Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV).

In view of presumed non-pathogenicity, tumor suppressive properties, and site-specific integration of the viral genome the human parvovirus, adeno-associated virus (AAV) has gained great interest as a gene transduction vector. Data on the seroprevalence of antibodies to AAV vary between reports, probably due to the different serological methods used. In order to understand better the immune response to AAV during natural infection, sera from different age groups and various geographical regions were compared for AAV antibodies using an ELISA. The data show that the prevalence of antibodies to AAV is similar in Europe (Germany, France, and Switzerland), Brazil, and Japan, indicating worldwide infection. It was confirmed that infection takes place during childhood. However, declining seropositivity thereafter and a second increase of seropositivity after 30 years of age suggests reinfection or reactivation of latent virus in particular as the prevalence of IgM antibodies in adults is relatively high. Furthermore, pregnant women were found to be significantly more frequently seropositive than non-pregnant controls, hinting at a reactivation of persistent AAV (up to 80% of women carry AAV in genital tissue) in specific hormonal conditions, e.g., pregnancy. Cross-reaction of serum antibodies with the different AAV types (defined by complement fixation) was observed by ELISA and neutralization tests confirming earlier results. The results suggest an unstable AAV antibody response allowing lifelong reinfection or reactivation of persisting virus possibly due to partial immunotolerance after an infection in utero, at delivery or during early infancy.     

Postoperative spindle cell nodules (PSCN) resembling sarcomas: an atypical granulation tissue or atypical pyogenic granuloma with exuberant myofibroblastic component?

Three cases of PSCN that developed 6-8 weeks after operations to the lower genital tract in two women, and after tooth removal in a 9-year-old boy are described. The lesions averaged 2 cm. in diameter and simulated spindle cell sarcomas because of their high mitotic rate, and marked cellularity. On follow-up (2-6 years) all patients were found to be free of disease. Immunohistochemical testing of the spindle cells showed a strong positivity for vimentin, and muscle actin and a weak, focal and inconstant positivity for F. VIII R.A., and Ulex E. The was total negativity for desmin, smooth muscle actin, S 100 Protein and Cytokeratins. We believe that these lesions represent an atypical form of granulation tissue in which the exuberant myofibroblastic component obscure the vascular elements of the lesion.     

Evaluating outcomes of hospital care following coronary artery bypass surgery in Rome, Italy.

OBJECTIVE: Monitoring health outcomes across hospitals has become a growing interest as a potential means to promote quality of care, but in Italy it is at the beginning stage. We aimed at comparing the performance of different cardiac surgery units and testing the utility of routinely collected data in this respect. METHODS: From the Lazio region hospital information system (HIS), we selected a cohort of 1603 individuals (84% males; mean age 63 years, SD 8) residing in Rome (2,685,890 inhabitants), who underwent isolated coronary artery bypass surgery (CABG, ICD-9-CM code: 36.1) in the period 1996-97 in seven major cardiac surgery units in the city. They were identified as A, B, C (teaching), D and E (non-teaching) units. Information on vital status at 30 days after the CABG surgery was obtained through an automatic record linkage with the Municipal Registry of Rome. The association between cardiac surgery units and outcome was evaluated through logistic regression taking into account the following a priori risk factors in different models: gender, age, socio-economic status, type of ischaemic heart disease and comorbidities. RESULTS: The overall mortality was 5.4% (range 2.1-11.4%). Statistically significant predictors of outcome included: age (OR=7.5 for age> or =70 vs. 35-49 years), acute myocardial infarction (OR=32.7 vs. acute-subacute forms/angina), chronic myocardial ischaemia (OR=4.2 vs. acute-subacute forms/angina), other heart diseases (OR=4.8), chronic renal disease (OR=16.0) and peripheral arterial disease (OR=2.9). Statistically significant variability in mortality was observed across hospitals; taking hospital A as reference, hospital D showed the highest risk (OR=5.7, 95% CI=1.9-17.3, in the fully adjusted model). CONCLUSIONS: We suggest that a true variation in quality of care play a role in the observed differences across hospitals, although chance and inaccurately measured risk factors cannot be excluded. Despite some limitations, the HIS is a valid tool for screening cardiac surgery units with poor performance.     

Chemiluminescent detection of blotted PCR products (CB-PCR) of two CAG dynamic mutations (Huntington''s disease and spinocerebellar ataxia type 1).

We have used a non-isotopic PCR assay based on the chemiluminescent detection of blotted PCR products (CB-PCR) for two dynamic mutation diseases (Huntington's disease and spinocerebellar ataxia type 1). This gives an accurate sizing of alleles and permits a rapid analysis of at risk persons. The system involves PCR of the samples, separation of alleles on polyacrylamide gels, Southern blotting, and hybridisation with specific primers 3' labelled with fluorescein (F1)-dUTP as probes. CB-PCR retains the isotopic sensitivity for accurate allele determination, avoids isotopic manipulation, and provides the advantages of safety, long term storage of probes, and recycling of hybridisation solutions.     

Red cell deformability alterations in normal late pregnancy: possible role of plasma components.

Red cell deformability of 30 nonpregnant volunteers and 20 normal pregnant women in the 3rd trimester was assessed by determination of filterability of red cells suspended either in autologous plasma or in buffer by St. George's filtrometer method. Total red cell deformability was decreased in normal pregnancy [transit time (Tc) = 7.79 +/- 0.86 vs. 6.99 +/- 0.65, p less than 0.01] as compared to nonpregnant women when erythrocytes were studied in buffer suspensions, while the number of profoundly rigid red cells was lower in pregnant patients [clogging particles (CP) = 0.864 +/- 0.225 vs. 1.103 +/- 0.246, p less than 0.01]. Total red cell deformability was no longer reduced in pregnant women when erythrocytes were suspended in autologous plasma (Tc = 7.25 +/- 0.66 vs. 7.13 +/- 0.69, p = NS) while the number of rigid erythrocytes was still lower (CP = 0.802 +/- 0.157 vs. 1.055 +/- 0.210, p less than 0.01). Our data suggest that by the end of normal pregnancy, red cell deformability decreases with a consequent accelerated turnover and a fast elimination of very poorly deformable erythrocytes; plasma alterations in late pregnancy partly counteract the intrinsic loss of deformability of red blood cells.     

Placas anulares en grandes pliegues: cuatro casos de liquen plano pigmentoso-inverso

We report 4 patients with relatively asymptomatic, annular brownish plaques arising in the skin creases. The lesions had remained stable for months despite many topical treatments. Histological amination revealed an atrophic epidermis with a dermal lichenoid inflammatory infiltrate showing marked pigmentary incontinence. These clinical and pathological features were consistent with lichen planus pigmentosus-inversus, a rare, recently described variant of lichen planus, with only 10 cases reported to date. It has been suggested that the intensity and speed of onset of the inflammatory response could be modulated by keratinocyte surface markers, which could also determine the typical morphology of the lesions of this disease.