CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS.

OBJECTIVE: To assess the relationship between CD56(bright) natural killer (NK) cells and multiple sclerosis (MS) disease activity in patients with relapsing-remitting MS treated with daclizumab high-yield process (DAC HYP). METHODS: Data were from patients enrolled in a 52-week randomized, double-blind, placebo-controlled study of DAC HYP and its extension study. Assessments included relationships of CD56(bright) NK cell numbers (identified using fluorescence-activated cell sorting) at weeks 4 and 8 with the numbers of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 and the annualized relapse rate. RESULTS: In DAC HYP-treated patients but not placebo-treated patients, the numbers of CD56(bright) NK cells increased over 52 weeks of treatment, and their numbers at weeks 4 and 8 predicted the number of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 of treatment (p ≤ 0.005 for each comparison). Similar but nonsignificant trends were observed between CD56(bright) NK cell counts and the annualized relapse rate in DAC HYP-treated patients. DAC HYP-treated patients who showed lower levels of expansion of CD56(bright) NK cells still developed fewer new or newly enlarging T2-hyperintense lesions than placebo-treated patients during the first year of treatment. CONCLUSIONS: CD56(bright) NK cells appear to mediate some of the treatment-related effects of DAC HYP, but their numbers do not account for the full effect of DAC HYP on MS-related outcomes.

Intramuscular interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) shares immunologic features with multiple sclerosis (MS). Because IM interferon beta-1a (IM IFNbeta-1a) is an effective and safe treatment for MS, we conducted a dose-ranging efficacy study of IFNbeta-1a in patients with CIDP. METHODS: Adults with IV immunoglobulin (IVIg)-dependent CIDP (n = 67) were enrolled in this 32-week double-blind trial and randomized to IM IFNbeta-1a. Patients received 30 microg once weekly plus placebo (n = 12), IM IFNbeta-1a 60 microg once weekly plus placebo (n = 11), IM IFNbeta-1a 30 microg twice weekly (n = 11), IM IFNbeta-1a 60 microg twice weekly (n = 11), or placebo twice weekly (n = 22). Participants were maintained on IVIg through week 16, when IVIg was discontinued. Patients who worsened were restarted on IVIg. The primary outcome was total IVIg dose (g/kg) administered from week 16 to 32. RESULTS: There was no difference in total IVIg dose administered after week 16 for patients treated with IFNbeta-1a (1.20 g/kg) compared with placebo (1.34 g/kg; p = 0.75). However, exploratory analyses suggested IFNbeta-1a significantly reduced total dose of IVIg compared with placebo for participants who required either high-dose IVIg (>0.95 g/kg per month) or had greater weakness at baseline (Medical Research Council sum score <51). Adverse events included flu-like symptoms, headache, and fatigue in the IFNbeta-1a groups. CONCLUSIONS: Interferon beta-1a (IFNbeta-1a) therapy did not provide significant benefit over IV immunoglobulin (IVIg) therapy alone for patients with chronic inflammatory demyelinating polyradiculoneuropathy. However, IFNbeta-1a might be beneficial for patients with more severe disability or those needing high doses of IVIg. LEVEL OF EVIDENCE: This study was designed to provide Class I evidence for the safety and efficacy of IM IFNbeta-1a in the treatment of CIDP but has been subsequently classified as Class II due to a >20% patient dropout rate. Thus, this randomized, controlled clinical trial provides Class II evidence of no effect on primary and secondary endpoints of 4 dosage regimens of IM IFNbeta-1a added to IVIg in persons with CIDP.

Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. Women's Interagency HIV Study Group.

BACKGROUND: Cervical neoplasia occurs with increased frequency among women infected with HIV-1. OBJECTIVE: To characterize prevalence of and risk factors for abnormal cervical cytology among women with HIV and to compare them to uninfected women. METHODS: Baseline cervical cytology was obtained from 1713 women seropositive for HIV and 482 at-risk control women who were enrolled in the Women's Interagency HIV Study, a multicenter prospective cohort study conducted in six U.S. cities. Associations with sociodemographic, medical, and sexual variables were assessed by Fisher's exact test, Mantel extension test, and logistic regression analysis. RESULTS: Cervical cytology was abnormal in 38.3% of HIV-infected women (atypical squamous cells of uncertain significance [ASCUS] 20.9%, low-grade squamous cells of uncertain significance [LSIL] 14.9%, high-grade squamous cells of uncertain significance [HSIL] 2.3%, cancer 0.2%) and 16.2% of HIV-uninfected women (ASCUS 12.7%, LSIL 2.3%, HSIL 1.2%, cancer 0.0%). Risk factors for any abnormal cytology in multivariate analysis included HIV infection, CD4 cell count, HIV RNA level, detection of human papillomavirus (HPV), a prior history of abnormal cytology, employment, and number of male sex partners within 6 months of enrollment. Prior abortion was associated with a decreased risk of cytologic abnormality. CONCLUSIONS: Cervical cytologic abnormalities were frequent among women infected with HIV, although high-grade changes were found in only 2.5%. Factors linked to sexual and reproductive history, HPV infection, and HIV disease all influenced risk.

Sexual, contraceptive, and drug use behaviors of women with HIV and those at high risk for infection: results from the Women's Interagency HIV Study.

OBJECTIVE: To document the sexual and contraceptive practices of women with HIV infection or who are at risk for infection. DESIGN: Data on the baseline behaviors of 561 HIV-negative and 2040 HIV-positive women were collected as part of the Women's Interagency HIV Study (WIHS). WIHS is a multisite, longitudinal study following the natural history of HIV infection among women in the United States. METHODS: Each participant contributed an interviewer administered, self-report interview including questions on sexual and contraceptive behavior. RESULTS: Women with HIV were less likely to report heterosexual activity in the previous 6 months (65% HIV-positive, 76% HIV-negative). Among sexually active women, there were no differences in the proportion of those reporting vaginal (97% HIV-positive, 98% HIV-negative) or anal sex (12% HIV-positive, 10% HIV-negative), although women with HIV were less likely to report cunnilingus (41% HIV-positive, 70% HIV-negative) and fellatio (48% HIV-positive, 57% HIV-negative). Of women with HIV, 63% always used condoms during vaginal sex (versus 28% HIV-negative), with lower rates reported during other sexual activities. Crack, cocaine, or injecting drug use, reported by 27% of HIV-positive and 35% of HIV-negative women, was associated with inconsistent condom use, independent of serostatus. HIV-positive women who reported using condoms and another contraception method were less consistent condom users (57% consistent versus 67%). CONCLUSIONS: The prevalence of sexual risk behavior in this sample suggests that, although women with HIV exhibit lower levels of sexual risk behavior than uninfected women, many have not been successfully reached with regard to implementing safer behaviors. These findings have implications for more widespread and effective behavioral intervention efforts.

Cervical dysplasia on cervicovaginal Papanicolaou smear among HIV-1-infected pregnant and nonpregnant women. Women and Infants Transmission Study.

OBJECTIVE: To assess the association of squamous intraepithelial lesions (SIL) on cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their pregnancy status, and historical and clinical factors. METHODS: Study enrollment Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic evaluation. The rates of SIL were compared with pregnancy status, immunosuppression, presence of sexually transmitted diseases (STDs) and demographic features. RESULTS: Rates of low grade SIL were similar for pregnant and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95% confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3) were associated with SIL. An association between herpes simplex and SIL (OR = 3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low prevalence of herpes simplex (17 of 456 women). CONCLUSIONS: Pap smears for a cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated with immunosuppression, cervical inflammation, and herpes simplex. Closer surveillance of HIV-1-infected women with these risk factors may be warranted.

Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study.

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.

Statistical evaluation of the role of Helicobacter pylori in stress gastritis: applications of splines and bootstrapping to the logistic model.

Stress gastritis is a serious problem in the intensive care unit population. The recent discovery of the causal nature of Helicobacter pylori (H. pylori) in the development of gastric ulcers led us to examine its relationship with stress gastritis. We investigated this relationship in 874 veterans admitted to intensive care units who were tested for the presence of H. pylori and followed for 6 weeks for the development of stress gastritis. We fit spline models to assess functional relationships and used the logistic model to determine the association between H. pylori and stress gastritis. The predictive ability of the model was assessed with receiver operating characteristic (ROC) curve analysis and validated with the bootstrapping technique. Increased anti-H. pylori immunoglobulin A concentrations were found to be an important predictor of stress gastritis independent of other known risk factors.

Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers. Women and Infants Transmission Study.

To determine if hepatitis C virus (HCV) infection affects vertical transmission of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the prospective, multicenter, Women and Infants Transmission Study had HCV antibody (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV-positive. HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%) versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a logistic regression model that included maternal drug use, a potential confounder, HCV infection was marginally associated with perinatal HIV transmission (OR, 1.64; P = .05), whereas drug use was not. Women who transmitted HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did not (337,561 copies/mL; P = .01). Maternal HCV infection is associated with increased HIV vertical transmission. Further studies are needed to ascertain if HCV directly affects perinatal HIV transmission or is a marker for another factor, such as maternal drug use.

Risk factors for upper gastrointestinal bleeding in intensive care unit patients: role of helicobacter pylori. Federal Hyperimmune Immunoglobulin Therapy Study Group.

OBJECTIVE: To determine the role of preexisting Helicobacter pylori infection in the development of acute upper gastrointestinal (GI) hemorrhage in intensive care unit (ICU) patients in relation to other potential predisposing risk factors. DESIGN: Prospective, multicenter, cohort study. SETTING: Medical and surgical ICUs in six tertiary care Department of Veterans Affairs Medical Centers. PATIENTS: Eight-hundred seventy-four patients without previous GI bleeding or peptic ulcer disease who were enrolled in a multicenter, randomized, controlled trial of prophylactic intravenous immunoglobulin to prevent ICU-associated infections. INTERVENTIONS: This substudy of the larger intravenous immunoglobulin study only involved data analysis and had no intervention. All patients were enrolled in the larger study where they received intravenous immunoglobulin or placebo as intervention. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively evaluated for the development of acute upper GI hemorrhage while in an ICU. Anti-H. pylori immunoglobulin G and immnoglobulin A concentrations were determined by enzyme immunoassay on preintervention serum samples. Seventy-six (9%) patients had over upper GI bleeding and a mortality rate of 49%, as compared with a 15% mortality rate in patients who did not bleed (p < .001). By logistic regression analysis, the following factors were associated with an increased risk of bleeding: acute hepatic failure, prolonged duration of nasogastric tube placement, alcoholism, and an increased serum concentration of anti-H. pylori immunoglobulin A. CONCLUSIONS: Increased anti-H. pylori immunoglobulin A concentrations, prolonged nasogastric intubation, alcoholism, and acute hepatic failure were found to be independently correlated with the development of acute GI bleeding in an ICU setting. These observations should be prospectively confirmed in an independent population before being used for treatment guidelines.

[Case examples of rare locations of aneurysms]. / Fallbeispiele seltener Aneurysmalokalisationen.

We describe four cases of rare aneurysm localisations, one case of an aneurysm of the hepatic artery, two cases of aneurysms of the superior mesenteric artery and its branches and, as an extreme rarity, one case of an aneurysm of the superior gluteal artery (only three known cases up to now). All cases were documented by arteriography/DSA, ultrasonography and computed tomography. We refer to incidence, aetiology, symptomatology, and possible complications as indicated by literature.

[Diagnostic value of clinical methods in the staging of abdominal Hodgkin's disease (author's transl)]. / Wertigleit klinischer Untersuchungsmethoden zur Stadieneinteilung beim abdominellen Morbus Hodgkin.

Explorative laparotomies were carried out on 68 patients with Hodgkin's disease in the University Hospital of Marburg from 1969 through 1978. These laparotomies were preceded by clinical examination, abdominal sonography in 27 cases, lymphography in 55 cases, scintigraphy of liver and spleen in 58 cases, and radiographic examinations of the intestinal tract in 18 cases. Sonography revealed a greater accuracy (90%) for splenic involvement than scintigraphy (74%); the results of sonography and scintigraphy of the liver were comparable. For the detection of para-aortal lymphomas ultrasound and lymphography can be regarded as complementary methods. Our results are compared with findings in the literature on abdominal sonography (n = 50), scintigraphy of liver and spleen (n = 185), and lymphography (n = 465) carried out before explorative laparotomy for lymphogranulomatosis. There was a better correlation for the systemic symptoms of the 68 patients with the clinical stage than with the pathologic stage. The importance of diagnosing different groups, e.g. in stage III, is stressed.

[Real-time B-scan ultrasonic evaluation of pleural effusion and intrathoracic masses adjacent to the pleura (author's transl)]. / Real-Time-Ultraschalltomographie von Pleuraergüssen und pleuranahen intrathorakalen Raumforderungen.

106 pleural effusions or pleural opacities suggesting fluid were evaluated in a prospective study by B-mode real-life sonography and radiography. 41 cases were first investigated by means of ultrasound, 65 by the conventional erect roentgenogram. The correct diagnosis of pleural fluid was made by ultrasound in 95.3% and by radiologic examination in 86.8% of the cases. Radiography failed to distinguish between pleural effusion and solid pleural thickening in 7.5%, sonography in 1.9% of the cases. In 8 patients with normal roentgenograms, small epidiaphragmal pleural effusions were detected by means of ultrasound. In diagnosis of pleural effusion, sonography was found to be superior to the conventional radiologic technique both in sensitivity and in diagnosing the consistency. The value of the ultrasonic method both in establishing the quality of intrathoracic masses adjacent to the pleura and in sonographically guided needle puncture is emphasized.