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The term inflammatory bowel diseases (IBD) refers to a group of idiopathic, chronic intestinal diseases characterized by a diffuse infiltration of inflammatory cells into the lamina propria of the intestine. The pathogenesis of IBD is unknown. The most common signs described are diarrhoea, vomit, and progressive weight loss. In order to make a definitive diagnosis, though, the presence of inflammatory cells infiltration must be evident on histopathologic analysis. The therapeutic approach has 2 main goals: decrease the inflammatory response and remove possible antigenic sources, such as food components or intestinal microflora. Therefore, the most common therapy is the association of Prednisone with a single protein diet, especially when the inflammatory cells infiltration is severe. Another way to reduce the antigenic stimulation is to control the intestinal microflora, so antibiotics and pre/ probiotics may be used. This retrospective study tested and compared the therapeutic value of Prednisone and specific diets, used as a single therapy or combined together. The results show a significative clinical improvement in dogs fed with hydrolized protein diets rather than novel protein diets. Finally, fish is the more reliable source of protein to use during therapy, because of its low ability to trigger an antigenic reaction.

Obsessive–compulsive disorder (OCD) and the spectrum of associated conditions, such as trichotillomania (TTM), Tourette syndrome and body dysmorphic disorder, affect about 2–4% of the world population. 1,2 Clinically OCD spectrum disorders are characterized by persistent intrusive thoughts (obsessions), repetitive actions (compulsions) and excessive anxiety. Although heritability studies in OCD have shown a 3–12 times increased risk for first-degree relatives and twin studies revealed higher concordance amongst monozygotic twins (80–90%) compared to dizygotic twins (47–50%), the identification of the underlying risk-conferring genetic variation by means of classic genetic association studies has proven to be difficult.3 Recently, it has been shown that mice deficient of the postsynaptic synapse-associated protein 90 (SAP90)/postsynaptic density-95 (PSD95)-associated protein 3 (SAPAP3, also known as Dlgap3) develop an OCD-like phenotype, which includes compulsive grooming and increased anxiety. Interestingly, the phenotype of Sapap3 knock-out mice can be rescued by administering selective serotonin reuptake inhibitors.4 We hypothesized that rare variants in the human orthologue SAPAP3 could contribute to disorders in the OCD spectrum. To test this, we resequenced SAPAP3 in three case populations, including 77 unrelated TTM probands collected at Duke University, 44 OCD with TTM probands from National Institute of Mental Health (NIMH), and 44 OCD cases without TTM from NIMH.5,6 Controls were 48 OCD spectrum-negative subjects from NIMH6 and a psychiatric comparison sample of 138 subjects screened for depression but not specifically for OCD from Duke University.7 A board-certified psychiatrist saw all patients and controls and diagnoses met Diagnostic and Statistical Manual of Mental Disorders, 4th edn. criteria. Samples were collected under approved institutional review board protocols. In 165 cases and 178 controls the complete coding region and flanking intronic sequence of SAPAP3 was resequenced using standard capillary sequencing methods (Applied Biosystems, Foster City, CA, USA). We detected seven novel nonsynonymous heterozygous variants, with all but A189V occurring only once (Table 1; Figure 1). Thus, in total, heterozygous SAPAP3 variants were present in 4.2% of diagnosed TTM/OCD patients, but only in 1.1% of controls (two changes in Duke control samples, with one developing depression subsequent to entry into the study). The majority of changes presented missense mutations; one variant was an in-frame insertion of five amino acids, A148insGPAGA. In silico analysis of the missense variants applying PMut and PolyPhen predicted two, or three, respectively, variants as of functional relevance (Table 1). The remaining polymorphisms were considered benign, including the two changes detected in controls. Further, we genotyped 6 of the identified variants in the TTM/OCD subjects in an additional sample of 281 OCD cases and in 751 general population controls.6 R13C and P606T were found in one control each, whereas A189V was present in three controls. This suggests that these specific variants are not by themselves disease-causing abnormalities, but still leaves open the possibility that an aggregate of susceptibility variants may prove contributory to disease, as suggested for some other disorders including autism as well as OCD. The combined analyses of 2766 alleles showed that all changes are very rare, with minor allele frequencies between 0.00036 (T523K, K910R) and 0.002 (A189V). Figure 1 Identified rare nonsynonymous polymorphisms in synapse-associated protein 90/postsynaptic density-95-associated protein 3 (SAPAP3). (a) Schematic of SAPAP3, which consists of 10 coding exons (blue boxes). Seven rare changes were identified in trichotillomania ... Table 1 Identified rare variants in SAPAP3 and predicted functional relevance Available pedigrees from TTM/OCD mutation carriers were enriched for a diverse set of psychiatric conditions, including panic disorder, attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder and substance abuse as well as OCD spectrum disorders (details are given in Supplementary Figure 1 and Supplementary Table 1). This situation is quite typical for psychiatric genetic studies and complicates allele segregation studies. Cosegregation of genotype and phenotype is also confounded by phenotypic penetrance rates, limited psychometric instruments and assortative mating. Thus, we consider it more significant to study the combined mutation load of SAPAP3 comparing cases to controls. Similar approaches were recently adopted by other studies.8 We observed a significant case–control association in our moderately sized sample (Fisher’s one-sided exact test P = 0.045). With generally still limited abilities to determine functional consequences of genetic variants, we speculate that the predicted moderate functional consequences (Table 1) are not detrimental for protein function but rather increase susceptibility for OCD spectrum behavior, possibly through permissive or epistatic interactions with additional genetic and environmental factors. A recent study estimated that up to 70% of low-frequency missense alleles in humans have mildly deleterious effects.9 The excess of rare mildly deleterious variants in any OCD risk gene could be promoted by an inefficient evolutionary selection against OCD risk alleles, which is supported by the high OCD spectrum frequency of 2–4% in the population, early disease onset and normal reproductive fitness. In summary, on the background of an intriguing Sapap3-OCD mouse model we suggest that the present data support a role for SAPAP3 in TTM and OCD. Expansion of our approach and modeling of rare genetic variants in SAPAP3 will be essential to further test this hypothesis.

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV-1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose-response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast-feeding was considered as the level of exposure in 168 ever breast-fed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast- versus exclusive formula-feeding was 1.19 with narrow confidence limits (1.10-1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03-6.37) was calculated in breast- versus exclusively formula-fed children. Several lines of evidence, including the above-mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast-feeding to mother-to-child HIV-1 transmission. Thus, this practice is now discouraged in HIV-1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV-1 infected mothers since 1981. It could be observed that feeding habits of at-risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth.(ABSTRACT TRUNCATED AT 250 WORDS)

The signs that may arise after perinatal infection with human immunodeficiency virus type 1 (HIV-1) have been classified by the Centers for Disease Control, but the clinical usefulness of the classification system and the prognostic importance of each disease pattern have not been established. We sought to address these issues by analysing data from the Italian Register for HIV infection in children. We studied 1887 children born to HIV-1-seropositive mothers. 1045 were identified at birth and the others were registered later (median age 4.8 [range 0.4-72] months). HIV-1-associated signs developed in 433 (81.8%) of 529 seropositive infected children at a median age of 5 (0.03-84) months. These signs appeared significantly earlier in the 102 children who died of HIV-1-related illness than in those who are still alive (median 3 [0.03-55] vs 6 [0.03-84] months; p less than 0.001). The cumulative proportion surviving at age 9 years was 49.5% (95% confidence interval 27-65%) and the median survival time was 96.2 months. Separate analysis of the 112 seropositive infected children followed from birth and older than 15 months gave similar results. Hepatomegaly, splenomegaly, lymphadenopathy, parotitis, skin diseases, and recurrent respiratory tract infections formed the mildest disease pattern. Lymphoid interstitial pneumonitis and thrombocytopenia were signs of intermediate disease. By contrast, in multivariate analysis specific secondary infectious diseases, severe bacterial infections, progressive neurological disease, anaemia, and fever were significant and independent negative predictors of survival. Growth failure, persistent oral candidosis, hepatitis, and cardiopathy were associated in univariate analysis with significantly shorter survival. Our findings suggest that the outlook for children with perinatal HIV-1 infection is better than previously thought and that a new clinical staging system of single disease patterns is needed.

A retrospective study on 357 children admitted to four Pediatric Infectious Disease Centers in Rome, affected by acute meningitis, during 10 years period, between January, 1, 1985 and December, 31, 1994 was carried out. Haemophilus influenzae type b was detected in 110 patients; all children aged between 1 month and 5 years; the maximum incidence (74.5%) was observed in patients under two years. The following diagnostic criteria were utilized: Gram stain of CSF; Latex test on CSF, blood, urine; CSF and blood cultures. The in vitro sensitivity of 65 isolates was tested by using the Kirby-Bauer method. We detected 15.3% of strains resistant to Ampicillin and 1.5% resistant to CAF. We also observed a high number of Hib strains resistant to Erythromycin and Cotrimoxazole. Only one strain Ceftriaxone resistant was isolated, confirming the high in vitro sensibility Hib to III generation cephalosporins that still remain the first choice drugs in Hib meningitis.

We agree that the ideal strategy in patients withan SMT would be to follow them with periodic USand perform surgery only in those who show sig-nificant growth during followup. This is our actualpolicy in masses less than 5 mm in diameter. Inthis group few patients required surgical explora-tion during followup. It is likely that in cases ofsuch small lesions strict surveillance may notchange the progression of germinal tumors, as re-ported by Bieniek et al, who noted a mean lesiondiameter of 4.142.0 mm (reference 1 in EditorialComment).However, sparse data are available in the litera-ture on the natural history of larger masses whenleft untreated. Our study shows that even largerlesions up to 20 mm in diameter may be benign, indicating that strict surveillance might be justifiedeven for masses larger than 5 mm. Our experiencealso demonstrates that with increasing lesion sizethe risk of cancer significantly increases 7 times permm. This information could be used to bettercounsel patients about the risk of harboring TC andeventually better support a followup strategy inpatients with an STM.We believe that 2 research lines which might helpus in the near future are 1) study of the individuallesion growth rate, which could differentiate benignfrom malignant lesions, and 2) new imaging diag-nostic tests such as contrast enhanced US1ortesticular magnetic resonance imaging, whichmight improve the diagnostic performance of scrotalUS.