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Biomedical subjects

C Casper

Publications and source records attributed to C Casper.

At least 19 recordsLinked to original sources

The use of antiviral drugs in the prevention and treatment of Kaposi sarcoma, multicentric Castleman disease and primary effusion lymphoma.

Kaposi sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus 8 (HHV-8)] is the most recently identified member of the human herpesvirus family. Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease are all associated with KSHV infection. Although the incidence of KS has declined dramatically in areas with access to highly active antiretroviral therapy, it remains the most common AIDS-associated malignancy in the developed world and is one of the most common cancers in developing nations. Current treatment options for KSHV-associated disease are ineffective, unavailable, or toxic to many affected persons. A growing body of basic science, preclinical, and observational data suggests that antiviral medications may play an important role in the prevention and treatment of KSHV-associated disease.

Animals↗

HIV serodiscordant sex partners and the prevalence of human herpesvirus 8 infection among HIV negative men who have sex with men: baseline data from the EXPLORE Study.

OBJECTIVES: Human herpesvirus 8 (HHV-8) infection is common among men who have sex with men (MSM), especially those infected with HIV, and is frequently detected in saliva. We sought to determine whether oral or anogenital contact with HIV discordant, or unknown serostatus sexual partners is associated with HHV-8 seroprevalence among HIV negative MSM. METHODS: HIV negative MSM participating in a behavioural intervention trial for the prevention of HIV infection (the EXPLORE study) were recruited from the Seattle and Denver areas for participation in this cross sectional study. Participants completed detailed questionnaires regarding sexual behaviour, focusing on activities with possible exposure to the oropharynx. Serum samples from study enrollment were tested for the presence of HHV-8 antibodies using whole virus enzyme immunoassay and immunofluorescence assay to latent and lytic proteins. RESULTS: 198/819 MSM (24.3%) were HHV-8 antibody positive. Exposure to saliva with HIV positive and HIV unknown serostatus sex partners was reported by 83% and 90% of all men, respectively. In a multivariate model, reporting more than the median number of lifetime sex partners (OR 2.2, p = 0.03) or lifetime sex partners of unknown HIV status (OR 1.7, p = 0.03), and the performance of oro-anal sex ("rimming") on partners whose HIV status is unknown (OR 2.7, p = 0.04) were independently associated with HHV-8 infection. CONCLUSIONS: The oropharynx may be an important anatomical site in HHV-8 acquisition, and contact with HIV serodiscordant or unknown sex partners is associated with higher HHV-8 seroprevalence among HIV negative MSM.

Adult↗

Defining a role for antiviral drugs in the treatment of persons with HHV-8 infection.

Human herpesvirus type 8 (HHV-8) is the most recently identified member of the human herpesvirus family and the aetiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. While highly active antiretroviral therapy has led to impressive declines in the incidence of Kaposi's sarcoma, HHV-8- associated infections remain common and morbid across the globe. Although comprehensive clinical trials of therapy for HHV-8-associated infections are lacking, numerous studies have found current treatment modalities to be ineffective for many patients. A growing body of basic scientific and clinical work suggests that antiviral drugs may have a role in the treatment and (more significantly) in the prevention of HHV-8-associated infections. This review discusses current evidence for the efficacy of antivirals against HHV-8 and proposes novel uses for such medications in HHV-8 treatment.

Antiretroviral Therapy, Highly Active↗

[Antenatal closure of ductus arteriosus following maternal intoxication by niflumic acid].

Antenatal closure of the ductus arteriosus is an uncommon event that has been considered as a risk factor for development of congestive heart failure and persistent pulmonary hypertension of the newborn. We report here on a case of antenatal ductus arteriosus closure due to niflumic acid maternal intoxication at 32 weeks of gestation. Fetal extraction was performed few days later because of echographic signs of congestive heart failure. The child survived after 3 days of severe persistent pulmonary hypertension. This case emphasizes the potential risk of niflumic acid during pregnancy and the need of antenatal echographic monitoring for optimal management.

Adult↗

[Determinants of doxapram utilization: a survey of practice in the French Neonatal and Intensive Care Units].

UNLABELLED: Methylxanthines and doxapram have been used to stimulate breathing and to prevent apnea in preterm infants. The use of doxapram is controversial because the therapeutic index seems to be narrow and short-term adverse effects have been described. OBJECTIVE: To determine the use of doxapram in the French neonatal and intensive care units. METHODS: A structured postal questionnaire was sent to all the 236 neonatology and neonatal intensive care units of level IIa, IIb and III in France. The questionnaires were analysed after four months. RESULTS: Answers were obtained from 159 chiefs of department (67.4%), 102 used doxapram (64.1%). Doxapram was mainly used as a second step, if methylxanthines failed to reduce the frequency of apneic spells (102/159 units, 64.1%). Doxapram was usually administered intravenously (91/102 units, 89.2%). Only 57 respondents (35.8%) did not use doxapram, because they were aware of the potential adverse effects or they did not know the drug. Monitoring of drug plasma concentrations was rarely performed (11/102 services, 10.8%). Nevertheless, there was a significant interest in this monitoring. CONCLUSION: Doxapram is frequently used in France to reduce apnea of prematurity if methylxanthine therapy fails. Further studies are needed to determine safety of doxapram at short and long-term. A multicenter, randomised, double-blinded clinical trial would be interesting to perform, similar to the ongoing caffeine for Apnoea of Prematurity trial (CAP) . The French setting seems appropriate for this kind of study.

Apnea↗

The X4 phenotype of HIV type 1 evolves from R5 in two children of mothers, carrying X4, and is not linked to transmission.

Previously, we found that emergence of the X4 viral phenotype in HIV-1-infected children was related to the presence of X4 in their mothers (C.H. Casper et al., J Infect Dis 2002; 186:914-921). Here, we investigated the origin of the X4 phenotype in the child, analyzing two mother-child pairs (Ma-Ca, Mb-Cb) where the mothers carried X4 and their children developed X4 after an initial presence of R5. We used nested polymerase chain reaction of the env V3 region to generate 203 HIV-1 clones for sequencing (Ma, n = 44; Ca, n = 73; Mb, n = 61; Cb, n = 25) from DNA of peripheral blood mononuclear cell (PBMC) lysates, altogether 167 clones, or from cDNA of plasma RNA, 36 clones. PBMC and plasma isolate sequences from each time point enabled us to assign the probable phenotype to clone sequences in a phylogenetic tree. The transmission and evolution were reconstructed using the maximum likelihood method. In mother-child pair Ma-Ca, one maternal R5 isolate clustered with the child's R5 sequences, at the earliest time when R5 was isolated in the child, confirming this as a likely source of the transmitted R5 phenotype. At age 3, an X4 population was present in the child that had evolved from the child's own R5-associated population, clearly distinct from the maternal X4 sequences. The second mother-child pair (Mb-Cb) displayed a similar pattern. Amino acid substitution patterns corroborated the conclusions from the phylogenetic tree. Thus, in both children, the X4 virus developed from their own R5 population, and was not caused by transmission of X4.

Amino Acid Sequence↗

Jessner-Kanof lymphocytic infiltration of the skin associated with glatiramer acetate.

Glatiramer acetate (GLAT) is a well tolerated and safe immunomodulatory drug for the treatment of relapsing-remitting multiple sclerosis. The most commonly recognized side effects are localized injection site reactions consisting of pain, pruritus, mild erythema and induration, which sometimes persist for several days. We describe the first case of a biopsy-proven lymphocytic infiltration (T-cell pseudolymphoma) with the clinical appearance of a figured erythema on the ventrolateral thighs in the first four weeks under GLAT treatment, resolving without any evidence of recurrence despite ongoing therapy. A T-cell pseudolymphoma is a very rare side effect of GLAT treatment. For clinical purposes it is important to state that re-exposition after GLAT-induced pseudolymphoma is possible without permanent sequelae.

Adult↗

Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes.

Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n = 2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4+ cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.

Acquired Immunodeficiency Syndrome↗

Genetic analysis of a severe case of Netherton syndrome and application for prenatal testing.

Netherton syndrome (NS) is a rare autosomal recessive disease with variable expression. It is defined by a triad of symptoms: congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy. Recently, genetic linkage has been established to the SPINK5 gene locus on chromosome 5q32 encoding the serine protease inhibitor LEKTI. In this study, we present a recurrent homozygous mononucleotide deletion (153delT) resulting in a severe case of NS exhibiting exfoliative erythroderma with lethal outcome at the age of 4 months and its application in prenatal testing in a subsequent pregnancy of the mother.

Carrier Proteins↗

Mother-to-child transmission of HIV-1: the role of HIV-1 variability and the placental barrier.

The acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus (HIV), was first described in the United States of America in 1981 [1]. The worldwide spread of HIV has soon been recognized and AIDS has become one of the most alarming infectious diseases of our days. Its impact has been tremendous, high morbidity and mortality has caused a reversal of socioeconomic gains previously recorded in several developing countries, especially those in Sub-Saharan Africa [2]. Epidemiological data about the HIV and AIDS pandemic are updated by the Joint United Nation Programme on HIV/AIDS, UNAIDS (http://www.unaids.org). Their latest report from December 2000 states that in year 2000 approximately 5.3 million people have become newly infected with HIV, of which 2.2 were women and 600,000 children younger than 15 years of age. The estimated number of people living with HIV/AIDS globally is 36.1 million, of which 16.4 million are women and 1.4 million are children younger than 15 years of age. Approximately 25.3 million (70%) of these HIV infected people live in Sub-Saharan Africa, 5.8 million in South- and South-East Asia (15%), and 1.4 million in Latin-America (5%). During year 2000, 3 million people died of AIDS (1.3 million women and 500,000 children younger than 15 years of age). This means that an estimated total of 21.8 million persons have died of AIDS since the beginning of the epidemic, including 4.3 million children younger than 15 years of age.

Adult↗

[Reduced mother-to-child transmission of HIV-1 infection. Exclusive breast feeding and weaning--a possible model in developing countries?].

Antiretroviral therapy with zidovudine during pregnancy, delivery, and to the newborn in combination with Cesarean section has markedly reduced the rate of mother-to-child transmission of HIV-1 in industrialized countries. These strategies are not realistic in the less developed world. Nevertheless, short-term antiretroviral therapy during delivery and shortly after birth has proven feasible as a means of reducing the rate of vertical transmission in less developed countries, in some studies even in combination with exclusive breast-feeding. The risks and benefits of breast-feeding among HIV-1 infected mothers are discussed.

Anti-HIV Agents↗

Mapping of a mouse mammary tumor virus integration site by retroviral LTR--arbitrary polymerase chain reaction.

The de novo integration of retroviral genomes within the mammalian genome is believed to contribute to the tumorigenic process. Integration may result in the disruption or inappropriate transcription of key regulatory genes. We describe the application of an arbitrarily primed PCR method for the mapping and cloning of genomic integration sites of the mouse mammary tumor virus (MMTV). We have amplified DNA sequences between a selected retroviral MMTV-LTR and random sites in the 3' flanking DNA. Using this technique we were able to visualize several proviral integration sites present in a MMTV-induced mammary tumor derived cell line that were absent from the germ line. Cloning and sequencing of the PCR product corresponding to one site established its identification as an unique 3' flanking sequence.

Animals↗

The transcontinental transmission of tuberculosis: A molecular epidemiological assessment.

Many tuberculosis control activities are based on principles learned from studies of tuberculosis transmission. To date, these have largely been limited to outbreak investigations in confined geographical regions. In this report conventional and computerized DNA fingerprint- based approaches were integrated to demonstrate that the most widely prevalent strain of Mycobacterium tuberculosis from New York City was cultured from only 1 of 755 patients in San Francisco, Calif, who was a traveling salesman. Large-scale molecular epidemiologic studies may provide a better understanding of the dynamics of tuberculosis transmission between geographic regions and suggest rational measures to interrupt such transmission.

Adult↗

[In vitro diagnosis of coronary plaque morphology with intravascular ultrasound: comparison with histopathologic findings].

The aim of this study was to validate the accuracy of a commercially available intravascular ultrasound system in diagnosing plaque composition in human coronary arteries. Thirty-five coronary arteries of 18 human autopsy hearts were perfused with NaCl under a pressure of 100 mmHg and examined using a Diasonics ultrasound system and 4.8 F 20 MHz catheters. An ultrasound diagnosis was made of 139 coronary sections using previously published standard criteria and compared with histologic findings. In addition, the influence of the histologic pattern of lipid and calcific deposits on the accuracy of the ultrasound diagnosis was evaluated. Of the 25 sections with a histologically normal intima, 14 (56%) were correctly identified by ultrasound, whereas fibrotic thickening was diagnosed in the remaining 11 sections. There were 114 plaques by histology which were correctly visualized by ultrasound as plaques in all instances. Plaque calcification was correctly diagnosed in 54 of 63 (86%) sections, but massive calcifications were more reliably identified by ultrasound than small speckled calcifications (43/44 = 98% vs 11/19 = 58%, p < 0.001). Fibrosis was present in all 114 plaques and was correctly visualized by ultrasound in all instances. When lipid was diagnosed by ultrasound as a homogeneous zone of low signal intensity within a fibrous plaque as suggested in the literature, lipid accumulations were identified with a sensitivity of 26% (16/62) and a specificity of 92% (71/77). When lipids were diagnosed if more than a quarter of the plaque area showed lower signal intensity than the tissue surrounding the vessel, the sensitivity of ultrasound was improved to 73% (45/62) but specificity fell to 30% (23/77). The entire histologic composition of a section was correctly diagnosed by ultrasound in only 42% of the 139 sections. Further technical improvements are therefore mandatory before intracoronary ultrasound will be able to provide a reliable analysis of plaque composition, especially of the lipid content.

Adult↗