[Experimental value of formaldehyde exposure to preserve anatomical findings]. / Valutazione sperimentale dell'esposizione a formaldeide durante il suo utilizzo per la conservazione di reperti anatomici.

Formaldehyde, already classified as potentially carcinogen and recently as "human carcinogen" by IARC, is generally used for fixing and preserving anatomical findings. This reason causes a problem of professional exposure for the operators who use the formaldehyde for this purpose. In this work we present the results of the periodical monitoring which is done for the determination of the exposure at formaldehyde in operating theatres and surgeries, where the operator fill the special container with the anatomical findings andformaldehyde for following tests. The measurements have been done using an instrument that continuously measure the concentration of formaldehyde, based on the infrared spectrometry, in 54 rooms which are operating theatres or surgeries in 9 public hospitals in Campania (Italy). The results show that the long-term exposure limits are not exceeded and that the average of the highest values of concentration obtained during its use was 0.15 +/- 0.04 ppm, that is below the limits. It is important to point out that such a limit was never exceeded during every single measurement. Finally, analyzing statistically the data, we can infer that the probability of exceeding the short-term limit is less than 0.1%, when formaldehyde is used for the purposes mentioned above.

Proposal for a systematic preoperative assessment of pelvic endometriosis.

AIM: Severe endometriosis represents one of the most challenging clinical and surgical cases in gynecology. Preoperative assessment of the extension of the disease is of key relevance to opt for medical or surgical therapy and, sometimes, to plan a multidisciplinary approach. METHODS: A systematic diagnostic approach is proposed and evaluated in a tertiary referral centre. It is based on an initial clinical evaluation and a second level ultrasound of the pelvis. Further exams, whenever required, have to be aimed at demonstrating specific involvements of organs other than ovaries and peritoneum such as bowel, urinary tract and nerves. RESULTS: The application of the proposed protocol has led to a reduction of the number of non-radical surgical procedures due to incomplete consent associated with missed diagnosis over the years (P<0.001). CONCLUSION: Our findings support the efficacy of a systematic diagnostic approach to endometriosis. This allows a correct planning of therapy with a multidisciplinary approach when necessary.

Evaluation of colonic involvement in endometriosis: double-contrast barium enema vs. magnetic resonance imaging.

BACKGROUND: The purpose of the study was to compare the accuracy of double-contrast barium enema (DCBE) and magnetic resonance imaging (MRI) in the diagnosis of intestinal endometriosis using the histological examination on resected specimen as comparative standard. METHODS: Eighty-three consecutive patients with suspected intestinal endometriosis, resected between 2005 and 2007, were prospectively evaluated. All of the women underwent preoperative DCBE and MRI on the same day. We evaluated number, site (rectum, sigmoid, cecum), and size of the lesions. The imaging findings were correlated with those resulting at pathology. RESULTS: Among the 65 women who underwent surgery, 50/65 (76.9%) were found to have bowel endometriosis, with 9/50 (18%) patients presenting two lesions; DCBE allowed to detect 50/59 (84.7%) lesions. MRI allowed to detect 42/59 (71.1%) lesions. DCBE showed sensibility, specificity, PPV, NPV, and accuracy of respectively 84.7, 93.7, 98.0, 62.5, and 86.6%, MRI of 71.1, 83.3, 93.3, 46.8, and 74.6%. CONCLUSION: DCBE is more accurate than unenhanced MRI in the diagnosis of bowel endometriosis, and should be preferred in the preoperative management of this disease, since it usually enables a proper surgical planning.

Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.

Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.

Is the antiepileptic effect of the ketogenic diet due to ketones?

For many years, the ketogenic diet, including recent variants such the medium-chain triglyceride (MCT) diet, has been used with good clinical results in the management of refractory epilepsies, particularly in children. The antiepileptic effects of the diet, like the antiepileptic effects of starvation, have been attributed to accumulation of ketones, and there are experimental data in animal models to support this hypothesis. Recently, new data about the neuroendocrine response to the acute phase reaction (stress) have emerged, indicating involvement of various neuropeptides, including neuropeptide Y (NPY), which is considered as an endogenous anticonvulsant. The release of NPY is also stimulated by nutrients in the gut, particularly fats. Long-chain and, to a greater extent, medium-chain triglycerides, which are components of the ketogenic diet, stimulate NPY secretion. This effect may explain the improvement in seizure control after starvation, use of the classical ketogenic diet, and use of the MCT diet.

Potentiation of brain serotonin activity may inhibit seizures, especially in drug-resistant epilepsy.

In spite of the large number of antiepileptic drugs (AEDs) actually available, the problem of drug-resistant epilepsy has not been solved. No AEDs are efficacious in patients with pharmacoresitant epilepsy, so new hypothesises about the mechanisms of pharmacoresistance are needed. In the last years the ideas on the role of brain serotonin in epilepsy have been turned upside down: increasing the available brain serotonin is thought now to have an antiepileptic effect. Antidepressant drugs like selective serotonin re-uptake inhibitors, i.e., fluoxetine, have proved to be useful in seizure control. Tryptophan (Trp), an essential amino acid, is the only brain precursor of serotonin, it competes with the other large neutral amino acids (LNAAs) for the carrier of blood-brain barrier (BBB). Our own data has shown a lowering of plasmatic LNAA levels in epileptic patients, on the basis of these results we could estimate a decrease of a 1/3 in the Trp brain intake rate in epileptics in respect to controls. Increasing plasmatic Trp levels increases brain serotonin synthesis. Trp and 5-hydroxytryptophan (5-HTP) were tested as an add on in epilepsy, but the clinical outcome was controversial. Free amino acids are not fully adsorbed by the gastro-intestinal system, furthermore LNAAs, and also 5-HTP is a LNAA, compete to cross the intestinal membrane for the same carrier, like for the BBB. The best way to increase the plasmatic Trp level is a protein rich in Trp and poor in the other LNAAs. Unfortunately Trp is a limited amino acid in proteins. We report the clinical results obtained by adding a whey protein to the antiepileptic therapy of drug-resistant epileptic patients: alpha-lactoalbumin, rich in Trp and poor in the other LNAAs.

[Evaluation of the environmental monitoring's effects on the anaesthetic gases concentrations in the operating theatres]. / Valutazione degli effetti del monitoraggio ambientale sulle concentrazioni di gas anestetici nelle sale operatorie.

The aim of this study was to evaluate the efficacy of anaesthetic gases monitoring in the operating theatre. From January 1997 to December 2007, in compliance with the Ministerial Circular on Professional anaesthetic exposure in operating theatres (5/89), we conducted an environmental monitoring of nitrous oxide (N2O) in 71 operating rooms of 31 public hospitals to determine the respect of limits established by circular (50 ppm). The results show that number of surgery rooms with airborne concentrations of nitrous oxide outside normative limits reduced varying approximately from 40% without monitoring activity, to 15% after a cycle of 10 monitorings. This study demonstrate that the environmental monitoring is crucial, efficacy and should be the first step in developing work practices and worker education programs. To the best of our knowledge, this study demonstrates the efficacy of anaesthetic gases monitoring in the operating theatre was evaluated.

[Environmental quality of the operating theatres in Campania: long lasting monitoring results]. / La qualità ambientale di sale operatorie nella regione Campania: i risultati di un monitoraggio pluriennale.

In this study the microbiological, physical and chemical results of an investigation concerning the environmental conditions of operating theatres in 38 public hospitals of the Campania Government are presented. The analysis of the results has been made by considering specific standards suggested by national and international regulations. The results showed that 84% of the operating theatres presented normal microbiological values, in relation to the total bacterial load, while 16% did not. By considering the microclimatic monitoring 55% of the operating theatres showed normal values while 45% at least a microclimatic index did not. In relation to the concentrations of anaesthetics gases the survey pointed out that the nitrous oxides was within non prescribed environmental limits (50 ppm for N2O); while 15% of the halogenated was not in normal values.

Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation.

The majority of deletions of the short arm of chromosome 5 are associated with cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic variability. To perform a genotype-phenotype correlation, 80 patients from the Italian CdCS Register were analysed. Molecular cytogenetic analysis showed that 62 patients (77.50%) had a 5p terminal deletion characterised by breakpoint intervals ranging from p13 (D5S763) to p15.2 (D5S18). Seven patients (8.75%) had a 5p interstitial deletion, four (5%) a de novo translocation, and three (3.75%) a familial translocation. Of the remaining four patients, three (3.75%) had de novo 5p anomalies involving two rearranged cell lines and one (1.25%) had a 5p deletion originating from a paternal inversion. The origin of the deleted chromosome 5 was paternal in 55 out of 61 patients (90.2%). Genotype-phenotype correlation in 62 patients with terminal deletions highlighted a progressive severity of clinical manifestation and psychomotor retardation related to the size of the deletion. The analysis of seven patients with interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731. Furthermore, this study lends support to the hypothesis of a separate region in p15.3 for the speech delay.

Anticonvulsant effect of fluoxetine in humans.

We report an unblinded, open-label, add-on trial of fluoxetine, a selective serotonin reuptake inhibitor, in 17 patients with complex partial seizures with and without secondary generalization (mean follow-up duration, 14 +/- 1.1 months). Six patients showed complete disappearance of their daily seizures; in the others the seizure frequency was lowered by 30%. No patient reported side effects.

Antipyretic and platelet antiaggregating effects of nimesulide.

Nimesulide strongly inhibited ex vivo platelet aggregation in guinea-pigs after both single and repeated (once daily for 5 days) oral dosing, irrespective of the aggregating agent used (adenosine diphosphate, arachidonic acid or collagen). Its potency was consistently greater than that shown by either ticlopidine or acetylsalicylic acid. In both oral and rectal administration, nimesulide proved to be more active and longer lasting than paracetamol in inhibiting fever induced in rats injected subcutaneously with brewer's yeast.

Growth charts for cri-du-chat syndrome: an international collaborative study.

Low birth weight and slow growth are frequently observed in the patients with cri-du-chat syndrome. To provide a growth reference standard for children with cri-du-chat syndrome, syndrome-specific growth charts have been developed from a combination of cross-sectional and longitudinal measurements on 374 patients from North America, Italy, Australia, and the British Isles. The data were obtained from pediatric records, parent reporting, and personal examinations at national 5p- parent support group meetings in the U.S., Italy, U.K., and Australia. The growth curves include height and weight measurements for patients ages 0 to 18 years and head circumference measurements for patients ages 0 to 15 years. Birth weight was above the 5th percentile of general population in 50% of cases: mean weight 2.8 kg +/- 1.85 SD for males and 2.6 kg +/- 1.51 SD for females. Growth curve medians were usually at or below the 5th centile of reference populations throughout life. The median head circumference falls below the 2nd centile, and this change increases with age. The charts show that compared with the standard population, most children with cri-du-chat syndrome are small at birth and as they grow most, but not all, have significant microcephaly and compromised weight for age, and to a lesser extent, compromised height for age. Am. J. Med. Genet. 94:153-162, 2000.

The excitatory amino acid antagonist amino-phosphono-valeric acid (APV) provides protection against penicillin-induced epileptic activity in the rat.

The effects of intraperitoneal injection of 2-amino-5-phosphono-valeric acid (APV) on EEG-monitored penicillin-induced epileptic activity in rats were evaluated. A significant decrease in the frequency of spikes occurred with low APV dosages (10 and 20 mg/kg), while an almost complete disappearance of spike activity was observed at higher APV doses (40 and 160 mg/kg). Our data suggest that excitatory amino acids play a relevant role in penicillin-induced epileptic activity in rats.

The antiepileptic effect of low-dose amino-phosphono-valeric acid (APV) is not enhanced by phosphatidylserine association.

We investigated the effects of the NMDA antagonist amino-phosphono-valeric acid (APV), alone or in combination with phosphatidylserine (PS) in the penicillin model of epilepsy. After penicillin injection, rats were treated i.p. with either APV alone (5 mg/Kg) or APV (5 mg/Kg) + PS (740 mg/Kg). EEG epileptic activity decreased significantly in the group treated with APV alone, even at the very low dose used. This effect was not further enhanced by PS, suggesting that the previously reported effects of PS on GABA activity may be related to a specific interaction between these compounds.

Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures.

Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.

Parenteral penicillin model of epilepsy in the rat: a reappraisal.

A parenteral penicillin model of epilepsy in the rat was investigated with the aim of evaluating its reliability. Behavioral and EEG patterns were strongly variable in a group of 100 rats injected with 1,000,000 IU/kg of penicillin i.p. Gross counts of spikes were Fourier transformed and grouped into two time windows in 24 out of the 100 rats. Analysis of variance applied to compare the two time windows showed a sufficient suitability of the phenomenon for antiepileptic drug testing purposes. Five subsequent injections of penicillin performed in 8 rats showed that a spontaneous decrease of the response takes place, preventing a crossover design in pharmacological analyses. Evans Blue studies demonstrated that there was not a breakdown of the blood-brain barrier; this model can be used for testing anticonvulsants unable to penetrate the blood-brain barrier.

[Hypophosphatasia: a family study]. / Ipofosfatasia: studio di una famiglia.

Diagnostic pathway and 5-years follow-up of a case of childhood-form hypophosphatasia (a severe form of vitamin D resistant rickets) are described. Family study led to the identification of five affected relatives (father, sister, paternal uncle, first-cousins), two with severe clinical evidence. Inheritance pattern in this family is compatible with autosomal dominant transmission.

[Resumption of breast feeding in low-birth-weight newborn infants]. / Recupero dell'allattamento al seno nei nati di basso peso.

It has been inquired into the possibility of the resumption of breast feeding in low birth weight babies, in the 101 survivors of the 128 infants weighing less than 2000 g at birth, who were born at St. Andrea Hospital in Vercelli between 1974-82. 86% of the mothers accepted to attempt breast feeding after the separation period for intensive care and the attempt the successful in 85% of the cases (73 infants). The resumption was successful with more than 90% of the infants weighting more than 1250 g at birth and 68.6% of these infants were exclusively breast-fed. 57% of those infants weighting less than 1250 g at birth resumed breast feeding. No infant developed an infectious disease nor necrotizing enterocolitis. Almost all of the mothers succeeded in maintaining breast feeding for a mean period of 5 months and all of them considered the experience extremely positive. The study demonstrated that it is possible to resume breast feeding in low birth weight babies with suitable encouragement and care on the part of the family, the doctors and the nurses.

[Mannosidosis. Study of two families and prenatal diagnosis]. / La mannosidosi. Studio di due famiglie e diagnosi prenatale.

Mannosidosis is a human lysosomal storage disease caused by and acid alpha-mannosidase deficiency. We have studied two affected Italian families and in this paper discuss the problems concerning the clinical and radiological findings, and laboratory assay as an access to diagnosis. Reference is made to our personal experience, as concerns the difficulties of carrier detection and of prenatal diagnosis.

[Malformations of the midline. A case-control study]. / Malformazioni della linea mediana. Uno studio caso-controllo.

Defects of the middle line are an heterogeneous group of congenital malformations due to commune pathogenetic mechanisms. We have made a case-control study about 150 newborns, who have at least 1 defect of the middle line. Results prove an excess of males between the cases, due mostly to hypospadias. We haven't found families with defects of the middle line with x-linked manner of hereditary transmission. We haven't found any particular risk present in cases and not in controls. We haven't found any case with 2 or more middle line defects.