Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments

ONE OF THE RISK FACTORS FOR HUMAN PAPILLOMAVIRUS (HPV) INFECTION and subsequent lower genital tract neoplasias and cancers is impaired cell-mediated immunity. HIV-positive women with severe immunosuppression are 5 times more likely than HIV-negative women to have lower genital tract neoplasias. A corresponding increase in the risk of invasive vulvar and anal cancers, but not of cervical cancer, has also been observed among HIV-positive women. Treatment failure and recurrence of neoplasia occur much more frequently among HIV-positive than among HIV-negative women. In this review, we discuss recent advances in the understanding of the relation between HIV and HPV coinfection and the development of lower genital tract neoplasias and cancers in women. In addition, we present strategies for monitoring and treating noninvasive and invasive neoplasias of the lower genital tract in HIV-positive women.     

Epitope Context and Reshaping of Activated T Helper Cell Repertoire

In recent years, a growing interest in the study of peptide antigenicity in relation to the role of flanking sequences and protein topology in processing, presentation, and recognition has been observed. However, the information available on the antigenicity of recombinant fusion proteins and their effect on the selection of antigen receptor repertoires is limited. To analyze the role of molecular topology of T epitopes in a system relevant to human pathology, we have used the bacterially expressed Schistosoma japonicum glutathione S transferase (GST) to construct recombinant antigens containing HIV-1 derived T cell determinants, and human T cell clones specific for these determinants. We found that antigenicity of a given GST—peptide combination was not the same when T cells and antigen presenting cells from different individuals were tested. Our results show that differences in processing and presentation of chimeric proteins are not dictated by the use of diverse restriction elements. We also found that the context in which an antigenic peptide is delivered affects the recruited repertoire as defined according to T cell receptor Vβ usage and fine specificities of selected T cells.     

Usefulness of fibrin glue in oncologic plastic surgery

Summary Human fibrin glue (Tissucol) is a plasma-derived compound endowed with adhesive and hemostatic properties and possessing a specific local anti-infection function mediated through activation of nonspecific immunity elements. The aim of this study is to show that in patients who have undergone prolonged reconstructive plastic surgery following cancer resection, Tissucol decreases infectious complications as compared to a control group. Between June 1985 and February 1988, 51 subjects were treated with fibrin glue during reconstruction operations. Analysis of the results showed that Tissucol produced a statistically significant reduction both of immediate complications, such as inflammation and partial separation of the surgical wound, and of delayed complications, such as scar hypertrophy and cutaneous fistulae. In conclusion, patients treated with Tissucol showed a better quality of surgical wound, a more rapid postoperative functional recovery and consequently a decrease in the duration of hospitalization.     

Hepatitis B and Delta virus infection among heterosexuals,homosexuals and bisexual men

The hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection rates were estimated in patients attending a venereal disease outpatient clinic: 759 heterosexuals and 154 homosexual-bisexual men. The anti-HBC prevalence was higher in homo-bisexual men (68.8 per 100) than in heterosexuals (41.8 per 100), whereas HBsAg was roughly the same in the two groups (about 6 per 100). The anti-HBc prevalence rate among heterosexuals was higher than that estimated in hospital personnel from the same geographical area. A positive association between anti-HBc prevalence and present or past sexually transmitted diseases (STD) was found among homo-bisexual men. Anti-HBc was also positively associated with herpes simplex type 2 antibodies in both heterosexuals and homo-bisexual men. These data are consistent with the hypothesis that sexual behavior also plays a role in the spread of infection among heterosexuals. Ten of the 46 HBsAg-positive subjects were anti-HDV positive: 6 of the 36 heterosexuals and 4 of the 10 homosexuals. All HDV-positive subjects had present or past STDs. These findings suggest sexual transmission of HDV infection.     

Intraocular penetration of fosfomycin in man and rabbits

The intraocular distribution of fosfomycin was studied in 32 patients undergoing cataract surgery and or vitrectomy and in 8 rabbits after experimental infection of one eye by Staphylococcus aureus. In subjects perfused with 4 g of fosfomycin, concentrations ranged from 14 to 18.8 mg/l in aqueous humour (AH) and from 8 to 12.5 mg/l in vitreous fluid (VF) between 1 and 6 hours after the end of the perfusion; these levels were higher than MICs for 80-90 per cent of bacteria found in endophthalmitis. In rabbits the concentration in infected eyes with respect to healthy eyes was found to be from 2.5 to 5 times in AH and from 4.9 to 19.2 times higher in VF. Therefore fosfomycin in association with third generation cephalosporins (ceftriaxone) or with new quinolones can be recommended in the prevention and early treatment of endophthalmitis.     

Acute toxicity of two pyrethroids,permethrin, and cypermethrin in neonatal and adult rats

The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X²=5.97;p<0.05) and PERM (X²=4.37;p<0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.     

Assessing postoperative discomfort after third molar surgery: a prospective study.

PURPOSE: The purpose of this study was to identify the risk factors for severe discomfort after mandibular third molar surgery and to assess the validity of the Postoperative Symptom Severity (PoSSe) scale. PATIENTS AND METHODS: In a 2-year prospective study, a total of 255 unilateral impacted mandibular third molar teeth were surgically removed under local anesthesia by 3 surgeons. Standardized surgical and analgesic protocols were followed. At the review appointment, 1 week after surgery, all patients returned a completed follow-up questionnaire (PoSSe scale) and were evaluated clinically for postoperative pain (number of painkillers taken) and trismus (differences in mouth opening). Sixteen predictive variables were evaluated using stepwise logistic regression analysis to identify the risk factors associated with severe discomfort. RESULTS: Severe postoperative discomfort was predicted by these independent variables: gender, tobacco use, ramus relationship/space available, and antibiotic prophylaxis. Oral contraceptive use and operation time were not identified as risk factors. The patients' perceptions of the severity of symptoms (PoSSe scale score) was strongly correlated with clinical assessment of trismus (r = 0.54) and pain (r = 0.42). CONCLUSION: The PoSSe scale resulted in a valid and responsive measure of the severity of symptoms after surgical extraction of lower third molars and reflected the clinical severity of the postoperative discomfort. From a patient's perspective, operative factors had little bearing on the quality of life after removal of mandibular third molars.     

Detection of Apoptosis in Peripheral Blood Cells of 31 Subjects Affected by Down Syndrome Before and After Zinc Therapy

Thirty-one patients affected by Down syndrome (DS) were investigated to study the presence of apoptosis in peripheral blood cells in relation to the plasma levels of zinc. Twelve patients had undergone therapy with ZnSO₄, while the remaining 19 were untreated. The presence of programmed cell death was evaluated by means of electron microscopy, in situ nick translation (NT), and agarose gel electrophoresis of DNA. These approaches evidenced the presence of apoptosis in peripheral blood cells of patients before therapy with ZnSO₄, while after zinc supplementation there was a reduction in the number of apoptotic cells. These results suggest that the process of programmed cell death in peripheral blood cells of patients with Down syndrome is related to the plasma levels of zinc ion.