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Biomedical subjects

Jeffrey L Lennox

Publications and source records attributed to Jeffrey L Lennox.

13 recordsLinked to original sources
PubMed2006

A dangerous dilemma: management of infectious intracranial aneurysms complicating endocarditis.

A 41-year-old right-handed man with bicuspid aortic valve and a 3-month history of chronic fever and weight loss presented with sudden onset of severe headache. Computerised tomography of the head revealed a right basal ganglia haemorrhage. Further investigation documented Streptococcus mitis bacteraemia, a fusiform right middle cerebral artery aneurysm, and an abscess at the base of the anterior leaflet of the mitral valve. The patient subsequently died when repeat aneurysmal haemorrhage resulted in cerebral herniation and brain death while on antibiotic therapy. Infectious intracranial aneurysms (IIAs) are uncommon but severe complications of bacterial endocarditis. Several case series have been published evaluating the management of IIAs, but no randomised controlled trials exist to guide treatment decisions. Improved diagnostic techniques, microvascular neurosurgical approaches, and endovascular therapies hold the promise of improved outcomes in the future. This difficult case is used to show an approach towards the management of IIAs complicating bacterial endocarditis based on a review of the published work.

Adult↗
PubMed2005

Imported malaria at an inner-city hospital in the United States.

BACKGROUND: More than 1000 cases of malaria are reported to the Centers for Disease Control and Prevention each year among travelers or immigrants. METHODS: Retrospective study of patients with malaria seen at Grady Memorial Hospital in Atlanta, Georgia, between October 1988 and September 2000. RESULTS: One hundred twenty-six cases of malaria were diagnosed at Grady Memorial Hospital during the study period. Fourteen patients had seen a physician prior to coming to Grady Memorial Hospital, and in 71% the diagnosis was missed. Half had recently immigrated and half recently traveled to an endemic area, yet only 22% of travelers took prophylaxis. Plasmodium falciparum was the most commonly identified species (52.4%), followed by Plasmodium vivax (23.9%). Seventy-two patients (57.1%) required hospitalization. Presenting symptoms included fever (94%), chills (56%), nausea/vomiting (38%), headache (26%), and abdominal pain (26%). Most patients were diagnosed correctly on the day of admission (79%). Twelve patients (16.7%) had severe malaria, and their complications included severe anemia (9.7%), acute renal failure (4.2%), bleeding and/or disseminated intravascular coagulation (4.2%), shock (2.8%), seizures (2.8%), and hypoglycemia (2.8%). One patient died, and two pregnant women had premature deliveries. Median hospital stay was 3.9 days. One third of the hospitalized patients with P vivax failed to receive primaquine, and in 15% of patients with P falciparum, the treatment was considered to be inappropriate. CONCLUSIONS: Although some patients with malaria have a benign course and a good outcome, many patients require hospitalization, and some have severe complications. Increased efforts are needed to educate travelers about the need for prophylaxis.

Adolescent↗
PubMed2005

Diversity, divergence, and evolution of cell-free human immunodeficiency virus type 1 in vaginal secretions and blood of chronically infected women: associations with immune status.

Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P = 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4(+) cell levels (VS, P = 0.05; BP, P = 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4(+) cell levels decreased to low levels (<50 cells/microl). Quasispecies changes over time were associated with fluctuations in CD4(+) cell levels; concordant increases or decreases in VS and BP divergence had greater CD4(+) cell level changes than intervals with discordant changes (P = 0.05), and women with evolving quasispecies had greater decreases in CD4(+) cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4(+) cell levels.

Adolescent↗
PubMed2004

Specificity of the antibody response to the pneumococcal polysaccharide and conjugate vaccines in human immunodeficiency virus-infected adults.

Nonspecific antibodies, which are thought to be nonprotective, have been shown to contribute a substantial proportion of the measured concentration in the standardized immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for pneumococcal polysaccharide capsular antibodies. The presence of such antibodies in human immunodeficiency virus (HIV)-infected persons has not been evaluated. The amount of nonspecific antibodies is proportional to the reduction in IgG antibody concentration that occurs with serum absorption with the heterologous polysaccharide 22F. We measured the amount of nonspecific antibodies before and after vaccination with the pneumococcal conjugate vaccine (PCV; n = 33) or the pneumococcal polysaccharide vaccine (PPV; n = 34) in HIV-infected adults with CD4 counts of >/== 200 cells/mm3. Blood was drawn before and 2 months after vaccination. For prevaccination sera, we found a substantial amount of nonspecific antibodies for serotypes 4, 6B, 9V, and 23F (23 to 47% of measured IgG concentration), but not for serotype 14. There tended to be proportionately less nonspecific antibodies in postvaccine sera than prevaccine sera for PCV, but not for PPV. Subjects with a low HIV viral load (</= 400 copies/ml) had proportionately more nonspecific antibodies than those with higher viral load before and after both vaccines. After 22F absorption, the geometric mean concentrations of antibodies were significantly higher post-PCV than post-PPV for the high viral load group for all five serotypes, but for no serotypes in the low viral load group. These findings confirm that absorption with a heterologous pneumococcal polysaccharide (e.g., 22F) is necessary to remove nonspecific antibodies in a standardized IgG ELISA for pneumococcal capsular antibodies in HIV-infected adults.

Adult↗
PubMed2003

Envelope diversity, coreceptor usage and syncytium-inducing phenotype of HIV-1 variants in saliva and blood during primary infection.

OBJECTIVE: To determine whether oral fluids can serve as a model for studying HIV-1 shedding, we compared the genetic diversity, coreceptor use, and syncytium-inducing (SI) phenotype of viral variants in saliva and blood during primary HIV-1 infection. DESIGN: Observational cross-sectional cohort study. METHODS: Blood plasma and saliva were sampled from 17 men early in primary HIV-1 infection. Viral diversity, predicted X4/R5 genotype and SI phenotype in samples were determined by heteroduplex tracking assays (HTAs) targeting the V1/V2 and V3 gp120 regions, sequence analyses and MT-2 cell assay. RESULTS: Identical or very similar HTA banding and deduced amino acid sequence patterns in the V1/V2 and V3-encoding regions were observed between paired fluids of each subject. As assessed by V1/V2 HTA, 10 subjects had a single major viral variant and seven subjects exhibited multiple yet highly related variants. Two subjects had V1/V2 variants in blood that were identical to saliva but present in different relative abundances. A sexual transmission pair exhibited genetically dissimilar variants, suggesting transmission of a minor variant or rapid evolution during initial viremia. All subjects harbored R5 non-SI variants. CONCLUSIONS: Relatively homogenous viral populations detected in plasma and saliva prior to seroconversion suggests that HIV-1 is disseminated to oral fluids early in infection and reflects the quasispecies in blood. These findings suggest that the oral cavity may serve as an easily accessible surrogate model for studying the dynamics of HIV-1 shedding at mucosal sites.

Adult↗
PubMed2003

Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy.

This cross-sectional study of 110 individuals examined skin testing for latent tuberculosis infection (LTBI) after the initiation of highly active antiretroviral therapy. Skin test reactivity to one or more of four antigens was found in 98 out of 110 subjects (89%), and was maximal in those whose CD4 cell counts recovered to >= 100 cells/mm3. Skin testing is reliable for the identification or exclusion of LTBI once the CD4 cell count recovers to >= 100 cells/mm3.

AIDS-Related Opportunistic Infections↗
PubMed2003

A study of discontinuing maintenance therapy in human immunodeficiency virus-infected subjects with disseminated Mycobacterium avium complex: AIDS Clinical Trial Group 393 Study Team.

The present nonrandomized prospective study evaluated whether antimycobacterial therapy for disseminated Mycobacterium avium complex (MAC) could be withdrawn from human immunodeficiency virus-infected subjects who experienced immunologic recovery while receiving highly active antiretroviral therapy (HAART). Eligible subjects had received macrolide-based therapy for least 12 months, were asymptomatic for MAC, had received HAART for at least 16 weeks, and had CD4+ T cell counts >100 cells/microL. Forty-eight subjects were enrolled, with a median CD4+ T cell count of 240 cells/microL at the time of discontinuation of MAC therapy. Forty-seven subjects remained MAC free, whereas 1 subject developed localized MAC osteomyelitis. The median duration of follow-up while not receiving therapy was 77 weeks, and the incidence of MAC infection was 1.44/100 person-years (95% confidence interval, 0.04-8.01). Withdrawal of anti-MAC therapy appears to be safe in patients who have been treated with a macrolide-based regimen for at least 1 year and have an immunologic response on HAART.

AIDS-Related Opportunistic Infections↗
PubMed2003

Macrolide-resistant pneumococcal endocarditis and epidural abscess that develop during erythromycin therapy.

Suppurative complications of Streptococcus pneumoniae infections have become uncommon in the antibiotic era. We report a case of pneumococcal bacteremia and pneumonia complicated with epidural abscess and endocarditis in which macrolide resistance (the MLS(B) phenotype) emerged during erythromycin therapy. Genetic determinants known to mediate the most common mechanisms of macrolide resistance (methylation of the 23S rRNA and antibiotic efflux) were not detected by polymerase chain reaction or DNA hybridization. Sequence analysis of the DNA encoding the 23S rRNA of the macrolide-resistant isolate from the patient demonstrated the replacement of adenine by thymine at position 2058 (A2058T) in 2 of 4 alleles. Clinicians should be alert to the possibility of the emergence of resistance during macrolide therapy for community-acquired pneumonia, particularly if suppurative complications of pneumococcal infection are suspected.

Anti-Bacterial Agents↗
PubMed2003

Detection of infectious human immunodeficiency virus type 1 in female genital secretions by a short-term culture method.

Infectious human immunodeficiency virus type 1 (HIV-1) is difficult to detect in female genital secretions by standard virus culture techniques. To improve detection of cell-free HIV-1 in female genital secretions, we adapted a short-term assay that uses the multinuclear-activation galactosidase indicator (MAGI) assay. When vaginal lavages from HIV-1-infected women were tested with the adapted MAGI assay, 25 (64%) of 39 lavages with detectable, cell-free HIV-1 RNA were shown to have infectious virus. No infectious virus was found in 10 vaginal lavages from HIV-1-infected women with undetectable vaginal viral loads. Significantly (P < 0.01) more lavages from HIV-1-infected women tested positive for infectious virus by the MAGI assay than by standard peripheral blood mononuclear cell (PBMC) coculture, which detected infectious virus in only 6 (17%) of 35 vaginal lavages. Lavages with viral loads of >10,000 copies per lavage yielded significantly (P < 0.01) more positive cultures than those with <10,000 copies by using the MAGI assay. Detection of infectious HIV-1 in vaginal lavages was not associated with the presence of genital tract infections or CD4(+)-T-cell counts. However, although the results were not significant (P = 0.08), the MAGI assay detected infectious virus from more vaginal lavages at a vaginal pH of >/=4.5 than at a pH of <4.5. These results indicate that the MAGI assay is more sensitive than PBMC culture methods for detecting infectious virus in female genital secretions. Accurate measurements of infectious virus in genital secretions will improve studies that evaluate sexual transmission of HIV-1.

Adolescent↗
PubMed2002

Viral load response to a pneumococcal conjugate vaccine, polysaccharide vaccine or placebo among HIV-infected patients.

We determined the HIV viral load in 66 adults randomly assigned to receive pneumococcal immunization with one or two doses of protein conjugate vaccine, one dose of polysaccharide vaccine, one dose of each, or placebo. Second doses were given 8 weeks after the first. Mean baseline viral load and CD4 cell count were 3.41 copies/ml (log10) and 457 cells/microl, respectively. We found no change in viral load during 24 weeks of follow-up for any vaccine or combination of vaccines or placebo.

AIDS-Related Opportunistic Infections↗
PubMed2002

Increased survival of persons with tuberculosis and human immunodeficiency virus infection, 1991--2000.

To determine factors associated with the occurrence of human immunodeficiency virus (HIV) infection and tuberculosis (TB) disease (HIV-TB) and the associated survival rate, we analyzed patients with HIV-TB at Grady Memorial Hospital, Atlanta, Georgia, from 1991 through 2000. Overall, 644 patients with HIV-TB were seen. The number of HIV-TB cases per year was highest in 1992 (102 cases) and declined to 39 cases in 2000. Over time, patients were more likely to be enrolled in the HIV outpatient clinic (P<.01), but, in 1997, only 21 (51%) of 41 patients were enrolled in HIV-infection care programs and only 9 (22%) of 41 received HAART. The 1-year survival rate for patients with HIV-TB was 58% in 1991, 81% in 1994, and 83% in 1997 (P<.001). The increase in survival for patients with HIV-TB between 1991 and 1994 was likely due to improved TB and HIV therapy. More effective strategies for enrolling and maintaining HIV-TB patients in HIV-infection care programs could further increase survival.

AIDS-Related Opportunistic Infections↗
PubMed2002

The menstrual cycle does not affect human immunodeficiency virus type 1 levels in vaginal secretions.

To determine whether the menstrual cycle affects human immunodeficiency virus (HIV) type 1 levels in vaginal secretions, vaginal lavage samples were collected at 7, 14, and 21 days after initiation of menses, to compare virus levels during the follicular, ovulatory, and luteal phases. During 33 menstrual cycles in 25 women, HIV-1 RNA levels in vaginal secretions ranged from <1000 to 5.3x10(7) copies per lavage, and weekly changes ranged from <0.5 to 2.5 log(10) copies per lavage. HIV-1 RNA levels in vaginal lavage samples from days 7, 14, and 21 were not significantly different. No discernible pattern was found in changes of vaginal virus loads (VVLs) during the menstrual cycle. VVLs were not correlated with plasma estradiol or progesterone levels (P>.05). These results suggest that hormonal changes during the menstrual cycle do not have a significant effect on HIV-1 RNA levels in vaginal secretions.

Adolescent↗