[Masuda's Central Serous Chorioretinopathy (C.S.C.R.) and its somatic investment in Narcissism: our observations on new psychiatric nosography]. / Corioretinopatia sierosa centrale (C.R.S.C.) di Masuda quale investimento somatico nel Narcisismo: nostra rifl essione sulla nuova nosografi a psichiatrica.

Case report. Co-morbidity between central serous chorioretinopathy (C.R.S.C.) and narcissistic personality disorder. A reflection on the importance of an integrated approach to this ophthalmological disease through the description of its psychosomatic aspects and the evaluation of the nosographic definition in psychiatry. The central serous chorioretinopathy (C.R.S.C.) is a transudative disease affecting the posterior pole of the eye, that rapidly compromises the visual acuity, although it is a self-limited disease. Narcissism is a personality disorder characterised by an extreme gratification of self, without actually taking care of other people. In the current work both the diseases, along with the respective psychosomatic consequences the patient received, are examined.

Van-Gogh-like 2 antagonises the canonical WNT pathway and is methylated in colorectal cancers.

BACKGROUND: Aberrant activation of the canonical WNT signaling is a feature of colorectal cancer (CRC). Van-Gogh-like 2 (VANGL2) belongs to the non-canonical WNT pathway whose activation inhibits canonical WNT signaling. In this study, we investigated the role of VANGL2 and its epigenetic regulation in CRC. METHODS: Van-Gogh-like 2 expression and promoter methylation after 5-aza-2'-deoxycytidine (5-aza) treatment were evaluated in CRC cells. DNA samples from 418 sporadic CRCs were tested for VANGL2 promoter methylation and microsatellite instability (MSI). Proliferation, colony formation and activation of the WNT pathway were tested in cells after VANGL2 overexpression. RESULTS: Van-Gogh-like 2 mRNA was significantly higher in 5-aza-treated RKO, LOVO and SW48, whereas no differences were found in SW480. Van-Gogh-like 2 was fully methylated in RKO, SW48, HCT116, DLD1 and Caco2; partially methylated in LOVO, LS174T and SW837; and unmethylated in SW480, SW620 and HT29. Higher expression of VANGL2 mRNA was found in the unmethylated cell lines. In CRC specimens (8.93% MSI), methylated VANGL2 was associated with MSI, higher grade, proximal colon location and BRAF mutation. Van-Gogh-like 2 overexpression in SW480 significantly decreased proliferation, colony formation and ß-catenin levels. CONCLUSION: Van-Gogh-like 2 is frequently methylated in MSI-CRCs with BRAF mutation and may act as a tumour suppressor gene, counteracting WNT/ß-catenin signaling.

Long-term safety of ziprasidone in schizophrenic patients: an open trial.

OBJECTIVES: The Authors report the safety results of the extension phase of three multicenter, phase III studies, which evaluated ziprasidone in schizophrenic patients switching from another antipsychotic agent or who required a transition from intramuscular to oral ziprasidone. PATIENTS AND METHODS: A total of 331 patients were evaluated, with a mean follow-up of 22 months (range: 3-73 months). RESULTS AND CONCLUSIONS: Ziprasidone appeared well tolerated; most adverse events were of mild or moderate severity. No new safety or tolerability issues emerged. However, the authors observed a high number of withdrawals, possibly associated with a lack of long-term compliance, which is a common feature in schizophrenic patients.

Molecular detection of epidermal growth factor receptor in colorectal cancer: does it still make sense?

AIM: The aim of the study was to detect and compare the epidermal growth factor receptor (EGFr) content using different methods, to establish whether the quantitative detection and functional study of EGFr in colorectal cancer, using methods other than immunohistochemistry (IHC), are appropriate. METHOD: Analysis of EGFr by IHC was performed in 230 colorectal cancer patients using monoclonal anti-EGFr. Total and activated EGFr (pY1068) contents were determined in 92 patients and real-time PCR, to determine the level of EGFr messenger RNA, was carried out in 60 patients. RESULTS: There was no association between EGFr IHC groups and the mean total EGFr levels measured using ELISA. CONCLUSION: The study shows that the results of different EGFr detection methods do not correlate with each other. Hence, the real role of EGFr in colorectal cancer remains unsettled. Clinically, the receptor itself does not seem to be important and it would be better to focus on EGFr signalling in downstream pathways.

Chronic intestinal pseudo-obstruction related to viral infections.

Chronic intestinal pseudo-obstruction (CIPO), one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Analysis of full-thickness biopsy samples may unravel structural changes of the neuromuscular layer involving the whole gut, although the midgut is usually worst affected. Intestinal pseudo-obstruction can occur in association with systemic neurological, endocrine, and connective tissue diseases or malignancy but, when no recognizable etiology is found, CIPO is referred to as idiopathic (CIIPO). The latter form can be diagnosed early in life due to a genetic etiology or in adulthood when a viral origin may be considered. This review addresses the hypothesis that some systemic neurotrophic viral infections can affect the enteric nervous system thereby altering normal peristaltic activity. Available data are reviewed, focusing specifically on herpesviruses or polyomaviruses (JC virus). These suggest that in comparison to a proportion of CIIPO patients, healthy controls rarely harbor viral DNA in the myenteric plexus, leaving open the possibility that a viral infection might have an etiologic role in the development of CIIPO. The review thus provides some new perspectives in the pathophysiology and perhaps targeted treatment of CIIPO.

Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model.

The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

Gene expression profiling of liver metastases from colorectal cancer as potential basis for treatment choice.

At present no reports on gene expression profiling of liver metastases from colorectal cancer are available. We identified two different signatures using Affymetrix platform: epidermal growth factor receptor pathway was upregulated in metachronous lesions, whereas the pathway mainly related to angiogenesis was in synchronous lesions. Synchronous or metachronous liver metastases could be treated differently on the basis of different molecular pathways.

Surgical debulking of gastrointestinal stromal tumors: is it a reasonable option after second-line treatment with sunitinib?

INTRODUCTION: After imatinib treatment, the surgical management of patients affected by gastrointestinal stromal tumor (GIST) has been widely reported and often considered by many oncologists in clinical practice. Surgical results are correlated with disease responsiveness to tyrosine kinase inhibitors and with complete extirpation of all tumor sites. By now, no report specifically addressing surgical management after second-line treatment with sunitinib is still available. Most patients have an unresectable disease and do not have any other therapeutical options except for clinical trials. MATERIALS AND METHODS: We report two clinical cases of patients with metastatic GISTs, who underwent surgery after sunitinib, and discuss the surgical management option in this clinical setting. RESULTS: Both our patients had a long, durable stable disease on sunitinib, but one developed a chronic mild bleeding that does not call for emergency surgical interventions and the other one developed chronic heart toxicity. They were proposed to undergo surgery despite the unresectable diseases and received an incomplete resection because of residual metastatic lesions. They restarted sunitinib after surgery. CONCLUSIONS: The poor prognosis after sunitinib treatment and the absence of alternative validated options open the debate on the assessment of surgical management of metastatic GISTs in this setting. The role of surgery should be investigated in clinical trials; however, the enrollment may be difficult. In clinical practice and after a multidisciplinary case patient discussion, surgery could represent a reasonable choice for advanced GISTs especially if the risk of surgery-related death is not too high.

Molecular determination of epidermal growth factor receptor in normal and neoplastic colorectal mucosa.

The epidermal growth factor receptor (EGFr) is considered a major target for treatment of colorectal cancer (CRC). We found a mean EGFr content significantly lower but more activated in colonic neoplastic tissue than in paired normal mucosa. Phosphorylated (pY1068) EGFr detection in CRC may be a better tool than EGFr detection to select patients for targeted therapies.

Concurrent EGFr and Cox-2 expression in colorectal cancer: proliferation impact and tumour spreading.

BACKGROUND: Many reports were produced on single epidermal growth factor receptor (EGFr) and cyclo-oxygenase-2 (Cox-2) evaluation using immunohistochemical techniques (IHC), but very few works considered concurrent expression of these two proteins in the light of their impact on proliferation and tumour spreading. At least three molecular pathways (EGFr, Cox-2, and APC/beta-catenin molecular cascade) may interact in this malignancy giving rise to cross talking effects on proliferation and cancer spreading. PATIENTS AND METHODS: To better detail these two latter aggressive features, we studied 205 sporadic colorectal cancer patients, comparing concurrent expression of EGFr, Cox-2, Ki-67, Cyclins D1-A, and E, with tumour spreading (budding) (BUD) and pN status. RESULTS: Our results point to a different aggressive molecular profile due to Cox-2 expression. Cox-2 High expressing cases showed a clear EGFr proliferation-promoting role. On the contrary, EGFr seems directly involved in cancer cells spreading rather than in promoting cancer proliferation in Cox-2 Low/Negative cases. CONCLUSIONS: Immunohistochemical profiling of colorectal cancer seems to be a promising approach, not only to define prognostic impact, but also to detail proliferation-related molecular interplays between EGFr and Cox-2 pathways, with these two latter proteins, at present, being the hottest pharmacological targets for colorectal cancer (CRC) chemoprevention and therapy.

Immunophenotypic changes of fetal cord blood hematopoietic progenitor cells during gestation.

We measured cell surface expression of CD34, HLA-DR, CD38, CD19, CD33, CD71, and CD45 antigens in the hematopoietic progenitor cells of fetal cord blood to investigate immunophenotypic changes at different gestational ages. These antigens were identified by flow cytometry in 11 fetuses (gestational age 19-24 wk, in 12 preterm (25-28 wk) and in ten newborn infants born at term. The frequency and number of CD34+ cells were higher in the blood of the 11 fetuses; in addition, a statistically significant inverse correlation between number of CD34+ cells and advancing gestational age was noted. The numbers of CD34+ CD19+, CD34+ CD33+, and CD34+ CD45+ coexpressing cells were significantly higher in the fetuses, whereas CD34+ CD38+ cells were more represented in the neonates at term. Gestational age was inversely correlated with the number of CD34+ CD19+ and CD34+ CD33+ coexpressing cells. A positive correlation between gestational age and CD34+ CD38+ cells was noted. The number of CD34- CD19+, CD34- CD38+, and CD34- CD45+ cells was higher in term infants; furthermore, a significant correlation between advancing gestational age and CD34- CD38+ or CD34- CD45+ cells was demonstrated. The proliferative capacity was also higher at lower gestational ages. These data suggest that the development and lineage commitment of fetal cord blood hematopoietic progenitor cells are very active during the last two trimesters of pregnancy. The most significant changes of hematopoietic cells maturation seem to occur within 25 wk of gestation.

Antenatal molecular diagnosis of X-linked ichthyosis by maternal serum screening for Down's syndrome.

A case of X-linked ichthyosis diagnosed antenatally by molecular analysis of fetal DNA is described. The diagnosis was made at 16 weeks gestation, following the finding of a maternal serum unconjugated estriol level lower than 0.1 MoM when performing a triple test. Fetal DNA was obtained from cultured amniocytes; two specific regions were amplified by polymerase chain reaction at 5' and 3' ends of the steroid sulfatase (STS) gene on Xp22.3 region. Analysis showed complete deletion of the STS gene on the distal tip of the X-chromosome short arm.

Adequacy of screening cervical cytology among human immunodeficiency virus-seropositive women.

OBJECTIVE: To evaluate the adequacy of cytology in detecting cervical intraepithelial neoplasia (CIN) among human immunodeficiency virus (HIV)-seropositive women compared to controls. METHODS: A cross-sectional study was carried out evaluating 241 HIV-seropositive women and 991 controls (404 HIV seronegative and 587 of unknown HIV status) at risk for CIN attending a vaginitis clinic. All patients had a Pap smear and a standard colposcopic examination of the lower genital tract. Cervical biopsies were taken as indicated by colposcopy. Cytology and histology slides were read by a cytopathologist blinded to patients' serostatus. False-negative cytologic cases were reviewed by three independent cytopathologists to estimate sampling and screening error rates. Sensitivity, specificity, and false-negative rate of cytologic smears were compared between HIV seropositives and controls. We estimated the sampling and screening error rates among cases with false-negative cytology. RESULTS: Among seropositives, the sensitivity, specificity, and the false-negative smear rate for CIN were 73.4% (47/64), 97.1% (134/138), and 26.6% (17/64), respectively. The corresponding figures in controls were 83.8% (83/99), 99.04% (825/833), and 16.2% (16/99), respectively, and did not differ significantly from those of seropositives. The negative predictive value of cytology was lower among seropositives (134/151) than in controls (825/841, chi2 = 34.8, P < .001). The agreement between cytologic readings and combined colposcopy and histology was stronger among controls (kappa = 0.789, 95% CI 0.723 to 0.856) than among seropositives (kappa = 0. 593, 95% CI 0.475 to 0.712). Three independent cytopathologists were unable to detect atypical cells in 52.9% (9/17) of false-negative smears taken from seropositive women as opposed to 37.5% (6/16) of controls. CONCLUSIONS: The sensitivity, specificity, and false negative rate of screening cytology for CIN among HIV seropositive women are comparable with those in the general population. Since almost 50% of false-negative results could be attributed to sampling errors, more frequent cytological screening may prove to be beneficial to this high-risk group.

Risk for spontaneous preterm delivery by combined body mass index and gestational weight gain patterns.

BACKGROUND: To investigate whether maternal anthropometric factors interact with one another or with other risk factors, thus modifying the risk of spontaneous preterm delivery. METHODS: We carried out a case-control study of 230 spontaneous preterm births with intact membranes between 24 and 35 weeks gestation and 460 control term births. All the patients had prenatal care at the same institution. Logistic regression analysis was used to test for possible interactions adjusting for potential confounders. RESULTS: A pre-pregnancy body mass index < or = 19.5 Kg/m2 (odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.20-2.38) and a rate of weight gain < or = 0.37 Kg/week during the second and third trimesters (OR = 2.4, 95% CI = 1.69-3.42) were associated with an increased risk of spontaneous preterm delivery. The risk of spontaneous preterm delivery associated with a low second/third trimester weight gain was greater among patients with a body mass index < or = 19.5 (OR = 5.63, 95% CI = 2.35-13.8) compared to those with a body mass index > 19.5 (OR = 2.45, 95% CI = 1.60-3.75, adjusted p value for interaction = 0.05). The risk of spontaneous premature delivery associated with a maternal pre-pregnancy weight < or = 48 Kg was higher among smokers (OR = 5.81, 95% CI = 1.60-22.9) than among non-smokers (OR = 2.4, 95% CI = 1.53-3.74, adjusted p value for interaction = 0.05). CONCLUSIONS: The risk of spontaneous preterm delivery associated with a low pre-pregnancy body mass index is greater among patients with low rate of gestational weight gain during the second and third trimesters compared to those with a higher rate. The results of this study support the recommendation for increased rates of weight gain to patients with low body mass index compared to those with a higher body mass index.

Meconium-stained amniotic fluid and risk for cerebral palsy in preterm infants.

OBJECTIVE: To estimate the risk for cerebral palsy in preterm infants in relation to the presence of meconium in the amniotic fluid (AF). METHODS: A cohort study was conducted of 404 consecutive preterm infants delivered between 24 and 33 weeks' gestation at a single institution. Sociodemographic and clinical data were collected at birth. The diagnosis of cerebral palsy was made at 2 years' corrected age. Politomous logistic regression models were used to evaluate the odds for cerebral palsy while adjusting for potential confounders. RESULTS: The overall prevalence of cerebral palsy among survivors was 11.6% (40/345). The cerebral palsy rate was 41.2% (7/17) among infants who were meconium-stained at birth and 10% (33/328) among those who were not (P = .006 by Fisher exact test). After adjustment for potential confounders (gestational age and fetal gender), the odds ratio of cerebral palsy among infants delivered to women with meconium-stained AF was 6.9 (95% confidence interval 2.32, 20.81, P = .001) relative to those delivered to women with clear AF. CONCLUSION: The results of the present study support the view that the presence of meconium in the AF is a gestational age-independent risk factor for cerebral palsy among preterm infants.

Significance of low birthweight for gestational age among very preterm infants.

OBJECTIVE: To estimate the risk of specific adverse neonatal events resulting from the combined effects of prematurity and low birthweight in very preterm infants (delivered at 24-31 weeks of gestation). DESIGN: A cohort study of specific adverse neonatal events in preterm infants born at between 24 and 31 weeks of gestation. SETTING: Pavia, Italy. POPULATION: Two hundred and thirty singleton infants with sonographically confirmed gestational age, delivered at 24 to 31 weeks of gestation. METHODS: To evaluate the impact of a lower than expected birthweight on selected neonatal events independently of gestational age, we calculated birthweight standard deviation scores (differences between actual birthweight and fitted birthweight divided by fitted standard deviation) for each week of gestation. RESULTS: After adjustment for gestational age and other confounders, there was a significant linear trend relating a decreasing birthweight SDS to an increased likelihood of neonatal death, intraventricular haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with infants with SDS > or = 0 (> or = 50th centile of birthweight), infants with birthweight SDS < -1 (< 16th centile) had increased odds for neonatal death [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.42-9.6], grade III-IV intraventricular haemorrhage (OR 17.5, 95% CI 4.04-75.9), and neonatal acidosis (OR 3.22, 95% CI 1.41-7.4). The significance of birthweight SDS as a predictor of neonatal outcome, however, was lower than that of gestational age. CONCLUSIONS: A lower than expected birthweight affects the likelihood of several adverse neonatal events in very preterm infants. However, a decreasing birthweight SDS affects neonatal outcome less than decreasing gestation does.

Managing recurrent vulvovaginal candidiasis. Intermittent prevention with itraconazole.

OBJECTIVE: To evaluate the efficacy of one-day, intermittent, monthly prophylaxis with 400 mg itraconazole in the management of recurrent vulvovaginal candidiasis. STUDY DESIGN: In a randomized trial, 57 patients and 57 controls with recurrent vulvovaginal candidiasis were assigned either to receive one-day monthly itraconazole prophylaxis for six months or no treatment. Clinical and mycologic evaluations were carried out 3, 6 and 12 months after enrollment. RESULTS: During the first six months of follow-up, the rate of symptomatic recurrences was 36.4% (20/55) among the treated women and 64.2% (34/53) in the controls. The mean time +/- SEM to symptomatic recurrence was 149 +/- 6 days among patients receiving prophylaxis and 120 +/- 6 days in the controls (P = .003 by log-rank test). These differences disappeared almost completely after the cessation of intermittent prophylaxis. In fact, the proportion of patients still asymptomatic after one year of follow-up was 38.9% (21/54) among treated women and 28.8% (15/53) in the controls (P = .83 by Fisher's exact test). CONCLUSION: One-day monthly, intermittent itraconazole prophylaxis reduced the rate of recurrence in patients with recurrent vulvovaginal candidiasis, but the beneficial effect of itraconazole was lost within a few months after cessation of prophylaxis.

Prevalence of and risk factors for fungal vaginitis caused by non-albicans species.

OBJECTIVE: Our purpose was to evaluate the prevalence of symptomatic yeast vaginitis caused by non-albicans species among patients attending a vaginitis clinic over an 8-year period. STUDY DESIGN: A retrospective study of 1263 patients with symptomatic yeast vaginitis confirmed by culture techniques was performed. RESULTS: The prevalence of symptomatic fungal vaginitis caused by non-albicans species increased from 9.9% (10/101) in 1988 to 17.2% (36/209) in 1995 (chi 2 for trend = 9.33, p = 0.002). Non-albicans species were found more frequently in known human immunodeficiency virus-seropositive patients (23/102 vs 143/1161, odds ratio 2.07, 95% confidence interval 1.2 to 3.46) than in seronegative subjects or subjects of unknown status for the virus. Recurrent vaginal candidiasis was an additional risk factor for vaginitis caused by non-albicans species (odds ratio 2.47, 95% confidence interval 1.72 to 3.52). The increase in non-albicans isolates during the study period was confirmed in stratified analysis and in the subgroup of self-referred patients with no history of either human immunodeficiency virus infection or recurrent vaginal candidiasis. CONCLUSION: The prevalence of fungal vaginitis caused by non-albicans species has increased sharply in the setting of a vaginitis clinic. The characteristics of risk factors suggest that fungal cultures should be done routinely in human immunodeficiency virus-seropositive subjects with suspected vaginal candidiasis and in patients with recurrent vaginal infection.

The impact of oral contraception on chlamydial infection among patients with pelvic inflammatory disease.

The prevalence of oral contraceptive use in association with chlamydial pelvic inflammatory disease (PID) and the presence of anti-chlamydial IgG and IgA in a population of 144 hospitalized and outpatient subjects with a standard diagnosis of PID was studied. The rates of chlamydial PID and IgA detection were 15.3% (22/144) and 13.9% (20/144), respectively. After stratification for age, number of pregnancies, and lifetime sexual partners, the rates of chlamydial PID (odds ratio = 0.30, 95% CI = 0.10 - 0.89) and IgA detection (odds ratio = 0.23, 95% CI = 0.07 - 0.73) were lower among previous or current oral contraceptive users than in women who had never used birth control methods. Analyses of linear trend indicated a negative association between increasing duration of exposure to hormonal contraception and anti-chlamydial IgG and IgA. This study confirms that among patients with chlamydial PID, the frequency of oral contraceptive use is lower than that in patients with PID of other etiology. Serologic studies suggest a possible relationship between hormonal contraception and changes in immune response or susceptibility to chlamydial infection.

Cervical intraepithelial neoplasia in pregnant intravenous drug users infected with human immunodeficiency virus type 1.

OBJECTIVE: The purpose of this study was to evaluate the frequency and natural history of cervical intraepithelial neoplasia (CIN) during pregnancy in past or current intravenous drug users infected with human immunodeficiency virus type 1 (HIV-1). STUDY DESIGN: We prospectively evaluated 48 pregnant HIV-1 seropositive patients and 38 HIV seronegative controls. All the subjects were current or past intravenous drug users. Follow-up visits were carried out each trimester of pregnancy and 8-12 weeks post-partum with Papanicolau smears, colposcopic examinations and, when necessary, colposcopically directed cervical biopsies. RESULTS: Thirteen of 48 HIV-seropositive women (27.1%) and three of 38 HIV-seronegative controls (7.9%) (P = 0.027 by Fisher exact test) had biopsy-proven CIN at the beginning of pregnancy. High-grade CIN was detected in 10 cases (20.8%) and in two (5.3%) controls (P = 0.058 by Fisher exact test). None of the cervical squamous intraepithelial lesions progressed throughout pregnancy, in both cases and controls. Post-partum cold-knife cervical conization was performed on seven patients with CIN III and examination of the cone biopsy specimens demonstrated persistence of CIN III. CONCLUSIONS: HIV-infected intravenous drug users are at high risk of CIN during pregnancy, thus requiring adequate screening programs. Our preliminary data suggest that the progression rate of CIN during gestation is low in this high-risk group.