Disease- and treatment-related predictors of hepatic mitochondrial dysfunction in chronic HIV infection assessed by non-invasive (13)C-methionine breath test diagnostic.

OBJECTIVES: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons are due to hepatic complications. Hepatitis coinfection, antiretroviral treatment and co-occurrence of metabolic risk factors contribute to hepatic mitochondrial damage manifesting in hepatic steatosis and steatohepatitis. The aim was to assess disease- and treatment-related predictors on hepatic mitochondrial dysfunction in HIV infection by means of a new (13)C-methionine breath test (MeBT). PATIENTS AND METHODS: 148 HIV positive individuals with and without antiretroviral treatment (ART) [44 therapy-naives; 89 patients on combination ART and 15 patients on structured treatment interruption (STI)] and 20 HIV-negative controls were studied prospectively by MeBT. RESULTS: A decay of (13)C-methionine metabolism, expressed as cumulated percentage dose recovered over 1.5h (cPDR(1.5h)), in the subgroups of treatment-naives and patients on STI compared to controls was detected (cPDR(1.5h): 3.4 +/- 1.3% and 4.0 +/- 2.4% vs. 6.3 +/- 1.2%; p<0.01). Multivariate analyses including metabolic, treatment- and disease-related variables showed that antiretroviral treatment with stavudine, didanosine or zalcitabine and treatment-naivety were best predictors of a reduced MeBT result (cPDR(1.5h)) (beta = -0.56 and -0.50, p<0.05). CD4 count had only a minor association (beta = 0.15, p<0.05). No other variable including disease and treatment duration was associated with MeBT outcome. These factors explained 39% of the variance of MeBT results (p<0.05). CONCLUSIONS: Therapy naivety and treatment with d-drugs were the best predictors of poor MeBT outcome. MeBT may be proposed as a feasible, noninvasive diagnostic instrument for clinical assessment of hepatic mitochondrial function and early detection of drug-induced mitochondriotoxity in chronic HIV infection.

Treatment of condylomata acuminata with pegylated interferon alfa-2b in HIV-infected patients.

BACKGROUND: Interferon in a variety of topical, interlesional, and parenteral preparations has been used for condylomata acuminata (CA) in HIV negative patients. - STUDY GOALS: This open trial was initiated to determine the safety and efficacy of a new formulation of interferon, pegylated interferon-alpha2b (PEG-IFN, PegIntron in the treatment of recalcitrant CA in patients with HIV infection. - STUDY DESIGN: 22 HIV-1 infected patients in virologic steady state with clinically demonstrable anogenital CA were enrolled in this study (treatment group, n=12; control group, n=10). Patients in the treatment group received 80 microg PEG-IFN s.c. once a week for 24 weeks. Follow-up period was 6 month. The effects were assessed by a clinical scoring system (complete response; major response; minor response; stable disease; progression of disease). - RESULTS: 2 patients did not finish the study because of side effects. PEG-IFN was well accepted and completed by ten patients. Four patients revealed complete response, four patients had major response and two had minor response after PEG-IFN. In the control group, all patients showed progression of CA during the 24 weeks of this study (p < 0.001). 7/10 patients of the treatment group and 8/10 patients of the control received HAART. - While the differences of CD4 cell counts between treatment group and control group were not significant (increase of the mean CD4 cell count in the treatment group was 31.5 (75.33 without patient 1 with leucopenia under ribavirine), in the control group 69.75 CD4 cells), the HIV RNA decline in the PEG-IFN group was impressive (0.74 log subset10). Biological side effects of PEG-IFN treatment included flu-like symptoms, fatigue, local reaction, leucopenia, and increase of AST. This result makes an educated guess that PEG-IFN enhances the benefit of HAART. - CONCLUSION: PEG-IFN is an effective and safe therapy option in HIV infected individuals with CA with concomitant positive effects on the suppression of HIV-1 replication and CD4 cell count. It might be considered as an alternative in patients that have failed to standard therapies of CA and - at the same time -could improve the benefit of HAART to a great extent. This last hypothesis needs further research.

Expression of beta-defensin 1 and 2 in nasal epithelial cells and alveolar macrophages from HIV-infected patients.

BACKGROUND: The incidence of respiratory infection is high in HIV-infected patients. beta-defensins are anti-microbial peptides derived from epithelia on the mucosal surfaces of the respiratory, gastrointestinal and urinary tract. Nothing is known about the rate of expression of beta-defensin 1 and 2 mRNAs in nasal epithelial cells and alveolar macrophages in HIV-infected patients. METHODS: Semiquantitative rt-PCR measurement of beta-defensins 1 and 2 and beta-actin were carried out on nasal epithelial cells of 109 patients (76 HIV-infected) and alveolar macrophages from 56 patients (18 HIV-infected). RESULTS: The levels of beta-defensin 1 and 2 mRNAs in nasal epithelial cells did not differ significantly between HIV-infected and non-infected patients. In the nasal epithelial cells of HIV-negative patients who suffered from respiratory infections beta-defensin levels were decreased. beta-defensin 1 mRNA expression was significantly reduced in alveolar macrophages from HIV infected patients. beta-defensin 2 mRNA expression in alveolar macrophages was very low. beta-defensins 1 and 2 mRNA expression did not correlate with CD 4 cell numbers in the blood of HIV-infected patients. CONCLUSION: HIV infection and CD 4 cell numbers in the blood do not influence beta-defensin 1 and 2 expressions in nasal epithelial cells. In alveolar macrophages, beta-defensin 1 expression is decreased in HIV-infected patients.

Are the MMPI subtle subscales subtle measures of their scales?

This study investigated the ability of the MMPI Wiener-Harmon subtle subscales (on scales D. Hy, Pd, Pa, and Ma) to serve as subtle or unobtrusive measures of their scales. Forty outpatients completed the MMPI under standard instructions, followed by a fake-good or fake-bad instructional set. First, we investigated the paradoxical effect found in the MMPI faking literature (in which, overall, the subtle subscale T-scores change in a direction opposite of the faking instructions) and found that not every subtle subscale shows this effect. Secondly, the subtle subscale T-scores achieved under faking conditions showed no significant relationship to their respective full-scale T-scores achieved under standard conditions. Therefore, our results do not support the Wiener-Harmon subtle subscales as subtle measures of their scales.

Instructed faking and MMPI-2 response latencies: the potential for assessing response validity.

Differences in Minnesota Multiphasic Personality Inventory-2 (MMPI-2) response latencies between groups instructed to respond honestly or fake were explored. There were 120 undergraduate students who completed a computer administered MMPI-2 with instructions to either respond honestly, to underreport psychopathology, or to overreport psychopathology. Results showed that subjects required significantly more time to respond in a manner that was inconsistent with their response set when pattern of endorsement (acceptance vs. rejection) was considered and less time when pattern of endorsement was not considered. The differential response of subjects across groups suggests that response latencies are related to response styles and that future research may indicate a methodology for utilizing response latencies in assessing response validity.

Measurement of premorbid intellectual ability following brain injury.

Prediction of premorbid intellectual ability in brain-injured patients was investigated using two sets of regression equations and the Intellectual Correlates Scale (ICS). Eighty subjects completed the WAIS-R and the ICS. The four subject groups included a control group and right-hemisphere, left-hemisphere, and diffuse brain-injured groups. As expected, brain-injured groups obtained lower IQs than controls. Also, estimated IQs approximated obtained IQs for controls, while overestimating IQs for brain-injured groups. Support was provided for the continued use of the Barona, Reynolds, and Chastain (1984) and the Barona and Chastain (1986) regression equations as measures of premorbid intellectual functioning. Previous findings (Schlottmann & Johnsen, 1991), suggesting the ICS may also serve as a measure of premorbid intellectual functioning, were not replicated.

Validity of the MMPI subtle items.

This article presents a review and critique of research on the Minnesota Multiphasic Personality Inventory (MMPI) subtle items in regard to their validity as measures of their scales' characteristics. The main categories of focus are their convergent and discriminative validity, the paradoxical effect, and the issue of whether removing these items would improve MMPI validity. Important problems in the methodologies are noted and discussed in some detail. These methodological concerns and the conflicting results across studies obscure firm conclusions on the validity of the subtle items, although strong support is lacking. However, more evidence is needed before deciding to remove these items from the MMPI; therefore, this article provides recommendations for future research.

The intellectual correlates scale and the prediction of premorbid intelligence in brain-damaged adults.

An attempt was made to determine if premorbid intelligence could be estimated in brain-damaged persons through the use of regression equations developed from a scale of items reflecting interests, attitudes, personal values, and personality characteristics that correlated with WAIS-R IQs. A total of 33 adults with no reported history of brain damage were used in the item selection study. The resulting scale, the Intellectual Correlates Scale (ICS), was then administered to 30 brain-damaged persons and a group 28 normal controls, none of whom participated in the item selection study. Comparisons between the ICS equations for estimating WAIS-RIQs and two sets of demographic equations were made. As expected, all estimates of Full-Scale IQs were higher than actual IQs for brain-damaged subjects, but no differences were found between estimated and actual Full-Scale scores for normals. Results for Verbal and Performance IQs were more complex. Semi-partial correlations were used to compare the ICS equations with the corresponding demographic equations to assess the unique contributions of each.

Gender-bound definitions of mental health.

Fifteen male and 15 female American therapists-in-training (clinical and counseling psychology graduate students) were asked to take the Minnesota Multiphasic Personality Inventory (MMPI) under each of two instructional sets. In one set, they were instructed to respond to the items as a healthy male would respond, and in the other, as a healthy female would respond. The MMPI profiles obtained from male and female subjects were not significantly different, indicating that these male and female therapists-in-training did not differ in their perceptions of healthy men and women. When the data for male and female subjects were combined, however, healthy women were perceived differently than healthy men on several scales, although the MMPI profiles obtained under both instructional sets were well within normal limits.

The predictive validity of subtle and obvious empirically derived psychological test items under faking conditions.

The relative contributions of subtle and obvious item endorsements to the prediction of a relevant criterion were assessed under faking and control ("honest") conditions. The MMPI and a nonconformity questionnaire were first administered to 100 male college students. Items on the Pd scale and 101 additional MMPI items that correlated significantly with the nonconformity questionnaire were then rated by 38 other male college students for apparent relationship to psychopathology. From these ratings, a scale (designated PdX) was constructed, which consisted of 21 subtle and 21 obvious items. After a third group of 98 male college students completed the nonconformity questionnaire, they were asked to respond to the items of the Pd and PdX subscales under control, fake-good, and fake-bad instructions. Significant correlations between the nonconformity scale and certain PdX and Pd subscales were found only for the control group. Implications for test construction and for clinical interpretation under faking conditions are discussed.

Prediction of developmental attainments of institutionalized mentally retarded children.

Two regression equations using chronological age and either IQ or the Fisher and Zeaman K score were developed to predict Developmental Record ratings of institutionalized mentally retarded children over a 2-year interval (N = 200), a 4-year interval (N = 165), and an 8-year interval (N = 95). Although the correlations between predicted and obtained scores for both equations were quite high even over an 8-year interval, analysis of mean differences revealed that the equation using IQ yielded more accurate predictions. If future studies support the use of such equations with other subjects in other settings, they should be useful in estimating later developmental attainments of mentally retarded children.

Developmental changes of institutionalized mentally retarded children: a semilongitudinal study.

Developmental Record ratings were obtained for 200 institutionalized mentally retarded children over a 3-year period. Following a principal components analysis to determine the most appropriate form of inputting data, we obtained semilongitudinal developmental curves for children at each of four levels of retardation and for boys and girls separately. Results indicated that differences in measured intelligence are associated with differences in various kinds of developmental behavior and that between the ages of 7 and 20 years the relationship is primarily a linear one. When subjects were divided according to sex instead of level of retardation, differences appeared to be minimal. These results should be helpful in predicting later attainments of institutionalized retarded children since ratings on the Developmental Record can be translated into specific types of developmental behavior.