The prognostic impact of the extent of ulceration in patients with clinical stage I-II melanoma: a multicentre study of the Italian Melanoma Intergroup (IMI).

BACKGROUND: The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). OBJECTIVES: To investigate whether the extent of ulceration (EoU) predicts relapse-free survival (RFS) and overall survival (OS) in PCM. MATERIALS AND METHODS: We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. RESULTS: A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1-mm increase) 1·26, 95% confidence interval (CI) 1·08-1·48, P = 0·0047] and OS [HR (1-mm increase) 1·25, 95% CI 1·05-1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour-infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01-4 mm and > 4 mm BT. CONCLUSIONS: This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports.

Myeloperoxidase-positive cell infiltration of normal colorectal mucosa is related to body fatness and is predictive of adenoma occurrence.

Body fatness is a risk factor for colorectal cancer, and promotes an inflammatory environment. Indeed, inflammation in normal colorectal mucosa may be a factor linking body fatness to colorectal carcinogenesis. In this study, we evaluated myeloperoxidase (MPO)-positive cells infiltration of normal colorectal mucosa as a marker of cancer-promoting inflammation in overweight and obese subjects. One hundred and three subjects with normal colonoscopy entered the study. Waist circumference (WC) and body mass index (BMI) were measured, and MPO-positive cells on histological sections of biopsies of normal colorectal mucosa were counted under a light microscope. The occurrence of adenomas was then evaluated on follow-up colonoscopies. Mean MPO-positive cell count (±s.e.m.) was higher in subject with a WC equal or above the obesity cutoff values according to gender (2.63±0.20 vs 2.06±0.18, P=0.03), and in subjects with BMI equal or above 25 kg m-2 (2.54±0.18 vs 1.97±0.20, P=0.03). A Cox proportional hazard model showed that mean MPO-positive cell count in normal colorectal mucosa was the only factor independently related to occurrence of adenomas in follow-up colonoscopies. Though preliminary, these results show that MPO-positive cell infiltration in normal colorectal mucosa is related with body fatness, as evaluated by WC and BMI, and it may be considered a useful and simple marker to estimate adenoma occurrence risk.

MATER protein as substrate of PKCepsilon in human cumulus cells.

High activity of the phosphoinositide 3-kinase/Akt pathway in cumulus cells plays an important role in FSH regulation of cell function and Protein Kinase C epsilon (PKCepsilon) collaborates with these signalling pathways to regulate cell proliferation. Relevant roles in follicular development are played by Maternal Antigen That Embryos Require (MATER) that is a cumulus cell- and oocyte-specific protein dependent on the maternal genome. We recently demonstrated that human MATER localizes at specific domains of oocytes and, for the first time, also in cumulus cells. MATER contains a carboxy-terminal leucine-rich repeat domain involved in protein-protein interactions regulating different cellular functions. Here we investigated the functional role of MATER. Thus, we performed coimmunoprecipitation experiments using HEK293T cells expressing human MATER; a similar approach was then followed in human cumulus/follicular cells. In MATER(+)HEK293T cells, we observed that this protein acts as a phosphorylation substrate of PKCepsilon. Western blot experiments indicate that, unlike oocytes, human cumulus cells express PKCepsilon. Immunoprecipitation and confocal analysis suggest for the first time that MATER protein interacts with this protein kinase in cumulus cells under physiological conditions. Since PKCepsilon is known to collaborate with antiapoptotic signalling pathways, this suggests a novel mechanism for the function of MATER in follicular maturation.

Risk factors for HIV infection in adults attending sexually transmitted disease clinics in Italy.

We assessed prevalence and risk factors for human immunodeficiency virus (HIV) infection in 637 patients (506 men, 131 women; median age 30 years, range 17-64) attending between September 1988 and July 1989 for the first time two sexually transmitted disease (STD) clinics in Northern Italy, for suspected or STD treatment. A total of 44 subjects (6.9%, 95% confidence interval, (Cl): 4.9-8.9) were seropositive for HIV antibodies. The prevalence of HIV infection decreased with age, from 9% in patients aged 24 years or less to 3% in those aged 45 years or more (chi 21 trend 4.97, p less than 0.05). Women tended to have a lower prevalence of infection than men (5.3% versus 7.3%) but this was not statistically significant. Compared with men reporting no homosexual intercourse, HIV infection risk was about 50% higher in those reporting bisexual intercourse (age- and sex-adjusted odds ratio (OR) 1.5,95% Cl: 0.6-3.6) and about fourfold in those reporting only homosexual intercourse (OR 3.8, 95% Cl: 1.7-8.5). No clear trend in risk was observed with number of sexual partners both in men and in women. Intravenous drug users had an increased risk of HIV infection; compared with non-users, the OR was 5.6 (95% Cl: 3.0-10.5) in users, and the point estimates increased with frequency of use, from 3.3 (95% Cl: 0.8-11.5) in occasional users to 6.4 (95% Cl: 3.2-12.8) in regular users. The risk of HIV infection was 2.2 (95% Cl: 1.1-4.3) in patients reporting a history of STD, and 1.6 (95% Cl: 0.8-3.3) in those reporting syphilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis in different stages of human oogenesis.

Apoptosis is an active form of cell death characterized by a series of morphological changes that become particularly evident at the ultrastructural level. The majority of ovarian germ cells undergo degeneration during prenatal and reproductive life and only in recent studies has it been demonstred that this drop is due to an apoptotic process. We evaluated this process during human oogenesis in prenatal life and we studied the ultrastructural changes that occur in apoptosis in various phases of the meiotic process. From our observations it is clear that apoptosis involves two main phases of the meiotic process: an earlier one concerning the oogonia and oocytes in the preleptotene stage, and a later one that mainly concerns the oocytes in the pachytene stage.

Effects of estrogens and oxytocin on the development of neonatal mammalian ovary.

The preservation and death of germ cells in the neonatal mammalian ovary are linked with the presence of hormones. Estrogens and oxytocin are present at birth in all mammalian vertebrates. The aim of this study was to examine their role in the development of the neonatal ovary and also in the preservation and death of germ cells in the neonatal period: apoptotic phenomena play a fundamental role in the control of their number. Female neonatal mice were treated at birth with estradiol monobenzoate or oxytocin and sacrificed after 5 days. The ovaries were sectioned in toto into semi-thin sections, in order to calculate their volume. Thin sections were also carried out to verify, under the transmission electron microscope (T.E.M.), the cells in apoptosis. The ovaries treated with the greater concentration of estradiol monobenzoate showed a volume that was significantly greater than that of the controls and a reduction of germ cells in apoptosis. The ovaries treated with oxytocin at all degrees of concentration had a volume significantly less than the controls and they also had a higher number of germ cells in apoptosis.

Urea kinetic modeling in continuous peritoneal dialysis patients. Effect of body composition on the methods for estimating urea volume of distribution.

Body composition can have a significant effect on methods for estimating urea volume (V) and fractional clearance (KT/V) in patients with renal failure. These effects were examined in 27 men on continuous ambulatory peritoneal dialysis (CAPD). Urea volume was calculated as 0.6% of body weight (V.6), by the Watson formula (VW) and by the Hume formula (VH). Patients were classified as obese (> 120% of ideal body weight), normal (90%-120% of ideal weight), or wasted (< 90% of ideal weight). A patient was considered adequately dialyzed if his weekly KT/V urea exceeded 1.70. Only 75% of subjects were classified as adequately or inadequately dialyzed by all three methods. Six subjects had KT/V0.6 < 1.70 and KT/VW > 1.70; five subjects had KT/VH < 1.70 and KT/VW > 1.70; and two subjects had KT/V0.6 < 1.70 and KT/VH > 1.70. In the obese group, KT/V0.6 (1.62 +/- 0.67) was significantly less than KT/VW (1.93 +/- 0.76; p < 0.001) and KT/VH (1.92 +/- 0.78; p < 0.001). Fractional errors in V and KT/V between any two methods were highly correlated with percent deviation from ideal body weight (r = 0.81 or higher). In peritoneal dialysis patients, excessive body weight affects the estimates of V and KT/V urea by certain methods, and may lead to erroneous impressions about the adequacy of CAPD.

[Electromyographic and neurological aspects of leprosy. Study of 100 cases]. / Aspectos neurologicos e electromiograficos da hanseniase. Estudo de 100 casos

By the neurological, electromyographic, anatomopathological and bacterioscopic examinations of 100 pacients with leprosy the following conclusions have been drawn: There was a high incidence of reflex abnormalities. The proprioceptive reflexes were abnormal in 64.5% and the superficial reflexes in 70.8% of the cases. According to the topography of the segments examined, the deep reflexes showed the following abnormal values: 25.3% in the cephalic segment; 69.1% in the upper limbs and 74.5% in the lower limbs. Of the 2,289 reflexes investigated, abnormalities were found in 773 superficial reflexes (70.8%), while in relation to the proprioceptive reflexes the figures rose to 901 (64.5%). In the early stages of the infirmity, the reflexes were normal in 41.2% of the cases examined, and in all the stages of the evolution of the disease those numbers were always high. Also in the first stage, whose average duration was of 4.9 years, several alternations were noted, although there was a predominance of brisk reflexes (25.1%) over diminshed reflexes (17%), followed by hyperactive (8.6%) and absent reflexes (8%). In the final stage of the infirmity there was a decrease of normal reflexes, in contrast to absent and decreased reflexes, whose rates increased to 32.7% and 30.6% respectively. The disappearance of hyperactive reflexes and the clear decrease of brisk reflexes should also be noted. There was a high percentage of patients (31%) who suffered agression of the eighth nerve, 17 of which (54.8%) were found to suffer from neural deafness. The values related to hearing deficit were rarely in accordance with the histopathological and bacterioscopic positive results. The indexes of abnormalities found out in the examination of the fifth and of the seven nerve (7% and 5% respectively) were much lower in relation to the eighth nerve. These results are in contradiction with the ones stated in the literature. In some of the patients, hyperesthesia of the skin of the plantar region prognosticated the appearance of the infirmity. Among the objective changes, anesthesia of superficial sensibilities combined with deep hyperesthesia and anesthesia of superficial sensibilities with abolition of profound sensibilities were rarely observed. No case was found with exclusive alterations of deep sensibilities. Peripheral motor neuron lesions demonstrable by electromyography were observed in 82 patients (82%)...

[Recurrent polychondritis (report of a case)]. / Policondrite recidivante (relato de um caso).

A case of relapsing polychondritis with atrophic lesions in nose and ears and conjunctivitis is presented. The patient was treated with dapsone during 18 months with remission of the acute breaks.

Application of poly-L-lactide screws in flat foot surgery: histological and radiological aspects of bio-absorption of degradable devices.

The flat foot in childhood is a condition frequently observed in orthopedic practice but it is still debated when and in which patients surgical corrective treatment is appropriate; recently, the application of poly-L-lactic-acid (PLLA) screws was proposed. The present study investigates a group of 33 patients treated with PLLA expansion endorthesis in order to evaluate the deformity correction. Clinical and radiological outcomes in patients were correlated with: a) morphological characterization of screws both before and after being removed from patients, when necessary; b) histological and bio-molecular evaluation of degradation processes of the implants, focusing attention on the correlation between the cellular cohort involved in inflammatory reaction and the bio-absorption degree of PLLA screws. Deformity correction was mostly achieved, with minimal need of screw removal; the results obtained clearly show the occurrence of chronic rather than acute inflammation in removed screw specimens. At the histological level, after biomaterial implantation, the sequence of events occurring in the surrounding tissues ultimately ends in the formation of foreign body giant cells (FBGCs) at the tissue/material interface; but the mechanisms which influence the fate of screw implants, i.e. the resolution of acute inflammation rather than the progression towards chronic inflammation, are of crucial importance for biodegradable materials like "polylactic acid". In fact, the FBGC response ensures a long-term mechanism which eliminates the foreign material from the body, but at the same time the implications of prolonged FBGC responses, which generate negative side effects, could significantly impede the healing progress.