Kneelike structure in the spectrum of the heavy component of cosmic rays observed with KASCADE-Grande.

We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.

Longitudinal variable selection by cross-validation in the case of many covariates.

Longitudinal models are commonly used for studying data collected on individuals repeatedly through time. While there are now a variety of such models available (marginal models, mixed effects models, etc.), far fewer options exist for the closely related issue of variable selection. In addition, longitudinal data typically derive from medical or other large-scale studies where often large numbers of potential explanatory variables and hence even larger numbers of candidate models must be considered. Cross-validation is a popular method for variable selection based on the predictive ability of the model. Here, we propose a cross-validation Markov chain Monte Carlo procedure as a general variable selection tool which avoids the need to visit all candidate models. Inclusion of a 'one-standard error' rule provides users with a collection of good models as is often desired. We demonstrate the effectiveness of our procedure both in a simulation setting and in a real application.

Between-breed variability of stillbirth and its relationship with sow and piglet characteristics.

Litter characteristics at birth were recorded in 4 genetic types of sows with differing maternal abilities. Eighty-two litters from F(1) Duroc x Large White sows, 651 litters from Large White sows, 63 litters from Meishan sows, and 173 litters from Laconie sows were considered. Statistical models included random effects of sow, litter, or both; fixed effects of sow genetic type, parity, birth assistance, and piglet sex, as well as gestation length, farrowing duration, piglet birth weight, and litter size as linear covariates. The quadratic components of the last 2 factors were also considered. For statistical analyses, GLM were first considered, assuming a binomial distribution of stillbirth. Hierarchical models were also fitted to the data to take into account correlations among piglets from the same litter. Model selection was performed based on deviance and deviance information criterion. Finally, standard and robust generalized estimating equations (GEE) procedures were applied to quantify the importance of each effect on a piglet's probability of stillbirth. The 5 most important factors involved were, in decreasing order (contribution of each effect to variance reduction): difference between piglet birth weight and the litter mean (2.36%), individual birth weight (2.25%), piglet sex (1.01%), farrowing duration (0.99%), and sow genetic type (0.94%). Probability of stillbirth was greater for lighter piglets, for male piglets, and for piglets from small or very large litters. Probability of stillbirth increased with sow parity number and with farrowing duration. Piglets born from Meishan sows had a lower risk of stillbirth (P < 0.0001) and were little affected by the sources of variation mentioned above compared with the 3 other sow genetic types. Standard and robust GEE approaches gave similar results despite some disequilibrium in the data set structure highlighted with the robust GEE approach.

Video-assisted coronary artery bypass in patients with preexisting tracheostomy.

A new technique allowing revascularization of the left coronary artery through a small thoracotomy after videoscopic harvesting of both mammary arteries is proposed in patients with total laryngectomy. This anterior thoracotomy approach, of real interest in patients with a preexisting tracheostomy, needs to be compared with a classic sternotomy in terms of functional recovery and the prevention of mediastinal sepsis in certain high-risk categories of patients (e.g., obesity, diabetes) for bilateral mammary artery harvesting.

[Panendoscopy in the research of multiple malignant synchronous occult tumors in patients with cancer of the upper aero-digestive tract]. / La panendoscopia nella ricerca dei tumori maligni multipli sincroni occulti in pazienti portatori di cancro delle vie aero-digestive superiori.

The Authors consider the result obtained in the diagnosis of malignancies simultaneous neoplasia in patients with a tumour of the head and neck. The study was conducted on 337 patients on 750 observed in the last seven years with a squamous-cell carcinoma at different stages of keratinization, who underwent an ORL examination, bronchoscopy and esophagogastroduodenoscopy, sometimes with intravital staining. Bronchoscopy was conducted on 297 patients, esophagogastruoduodenoscopy on 300. Altogether 260 were subject to both techniques and 77 to only one procedure. Endoscopy released a second tumour in 4 cases on 297 (1.34%) of the bronchus and in 5 cases on 300 (1.66%) of the esophagus. The percentage amounts to 3.46% in 260 patients subject to both examinations. Our study released a malignancies cells (18 cases on 216); this number was not confirmed by istological examination on bronchial biopsy. Our collaborators consider this result as pollution derived from cells coming from clear tumour in expansion. Our study, obtained from a substantial number of cases, justify the use of panendoscopy screening in conjunction with routine studies; although this procedure is aggressive, it is acceptable, because these second tumours have been discovered in early and asintomatic stage and were not found in the radiological examination.

Clinical and biologic features of adenomatosis coli in Northern Italy.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary disease characterized by more than 100 adenomas scattered in the large bowel and by various extracolonic manifestations. We proposed a) to establish the frequency of the disorder in Northern Italy, b) to describe the most relevant clinical findings, and c) in a subgroup of 21 patients (from 8 families), to evaluate the spectrum of mutations of the APC gene. METHODS AND RESULTS: Patients with FAP diagnosed between 1961 and 1991 were referred to our Study Group from surgery and gastroenterology units of the region Emilia-Romagna. The incidence of FAP was in the order of 1 in 16,500, with about a third of patients being 'single' cases. Colorectal malignancies were present in 75.6% of symptomatic patients but absent in most (93.75%) of the asymptomatic family members ('call-up' individuals). Gastric, duodenal, and jejunal adenomas were found in 8.2%, 30.6% and 53.3% of the investigated patients, respectively. Congenital hypertrophy of the retinal pigment epithelium and occult jaw lesions were seen in 64.7% and 39.5% of FAP patients but only in 0.5% and 2.5% of a matched, by age and sex, control population. These two clinical markers had a specificity of 99% and 97%, although their sensitivity was 64% and 39%. Finally, mutations of the APC gene were detected in 6 families (16 affected individuals) of the 8 families (21 affected individuals) tested; no correlation could be found between genotype and phenotype. CONCLUSIONS: This study confirms that early diagnosis is essential for an appropriate management of FAP patients, although this aim remains elusive in single cases. High-risk individuals are ideal candidates for APC gene mutation analysis, which should be offered to all first-degree relatives of affected patients.

Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas.

A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials.

[Results of myocardial revascularization in patients aged 70 years and over]. / Résultats de la revascularisation myocardique chez les malades âgés de 70 ans ou plus.

The purpose of this study was to bring up-to-date the immediate risks and long-term benefits of coronary surgery in elderly people. The results obtained in a series of 475 patients in their seventies suffering from coronary disease who underwent myocardial revascularization alone or combined with heart valve replacement at the La Pitié Hospital, Paris, between 1984 and 1989 were analyzed. Coronary disease was associated with heart valve disease in two-thirds of the cases. The mean number of bypasses was 2.3 per patient. Aortic valve replacement was performed in 119 cases and mitral valve replacement in 12 cases. The operative mortality rate was 10.8 percent in patients with stable angina who underwent elective surgery. The factors which increased the mortality rate were: age (19.6 percent over 75 versus 13 percent under 75, P = 0.05); sex (23.5 percent in women versus 13.2 percent in men, P = 0.01) and emergency (25.8 percent, P = 0.02). No significant difference in mortality was noted between patients who had and those who did not have aortic valve replacement (15.8 versus 10.8 percent, P = 0.14). Fifteen patients (3.1 percent) developed perioperative myocardial infarction. During the follow-up, period myocardial infarction occurred in 7 patients. Out of 29 late deaths, 8 were of cardiac origin (infarction in 5, terminal heart failure in 3). The survival rate at 4 years was 76 percent. Among the patients who could be followed up, 80 percent are now asymptomatic, 15 percent are in stage I or II and 5 percent in stage III or IV of the Canadian Cardiovascular Society classification. Thus, despite a non negligible operative risk the functional improvement and survival rates obtained justify an increase in the indications for myocardial revascularization in elderly patients.

[Total atrophy of the mandibular alveolar crest. A new therapeutic proposal (the use of a tissue expander) and a clinical case report]. / Le atrofie totali della cresta alveolare mandibolare. Nuova proposta terapeutica (uso dell'espansore tissutale) e presentazione di un caso clinico.

Atrophy of the alveolar crest, meant as a syndrome due to a certain variety of pathogenetic episodes developing in a more or less marked framework of resorption of the alveolar to the maxillary processes, represents an issue of debated and uncertain solution, especially in a view of the extreme degrees of the phenomenon. Various kinds of surgical approach have been suggested over time: among them mention should be made of the onlay graft technique, the osteotomy intervention visor type, the osseous interposition sandwich type, and other methods, which were often the result of a pontered mediation of the above mentioned, and which should have therefore enjoyed their single advantages. In consideration of the different techniques, the results were more or less noteworthy and it was clear, however, that a certain "gap" was still existing between the results aimed to and the results reached. Today, thanks to the tissue-expander technique, combined with the use of alloplasty materials (hydroxylapatite), we can give a new contribution to the solution of this invalidating pathology, thus reaching more complete and lasting results in the plastic reconstruction of the alveolar crest, and avoiding at the same time the disadvantages, even of iatrogenic kind, of an osteotomy intervention.

Treatment of oral leukoplakia with beta-carotene.

Over the past few years, beta-carotene has progressively gained ground as a drug chosen in the treatment of oral leukoplakias, thus making it possible to reduce the use of 13-cis-retinoic acid, which was shown by many studies to be highly toxic while beta-carotene has proved to have no significant side effects and hence to be much more suitable in oral premalignancy. In 1989, a phase II study of patients showing oral leukoplakias and treated with beta-carotene (90 mg/day) was begun. A total of 23 patients (aged between 17 and 85) were included in the study and 18 (8 male and 10 female) were evaluated. Eight patients (44.4%) had objective responses (6 complete, 2 partial). Four CR and a PR appeared unexpectedly within 2-7 months after the end of the therapy. The lesions were macroscopically and histologically examined at entry; in the evaluated patients, two types of alterations were found: atypical hyperplasia (16 patients) and dysplasia (2 patients). No signs of significant toxicity were detected; only in 1 patient treatment had to be interrupted for 1 week. The results of this study show the fair efficacy of beta-carotene against oral leukoplakias, but further confirmations through controlled clinical studies are needed.

[Hemimandibular reconstruction via an autologous transplant of vascularized fibula. A report of a clinical case]. / Ricostruzione di un emicorpo mandibolare mediante trapianto autologo di perone vascolarizzato. Presentazione di un caso clinico.

The authors illustrate the advantage of vascularised as opposed to conventional edges in the reconstruction of the jaw, focusing in particular on the use of a fibular autologous transplant. After a rapid description of the surgical technique used to remove the graft, they report a case of mandibular reconstruction in a young patient who had been involved in a shooting accident which had led to the loss of the left of this jaw.

[Infectious complications of heart-lung transplantation]. / Les complications infectieuses des transplantations coeur poumons.

This study describes the infectious complications in 68 heart-lung transplant patients. We focused interest on early post-transplant infections so called nosocomial pulmonary infections, their exacerbating cofactors their clinical expression, and elements of diagnosis and treatment. Furthermore we describe the principal infections seen during long-term followup, which are opportunist infections caused most often by immunosuppression: Cytomegalovirus infections have a high incidence with serious clinical consequences in heart-lung transplant patients. As well as pneumocystis carinii infections and fungal infections, such as aspergillosis.

[The adverse effects induced by ornipressin during oral and maxillofacial surgical interventions under general anesthesia]. / Effetti indesiderati indotti dall'ornipressina durante interventi di chirurgia orale e maxillo-facciale in anestesia generale.

There are various methods used in maxillofacial surgery for the control of superficial hemorrhage. The purpose is to achieve a better identification of the anatomical structures and reduce operating times without side effects. Ornipressin has no arrhythmogenic effects in presence of inhalational anesthetics and should therefore be considered safer then adrenalin. The authors examined the cardiocirculatory effects of this drug by means of an invasive hemodynamic study on five patients. The results showed that ornipressin causes worrying increases in blood pressure and peripheral vascular resistances, with reduction in the cardiac output.

Selenium therapy in patients with precancerous and malignant oral cavity lesions: preliminary results.

Baseline selenium (Se) levels in serum samples were collected from 22 patients with precancerous and 19 with malignant oral cavity lesions as well as from 13 healthy controls of the same geographic areas. Mean serum Se levels were 105, 101, and 77.03 ng/ml in the precancerous, controls, and malignancy groups, respectively. A statistically significant difference (p less than 0.005) was found between the neoplastic and both the precancerous and control groups. After careful clinical evaluation, precancerous patients received three 4-week cycles of Se, in either inorganic or organic form. Of the 22 precancerous patients entering the study, 18 were available for evaluation of clinical response. The analysis of serum Se variations revealed that serum Se levels tended to increase after the first and second cycles and then gradually returned to baseline values. At the end of the therapy, there were two complete responses (CR), five partial responses (PR), six minor responses (MR), and five stable diseases (SD) with an objective response (CR + PR) of 38.8%. Progression after suspension of therapy occurred in 7 of 18 patients; this may indicate the need of a longer treatment period with this essential trace element.

[Biological aspects and perspectives applicable to the chemoprevention of cancer of the upper respiratory-digestive tract]. / Aspetti biologici e prospettive applicative della chemioprevenzione nel cancro delle vie aero-digestive superiori.

After defining chemoprevention a description is given of the phases of differentiation in normal epithelial cells and the features of proliferation in neoplasias developing in this epithelium. The latest studies on carcinogenesis indicate various types of prevention with which one can alter this transformation process. Epidemiological studies have shown that subjects with low serum levels of Vit-A or Beta carotenoids are at high risk of developing epithelial cancer. Three main categories of agents inducing cell transformation are described: a) physiological induction agents; b) non physiological induction agents; c) cytotoxic drugs. In regard to clinical use, some studies have focussed on the importance of Vit-A in chemoprevention of risk conditions (pre-cancerous lesions) and in prevention of cancer recurrence. The authors point out the increasing interest in the use of retinoids in the chemoprevention of head and neck cancer and report some personal clinical experience.

[The visual fixation test in the study of visual-vestibular interactions. General aspects and results in normal subjects and patients]. / II test di fissazione visiva nello studio delle interazioni visivo-vestibolari. Generalità e risultati in soggetti normali e patologici.

Whenever we need to study visual-vestibular interactions, our method of choice among the ones based on thermal stimulation is the visual suppression test. In the vestibular laboratory of the II E.N.T. Clinic of the University of Parma the V.S.T. has been employed since 6 years systematically in all patients undergoing Electronystagmography. Our study was based on 10 normal patients and on 30 patients suffering from different pathologies. These patients were divided into groups according to the site of the lesion. The results we obtained are interesting: this test gives us important clinic data that we cannot obtain using other methods and allows us to discriminate the central or the peripheral site of the vestibular system lesion.

[Madrepore as a bone filler]. / La madrepora come riempitivo osseo.

The authors studied the behaviour of the porite type coral which has been previously implanted in man in order to get a reparation of osseous and parodontal defects. The histomorfological exam (at the optical microscope, SEM and X-Ray microscope) of a non decalcified bioptic piece, which had been obtained with an appropriate instrument, shows a deposition of neoformed bone around the coral. Six months after the implantation the tissue was stable without any osteoclasts in activity; even the implanted coral grains had not been attached by them. The Authors agree with most of the statements made by Souyris et Al., but they do not believe in the total substitution of the coral with the bone, at least not in short terms: therefore further scientific works will be necessary to clear this point.