Ultrastable, high-repetition-rate attosecond beamline for time-resolved XUV-IR coincidence spectroscopy.

The implementation of attosecond photoelectron-photoion coincidence spectroscopy for the investigation of atomic and molecular dynamics calls for a high-repetition-rate driving source combined with experimental setups characterized by excellent stability for data acquisition over time intervals ranging from a few hours up to a few days. This requirement is crucial for the investigation of processes characterized by low cross sections and for the characterization of fully differential photoelectron(s) and photoion(s) angular and energy distributions. We demonstrate that the implementation of industrial-grade lasers, combined with a careful design of the delay line implemented in the pump-probe setup, allows one to reach ultrastable experimental conditions leading to an error in the estimation of the time delays of only 12 as over an acquisition time of 6.5 h. This result opens up new possibilities for the investigation of attosecond dynamics in simple quantum systems.

Attosecond photoionisation time delays reveal the anisotropy of the molecular potential in the recoil frame.

Photoionisation time delays carry structural and dynamical information on the target system, including electronic correlation effects in atoms and molecules and electron transport properties at interfaces. In molecules, the electrostatic potential experienced by an outgoing electron depends on the emission direction, which should thus lead to anisotropic time delays. To isolate this effect, information on the orientation of the molecule at the photoionisation instant is required. Here we show how attosecond time delays reflect the anisotropic molecular potential landscape in CF4 molecules. The variations in the measured delays can be directly related to the different heights of the potential barriers that the outgoing electrons see in the vicinity of shape resonances. Our results indicate the possibility to investigate the spatial characteristics of the molecular potential by mapping attosecond photoionisation time delays in the recoil-frame.

Age assessment in puppies: Coming to terms with forensic requests.

Age estimation in growing dogs is crucial not only in clinical practice but increasingly so in forensic practice as well. In the last few years, it has assumed great importance for correctly identifying the age of puppies illegally imported to Italy as well as to other European countries. Puppies are, in fact, transported when they are too young to be moved, which can cause both animal/public health and animal welfare issues. Therefore, the movement of animals within the European Community is governed by strict rules, and veterinarians are often required to evaluate the age of the imported puppies in a forensic scenario as accurately as possible. To date, X-ray evaluation of limb bones ossification centers (OCs) is generally accepted as a valid tool to assess the age of puppies. A wealth of information exists on this topic but it is not always easily available. This work is a historical review of the existing literature and proposes two tables illustrating the timelines of limb OCs appearance and closure, coming to terms with forensic requests to evaluate the age of a puppy. The timelines reported indicate the need to improve methodology to enhance the accuracy and to reduce the error in age estimation.

Small-sized newborn dogs skeletal development: radiologic, morphometric, and histological findings obtained from spontaneously dead animals.

BACKGROUND: Very little is known about neonatal skeletal development in small-sized purebred dogs. In order to improve this knowledge, 27 spontaneously dead puppies belonging to small-sized breeds were enrolled in this study for radiologic, histological and morphometric investigations. RESULTS: The appearance of the limb secondary ossification centers and the onset of their formation were clearly observed by x rays and confirmed by histological evidences. Radiographic and anatomic measurements of limb bones length and skull length and width were positively correlated with body weight and age of the subjects and the body weight was positively correlated with radius bone mineral density, as demonstrated by dual-energy x-rays absorptiometry. CONCLUSIONS: These data provided original information on the growth of newborn small-sized breed dogs, and suggest that cadavers may be useful to study skeletal development.

Obstetrical, fetal and postnatal effects of gestational antiblastic chemotherapy: how to counsel cancer patients.

At least one in a thousand pregnancies is complicated by cancer and, as the maternal age at pregnancy increases, numbers are growing. If chemotherapy cannot be postponed, both doctors and patients face complex medical and ethical issues. There is a conflict between optimal maternal therapy and fetal wellbeing. Treatment during the first trimester increases the risk of congenital malformations, spontaneous abortions and fetal death. Second and third trimester exposure is less risky, but it can cause intrauterine growth retardation and low birth weight. Other effects on pregnancy after the first trimester include premature birth, stillbirth, impaired functional development, myocardial toxicity and myelosuppression. Counseling and management of these cases are difficult, because literature is mostly represented by case reports or retrospective series while randomized prospective studies or guidelines are lacking. Moreover, personal experience is often scanty due to the rarity of the condition. This article reviews the available data regarding the different aspects of systemic treatment of cancer during pregnancy to help oncologist and obstetricians in counseling their patients and treat them accordingly.

Chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer: has this regimen still a role as neoadjuvant setting?

AIM: Neoadjuvant chemotherapy represents a promising alternative to concomitant chemo-radiation therapy in locally advanced cervical cancer patients. The aim of this study was the evaluation of pathologic response rates, toxicity and predictors of response in locally advanced cervical cancer patients treated with neoadjuvant cisplatin and paclitaxel followed by radical surgery. METHODS: Fourteen patients with stage IB2 to IIB cervical cancer received three cycles of cisplatin 75 mg/m2 and paclitaxel 175 mg/m2 intravenously every three weeks followed by radical hysterectomy and bilateral pelvic lymphadenectomy. Toxicity, pathologic response and predictors of response were evaluated. RESULTS: Chemotherapy related toxicities we-re as follows: alopecia 100%, asthenia 35.7%; nausea and vomiting 14.3%; paclitaxel hypersensitivity 7.1%, neutropenia 7.1%. Optimal, partial and no pathologic response was achieved in 21.4%, 64.3% and 14.2% of the patients, respectively. Based on lack of pathologic risk factors, 43% of the patients did not receive any adjuvant radiotherapy. Better response rates were obtained in patients with stage IIB, tumor diameter <5 cm, Hb >12 g/dL and SCC antigen <1.5 mg/dL. None of these variables reached statistical significance. CONCLUSION: Neoadjuvant chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer appeared to be well-tolerated. Even though the TIP regimen has been shown to be more effective than the TP regimen in randomized controlled prospective trial, the TP regimen remains a reasonable alternative in those patients in whom the TIP regimen is considered or shown to be too toxic.

Is magnetic resonance imaging useful in early evaluation of women on neoadjuvant chemotherapy for locally advanced cervical cancer?

OBJECTIVE: To evaluate the accuracy of magnetic resonance imaging (MRI) in staging cervical tumors after neoadjuvant chemotherapy (NACT). METHODS: 26 women, affected by locally advanced cervical cancer and triaged for surgery after NACT, were submitted to three cycles of neoadjuvant chemotherapy. All patients were submitted to MRI before and after NACT. We evaluated the MRI sensitivity and specificity in staging cervical tumors after chemotherapy, relating MRI findings after NACT with the pathological findings as the gold standard. RESULTS: In our series, MRI sensitivity was 58.8% and specificity was 66.7%. CONCLUSIONS: In our study MRI accuracy after NACT was lower than that of MRI used to stage patients with early cervical cancer scheduled for primary surgery, reported by the literature. MRI false negative cases are the major problem because of the delay in application of an effective therapy in non responders to NACT.

[Proposal for a protocol for the staging of incontinentia pigmenti in pediatric age]. / Proposta di un protocollo per la stadiazione della Incontinentia Pigmenti in età pediatrica.

Incontinentia Pigmenti (IP) is an X-linked dominant disorder of skin with neurologic and ophthalmologic involvement. IP predominantly affects females because the mutations are usually lethal in males in utero. IP is characterized by abnormalities of neuroectodermal tissues. IP is caused by mutations in a gene called NEMO, which is required to activate the NF-kB pathway. We present a diagnostic protocol for IP and a meta-analysis of the clinical spectrum of IP in 82 patients cited by MEDLINE in the European literature from 2000 to 2006.

[Incontinentia pigmenti: case report]. / Incontinentia pigmenti: descrizione di un caso clinico.

IP is an uncommon X-linked dominant disorder (incidence: 1/40.000 newborn). It is caused by mutations in NEMO. It is characterized by cutaneous lesions and dental, ocular, neurologic, nails, hair disorders. The ocular and neurologic sequelae represent the major morbidity in IP. We present a case-report with classical cutaneous features diagnostic for IP. The clinical, ophtalomologic and neurologic examinations revealed no other pathological manifestations.

Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation.

OBJECTIVES: To evaluate the risk factors for lopinavir/ritonavir (LPV/r)-related liver enzyme elevation (LEE) in HIV antiretroviral-experienced patients. METHODS: An open prospective observational study was carried out to analyse the incidence and time of LEE development during LPV/r treatment, and to determine whether LEE development was correlated with epidemiological, clinical and biochemical data, immune and virological profiles, concomitant hepatic diseases, antiretroviral therapy, or histological and ultrasonography liver examination results. A diagnosis of LEE was considered when LEE symptoms occurred after LPV/r introduction and was confirmed by a second control within 2 weeks. RESULTS: A total of 782 HIV-positive outpatients have been enrolled in six different Infectious Diseases Departments in Northern Italy since August 2000. Of these patients, 71 (9.1%) developed LEE within 115+/-85 days (mean+/-standard deviation); 13 of these subjects discontinued LPV/r and four were hospitalized. Of the patients with LEE, 74.6% and 25.4% had grade 2 and > or =3 toxicity, respectively. No correlation between LEE and sex, baseline CD4 cell count, viral load, HIV stage, triglyceride values, histological and ultrasonography liver examination results, nevirapine use, or increase in CD4 cell count was observed. Higher baseline alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values (P < 0.0001 and P=0.004, respectively), younger age (P=0.008), previous hepatitis B virus (HBV) infection (P=0.012), efavirenz use (P=0.04), and hepatitis C virus (HCV) and/or HBV coinfection (P < 0.0001, relative risk 4.78) were significantly related to LEE. No correlations between LEE and the same risk factors as investigated in the whole study population were found in subgroups of patients with HCV and/or HBV infection. CONCLUSIONS: HCV and HBV testing and measurement of baseline ALT values are essential for screening subjects at risk of LEE before starting LPV/r. Strict monitoring of clinical and biochemical parameters should be performed in these patients.

[CVS-cardiac thrombosis related in a child with an intracranial germinoma]. / Trombosi intracardiaca grave in paziente affetta da germinoma intracranico portatrice di CVC.

We report a case of a CVC infection with a grave cardiac thrombosis in a child afflicted with intracranial functioning germinoma. During the second chemotherapeutic cycle we found a positive blood culture and a partial CVC occlusion; echocardiography showed a 2 cm diameter interatrial thrombus. After removal of the CVC a voluminous thrombus in the right atrium persisted. The profibrinolytic factor's concentration was normal, and so we preferred to use aspirin, the most common antiplatelet agent, combined with antibiotic and antimycotis therapy. This treatment allowed us to observe the disappearance of the thrombus by 25 days.

Cognitive and affective disorders associated to HIV infection in the HAART era: findings from the NeuroICONA study. Cognitive impairment and depression in HIV/AIDS. The NeuroICONA study.

OBJECTIVE: To assess the natural story of HIV-associated affective and cognitive disorders and the relationship with clinical, pharmacological, immunological and behavioural factors. METHOD: A total of 395 HIV-positive patients, naive to Highly Active Antirectroviral therapy (HAART), with no severe psychiatric disorders have been enrolled in the Neuro-ICONA Study. All participants were administered a comprehensive data collection instrument including an addiction behaviour survey, a medical problem list, a psychiatric assessment, a validated neuropsychological test battery. RESULTS: The global prevalence of cognitive impairment and of prominent depressive symptomatology were 17.9 and 15.5%, respectively. A significant difference in the prevalence of prominent depressive symptomatology was observed between patients in HAART and those not taking HAART(14.1 vs. 23.8%; P = 0.05). CONCLUSION: Depressive and cognitive disorders affect a substantial proportion of HIV-seropositive subjects. The prevalence of prominent depressive symptomatology appears to significantly vary in relationship to the therapeutic protocol.

Motor control performance in the lower extremity: normals vs. anterior cruciate ligament reconstructed knees 5-8 years from the index surgery.

We compared motor control function in 50 patients who had undergone anterior cruciate ligament reconstruction using a bone-tendon-bone graft to that in 50 normal controls. Surgical subjects patients had undergone reconstruction with a one- (n=37) or two-incision (n=13) technique with the same rehabilitation protocol; mean time from the index surgery was 6.1 years (range of 5-8 years). For inclusion patients required an excellent outcome, category A IKDC score, and a KT-1000 side-to-side difference of 3 mm or less. Motor control evaluations were conducted using the KAT 2000 with static and dynamic tests. Normal controls had substantially better scores than did the surgical patients. There was no statistical difference the single-limb static test between scores of operated and nonoperated limbs. However, the operated limb scores were slightly better overall than those for the nonoperated limb, and the right knee scores tended to be better than those for the left knee. This may be explained by limb dominance. The test method employed in this investigation shows that anterior cruciate ligament reconstructed patients had a clear motor control deficit compared to normal control subjects even after several years.

Features of chronic hepatitis in alcoholics. A survey in Milan.

A study was carried out to confirm the pathogenetic role of ethanol in the development of chronic active hepatitis (CAH) and to assess if previous or current superimposed hepatitis B virus (HBV) infection could be relevant to the course of alcoholic liver disease (ALD). We examined clinical and laboratory reports of 57 alcoholics with biopsy-proven CAH. Serum and/or tissue HBV markers and the presence or absence of cirrhosis were investigated. Alcohol was the only aetiological factor present in a small group of CAH, with or without histological findings suggestive of alcoholic damage. Age, sex and survival were similar among the subgroups of CAH with and without previous or current HBV infection and among the subgroups of CAH with and without associated histological alcoholic features. Among the laboratory data, the AST/ALT ratio was higher in CAH without previous or current HBV infection. The mean age was comparable in CAH patients with and without cirrhosis, whereas the cumulative 5-year survival was worse in CAH with cirrhosis (87% vs. 49%). These data suggest a difference in alcohol susceptibility in our subjects.