients increases with age, male sex, diabetes, SHP, hypertension, increased CRP levels, HOC, smoking, time on HD and inadequacy of HD.

Clinical effectiveness of leukocyte filtration during cardiopulmonary bypass in patients with chronic obstructive pulmonary disease.

BACKGROUND: We tested the hypothesis that leukocyte filtration during pulmonary reperfusion preserves pulmonary function and results in improved oxygenation after cardiopulmonary bypass (CPB) in patients with chronic obstructive pulmonary disease (COPD). METHODS: In a prospective, randomized study, the treatment group consisted of 20 patients with COPD from consecutive open-heart procedures. A primed leukocyte filter was connected to the arterial line downstream of the standard arterial filter but was excluded from circulation. Circulated blood was directed through the leukocyte filter approximately 10 minutes before aortic cross-clamp removal and at early reperfusion for up to 30 minutes. These patients were compared to 20 additional COPD patients (controls) on whom systemic leukocyte filtration was not used during open-heart surgery. RESULTS: There was no significant difference in gender, age, left ventricular ejection fraction, type of procedure, aortic cross-clamp time, perfusion time, preoperative FEV1 and preoperative respiratory index (Pao2/FiO2 ratio) between treatment and control groups. The respiratory index changed in the treatment group by +9.8% of baseline after completion of CPB, by -14.2% upon arrival in the intensive care unit (ICU), and by -19.6% 12 hours later, whereas in the control group, it changed by -14.5% (p < 0.05), -27.7%, and -24%, respectively. Leukocyte-depleted patients required shorter intubation time (20.4 +/- 16.1 hours), ICU stay (46.2 +/- 40.1 hours) and length of hospitalization (8.3 +/- 2.8 days) than controls (29.5 +/- 21.9 hours, p < 0.05; 75.5 +/- 34.9 hours, p < 0.005; and 10.4 +/- 3.5 days, p < 0.05, respectively). Surgical (30-day) mortality was zero in both groups. CONCLUSIONS: In COPD patients having CPB, systemic leukocyte depletion at early reperfusion was associated with better oxygenation, shorter intubation time, and shorter ICU and hospital stays. Leukocyte filtration during CPB most likely preserves pulmonary function by ameliorating pulmonary reperfusion injury.

Neutrophil depletion reduces myocardial reperfusion morbidity.

BACKGROUND: We tested the hypothesis that depletion of neutrophil leukocytes from the cardioplegic and the initial myocardial reperfusion perfusates reduces clinical indices of reperfusion injury in patients undergoing elective coronary artery bypass. METHODS: We studied 160 consecutive patients who underwent standard coronary revascularization with cardiopulmonary bypass. Patients with recent myocardial infarction or coronary angioplasty were excluded. Cold blood cardioplegia was used. Just before aortic unclamping, the hearts were perfused retrograde with 250 mL of normothermic cardioplegic solution and 750 mL of blood (pump perfusate). Patients were randomly assigned to two groups. In 80 patients (treated), neutrophils and platelets were removed from all cardiac perfusate during aortic crossclamping with leukocyte filtration. In the remaining 80 patients (control group), leukocyte filtration was not used. RESULTS: There was no significant difference between groups in age, sex, severity of disease, and number of bypass grafts implanted. Treated patients showed lower prevalence of low cardiac index and reperfusion ventricular fibrillation and lower levels of creatinine kinase MB isoenzyme and troponin I early postoperatively (p < 0.05). CONCLUSIONS: Neutrophil-filtered blood cardioplegia/reperfusion significantly reduced clinical and biochemical indices of myocardial reperfusion injury after elective coronary revascularization with cardiopulmonary bypass.

Targeted gene delivery to vascular tissue in vivo by tropism-modified adeno-associated virus vectors.

BACKGROUND: Gene therapy offers an unprecedented opportunity to treat diverse pathologies. Adeno-associated virus (AAV) is a promising gene delivery vector for cardiovascular disease. However, AAV transduces the liver after systemic administration, reducing its usefulness for therapies targeted at other sites. Because vascular endothelial cells (ECs) are in contact with the bloodstream and are heterogeneous between organs, they represent an ideal target for site-specific delivery of biological agents. METHODS AND RESULTS: We isolated human venous EC-targeting peptides by phage display and genetically incorporated them into AAV capsids after amino acid 587. Peptide-modified AAVs transduced venous (but not arterial) ECs in vitro, whereas hepatocyte transduction was significantly lower than with native AAV. Intravenous infusion of engineered AAVs into mice produced reduced vector accumulation in liver measured 1 hour and 28 days after injection and delayed blood clearance rates compared with native AAV. Peptide-modified AAVs produced enhanced uptake of virions in the vena cava with selective transgene expression. Retargeting was dose dependent, and coinfusion of either heparin or free competing peptides indicated that uptake was principally independent of native AAV tropism and mediated via the peptide. CONCLUSIONS: AAV tropism can be genetically engineered by use of phage display-derived peptides to generate vectors that are selective for the vasculature.

A prospective, double-blind study on the efficacy of the bioline surface-heparinized extracorporeal perfusion circuit.

BACKGROUND: We evaluated the newly introduced Bioline heparin coating and tested the hypothesis that surface heparinization limited to the oxygenator and the arterial filter will ameliorate systemic inflammation and preserve platelets during cardiopulmonary bypass (CPB). METHODS: In a prospective double-blind study, 159 patients underwent coronary revascularization using closed-system CPB with systemic heparinization, mild hypothermia (33 degrees C), a hollow-fiber oxygenator, and an arterial filter. The patients were randomly divided in three groups. In group A (controls, n = 51), surface heparinization was not used. In group B (n = 52), the extracorporeal circuits were totally surface-heparinized with Bioline coating. In group C (n = 56), surface heparinization was limited to oxygenator and arterial filter. RESULTS: No significant difference was noted in patient characteristics and operative data between groups. Operative (30-day) mortality was zero. Platelet counts dropped by 12.3% of pre-CPB value among controls at 15 minutes of CPB, but were preserved in groups B and C throughout perfusion (p = 0.0127). Platelet factor 4, plasmin-antiplasmin levels, and tumor necrosis factor-alpha increased more in controls during CPB than in groups B or C (p = 0.0443, p = 0.0238 and p = 0.0154 respectively). Beta-thromboglobulin, fibrinopeptide-A, prothrombin fragments 1 + 2, factor XIIa levels, bleeding times, blood loss, and transfusion requirements were similar between groups. Intensive care unit stay was shorter in groups B and C than in controls (p = 0.037). CONCLUSIONS: Surface heparinization with Bioline coating preserves platelets, ameliorates the inflammatory response and is associated with a reduced fibrinolytic activity during CPB. Surface heparinization limited to the oxygenator and the arterial filter had similar results as totally surface-heparinized circuits.

Fractional allele loss is a valuable marker for human lung cancer detection in sputum.

Using PCR-based microsatellite DNA analysis with 48 markers we examined sputum and bronchial washing for genetic alterations compared with lymphocyte extracted DNA from 124 lung cancer patients and 36 healthy donors as normal control. Microsatellite alterations (MA) in at least one locus were detected in all cancer patient-derived specimens but only in 22.2% of the healthy donors. Loss of heterozygosity (LOH) was detected in bronchial washings from 101 non-small cell lung cancer (NSCLC) predominantly on 17p13.1-p13.3 (69.7%), 9p13.3-p24.1 (63.3%), 1p34.2-p36.22 (48.5%), 13q12.1-q13.1 (47.7%) and 3p22.3-p23 (42.7%). In bronchial washings from 23 small cell lung cancer (SCLC) LOH was detected mostly on 3p22.3-p23 (88.6%), 17p13.1-p13.2 (82.3%), 5q32-q33.1 (66.6%), 13q12.2-q13.1 (65.6%) and 9q22.33-q31.3 (52.9%). The different LOH patterns indicate that different genetic background may be responsible for the different physiology of NSCLC and SCLC. The fractional allele loss (FAL) mean value of all cancer specimens was 0.243+/-0.021 compared with 0.007+/-0.008 of healthy donors with a confidence interval (CI) 99.5%. Only seven out of 124 lung cancer specimens (5.2%) exhibited FAL value less than 0.083, the highest was observed in the healthy donors group. FAL appears to be a likely indicator for lung cancer detection. Microsatellite instability (MIN) was detected in 8.7% of SCLC and 4.0% of NSCLC bronchial washings in at least three loci tested. LOH and MIN detection in sputum and bronchial washing from the same patient was 77.6%. Calculation of these indexes per marker exhibits significant variations that could be attributed to diffuse lung disorders or non-cancer specific genetic alterations.