Proliferative verrucous vs conventional leukoplakia: no significantly increased risk of HPV infection.

Proliferative verrucous leukoplakia (PVL) is a very aggressive form of oral leukoplakia (OL) with high morbidity and mortality rates, hypothesised to be linked to HPV infection. This study aimed to determine the presence of HPV DNA in PVL in comparison with OL, and in relation to social-demographical variables (age, gender, smoking and drinking habits) in an Italian multi-centric hospital-based study. The study group consisted of 58 cases of PVL and 90 cases of OL as controls (47 homogeneous (H) and 43 non-homogeneous (non-H) form), both recruited from four Italian cohorts. HPV DNA was identified in exfoliated mucosal cells by nested PCR (nPCR) with MY09/MY11 and GP5+/GP6+ primer pairs and the HPV genotype determined by direct DNA sequencing. HPV DNA was found in 24.1% (14/58)of PVL and in 25.5% (23/90) of OL; there was thus no significant difference found between PVL and OL (both forms) for risk of HPV infection (OR=0.93; 95% IC:0.432-1.985). Similarly, in both groups of PVL and OL lesions, no statistic association was found between any demographical variable considered and HPV infection. HPV-18 was the most frequently detected genotype in all tissues, being found in 78.5% and 60.8% of HPV+ve PVL and OL, respectively. Other more rarely detected genotypes were HPV-16 (28.6% in PVL and 13% in OL), HPV-6 (17.4% in OL) and HPV-53 (8.8% in OL). PVL does not appear more likely to be associated to HPV infection than conventional OL lesions.

Presence of Epstein-Barr virus, cytomegalovirus and human papillomavirus in normal oral mucosa of HIV-infected and renal transplant patients.

OBJECTIVES: To determine the prevalence of EBV-DNA, CMV-DNA and HPV-DNA in oral healthy mucosa of HIV-infected and renal transplant patients. To associate the detection of viral genomes with laboratory parameters of immunodeficiency, gender, antiretroviral and immunosuppressive therapy. DESIGN: A cross-sectional analysis of lingual and buccal cytobrushings from HIV-infected and renal transplant patients. SUBJECTS AND METHODS: Lingual and buccal cytobrushings were obtained from clinically normal oral mucosa of 57 HIV+, 40 renal transplant patients and 30 healthy uninfected controls, all matched for age at baseline of examination. Presence of EBV-, CMV- and HPV-DNA was assessed by polymerase chain reaction (PCR). We evaluated their association, in HIV+ subjects, with gender, CD4+ cell count, HIV-RNA load, and antiretroviral therapy; and in renal transplant patients, with gender, CD4/CD8 ratio, and immunosuppressive therapy. Data were managed and analysed by Epi-Info 6.0. RESULTS: EBV-DNA was detected in 42.1% of HIV+ (24/57), in 65.0% of transplant patients (26/40), and in 16.6% of controls (5/30) (P = 0.03 and P = 0.0001, respectively). Furthermore, male gender in HIV+ group was found to be significantly associated with the presence of EBV-DNA (P = 0.02) vs females, after adjusting for CD4+ cell count and HIV-RNA load. CMV- and HPV-DNA were detected in 3.5% and 7.0% of HIV+, and in none and 20.0% of transplant patients, respectively. No relationship was found between the epithelial detection of these two viruses and any parameter evaluated. CONCLUSIONS: EBV genome was significantly detected in clinically normal oral mucosa of renal transplant and HIV+ patients. A significant gender association was found among HIV+, suggesting that oral hairy leukoplakia (OHL) is more likely to occur in HIV+ men than women.

Presence of human papillomavirus and Epstein-Barr virus in the cervix of women infected with the human immunodeficiency virus.

The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) was sought in cervical scrapings from 110 human immunodeficiency virus (HIV)-infected women to evaluate the role of these viruses as risk factors for squamous intraepithelial lesions of the cervix. By using PCR, presence of HPV-DNA and EBV-DNA was found in 60.9% (67/110) and in 10% (11/110) of clinical samples, respectively. Identification of oncogenic group of HPV by hybrid capture (HC II, Murex-Digene) indicated the presence of low-risk HPV in 13 (19.4%) patients, high-risk HPV in 28 (41.8%), and both types of HPV in 26 (38.8%) patients. Squamous intraepithelial lesions were present in 59 cases, being low-grade (n = 52) and high-grade (n = 7) lesions. HPV was detected in 84.7% of patients with lesions, in association with low-grade (43/52) and high-grade lesions (7/7), and in 33% of patients without lesions. EBV-DNA was detected in 8 patients with low-grade lesions and in 3 patients without lesions. Concurrent genital HPV and EBV infection was observed in 9 cases. HPV was associated with detection of squamous intraepithelial lesions [OR = 3.55; 95% CI = (1.96; 6.48)]. No significant association was found between presence of EBV and detection of lesions, both in case of EBV infection alone [OR = 1.4; 95% CI = (0. 93; 2.12)] and in case of HPV/EBV combined infection [OR = 0.87; 95%CI = (0.54; 1.42)]. These data confirm the significant role of HPV as risk factor for squamous intraepithelial lesions and suggest that EBV could not be involved in the pathogenesis of the lesions that arise in the cervix of HIV-positive women.

Detection of Epstein-Barr virus (EBV) DNA and antigens in oral mucosa of renal transplant patients without clinical evidence of oral hairy leukoplakia (OHL).

The use of the polymerase chain reaction (PCR) to detect the presence of Epstein-Barr virus (EBV) DNA in oral mucosa in the absence of specific lesions gives rise to the problem of identifying the real viral replication sites. To verify whether the detection of EBV is due to salivary contamination or its true replicative capacity in oral mucosa, saliva samples and exfoliated cells from four different oral mucosa sites were taken from 40 renal transplant patients and 20 normal subjects for examination by PCR using two pairs of primers specific for the BamHI-L and BamHI-K genomic regions. EBV-specific sequences were detected in one or more of the oral mucosa samples from 29 transplant patients (72.5%) and six healthy controls (30%), and in the saliva samples of 16 transplant patients (40%) and three healthy controls (15%). A total of 89 oral mucosa smears from 29 transplant patients, and 13 from healthy subjects, were EBV-positive. The positive samples were also investigated by means of in situ hybridization in order to confirm the intracellular presence of the viral genome, and by means of immunofluorescence testing with monoclonal antibodies to assess the possible expression of viral antigens. Hybridization with the EBV-specific probe was observed in 40/ 89 and 2/13 samples, respectively. Latent antigens (with or without lytic antigens) were detected in only 23 of the 40 samples (collected from eight different transplant patients) that were positive by in situ hybridization. Our data show that EBV is more frequently present in the oral mucosa of immunodeficient patients (where it can efficiently replicate) than in normal subjects.

Occurrence of invading bacteria in radicular dentin of periodontally diseased teeth: microbiological findings.

Bacterial invasion in roots of periodontally diseased teeth, which has been recently documented using cultural and microscopic techniques, may be important in the pathogenesis of periodontal disease. The purpose of this investigation was to determine the occurrence and the species of invading bacteria in radicular dentin of periodontally diseased teeth. Samples were taken from the middle layer of radicular dentin of 26 periodontally diseased teeth. 14 healthy teeth were used as controls. Dentin samples were cultured anaerobically. The chosen methodology allowed the determination of the numbers of bacteria present in both deeper and outer part of dentinal tubules, and the bacterial concentration in dentin samples, expressed as colony forming units per mg of tissue (CFU/mg). Invading bacteria was detected in 14 (53.8%) samples from periodontally diseased teeth. The bacterial concentration ranged from 831.84 to 11971.3 CFU/mg (mean+/-standard deviation: 3043.15+/-2763.13). Micro-organisms identified included putative periodontal pathogens such as Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum, Bacteroides forsythus, Peptostreptococcus micros and Streptococcus intermedius. These findings suggest that radicular dentin could act as bacterial reservoir from which periodontal pathogens can recolonize treated periodontal pockets, contributing to the failure of therapy and recurrence of disease.

HLA-B8,DR3 phenotype and the antibody response against Epstein-Barr virus.

Antibodies against the viral capsid antigen (VCA) and nuclear antigens (EBNAs) of the Epstein-Barr virus (EBV) were determined in a sample of Sicilian population. A significant correlation was observed between HLA-B8,DR3 phenotype and reduced titres of antibodies to EBNAs, whereas HLA-B8,DR3 positive individuals displayed levels of antibodies to VCA comparable to those of HLA-B8,DR3 negative ones. These results further strengthen the suggestion that HLA-B8,DR3 positive subjects are low responders and that the depth of immune response depends on the fashion of antigenic challenge.

[Concentration of aztreonam in plasma, urine, and seminal fluid of patients with chronic prostatitis]. / Concentrazioni di aztreonam nel plasma, nell'urina e nel liquido seminale di soggetti affetti da prostatite cronica.

The authors consider the concentration of antibacterial drugs in the seminal fluid as a reliable experimental model for the study of pharmacokinetics in chronic prostatitis (c.p.). The study was conducted on 32 subjects, 20 of whom were affected by c.p. and 12 were normal controls. All subjects were treated with aztreonam at a dosage of 1 g.i.m. The assay was performed 1 hour after the injection, on seminal fluid, urine and serum samples. No difference was observed between normal subjects and patients with c.p. with regard to serum and urinary levels of the drug. There was a trend towards a higher concentration of the drug in the seminal fluid of patients with c.p. when compared to normal subjects, with mean values of 1.8 and 0.9 mcg/ml respectively. This difference was not statistically significant. Furthermore, the drug concentration of the drug in semen was below the sensitivity limits of the assay in 43% of normal subjects and in 10% of patients with c.p. In the latter group of patients the mean values of aztreonam concentration exceeded the minimal inhibitory concentrations for most aetiological agents causing c.p. In conclusion, it is suggested that aztreonam is likely to be effective in acute prostatitis, caused by Gram negative strains and may be indicated in selected cases for the treatment of c.p.

Treatment of prepubertal periodontitis. A case report and discussion.

This paper reports the treatment of prepubertal periodontitis in a 3-year-old girl with Papillon-Lefèvre Syndrome. Initially, the patient was found to have a myeloperoxidase deficiency and microbiological tests have identified Bacteroides and Fusobacterium, in 60% and 25%, respectively of the total number of microbial flora cultivated. The initial treatment was extraction of all the primary teeth with grade 3 mobility, scaling, root planing and daily subgingival irrigation with a 0.2% solution of chlorhexidine. Several months before the eruption of the first permanent molars, the rest of the primary teeth were extracted. The patient was treated with daily subgingival irrigation of chlorhexidine and weekly professional oral hygiene. At the age 6 1/2 years, the permanent teeth have normal gingiva and crevice depths; microbiological investigation reveals a prevalence of the coccoid forms, and radiographs show no evidence of periodontal pathology.

[Clinical and pathogenetic observations on children with chronic mononucleosis]. / Rilievi clinico-patogenetici su bambini con mononucleosi cronica.

Epstein-Barr virus is seldom the causative agent of a prolonged atypical illness, known as chronic mononucleosis syndrome, characterized by a persistent pattern of clinical manifestations and by a defective immune response to specific viral antigens. This paper refers about 6 children for whom clinical and serological findings suggest the chronic Epstein-Barr virus infection. The authors believe that this chronic state might be explained by the unusual antibody pattern to EBV virus, with the persistent presence of anti-EA and the absence of anti-EBNA titers, expression of a reduced EBV-specific cytotoxic T cell activity.

[Serological determination of anti-mumps immunity in a population sample from Palermo]. / Determinazione sierologica di immunita antiparotitica in un campione di popolazione palermitana.

A seroepidemiological survey was performed by an immunoglobulin G antibody-capture immunoassay on 1061 subjects from Palermo (Sicily), throughout the age range from birth up to 50 years. A proportional increase of seropositivity rate to mumps virus was shown in relation to increasing age, from 17.5% in the earliest years up to 60.3% in children aged 10 years. After the first decade of life, seropositivity rate reached a plateau staying constant up to the upper age classes explored. Given the relatively high frequency of complications upon mumps infection, it is suggested that an extended vaccination policy could cover a proportion of the non-immune adult subjects.

Immune status towards Epstein-Barr virus in a group of Sicilian children.

The prevalence of antibodies to Epstein-Barr virus-determined antigens was studied in 17 children with acute infectious mononucleosis (IM) and in 263 children hospitalized for diseases unrelated to EBV infection. Antibodies against Epstein-Barr viral capsid antigens (VCA) were observed in 173 patients of the control group (66%), but 58 of them (33,5%) had not yet developed antibodies against Epstein-Barr virus-associated nuclear antigen (EBNA). IgM-specific antibodies were not found in any of the children of the control group but were present in all of the 17 patients with IM. The rates of positivity for IgA anti-VCA and IgG anti-early antigen (EA) were similar in all age groups. Anti-viral capsid antigen IgG seropositivity increased to 83% by the age of six years, the mean geometric titre being highest between the ages of 2 and 4 years. Our results suggest that in Sicilian children the primary infection occurs prevalently early in life, in parallel with the occurrence of IM.

Pharmacokinetic study on adenomatous prostate tissue concentrations of cefoperazone. Clinical efficacy and patient tolerance of intramuscular cefoperazone treatment of chronic bacterial prostatitis.

Cephalosporins do not reach active therapeutical concentrations in the prostatic tissue in patients suffering from chronic bacterial prostatitis. Cefoperazone is an exception. Its efficacy in the treatment of chronic bacterial prostatitis in 20 patients was studied and the concentrations, obtained after intramuscular administration, evaluated in patients who underwent transurethral operation due to prostatic hypertrophy (in 14 patients). The cefoperazone concentrations in the prostate have been evaluated 60, 90 and in some cases 120 min after the administration of the drug and compared to those obtained in serum. The clinical cure has been obtained in 16 patients. The average drug concentration in the prostate after 60 min was 22.8 +/- 13.6 versus 39.8 +/- 20.0 micrograms/ml in serum; 90 min after administration the average concentration in the prostate was 23.2 +/- 14.1 versus 35.7 +/- 18.1 micrograms/ml in serum. The correlation was significant both at 60 min (r = 64, p less than 0.05) and at 90 min (r = 64, p less than 0.05).

Serological and immunohistological assessment of Epstein-Barr virus infection in Sicilian patients with suspected nasopharyngeal carcinoma.

An evaluation of antibodies to Epstein-Barr virus (EBV) was carried out on 18 patients with suspected nasopharyngeal carcinoma (NPC). With one exception, 9 patients, with histologically confirmed NPC, had high levels of IgG and IgA antibodies to EBV-related antigens, VCA and EA. Out of 4 patients, without histologically confirmed NPC and an antibody pattern compatible with the disease, one developed NPC 22 months later. These data confirm the usefulness of serological markers as a diagnostic aid in NPC and indicate that the occurrence of this malignancy might be higher in Sicily than in low-risk zones.

Comparison of serological methods for the detection of IgG and IgM antibodies to rubella virus.

Four commercial kits- the hemagglutination inhibition test Behring (HI-B), the HI Rubenosticon, the latex test Rubalex, the enzyme-linked immunosorbent assay (ELISA) ETI-RUBEK G--and a non-commercial hemolysis test in gel (SRH) were compared for the measurement of rubella IgG antibodies by testing 126 serum samples, submitted for rubella immune status determination. Two commercial ELISAs (ETI-RUBEK M and Rubazyme M) were also evaluated for the detection of rubella IgM antibodies on 64 sera from patients with suspected acute rubella infection. In the assay for rubella specific IgG antibodies, HI-B and ETI-RUBEK G tests exhibited the most sensitivity, whereas Rubenosticon and Rubalex tests showed more specificity. In the IgM evaluations, six false positive results were shown by Rubazyme M, whereas the ETI-RUBEK M kit was sensitive and specific. On the basis of all the determinations, a combination of two tests (HI-B and SRH) appears to be a good simple system to obtain valid indications in serological rubella diagnosis.

Intravesical bleomycin in bladder tumour prophylaxis.

The authors have evaluated the efficacy, tolerability and systemic absorption of bleomycin administered by intravesical route in the prophylaxis of recurrences of superficial vesical tumours after endoscopic resection (TUR). Thirty mg of bleomycin dissolved in 30 ml of saline solution were instilled in the bladder once a week for the first month and then once a month for 12 months. The instilled fluid was held in the bladder for 1 hour. The systemic absorption of the drug was evaluated by a microbiological assay of bleomycin in plasma and in the perfusion liquid recovered from the bladder. Fifteen patients were treated; most had a long history of multiple recurrent tumours despite previous intravesical treatments. Thirteen patients presented tumour recurrences during the treatment; 4 of them were given a second course of instillations following a second TUR and 3 of these presented further recurrences. The authors conclude that the drug, administered intravesically to high-risk patients with the modalities employed in the present study, was not effective in preventing recurrences. It was well tolerated locally and was free from systemic toxicity. The amount of bleomycin that was not recovered from the bladder after a contact time of one hour was relatively high but the drug did not reach measurable levels in the peripheral blood.

Measles virus variants: viral replication and cytopathogenicity in human T lymphocytes and B lymphoblastoid cells.

Measles virus can replicate in circulating T cells, B cell and monocytes of man as well as in different human lymphoblastoid cell lines. In the present report we describe the effects on lymphoblastoid cells and on a defined population of human T lymphocytes of infection with three measles virus variants characterized by different cytopathogenicity in human and simian epithelial cell lines. The aim of the investigation was to establish some evidence that the evolution of the viral infection and the cellular damage in lymphocytes can be directly controlled by viral properties.

[Serological assay of measles and rubella immunity in a sample of infantile population in palermo (author's transl)]. / Determinazione sierologica di immunita' antimorbillosa ed antirubeolica in un campione di popolazione infantile della citta' di Palermo.

The antibodies to measles and rubella viruses were titrated in a sample of infantile population in Palermo in 1978. Measles antibodies were investigated in 900 children aged 0-15 years by the HI test; rubella antibodies in 120 girls aged 12-14 years by the hemolysis-in-gel test. A "saturation" level of immunity against measles virus as can be found in the adult population appeared to be attained at the age of 12-13 years. At this age however, about 28% of the girls were still not immunized against rubella virus.