Direct measurement of nutrient concentrations in freshwaters with a miniaturized analytical probe: evaluation and validation.

This work deals with the evaluation of the aqueous concentrations of dissolved reactive phosphorus (DRP), total phosphorus (TP), and ammonium nitrogen (N-NH4) in surface water by means of direct online instrumentation. A portable, submersible, and automated analyzer designed to measure dissolved and total nutrient concentrations characterized by miniaturization of the entire analytical process was tested against laboratory methods. A total number of 36 water samples of different origin (i.e., rain, river, lake, and sewage waters) were analyzed and used in the comparison of DRP, TP, and N-NH4 data. Raw data were distributed in a broad range of concentrations: 5-299 µg P/L for DRP, 7-97 µg P/L for TP, and 11-332 µg N/L for N-NH4. Regression analysis underlined a high significant correlation between the measures of the probe and those of the laboratory (0.6 < R 2 < 0.9; p < 0.001) and pointed out the effectiveness of the new instrument in representing a broad range of nutrient concentrations.

Hypertension negatively affects the pregnancy outcome in patients with antiphospholipid syndrome.

The impact of hypertension in the pregnancies from autoimmune patients is not unequivocally defined. We have prospectively followed 168 pregnancies from 135 patients from four Italian centres to verify the potential impact of hypertension in the antiphospholipid syndrome (APS). The rate of preeclampsia, mean neonatal weight and gestational age at delivery were significantly lower in patients with both APS and hypertension than in patients with hypertension or APS alone. This information may be relevant for counselling and care of these patients.

Transvaginal ultrasound predicts delayed response to chemotherapy and drug resistance in stage I low-risk trophoblastic neoplasia.

OBJECTIVES: Methotrexate (MTX) resistance is defined on the basis of the human chorionic gonadotropin (hCG) curve. The aim of this study was to identify low-risk non-metastatic patients with gestational trophoblastic neoplasia (GTN) who can achieve resolution by continuing MTX treatment despite a transient hCG plateau. METHODS: Before starting chemotherapy, 24 patients with FIGO Stage I GTN underwent transvaginal ultrasonography with power Doppler in order to identify myometrial lesions (areas of increased echogenicity and increased power Doppler signal). Ultrasound response to chemotherapy was defined when myometrial lesions decreased in echogenicity, Doppler signal or size. When ultrasound response occurred, despite chemoresistance defined by hCG values, MTX treatment was continued. RESULTS: MTX was continued in three out of seven chemoresistant patients because ultrasound suggested response to MTX. All three of these patients achieved a complete response, thus nearly halving the MTX-resistance rate. CONCLUSION: Among patients who are candidates for second-line treatment on the basis of hCG, ultrasound may identify those in whom further MTX administration can induce a delayed complete response.

Relations between cardiovascular risk estimates and subclinical atherosclerosis in naive HIV patients: results from the HERMES study.

The aim of the study was to evaluate the cardiovascular risk factors associated with subclinical carotid atherosclerosis in antiretroviral therapy-naïve HIV-infected patients. The HERMES (HIV Exposure and Risk of Metabolic Syndrome) study enrolled therapy-naïve patients attending hospitals in the Italian coordination group for the study of allergies and HIV infection (CISAI [Coordinamento Italiano per lo Studio Allergia e Infezione da HIV]) in 2007. It was designed to identify metabolic syndrome (MS) and cardiovascular risk factors. The present analysis is a nested cross-sectional study with a subset of patients examined by carotid ultrasonography. Consecutive antiretroviral therapy-naïve HIV patients attending the facilities involved in the CISAI were included. Their 10-year probability of cardiovascular events was calculated using the Framingham Risk Score (FRS) and three other cardiovascular algorithms (the Global Framingham Risk Score - GFRS, 'Progetto Cuore' and 'SCORE'). Vascular age was estimated using a new model derived from GFRS and was compared with chronological age. The diagnosis of MS was based on the National Cholesterol Education Programme and International Diabetes Federation (IDF) definitions. Subclinical atherosclerosis was determined as ultrasound carotid intima-media thickness >0.9 mm. Out of 140 patients enrolled in the HERMES study by the four centres participating in the nested study, a total of 72 (51.4%) subjects, with no overt cardiovascular disease, were examined using carotid ultrasonography. The median age was 40 years, 79.2% men. The vascular age was 7.6 years higher than the chronological age. The factors associated with subclinical atherosclerosis were age (P < 0.0001), vascular age (P = 0.0002), body mass index (P = 0.003), waist circumference (P = 0.0002), MS (IDF definition, P = 0.004) and all the cardiovascular (CV) models (FRS, P = 0.01, GFRS, P = 0.002, Progetto Cuore, P = 0.018, SCORE, P = 0.03). Independent of other significant factors, waist circumference was significantly associated with pathological results (P = 0.007). The GFRS (area under the receiver-operating characteristic curves, 0.78; P < 0.001) had slightly better predictive accuracy than the other three CV models (FRS, areas under the curve [AUC] = 0.71, P = 0.003; Progetto Cuore, AUC = 0.74, P = 0.0005; SCORE, AUC = 0.77, P < 0.0001); 55% of patients at intermediate risk (6-20%) had subclinical carotid lesions. Subclinical carotid lesions had a highly significant direct association with all the CV risk predictors. The GFRS and vascular age were highly predictive. We recommend a carotid ultrasonographic examination at least among HIV patients with GFRS > or =6% or with an elevated waist circumference.

Actual controversies in twin delivery: from the analysis of the case histories to a reasoned protocol.

AIM: Twin pregnancy has to be considered a risk pregnancy. One of its most controversial aspects is delivery. There is no agreement on the following topics: gestational age at term (GA), mode of delivery, use of epidural analgesia or oxytocic acceleration, impact of chorionicity and amnionicity. The aim of this study was to develop a twin delivery management protocol. METHODS: A retrospective study over a cohort population of 481 twin deliveries that occurred in the Department of Obstetrics of the San Raffaele Hospital of Milan (Italy) from 1996 to 2007 was conducted, and the results were compared with those present in literature. RESULTS: Management of twin pregnancies that exceed the 37 week is controversial. There is an inclination towards fixing bichorionic and monochorionic pregnancy terms at 38 and 35 weeks respectively. In our case history, 73.8% of monochorionic and 15% of bichorionic pregnant women delivered after the 35 and 38 week respectively, without repercussions on the neonatal outcome. A longer gestational age appears to decrease the occurrence of lower Apgar scores and neonatal morbidity. This study, which exclusively considered twin pregnant women with both fetuses in cephalic presentation eligible for a vaginal delivery, did not find any significant differences in neonatal outcome among the types of deliveries. Moreover, the authors observed that the average maternal blood loss in cesarean section (CS) is significantly greater than that of vaginal deliveries. CONCLUSIONS: In consideration of its safety for mother and fetuses, vaginal delivery of two cephalic fetuses at 38 and 35 weeks for bichorionic and monochorionic pregnancies respectively may be considered as a valid alternative to elective cesarean section.

Toxicity risk assessment of mercury, DDT and arsenic legacy pollution in sediments: A triad approach under low concentration conditions.

The determination of sediment toxicity is challenging due to site-specific factors affecting pollutants distribution and bioavailability, especially when contamination levels are close to expected non-effect concentrations. Different lines of evidence and sensitive tools are necessary for a proper toxicity risk assessment. We examined the case study of the Toce River (Northern Italy), where past industrial activities determined Hg, DDT and As enrichment in sediments. A triad approach comprising chemical, ecotoxicological and ecological analyses (benthic invertebrates) was carried out for risk assessment of residual contamination in river sediments. A "blank" site upstream from the industrial site was selected to compare the other sites downstream. Sediment, water and benthic invertebrate samplings were carried out following standard protocols. Results emphasized that despite the emissions of the industrial site ceased about 20years ago, sediments in the downstream section of the river remain contaminated by Hg, DDT and As with concentrations exceeding Threshold Effect Concentrations. A chronic whole-sediment test with Chironomus riparius showed decreased development rate and a lower number of eggs per mass in the contaminated sediments. Benthic community was analyzed with the calculation of integrated (STAR_ICMi) and stressor-specific metrics (SPEARpesticide and mean sensitivity to Hg), but no significant differences were found between upstream and downstream sites. On the other hand, multivariate analysis (partial Redundancy Analysis and variation partitioning) emphasized a slight impact on invertebrate community, accounting for 5% variation in taxa composition. Results show that legacy contaminants in sediments, even at low concentrations, may be bioavailable and possibly toxic for benthic invertebrates. At low concentration levels, sensitive and site-specific tools need to be developed for a proper risk analysis.

Predictive value of plasma thrombomodulin in preeclampsia and gestational hypertension.

In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin (pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or gestational hypertension (n = 12) between weeks 32 and 39 of gestation and in 25 (age-matched) primigravidae who had uneventful pregnancies. pTM elevations were not observed until week 32 in uneventful pregnancies, but were present by week 24 (p = 0.002) in patients who later developed hypertensive complications. A net individual pTM increase > or = 4.2 ng/ml between weeks 12 and 24 (more than 8 times that of normotensive primigravidae) and/or pTM level > or = 47.5 ng/ml at week 32 predicted the development of hypertensive complications with 80% accuracy. Serial pTM determinations can be useful to select pregnancies who may benefit from early pharmacological intervention.

Quantitative analysis of fetal DNA in maternal plasma in pathological conditions associated with placental abnormalities.

An increased fetal DNA concentration in maternal plasma has been observed in placental pathological conditions associated with hypertension and preeclampsia. To confirm these data, we performed real-time quantitative PCR on the SRY gene in a group of physiological and pathological male-bearing pregnancies. In 78 physiological pregnancies, fetal DNA concentration in maternal plasma was 20.7, 13.4, 23.6, and 74.8 genome-equivalents (g.e.)/mL during the first, second, and third trimesters and at term, respectively. In 10 preeclamptic women, fetal DNA concentration ranged from 59.3 to 615.2 g.e./mL (median: 332.9). In 7 women with preeclampsia and IUGR (intrauterine growth retardation), fetal DNA ranged from 96.5 to 859 g.e./mL (median: 146.8). In 4 women with IUGR and hypertension, fetal DNA ranged from 34 to 473.5 g.e./mL (median: 142.4). In 3 patients with IUGR, fetal DNA ranged from 168.6 to 519.7 g.e./mL (median: 308.1). In 2 patients with IUGR and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, fetal DNA concentration ranged from 105 to 394.1 g.e./mL (median: 249.7). Four women who developed preeclampsia some weeks later showed fetal DNA levels within the physiological range. These data suggest that increased fetal DNA concentrations might represent a valuable marker of placental abnormalities and suggest that this rise may precede clinical manifestation of preeclampsia by only a few weeks.

Predictors of protease inhibitor-associated adverse events.

Risk factors in the development of adverse reactions in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART) containing protease inhibitors are poorly understood. To identify predictors of protease inhibitor-associated adverse events, we are conducting a prospective, cohort, multicenter study on HIV-positive patients starting treatment with at least one protease inhibitor. Rate ratios (RR) of adverse events were calculated, and logistic regression was used to adjust simultaneously for the potentially confounding effects of selected variables, according to the Cox model. A total of 1477 patients have been enrolled up to April 2000, having an average age of 37.1 years (SD +/- 8.1); 1066 (72.2%) were male. Where risk factors for HIV infection are concerned, the distribution was as follows: 48.1% intravenous drug users, 31.6% heterosexual contacts, 16.2% homosexual males and 0.7% blood transfusion. Average CD4+ lymphocyte count at enrollment was 265 cells/mmc (SD +/- 201). Average follow-up time is equal to 17.8 months (range 1-32). The risk of developing adverse reactions is significantly increased in female patients, older patients, hemophiliac subjects and in subjects with hepatitis. Patients treated with ritonavir, the association ritonavir-saquinavir HGC, stavudine and efavirenz have significantly increased incidence of adverse reactions in PI-containing regimens; conversely, saquinavir HGC, zidovudine and lamivudine use was associated with a lower risk of developing adverse reactions.

Serum levels of alpha-tocopherol in hypertensive pregnancies.

OBJECTIVE: Assess alpha-tocopherol serum levels in a population of pregnant women affected by different hypertensive disorders. METHODS: Alpha-tocopherol serum levels were determined by high-pressure liquid chromatography in 177 third-trimester pregnant women: 63 affected by gestational hypertension, 69 by preeclampsia, 26 by chronic hypertension, and 19 normotensive controls. In 39 out of the 158 hypertensive patients, pregnancy was complicated by intrauterine growth retardation (IUGR). RESULTS: Alpha-tocopherol serum levels did not show any significant difference among gestational hypertensive, preeclamptic, chronic hypertensive patients, and controls. A significant reduction of alpha-tocopherol levels was observed when we compared patients with IUGR and patients with a normally grown fetus. Such significant reduction was maintained when we analyzed the different classes of hypertension. CONCLUSIONS: The reduction of antioxidant nutrients and, in particular, of alpha-tocopherol is not a feature of preeclampsia and seems better correlated with the presence of placental insufficiency, rather than maternal disease.

Chilblain lupus erythematosus is associated with antibodies to SSA/Ro.

Chillblain Lupus Erythematosus (CL) of Hutchinson is a subtype of Lupus Erythematosus characterized by erythematous lesions symmetrically distributed on the face, nose, fingers and toes, knees and heels. The lesions are induced by cold, damp climates. A number of patients affected by CL eventually develop features of Systemic Lupus Erythematosus (SLE). We report here 7 patients, all but one affected by SLE, with chilblain cutaneous lesions on their hands, feet and face. The onset of CL preceded the diagnosis of SLE, from 1 to 10 years in 3 cases, it was concurrent in one case and was subsequent in the other 2 cases. Six out of the seven patients referred typical Raynaud's phenomenon and one had acrocyanosis. CL lesions developed and were aggravated by the cold during autumn and winter, they improved during summer. Skin biopsy performed in 5 patients from the lesions showed, on histology, a typical pattern of alterations with granular deposits at the dermo-epidermal junction on direct immunofluorescence. Laboratory findings showed: ANA and anti-SSA/Ro were detected in all the patients, anti-SSA/Ro were isolated in 4 patients and associated with anti-Sm in one case, anti-U1 RNP in one case and with anti-Sm and anti-RNP in a third case. Complement consumption was observed in 5 patients, anti-dsDNA in the six patients with SLE, hypergammaglobulinemia in 4 and rheumatoid factor in one. The fine specificity of anti-SSA/Ro as determined by immunoblotting using a human spleen extract as a substrate, showed: anti-60kD and anti-52 kD in two sera, anti-60kD isolated in 2 sera, anti-52kD isolated in one serum (from the patient without SLE) while 2 sera did not blotted. In conclusion, our study confirms the previous report of anti-SSA/Ro antibodies in association with CL. This clinical and serologic association widens the spectrum of cutaneous disease that is associated with antibodies to SSA/Ro to include conditions such as to SCLE, hypergammaglobulinemic purpura and neonatal lupus.

Reliability of preoperative evaluation of prognostic factors in endometrial carcinoma.

OBJECTIVE: To define the accuracy of preoperative evaluation of prognostic factors in detecting patients with low risk of node metastasis in which different surgical approaches can be proposed. SUBJECTS: Seventy-five patients with a histologically proven endometrial carcinoma were considered in this study. METHODS: All the patients underwent a preoperative evaluation of grading (G), and myometrial invasion (M) by endometrial biopsy and transvaginal ultrasound (TVS). In 41 patients preoperative ploidy of carcinoma cells (P) was determined by flow cytometry. Pre-surgical G, M and P were then compared with surgical specimens. We considered 'low risk', patients with no or moderate myometrial invasion, well-differentiated histological grading and diploid DNA. RESULTS: We were able to identify 19/23 (82.6%) low risk cases. Correct identification of high risk patients was obtained in 49/52 (94%) patients. In three low risk patients, correctly diagnosed preoperatively, the final FIGO stage was IIIA (two for adnexal involvement and one for positive peritoneal washing). CONCLUSIONS: Our findings suggest that it is possible to detect preoperatively patients with a low risk of node metastasis. Alternative surgical approaches, i.e. vaginal surgery, can be taken into account in such patients.

[Causality relationship of drug adverse reactions: experience in the use of HIV-protease inhibitors]. / Relazione di causalità delle reazioni avverse a farmaci: un'esperienza nell'utilizzo degli inhibitori della proteasi di HIV.

PURPOSE: To establish the exact cause and effect relationship between protease inhibitors (PIs) and adverse events. MATERIALS AND METHOD: Prospective, cohort, multicenter study on HIV-positive patients who are beginning treatment with a PI. Causal relationships are evaluated using the RUCAM algorithm. RESULTS: Since the beginning of the study 1207 patients have been enrolled. Average time of observation is 10.7 months. To date, 784 adverse events have been observed, distributed as follows: excluded 3.8%, improbable 18.5%, possible 41.3%, probable 30.1%, and highly probable 6.3%. Saquinavir shows a statistically significant difference in the rate of non-correlated events with respect to other groups. CONCLUSIONS: Over 20% of adverse events during PI treatment are shown to be non-correlated to these drugs. Saquinavir shows the highest rate of non-correlated events.

The risk of preeclampsia beyond the first pregnancy among women with type 1 diabetes parity and preeclampsia in type 1 diabetes.

AIM: To estimate the incidence of preeclampsia (PE) among nulliparous and multiparous patients with type 1 diabetes and to study predictors of PE. METHODS: We prospectively collected data on all pregnancies of patients with pregestational type 1 diabetes, followed at our Prenatal Medicine Unit between 1993 and 2008. Medical records were prospectively reviewed by two obstetricians for maternal demographics, pregnancy data, maternal and fetal outcomes. Data were analyzed according to the development of PE and parity. RESULTS: We identified and collected data on 291 eligible pregnancies (195 among nulliparae and 96 among multiparae). The incidence of PE was 9.2% (95% CI: 5.6-14.2) among nulliparae and 9.4% (95% CI: 4.4-17.0) among multiparae. Patients who developed PE had higher HbA1c during pregnancy compared to patients who did not (p=0.026 among nulliparae and p=0.032 among multiparae). Chronic hypertension [OR 17.12 (3.22, 91.00)], microalbuminuria at the beginning of the pregnancy [OR 3.77 (1.22, 11.61)], weight gain during pregnancy [OR 1.13 (1.04, 1.23)] and HbA1c in the first trimester [2.81 (1.12, 7.05)], but not parity, were significant predictors of PE. CONCLUSIONS: Among patients with type 1 diabetes the incidence of PE was similar among nulliparae and multiparae, unlikely in the general population where PE is a disease of the first pregnancy. An increased risk of PE should be assumed for both nulliparous and multiparous women with pregestational diabetes.

Transvaginal ultrasonography in persistent trophoblastic tumor.

OBJECTIVE: We assessed the reliability of transvaginal ultrasonography in the detection of uterine involvement in cases of gestational trophoblastic tumor, to establish a possible role of this procedure in the management of such neoplasia. STUDY DESIGN: Transvaginal ultrasonography was performed in six women with gestational trophoblastic tumor at initial diagnosis, during the cytotoxic course when negative beta-human chorionic gonadotrophin levels were obtained, and within 3 to 6 months after the end of chemotherapy. RESULTS: In all cases in which metastatic disease was absent intrauterine localization was easily detected by transvaginal ultrasonography; it appeared as endometrial hypoechoic areas and intramyometrial nodules. Favorable response to chemotherapy was determined by a negative serum beta-human chorionic gonadotropin determination accompanied by the finding of regression of nodules at transvaginal ultrasonography. CONCLUSION: Our data support the introduction of transvaginal ultrasonography in the management of gestational trophoblastic tumor.

Opportunistic infections of the esophagus not responding to oral systemic antifungals in patients with AIDS: their frequency and treatment.

To determine the spectrum of esophageal disease responsible for dysphagia/odynophagia in AIDS patients not responding to current oral antifungals, we studied 49 consecutive patients whose esophageal symptoms failed to improve after a minimum of 3 wk of therapy with oral ketoconazole or fluconazole. An esophageal candidiasis resistant to oral antifungals was the most frequent disease found (22 single infections and four mixed with viruses). Viral esophagitis was identified in 13 cases (eight herpes simplex virus and five cytomegalovirus), and an esophagitis of unknown origin was documented in two patients. Other causes of symptoms included peptic esophagitis (four cases), esophageal stenosis (two cases), and Kaposi's sarcoma of the esophagus (one patient). Most patients with esophageal opportunistic infection experienced prompt relief of symptoms and complete endoscopic resolution on the specific antifungal (amphotericin B or fluconazole iv) or antiviral (acyclovir or gancyclovir iv) therapy, with the exception of those with concomitant fungal and viral infection who responded poorly to treatment. We conclude that most AIDS patients with dysphagia/odynophagia who do not respond to oral antifungals have an opportunistic infection of the esophagus. Nevertheless, specific antifungal or antiviral therapy is worthwhile, because it will eradicate, at least temporarily, the causative pathogens in most such patients.

Clinical and histologic aspects of chronic delta hepatitis.

Clinical and histologic valuation of delta chronic hepatitis is performed by a comparison between 46 HDV markers seropositive patients and an analogous group of HBsAg seropositive and delta system negative patients. It is possible to point out a greater seriousness of clinical and biohumoral situation during a HDV induced disease which is joined up with a more marked histologic damage and a greater inflammatory activity. The presence of specific viral antigen in hepatocyte nucleus suggests a delta-virus direct cytopathic effect.

Acute upper gastrointestinal bleeding in patients with AIDS: a relatively uncommon condition associated with reduced survival.

To determine the cumulative incidence of acute upper gastrointestinal bleeding and its effect upon survival in patients with AIDS, 453 consecutive AIDS patients diagnosed in our hospital between June 1985 and March 1989 were followed for a median period of six months (maximum 42 months). The cumulative probability of acute gastrointestinal bleeding was 3% at six months and 6% at 14 months. This event was associated with significantly reduced survival. Independent risk factors for bleeding were: severe thrombocytopenia at the time of diagnosis and non-Hodgkin's lymphoma as the first clinical manifestation of AIDS. The potential causes of bleeding were investigated in all cases by emergency endoscopy or by necropsy examination in those patients whose clinical condition precluded the procedure. In nine of 15 patients, bleeding was due to lesions specifically associated with AIDS, but in the remainder the source of bleeding was not a direct consequence of HIV infection. We conclude that acute upper gastrointestinal bleeding rarely complicates the course of AIDS, but its occurrence is associated with decreased survival. As many of the causes are potentially treatable, a complete diagnostic approach is indicated in these patients, except those who are terminally ill.