Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network.

BACKGROUND: Angiosarcoma is a highly aggressive soft tissue sarcoma. Responses to anthracyclines plus/minus ifosfamide, and taxanes alone or in combination with gemcitabine are well documented. Very few data are available on gemcitabine as a single agent. PATIENTS AND METHODS: We retrospectively reviewed all cases of advanced progressive angiosarcoma treated with gemcitabine as a single agent (1000 mg/m(2) i.v. every week for 3 weeks every 4 weeks), at Istituto Nazionale Tumori and within the Italian Rare Cancers Network from January 2008 to November 2010. RESULTS: Twenty-five patients [mean age: 52 years; radiation therapy (RT)-related: 8] received gemcitabine. Best tumor response by RECIST was as follows: complete response = 2, partial response = 14, stable disease = 2, progressive disease = 7 cases, for an overall response rate (PR + CR) of 68%. Six of eight post-RT angiosarcomas responded to treatment. Median overall survival (OS) was 17 months. Median progression-free survival (PFS) was 7 months (range 1-40 months). One patient with a locally advanced thyroid angiosarcoma became resectable after 5 months of gemcitabine, with <10% residual viable tumor cells seen on surgical specimen. Overall, gemcitabine was well tolerated. CONCLUSIONS: Gemcitabine is active in both RT- and non-RT-related angiosarcoma, with dimensional and possibly long-lasting responses. A formal phase II study on gemcitabine as a single agent is warranted.

Influence of body mass index on extent of coronary atherosclerosis and cardiac events in a cohort of patients at risk of coronary artery disease.

BACKGROUND AND AIM: To estimate if a meaningful relationship exists between body mass index (BMI) and the entity of coronary atherosclerosis, coronary events and mortality in a cohort of consecutive patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: In this prospective study, we enrolled 1299 consecutive patients (905 [69.7%] males) who had undergone coronary angiography. Our sample consisted of 477 patients (36.8%) of normal weight; 567 (43.6%) overweight and 255 (19.6%) obese, according to the WHO classification. Conventional cardiovascular risk factors, BMI, endothelial function and subclinical inflammation were studied. Different angiographic CAD scores were used to quantify coronary atherosclerotic burden. In overweight and obese patients, respect to normal weight population, there is a higher prevalence of hypertension, hypercholesterolemia and diabetes mellitus, but BMI was not significantly associated with greater extent of coronary atherosclerosis. At follow-up (mean: 40; range: 24-82 months) obese and overweight patients showed a higher incidence of coronary events compared to the normal weight population (74.9% [obese] versus 62.7% [overweight] versus 53.2% [normal weight]; adjusted relative risk [obese versus overweight]: 1.08 [95% confidence interval: 1.02-1.23]; P<0.05; and adjusted RR [obese versus normal weight]: 1.17 [95% CI: 1.10-1.42], P<0.01). Mortality from cardiac events was not significant within the categories. The Cox regression model showed flow mediated dilation (P<0.0001), high-sensitive C reactive protein (P=0.022) and BMI (P=0.045) as independent predictors of acute coronary events. CONCLUSION: BMI is not associated with the extent of coronary atherosclerosis and mortality. The higher incidence of coronary events in obese subjects is only partly explained by conventional associated risk factors. Impaired endothelial function and sub-clinical inflammation could be involved in this association but BMI itself is related to cardiovascular events suggesting that other unknown (or not considered) pathways are involved.

Inositols and metabolic disorders: From farm to bedside.

Inositol and its derivates are catching interest in metabolism since taking part in several physiological processes, including endocrine modulation. Through several mechanisms mostly mediated by insulin signaling, these compounds regulate the activities of several hormones and are essential in oocytes maturation. It is interesting to point out the contribution of an inositol deficiency in the development of several diseases, mainly in the metabolic and endocrine setting. Inositols derive from both diet and endogenous production; among causes of inositol deficiency reduced dietary intake, increased catabolism and/or excretion, decreased biosynthesis, inhibition of gut and cellular uptake and altered microbiota could be considered. Mounting direct and indirect evidence suggests that the two main isoforms (Myo-inositol-inositol, D-chiro-inositol) are implied in glycemic and lipidic metabolism and supplementation yield a beneficial effect on these parameters without hazards for health. Moreover, they have a role in polycystic ovary syndrome, acting as insulin-sensitizing agents and free radical scavengers, helping to regulate metabolism and promoting ovulation. The aim of this narrative review is to discuss the role of inositols in metabolic function disorders paying attention to whether these compounds could be efficacious and safe as a therapeutic agent with a focus on dietary intake and the role of gut microbiota.

Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study.

BACKGROUND & AIMS: Teduglutide, a GLP-2-analog, has proven effective in two placebo-controlled studies in reducing parenteral support (PS) in patients with short bowel syndrome-associated intestinal failure (SBS-IF) after 24 weeks. The aim of this study was to describe in a real-life situation the effects of teduglutide treatment and their predictive factors. METHODS: We included 54 consecutive SBS-IF patients treated with teduglutide in France for at least 6 months from 10 expert centers. Small bowel length was 62 ± 6 cm and 65% had colon in continuity. PS was 4.4 ±0 .2 infusions per week, started 9.8 ± 1.2 years before. Response (PS reduction ≥ 20%) and PS discontinuation rates were assessed at week 24. Adjusted p values of factors associated with response and weaning were calculated using a multivariate logistic regression model. RESULTS: At week 24, 85% of patients were responders and 24% had been weaned off PS, with a 51% reduction of PS needs and 1.5 ± 0.2 days off PS per week. Response to teduglutide was influenced by a higher baseline oral intake (p = 0.02). Weaning off PS was influenced by the presence of colon (p = 0.04), a lower PS volume (p = 0.03) and a higher oral intake (p = 0.01). There were no differences based on age, bowel length or SBS-IF causes. CONCLUSIONS: Our study confirms the effectiveness of teduglutide in reducing PS needs in SBS-IF patients. We associated reduced parenteral support volume with baseline parenteral volume support, bowel anatomy, and oral intake. These findings underline the role of nutritional optimization when starting the treatment.

The management of pre-hypertension and metabolic syndrome.

The new guidelines for diagnosis and treatment of arterial hypertension introduce the new concept of "pre-hypertension", that comprises those individuals who have either systolic blood pressure (BP) of 120-139 mmHg or diastolic BP of 80-89 mmHg. The Committee recommended the identification of these individuals as they are at increased risk for progression to hypertension and subsequently other cardiovascular disease (CVD). Metabolic syndrome (MS) is a constellation of CVD risk factors, including atherogenic dyslipidemia, elevated BP, impaired glucose regulation, and abdominal obesity. Compared to those without MS, individuals with MS have a 61% increased risk of CVD. The aim of the review was explain the "real" relationship between these two clinical conditions describing the pathogenic mechanisms that put them in correlation. These findings may also offer compelling evidence for screening and early detection in vulnerable groups predisposed to CVD. Randomized intervention studies are needed to quantify the extent of any potential benefit of therapy among individuals with BP levels usually considered normal.

Correction to: Transsphenoidal surgery for pituitary adenomas: early results from a single center.

Unfortunately in the original publication, the affiliation of the author Paolo Marzullo was incorrect. The author inadvertently missed out to include his second affiliation.

Acute mesenteric ischemia: A critical role for the radiologist.

Acute mesenteric ischemia is defined as an inadequate blood supply to the gastrointestinal tract resulting in ischemic and inflammatory injury that may progress to necrosis of the bowel wall. Prognosis is poor with a mortality rate greater than 95% without treatment, dropping to around 70% when surgical treatment is performed. Contrast-enhanced computed tomography (CT) has become the cornerstone of the diagnosis by showing features of vascular disorders (occlusion and/or insufficient blood supply) and features of intestinal ischemic injury. CT should be performed as rapidly as possible. Imaging-based patient management is required, and multimodal and multidisciplinary management should be introduced. The treatment involves multidisciplinary management by gastroenterologists, vascular and digestive surgeons, cardiologists, intensivists, and diagnostic and interventional radiologists. Based on our experience at a dedicated mesenteric stroke center, this article gives an overview of the diagnosis of acute mesenteric ischemia. The goal of this review is to improve the understanding of the imaging-based diagnosis to further improve the management of this life-threatening condition.

Transsphenoidal surgery for pituitary adenomas: early results from a single center.

OBJECTIVE: To evaluate early results of transsphenoidal surgery for pituitary adenomas. DESIGN: Retrospective evaluation of 90 consecutive patients undergoing endoscopic pituitary adenoma surgery (2007-2016) at "Maggiore della Carità" Hospital in Novara, Italy. Age at diagnosis, sex, symptoms at presentation, hormonal and radiological data, complications of surgery, and short-term follow-up information were collected. RESULTS: The majority of patients were male (M/F: 1.5/1, mean age at diagnosis 62.1 ± 1.5 years mean ± SEM). Most patients (91.1%) presented with a macroadenoma (27.4 mm ± 1.1 mm mean ± SEM), while 77.8% were non-functioning pituitary adenomas. Clinical presentations related to mass effect were visual impairment (74.0%) and/or hypopituitarism (55.1%). The main surgery complication was insipidus diabetes (12.2%), followed by cerebral hemorrhage (4.4%), cerebrospinal fluid (CSF) leaks (4.4%), syndrome of inappropriate antidiuresis (SIAD) (2.2%), and epistaxis (2.2%); only one patient died because of stroke. Risk of complications was not associated with tumor size (OR = 0.588, 95% CI 0.967-1.081, p = 0.443). Visual function improved in 70.6% of patients, while recovery of normal pituitary function occurred in 48.1%. Early neuroimaging studies demonstrated no residual tumor in 27.6% of patients. Invasion of cavernous sinus (OR = 3.293, 95% CI 0.897-16.738, p = 0.05) and maximum tumor diameter (OR = 6.857, 95% CI 1.039-1.309, p < 0.01) were associated with an unfavorable surgical outcome. CONCLUSIONS: Transsphenoidal endoscopic surgery for pituitary adenomas is safe and is frequently followed by improvement in visual symptoms, whereas recovery of pituitary function is less common. In our patients, complete surgical removal of adenomas is comparable to that of other series, but further investigations will be necessary to clarify the long-term risk of tumor recurrence.

Automatic pedigree reconstruction for genetic studies in isolated populations.

This paper describes a tool implemented to automatically reconstruct the pedigree of an isolated population of Northern Italy with the aim of supporting genetic studies. The goal of such studies is to analyze genealogic, clinical and genetic data for genetic dissection of complex diseases. In this context the reconstruction of the population pedigree is fundamental to verify that such population is a genetic isolate and obtain the parental relationships among the individuals participating to the study. The algorithm presented in the paper, from heterogeneous data sources (demographic municipal and parish archives and other data sources), derives the pedigree applying several heuristic rules in a predefined order. One of the main difficulties in performing such task stands in the "record linkage" process that requires the definition of a sufficiently general strategy for managing the ambiguities caused by missing or imprecise/erroneous input data. The paper, finally, presents and discusses the preliminary results obtained by reconstructing the pedigree of four villages from the data collected during the first eighteen months of project.

[Management of mesenteric ischemia in the era of intestinal stroke centers: The gut and lifesaving strategy]. / L'ischémie mésentérique à l'ère des structures d'urgences vasculaires intestinales.

Mesenteric ischemia is a gut and life-threatening, medical and surgical, digestive and vascular emergency. Mesenteric ischemia is the result of an arterial or venous occlusion, a vasospasm secondary to low-flow states in intensive care patients, aortic clamping during vascular surgery or intestinal transplantation. Progression towards mesenteric infarction and its complications is unpredictable and correlates with high rates of mortality or a high risk of short bowel syndrome in case of survival. Thus, mesenteric ischemia should be diagnosed and treated at an early stage, when gut injury is still reversible. Diagnostic workup lacks sensitive and specific clinical and biological marker. Consequently, diagnosis and effective therapy can be achieved by a high clinical suspicion and a specific multimodal management: the gut and lifesaving strategy. Based on the model of ischemic stroke centers, the need for a multidisciplinary and expert 24/24 emergency care has led, in 2016, to the inauguration of the first Intestinal Stroke Center (Structure d'urgences vasculaires intestinales [SURVI]) in France. This review highlights the pathophysiological features of chronic and acute mesenteric ischemia, as well as the diagnosis workup and the therapeutic management developed in this Intestinal Stroke Center.

Characterization of typical aquatic humic substances in areas of sugarcane cultivation in Brazil using tetramethylammonium hydroxide thermochemolysis.

Aquatic humic substances (AHSs) differ from one environment to another depending on land use and occupation. In addition, the effects of planting sugarcane on AHSs are not well known. Thus, the aim of this study was to characterize AHSs extracted from a river in a typical region of sugarcane cultivation during dry and rainy seasons. The main characteristics of the AHSs were obtained using Fourier transformation infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and off-line pyrolysis coupled with gas chromatography and mass spectrometry (off-line tetramethylammonium hydroxide (TMAH)-GC-MS-thermochemolysis). The FTIR and NMR results were used to infer that no distinctions occurred between the sampling periods. The samples were composed of aromatic groups that were potentially associated with the presence of residual vegetable materials (lignin). The results of the off-line TMAH-GC-MS-thermochemolysis indicated that the structures of the AHSs had uniform compositions that were rich in fatty acid methyl esters (FAMEs), polysaccharide derivatives, aliphatic biopolymers derived from plants, long hydrocarbon chains, branched alkyl groups and methylene carbons. Thus, the results showed that the AHSs obtained from the sugarcane cultivation area during the crop period mainly consisted of resistant aliphatic hydrocarbons, which are derivatives of lignin and FAMEs in compounds rich in humic acid. Therefore, we concluded that sugarcane cultivation produces changes in AHSs because greater amounts of lignin derivatives were observed during the dry season, corresponding to sugarcane cultivation.

Detection of vancomycin resistance in enterococci by the Vitek AMS system.

The ability of the Vitek AMS system to detect vancomycin resistance in enterococci was evaluated by comparing the results to an agar dilution screen method. Of 100 strains tested, 43 were resistant and 51 were susceptible by both tests. Two strains were intermediate by Vitek but susceptible by agar screen, one was intermediate by Vitek but resistant by agar screen, and four were susceptible by Vitek but resistant by agar screen. When the Vitek intermediate and resistant results were combined, the false resistant rate was 4.4% and false susceptible rate was 8.5%. In its current format, the Vitek system appears not to have acceptable accuracy for the detection of vancomycin resistance in enterococci.

Multicenter phase II study of fractionated bimonthly oxaliplatin with leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer, pre-treated with chemotherapy.

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.

Multicenter phase II study of CPT-11 fractionated over two days with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer.

PURPOSE: This multicenter phase II study evaluated the activity and toxicity of the combination of fractionated camptothecin (CPT-11) and 5-fluorouracil/leucovorin (5-FU/LV) (de Gramont regimen) for the treatment of metastatic colorectal cancer (MCC) patients who had received no prior chemotherapy for metastatic disease. PATIENTS AND METHODS: Fifty-four patients with a median age of 63.5 years (range: 43-75), received, every two weeks, a regimen consisting of 2 daily doses of CPT-11, 90 mg/m2 administered over a period of 90 minutes, followed by LV, 200 mg/m2 administered over 2 hours and 5-FU 400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour continuous infusion. Sixty-five percent of patients had synchronous metastatic disease at diagnosis, while 35% of the patients had received adjuvant chemotherapy after radical surgery. RESULTS: All 54 patients, receiving a total of 561 cycles of chemotherapy (median 12 per patient, range 1-26), were assessable for toxicity and response to treatment. The most common toxicities (grade 3-4) among treated patients were as follows: diarrhea in 3 patients, (6%), neutropenia in 9 patients (17%) and asthenia in 3 patients (6%), with no treatment-related death. We observed 4 complete (7.4%) and 18 partial responses (33.3%), giving an overall response rate of 40.7% (95% CI: 28% to 55%); 22 patients had stable disease (40.7%) and 10 patients progressed (18.5%). After a median follow-up of 22 months, the median time to progression was 8.7 months (range 2.3-43.9+), while overall median survival was 18.8 months (range 0.7-43.9+). CONCLUSION: The fractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed a lower gastrointestinal toxicity profile than expected, with substantial activity in patients with MCC.

Activity of standard-dose carboplatin, cyclophosphamide, and etoposide in patients with metastatic breast cancer with previous exposure to anthracyclines.

The prognosis for patients with metastatic breast cancer, progressing after anthracycline-based cytotoxic therapy, is poor, and new treatment strategies are needed. Carboplatin (CBDCA), etoposide (VP-16), and cyclophosphamide (CTX) combination therapy has proved activity against a wide variety of tumors. This study was undertaken to evaluate the activity and toxicity of standard doses of CBDCA, VP-16, and CTX administered as salvage chemotherapy in a group of patients with metastatic breast cancer previously treated with two chemotherapy regimens, including anthracyclines. Thirty patients received an average 3.5 courses of the following treatment: CBDCA, 300 mg/m2, and CTX, 500 mg/m2, on day 1; VP-16, 60 mg/m2, on days 2, 3, and 4. Thirteen patients (43%) achieved an objective response, seven (23%) stabilized, while 10 (34%) progressed. The median response duration was 11.5 months (range, 1-19); the median overall survival from protocol entry was 9.1 months (range, 1.5-26). Gastrointestinal toxicity was noted in six patients, and hematologic toxicity of grade 3-4 was found in 11 patients. The combination of CTX, CBDCA, and VP-16 at this dose and schedule is active as salvage treatment of patients with breast cancer. Even when the toxicity was severe, responders had good symptom palliation with a substantial improvement in performance status.

Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer.

We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, to either a combination chemotherapy of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or the same regimen plus interferon. Between January 1990 and March 1992, 100 untreated patients (PTS) with advanced colorectal cancer, 53 men and 47 women, with an ECOG performance status (PS) of < or = 3, were randomized to either HDFA 200 mg/m2 iv bolus and 5FU 370 mg/m2 in 15-min iv infusion days 1-5 every 4 weeks (arm A), or the same chemotherapy plus IFN 3 x 10(6) IU subcutaneously three times a week in chemotherapy intervals (arm B). A total of 97 PTS are evaluable for response, toxicity, and survival; 3 PTS are not evaluable in arm B for major protocol violations. PTS characteristics were well balanced in both arms for age (median, 64 years), disease-free survival, and disease site. ECOG PS was 0 in 28% of PTS in arm A and in 13% in arm B. Response rates were as follows: arm A, 40%; and arm B, 23%. Median time to failure was as follows: 10.2 months arm A versus 9 months arm B. Median survival was as follows: 13.3 months arm A versus 10.9 months arm B. Grade 3 haematological toxicity was 9% of PTS in both arms. Gastrointestinal toxicity was as follows: 17% arm A versus 22% arm B. The cost of drugs expressed per m2/month was $60 in arm A and $390 in arm B. The results show that IFN at the schedule and doses employed adds no benefit to the combination of 5FU/HDFA.

[Intraoperative esophageal manometry in the surgical treatment of achalasia]. / Manometría esofágica intraoperatoria en el tratamiento quirúrgico de la acalasia.

Since 1985 we have done intraoperative manometry in 54 patients operated for achalasia. Manometry allows the assessment of the completeness of the division of the high pressure zone and ascertain the length of fundoplication (Nissen) as well as its pressure. In 26 patients pH and manometric controls were done postoperatively. Absence of reflux was noted in all and the pressure level after operation was 12.53 +/- 4.94 mmHg. Pressure measurements were not different from those of a group of 15 healthy subjects (15.2 +/- 2.45 mmHg). Dynamic studies of the high pressure zone revealed a post-deglutition relaxation of 72.5 +/- 16.32% over the basal tone. We believe that intraoperative manometry is essential in the surgical treatment of achalasia as it allows a precise control of myotomy as well as the fashioning of a high pressure zone to avoid reflux.

[Evaluation of esophageal function in surgically-treated patients]. / Valutazione funzionale esofagea del paziente operato.

The authors report on their experience acquired in the surgical treatment of functional esophageal disease (achalasia, diffuse esophageal spasm, diverticula and gastroesophageal reflux). The authors affirm that a correct and meticulous functional study of the esophagus is fundamental for the adoption of precise surgical plotting, in order to circumvent all of the complications and failures described in Literature. Such an objective can be achieved intraoperatively thanks to myotomy and fundoplication with the aid of intraoperative manometry (IEM) that, when performed in the course of myotomy, circumvents the execution of incomplete procedures (incomplete myotomies). The same holds true in the case of anti-reflux plasty (Nissen's in particular) where IEM enables a plication that is neither too wide nor too narrow, too long, too short, but "calibrated". Then, instrumental probes are even more capable of assessing the effects of functional surgery, by enabling the documentation of perfect postoperative results. More precisely they make it possible to study patients presenting with motor disorders pre-operatively, as in the case of achalasia or diverticula, and to sanction their resolution postoperatively. In addition they enable documentation of the effectiveness of Nissen's fundoplication, performed either to prevent gastroesophageal reflux after myectomy or to treat primary reflux. This is made possible by studying not only the tone at a distance, but especially relaxation in the course of deglutition. Finally, pH-metry permits the documentation of the complete clearing of gastroesophageal reflux, even when physiologic and post-prandial (hypercompetent Nissen).

JunB/cyclin-D1 imbalance in placental mesenchymal stromal cells derived from preeclamptic pregnancies with fetal-placental compromise.

INTRODUCTION: In the present study, we characterized the expression of Activating Protein 1 (AP-1) factors, key cell cycle regulators, in primary placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) pregnancies with fetal-placental compromise. METHODS: PDMSCs were isolated from control (n = 20) and preeclamptic (n = 24) placentae. AP-1 expression was determined by semi-quantitative RT-PCR (sqRT-PCR), Real Time PCR and Western Blot assay. PDMSCs were plated and JunB siRNA was performed. JunB and Cyclin-D1 expression were assessed by Real Time and Western Blot analyses. RESULTS: JunB expression was significantly increased while Cyclin-D1 expression was significantly down-regulated in PE relative to control PDMSCs. JunB siRNA was accompanied by JunB down-regulation and increased Cyclin-D1 in normal PDMSCs. CONCLUSIONS: We described, for the first time, AP-1 expression in PDMSCs derived from physiological and PE placentae. Importantly, we demonstrated that JunB over-expression in PE-PDMSCs affects Cyclin-D1 regulation. Our data suggest a possible contribution of these pathological placental cells to the altered cell cycle regulation typical of preeclamptic placentae.