Oral mucosal color changes as a clinical biomarker for cancer detection.

Screening is a key tool for early cancer detection/prevention and potentially saves lives. Oral mucosal vascular aberrations and color changes have been reported in hereditary nonpolyposis colorectal cancer patients, possibly reflecting a subclinical extracellular matrix abnormality implicated in the general process of cancer development. Reasoning that physicochemical changes of a tissue should affect its optical properties, we investigated the diagnostic ability of oral mucosal color to identify patients with several types of cancer. A total of 67 patients with several histologically proven malignancies at different stages were enrolled along with a group of 60 healthy controls of comparable age and sex ratio. Oral mucosal color was measured in selected areas, and then univariate, cluster, and principal component analyses were carried out. Lower red and green and higher blue values were significantly associated with evidence of cancer (all P<0.0001), and efficiently discriminated patients from controls. The blue color coordinate showed significantly higher sensitivity and specificity (96.66±2.77 and 97.16±3.46%, respectively) compared with the red and green coordinates. Likewise, the second principal component coordinate of the red-green clusters discriminated patients from controls with 98.2% sensitivity and 95% specificity (cut-off criterion≤0.4547; P=0.0001). The scatterplots of the chrominances revealed the formation of two well separated clusters, separating cancer patients from controls with a 99.4% probability of correct classification. These findings highlight the ability of oral color to encode clinically relevant biophysical information. In the near future, this low-cost and noninvasive method may become a useful tool for early cancer detection.

Placental ischemia and changes in umbilical and uteroplacental arterial and venous hemodynamics.

OBJECTIVE: To relate Doppler velocimetry findings in fetoplacental and uteroplacental circulation to placental histomorphology. MATERIAL AND METHODS: In 14 uncomplicated and 31 high-risk pregnancies Doppler velocimetry was performed in umbilical artery and vein, and in maternal uterine veins and arteries during the second half of gestation. Histopathology of the placentas was examined, especially for signs of ischemia and inflammation. RESULTS: All fetuses in uncomplicated pregnancies had normal flow velocity waveforms in umbilical artery; in the high-risk group, 18 fetuses had abnormal flow (increased PI or absent/reverse end-diastolic flow). The latter group had more often high ischemic score and infarctions in the placenta than found in pregnancies with normal umbilical artery flow (p < 0.001 and p = 0.02, respectively). Similarly, the abnormal uterine artery flow pattern (uterine artery score 3-4) occurred more often with high ischemic score and placenta infarctions (p < 0.001 and p < 0.001, respectively). No significant associations were found between the uterine venous flow type and placental ischemia. CONCLUSION: Placental ischemic morphological changes were associated with Doppler ultrasound signs of increased resistance to arterial blood flow, both on the fetal and maternal sides of the placenta. No significant relation to the uterine venous flow velocities was found.

[A 61-year-old man with sciatica]. / En 61 år gammel mann med isjias.

A 61-year-old man was admitted to our department with radicular back-pain and progressive gait-difficulties. On examination he had flaccid paraparesis and bladder-retention. He subsequently developed palsy of n. oculomotorius, dysarthria, right-sided Bells palsy and weakness of his right arm over a 4-week period. He became disoriented and died without a diagnosis. MRI of the brain and columna were negative. Extensive search for malignancies yielded negative results. Cytology specimens were inconclusive and repeated liquor-examinations showed very low glucose levels, mild pleocytosis, elevated protein. Autopsy revealed a small adenocarcinoma of the lung and meningeal carcinomatosis originating from the adenocarcinoma.

[Pregnancy shortly after bariatric surgery]. / Svangerskap like etter fedmeoperasjon.

Bariatric surgery is increasingly used to treat morbidly obese patients. Fertility in women may be enhanced after these procedures, owing to substantial weight loss and possibly a decreased absorption of oral contraceptives. We report a pregnancy that occurred two months after biliopancreatic diversion with duodenal switch in a 32-year-old woman. She subsequently developed haemolysis, elevated liver enzymes and low platelets count (HELLP) syndrome and had a weight loss of 43 kg (from the bariatric procedure) until the infant was delivered preterm by caesarean section (due to low activity). The infant was small in relation to the gestational age, with a weight of less than 50 % of the expected (780 g at 29.6 weeks). Histological examination demonstrated a small placenta with insufficient spiral artery trophoblast infiltration, possibly caused either by severe preeclampsia or by maternal nutritional deficiencies. Severe metabolic aberrations may complicate pregnancies after malabsorptive bariatric surgery. Patient preparations before weight-loss operations should include information on fertility and birth control in the postoperative period. Protocols for monitoring of patients that become pregnant after bariatric surgery are needed.

Congenital laryngomucocoele: a rare cause for CHAOS.

Congenital high airway obstruction syndrome (CHAOS) is a rare but life-threatening condition that results from the obstruction of the upper airways.We describe a female newborn, from a Grávida II, Para 0, 36-year-old woman, with a routine ultrasound at 30 weeks' gestation that showed polyhydramnios. She delivered a live-born female baby at 36 weeks without any dismorphic features but with respiratory distress. Attempts at endotracheal intubation were unsuccessful due to the presence of a mass obstructing the larynx. The reanimation process was stopped after 20 minutes. Post-mortem examination demonstrated the presence of a total occlusion of the larynx by a laryngomucocoele. Laryngocele, a congenital cyst of the larynx, occurs rarely and hardly ever as a cause of CHAOS. What is more, laryngomucocoele has not been previously reported as a cause of CHAOS. These conditions represent a neonatal emergency with reserved prognosis unless diagnosed antenatally allowing for a programmed ex utero intrapartum treatment (EXIT) by performing tracheostomy while maintaining the placental circulation.

Recurrent otitis media with effusion in preterm infants with histologic chorioamnionitis--a 3 years follow-up study.

BACKGROUND: Recurrent otitis media with effusion (OME) is a leading cause of acquired hearing loss in childhood. Histological chorioamnionitis (HCA) is an important cause of preterm delivery and neonatal morbidity and mortality. Here, we tested the hypothesis of an association between recurrent OME during the first 3 years of life and HCA in very low birth weight (VLBW) infants. METHODS: A total of 110 randomly selected VLBW preterm newborns with HCA and 135 gestational age and gender-matched, HCA-negative VLBW infants were evaluated prospectively during the first 3 years of life for the presence of OME, as diagnosed on the basis of otoscopy, type B or C tympanogram, ipsilateral absence of transient evoked otoacoustic emissions responses, and ipsilaterally increased threshold at diagnostic auditory brain responses evaluation. Potential risk factors for OME were also examined in the two groups. RESULTS: The HCA-positive infants showed a approximately six times higher frequency of recurrent OME (P<0.0001), increased frequency (>5/yr) of clinical otitis media episodes (P=0.000020), approximately five times higher frequency of adenoid hypertrophy (P<0.00001), a significant seasonal pattern of birth with autumn predominance (P<0.00001), and the first OME occurred earlier (P<0.0001), as compared to the HCA-negative counterparts. Recurrent OME was significantly associated with HCA (O.R.=17.76, 95% CI: 8.98-35.13, P<0.00001), adenoid hypertrophy (O.R.=9.96, 95% CI: 5.17-19.18, P<0.00001), frequency of acute otitis episodes >5/yr (O.R.=8.91, 95% CI: 1.96-40.41, P=0.0005), and birth in autumn (O.R.=5.58, 95% CI: 2.79-11.12, P<0.00001). CONCLUSIONS: These findings indicate that HCA is a previously unrecognized risk factor for the development of recurrent bilateral OME in VLBW preterm infants during the first 3 years of life.

Expression of cytokines and chemokines in cervical and amniotic fluid: relationship to histological chorioamnionitis.

OBJECTIVE: To correlate cervical and amniotic fluid cytokines and macrophage-related chemokines to the development of histological chorioamnionitis (HCA) in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PPROM). STUDY DESIGN: Cervical and amniotic fluid interleukin (IL)-6, IL-8, IL-18, monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 from pregnant women (at

Abnormal oral vascular network pattern geometry: a new clinical sign of down syndrome.

Down syndrome is a leading genetic cause of mental retardation. Here, we show high fractal dimensions and Lempel-Ziv complexity and lower minimum path fractal dimension (P < or = .0006) for the oral vascular networks of patients (n = 14) and their unaffected parents. This newly recognized sign may provide a useful phenotypical marker for identifying couples potentially at risk for offspring with Down syndrome.

Massive feto-maternal hemorrhage: diagnosis by cardiotocography, Doppler ultrasonography and ST waveform analysis of fetal electrocardiography.

A 34-year-old healthy gravida 2 para 1 presented after an uncomplicated pregnancy at term with a 2-day history of diminished fetal movements. Fetal anemia was suspected by fetal heart rate monitoring and Doppler estimation of the fetal peak blood flow velocity of the middle cerebral artery. We were also fortunate to register pathological ST waveform changes of the fetal ECG indicating fetal hypoxia. The diagnosis of a massive feto-maternal hemorrhage was confirmed by an extremely high fraction of erythrocytes containing fetal hemoglobin in maternal blood and, after delivery, by placental histology.

Late-onset postpartum hemorrhage from placental bed subinvolution: a case report.

BACKGROUND: Placental bed subinvolution is an underestimated cause of severe, late-onset postpartum hemorrhage. CASE: A case of placental bed subinvolution caused abnormal uterine bleeding in the late postpartum period. Because of difficulties in establishing the diagnosis, massive, intractable and life-threatening uterine hemorrhage occurred, leading to hysterectomy. CONCLUSION: Early recognition of placental bed subinvolution allows the use of treatment options capable of preserving the uterus and subsequent fertility.

DNA-ploidy in advanced gastric carcinoma is less heterogeneous than in early gastric cancer.

This analysis of DNA-ploidy heterogeneity in advanced gastric carcinomas is consistent with the hypothesis of the emergence of a single aneuploid cell clone as a crucial mechanism in the progression from early gastric carcinoma to advanced gastric cancer. The prognostic value of DNA-ploidy in gastric cancers has been a matter of controversy. Tumour DNA-ploidy heterogeneity, the presence within the same tumour of multiple stemlines differing in DNA content, has been described in various tumours including gastric cancers. The occurrence of such heterogeneity has been accepted as an explanation for the divergent DNA-ploidy results in this type of tumours. A previous study of early gastric cancers suggested that in pure diploid superficial carcinomas, genetic instability might lead to a cell clone which has undergone a ploidy shift and is more aggressive. If so, this would initially result in DNA-ploidy heterogeneity. Proliferative dominance of the aneuploid clone could eventually evolve to a homogeneous aneuploid tumour. In order to test this hypothesis, we studied DNA-aneuploidy and DNA-ploidy heterogeneity in advanced gastric carcinomas. We performed DNA cytophotometry on multiple samples collected from 16 advanced gastric carcinomas and found 15 DNA-aneuploid tumours (94%) and one diploid tumour. Multiple DNA-stemlines were found in 4 cases (26%). Analysis of proliferative activity performed on the same samples revealed higher proliferation rate in DNA-ploidy homogeneous tumours than in aneuploid heterogeneous tumours. Heterogeneous tumours did not overexpress p53. These results confirm that DNA-aneuploidy is frequent in advanced gastric cancer and demonstrate that a majority of these aneuploid tumours are not DNA-ploidy heterogeneous. Furthermore, the higher proliferative activity in homogeneous-aneuploid carcinomas and their more frequent overexpression of p53 support the hypothesis that in gastric cancer tumour progression implies the development of a dominant and more aggressive (higher proliferative activity, p53 overexpression) aneuploid cell clone.

Congenital oral mucosal abnormalities in true umbilical cord knots.

OBJECTIVE: The pathogenesis and clinical significance of true umbilical cord knots remain controversial. Here, we tested the hypothesis of the presence of congenital oral mucosal changes in newborns with true umbilical cord knots. STUDY DESIGN: Seven consecutive infants with true umbilical cord knots and 50 gestational age- and sex-matched controls were enrolled. The proportion of oral frenulum abnormalities and the two-dimensional vascular network geometry [fractal dimension, D, at two scales: D(1-46), and D(1-15), with the relative Lempel-Ziv complexity, (L-Z)], were analyzed. RESULTS: Infants with true umbilical cord knots showed significantly higher proportions of mandibular frenulum agenesis compared to controls (p = 0.000006). The oral vascular networks of these infants exhibited a significantly higher D(1-46) and D(1-15) (p < 0.0001, respectively), and higher L-Z values (p < 0.0001) than control networks. CONCLUSION: These findings indicate the presence of significant congenital oral mucosal changes in newborn infants with true umbilical cord knots, thus suggesting a previously unrecognized association between true umbilical cord knots and a subclinical extracellular matrix disorder.

Nephrogenic adenoma of the urethra: an unusual cause of hematuria in the child.

The authors describe a 9-year-old boy who had an accident with his bicycle. He presented with hematuria a few weeks later, and cystoscopy results showed a polypod lesion near the veru montanum. The lesion was resected, and histologic examination showed a nephrogenic adenoma (NA), which recurred 6 years later with hematuria. NA is a rare lesion in a child's urethra and can be a source of hematuria.

Non-viable cervico-isthmic pregnancy: the importance of an accurate sonographic diagnosis to preserve fertility.

BACKGROUND: Cervico-isthmic pregnancy is a rare occurrence and until the use of current ultrasonographic techniques was associated with a disastrous outcome for women desiring to maintain their fertility. CASE REPORT: A 39-year-old woman was diagnosed at 12 weeks of amenorrhoea with an intra-uterine non-viable pregnancy and a low implantation of the gestational sac. Medical management of this situation with a regimen of intravaginal misoprostol was unsuccessful. At introduction of a cervical expander severe vaginal bleeding ensued, leading to an emergency curettage followed by a life-saving hysterectomy. Pathologic examination confirmed the peroperative impression of an isthmic implantation of the gestational sac. CONCLUSION: Early ultrasonographic diagnosis is essential to make conservative management of cervico-isthmic pregnancy possible.

Nitric oxide synthase activity in human trophoblast, term placenta and pregnant myometrium.

To investigate the possible role of nitric oxide (NO) produced locally or intramurally in the quiescence of the pregnant myometrium, nitric oxide synthase (NOS) activity was measured in samples from first trimester (villous, and non villous-trophoblast), term placenta and pregnant myometrium. Trophoblast tissue was obtained from psychosocial termination of pregnancy (9-12 weeks' gestation) whereas placenta and myometrium, from the same patient, at deliveries by Caesarean section. NOS activity was measured in both cytosolic and particulate fractions by the formation of 14C-citrulline from 14C-arginine. Western immunoblotting was used to identify the endothelial NOS (eNOS) and neuronal (nNOS) isoforms. The activity of NOS in particulate fractions from all preparations was considerably higher than the cytosolic fractions. Activity in all fractions except the myometrium was highly Ca-dependent. More than 50% of particulate NOS from the myometrium was Ca-independent. NOS activity was highest in the villous trophoblast and there was a significant difference between the villous and non-villous trophoblast. In placenta and myometrium, NOS was 2-4 fold and 20-28-fold lower than the villous trophoblast, respectively. Western blot analysis showed clearly eNOS in the particulate fraction and a weak eNOS band in the cytosolic fractions, whereas nNOS was not detectable in any of the fractions. In view of the marginal activity of NOS in the myometrium, NO produced by the trophoblast and placenta could play a significant role in maintaining uterine quiescence by paracrine effect.

Co-infection with Chlamydia pneumoniae and Helicobacter pylori results in vascular endothelial dysfunction and enhanced VCAM-1 expression in apoE-knockout mice.

BACKGROUND: Upregulation of proinflammatory endothelial cell adhesion molecules and decreased bioactivity of endothelial nitric oxide (NO) are important in the pathogenesis of atherosclerosis. We investigated the effects of co-infection with Chlamydia pneumoniae and Helicobacter pylori on these two events in apoE-KO mice. METHODS: Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either C. pneumoniae or H. pylori, while the 3rd group was infected with both C. pneumoniae and H. pylori. Mice from the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal aortas were harvested after 10 weeks, and staining for vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to methacholine were studied in organ chambers in the absence and presence of L-NAME. The plasma levels of nitrate/nitrite were measured. RESULTS: Staining for VCAM-1 was more intense at the branching sites of aortas from mice with co-infection than in mono-infected or noninfected apoE-KO mice. The relaxation responses to methacholine and the plasma levels of nitrate/nitrite were significantly less in the co-infected group than in the other groups (p < 0.05). CONCLUSION: Co-infection of apoE-KO mice with C. pneumoniae and H. pylori seems to be associated with impaired bioactivity of endothelial NO and increased expression of VCAM-1 at branching sites. The findings may suggest an additive interaction of these pathogens in atherogenesis.

Structural, functional and circulatory placental changes associated with impaired glucose metabolism.

OBJECTIVE: To investigate associations between structural, functional and circulatory placental changes in pregnancies complicated by impaired glucose metabolism. DESIGN: Umbilical artery (UA) blood flow resistance was measured by Doppler velocimetry in 21 gravidae with diabetes/impaired glucose tolerance (IGT) and 10 healthy gravidae. Umbilical and placental vessel segments were incubated for determination of prostacyclin and thromboxane synthesis, and tissues histologically examined. Non-parametric statistical tests at a two-tailed P<0.05 were used. RESULTS: Placental lesions were more common in diabetes/IGT and, although not being an uniform finding, in general associated with a higher vascular synthesis of thromboxane and/or lower prostacyclin/thromboxane synthesis ratio. As an exception, ischemic villitis was associated with a higher ratio and higher UA flow resistance. CONCLUSIONS: Placental lesions are associated with an altered vascular prostanoid synthesis in diabetes/IGT, but not until structural signs of ischemia develop is a rise of UA blood flow resistance detected.

PPAR expression and function during vertebrate development.

The peroxisome proliferator activated receptors (PPARs) are ligand activated receptors which belong to the nuclear hormone receptor family. As with other members of this superfamily, it is thought that the ability of PPAR to bind to a ligand was acquired during metazoan evolution. Three different PPAR isotypes (PPARalpha, PPARbeta, also called 6, and PPARgamma) have been identified in various species. Upon binding to an activator, these receptors stimulate the expression of target genes implicated in important metabolic pathways. The present article is a review of PPAR expression and involvement in some aspects of Xenopus laevis and rodent embryonic development. PPARalpha and beta are ubiquitously expressed in Xenopus early embryos but become more tissue restricted later in development. In rodents, PPARalpha, PPARbeta and PPARgamma show specific time- and tissue-dependent patterns of expression during fetal development and in the adult animals. PPARs are implicated in several aspects of tissue differentiation and rodent development, such as differentiation of the adipose tissue, brain, placenta and skin. Particular attention is given to studies undertaken by us and others on the implication of PPARalpha and beta in rodent epidermal differentiation.