Laser photocoagulation therapy for thyroid nodules: long-term outcome and predictors of efficacy.

PURPOSE: The aim of the present study was to retrospectively evaluate the efficacy of interstitial laser photocoagulation (ILP) ablation of thyroid nodules during a 6-year follow-up period and to identify possible predictors of the final outcome. METHODS: Forty-three outpatients (38 women) were assigned to ILP therapy. The study group included euthyroid patients with benign thyroid nodules. Thyroid size, nodule volume and features, and autoimmune test were collected at baseline. Patients underwent US control after the ILP procedure and 1 month, 6 months, 12 months later and then annually. RESULTS: During the follow-up, two distinct groups of patients emerged: the responders (N = 33) and the non-responder (N = 10) ones to ILP. In the responder group, the nodule volume significantly decreased during the follow-up, but a trend toward a slight increase in nodule volume was recorded up to the end of follow-up. No significant decrease in nodule volume was observed in the non-responder group. Neither baseline clinical nor demographic features were significantly different between responders and non-responders groups. In the whole group of patients, the energy delivered per mL of nodule tissue was significantly correlated with the percent volume decrease at the end of follow-up. CONCLUSIONS: Interstitial laser photocoagulation is a safe technique able to reduce byabout 50% the volume of benign thyroid nodules in the majority of treated patients. However, due to the great variability of results, an active follow-up is required. The only independent predictor of ILP outcome is the energy delivered per mL of nodule tissue.

Synthesis and biological evaluation of N-biphenyl-nicotinic based moiety compounds: A new class of antimitotic agents for the treatment of Hodgkin Lymphoma.

We previously demonstrated that some N-biphenylanilides caused cell-cycle arrest at G2/M transition in breast cancer cells. Among them we choose three derivatives, namely PTA34, PTA73 and RS35 for experimentation in solid tumor cell lines, classical Hodgkin Lymphoma (cHL) cell lines and bona fide normal cell lines. Almost all tumor cells were sensitive to compounds in the nanomolar range whereas, they were not cytotoxic to normal ones. Interestingly the compounds caused a strong G2/M phase arrest in cHL cell lines, thus, here we investigated whether they affected the integrity of microtubules in such cells. We found that they induced a long prometaphase arrest, followed by induction of apoptosis which involved mitochondria. PTA73 and RS35 induced the mitotic arrest through the fragmentation of microtubules which prevented the kinethocore-mitotic spindle interaction and the exit from mitosis. PTA34 is instead a tubulin-targeting agent because it inhibited the tubulin polymerization as vinblastine. As such, PTA34 maintained the Cyclin B1-CDK1 regulatory complex activated during the G2/M arrest while inducing the inactivation of Bcl-2 through phosphorylation in Ser70, the degradation of Mcl-1 and a strong activation of BIML and BIMS proapoptotic isoforms. In addition PTA34 exerted an antiangiogenic effect by suppressing microvascular formation.

Occurrence of medullary thyroid carcinoma, bronchial carcinoid tumor, and papillary thyroid carcinoma in a family bearing the RET G691S polymorphism.

RET mutations play an important role in the development of human neuroendocrine tumors. The prevalence of the RET polymorphism G691S of exon 11 is higher in patients with medullary thyroid carcinoma (MTC) as compared to the general population. A weak association between RET polymorphisms and sporadic papillary thyroid carcinoma (PTC) has also been described. We hereby describe the association of MTC, bronchial carcinoid tumor, and PTC in a familial setting. A 75-yr-old woman developed MTC 7 yr after successful treatment of a bronchial carcinoid. Serum calcitonin was 12.9 pg/ml with a peak response to pentagastrin (151.0 pg/ml). The patient underwent total thyroidectomy and a genetic mutational analysis of the RET gene. Histological evaluation confirmed MTC with no evidence of lymph nodes involvement. After thyroidectomy serum calcitonin was <2.0 pg/ml. A germline missense mutation at codon 691 in exon 11 of the RET gene was found. The mutational analysis was extended to the patient's offspring, and her daughter was found to bear the G691S polymorphism of RET. Wild type RET gene was found in the son. The daughter, who showed a nodular goiter, autoimmune thyroiditis and normal serum calcitonin, also underwent thyroidectomy. Histologic examination of the thyroid revealed an incidental PTC. This is the first description of a bronchial carcinoid tumor occurring in association with MTC. The occurrence of apparently unrelated NET in the same subject, or within a family, should be regarded as a challenge for deeper investigations into the possible oncogenic role of this genetic alteration.

Silicotuberculosis in the elderly: report of two cases.

Silicotuberculosis is observed rarely in the current clinical practice. We present two patients (a 72-year-old man and a 84-year-old woman) who developed silicosis after having worked for several decades in the ceramics industry. In both, pulmonary tuberculosis complicated the clinical picture several years after retirement. The first subject presented a multicavitary lesion in the apex of the right lung, which subsequently evolved with fibrosis. The other developed bilateral tubercular bronchopneumonia and right tubercular pleurisy, that improved after prolonged antimycobacterial polychemotherapy. The two cases confirm that patients with silicosis are at an increased risk of developing tuberculosis, and show that, nowadays, silicotuberculosis may represent a geriatric problem. In the elderly, recognition of tuberculosis associated with silicosis is often difficult. Occupational history, radiology (conventional chest radiography and computed tomography) and microbiology (identification of Mycobacterium tuberculosis in sputum and pleural exudate) are helpful for the correct diagnosis, which, in turn, is important for prognosis and treatment, as well as in relation to medico-legal issues and occupational-related compensation claims.

Immunocytological and mineralogical study of bronchoalveolar lavage in a group of subjects exposed to asbestos.

Twenty-five subjects (24 males and 1 female, mean age 57.4 years) who have been exposed to asbestos underwent chest radiography, high resolution computed tomography (HRCT) of the chest, lung function tests and bronchoalveolar lavage (BAL) for evaluation of cell components (total cell count, percentages of macrophages, lymphocytes, neutrophil and eosinophil granulocytes and the lymphocyte subpopulations CD3+, CD4+, CD8+, CD19+ and HLADR+), soluble factors (IL-8, IL-10, IL-12 and MCP-1 in the supernatant) and concentration of asbestos fibre. The subjects were subdivided according to the degree of their exposure, to the concentration of asbestos fibres in the BAL and to chest X-ray findings using the I.L.O. classification (0/0pl, 0/1 and 1/0 and above). According to the exposure index, we showed statistically significant (p < 0.05) higher lymphocytes percentage in the BAL of subjects with moderate exposure and significantly higher levels of IL-10 (p < 0.05) in the supernatant of subjects showing an absence of asbestos fibres in their BAL. In the group of subjects with a 0/0 and 0/1 radiological profile, the cellular component of the BAL was characterised by a higher percentage of lymphocytes (p < 0.02), whereas a trend toward an increase in the number of neutrophils was noted in subjects with obvious pulmonary fibrosis. The percentage of neutrophils was inversely correlated with some parameters of respiratory function such as vital capacity (p = 0.03) and the partial pressure of oxygen (p = 0.05) in the blood. Investigating the cytokines in the supernatant of the BAL, we found a trend toward lower concentration of IL-10 in the group showing the worst radiological picture (I.L.O. > or = 1/0), and a statistically significant negative correlation between this cytokine and pO2 (p = 0.048). Concerning the other cytokines and chemokines studied (MCP-1, IL-8 and IL-12), no significant differences were found to be associated with the radiological profiles. There were, however, positive correlations between the concentration of IL-8 and the percentage of neutrophils (p = 0.038) and between the concentration of MCP-1 and the percentage of lymphocytes (p = 0.006). A negative relationship between the concentrations of IL-12 and IL-10 has been also observed (p = 0.028). This research allows us to hypothesise that IL-10 may have a pathogenetic role in the evolution of asbestosis.

[Neuropsychological study of 8 to 15-year-old children with lateralised sub-clinical paroxysmal discharges and poor academic achievement]. / Estudio neuropsicológico de niños de 8 a 15 años que presentan descargas paroxísticas subclínicas lateralizadas y bajo rendimiento escolar.

Paroxysmal discharges have been observed in non epileptic children who, at the same time, display learning disorders. In this study our aim is to determine whether the association between sub clinical discharges (SCD) and learning disorders reflects specific neuropsychological deficiencies and, more particularly, whether the possible deficits are defined according to the brain hemisphere in which the paroxysmal activity is located. Neuropsychological evaluation was performed in 17 children between the ages of 8 and 15, with unspecific learning disorders, who presented sub clinical paroxysmal discharges localised in the left hemisphere (nine cases) or in the right hemisphere (eight cases). The children with paroxysmal activity in the left hemisphere obtained similar results to those in which it was found on the right, except in the tests that evaluate visuo constructive skills, in which their scores were higher, and in the executive function tasks, in which they displayed a deficit that was not observed in the children with paroxysmal activity in the right hemisphere. We interpreted the presence of SCD discharges in the left hemisphere as reflecting a slower or more deficient process of brain maturation, which could be compensated with a suitable programme of neuropsychological intervention.

Estudio neuropsicológico de niños de 8 a 15 años que presentan descargas paroxísticas subclínicas lateralizadas y bajo rendimiento escolar / Neuropsychological study of 8 to 15-year-old children with lateralised sub-clinical paroxysmal discharges and poor academic achievement

Introducción. Se han observado descargas paroxísticas en niños no epilépticos que presentan, al mismo tiempo, trastornos de aprendizaje. En este trabajo nos proponemos determinar si dicha asociación entre descargas subclínicas (DSC) y trastornos de aprendizaje refleja déficit neuropsicológicos concretos y, particularmente, si los posibles déficit se definen en función del hemisferio cerebral en el que se localiza la actividad paroxística. Pacientes y métodos. Realizamos una evaluación neuropsicológica a 17 niños de edades comprendidas entre los 8 y los 15 años, con trastorno inespecífico del aprendizaje, que presentaban descargas paroxísticas subclínicas localizadas en el hemisferio izquierdo (nueve casos) o en el hemisferio derecho (ocho casos). Resultados. Los niños que presentaban la actividad paroxística en el hemisferio izquierdo obtuvieron resultados semejantes a los niños que la presentaban en el derecho, salvo en las pruebas que evalúan habilidades visuoconstructivas, en las que sus puntuaciones fueron superiores, y en las pruebas sobre funciones ejecutivas, en las cuales mostraron déficit que no se observaron en los niños que presentaban la actividad paroxística en el hemisferio derecho. Discusión. Interpretamos que la presencia de DSC en el hemisferio izquierdo refleja un proceso de maduración cerebral más lento o deficitario, que podría compensarse con un programa adecuado de intervención neuropsicológica (AU)

Paroxysmal discharges have been observed in non-epileptic children who, at the same time, display learning disorders. In this study our aim is to determine whether the association between sub-clinical discharges (SCD) and learning disorders reflects specific neuropsychological deficiencies and, more particularly, whether the possible deficits are defined according to the brain hemisphere in which the paroxysmal activity is located. Neuropsychological evaluation was performed in 17 children between the ages of 8 and 15, with unspecific learning disorders, who presented sub-clinical paroxysmal discharges localised in the left hemisphere (nine cases) or in the right hemisphere (eight cases). The children with paroxysmal activity in the left hemisphere obtained similar results to those in which it was found on the right, except in the tests that evaluate visuo-constructive skills, in which their scores were higher, and in the executive function tasks, in which they displayed a deficit that was not observed in the children with paroxysmal activity in the right hemisphere. We interpreted the presence of SCD discharges in the left hemisphere as reflecting a slower or more deficient process of brain maturation, which could be compensated with a suitable programme of neuropsychological intervention (AU)

Alcoholic polyneuropathy: a clinical and epidemiological study.

In the present study, we investigated the frequency of polyneuropathy in a sample of 296 alcoholics who were admitted to the 'S. Maugeri' Medical Centre for detoxification from October 1997 to November 1999. Results revealed a high frequency of polyneuropathy in the sample under study. The disorder was often clinically asymptomatic and demonstrable only on electroneurographic investigation. Significant correlations were found between polyneuropathy, the duration of alcoholism, the type of alcoholic beverage consumed (wine) and the presence of liver disease and macrocytosis.

Differences between the quantitative antigenemia assay and the cobas amplicor monitor quantitative PCR assay for detecting CMV viraemia in bone marrow and solid organ transplant patients.

The relationship between quantitative PCR (COBAS Amplicor CMV Monitor, Roche Diagnostics) and quantitative antigenemia (Monofluor pp65, Sanofi Diagnostics) was examined for monitoring CMV viraemia. A total of 469 specimens from immunocompromised haematology and solid organ transplant patients were tested by quantitative antigenemia and qualitative PCR. Quantitative PCR (QPCR) was performed on the 245 specimens in which CMV DNA was detected by qualitative PCR. To exclude any effect due to specific anti-CMV treatment, analysis of antigenemia and QPCR results was only performed on the 164 of 245 specimens collected from patients not on ganciclovir or foscarnet treatment. Forty seven specimens had <400 CMV copies/mL and a negative antigen result, four specimens were antigen positive (all between 1 to 10 positive CMV cells/2 x 10(5) leucocytes) and had <400 CMV copies/mL. Fifty-one specimens had a CMV viral load > or = 400 copies/mL and a negative antigen result and 62 specimens had a CMV viral load > or = 400 copies/mL and a positive antigen. The viral load was shown to be as high as 43,000 copies/mL in some patients with a negative antigen and occurred in non-neutropenic patients. The correlation coefficient for antigen and QPCR results for specimens from bone marrow transplant patients, was 0.69 with an average CMV viral load of 3,200 copies/mL (SEM = 800) and an average antigen of nine positive CMV cells/2 x 10(5) leucocytes (SEM = 3). In the corresponding solid organ transplant group, the correlation coefficient for antigen and QPCR results was 0.71 with an average CMV viral load of 9,900 copies/mL (SEM = 2,100) and an average antigen of 26 positive CMV cells/2 x 10(5) leucocytes (SEM = 6). Both the average viral load and the average antigen result in specimens from solid organ transplant patients, were significantly higher than the average viral load and antigen result in the corresponding group of bone marrow transplant patients (Two-Sample-for-Means z-Test, P = 0.001 and P = 0.003, respectively). The differences in the kinetics of the two assays in monitoring CMV and their ability to predict CMV disease was also assessed in a sub-group of patients. In conclusion, the two assays used in this study do not always show parallel changes in CMV viral load, but may be complementary for the diagnosis and management of CMV disease. The observation that non-neutropenic patients can have a high viral load in plasma and a negative antigenemia has implications for laboratories using antigenemia alone to monitor patients for CMV disease.

Use of real-time PCR and the LightCycler system for the rapid detection of Pneumocystis carinii in respiratory specimens.

Pneumocystis carinii pneumonia (PCP) remains a major cause of morbidity and mortality in immunocompromised patients, including those infected with human immunodeficiency virus (HIV). The advent of real-time PCR technology offers the potential for rapid PCR results for the detection of P. carinii. In this report we describe the modification and evaluation of an existing PCR-based method for the detection of P. carinii DNA, into a real-time PCR assay suitable for use with the LightCycler system. Twenty eight induced sputum and bronchial washing specimens from 28 patients were tested by both a conventional PCR assay and a real-time PCR assay. Twelve specimens (42.9%) were positive in both the conventional and real-time PCR assays and sixteen (57.1%) were negative in both assays. The melting points of the amplified P. carinii DNA product obtained by melting curve analysis by the LightCycler of all P. carinii positive specimens ranged from 81.5 degrees C to 83.9 degrees C. There were no discordant results between the two assays for any of the specimens tested and results were available within 2 h for the real-time PCR assay compared to up to 11 h for the conventional PCR assay.

[Small cell carcinoma of the prostate. Description of a case]. / Carcinoma a piccole cellule della prostata. Descrizione di un caso.

The case of a 73-year-old man with metastatic small cell carcinoma (SCC) of the prostate is described. Seric neuron-specific enolase (NSE) was enhanced (75.4 ng/mL), while the prostate-specific antigen (PSA) was in the normal range. Therapy with etoposide and carboplatin induced a temporary partial remission, with fairly good quality of life and decrease of the NSE levels (down to 15.0 ng/mL). The patient died approximately 12 months after the initial diagnosis. The case confirms that prostatic SCC (a rare and very aggressive neoplasm) is usually diagnosed in an advanced stage. Treatment is problematic, however chemotherapy may prolong survival allowing, at least temporarly, an acceptable life quality. NSE measurement is useful to differentiate SCC from the more common adenocarcinoma (typically associated with elevated PSA values) and for follow-up.

[Work and alcohol: considerations on a caseload of patients undergoing treatment]. / Lavoro e alcol: considerazioni su una casistica di pazienti in trattamento.

An enquiry into alcohol dependent subjects admitted to the clinical wards of the first section of Occupational Medicine belonging to Medicina Preventiva Occupazionale e di Comunità of University of Pavia for an alcohol disaddiction treatment has been performed through a phone interview. 289 patients have been contacted and time elapsed from admission to interview was one to three years. The questions focused alcohol abstinence, occupational position before and after admission, any improvement in the work sphere (relationship with the collegues), any feeling of empowerment of the work abilities and any increase in the responsibilities load. From our results we can conclude that alcohol disaddiction carried on during admission has positively contributed to the reinstatement of alcoholics patients.

[High resolution computerized tomography in the diagnosis of asbestosis]. / La tomografia computerizzata ad alta risoluzione nella diagnosi di asbestosi.

The clinical observation, the work history, the analysis of pulmonary function tests and, mainly, the conventional x-ray chest radiograms have represented, til now, the diagnostic basis for pneumoconiosis (silicosis, mixed dust pneumoconiosis, asbestosis). Recently, the high resolution chest tomography (HRCT) has been introduced into the diagnostic procedures: such method seems to have its main application in the assessment of incipient clinical pictures of pneumoconiosis, particularly when characterized by normal pulmonary function tests. Asbestos fibers exposed workers were submitted to both radiologic methods. The great majority of them had already been recognized to be affected by asbestosis. A considerable statistical agreement (Cohen K) was observed between radiographic and tomographic I.L.O. classes. In conclusion, high resolution chest tomography doesn't appear to be an indispensable test for the diagnosis in admitted subjects, but we underline its importance in the evaluation of pleural thickenings.

[High resolution computerized tomography in the diagnosis of silicosis and mixed dust pneumoconiosis]. / La tomografia computerizzata ad alta risoluzione nella diagnosi di silicosi e di pneumoconiosi da rischio misto.

The clinical observation, the work history, the analysis of pulmonary function tests and, mainly, the conventional x-ray chest radiograms have represented, til now, the diagnostic basis for pneumoconiosis (silicosis, mixed dust pneumoconiosis, asbestosis). Recently, the high resolution chest tomography (HRCT) has been introduced into the diagnostic procedures: such method seems to have its main application in the assessment of incipient clinical pictures of pneumoconiosis, particularly when characterized by normal pulmonary function tests. 75 silica- and mixed dust exposed workers were submitted to both radiologic methods. The great majority of them had already been recognized to be affected by asbestosis. The statistical analysis (Cohen K) showed a satisfactory agreement between radiographic and tomographic I.L.O. classes. However, high resolution tomography appeared to be more accurate in the assessment of less severe clinical pictures. In conclusion, we underline the importance of high resolution chest tomography in the evaluation of individual clinical cases, particularly when forensic problems are involved.

[Evaluation of trends in occupational pathology in clinical cases]. / Valutazione della tendenza della patologia occupazionale in una casistica clinica.

The study considered all patients admitted to the 1st Division of Occupational Medicine, Department of Preventive, Occupational and Community Medicine of the University of Pavia between January 1st 1989 and December 31st 1995 with a diagnosis of occupational disease. It was useful in illustrating the evolution of occupational disease as regards both changes in etiology and in the symptoms and systems involved. A decrease in the number of occupational diseases diagnosed from 1993 to 1995 was revealed, but it is difficult to draw any significant conclusions from these data since the need for hospitalization when diagnosing this type of disease has diminished greatly. Changes in legislation which have obliged employers to take precise preventive measures could also be partly responsible for this downward trend. The patients were, in almost all cases, at an initial stage of their disease. This is reassuring as far as the therapeutic and legal need for an early diagnosis is concerned. However, it remains unknown how often the causal relationship between work and disease was not suspected and therefore how many cases did not arrive to observation. Finally, the study confirmed the disappearance of some occupational diseases, such as benzene intoxication, common in the past, and the increase in "emerging" pathologies like allergies.

[Employment and alcohol: analysis of a clinical casuistic]. / Lavoro e alcol: analisi di una casistica clinica.

The relationship between alcohol and work was studied in a group of 537 voluntary patients (393 male and 144 female) admitted to the department of Medicina del Lavoro, Pavia University for alcohol rehabilitation. The highest incidence of alcohol abuse was found in non-working subjects (pensioners, unemployed, housewives) although the start of excessive drinking takes place after beginning a working activity; a cause-effect relationship between these two factors can not be clearly determined, however. It is true that the stress provoked by this new condition (introduction to the work experience) can, in certain subjects, be a contributing factor in alcohol abuse. The increasingly lower age of initiation to alcohol reconfirms the need for prevention and instruction even at scholastic level. We can deduce how no working condition, low age and low education can constitute makers of risk for alcohol abuse.

[Acute alcoholic myopathy]. / Miopatia alcolica acuta.

A case of acute alcoholic myopathy in a subject with a 20 year history of alcohol abuse is described. The condition emerged during an episode of delirium tremens and had a quickly deadly outcome. The rapid evolution of the clinical situation accompanied by variation in the biohumoral indices (CPK, LDH, myoglobin) is stressed and although this prevented from obtaining anatomopathological samples of the rhabdomyolisis, the specific diagnosis was made with reasonable certainty. The onset of the condition was not foreseeable because of the absence of an accurate history of the subject's alcohol abuse on his admission and of significant biohumoral data indicating the existence of an alcohol correlated pathology.

Advances in evaluating liver response to operating theatre work: urinary D-glucaric acid as an index of effect.

The contribution of operating theatre work to specific diseases is still a controversial matter involving a variety of risk factors. The concept that the liver plays a central role in anaesthetics biotransformation stimulated numerous studies aimed at establishing the occurrence of liver changes and at verifying the relationship between liver disease and anaesthetics. The liver microsomal enzyme system has received particular attention in order to clarify the mechanism involved in anaesthetics hepatotoxicity and an increased microsomal activity has been detected in experimental conditions and in humans. In particular, a significant increase in the excretion of urinary D-glucaric acid (UDGA) in subjects occupationally exposed to anaesthetic mixture was observed. Nevertheless, few results exist about the relationship between UDGA increase and environmental anaesthetic concentration, and mechanisms responsible for UDGA increase still need to be clarified. Attention is focused, however, on the possibility of using UDGA as an index reflecting an adaptation effect (rather than an injury effect), which may represent a more adequate approach for evaluating any change related to working in the operating theatre.