Prenatal diagnosis of Crigler-Najjar syndrome type I by single-strand conformation polymorphism (SSCP)

Crigler-Najjar syndrome type I (CN-I) is a rare and severe inherited disorder of bilirubin metabolism, caused by the total deficiency of bilirubin-UDP-glucuronosyltransferase (UGT) activity. Enzymatic diagnosis cannot be performed in chorionic villi or amniocytes as UGT is not active in these tissues. The cloning of the UGT1 gene and the identification of disease-causing mutations have led to the possibility of performing DNA-based diagnosis. Here we report DNA-based prenatal diagnosis of CN-I in two Tunisian families in whom CN-I patients were diagnosed. As we had previously shown that CN-I was, in Tunisia, associated with homozygosity for the Q357R mutation within the UGT1 gene, we were able to detect this mutation in both families and to show that it was easily recognized by single-strand conformation polymorphism (SSCP) analysis. In both cases, SSCP analysis of fetal DNA showed that the fetus was heterozygous for the Q357R mutation. In one family, the pregnancy was carried to term and a healthy baby was born, whereas, in the other family, the pregnancy is still continuing. Thus the prenatal diagnosis of CN-I is possible, provided disease-causing mutations have been identified. SSCP analysis of DNA prepared either from amniocytes or from chorionic villi is a simple, reliable and fast method for prenatal diagnosis.     

Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation

Some exogenous antigens, such as heat shock proteins or apoptotic bodies, gain access to the MHC class I processing pathway and initiate CTL responses, a process called cross-priming. To be efficient in vivo, this process requires endocytosis of the antigen by dendritic cells via receptors which remain unidentified. Here, we report that scavenger receptors are the main HSP binding structures on human dendritic cells and identify LOX-1 as one of these molecules. A neutralizing anti-LOX-1 mAb inhibits Hsp70 binding to dendritic cells and Hsp70-induced antigen cross-presentation. In vivo, to target LOX-1 with a tumor antigen using an anti-LOX-1 mAb induces antitumor immunity. Thus, the scavenger receptor LOX-1 is certainly a promising target for cancer immunotherapy.     

Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients

Systemic mastocytosis (SM) is characterized by proliferation of mast cells in various organs, which may release a wide variety of mediators, thereby explaining the broad clinical spectrum of disease manifestations. The potentially life-threatening systemic symptoms and tumoral proliferation are poorly controlled despite the use of several cytotoxic chemotherapies and/or symptomatic treatments. Twenty consecutive adult SM patients with histologically confirmed bone marrow (BM) involvement received interferon-alpha subcutaneously (1-5 million units/m2/d, with progressive dose intensification over the first month of treatment) and were evaluated after 6 months of therapy. Seven of them had previously received symptomatic treatments, including steroids, which were ineffective. Among the 13 patients treated for at least 6 months, seven partial and six minor responses, mainly concerning vascular congestion and skin lesions, were obtained, while BM infiltration remained unchanged in 12 patients. The significant reduction of mast-cell mediator levels after 6 months of treatment was not predictive of clinical remission. The rate of depression was unexpectedly high (seven patients; 35%). Two patients died soon after starting therapy (one myocardial infarction, one septic shock). Six months of interferon-alpha may relieve vascular congestion in adults with SM, probably by inhibiting mast-cell degranulation.     

Housemaids and non-fatal occupational injuries

OBJECTIVE: To estimate the annual incidence of non-fatal work injuries according to sociodemographic and occupational variables among housemaids. METHODS: A community-based survey was conducted in a population of 1,650 women aged 10 to 65 years who reported a paid occupation randomly selected in a household sample of the city of Salvador, Brazil. Data was collected through individual questionnaires on living and work conditions and health status. Fisher Exact test was performed for frequency analysis. RESULTS: It was estimated an overall annual incidence of non-fatal work injuries in the study population of 5.0%, which was statistically significant (p<0.05) higher among housemaids (7.3%) than in the group with other occupations (4.5%). Half of the injuries among housemaids were not related with long-term disabilities, and 38.1% women referred not being able to work for two weeks on average after the injury. CONCLUSIONS: Housemaids represent a major contingent of the work force in Brazil and other Latin America countries. The high incidence of non-fatal work injuries in this working group reveals its public health relevance and the need for preventive programs.     

Trends in asthma mortality in Italy and Spain, 1980–1996

Asthma is a major public health problem, with variable trends in several countries. We analysed mortality trends from asthma in Italy and Spain between 1980 and 1996. Overall asthma-related mortality at all ages increased between 1980 and 1987 in both sexes in Italy, from 16.6 in 1980–1981 to 29.0 in 1986–1987 per million males, and from 8.0 in 1980–1981 to 13.8 in 1986–1987 per million females, but decreased thereafter to reach 14.6 per million in males and 8.7 in females in 1996. The downward trends after 1987 were consistent in middle age and elderly population, but asthma mortality tended to rise in children and young adults over the last few years. In Spain, overall age-standardized mortality rates from asthma declined in men from 37.8 in 1980–1981 to 10.1 in 1996, and from 19.5 in 1980–1981 to 13.2 per million females in 1996. In women, the fall in mortality rates was smaller, and overall mortality was higher than in males since early 1990s. Trends of asthma mortality in Italy and Spain were favourable over the last decade.     

Paternal and Maternal Smoking Habits before Conception and During the First Trimester: Relation to Spontaneous Abortion

PURPOSE: This study examined the association between maternal smoking before and during the first trimester of pregnancy and spontaneous abortion.

METHODS: We have been conducting a hospital-based case-control study on risk factors for spontaneous abortion in the greater Milan area. We collected information from 782 cases of spontaneous abortions and 1543 controls (women who delivered at term healthy infants).

RESULTS: With respect to never smokers, the odds ratio (OR) were 0.7 (95%, confidence interval (CI), 0.5–1.0) for women who quit smoking and 1.3 (95% CI, 1.0–1.6) for those who continued during pregnancy. Women who smoked more than 10 cigarettes/day in the first trimester were at increased risk of miscarriage, with an OR of 1.4 (95% CI, 1.0–2.1). No relationship was evident between the number of cigarettes smoked before conception and the risk of abortion. Likewise, no association emerged between paternal smoking and miscarriage. Moreover, no significant interaction or modification effect was obtained when strata of age and other major characteristics were investigated.

CONCLUSIONS: The risk of abortion associated with cigarette smoking during the first trimester of pregnancy was measurable and noticeable in this population, and accounted for 9% (95% CI, 6–13%) of all cases. The increased risk of spontaneous abortion in women smoking during pregnancy is a further reason to encourage pregnant women to quit.     

In vitro activities of antifungal agents alone and in combination against fluconazole-susceptible and -resistant strains of Candida dubliniensis

In the present study we used two groups of Candida dubliniensis strains: one containing fluconazole-susceptible clinical isolates and another containing fluconazole-resistant laboratory derivative from the former to examine the changes on susceptibility accompanying the development of resistance to fluconazole. Our findings confirmed the ability of C. dubliniensis isolates to become resistant to fluconazole and indicated that this resistance was crossed with ketoconazole, itraconazole, ravuconazole and terbinafine. We also tested combinations of terbinafine, amphotericin B, itraconazole and voriconazole against both groups of isolates in a checkerboard assay. Surprisingly, most combinations evidenced indifferent interactions, and the best synergism appeared when terbinafine and itraconazole were combined against the fluconazole-resistant group.     

Measuring Dimensions of Spirituality in Chemical Dependence Treatment and Recovery: Research and Practice

Spirituality and religiousness have long been associated with physical and mental health. The scientific treatment of religiosity as a multi-dimensional phenomenon is well established, especially in relation to chemical dependence treatment. Indeed, over 100 instruments are available for measuring various dimensions of religiosity. The more recent emergence of spirituality as an accepted construct in research has seen the development of a growing number of instruments to measure aspects of spirituality. The authors selected ten spirituality scales for review and discussion, and provided information relating to the scales’ development, psychometrics, format, scoring, and availability. The scales are then conceptualized in terms of their aggregate and overlapping usefulness for research and practice, and suggestions are made concerning the salient dimensions of spirituality measured by each scale. The scales are presented as defining an increased sense of internalized spirituality that contributes to positive psychological and emotional outcomes underpinning recovery from chemical dependence.     

Congenital Erosive and Vesicular Dermatosis with Reticulated Scarring in a Newborn: An Innovative Treatment Using a Silicone Dressing

Abstract: Congenital erosive and vesicular dermatosis healing with reticulated supple scarring is a rare entity presenting in the newborn with crusted erosions and vesicles that heal relatively rapidly, forming unique reticulated scars. We report the case of a premature baby 31 weeks old. Diagnosis was confirmed by skin biopsies, and the clinical improvement was excellent, with complete healing observed within 7 weeks. This report highlights clinical and histopathologic features, and a new successful treatment approach using a silicone dressing.