The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance.

The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are described.

Estimation of genetic risk for Type 1 diabetes mellitus in newborns on dried blood spot.

BACKGROUND: The main contribution to genetic susceptibility for Type 1 Diabetes Mellitus (T1DM) is conferred by the Human Leukocyte Antigens (HLA). AIM: We evaluated the feasibility of large scale screening on Dried Blood Spot (DBS) to estimate the genetic risk for T1DM in newborns. SUBJECTS AND METHODS: Peripheral blood DBS samples from 256 newborns, were genotyped for HLA DRB1 and DQB1 alleles identification by a commercially available assay based on a dissociation enhancer lanthanide fluorescence system available in many newborn screening laboratories. Results were compared with those obtained in two wide multicentric studies on cord blood (DIABFIN and PREVEFIN). RESULTS: Genotyping on DBS revealed 6 subjects at high risk for T1DM, 99 at moderate risk for T1DM and the remaining at low risk for T1DM. We found 100% concordance between both techniques for HLA-DQB1 and DRB1 determination, confirming the feasibility of large scale screening on DBS. CONCLUSIONS: DBSs represent a resource for future studies about new genetics markers. This assay for estimate the genetic risk of T1DM on DBS showed an excellent sensitivity, specificity and accuracy compared with conventional techniques. Moreover, this assay resulted less expensive, and it could be easily performed on material already collected for newborn screening programs.

Association between threatened pre-term labour and periodontal disease: does a relationship exist? A matched case-control study.

AIM: The relationship between periodontal disease and preterm labour has been target of several studies with contrasting findings. The aim of this study is to verify the association between periodontal diseases in pregnant women and threatened preterm labour (TPL). METHODS: Two hundred and twenty pregnant women were enrolled in a matched prospective case-control study. Matching factors were age, parity and date of admission. Cases were defined as women admitted with a diagnosis of TPL before the 37th week; controls were defined as women with term labour (= or > 37 weeks) in the same ward. Primary exposure was defined as the presence of at least one tooth with probing depth (PD) >6 mm and BOP+. Average pocket depth, full-mouth bleeding on probing (FMBS) and the presence of plaque (FMPS) were also investigated. Matched univariate (McNemar's test and Wilcoxon signed rank test) and multivariate (conditional logistic regression model) analyses were performed. RESULTS: At least one PD >6 mm BOP+ was found in 30 TPL cases (27.3%) and 37 controls (33.6%), without significant difference (P=0.27). There was also no difference was found in shallow pockets. The average pocket depth was similar in TPL cases (2.67 mm) and controls (2.78 mm) (P=0.29). The average FMPS was 56.4% in the cases and 50.7% in the controls, while FMPS was 36.5% and 39.6%, respectively, though these differences are not statistically significant (P=0.26 and P=0.42, respectively). CONCLUSION: From our study, there seems to be no association between threatened pre-term labour and periodontal disease.

Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome.

Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations in the encoding MVK gene. Thus far, disease-causing mutations only could be detected by analysis of MVK cDNA. We now describe the genomic organization of the human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA.

Spherophakia associated with molybdenum cofactor deficiency.

Molybdenum cofactor deficiency is an autosomal recessive disorder characterized by lack of activity of the enzymes sulfite oxidase, aldehyde oxidase, and xanthine dehydrogenase or oxidase. The clinical manifestations are indistinguishable from those of isolated sulfite oxidase deficiency: craniofacial alterations, intractable neonatal convulsions, very severe mental retardation, lens dislocation, and death in the first decade of life. Lens dislocation is found in nearly all patients after neonatal age. In the present case it developed late (at the age of 8 years) and was preceded by bilateral spherophakia. We hypothesize that an abnormal relaxation of the zonular fibers is the cause of spherophakia in this disease; this causes lens dislocation eventually, after days, months, or years.

Outcome of thiamine treatment in a child with Leigh disease due to thiamine-responsive pyruvate dehydrogenase deficiency.

We describe a child with severe psychomotor retardation, peripheral neuropathy and bilateral abnormal signal in basal ganglia on magnetic resonance imaging, consistent with Leigh disease. Fibroblast pyruvate dehydrogenase assayed with routine method was normal. However, because of neurological improvement after treatment with thiamine, pyruvate dehydrogenase activity was studied again with thiamine pyrophosphate concentration adjusted to the normal human tissue level and found to be deficient. We report here on diagnostic difficulties and clinical follow-up of this patient.

Purines and pyrimidines determination in urine using high-performance liquid chromatography.

Single purine and pyrimidine bases are involved in two fundamental metabolic pathways that lead to formation of the building stones of DNA and RNA. Purine and pyrimidine nucleotides are also critically important metabolites in many cellular functions. The main breakdown of purines and pyrimidines produces uric acid and B-minoacids, respectively. Therefore, the study of purine and pyrimidine compounds in body fluid has high clinical relevance. We report, in this work, our experience in purines and pyrimidines determination in urine from children presenting with a clinical picture suggesting an inborn these pathways.

Digestive tract endoluminal perfusion of cisapride (R 51619) and effects on gastrointestinal hormone levels in anaesthetized pigs.

The authors evaluated the in vivo effects of the new drug Cisapride on gastrointestinal hormone release in the mini-pig. Cisapride has been reported to stimulate and coordinate peristalsis of the GI tract. Selective endoluminal perfusion with Cisapride solution of the isolated but not denervated gastric antrum, duodenum and distal ileum demonstrated a significant increase of gastrin levels following perfusion of the gastric antrum and a decrease in vasoactive intestinal peptide following perfusion of the duodenum, only at very high doses.

Plasma levels of beta-endorphin in uraemic patients during haemodialysis.

Plasma levels of beta-endorphins (h-beta-END) are reported to increase under condition of stress. The authors have determined the plasma levels of h-beta-END in six uraemic patients before, during and after haemodialysis. They have found a significant increase at each subsequent time. It is suggested that the cause of the increasing h-beta-END concentrations is the intradialytic stress.

The role of medical counseling in secondary prevention of cancer in the elderly.

In western countries the elderly are those who experience the major impact of cancer, as epidemiologic data clearly show. Thus, secondary prevention of cancer (SPC) in older persons deserves more attention than it has received until now. Target subjects, however, are often reluctant to enter SPC plans. The reasons range from the lack of knowledge about the importance of SPC to the underevaluation of the risk of cancer, or, even more often, to the anxiety and fear that may stem from such a clinical investigation. In this context, the intervention known as counseling finds its natural and essential role. In the paper some general considerations on the significance of medical counseling is given, with particular emphasis on its role in SPC in the elderly. The analysis herein reported points out the specific skills and methods that physicians can adopt to cope with the eventually adverse influences that may affect the participation of the elderly in SPC initiatives. However, such action should avoid any paternalistic approach and respect the patient's will and autonomy.

[Cancer in the elderly. Clinico-epidemiologic considerations]. / Il cancro negli anziani. Considerazioni clinico-epidemiologiche.

The elderly population is rapidly increasing in Western countries. Old age indirectly represents one of the most important risk factors for the development of neoplasias. In Italy in 1991 a total of 14,572 deaths from tumours were recorded, equivalent to 27% of all deaths; of these over 66% affected individuals aged over 65 years old. In the 65-74 age bracket mortality caused by tumour is the prime cause of death in Italy and is undergoing an exponential increase over time. The most frequently found tumours and above all the cause of the greatest number of deaths in the elderly population are lung cancer, prostate cancer, breast cancer, colorectal cancer, stomach cancer. To date the only weapon that has proved efficacious in some tumours (breast, colon-rectal, prostate, melanoma) is early diagnosis through screening and adequate treatment. The elderly are an extremely heterogeneous population and it is therefore not easy to provide guidelines that are applicable to the entire population. Firstly, it is important to provide more information in order to permit effective and targeted prevention. In order to fulfil this objective, structures offering the necessary equipment and skills will have to be create; training must be provided for personnel in this type of preventive medicine; lastly, the awareness of doctors towards this type of medicine must be increased by providing the correct information.

[Clinico-epidemiological findings in breast carcinoma in elderly patients]. / Rilievi clinico-epidemiologici del carcinoma mammario nelle pazienti anziane.

Old age certainly represents one of the major risk factors for the development of neoplasia. In breast cancer the incidence rises with age and continues until the age of 84. In EEC countries approximately 140,000 new cases are reported every year and at the end of the 80s there were 10,983 deaths from breast cancer in Italy, an increase of over per 1000 women each year. Fifty par cent of new cases were diagnosed in women aged over 65. The efficiency of a screening programme is evaluated by the fall in mortality rates in the population included in the programme compared to that not included. Results from controlled studies have confirmed the efficacy of breast cancer screening in women aged between 50-70, showing a significant drop in mortality rates which range between 21 and 36%. Adequate diagnostic and therapeutic management are of primary importance and screening programmes are organised in highly efficient structures using specifically trained staff. This underlines the need to set up appropriate services and structures for the prevention and treatment of breast cancer in elderly women, given that the latter represent the most frequently affected age group. Old age should be considered a natural extension of life and all elderly women have the right to receive treatment to prevent breast cancer.

Evaluation of liver regeneration after exeresis by determination of plasma carnitine levels in rats.

The relationship between plasma carnitine levels and liver regeneration was studied in 28 female rats subjected to lobectomy using the technique of Higgins and Anderson. The results show that the determination of plasma carnitine can be considered as a liver regeneration index.

[Venous hypertension of the arm. A complication of vascular access in hemodialysis]. / Ipertensione venosa dell'arto superiore. Una complicazione degli accessi vascolari in emodialisi.

Hand venous hypertension is a rare complication of Cimino-Brescia vascular access. The authors report their experience in a case of hand and forearm venous hypertension in a brachial arterio-venous fistula.

[Nonpalpable lesions of breast carcinoma in elderly patients]. / Lesioni non-palpabili da carcinoma mammario nelle pazienti anziane.

Breast cancer is the most frequent form of tumour in women. The only weapon at our disposal to reduce the mortality rate for breast cancer is early diagnosis. A number of studies have shown, using appropriate prevention programmes, an increasing number of minimum 20-30% lesions. The probability that a non-palpable lesion is malignant increases with age, with a positivity of 37-39% is women aged over 50. Localisation using FNAB requires studies with greater statistical value so that it can be inserted in current prevention programmes, given that the percentage of false negative is > 8%. At present, excisional biopsy with bioptic tests continues to be the standard reference method for the diagnosis of non-palpable lesions; this diagnostic procedure allows the lesion to be removed in positive cases, and avoids re-operating as in the case of suspected or inadequate cytological tests.

[The surgical therapy of prostatic tumors]. / La terapia chirurgica dei tumori della prostata.

In this paper the authors review the latest international literature regarding prostate tumour surgery, comparing surgery with the so-called "wait and see" approach. Together with hormone treatment, the latter method has been used by many researchers over the past few years given the low mortality caused by this tumour in spite of the increasing number of cases diagnosed. The wait-and-see approach is now rendered controversial by improved diagnostic methods and the widespread introduction of early diagnosis programmes. The authors report a number of studies on the use of "wait-and-see" in relation to radical prostatectomy and compare the results of the two techniques in terms of morbidity, mortality and survival. They go on to describe the various types of surgical technique used and their respective pros and cons as well as the complications typical of each technique. In conclusion, the authors discuss the indications for radical prostatectomy which, if performed in selected patients, appears to be a promising therapeutic approach in terms of disease-free survival and with a low operating mortality with complications that are not impossible to resolve using appropriate treatment.

[Domperidone as an anti-emetic in antineoplastic chemotherapy]. / Il domperidone come antiemetico in corso di chemioterapie antiblastica.

The antiemetic effects of domperidone in patients undergoing post-surgical cytostatic treatment for stomach and colorectal carcinoma have been evaluated. The study has been performed on 3 groups of patients treated with domperidone, metoclopramide and placebo respectively. The antiemetic activity of domperidone proved to be better than that of metoclopramide. No side effects were observed in patients treated with domperidone.

[Plasma amino acids in dialyzed children: comparison of hemodialysis and continuous ambulatory peritoneal dialysis]. / Studio degli aminoacidi plasmatici nel bambino dializzato: confronto tra emodialisi e dialisi peritoneale ambulatoriale continua.

Plasma protein and amino acid concentrations have been reported to be abnormal in patients with chronic renal failure, whether on conservative or regular dialysis treatment. These abnormalities may be related to impaired protein and amino acid metabolism associated with uremia, to dietary deficiencies of calories and proteins or to amino acid and protein losses due to peritoneal dialysis or hemodialysis. Plasma free amino acid concentrations were evaluated in 17 children undergoing hemodialysis (HD) and 13 children treated by continuous ambulatory peritoneal dialysis (CAPD). Plasma levels of free amino acids showed a reduction of EAA and of the ratio EAA/NEAA. There were some abnormalities in plasma amino acid concentrations; these included decreased levels of valine, threonine, lysine, serine, tyrosine, arginine, alpha-ABA. Aspartate, glycine, citrulline, and, only in HD, cystine and methionine were increased. Plasma protein and amino acid concentrations in CAPD patients are similar to those found in HD patients; thus they result poorly affected by different dialysis techniques and the uremic state itself seems to play a more decisive role.