Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.     

Intrathecal synthesis of IgG subclasses in multiple sclerosis and in acquired immunodeficiency syndrome (AIDS)

Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.     

Chronic cryptococcal meningitis in an intravenous drug addict without evidence of infection by HIV-1,2 in southern Italy

Before the emergence of AIDS, extra-pulmonary cryptococcosis was very rare. By contrast, meningeal cryptococcosis is a very common opportunistic infection in AIDS patients. We report an intravenous drug addict with cryptococcal meningitis, who was not infected with HIV and had no apparent predisposing conditions. This case, as those elsewhere described, supports the potential existence of viral agents, other than HIV-1,2, capable of encouraging the occurrence of unusual infections as have emerged during the AIDS pandemic.     

Simultaneous Pulmonary Leiomyosarcoma and Leiomyoma in Pediatric HIV Infection

The case of a 7-year-old girl with acquired immunodeficiency syndrome treated for 5 years with AZT and intravenous gamma globulin is reported. Shortly before her demise she developed a pulmonary leiomyosarcoma and leiomyoma. Does prolonged survival in pediatric acquired immune deficiency syndrome increase the incidence of secondary malignancies?     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Reproductive health knowledge and implications: A study in Nigeria

Forty-five percent of Nigeria's population is under age 15. This study employed a questionnaire to learn the level of reproductive health knowledge of 416 male and female Nigerian students ages 10 through 16.

The Chi-square statistical procedure was used as demographic characteristics were related to reproductive health knowledge among the pre-teen and teenage youth. Statistically significant (p #lt 0.05) relationships were found between variables such as knowledge of reproduction, family planning, and AIDS when each was compared separately to age, gender, living situation while at school, school club memberships, and so on. With respect to reproduction and related topics, older teenagers indicated more knowledge than pre-teenagers, girls more than boys, and those living in dormitories more than those living at home or in other housing while attending school.

Television ranked first in terms of students' sources of information on reproduction, pregnancy, birth control, and AIDS. Newspapers ranked second, radio third, teachers fourth, and parents fifth. Perhaps the most striking data are the “I don't know” responses with respect to AIDS. Thirteen percent had not heard of AIDS, 27 percent did not know how AIDS is transmitted, 29 percent did not know the seriousness of AIDS, 37 percent did not know how to avoid AIDS, and 14 percent did not know that a mother with AIDS might infect her baby. Recommendations are made for increasing health services and education concerning reproductive health for pre-teen and teenage students.     

Demand patterns for HIV-tests in general practice: Information collected by sentinel networks in 5 European countries

This study describes a p. year international data collection on the demand pattern for HIV-antibody tests in general practice recorded by 6 sentinel networks in 5 European countries. The purpose of the recording was to evaluate the use of HIV-antibody testing by general practitioners and the demand for testing among the general population. Sentinel networks of general practitioners are a possible and available instrument for monitoring the perception of the HIV-test, and indirectly of the threat of the HIV-epidemic by the public and by the general practitioners (GPs). Differences were found between the countries in the frequency of testing, the person asking the test and the reason for testing. Possible explanatory factors, such as differences in the routine testing of specific groups, differences in the training and in the role of the GP, differences in the characteristics of prevention policy, are discussed. The European comparison also offers the opportunity to reflect on common medical practice in dealing with demands for HIV-tests.     

Focal lung uptake of Gallium-67 in patients with acquired immunodeficiency syndrome secondary to pneumocystis carinii pneumonia

It is generally accepted that the lung uptake of ⁶⁷Ga in patients with pneumocystis carinii pneumonia (PCP) is diffuse and bilateral. Three cases of focal lung uptake of ⁶⁷Ga in AIDS patients with PCP but without other opportunistic infection are described. While focal lung uptake is characteristic of opportunistic infections other than PCP, we wish to emphasize that focal uptake of gallium in the chest does not rule out PCP and may represent its earliest stage of presentation.     

Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia

Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.     

Detection of Epstein Barr virus in an hepatic leiomyomatous neoplasm in an adult human immunodeficiency virus 1-infected patient

We report the first case of a human immunodeficiency virus (HIV)-related primary hepatic leiomyoma in an adult patient. The diagnosis was made at autopsy and confirmed by immunohistochemistry. Epstein Barr virus (EBV) was identified in tumour cells by in situ hybridization. Review of the literature revealed 13 cases of visceral myogenic tumours occuring in acquired immunodeficiency syndrome children, and only 2 cases in adults. One was a spinal epidural leiomyoma, the other multiple smooth muscle tumours of the colon and adrenal gland. This is the first report of EBV in smooth muscle neoplastic cells in an HIV-infected adult patient.