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1.
Neurology ; 77(12): 1135-42, 2011 Sep 20.
Article in English | MEDLINE | ID: mdl-21900636

ABSTRACT

OBJECTIVE: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment. METHODS: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination. RESULTS: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group. CONCLUSION: Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.


Subject(s)
Cognition Disorders/drug therapy , Cognition Disorders/psychology , HIV Infections/drug therapy , HIV Infections/psychology , HIV-1 , Minocycline/therapeutic use , Adult , Cognition Disorders/complications , Cohort Studies , Double-Blind Method , Female , Follow-Up Studies , HIV Infections/complications , Humans , Male , Middle Aged , Treatment Outcome
2.
J Infect Dis ; 203(6): 765-72, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21343146

ABSTRACT

BACKGROUND: The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector vaccine, which elicits T cell immunity, can lead to control of human immunodeficiency virus (HIV) replication in participants who became HIV-infected after vaccination. METHODS: We evaluated the effect of the vaccine on trends in HIV viral load, CD4+ T cell counts, time to initiation of antiretroviral therapy (ART), and AIDS-free survival in 87 male participants who became infected with HIV during the Step study and who had a median of 24 months of post-infection follow-up. RESULTS: There was no overall effect of vaccine on mean log(10) viral load (estimated difference between groups, -0.11; P = .47). In a subset of subjects with protective HLA types (B27, B57, B58), mean HIV-1 RNA level over time was lower among vaccine recipients. There was no significant difference in CD4+ T cell counts, time to ART initiation, or in AIDS-free survival between HIV-1-infected subjects who received vaccine versus those who received placebo. CONCLUSIONS: HIV RNA levels, CD4+ T cell counts, time to initiation of ART, and AIDS-free survival were similar in vaccine and placebo recipients. There may have been a favorable effect of vaccine on HIV-1 RNA levels in participants with HLA types associated with better control of HIV-1.


Subject(s)
AIDS Vaccines/immunology , HIV Infections/prevention & control , HIV-1/immunology , Adenoviruses, Human/genetics , Adenoviruses, Human/immunology , Adult , Anti-Retroviral Agents/therapeutic use , Blotting, Western , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , Circumcision, Male , Disease-Free Survival , Double-Blind Method , Genetic Vectors , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/genetics , HIV-1/physiology , Humans , Immunity, Cellular , Male , Middle Aged , Placebos , Proportional Hazards Models , RNA, Viral/blood , RNA, Viral/immunology , Viral Load/drug effects , Young Adult
3.
Int J STD AIDS ; 21(9): 611-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21097732

ABSTRACT

Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV-1 infection. We characterized HSV-2 serology assay performance in HIV-positive and HIV-negative Africans. Serostatus for HSV-2 and HIV-1 was determined in 493 serum specimens stored from a community HSV-2 prevalence survey in Kampala, Uganda. HSV-2 serology by Focus HerpeSelect ELISA, Biokit HSV-2 rapid assay and Kalon HSV-2 was compared with HSV-2 Western blot (WB) according to HIV-1 serostatus. Sensitivity/specificity was: 99.5%/70.2% for Focus, 97.0%/86.4% for Biokit and 97.5%/96.2% for Kalon. Focus with Biokit confirmation improved sensitivity/specificity (99.4%/96.8%, respectively). Use of a higher Focus index value cut-off of 2.2 instead of 1.1 increased specificity from 70.2% to 92.4%. Kalon had higher specificity than Focus (P < 0.001). Of commercially available HSV-2 serological assays, Kalon alone, or Focus ELISA followed by Biokit confirmation perform best. Improved HSV-2 assays are needed for HSV-2 and HIV-1 public health activities in Africa.


Subject(s)
Antibodies, Viral/blood , Herpes Simplex/diagnosis , Herpesvirus 2, Human/immunology , Virology/methods , Adult , Female , HIV Infections/diagnosis , Herpes Simplex/complications , Herpesvirus 2, Human/isolation & purification , Humans , Immunoassay/methods , Male , Reagent Kits, Diagnostic , Sensitivity and Specificity , Uganda
4.
N Engl J Med ; 362(5): 427-39, 2010 Feb 04.
Article in English | MEDLINE | ID: mdl-20089951

ABSTRACT

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , HIV Infections/transmission , HIV-1 , Herpes Genitalis/drug therapy , Herpesvirus 2, Human , Acyclovir/adverse effects , Adolescent , Adult , Antiviral Agents/adverse effects , CD4 Lymphocyte Count , Female , Follow-Up Studies , HIV Infections/complications , HIV-1/genetics , HIV-1/isolation & purification , Herpes Genitalis/complications , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Patient Compliance , Pregnancy , RNA, Viral/blood , Unsafe Sex/statistics & numerical data , Young Adult
5.
Arch Dis Child Fetal Neonatal Ed ; 93(4): F265-70, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18252818

ABSTRACT

BACKGROUND: Amylin, a 37-amino-acid peptide hormone, is a potent inhibitor of gastric emptying. It is co-secreted by the pancreatic beta cells in response to enteral nutrient intake. Feed intolerance is common in preterm neonates and often presents as increased gastric residual volume (GRV). It is therefore hypothesised that serum amylin concentrations are raised in preterm neonates with poor gastric emptying, which may contribute to this observed feed intolerance. OBJECTIVE: To determine serum amylin concentrations in feed-intolerant preterm neonates. PATIENTS AND METHODS: Feed-intolerant (nTOL) preterm neonates (GRV >50% of a previous 4 h feed volume on two consecutive occasions) were matched for gestation, birth weight and postnatal age with feed-tolerant (TOL) neonates. Blood samples were analysed for amylin concentration. Seventy neonates were studied with median (interquartile range) gestation of 29 weeks (28-33) and birth weight of 1.3 kg (1.0-1.8). RESULTS: Serum amylin concentration and percentage GRV (median (interquartile range)) were significantly higher in the nTOL (47.9 pmol/l (21.4-79.8), 150% (100-350)) than the TOL (8.7 pmol/l (5.7-16), 5% (0-5)) group (p<0.001). In the nTOL group, a positive correlation was observed between serum amylin and GRV (r = 0.78, 95% CI 0.59 to 0.89, p<0.001), days to reach full enteral feeds (r = 0.40, 95% CI 0.08 to 0.68, p = 0.02), and days to discharge (r = 0.43, 95% CI 0.09 to 0.68, p = 0.01). CONCLUSIONS: Amylin may be responsible for delaying establishment of enteral nutrition in preterm neonates by virtue of its inhibitory effect on gastric emptying. Serum amylin concentrations in these neonates correlate with GRVs and time to reach full enteral feeds.


Subject(s)
Amyloid/blood , Food Hypersensitivity/diagnosis , Infant, Premature, Diseases/diagnosis , Biomarkers/blood , Blood Glucose/analysis , Case-Control Studies , Enteral Nutrition , Female , Humans , Infant, Newborn , Islet Amyloid Polypeptide , Male
7.
BMJ ; 334(7583): 7; author reply 7-8, 2007 Jan 06.
Article in English | MEDLINE | ID: mdl-17204774
8.
Arch Dis Child ; 90(12): 1279-82, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16174639

ABSTRACT

BACKGROUND: Amylin is a novel 37 amino acid peptide hormone that is co-secreted with insulin from the pancreas in response to food intake. As a potent inhibitor of gastric emptying it plays an important role in the control of carbohydrate absorption. Feed intolerance is common in infants of diabetic mothers (IDM). AIMS: To establish a normal range of amylin levels in healthy neonates, and to determine whether serum amylin levels are raised in IDM. METHODS: A serial sample of 221 infants > or =28 weeks gestation was enrolled prior to delivery over a 12 month period. Blood samples collected immediately after birth (umbilical cord), and at the routine Guthrie test were analysed for amylin and insulin levels. RESULTS: Amylin levels in umbilical cord (n = 181) and Guthrie samples (n = 33) of healthy infants were 5.7 (3.0-9.1) and 6.9 (2.9-9.0) pmol/l respectively. IDM had significantly raised amylin levels in both cord (n = 31; 32.7 pmol/l, 25.9-48.1) and Guthrie samples (n = 8; 18.1 pmol/l, 15.3-23.6). Amylin correlated positively with insulin (n = 42; r = 0.67; 95% CI 0.4 to 0.81), birth weight (r = 0.22; 95% CI 0.08 to 0.36), and gestation (r = 0.18; 95% CI 0.03 to 0.32). Umbilical cord venous amylin levels showed agreement with arterial cord amylin levels (n = 34, mean bias -0.2, 95% CI 3.1 to -3.6). CONCLUSIONS: Amylin levels are significantly increased in the umbilical cord and Guthrie blood samples in IDM.


Subject(s)
Amyloid/blood , Fetal Blood/chemistry , Infant, Newborn/blood , Pregnancy in Diabetics , Birth Weight , Blood Specimen Collection/methods , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetes, Gestational , Female , Gestational Age , Humans , Insulin/blood , Islet Amyloid Polypeptide , Male , Pregnancy , Reference Values
9.
Lancet ; 365(9453): 29-35, 2005.
Article in English | MEDLINE | ID: mdl-15639677

ABSTRACT

BACKGROUND: There have been suggestions that when two or three unexpected unexplained infant deaths occur within a family they are more likely to be unnatural than natural. We aimed to estimate the probability that a second infant death is natural versus unnatural. METHODS: The Care of Next Infant programme (CONI) supports parents who have previously had an unexpected and apparently unexplained infant death and is currently available in over 90% of health districts in England, Wales, and Northern Ireland. We studied all deaths in 6373 infants who had completed the CONI programme by December, 1999. After a CONI death, we made detailed enquiries into the previous death and the CONI death, including a family interview, a review of autopsies, and case discussion. FINDINGS: 57 (8.9 per 1000) CONI infants died. Nine deaths were inevitable, and 48 were unexpected. 44 families lost one child, and two families lost two children. Of the 46 first CONI deaths, 40 were natural; the other six were probable homicides, five committed by one or both parents (two criminally convicted). The ratio of 40 natural to six unnatural deaths is 6.7 (95% CI 2.8-19.4). Enquiries identified 18 families with two SIDS(sudden infant death syndrome) deaths and two families with probable covert double homicides (ratio 9.0 [2.2 to 80.0]). There were no convictions in 13 incomplete cases. Families with three deaths are reported. INTERPRETATION: Repeat unexpected infant deaths are most probably natural.


Subject(s)
Infanticide , Sudden Infant Death , Humans , Infant , Infant, Newborn , Parents , Sudden Infant Death/diagnosis , Sudden Infant Death/etiology
10.
Pediatr Infect Dis J ; 23(4): 373-5, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15071303

ABSTRACT

An 8-week-old female infant presented with a history of active varicella complicated by Escherichia coli sepsis, oral thrush, hypoalbuminemia, intermittent fevers, diarrhea and feeding intolerance. Rhesus monkey kidney cells inoculated with cerebrospinal fluid revealed reovirus-like particles by electron microscopy. Virus neutralization and RNA-gel electrophoresis studies identified the isolated pathogen as reovirus serotype 2. This report represents one of only a few to isolate reovirus from the central nervous system in humans.


Subject(s)
Immunologic Deficiency Syndromes/diagnosis , Meningitis, Viral/cerebrospinal fluid , Meningitis, Viral/diagnosis , Orthoreovirus, Mammalian/isolation & purification , Reoviridae Infections/diagnosis , Combined Modality Therapy , Disease Progression , Fatal Outcome , Female , Humans , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/therapy , Infant , Meningitis, Viral/complications , Meningitis, Viral/therapy , Reoviridae Infections/complications , Reoviridae Infections/therapy , Risk Assessment , Severity of Illness Index
11.
Arch Dis Child ; 88(11): 1001-4, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14612368

ABSTRACT

AIMS: to describe a pattern of illness in "normal" infants, and to assess to what extent this may differ in infants who die suddenly and unexpectedly. METHODS: All infants are on the CONI (Care of the Next Infant) scheme in which mothers record symptoms and signs of illness prospectively, on a daily basis from birth to approximately age 6 months. The symptoms of infants who die suddenly and unexpectedly are compared with those of a consecutive sample of infants who survive. Twenty one babies died suddenly, of whom 11 were cot deaths and 10 had "known causes" of death. Ninety eight infants who survived were used as consecutive controls. Prospective daily records of the presence or absence of 26 signs and symptoms were kept by all of the mothers, commencing at birth and lasting an average of 176 days in survivors; 84 days in SIDS; and 93 days in infants who died of known causes. RESULTS: Standardised for age and the time of year, on any given day, the mothers of the SIDS infants were over eight times more likely to record their child as being pale, six times more likely to be sweating, and twice as likely to be irritable. Other signs and symptoms which were three times more likely to be recorded were sore gums, dry stools, and coldness. Infants who died of known causes generally had fewer symptoms. CONCLUSIONS: Cot death infants have a range of symptoms which appear to be of a general nature, and not related to any one system. Symptoms are seen throughout life and not related to the time of death.


Subject(s)
Sudden Infant Death/etiology , Apnea/complications , Body Weight , Follow-Up Studies , Humans , Infant , Infant, Newborn , Irritable Mood , Prospective Studies , Risk Factors , Sweating
12.
Neurology ; 60(8): 1388-90, 2003 Apr 22.
Article in English | MEDLINE | ID: mdl-12707454

ABSTRACT

The authors assessed CSF and plasma HIV-1 RNA and neuropsychological test performance (composite neuropsychological test Z score [NPZ-4]) in 25 HIV-1-infected subjects 4 and 8 weeks after beginning potent antiretroviral therapy that included a protease inhibitor. In the 14 subjects who entered the study on no antiretroviral treatment, NPZ-4 improvement was associated with decline in CSF HIV-1 RNA at both visits (p = 0.001 and p = 0.02), and those treated with zidovudine or indinavir had greater improvement in NPZ-4 at both visits compared to those treated with other drugs (p = 0.003 and p = 0.01).


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1/isolation & purification , RNA, Viral/cerebrospinal fluid , Viremia/drug therapy , Adult , Antiretroviral Therapy, Highly Active , Cognition Disorders/blood , Cognition Disorders/cerebrospinal fluid , Cognition Disorders/etiology , Cognition Disorders/virology , HIV Infections/psychology , HIV Infections/virology , Humans , Indinavir/blood , Indinavir/cerebrospinal fluid , Indinavir/therapeutic use , Male , Middle Aged , Neuropsychological Tests , RNA, Viral/blood , Time Factors , Viral Load , Viremia/psychology , Zidovudine/therapeutic use
13.
J Clin Laser Med Surg ; 20(5): 251-5, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12470454

ABSTRACT

OBJECTIVE: The objective of this study was to determine of the efficiency of holmium:YAG laser for bone ablation, compared to cartilage and soft tissue of the intervertebral foramen of the lumbosacral spine. BACKGROUND DATA: The holmium:YAG (Ho:YAG) laser has been used for ablation of bulging or prolapsed discs and also has the potential for decompression of the nerve root when there is narrowing of the foraminae (foraminoplasty). It is proposed that laser ablation of bone and ligament of the intervertebral foramen for nerve root decompression using the Ho:YAG laser is able to produce sufficient bone ablation without inducing significant thermal necrosis in surrounding tissues due to its short absorption length, which could result in significant clinical advantages. MATERIALS AND METHODS: Experiments were performed on samples of laminar bone, facet joint capsule, and cartilage for quantitative and qualitative determination of the effect of Ho:YAG ablation on tissue mass loss using a range of pulse energies from 0.5 to 1.5 J/P at 15 pulses/sec. RESULTS: The results showed a significant linear correlation between the mass loss and pulse energy, and between the mass loss and radiant exposure. Electron microscopy and histology showed that the Ho:YAG ablation resulted in a very sharp and clear border with little charring. Applying 0.01 k.J of total energy at two different settings (1.5 J/p, high power, and 0.5 J/p, low power) at 15 pulses/sec, the cross-sectional area/mm(2) of the ablated bone was measured, using light microscopy and the Scion Image analysis program. The ablated areas were 2.28 +/- 0.87 and 1.16 +/- 0.43 mm(2) at high and low power, respectively (p = 0.008).


Subject(s)
Lasers , Lumbar Vertebrae/radiation effects , Animals , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Bone and Bones/radiation effects , Cartilage, Articular/pathology , Cartilage, Articular/radiation effects , Cartilage, Articular/ultrastructure , In Vitro Techniques , Joint Capsule/pathology , Joint Capsule/radiation effects , Joint Capsule/ultrastructure , Lumbar Vertebrae/pathology , Lumbar Vertebrae/ultrastructure , Microscopy, Electron, Scanning , Sheep , Ultrasonography , Zygapophyseal Joint/pathology , Zygapophyseal Joint/radiation effects
14.
Child Care Health Dev ; 28 Suppl 1: 19-21, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12515433

ABSTRACT

Longitudinal day-to-day recordings of symptoms in the siblings of Sudden Infant Death Syndrome (SIDS) infant show a wide variety of symptoms varying with season and days of years. Implications are discussed.


Subject(s)
Siblings , Sudden Infant Death/pathology , Female , Humans , Infant , Longitudinal Studies , Male , Seasons
15.
Ann Intern Med ; 135(11): 954-64, 2001 Dec 04.
Article in English | MEDLINE | ID: mdl-11730396

ABSTRACT

BACKGROUND: A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure. OBJECTIVE: To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy. DESIGN: Observational analysis of one treatment group in a phase III trial. SETTING: 40 AIDS Clinical Trials units. PATIENTS: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 x 10(9) cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8. MEASUREMENTS: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death. RESULTS: Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or more and at least 2-log(10) copies/mL reduction since baseline, 29% of those with a level of 500 copies/mL or more with a 1- to 1.99-log(10) copies/mL reduction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log(10) copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log(10) copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1- to 1.99-log(10) copies/mL reduction since baseline, and 10.6% of patients with 500 copies/mL or greater and less than 1-log(10) copies/mL decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count >/= 0.10 x 10(9) cells/L, 1.47 [95% CI, 1.00 to 2.16] compared with <0.050 x 10(9) cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 x 10(9) cells/L, 0.98 [CI, 0.61 to 1.57] compared with <0.050 x 10(9) cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 x 10(9) cells/L or greater (compared with <0.05 x 10(9) cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [CI, 0.09 to 0.67]). CONCLUSIONS: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV-1 , Indinavir/therapeutic use , Lamivudine/therapeutic use , Zidovudine/therapeutic use , Adult , CD4 Lymphocyte Count , Clinical Protocols , Disease Progression , Drug Therapy, Combination , Female , HIV-1/genetics , Humans , Logistic Models , Male , Middle Aged , RNA, Viral/blood , Viral Load
16.
Int J Sports Med ; 22(8): 618-22, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11719899

ABSTRACT

Knee flexor strength recovery following anterior cruciate ligament reconstruction with the doubled semitendinosus and gracilis tendons was assessed for up to 12 months post-surgery. Twelve patients were followed up, four at 3 months, five at 6 months and three at 12 months post-surgery. Knee flexor moment was recorded using the Biodex System-3 isokinetic dynamometer. Three sets of five repetitions of reciprocal eccentric/ concentric knee flexion contractions were carried out with each set at 1.05, 2.09 or 3.14 rad x s(-1). T-tests were used to test for significant differences between and within groups. The uninjured leg produced greater average peak moments than the injured leg; significant differences (p < 0.05) were seen between the legs at 1.05 rad x s(-1) for the 3-month group concentrically, and all three groups eccentrically. There was no significant difference (p > 0.05) between groups for the percentage deficit between legs. On average, a 23% deficit in average peak moment was still evident at 12 months both eccentrically and concentrically at 1.05 rad x s(-1). Taken as a whole this evidence suggests that there is a deficit in knee flexor strength up to at least 12 months post-surgery following doubled semitendinosus and gracilis tendon graft reconstruction even after a full rehabilitation protocol.


Subject(s)
Anterior Cruciate Ligament/surgery , Knee Joint/physiopathology , Muscle, Skeletal/physiopathology , Tendons/transplantation , Adult , Anterior Cruciate Ligament Injuries , Athletic Injuries/physiopathology , Athletic Injuries/rehabilitation , Athletic Injuries/surgery , Humans , Knee Joint/surgery , Male , Movement , Torque
17.
J Infect Dis ; 184(9): 1187-91, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11598843

ABSTRACT

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection.


Subject(s)
Genetic Variation , Genitalia, Female/virology , HIV Infections/virology , HIV-1/physiology , RNA, Viral/analysis , Virus Shedding , Cervix Uteri/virology , Female , HIV-1/genetics , Humans , Menstrual Cycle , Nucleic Acid Amplification Techniques/methods , RNA, Viral/blood , Specimen Handling/methods , Vagina/virology
18.
AIDS ; 15(12): 1535-43, 2001 Aug 17.
Article in English | MEDLINE | ID: mdl-11504986

ABSTRACT

OBJECTIVES: To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. METHODS: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/microl during phases of the menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10, TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load. RESULTS: Vaginal IL-1beta, IL-4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner. CONCLUSION: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.


Subject(s)
Cytokines/metabolism , HIV Infections/immunology , HIV-1/physiology , Menstrual Cycle/immunology , Vagina/virology , Adolescent , Adult , Cytokines/blood , Female , HIV Infections/virology , HIV-1/isolation & purification , Humans , Middle Aged , RNA, Viral/blood , T-Lymphocytes/immunology , Vagina/immunology , Viral Load , Virus Shedding/physiology
19.
Lasers Surg Med ; 29(1): 33-7, 2001.
Article in English | MEDLINE | ID: mdl-11500860

ABSTRACT

BACKGROUND AND OBJECTIVE: The Holmium: YAG (Ho: YAG) laser has been used for the ablation of prolapsed discs but alternative techniques are available, and this application remains controversial. It also has potential for the decompression of nerve roots within narrowed foraminae with the technique of endoscopic laser foraminoplasty. Traditional methods of decompression necessitate a major surgical procedure with potential destabilisation of the lumbar spinal segment. Nevertheless, minimally invasive techniques are attractive only if serious complications can be avoided. This study reports the peak temperatures reached in surrounding tissues with and without saline irrigation. STUDY DESIGN/MATERIALS AND METHODS: Investigation of the hypothesis was carried out in excised sheep lumbar spines. T-type thermocouples were used for the measurement of tissue temperatures during laser ablation of nerve root foraminae. The temperature was assessed in the nerve root, dura mater, and disc space. RESULTS: The Ho: YAG laser was effective in widening the foraminae by approximately 1.5 mm with a total energy of 4.60 kJ. This was statistically significant in both vertical and horizontal directions (P < 0.0003 and P < 0.00005, respectively). The mean temperature of the nerve root, dura, and disc space during the procedure was 44 +/- 3.1 degrees C, 42.8 +/- 4.7 degrees C, and 41 +/- 3.4 degrees C respectively. There were transient high peaks seen in the temperature profiles. Using saline irrigation at 27 ml/minutes these temperatures were reduced to 34.1 +/- 1.8 degrees C (P = 0.0002), 34.9 +/- 1.5 degrees C (P = 0.002), and 37.2 +/- 1.2 degrees C (P < 0.014), for nerve roots, dura, and disc space respectively. CONCLUSIONS: Laser ablation of bone and ligament for nerve root decompression using the Ho: YAG laser may offer substantial advantages, but the risk of serious complication may only be avoided if the technique is combined with saline irrigation.


Subject(s)
Dura Mater/surgery , Intervertebral Disc/surgery , Laser Therapy , Lumbar Vertebrae/surgery , Spinal Nerve Roots/surgery , Therapeutic Irrigation , Animals , Body Temperature , Decompression, Surgical , Sheep , Sodium Chloride
20.
AIDS ; 15(5): 621-7, 2001 Mar 30.
Article in English | MEDLINE | ID: mdl-11317000

ABSTRACT

OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women. DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SETTINGS: Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma). RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS: This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.


Subject(s)
Cervix Uteri/metabolism , Disease Transmission, Infectious , HIV Infections/transmission , HIV-1 , Models, Biological , Models, Statistical , Receptors, CCR5/metabolism , Semen/virology , Viral Load , Female , HIV Infections/epidemiology , Humans , Male , United States/epidemiology
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