Biomedical subjects

J A Bartlett

Publications and source records attributed to J A Bartlett.

At least 19 recordsLinked to original sources

PubMed2005

Sociodemographic and clinical characteristics of clients presenting for HIV voluntary counselling and testing in Moshi, Tanzania.

HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. Factors associated with HIV infection in VCT clients have not been well characterized in northern Tanzania. We prospectively surveyed 813 VCT clients in Moshi, Tanzania. Clients were administered a questionnaire on sociodemographic characteristics, sexual behaviour, and health status. Blood was taken for rapid HIV antibody testing. Factors associated with HIV seropositivity were identified using multivariate logistic regression analysis. Of 813 clients, the seroprevalence was 16.7%. The strongest associations with seropositivity were reporting diarrhoea (odds ratio [OR] 10.4, 95% confidence interval [CI] 3.6-29.9), an ill sexual partner (OR 6.3, 95% CI 3.0-12.9), or being a woman (OR 3.5, 95% CI 2.0-6.3). In a separate regression, the number of symptoms also predicted HIV infection (OR 2.1, 95% CI 1.6-2.6). VCT clients who tested positive had more HIV-related symptoms suggesting presentation at a later stage of HIV infection.

AIDS Serodiagnosis↗

PubMed2004

HIV-associated morbidity, mortality and diagnostic testing opportunities among inpatients at a referral hospital in northern Tanzania.

Hospitalized patients with HIV infection are among the most likely to benefit from the expanding availability of anti-retroviral therapy in sub-Saharan Africa. Between 1990 and 2000, 3667 people known to be HIV-infected were admitted to Kilimanjaro Christian Medical Centre (KCMC) in Moshi, northen Tanzania. The level of inpatient mortality among these patients varied from 15%-21%, and the proportion of the HIV-infected patients admitted who were female increased significantly, from 45% at the start of the study period to 52% at the end (P <0.001). When the medical records for 1683 of the HIV-infected patients who had been admitted between 1996 and 2001 were reviewed, the most prevalent diagnoses on admission were found to be pulmonary tuberculosis (21%), malaria (14%) and gastro-enteritis/diarrhoea (12%) among the adults, and non-tubercular pulmonary infection (21%), pulmonary tuberculosis (19%) and gastro-enteritis/diarrhoea (12%) among the children. The crude odds ratios (OR) for inpatient death were greatest for adults presenting with meningitis [OR=3.7; 95% confidence interval (CI)=2.1-6.7], septicaemia (OR=2.9; CI=1.2-7.3) or renal disease (OR=2.6; CI=1.2-5.7), and mortality was higher for men than for women (OR=1.4; CI=1.1-1.8). A single-day, point-prevalence survey in September 2001, among the KCMC's inpatients, identified HIV infection in 21% of those surveyed, many (44%) of the patients found positive being previously unaware of their infection. HIV infection remains a major cause of hospitalization and mortality in Moshi. A policy of routine testing would increase the number of HIV infections detected, allowing improvements in case management and in the prevention of infection.

Adolescent↗

PubMed2002

Addressing the challenges of adherence.

Adherence to antiretroviral therapy is a crucial determinant of treatment success. Studies have unequivocally demonstrated the close association between adherence and plasma HIV RNA levels, CD4 cell counts, and mortality in patients with HIV infection and disease. Adherence levels of > or =95% are required to maintain virologic suppression. However, actual adherence rates are often far lower; most studies show that 40% to 60% of patients are <90% adherent. Adherence also tends to decrease over time. Patients offer a range of reasons for nonadherence, but the most frequently cited one is simply that they forget; other reasons include being away from home, being busy, or experiencing a change in daily routine. Additional barriers to adherence include psychiatric disorders, such as depression or substance use, uncertainty about the effectiveness of treatment and the consequences of poor adherence, regimen complexity, and treatment side effects. Several strategies can be employed in the effort to support patients' adherence, and all members of the multidisciplinary team should ideally employ these strategies in combination. Efforts should be made to educate and motivate patients, simplify treatment regimens and tailor them to individual lifestyles, prepare for and manage side effects, and address the concrete issues that may be a barrier to adherence. Recruiting an adherence monitor, providing memory aids to medication taking, and anticipating course corrections can also help patients achieve the adherence rates needed for successful treatment of HIV infection and disease.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Protease inhibitors are associated with a slowed progression of HIV-related renal diseases.

AIMS: While angiotensin-con-verting enzyme inhibitors and zidovudine may improve the course of the most common HIV-related renal disease, HIV-associated nephropathy (HIVAN), the effect of anti-retroviral combination therapy on this and other HIV-related renal diseases has not been assessed. This study describes the clinical course of HIV-related renal diseases and the effect of protease inhibitors on their progression. METHODS: This retrospective cohort study reviews the clinical course of 19 patients with a clinical or biopsy-proven diagnosis of HIVAN or other HIV-related renal diseases. Groups progressing and not progressing to ESRD were compared using longitudinal analyses to assess the association between creatinine clearance and clinical and therapeutic factors. RESULTS: The cohort consisted of 16 African-Americans, 2 Caucasians and 1 Native American. Their modes of HIV infection were intravenous drug use (7), a history of men having sex with men (3) and heterosexual behavior (5). Patients were followed for a median of 16.6 months. Seven patients reached ESRD. Loss of creatinine clearance over time did not differ among genders, races, or patients with different modes of HIV infection. Longitudinal analyses demonstrated an association between protease inhibitors and prednisone and a slower decline in creatinine clearance in multivariable models (p = 0.04 and 0.003, respectively). CONCLUSIONS: The epidemiology and clinical course of HIV-related renal diseases is more heterogeneous than previously described. This study suggests a benefit to the use of protease inhibitors and prednisone on the progression of these nephropathies.

AIDS-Associated Nephropathy↗

PubMed2001

Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy.

The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV-infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4+ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4+ CD45RA+ CD62L+ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4+ T cell counts increased from approximately 60/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4+ T lymphopenia.

Adolescent↗

PubMed2001

Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects.

The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4(+) T cells >400 per microl. CD4(+) T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-gamma-producing HIV-1-specific CD8(+) and CD4(+) T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8(+) T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4(+) T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4(+) T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4(+) T cell counts, and showed no enhancement of antiviral CD8(+) T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.

Adult↗

PubMed2001

Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults.

AIM: To estimate the effectiveness of triple combination therapy in antiretroviral-naive adults. METHODS: A systematic overview of results from clinical trials involving triple combination therapy with dual nucleoside reverse transcriptase inhibitors (NRTI) and: a protease inhibitor (PI triple); a non-nucleoside reverse transcriptase inhibitor (NNRTI triple); or a third NRTI (triple NUC). Data from 23 clinical trials involving 31 independent treatment groups, 19 unique antiretroviral regimens, and 3257 enrolled patients were included in this study. RESULTS: Median log(10) baseline plasma HIV RNA and CD4 cell count over all trials averaged 4.69 (49,329 copies/ml) and 375 x 10(6) cells/l, respectively. The overall estimated percentage of patients with plasma HIV RNA < or = 400 copies/ml at 24 weeks was 64% [95% confidence interval (CI), 60 to 67%]. The percentages of patients with plasma HIV RNA < or = 50 copies/ml at 48 weeks by drug class were: PI triple, 46% (95% CI, 41 to 52%); NNRTI triple, 51% (95% CI, 43 to 59%); triple NUC, 45% (95% CI, 36 to 54%). The CD4 cell count increase over all trials at 24 and 48 weeks averaged +123 x 10(6) cells/l (95% CI, 111 x 10(6) to 135 x 10(6) cells/l) and +160 x 10(6) cells/l (95% CI, 146 x 10(6) to 175 x 10(6) cells/l), respectively and did not differ between drug classes. In multivariable regression analysis, neither baseline plasma HIV RNA level and CD4 cell count nor treatment regimen predicted plasma HIV RNA < or = 50 copies/ml at week 48. However, pill count was significantly negatively associated with plasma HIV RNA < or = 50 copies/ml at week 48 (P = 0.0085). CONCLUSIONS: The results suggest that three drug regimens containing two NRTI with a PI, a NNRTI, or a third NRTI may provide comparable activity, and practical issues such as daily pill burden should be considered when choosing a treatment regimen.

CD4 Lymphocyte Count↗

PubMed2001

Immunologic profile of human immunodeficiency virus-infected patients during viral remission and relapse on antiretroviral therapy.

A dissociation between plasma human immunodeficiency virus (HIV) RNA levels and CD4(+) cell counts has been reported in patients experiencing viral relapse while receiving antiretroviral therapy. This study compared patients with stable CD4(+) lymphocytes during viral relapse while receiving treatment with patients who had sustained virus suppression. Plasma HIV RNA levels, lymphocyte immunophenotyping, and T cell receptor excision circle (TREC) levels were measured. Naive CD4(+) lymphocyte phenotype and TREC levels were not significantly different in patients with virus suppression or in those who had relapsed. However, CD8(+) lymphocyte activation, including the number and percentage of activated cells and CD38 antibody-binding capacity, was significantly elevated during viral relapse, compared with that in suppressed patients. By multivariable regression analyses, CD8(+) and CD4(+) lymphocyte activation were associated significantly with increasing plasma HIV RNA levels.

Adult↗

PubMed2001

Primary care for patients infected with human immunodeficiency virus: a randomized controlled trial.

OBJECTIVE: To measure the impact of a teaching intervention and to compare process and outcomes of care for HIV-infected patients randomly assigned to a general medicine clinic (GMC) or an infectious disease clinic (IDC) for primary care. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital in Durham, NC. PATIENTS: Two hundred fourteen consecutive HIV-infected patients presenting for primary care. INTERVENTION: Physicians at the GMC received HIV-related training and evidence-based practice guidelines. MEASUREMENTS: Utilization of services, health-related quality of life, preventive and screening measures, and antiretroviral use for one year. RESULTS: At baseline GMC patients were more likely to be African American (85% vs 71%; P =.03) and had lower baseline CD4+ cell counts than IDC patients (262 +/- 269 vs 329 +/- 275; P =.05). A similar and high proportion of patients in both groups received appropriate preventive care services including Pneumocystis carinii pneumonia (PCP) prophylaxis, pneumococcal vaccination, and antiretroviral therapy. Screening for TB was more frequent in GMC (89% vs 68%; P =.001). In the year following randomization, GMC patients made more visits to the emergency department than IDC patients (1.6 +/- 3.0 vs 0.7 +/- 1.5; P =.05). Hospital use was higher for GMC patients with average length of stay 7.8 +/- 6.3 days compared to 5.7 +/- 3.8 days for IDC patients (P =.01). In analyses, which adjust for potential baseline imbalances, these differences remained. CONCLUSIONS: Targeted education in GMC achieved similar provision of primary care for GMC patients, yet use of health care services was higher for this group. The delivery of adequate primary care is necessary but not sufficient to produce changes in health care utilization.

Continuity of Patient Care↗

PubMed2001

Immune function in healthy inner-city children.

The importance of investigating immunity in healthy children has been underscored in the last few years by studies of the immune pathology of childhood illnesses, including human immunodeficiency virus. This study reports both ennumerative and functional immune measures in healthy inner city children. A total of 152 of 207 children studied were completely heathy at the time of venipuncture and were included in this study. Laboratory immune batteries were completed (or begun) the same day as venipuncture. Relationships between age, gender, ethnicity, and immunity were then analyzed. We found that gender predicted both the absolute number and the percentage of T cells and helper cells and the percentage of natural killer cells. Total leukocyte counts and percentages of lymphocytes and granulocytes were related to ethnicity, as was the response to mitogen stimulation (concanavalin A and pokeweed mitogen) and phagocytic ability. In conclusion, age, gender, and ethnicity factors were found to contribute to differences in various immune measures in children and require further investigation.

Child↗

PubMed2000

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

Adult↗

PubMed2000

Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells.

Extensively conjugated cationic molecules with appropriate structural features naturally accumulate into the mitochondria of living cells, a phenomenon typically more prominent in tumor than in normal cells. Because a variety of tumor cells also retain pertinent cationic structures for longer periods of time compared with normal cells, mitochondrial targeting has been proposed as a selective therapeutic strategy of relevance for both chemotherapy and photochemotherapy of neoplastic diseases. Here we report that the triarylmethane dye crystal violet stains cell mitochondria with efficiency and selectivity, and is a promising candidate for photochemotherapy applications. Crystal violet exhibits pronounced phototoxicity toward L1210 leukemia cells but comparatively small toxic effects toward normal hematopoietic cells (murine granulocyte-macrophage progenitors, CFU-GM). On the basis of a comparative examination of chemical, photochemical, and phototoxic properties of crystal violet and other triarylmethane dyes, we have identified interdependencies between molecular structure, and selective phototoxicity toward tumor cells. These structure-activity relationships represent useful guidelines for the development of novel purging protocols to promote selective elimination of residual tumor cells from autologous bone marrow grafts with minimum toxicity to normal hematopoietic stem cells.

Animals↗

PubMed2000

The isolation of FOS-1, a gene encoding a putative two-component histidine kinase from Aspergillus fumigatus.

In fungi, two-component histidine kinases are involved in response mechanisms to extracellular changes in osmolarity, resistance to dicarboximide fungicides, and cell-wall assembly. In the human opportunistic fungus, Candida albicans, each of the three histidine kinases plays a role in virulence. Here, we identify, for the first time, a gene, FOS-1, from the human pathogenic fungus Aspergillus fumigatus that predicts a protein with homology to two-component histidine kinases. The predicted FOS-1 protein is highly homologous to bacterial and other fungal histidine kinases in several functional domains, but is divergent at the amino- and carboxy-termini. A mutant lacking the FOS-1 locus, DeltaFOS-1, did not exhibit a detectable defect in either hyphal growth or morphology when grown on solid or liquid medium. However, in liquid medium, conidiophore development of the DeltaFOS-1 mutant was delayed. Compared to wild type, the DeltaFOS-1 strain was neither osmotically sensitive nor sensitive or resistant to a number of nondicarboximide antifungal drugs, but was highly resistant to dicarboximide fungicides and resistant to novozym 234, suggesting that FOS-1p may play a role in the regulation of cell-wall assembly.

Amino Acid Sequence↗

PubMed2000

Influence of neurological level on immune function following spinal cord injury: a review.

Due to the high incidence of lifelong infections in persons with spinal cord injury (SCI), the authors examined level of injury-related immune characteristics in a cohort of subjects with chronic SCI. Since the sympathetic nervous system and the endocrine system are known to be modulators of immune function, one possible explanation for heightened incidence of infections includes dysregulation of sympathetic outflow tracts in individuals with tetraplegia or high paraplegia. Natural killer cell cytotoxicity (NKCC) and bactericidal function of circulating neutrophils were assayed in a group of 10 individuals with chronic complete cervical SCI, a group of 8 individuals with paraplegia with injuries below the main sympathetic outflow (T-10 and below) and a group of 18 age- and sex-matched controls. In addition, a psychiatric assessment of depression was performed as well as assays of pituitary and adrenal functions. Analyses revealed no significant differences in immune function between all subjects with SCI combined and their matched controls. Further analyses stratifying based on presence or absence of sympathetic dysregulation revealed significantly impaired phagocytic ability and a trend toward reduced NKCC in the group with tetraplegia compared with their controls. Hormonal assays showed that dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DS) were higher in individuals with tetraplegia than controls, but no such differences were observed in individuals with paraplegia compared with their controls. The results of this study suggest that individuals sustaining complete cervical SCI experience alterations in immune function, while those with lesions at or below T-10 do not. These findings of level of injury related immune alteration could not be explained by mood differences. This paper is a review of previously published work and the authors' current thinking regarding increased acquisition of infections in this population.

Adult↗

PubMed1999

Depression and immunity: clinical factors and therapeutic course.

While many reports describe associations between depressive disorders and altered immunity, findings have not been fully consistent. Diagnostic subtype, demographic factors such as age and gender, medical characteristics, and the immune measures selected for assessment may have contributed to the heterogeneous findings. In a study of 21 medically healthy young adults with major depression, we found, consistent with previous reports, evidence of increased lymphocyte activation to mitogen challenge and decreased natural killer (NK) cell numbers and function during acute depression. Fifteen subjects were followed longitudinally. T, CD4+, CD29+, and CD45RA+ lymphocytes and T-cell mitogen responses decreased significantly (P<0.05) during 6 weeks of pharmacotherapy and concurrent clinical improvement. There was no change in NK activity or CD56+ cells. The longitudinal effects appeared unrelated to tricyclic antidepressant levels. Changes in the immune system with short-term clinical improvement in depressed patients are not uniform providing further evidence that several mechanisms are involved in the altered immunity associated with clinical depression.

Adolescent↗

PubMed1999

Strategies of antiretroviral therapy in adults.

Recent progress in antiretroviral treatment has led to dramatic improvements in HIV-related morbidity and mortality. These improvements have been fostered by advances in our understanding of HIV-related pathogenesis, the use of plasma HIV RNA levels to monitor patients, and the availability of 13 licensed antiretroviral drugs. Numerous drug combinations, especially those containing three or more agents, can suppress plasma HIV RNA levels below the lower limit of detection in the majority of treated patients. Urologists should be familiar with the limitations of this therapeutic response: patient adherence, drug resistance, a residual burden of chronically infected cells which are refractory to treatment, an unknown impact on HIV in genital secretions, and potential transmissibility through sexual contact.

Adult↗

PubMed1999

Self-reported systemic, immune-mediated disorders in patients with and without proplast-teflon implants of the temporomandibular joint.

PURPOSE: This study investigates the self-reported immune-related health status of patients exposed to Proplast-Teflon (P/T) temporomandibular joint (TMJ) implants, comparing their health status with a group of patients who were not exposed to any alloplastic TMJ implants. It also compares those whose implants were removed with those in whom they were retained. PATIENTS AND METHODS: Patients seen in a single oral and maxillofacial surgical practice completed a detailed self-report questionnaire about physical symptoms and disorders. Sixty-four had received P/T implants, and 22 were unexposed to any TMJ alloplastic implant. Of the P/T-exposed group, 44 had removed and 20 had retained implants. RESULTS: In general, P/T-exposed patients did not differ from unexposed patients in rates of reported immune-mediated and somatization-related conditions, allergies, or symptoms of environmental sensitivity. However, patients with removed P/T implants reported significantly more problems in all categories of conditions than those with retained P/T implants. This difference was no longer statistically significant after controlling for pain severity and sex. CONCLUSIONS: Although P/T-exposed patients do not report more systemic health conditions than similar patients who were unexposed to alloplastic jaw implants, those with removed implants report more conditions and are more likely to be seen in clinical practice. This may lead to a bias in the general perception regarding the systemic health status of P/T-exposed patients. In addition, effects may be secondary to high levels of pain and dysfunction among patients with removed implants, rather than implant exposure itself. Future prospective research is needed to identify factors associated with implant failure.

Adult↗

PubMed1999

Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials.

Lamivudine population pharmacokinetics were investigated by using nonlinear mixed-effect modelling (NONMEM) analysis of data from 394 human immunodeficiency virus (HIV)-infected patients treated with lamivudine (150 to 300 mg every 12 h) in two large, phase III clinical efficacy-safety trials, NUCA3001 and NUCA3002. Analyses of 1,477 serum lamivudine concentration determinations showed that population estimates for lamivudine oral clearance (CL/F; 25.1 liters/h) and volume of distribution (V/F; 128 liters) were similar to values previously reported for HIV-infected patients in phase I pharmacokinetic studies. Lamivudine CL/F was significantly influenced by the covariates creatinine clearance and weight and not affected by age, Centers for Disease Control and Prevention (CDC) classification, CD4(+) cell count, HIV type 1 (HIV-1) RNA PCR, or gender and race when CL/F was corrected for differences in patient weight. The population estimate for lamivudine V/F was not significantly influenced by the covariates gender, race, age, weight, renal function, HIV-1 RNA PCR, or CDC classification and CD4(+) cell count when creatinine clearance was included with CL/F in the model. Lamivudine disposition was significantly influenced by renal function. However, as only three patients had an estimated creatinine clearance of <60 ml/min, dosage adjustments for patients with impaired renal function should not be determined based on the population parameters derived in this analysis.

Adult↗