Molecular identification and in vitro assessment of zoonotic-potential of a novel Orthobunyavirus isolated from broiler chicken in Malaysia.

We have previously isolated a novel avian Orthobunyavirus, Kedah Fatal Kidney Syndrome (KFKS) virus from a broiler farm in Kedah, Malaysia in 2020 with a severe kidney lesion in chickens. The virus was designated as KFKS2_CS virus. Sequence analysis of partial nucleocapsid (N) and nonstructural (NSs) sequence of this virus showed the highest sequence identity with previous KFKS1 from Malaysia (100%) and 97% with a zoonotic Umbre (UMB) virus, which was reported to cause encephalitis in immunocompromised humans in India. Phylogenetic analysis revealed that this virus was clustered together with previous KFKS1 virus from Malaysia, UMB and Cristoli viruses. This study aimed to assess the zoonotic potential of this KFKS2_CS virus in vitro by determining its ability to inhibit the production of interferon (IFN) in human glioblastoma multiforme (GBM) brain cells using reverse-transcriptase polymerase reaction (RT-PCR). This virus blocked the production of interferon-a in this human brain cells. In conclusion, this KFKS2_CS virus may have a zoonotic potential and become a public health concern in the future.

Molecular identification and in vitro assessment of zoonotic-potential of a novel Orthobunyavirus isolated from broiler chicken in Malaysia

@#We have previously isolated a novel avian Orthobunyavirus, Kedah Fatal Kidney Syndrome (KFKS) virus from a broiler farm in Kedah, Malaysia in 2020 with a severe kidney lesion in chickens. The virus was designated as KFKS2_CS virus. Sequence analysis of partial nucleocapsid (N) and nonstructural (NSs) sequence of this virus showed the highest sequence identity with previous KFKS1 from Malaysia (100%) and 97% with a zoonotic Umbre (UMB) virus, which was reported to cause encephalitis in immunocompromised humans in India. Phylogenetic analysis revealed that this virus was clustered together with previous KFKS1 virus from Malaysia, UMB and Cristoli viruses. This study aimed to assess the zoonotic potential of this KFKS2_CS virus in vitro by determining its ability to inhibit the production of interferon (IFN) in human glioblastoma multiforme (GBM) brain cells using reverse-transcriptase polymerase reaction (RT-PCR). This virus blocked the production of interferon-a in this human brain cells. In conclusion, this KFKS2_CS virus may have a zoonotic potential and become a public health concern in the future.

Sero-prevalence of and risk factors associated with Helicobacter pylori infections among individuals with peptic ulcer in Owerri, Imo State, Nigeria during 2020-2021

Background: Helicobacter pylori, which is a causative agent of chronic gastritis, duodenal ulcer and gastric cancer, presently affects approximately one half of the world population. This study was conducted to assess the epidemiology and risk factors for acquisition of H. pylori among individuals with and without peptic ulcer symptoms in Owerri, Nigeria, in order to provide baseline data and create awareness for effective management and prevention of infection caused by this pathogen. Methodology: A total of 384 participants, symptomatic and asymptomatic for peptic ulcer, were recruited from the three Local Government Areas (LGAs) of Owerri, Imo State, Nigeria. The symptomatic participants were randomly recruited among patients attending outpatient clinics with symptoms of peptic ulcer disease at the Federal Medical Center Owerri, general hospitals and primary healthcare centers across Owerri LGAs, while asymptomatic patients were recruited from the community. Information on socio-demographic characteristics of each participant and potential risk factors were collected with a pre-tested structured questionnaire. Blood samples were collected for detection of antibodies (IgG) using a one-step H. pylori test device while faecal samples were collected for detection of occult blood (from peptic ulceration) using faecal occult blood (FOB) test. Data were analyzed using SPSS version 25.0 and association of risk factors with H. pylori sero-prevalence was determined by the Chi-square or Fisher Exact test (with Odds ratio). P value < 0.05 was considered statistically significant.Results: The sero-prevalence of H. pylori infection among the study participants was 72.4% (285/384) while the prevalence of ulcer by FOB test was 71.1% (273/384). A total of 78.4% (214/273) of those with ulcers were seropositive for H. pylori while 64.0% (71/111) of those without ulcers were sero-positive for H. pylori (p=0.0045).Factors significantly associated with high sero-prevalence of H. pyloriwere age groups 41-50 (100%), 21-30 (78.4%) and 31-40 (67.6%) years (X 2=66.964, p<0.0001), illiteracy (OR=6.888, p<0.0001), unemployment (OR=2.427, p<0.0001), low social class status (X2=28.423, p=0.0003), drinking of unclean water (OR=5.702, p<0.0001), living in crowded rooms (OR=2.720, p<0.0001), eating food bought from food vendors (OR=3.563, p<0.0001), family history of ulcer (OR=12.623, p<0.0001), habits of eating raw vegetables and unwashed fruits (OR=6.272, p<0.0001), non-regular hand washing practices before meal (OR=2.666, p<0.0001) and presence of ulcer (OR=2.043, p=0.0045). However, smoking (OR=0.7581, p=0.2449) and gender (OR=0.6538, p=0.0796) were not significantly associated with sero-prevalence of H. pylori. Conclusion: There is need for comprehensive strategy including public health education campaign to create awareness on H. pylori, improve personal hygiene and environmental sanitation, provision of safe drinking water by the government to the populace, and discourage indiscriminate and open defecation

Antibiotic resistance, putative virulence factors and curli fimbrination among Cronobacter species.

This study aimed to investigate antibiotic resistance and putative virulence factors among Cronobacter sakazakii isolated from powdered infant formula and other sources. The following 9 cultures (CR1-9) were collected from our culture collection: C. sakazakii and 3 Cronobacter species: C. sakazakii ATCC® 29544™, C. muytjensii ATCC® 51329™, C. turicensis E866 were used in this study. Isolates were subjected to antibiotic susceptibility and the following virulence factors (protease, DNase, haemolysin, gelatinase, motility and biofilm formation) using phenotypic methods. All the bacteria were able to form biofilm on agar at 37 °C and were resistant to ampicillin, erythromycin, fosfomycin and sulphamethoxazole. It was observed from this study that tested strains formed weak and strong biofilm with violet dry and rough (rdar), brown dry and rough (bdar), red mucoid and smooth (rmas) colony morphotypes on Congo red agar. Rdar expresses curli and fimbriae, while bdar expresses curli. Both biofilm colony morphotypes are commonly found in Enterobacteriaceae including Salmonella species. This study also reveals a new colony morphotypes in Cronobacter species. Conclusively, there was correlation between putative virulence factors and antibiotic resistance among the tested bacteria. Further study on virulence and antibiotic resistance genes is hereby encouraged.

Electrocardiographic alterations in patients consuming synthetic cannabinoids.

INTRODUCTION: The aim of this study was to investigate the electrocardiographic parameters in patients consuming synthetic cannabinoids. METHODS: Thirty-five patients who were consuming synthetic cannabinoids were enrolled to the study, prospectively. The control group included 35 healthy age and sex-matched volunteers. The standard 12-lead surface electrocardiograms of the study population were recorded. P maximum (Pmax), P minimum (Pmin), P wave dispersion, interatrial duration, P wave area in D2 derivation, abnormal P terminal force in V1 derivation, heart rate, QT interval, corrected QT, QT dispersion, PR interval duration and macrovolt T-wave alternans were evaluated by two experienced cardiologists. The intra-observer and inter-observer variations for all measurements were non-significant. RESULTS: Pmax and Pmin duration was not different between the groups ( p=0.96, p=0.15, respectively). However, P wave dispersion was higher in the patient group compared to control group (34±9.4, 29.5±6.6, p=0.02, respectively). QT interval was significantly higher in the patient group than the control group (380.3±25, 365.6±22.8, p=0.01, respectively). Besides, corrected QT was higher in the patient group compared to control group (415±36.8, 392±15.5, p=0.001, respectively). QT dispersion was also higher in the patient group than the control group (39.8±10.0, 29.2±5.4, p<0.001, respectively). CONCLUSION: Altered electrocardiography parameters linked with atrial and ventricular arrhythmia development may be observed in patients consuming synthetic cannabinoids. These patients should be evaluated regularly for cardiovascular disease and arrhythmia development. The electrocardiogram, which is a cheap and easy test to apply, can be used to determine the pro-arrythmic risk in patients consuming synthetic cannabinoids.

Elevated serum fibrinogen levels and risk of contrast-induced acute kidney injury in patients undergoing a percutaneous coronary intervention for the treatment of acute coronary syndrome.

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is a common complication of diagnostic and therapeutic catheterizations, especially in the setting of acute coronary syndrome (ACS). Fibrinogen is a well-known cardiovascular risk factor. We evaluated whether serum fibrinogen level is associated independently with CI-AKI in patients with ACS who underwent a percutaneous coronary intervention (PCI). METHODS: Patients (n=710, aged 61 ± 13, 69% men) were classified into two groups: CI-AKI and non-CI-AKI. CI-AKI was defined as an increase of at least 0.5 mg/dl or at least 25% in the serum creatinine level within 72 h following PCI. RESULTS: CI-AKI occurred in 75 (10.6%) patients. We found significantly higher serum fibrinogen levels in patients who developed CI-AKI than in those who did not (498 ± 152 vs. 386 ± 96 mg/dl, P<0.001). Multivariate logistic regression analysis showed that serum fibrinogen level (odds ratio 1.006, 95% confidence interval 1.003-1.009, P<0.001), age, glomerular filtration rate, female sex, and white blood cell count were correlated with the development of CI-AKI. CONCLUSION: Serum fibrinogen level is associated independently with a higher risk of CI-AKI in patients with ACS undergoing PCI.

The association of serum procalcitonin level with the no-reflow phenomenon after a primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

OBJECTIVE: The no-reflow phenomenon is associated with adverse outcomes in patients with acute ST-elevation myocardial infarction (STEMI) treated by a primary percutaneous coronary intervention (PPCI). Procalcitonin (PCT) is a marker of systemic inflammatory states and an elevated serum PCT concentration is related to an increased risk of cardiovascular events. We aimed to assess whether serum PCT level at admission is an independent predictor of no-reflow in patients with STEMI treated with PPCI. PATIENTS AND METHODS: Between November 2012 and December 2014, 501 consecutive patients with STEMI who underwent PPCI within the first 12 h following the onset of symptoms were enrolled. Serum PCT levels were measured on admission. Patients (age: 59±13 years, 73.5% men) were divided into the two groups: no-reflow and reflow. The no-reflow phenomenon was defined as final Thrombolysis In Myocardial Infarction flow grade less than 3 after PPCI. RESULTS: No-reflow was diagnosed in 91 (18.2%) patients. PCT levels were significantly higher in patients who developed no-reflow than in those who did not [0.102 (0.063-0.247) vs. 0.042 (0.020-0.076) µg/l, P<0.001]. In receiver operating characteristics curve analysis, the cut-off value of PCT was 0.066 µg/l for the prediction of no-reflow (area under the curve: 0.776, 95% confidence interval: 0.720-0.831, P<0.001, sensitivity: 73%, specificity: 70%). On multivariate analysis, serum PCT (>0.066 µg/l) value was an independent predictor of no-reflow (odds ratio: 3.377, 95% confidence interval: 1.572-7.255, P=0.002), together with early patency of culprit artery (P=0.046), Killip class more than or equal to 2 at presentation (P=0.028), and total stent length (P=0.004). CONCLUSION: Increased admission PCT level is associated independently with no-reflow after PPCI in STEMI patients.

Increased apolipoprotein A-I levels mediate the development of prehypertension among Turks.

OBJECTIVE: We aimed to assess whether apolipoprotein (apo) A-I levels that generated type-2 diabetes and coronary disease among Turks contribute to prehypertension and hypertension. METHODS: A population-based sample of 2207 adults (mean age 53±11 years) was studied prospectively over a 6.5 years' follow-up. Individuals with hypertension and/or prehypertension were excluded at baseline. RESULTS: At baseline, levels of apoA-I increased in each sex, from the normotensive to prehypertensive and hypertensive group (by mean 7.6 mg/dL, p<0.001) concomitantly with age, waist circumference, fasting triglycerides, apoB, C-reactive protein (CRP) and homeostasis model assessment. In logistic regression models, adjusted for confounders comprising waist circumference or triglycerides, prehypertension was predicted independently by apoA-I at RRs of 1.23 (95%CI 0.97; 1.52)] or 1.32 (95%CI 1.04; 1.74), respectively. Despite showing a positive association, apoA-I did not independently predict in similar models the development of hypertension; the determinants were rather waist circumference, or fasting triglycerides or CRP [RR 1.16 (95%CI 1.05; 1.28)] and, in women, diabetes. In a linear regression analysis for circulating apoA-I including 10 variables, apoB and in men systolic blood pressure were positively associated. CONCLUSION: In contributing to prehypertension, the pro-inflammatory apoA-I, mediated by apoB, is independent of triglyceridemia. Other inflammatory processes conjointly are likely mechanistically involved in the development of hypertension in a population with prevalent metabolic syndrome.

Microbiological assessment and evaluation of rehydration instructions on powdered infant formulas, follow-up formulas, and infant foods in Malaysia.

A total of 90 samples comprising powdered infant formulas (n=51), follow-up formulas (n=21), and infant foods (n=18) from 15 domestic and imported brands were purchased from various retailers in Klang Valley, Malaysia and evaluated in terms of microbiological quality and the similarity of rehydration instructions on the product label to guidelines set by the World Health Organization. Microbiological analysis included the determination of aerobic plate count (APC) and the presence of Enterobacteriaceae and Cronobacter spp. Isolates of interest were identified using ID 32E (bioMérieux France, Craponne, France). In this study, 87% of powdered infant formulas, follow-up formulas, and infant foods analyzed had an APC below the permitted level of <10(4) cfu/g. These acceptable APC ranged between <10(2) to 7.2×10(3) cfu/g. The most frequently isolated Enterobacteriaceae was Enterobacter cloacae, which was present in 3 infant formulas and 1 infant food tested. Other Enterobacteriaceae detected from powdered infant and follow-up formulas were Citrobacter spp., Klebsiella spp., and other Enterobacter spp. No Cronobacter species were found in any samples. Rehydration instructions from the product labels were collated and it was observed that none directed the use of water with a temperature >70°C for formula preparation, as specified by the 2008 revised World Health Organization guidelines. Six brands instructed the use of water at 40 to 55°C, a temperature range that would support the survival and even growth of Enterobacteriaceae.

High serum apolipoprotein E determines hypertriglyceridemic dyslipidemias, coronary disease and apoA-I dysfunctionality.

The relevance of serum apolipoprotein E (apoE) levels to two hypertriglyceridemic dyslipidemias has not been clarified. We explored, in a cross-sectional (and short-term prospective) evaluation, the independent relationship of serum apoE to the atherogenic dyslipidemia, hypertriglyceridemia with elevated apoB (HtgB) and to apoA-I dysfunctionality, previously shown in Turkish adults to be independent of apoE genotype. Serum apoE concentrations were measured by immunonephelometry in 1,127 middle-aged adults. In multivariable regression analysis, apoE concentrations showed log-linear associations with apoB and apoA-I levels, waist circumference, independent of C-reactive protein (CRP), homeostatic model assessment (HOMA) index and other confounders. The likelihood of atherogenic dyslipidemia and of HtgB roughly tripled per 1-SD increment in apoE concentrations, additively to apoE genotype, HOMA, apoA-I, CRP concentrations and waist circumference; yet apoA-I, protective against atherogenic dyslipidemia, appeared to promote HtgB, a finding consistent with apoA-I dysfunctionality in this setting. Each 1-SD increment in the apoE level was moreover, associated in both genders with MetS (at OR 1.5), after adjustment for sex, age, apoB, apoA-I and CRP, or for apoE genotypes. Circulating apoE predicted in both genders age-adjusted prevalent and incident coronary heart disease (CHD), independent of apoE genotype and CRP (OR 1.32 [95 % CI 1.11; 1.58]). To conclude, in a general population prone to MetS, elevated apoE concentrations are strongly linked to HtgB and atherogenic dyslipidemia, irrespective of apoE genotype, are associated with MetS and CHD. Excess apoE reflects pro-inflammatory state and likely autoimmune activation.

Bacteriological quality of abattoir effluents discharged into water bodies in abuja, Nigeria.

Bacteriological characteristics of abattoir effluents (wastewater), abattoir water source, and water bodies receiving abattoir wastewater were investigated in Abuja, Nigeria using the multiple-tube fermentation technique. Source of water to the abattoirs and the usage of water bodies receiving abattoir effluents were determined using questionnaires. Bacterial counts ranged from 4.8 × 10(6) to 5.8 × 10(5) /100 mL of total coliform (TC), 8.2 × 10(4) to 3.2 × 10(4)/100 mL of Fecal coliform (FC), 5.2 × 10(4) to 2.0 × 10(4)/100 mL of Fecal streptococcus and 1.2 × 10(4) to 2.0 × 10(3)/100 mL of Escherichia coli for abattoir effluents 6.6 × 10(5) to 6.0 × 10(5)/100 mL of TC, 6.2 × 10(4) to 1.8 × 10(4)/100 mL of FC, 1.8 × 10(4) to 6.0 × 10(3)/100 mL of F. streptococcus, and 4.8 × 10(3) to 6.6 × 10(2)/100 mL of E. coli for water bodies receiving abattoir effluents 100 m downstream. TC bacteria counts for abattoir effluents exceeded recommended limit for discharge into surface water in Nigeria. No significant difference (P < 0.05) was observed between bacterial counts of abattoir effluents and receiving water bodies 100 m downstream: an indication of contamination of receiving water bodies by abattoir effluents and possible public and environmental health hazards.

High levels of serum uric acid impair development of coronary collaterals in patients with acute coronary syndrome.

We evaluated the association of serum uric acid (SUA) level and development of coronary collateral vessels (CCVs) in patients with acute coronary syndrome (ACS). Patients (n = 224) with ACS were included in the study. Coronary collateral vessels were graded according to the Rentrop scoring system. Rentrop grade 0 was accepted as absence of CCV (group 1; n = 117) and Rentrop grade ≥1 was accepted as presence of CCV (group 2; n = 107). Rentrop 0-1 (poor CCV) were determined in 167 patients and Rentrop 2-3 (good CCV) were determined in 57 patients. Both presence of CCV (P < .001) and development of good CCV (P = .003) were significantly associated with low levels of SUA. We suggest that high levels of SUA affect the CCV development negatively in nondiabetic and nonhypertensive patients with ACS.

Arrhythmic effects of ivabradine in patients with coronary artery disease.

OBJECTIVES: Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. The aim of the present study was to investigate the effects of ivabradine therapy on P-wave duration, dispersion and QT duration, dispersion in coronary artery disease patients. METHODS AND RESULTS: The study population consisted of 21 patients with CAD who have confirmed by coronary angiography previously. Written informed consent was obtained in all patients. Twelve-lead electrocardiogram was recorded for each subject at a rate of 50mm/s on admission and repeated after 1 month ivabradine therapy. QT duration, QT dispertion, maximum and minimum QT duration calculated. Maximum and minimum P wave and P wave dispersion has been calculated. Heart rate was decreased after ivabradine therapy. (75+/-15 and 63+/-10, P=0.02).There was no difference between Pmax, Pmin and Pdis values before and after treatment. QTmax value was prolonged after treatment. (410+/-43 and 431+/-14, P=0,005) but there was no difference between cQTmax value.(455+/-38 and 439+/-21) There was no difference between QTdis and cQTdis values before and after treatment. (44+/-18 & 49+/-14; and 49+/-22 & 48+/-15). QTmax was prolonged after ivabradine therapy but cQTmax, Pdis, QTdis and cQTdis were not prolonged. CONCLUSION: There is no relationship between ivabradine therapy and increased risk of ventricular and atrial arrhythmia in coronary artery disease patient.

International survey of Cronobacter sakazakii and other Cronobacter spp. in follow up formulas and infant foods.

A coordinated survey for Cronobacter and related organisms in powdered infant formula, follow up formula and infant foods was undertaken by 8 laboratories in 7 countries in recognition of and in response to the data needs identified in an FAO/WHO call for data in order to develop global risk management guidance for these products. The products (domestic and imported) were purchased from the local market and were categorised according to their principle ingredients. A total of 290 products were analysed using a standardised procedure of pre-enrichment in 225 ml Buffered Peptone Water (BPW), followed by enrichment in Enterobacteriaceae Enrichment (EE) broth, plating on the chromogenic Cronobacter Druggan-Forsythe-Iversen (DFI) agar and presumptive identification with ID 32 E. Presumptive Cronobacter isolates were identified using 16S rRNA gene sequence analysis. Aerobic plate counts (APC) of the products were also determined on nutrient agar. Fourteen samples had APC>10(5) cfu/g, 3 of which contained probiotic cultures. C. sakazakii was isolated from 27 products; 3/91 (3%) follow up formulas (as defined by Codex Alimentarius Commission), and 24/199 (12%) infant foods and drinks. Hence C. sakazakii was less prevalent in follow up formula than other foods given to infants over the same age range. A range of other bacteria were also isolated from follow up formulas, including Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Citrobacter freundii, and Serratia ficaria. There was significant variation in the reconstitution instructions for follow up formulas. These included using water at temperatures which would enable bacterial growth. Additionally, the definition of follow up formula varied between countries.

Comparative features and outcomes of malaria at a tertiary care hospital in Karachi, Pakistan.

OBJECTIVES: A comparison of clinical and laboratory features, diagnostic methods, drug treatment, and outcomes for patients hospitalized with malaria by Plasmodium species. METHODS: Records of 521 patients hospitalized during the four and half-year study period were analyzed. RESULTS: Infections were caused by Plasmodium vivax (51.8%), Plasmodium falciparum (46.5%), P. vivax plus P. falciparum (1.3%), and Plasmodium malariae (0.4%). Vomiting (odds ratio (OR)=1.86, p=0.001) and abdominal pain (OR=1.60, p=0.024) occurred more frequently in patients infected with P. falciparum compared to P. vivax; this was also the case for hepatomegaly, splenomegaly and jaundice. Low hemoglobin levels were common but were significantly lower with P. falciparum, and creatinine levels were significantly higher with P. falciparum. Treatment regimens consisted of single drug therapy (61.5%), appropriate combination therapy (15.8%), and inappropriate combination therapy (22.7%). Antimalarials given alone included chloroquine (38.7%), quinine (19%) and doxycycline (1.5%). The overall mortality was 1.7% (n=9) and nearly 56% of patients developed disease complications, most commonly thrombocytopenia (36.4%), anemia (23.4%), and thrombocytopenia plus anemia (32.7%). CONCLUSIONS: Despite resistance, chloroquine was prescribed in patients with malaria requiring hospitalization. We found a high proportion of single antimalarial drug use as well as inappropriate combination therapy (22.7%), and inadequate use of primaquine terminal prophylaxis. Physicians need to be acquainted with malaria treatment guidelines in an endemic zone.

Systematic screening of chromosome 18 for loss of heterozygosity in esophageal squamous cell carcinoma.

Esophageal cancer ranks among the 10 most common cancers in the world, and is almost uniformly fatal. The genetic events leading to the development of esophageal carcinoma are not well established. To identify genomic regions involved in esophageal carcinogenesis, we performed a systematic screening for loss of heterozygosity (LOH) in 24 samples of squamous cell carcinomas, initially focusing the analysis on chromosome 18. Thirteen short tandem repeat markers spanning 18p and 18q were used. We found a broad peak of LOH spanning 18p11.2 and 18q21.1 with the most frequent LOH (72%) at D18S978 on 18q12.2, which coincides with a known fragile site FRA18A. This region is 4 cM proximal to known tumor suppressor genes and therefore suggests the possible existence of a yet undiscovered tumor suppressor gene.

Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.