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Biomedical subjects

D Hom

Publications and source records attributed to D Hom.

At least 19 recordsLinked to original sources
PubMed2003

Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: results of the HIV Network for Prevention Trials 007 Vaccine Study.

In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.

AIDS Vaccines↗
PubMed2001

Quantification of tumor cell injury in vitro and in vivo using expression of green fluorescent protein under the control of the GADD153 promoter.

The GADD153 gene is strongly transcriptionally activated by many types of cellular injury and the magnitude of the change in GADD153 expression is proportional to the extent of damage. We developed a novel reporter system in which a chimeric gene containing the GADD153 promoter linked to the coding region of an enhanced green fluorescent protein (EGFP) gene was stably integrated into the genome of a clone of UMSCC10b head and neck carcinoma cells. Activation of the exogenous GADD153 promoter was quantified using flow cytometric measurement of EGFP expression following drug exposure. The exogenous GADD153 promoter in this clone was activated by N-methl-N'-nitro-N-nitrosoguanidine (MNNG) in a concentration-dependent manner with kinetics that closely paralleled perturbation of cell cycle phase distribution. EGFP expression was strongly activated by a variety of genotoxic agents including DNA cross-linking and methylating agents, oxygen free radicals, DNA intercalator, UV and gamma-radiation and hypoxia. When grown as a xenograft in nude mice, the stably transfected clone also demonstrated dose-dependent EGFP expression when measured 4 days after cisplatin treatment. The reporter system accurately categorized the relative potency of adducts produced by 6 related platinum-containing drugs. In conclusion, this reporter system can facilitate in vitro and in vivo screening for agents capable of producing cytotoxicity via a wide variety of different mechanisms, and can be utilized to investigate the relative potency of structurally related DNA adducts.

Animals↗
PubMed2001

Use of the neodymium: YAG laser for interstitial cystitis: a prospective study.

PURPOSE: Interstitial cystitis is a disorder of the bladder characterized by urgency and frequency of urination, and pelvic pain. The classic type of interstitial cystitis is characterized by Hunner's ulcers, which are focal regions of severe bladder inflammation. Patients with Hunner's ulcers tend to have more severe symptoms and are often refractory to medical management. We present a prospective series of patients who underwent ablative therapy of Hunner's ulcers using a neodymium (Nd):YAG laser. MATERIALS AND METHODS: A total of 24 patients with interstitial cystitis underwent ablative therapy for Hunner's ulcers. Medical therapy had failed in all cases. Using regional or general anesthesia the Nd:YAG laser under cystoscopic control was used to ablate the ulcers. The power setting was 15 W. with a firing duration of between 1 and 3 seconds. The procedure was performed on an outpatient basis. Symptoms were noted preoperatively and postoperatively. RESULTS: All patients had symptom improvement within 2 to 3 days. The mean pain scores decreased from 9.1 to 1.2 (p <0.003), the mean urgency score decreased from 8.2 to 1.9 (p <0.003), the mean voiding interval increased from every 30 minutes to every 102 (p <0.0001) and nocturia decreased from a mean of 7.9 voids per night to 2.9 (p <0.0001). There were no complications. Mean followup was 23 months. However, relapse in 11 patients required 1 to 4 additional treatments. The re-treatment response was similar to the initial treatment. CONCLUSIONS: Nd:YAG laser ablation of Hunner's ulcers is an excellent, minimally invasive method of treating interstitial cystitis. While it is not a cure, it offers patients an opportunity to have decreased symptoms for an extended period and it may be repeated as necessary.

Aged↗
PubMed2000

The role of nitric oxide in obstructive nephropathy.

PURPOSE: Ureteral obstruction leads to tubulointerstitial fibrosis and loss of renal function. Nitric oxide production ameliorates fibrosis due to obstructive uropathy. However, nitric oxide is produced by 3 isoforms of the enzyme, nitric oxide synthase. We evaluated the role of inducible nitric oxide synthase in obstructive uropathy using nitric oxide synthase knockout mice, and determined whether the administration of L-arginine to promote nitric oxide synthesis by alternative nitric oxide synthase isoforms modulates renal fibrosis in these animals. MATERIALS AND METHODS: Complete unilateral ureteral obstruction was created in wild-type C57 and inducible nitric oxide synthase knockout mice. Control animals of each strain underwent sham surgery. Throughout the experiment mice had free access to untreated tap water or water supplemented with 10 gm./l. L-arginine. Animals were sacrificed 1 and 2 weeks, respectively, after creation of unilateral ureteral obstruction. We obtained serum as well as bladder and obstructed renal pelvic urine, and determined the nitrite level in each fluid. Renal cortical thickness was measured in the normal and obstructed kidneys. The degree of tubulointerstitial fibrosis was evaluated by trichrome staining and type I collagen deposition in kidney tissue specimens. RESULTS: Nitrite was significantly decreased in the serum, bladder and renal pelvic urine of inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction compared with that in wild-type C57 mice at 1 and 2 weeks (p<0.05). In knockout mice with unilateral ureteral obstruction 1 week in duration that drank tap or L-arginine supplemented water nitrite in serum and each urine sample was higher than in sham operated knockout controls. The level returned to baseline after 2 weeks of obstruction (p<0.05). After 2 weeks of obstruction there was significantly greater cortical thinning in knockout than in C57 mice (p<0.05). Moreover, knockout mice given L-arginine supplemented water for 2 weeks had even greater cortical thinning than after 1 week or than mice given tap water for 1 to 2 weeks (p<0.05). Decreased renal cortical thickness in knockout mice after 2 weeks of obstruction was associated with less intense trichrome staining and a virtual absence of type I collagen deposition compared with findings in the wild-type C57 strain. CONCLUSIONS: Inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction have significantly lower nitrite in serum and urine than wild-type C57 mice. Knockout mice also have more severe renal cortical thinning than C57 animals after creation of unilateral ureteral obstruction. Providing L-arginine supplemented water to inducible nitric oxide synthase knockout mice exacerbates the loss of cortical thickness. Alterations in cortical thinning that we observed in knockout mice were associated with decreased tubulointerstitial fibrosis and a decreased net renal extracellular matrix accumulation. These data indicate that endothelial or neuronal nitric oxide synthase may be more important than inducible nitric oxide synthase for modulating renal fibrosis in obstructive uropathy.

Animals↗
PubMed2000

Efficacy of an unsupervised 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis in HIV-infected adults. Uganda-Case Western Reserve University Research Collaboration.

SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE: To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN: Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS: Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION: An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.

AIDS-Related Opportunistic Infections↗
PubMed1999

A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006).

OBJECTIVE: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. DESIGN: An open label phase I/II study. SETTING: Tertiary care hospital, Kampala, Uganda. PATIENTS AND INTERVENTIONS: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. OUTCOMES: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. RESULTS: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. CONCLUSION: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.

Anti-HIV Agents↗
PubMed1999

Neurodevelopmental outcomes of Ugandan infants with HIV infection: an application of growth curve analysis.

Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)-infected infants of non-drug-using mothers were assessed in a controlled, prospective study from birth to 24 months with 3 groups: 61 infants of HIV-infected mothers, 234 uninfected infants of HIV-infected mothers (seroreverters), and 115 uninfected infants of uninfected mothers. Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated lower mental and motor development on the Bayley Scales and greater deceleration in their rate of motor development. HIV-infected infants with abnormal neurologic exams had lower motor and mental test scores and lower rates of motor Bayley Scales scores than their HIV-infected counterparts with normal neurologic exams. Contrary to prediction, no group differences in mean performance or growth rates were found on visual information processing on the Fagan Test of Infant Intelligence.

AIDS Dementia Complex↗
PubMed1999

Heightened suspicion and rapid evaluation with CT for early diagnosis of partial renal infarction.

BACKGROUND AND OBJECTIVE: Although renal infarction has been well studied and clearly defined, it remains greatly underdiagnosed, resulting in significant morbidity. Acute segmental renal infarction is a diagnosis even more problematic, as the problem can appear insidiously and masquerade as other entities including stone, infection, and even tumor. The clinical manifestations and evaluation of partial renal infarction in our patients were reviewed. PATIENTS AND METHODS: Seven patients presenting to the emergency department who were subsequently found to have partial renal infarction were identified from the 5-year records of a single institution. Patients were evaluated for presenting complaints, physical findings, temperature, and blood pressure. Laboratory analysis consisted of a complete blood count (CBC); measurements of creatinine, lactate dehydrogenase (LDH), aspartate transaminase/alanine transaminase (AST/ALT), and alkaline phosphatase; and urinalysis. The sequence of the work-up was recorded, as well as time to diagnosis. The etiology of infarction was identified for all patients. RESULTS: All seven patients were eventually discovered to have partial renal infarction as a result of dysrhythmia (N = 4), mural thrombus (N = 2), or septic emboli (N = 1). The average time to diagnosis was 65.2 hours with a range of 9.5 to 168 hours. The chief complaint was flank pain (N = 3), nonspecific abdominal pain (N = 2), left lower-quadrant pain (N = 1), and mental status change (N = 1). The presenting signs and symptoms included abdominal tenderness (N = 4), nausea and vomiting (N = 4), temperature >100.5 degrees F (N = 3), and hypertension (N = 3). Laboratory studies revealed a white cell count >11,000/microL in six, microhematuria in four, proteinuria in four, elevated LDH in all patients, elevated AST/ALT in two, and elevated alkaline phosphatase in one. The work-up varied by presentation, but definitive diagnosis was made by CT in all five patients scanned and by angiography in two. Angiography confirmed the CT findings in four of the five patients. CONCLUSION: In evaluating partial renal infarction, a strong clinical suspicion is necessary. We found a history of dysrhythmia or other cardiac disease, the presence of abdominal or flank pain, fever with an elevated white cell count, and an elevated LDH to be clinically significant, and their presence should alert the clinician to the possibility of renal infarction. Once a degree of suspicion exists, early evaluation with CT should speed the diagnosis and effect decreased morbidity.

Adolescent↗
PubMed1999

Complete renal embolization as an alternative to nephrectomy.

PURPOSE: Simple nephrectomy is technically demanding in patients with recurrent inflammation or bleeding. It is also unwise to subject patients in poor health to the rigors of an extensive operative procedure. We report our experience with complete renal embolization as a safe and reliable alternative to surgical nephrectomy. MATERIALS AND METHODS: Eight patients underwent complete renal embolization as an alternative to nephrectomy. Patients were given antibiotics intravenously before and after embolization. Six patients with indwelling nephrostomy tubes received post-embolization instillation of 80 mg. gentamicin before tube removal. Narcotic analgesics were also given as needed for pain control. Post-embolization hospital course was noted. RESULTS: The indications for embolization included hydronephrotic, poorly functioning kidneys with pain in 5 cases, and recurrent bleeding from angiomyolipoma, bleeding after percutaneous resection of renal pelvic transitional cell carcinoma with metastases and spontaneous renal bleeding after hemodialysis in 1 each. Embolization was successful in 4 men and 4 women with a mean age of 58.8 years. In 6 patients severe flank pain required narcotic analgesics. One patient complained of nausea, 6 had fever and 6 had leukocytosis. In 1 case thrombosis of a limb of an aortobifemoral bypass graft required thrombectomy. Median hospital stay was 2.5 days. At a mean followup of 30.6 months presenting symptoms had resolved in all cases without hypertension, renal failure or abscess. CONCLUSIONS: Complete renal embolization is a viable alternative to nephrectomy in patients with poorly functioning kidneys who present with pain or bleeding and in those who are poor operative candidates. This procedure is safe, reliable and minimally invasive with few long-term sequelae, and it is well tolerated.

Adolescent↗
PubMed1999

Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats.

PURPOSE: In acute pyelonephritis renal scarring may be decreased by immediate antibiotic therapy. Unfortunately in children there is often a delay in starting treatment, which increases the likelihood of renal scarring. In rodents immediate antibiotic therapy is effective for preventing renal scar formation resulting from experimentally induced pyelonephritis. However, the same treatment beginning 72 hours after infection does not prevent renal scarring in this paradigm. We examined whether delayed administration of the nonsteroidal anti-inflammatory agent ibuprofen only or combined with antibiotics suppresses renal scarring in a model of ascending pyelonephritis in rats. MATERIALS AND METHODS: An inoculum of 5x10(9) organisms per ml. of Escherichia coli strain BH-5 was instilled into the bladder of rats and the urethra was occluded for 4 hours. Groups of animals were and were not treated with 15 mg./kg. cefadroxil or 10 mg./kg. ibuprofen given twice daily for 5 days, or the 2 drugs combined. Treatment began 72 hours after inoculation. In an additional group of rats sterile phosphate buffered saline was instilled into the bladder. In each rat the kidneys were examined grossly and microscopically 6 weeks later. RESULTS: Combined antibiotics and ibuprofen significantly inhibited gross renal scarring compared with no treatment or antibiotics only (p<0.05). No difference in renal scarring was detected in animals that received no treatment versus those that received antibiotics or ibuprofen only (p>0.05). CONCLUSIONS: Renal scarring resulting from acute pyelonephritis in this rat model is not decreased by delayed treatment with antibiotics only. The addition of ibuprofen to antibiotic therapy is effective for decreasing renal scarring due to acute pyelonephritis even when treatment is delayed for 72 hours.

Animals↗
PubMed1998

Pubovaginal sling using polypropylene mesh and Vesica bone anchors.

OBJECTIVES: To report preliminary results from a modified pubovaginal sling procedure using polypropylene mesh as the sling suspended by nonabsorbable sutures anchored to the pubic tubercle with Vesica bone anchors. METHODS: Thirty-five women with type III stress urinary incontinence (SUI) (with or without associated urethral hypermobility) or type II SUI with additional risk factors such as obesity, chronic obstructive pulmonary disease, or failed prior incontinence-correcting procedures underwent this modified pubovaginal sling procedure. Postoperative voiding status was evaluated during office follow-up visits and telephone surveys. RESULTS: With a mean follow-up of 8.4 months (range 2 to 18), 32 women (91.4%) were dry, 1 improved, and 2 remained incontinent. The pubovaginal sling procedure was the only operation performed in 46% of patients, with a mean operative time of 72 minutes, a mean estimated blood loss of 137 mL, and a mean hospital period of 2.3 days. Patients on whom concomitant gynecologic procedures were performed had a mean duration of surgery of 122 minutes, a mean estimated blood loss of 202 mL, and a mean hospitalization period of 2.9 days. Thirteen women had preoperative urgency that persisted in 31% of patients. De novo urgency developed in 3 patients. Seven women required prolonged suprapubic tube drainage but no patient remained in permanent retention. There has been no infection or erosion. CONCLUSIONS: Our experience with this modified pubovaginal sling procedure using polypropylene mesh and Vesica bone anchors showed excellent results with greater technical ease, minimal morbidity, and decreased hospitalization period when compared to a traditional pubovaginal sling performed in our hands. Additional follow-up will be needed to assess long-term efficacy.

Adult↗
PubMed1997

Role of Q-type Ca2+ channels in vasopressin secretion from neurohypophysial terminals of the rat.

1. The nerve endings of rat neurohypophyses were acutely dissociated and a combination of pharmacological, biophysical and biochemical techniques was used to determine which classes of Ca2+ channels on these central nervous system (CNS) terminals contribute functionally to arginine vasopressin (AVP) and oxytocin (OT) secretion. 2. Purified neurohypophysial plasma membranes not only had a single high-affinity binding site for the N-channel-specific omega-conopeptide MVIIA, but also a distinct high-affinity site for another omega-conopeptide (MVIIC), which affects both N- and P/Q-channels. 3. Neurohypophysial terminals exhibited, besides L- and N-type currents, another component of the Ca2+ current that was only blocked by low concentrations of MVIIC or by high concentrations of omega-AgaIVA, a P/Q-channel-selective spider toxin. 4. This Ca2+ current component had pharmacological and biophysical properties similar to those described for the fast-inactivating form of the P/Q-channel class, suggesting that in the neurohypophysial terminals this current is mediated by a 'Q'-type channel. 5. Pharmacological additivity studies showed that this Q-component contributed to rises in intraterminal Ca2+ concentration ([Ca2+]i) in only half of the terminals tested. 6. Furthermore, the non-L- and non-N-component of Ca(2+)-dependent AVP release, but not OT release, was effectively abolished by the same blockers of Q-type current. 7. Thus Q-channels are present on a subset of the neurohypophysial terminals where, in combination with N- and L-channels, they control AVP but not OT peptide neurosecretion.

Animals↗
PubMed1997

Site of disease and opportunistic infection predict survival in HIV-associated tuberculosis.

OBJECTIVE: Infection with HIV adversely affects survival in patients with tuberculosis (TB), even when TB is effectively treated. The aim of this study was to identify the determinants of survival in HIV-associated TB. DESIGN: Retrospective cohort study. SETTING: Four US academic medical centers. PATIENTS: An inception cohort of 112 HIV-infected patients (mean age 41 years, 96% men, 46% African American) with their first episode of culture-proven TB. OUTCOMES MEASURES: Observed survival from the date of diagnosis of TB to the date of death or censoring. Independent variables included demographics, HIV-related conditions, risk behavior for HIV, absolute CD4+ counts, and site of disease with Mycobacterium tuberculosis. RESULTS: Of the 112 patients, 54 (48%) had pulmonary TB alone, 36 (32%) had both pulmonary and extra-pulmonary TB and 22 (20%) had extrapulmonary TB alone. Median CD4+ count was 95 x 10(6)/l (range, 2-767 x 10(6)/l). During follow-up, 45 patients (40%) died. Median survival was shortest in patients with both pulmonary and extrapulmonary disease (8.4 months), followed by extrapulmonary disease alone (15.6 months), then pulmonary disease (30.4 months; P < 0.001, log-rank test). Median survival was also reduced in patients with previous opportunistic infection and in those with CD4+ < 200 x 10(6)/l. In a proportional hazards regression analysis, which adjusted for CD4+ count, extrapulmonary disease and previous opportunistic infection were the only factors independently associated with shorter survival. Of the extrapulmonary sites of disease, TB meningitis was associated with the greatest risk of death. CONCLUSION: The site of culture-proven TB at presentation and the history of previous opportunistic infection are important predictors of survival in HIV-infected patients with TB.

AIDS-Related Opportunistic Infections↗
PubMed1997

Neurodevelopmental outcomes of Ugandan infants with human immunodeficiency virus type 1 infection.

BACKGROUND: The neurodevelopmental outcomes of human immunodeficiency virus type 1 (HIV-1)-infected Ugandan infants of nondrug-using mothers were studied using controlled, prospective methodology. METHOD: The sample of 436 full-term infants included 79 HIV-infected infants of HIV-1-infected mothers, 241 uninfected infants of HIV-1-infected mothers (seroreverters), and 116 uninfected infants born to HIV-negative mothers. Neurologic status, information processing ability, and motor and mental development were assessed from 6 to 24 months of age. Observations of caretaker-child interaction and home environments were made at 6 and 12 months. All evaluators were blinded to the HIV status of the child and family. RESULTS: Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated greater deficits in motor development and neurologic status, and more frequent and earlier onset of motor and neurologic abnormalities. Compared with controls, HIV-infected infants had more abnormalities in mental development at 6 and 18 months and an earlier onset of abnormalities. By 12 months, 30% of HIV-infected infants demonstrated motor abnormalities and 26% cognitive abnormalities as compared with 11% and 6% among seroreverters and 5% and 6% among seronegative infants. HIV-infected infants (62%) demonstrated a higher probability of developing an abnormal neurologic examination by 12 months, compared with seroreverters (17%) or seronegative infants (15%). Information-processing abilities did not differ as a function of HIV infection. Home environments and infants' interactions with caretakers were similar across groups. CONCLUSION: We conclude that HIV infection results in more frequent and earlier abnormalities in infants' neurologic status and motor development that are not attributable to other biological and environmental risk factors. More frequent mental developmental abnormalities were evident at several ages. However, information-processing abilities, such as recognition memory, may be spared from HIV-related deficits.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Risk factors for adverse drug reactions during thiacetazone treatment of pulmonary tuberculosis in human immunodeficiency virus infected adults.

SETTING: Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda. OBJECTIVE: To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB. DESIGN: Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR). RESULTS: Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02). CONCLUSION: Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Generalized immune activation in pulmonary tuberculosis: co-activation with HIV infection.

Parameters of immune activation/differentiation were studied in a group of newly diagnosed HIV- and HIV+ pulmonary tuberculosis (TB) patients. Compared with controls, HLA-DR expression on both CD4 and CD8 T cells from the HIV- TB patients was approximately doubled; HLA-DR on T cells from the HIV+ group was tripled. The monocytes from both groups of patients expressed abnormally high levels of the Fc gamma receptors I and III. Serum levels of tumour necrosis factor-alpha (TNF-alpha), neopterin and beta 2-microglobulin were increased in HIV- and even more so in HIV+ TB patients. The expression of HLA-DR on T cell subsets and of Fc gamma R on monocytes correlated with each other, but not with serum activation markers. This pattern of non-specific activation during TB infection may be associated with enhanced susceptibility to HIV infection.

Adult↗
PubMed1996

Predictors of survival in human immunodeficiency virus-infected patients with pulmonary tuberculosis. The Makerere University-Case Western Reserve University Research Collaboration.

Infection with the human immunodeficiency virus (HIV) has changed both the epidemiology and natural history of tuberculosis. Despite a generally good response to effective antituberculous therapy, the prognosis remains poor. The objective of this analysis was to determine the independent predictors of survival in HIV-infected Ugandan adults with smear-positive pulmonary tuberculosis. A total of 191 HIV-infected Ugandan adults with smear-positive pulmonary tuberculosis were enrolled into a clinical trial of chemotherapy for tuberculosis. The subjects received either rifampin, isoniazid, and pyrazinamide for two months, followed by rifampin and isoniazid for six months (n = 101) or streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for eight months (n = 90). After standard measurements were made at baseline, the group was followed at regular intervals for a mean of 16 months to determine survival. During the course of follow-up, 82 (43%) of the patients died, six within the first month of therapy. The one-year survival proportion was 68% with an estimated median survival of 26 months and did not differ according to treatment regimen. The hazard for death was biphasic, high early in the course of therapy, and then again after about one year. After controlling for the treatment regimen, four independent predictors of survival were found: anergy to purified protein derivative, atypical chest roentgenogram, previous HIV-related condition, and lymphopenia. In this cohort of Ugandan adults, four simple and inexpensive predictors of survival were found. These factors suggest that the degree of immunosuppression was a major determinant of survival.

AIDS-Related Opportunistic Infections↗