Addressing Sexually Transmitted Infections Due to Neisseria gonorrhoeae in the Present and Future.

It was in the 1800s when the first public publications about the infection and treatment of gonorrhoea were released. However, the first prevention programmes were only published a hundred years later. In the 1940s, the concept of vaccination was introduced into clinical prevention programmes to address early sulphonamide resistance. Since then, tons of publications on Neisseria gonorrhoeae are undisputed, around 30,000 publications today. Currently, the situation seems to be just as it was in the last century, nothing has changed or improved. So, what are we doing wrong? And more importantly, what might we do? The review presented here aims to review the current situation regarding the resistance mechanisms, prevention programmes, treatments, and vaccines, with the challenge of better understanding this special pathogen. The authors have reviewed the last five years of advancements, knowledge, and perspectives for addressing the Neisseria gonorrhoeae issue, focusing on new therapeutic alternatives.

Mycoplasma pneumoniae at the rise not only in China: rapid increase of Mycoplasma pneumoniae cases also in Spain.

After the use of facemasks, other isolation measures enacted during the SARS-CoV-2 pandemic were lifted, respiratory pathogens, such as RSV, reappeared, but until the November 2023 WHO alert for China, M. pneumoniae had virtually disappeared. After observing a similar reappearance in our hospital, a retrospective analysis of the number of positive M. pneumoniae tests. Between 2018 and December 2023, 1619 PCR tests were ordered and 43 (2.6%) of them were positive. Two outbreaks, one in 2018 and one in 2023, accounted for the majority of cases. Tests were usually ordered in an outpatient setting (53.54%, n = 23) and most of them were paediatric patients with a mean age (sd) of 10.2 (6.2) years. As for the severity of the cases, in the 2018 outbreak, of 15 children who tested positive, 53.3% (n = 8) were admitted to the ward and 6.7% (n = 1) at the intensive care unit. Whereas in 2023, 2 patients were tested in the ward (10.5%) and one in the intensive care unit (5.2%) from a total of 19 patients. The positive rate in 2023 was significantly higher in comparison with years 2020, 2021 and 2022 and significantly lower in comparison with 2018 (P-value=0.003). The outbreak in late 2023 can be explained by the seasonality of Mycoplasma pneumonia alone, which has shown outbreaks every 3-5 years, and it does not appear to be more severe than the previous one.

Diagnóstico y tratamiento quirúrgico de una paciente con una neoplasia trofoblástica gestacional / Diagnosis and surgical treatment of a patient with gestational trophoblastic neoplasia

Resumen ANTECEDENTE: La neoplasia trofoblástica gestacional forma parte del grupo de afecciones derivadas de la proliferación anómala del trofoblasto con capacidad para invasión y metástasis. CASO CLÍNICO: Paciente de 42 años, asintomática, con sospecha ecográfica de mola hidatiforme. El legrado uterino y el estudio anatomopatológico confirmaron el diagnóstico de mola hidatiforme completa. Con la cuantificación consecutiva de tres elevaciones de la β-HCG se diagnosticó: neoplasia trofoblástica gestacional. Se estadificó en estadio I, bajo riesgo y ante el deseo genésico satisfecho la paciente aceptó la histerectomía más salpingectomía bilateral. En el seguimiento posterior la paciente se encontró asintomática, con determinaciones seriadas de b-HCG negativa y ecografías vaginales sin hallazgos. CONCLUSIÓN: La histerectomía con salpingectomía bilateral puede ser el tratamiento definitivo en casos seleccionados de neoplasia trofoblástica. La evidencia disponible es escasa, por lo que es necesario seguir investigando en este campo.

Abstract BACKGROUND: Gestational trophoblastic neoplasia is one of a group of conditions resulting from abnormal trophoblast proliferation with capacity for invasion and metastasis. CLINICAL CASE: 42-year-old asymptomatic patient with ultrasound suspicion of hydatidiform mole. Uterine curettage and anatomopathological study confirmed the diagnosis of complete hydatidiform mole. With the consecutive quantification of three elevations of β-HCG a diagnosis of gestational trophoblastic neoplasia was made. It was staged as stage I, low-risk, and the patient agreed to hysterectomy plus bilateral salpingectomy. At subsequent follow-up the patient was found to be asymptomatic, with negative serial determinations of β-HCG and vaginal ultrasound scans without findings. CONCLUSION: Hysterectomy with bilateral salpingectomy may be the definitive treatment in selected cases of trophoblastic neoplasia. The available evidence is scarce and further research is needed in this field.

Psychosomatic response to acute emotional stress in healthy students.

The multidimensionality of the stress response has shown the complexity of this phenomenon and therefore the impossibility of finding a unique biomarker among the physiological variables related to stress. An experimental study was designed and performed to guarantee the correct synchronous and concurrent measure of psychometric tests, biochemical variables and physiological features related to acute emotional stress. The population studied corresponds to a group of 120 university students between 20 and 30 years of age, with healthy habits and without a diagnosis of chronic or psychiatric illnesses. Following the protocol of the experimental pilot, each participant reached a relaxing state and a stress state in two sessions of measurement for equivalent periods. Both states are correctly achieved evidenced by the psychometric test results and the biochemical variables. A Stress Reference Scale is proposed based on these two sets of variables. Then, aiming for a non-invasive and continuous approach, the Acute Stress Model correlated to the previous scale is also proposed, supported only by physiological signals. Preliminary results support the feasibility of measuring/quantifying the stress level. Although the results are limited to the population and stimulus type, the procedure and methodological analysis used for the assessment of acute stress in young people can be extrapolated to other populations and types of stress.

Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection.

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).

Photoplethysmographic Waveform Analysis for Autonomic Reactivity Assessment in Depression.

OBJECTIVE: In the present study, a photoplethysmographic (PPG) waveform analysis for assessing differences in autonomic reactivity to mental stress between patients with Major Depressive Disorder (MDD) and healthy control (HC) subjects is presented. METHODS: PPG recordings of 40 MDD and 40 HC subjects were acquired at basal conditions, during the execution of cognitive tasks, and at the post-task relaxation period. PPG pulses are decomposed into three waves (a main wave and two reflected waves) using a pulse decomposition analysis. Pulse waveform characteristics such as the time delay between the position of the main wave and reflected waves, the percentage of amplitude loss in the reflected waves, and the heart rate (HR) are calculated among others. The intra-subject difference of a feature value between two conditions is used as an index of autonomic reactivity. RESULTS: Statistically significant individual differences from stress to recovery were found for HR and the percentage of amplitude loss in the second reflected wave ( A13) in both HC and MDD group. However, autonomic reactivity indices related to  A13 reached higher values in HC than in MDD subjects (Cohen's [Formula: see text]), implying that the stress response in depressed patients is reduced. A statistically significant ( ) negative correlation ( r=-0.5) between depression severity scores and A13 was found. CONCLUSION: A decreased autonomic reactivity is associated with higher degree of depression. SIGNIFICANCE: Stress response quantification by dynamic changes in PPG waveform morphology can be an aid for the diagnosis and monitoring of depression.

Pain in Older Adults With Dementia: A Survey in Spain.

The risk of suffering pain increases significantly throughout life, reaching the highest levels in its latest years. Prevalence of pain in nursing homes is estimated to range from 40 to 80% of residents, most of them old adults affected with dementia. It is already known that pain is under-diagnosed and under-treated in patients with severe cognitive impairment and poor/absent verbal communication, resulting in a serious impact on their quality of life, psychosocial, and physical functioning. Under-treated pain is commonly the cause of behavioral symptoms, which can lead to misuse of antipsychotic treatments. Here, we present two Regional and National Surveys in Spain (2015-2017) on the current practices, use of observational tools for pain assessment, guidelines, and policies. Results, discussed as compared to the survey across central/north Europe, confirm the professional concerns on pain in severe dementia, due to poor standardization and lack of guidelines/recommendations. In Spain, observational tools are scarcely used because of their difficulty and low reliability in severe dementia, since the poor/absent verbal communication and comprehension are considered limiting factors. Behavioral observation tools should be used while attending the patients, in a situation including rest and movement, should be short (3-5 min) and scored using a numeric scale. Among the pain items to score, "Facial expression" and "Verbalization" were considered essential and very useful, respectively. This was in contrast to "Body movements" and "Vocalizations," respectively, according to the survey in central/north Europe. Scarce time availability for pain assessment and monitoring, together with low feasible and time-consuming tools, can make pain assessment a challenge. The presence of confounding factors, the low awareness and poor knowledge/education of specific tools for this population are worrisome. These complaints draw future directions to improve pain assessment. More time available, awareness, and involvement of the teams would also benefit pain assessment and management in cognitive impairment. The experiences and opinions recorded in these surveys in Spain and other E.U. countries were considered sources of knowledge for designing the "PAIC-15 scale," a new internationally agreed-on meta-tool for Pain Assessment in Impaired Cognition and the "Observational pain assessment" in older persons with dementia.

A multicentre prospective study evaluating the impact of proton-pump inhibitors omeprazole and pantoprazole on voriconazole plasma concentrations.

Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantoprazole (n = 25), esomeprazole (n = 3) and no PPI (n = 18). Patients with no PPI had no significant difference in plasma voriconazole concentration when compared with those with PPI (2.63 ± 2.13 µg/mL [95% confidence interval {CI} 1.57-3.69] vs 2.11 ± 1.73 µg/mL [95%CI 1.67-2.55], P > .05). However, voriconazole plasma concentration was significantly lower in patients treated with pantoprazole vs those treated with omeprazole (1.44 ± 1.22 µg/mL [95%CI 0.94-1.94) vs 2.67 ± 1.88 µg/mL [95%CI 2.02-3.32], P = .013) suggesting a greater CYP2C19 enzyme inhibitory effect of omeprazole. This study demonstrates the greater CYP inhibition capacity of omeprazole and should be helpful for the choice of PPIs for patients treated with voriconazole.

Clinical factors associated with pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. / Factores clínicos asociados a enfermedad pulmonar por Aspergillus spp. en pacientes con enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To explore the clinical and epidemiological characteristics of chronic obstructive pulmonary disease (COPD) patients with Aspergillus spp. isolation from respiratory samples, and to identify which factors may help us to distinguish between colonisation and infection. METHODS: A retrospective cohort study was performed. All patients with COPD and respiratory isolation of Aspergillus spp. over a 12-year period were included. Patients were assigned to 2 categories: colonisation and pulmonary aspergillosis (PA), which includes the different clinical forms of aspergillosis. A binary logistic regression model was performed to identify the predictive factors of PA. RESULTS: A total of 123 patients were included in the study: 48 (39.0%) with colonisation and 75 (61.0%) with PA: 68 with probable invasive pulmonary aspergillosis and 7 with chronic pulmonary aspergillosis. Spirometric stages of the GOLD classification were not correlated with a higher risk of PA. Four independent predictive factors of PA in COPD patients were identified: home oxygen therapy (OR: 4.39; 95% CI: 1.60-12.01; P=.004), bronchiectasis (OR: 3.61; 95% CI: 1.40-9.30; P=.008), hospital admission in the previous three months (OR: 3.12; 95% CI: 1.24-7.87; P=.016) and antifungal therapy against Candida spp. in the previous month (OR: 3.18; 95% CI: 1.16-8.73; P=.024). CONCLUSIONS: Continuous home oxygen therapy, bronchiectasis, hospital admission in the previous three months and administration of antifungal medication against Candida spp. in the previous month were associated with a higher risk of pulmonary aspergillosis in patients with COPD.

Impact of CYP2C19 Genotype and Drug Interactions on Voriconazole Plasma Concentrations: A Spain Pharmacogenetic-Pharmacokinetic Prospective Multicenter Study.

BACKGROUND: Voriconazole, a first-line agent for the treatment of invasive fungal infections, is mainly metabolized by cytochrome P450 (CYP) 2C19. A significant portion of patients fail to achieve therapeutic voriconazole trough concentrations, with a consequently increased risk of therapeutic failure. OBJECTIVE: To show the association between subtherapeutic voriconazole concentrations and factors affecting voriconazole pharmacokinetics: CYP2C19 genotype and drug-drug interactions. METHODS: Adults receiving voriconazole for antifungal treatment or prophylaxis were included in a multicenter prospective study conducted in Spain. The prevalence of subtherapeutic voriconazole troughs was analyzed in the rapid metabolizer and ultra-rapid metabolizer patients (RMs and UMs, respectively), and compared with the rest of the patients. The relationship between voriconazole concentration, CYP2C19 phenotype, adverse events (AEs), and drug-drug interactions was also assessed. RESULTS: In this study 78 patients were included with a wide variability in voriconazole plasma levels with only 44.8% of patients attaining trough concentrations within the therapeutic range of 1 and 5.5 µg/ml. The allele frequency of *17 variant was found to be 29.5%. Compared with patients with other phenotypes, RMs and UMs had a lower voriconazole plasma concentration (RM/UM: 1.85 ± 0.24 µg/ml vs other phenotypes: 2.36 ± 0.26 µg/ml). Adverse events were more common in patients with higher voriconazole concentrations (p<0.05). No association between voriconazole trough concentration and other factors (age, weight, route of administration, and concomitant administration of enzyme inducer, enzyme inhibitor, glucocorticoids, or proton pump inhibitors) was found. CONCLUSION: These results suggest the potential clinical utility of using CYP2C19 genotype-guided voriconazole dosing to achieve concentrations in the therapeutic range in the early course of therapy. Larger studies are needed to confirm the impact of pharmacogenetics on voriconazole pharmacokinetics.

An Observational Study of the Efficacy and Safety of Voriconazole in a Real-Life Clinical Setting.

An observational retrospective study in patients treated with voriconazole was made to evaluate outcomes, safety, drug interactions and characteristics of the treatment. A total of 96 patients were included. In 78.12%, at least one inducer or enzyme inhibitor was detected. The most frequently observed potential interaction was the simultaneous administration of omeprazole. A large number of patients were concurrently treated with corticosteroids. The simultaneous administration of drugs acting as CYP450 enzyme inhibitors was associated with a higher risk of toxicity while concomitant administration of corticosteroids seemed a protective factor. Our study is one of the few ones, which evaluate the use of voriconazole in a real life clinical setting. We demonstrate the wide variety of strategies in the voriconazole using and the large number of dugs that are susceptible to pharmacokinetic interactions. This study reinforces the need to implement voriconazole pharmacokinetic monitoring in order to optimize antifungal treatment.

Personalized medicine into health national services: barriers and potentialities.

Research and innovation in personalized medicine (PM) are extensive and expanding, with several pharmacogenetic/pharmacogenomic (PGx) testing options currently available for a wide range of health problems. However, PGx-guided therapy faces many barriers to full integration into clinical practice and acceptance by practitioner/patient: utilization and uptake by payers in real-world practice are being discussed, and the criteria to guide clinicians and policy makers in PGx test selection are not fully incorporated. This review focuses on the advances of pharmacogenomics to individualize treatments, the relationship between pharmacogenetics and pharmacometabolomics, the new paradigm of the Big Data, the needs and barriers facing PGx clinical application and the situation of PGx testing in health national services. It is based on lectures presented by speakers of the European Society of Pharmacogenomics and Personalised Therapy (ESPT) Fourth Conference, held in Catania, October 4th, 2017.

Kidney-specific genetic deletion of both AMPK α-subunits causes salt and water wasting.

AMP-activated kinase (AMPK) controls cell energy homeostasis by modulating ATP synthesis and expenditure. In vitro studies have suggested AMPK may also control key elements of renal epithelial electrolyte transport but in vivo physiological confirmation is still insufficient. We studied sodium renal handling and extracellular volume regulation in mice with genetic deletion of AMPK catalytic subunits. AMPKα1 knockout (KO) mice exhibit normal renal sodium handling and a moderate antidiuretic state. This is accompanied by higher urinary aldosterone excretion rates and reduced blood pressure. Plasma volume, however, was found to be increased compared with wild-type mice. Thus blood volume is preserved despite a significantly lower hematocrit. The lack of a defect in renal function in AMPKα1 KO mice could be explained by a compensatory upregulation in AMPK α2-subunit. Therefore, we used the Cre-loxP system to knock down AMPKα2 expression in renal epithelial cells. Combining this approach with the systemic deletion of AMPKα1 we achieved reduced renal AMPK activity, accompanied by a shift to a moderate water- and salt-wasting phenotype. Thus we confirm the physiologically relevant role of AMPK in the kidney. Furthermore, our results indicate that in vivo AMPK activity stimulates renal sodium and water reabsorption.

Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation.

Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

Pleural antigen assay in the diagnosis of pediatric pneumococcal empyema.

PURPOSE: The purpose of the study was to assess the diagnostic value of rapid pneumococcal antigen detection (PAD) in pleural fluid samples of children with empyema. MATERIAL AND METHODS: We performed a prospective evaluation in a pediatric intensive care unit of a tertiary university hospital of children aged 1 month to 14 years admitted with empyema. Standard cultures (conventional microbiological culture [CMC]), PAD by immunochromatographic testing (Binax NOW Streptococcus pneumoniae; Binax, Portland, ME), and/or real-time polymerase chain reactions (RTPs) on pleural samples were performed in all included patients. RESULTS: Fifty-five cases with a mean (SD) age of 6.5 (6.1) years were enrolled. Streptococcus pneumoniae was identified in 28 cases (51%): by CMC in 15 cases and by RTP in a further 13 cases. Using CMC and/or RTP as the criterion standard, PAD showed a sensitivity of 96% (95% confidence interval, 86%-100%), a specificity of 100% (75%-100%), a positive predictive value of 100% (98%-100%), and a Youden index of 0.96 (0.88-1.04). CONCLUSIONS: Pneumococcal antigen detection in pleural fluid specimens from children provides a rapid, simple, sensitive, and reliable method of diagnosis for pneumococcal empyema at bedside.

[Pandoraea sputorum colonization in a patient with cystic fibrosis]. / Colonización por Pandoraea sputorum en un paciente con fibrosis quística.

Cystic fibrosis (CF) is a disease produced by a defect in the transmembrane conductance regulator protein, CFTR. Currently, the morbidity and mortality associated with CF are fundamentally related with the lung affectation that is a consequence of this defect. With the progression of the disease, there is an increase in the isolation of non-fermenting gram-negative bacilli colonizing these patients. The genus Pandoraea arises from a reclassification of species included within the "Burkholderia cepacia complex". It is made up of 9 species susceptible only to tetracycline, imipenem and cotrimoxazole. We report the first clinical case in Spain of colonization by Pandoraea sputorum in a patient diagnosed with CF at the age of eleven. After several previous colonizations by different Pseudomonas species in September 2005, a gram-negative bacillus was isolated in sputum, which was identified by sequencing and mass spectrometry (MALDITOF-MS) as P. sputorum, only sensitive to piperacillin-tazobactam, cotrimoxazole and imipenem. From 2005 to 2008, chronic colonization by this microorganism was associated with deterioration in lung function that was recuperated after treatment with piperacillin-tazobactam and imipenem. In 2010, this microorganism was once again isolated and treated with imipenem, to which the patient responded favorably. Currently, it is not known whether this microorganism is a chronic colonizer, whether it produces a transitory infection or whether it constitutes an important problem in CF patients, but given its special characteristics of sensitivity to anti-microbial drugs, the correct identification of this genus is essential. Mass spectrometry seems to be a valid technique that is faster than sequencing methods for identifying these species.

Immunophenotype and gene expression profiles of cell surface markers of mesenchymal stem cells derived from equine bone marrow and adipose tissue.

Bone marrow and adipose tissue are the two main sources of mesenchymal stem cell (MSC). The aim of this work was to analyse the immunophenotype of 7 surface markers and the expression of a panel of 13 genes coding for cell surface markers in equine bone marrow and adipose tissue-derived MSCs obtained from 9 horses at third passage. The tri-lineage differentiation was confirmed by specific staining. Equine MSCs from both sources were positive for the MSC markers CD29 and CD90, while were negative for CD44, CD73, CD105, CD45 and CD34. The gene expression of these molecules was also evaluated by reverse transcriptase real-time quantitative PCR along with the expression of 5 other MSC markers. Both populations of cells expressed CD13, CD29, CD44, CD49d, CD73, CD90, CD105, CD106, CD146 and CD166 transcripts. Significant differences in gene expression levels between BM- and AT-MSCs were observed for CD44, CD90, CD29 and CD34. Both cell types were negative for CD45 and CD31. The surface antigens tested revealed a similar phenotypic profile between horse and human MSCs, although specific differences in some surface antigens were noticed.

Expression of CYP2W1 in colon tumors: regulation by gene methylation.

INTRODUCTION: CYP2W1 is a novel enzyme shown to be selectively expressed in rat fetal colon and in human colon cancer and has previously been suggested as a potential drug target for cancer therapy. Here, the expression and gene methylation of CYP2W1 were analyzed in human colon carcinoma cell lines, colon tumors and in corresponding normal colon tissue. METHODS: CYP2W1 mRNA and protein expression in HepG2 and Caco-2TC7 cells and normal colon and colon tumor tissue samples were analyzed using real-time PCR and Western blotting. CYP2W1 gene methylation status in the same samples was analyzed using the sodium bisulfite sequencing method. RESULTS & DISCUSSION: CYP2W1 mRNA was detected in all (n = 39) tumor samples analyzed. Moreover, in 60% (12/20) of the colon tumors, CYP2W1 mRNA levels were substantially higher than in corresponding normal tissues. CYP2W1 protein was detected in most of the colon tumor samples analyzed (n = 16), which appeared to be of two apparent phenotypes: those with five- to ten-fold induced CYP2W1 (approximately 50% of the tumors), and those with low expression, harboring similar or only slightly higher amounts of CYP2W1 as compared with surrounding control tissue. Methylation analysis of the CpG island in the exon 1-intron 1 junction of the CYP2W1 gene from both cell lines, tumors and normal tissues revealed that demethylated CpG dinucleotides appeared as a requirement for high CYP2W1 gene expression. CONCLUSION: The expression of CYP2W1 is colon tumor-specific and is associated with methylation status of the CYP2W1 gene, suggesting a potential causal link between the gene hypomethylation and its enhanced expression.