Neuropsychological functions,sleep, and mental health in adults with Klinefelter syndrome

A few studies have examined neuropsychological functions, sleep, and mental health combined in Klinefelter syndrome (KS; 47,XXY). We investigated neuropsychological functions with standard tests, sleep with actigraphy, and self‐reported mental health in 30 men with KS (Mean age = 36.7 years) compared to 21 controls (Mean age = 36.8 years). Men with KS scored significantly lower on mental speed, attention span, working memory, inhibition, and set‐shifting tests, as well as overall IQ (mean effect size difference Cohen's d = 0.79). Men with KS had significantly longer night wakes, with no differences in other sleep variables (mean d = 0.34). Men with KS reported poorer mental health than controls (mean d = 1.16). Regression analyses showed neuropsychological functions explained variance in some sleep domains for men with KS but not for controls. Neuropsychological functions explained variance in some mental health domains for controls. For men with KS, however, verbal IQ was the only significant predictor of mental health. Altogether, men with KS display problems in neuropsychological functions and mental health but do not appear different from controls on most sleep parameters. Our findings indicate that relations between neuropsychological functions, sleep, and mental health differ between men with KS and controls.     

Differential regulation of IL-13 and IL-4 production by human CD8+ and CD4+ Th0, Th1 and Th2 T cell clones and EBV-transformed B cells

In the present study, the requirements and characteristics forthe production of IL-13 by human T cells, T cell clones andB cells were determined and compared with those of IL-4. IL-13was produced by human CD4⁺ and CD8⁺ T lymphocyte subsets isolatedfrom peripheral blood mononuclear cells and by CD4⁺ and CD8⁺T cell clones. CD4⁺ T cell clones belonging to T_h0, T_h1-likeand T_h2-like subsets produced IL-13 following antigen-specificor polyclonal activation. In addition, EBV-transformed B celllines expressed IL-13 mRNA and produced small amounts of IL-13protein. Expression of IL-13 mRNA and production of IL-13 proteinby peripheral blood T cells and T cell clones was induced rapidlyand was relatively long lasting, whereas IL-4 production bythese cells was transient In addition, IL-13 mRNA expressionwas induced by modes of activation that failed to induce IL-4mRNA expression. IL-13 shares many biological activities withIL-4 which Is compatible with the notion that the IL-13 andIL-4 receptors share a common component required for signaltransduction. However, IL-13 lacks the T cell-activating propertiesof IL-4. Here we have shown that this is related to the factthat T cells fall to bind radiolabeled IL-13 and do not expressthe IL-13-speclflc receptor component Taken together, theseresults indicate that the differences In expression and biologicalactivities of IL-4 and IL-13 on T cells may have consequencesfor the relative roles of these cytokines In the immune response.     

The CR2/CD19 complex on human B cells contains the src-family kinase Lyn

The complement receptor 2 (CR2 or CD21) can be found in non-covalentassociation with the Blymphocyte specific CD19 complex at thesurface of mature human B cells. Upon ligation of the B cellantigen receptor complex (BCR), members of the CR2-CD19 complexmay associate with membrane immunoglobulin (mlg). Moreover,CD19 and CD21 ligands, either murine mAb, C3d fragments or Epstein—Barrvirus, are known to have profound effects on B cell activation.We here show that CD19 is tightly linked to the non-receptorsrc kinase Lyn and that the CD19 glycoprotein itself servesas a substrate for a yet undefined serine/threonine kinase presentwithin the complex. In the process of antigen recognition, mlgand the CR2-CD19 complex may bind different sites of a complement-opsonizedantigenic particle. We hypothesize that in this process, approximationto the BCR allows CD19-associated Lyn kinase to phosphorylatepotential substrates within the antigen—receptor complex,thereby effecting its coupling to the intracellular compartment.     

The Effect of Functional Pelvic Tilt on the Three-Dimensional Acetabular Cup Orientation in Total Hip Arthroplasty Dislocations

BackgroundAnterior and posterior pelvic tilt appears to play a role in total hip arthroplasty (THA) stability. When changing from the standing to the sitting position, the pelvis typically rotates posteriorly while the hips flex and this affects the femoro-acetabular positions. This case-control study compares changes in 3-D acetabular cup orientation during functional pelvic tilt between posterior THA dislocations vs stable THAs.MethodsStanding and sitting 3-D cup orientation was compared between fifteen posterior dislocations vs 233 prospectively followed stable THAs. 3-D cup orientation was calculated using previously validated trigonometric algorithms on biplanar radiographs. Those algorithms combine the angles in the three anatomical planes (coronal inclination, transverse version, and sagittal ante-inclination) in the standing position with the change in sagittal pelvic tilt from standing to sitting to calculate the 3-D orientation in the sitting position.ResultsThe standing cup orientation of the dislocated THAs was only characterized by a lower coronal inclination (P = .039). Compared with the controls, from standing to sitting, they showed less posterior pelvic tilt (P < .001). This led to a significant lower coronal inclination (P < .001) and sagittal ante-inclination (P < .001) in the sitting position but similar transverse version (P = .366).ConclusionsComparing posterior THA dislocations to stable THAs, there is a lower increase of all three orientation angles from standing to sitting. This leads to a decreased sitting coronal inclination and sagittal ante-inclination which may lead to an increased risk of impingement ensued by THA instability. By contrast, the transverse version was not significantly different in both positions. This confirms the importance of biplanar data on functional cup orientation.Level of EvidenceDiagnostic, Level III.     

Sexual dysfunction in male and female patients with epilepsy: A study of 86 outpatients

Sexual dysfunction is a well-known complication of chronic somatic illness. Eighty-six consecutive epileptic outpatients, 38 men and 48 women, without accompanying disorders, were studied. The frequency and symptoms of sexual dysfunction were compared with results from previous studies using identical sexological methodology. The previous studies were of diabetic patients and healthy controls. Eight percent of the epileptic men reported a sexual dysfunction compared to 44% of the diabetics and 13% of the controls. Epileptic women, diabetic women, and controls showed no significant differences in sexual dysfunction (29%, 28%, and 25%, respectively). In both sexes, the sexual function measured by frequencies of coitus and masturbation was normal. Most patients had good control of epileptic attacks on a treatment of monotherapy. Hormonal status was generally within normal limits in both men and women; only a few minor differences were found and they showed no correlation with sexual dysfunction. Psychologically and socially the patients did not differ appreciably from normals, and they exhibited a high degree of disease acceptance. This study, using a biopsychosocial approach in understanding sexual dysfunctions, is in contrast with previous, mainly uncontrolled, studies of epileptic patients that reported high frequencies of hyposexuality in males. We conclude that epilepsy does not necessarily increase the risk of sexual dysfunction in male or female.     

Effects of intermittent exposure to aflatoxin B1 on DNA and RNA adduct formation in rat liver: dose-response and temporal patterns.

We studied the effects of intermittent exposure to aflatoxin B1 (AFB1) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm of AFB1 intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB1 continuously for 4, 8, 12, and 16 weeks. Control rats received AFB1-free NIH-31 meal diet. AFB1-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after 1 or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB1 after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB1-RNA adducts were three to nine times more sensitive than AFB1-DNA adducts but showed greater variability. These results suggest that binding of AFB1 to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA.     

Low-dose outpatient chemobiotherapy with temozolomide, granulocyte-macrophage colony stimulating factor, interferon-alpha2b, and recombinant interleukin-2 for the treatment of metastatic melanoma.

PURPOSE: The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). RESULTS: Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. CONCLUSION: This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases.     

Antitumor alkylating agents: in vitro cross-resistance and collateral sensitivity studies

Cell lines resistant to five antitumor alkylating agents (CDDP, PAM, 4-HC, HN2, and BCNU) were developed from five parental human tumor lines representative of solid tumors with a range of sensitivities to antitumor alkylating agents. The parental cell lines were SCC-25 squamous carcinoma of the head and neck, MCF-7 breast carcinoma, SW2 small-cell lung cancer, SL6 non-small-cell lung carcinoma, and G3361 melanoma. Survival curves using colony formation as the endpoint were generated for each of the 25 cell lines to each of the five alkylating agents. Comparison of the drug concentrations that reduced the survival of the alkylating agent-resistant cell lines by 90% (IC₉₀ values) with the IC₉₀ values obtained for the corresponding parental cell lines was used as a measure of the resistance/sensitivity of the alkylating agent-resistant lines to each drug tested. Although cross-resistance among the alkylating agents was generally uncommon, several patterns of response emerged. Cross-resistance occurred in 27 of the 105 determinations and occurred most frequently in the cell lines in which resistance was developed to PAM (57%) or BCNU (38%). Cross-resistance to HN2 occurred most frequently. Collateral sensitivity was equally as common, occurring in 25 of the 105 determinations. Collateral sensitivity occurred most frequently in the cell lines made resistant to 4-HC. The 4-HC-resistant cell lines were most frequently collaterally sensitive to PAM and to BCNU. Cross-resistance developed most frequently in the MCF-7 breast carcinoma and SCC-25 squamous-cell carcinoma cell lines, whereas collateral sensitivity developed most frequently in the SW2 small-cell lung cancer line and the G3361 melanoma cell line and least frequently in the MCF-7 breast carcinoma cell line and the SL6 non-small-cell lung cancer cell line. The implication of these findings for the development of strategies for clinical treatment are discussed.Abbreviations AAs antitumor alkylating agents - CDDP cisplatin,cis-diamminedichloroplatinum(II) - HN2 nitrogen mustard - BCNU N,N-bis(2-chloroethyl)-N-nitrosourea - PAM l-phenylalanine mustard, melphalan - 4-HC 4-hydroxyperoxycyclophosphamide - CPA cyclophosphamide - THIO trimethyleneiminethiophosphoramide - DME Dulbecco's modified Eagle's medium - IC₉₀ 90% inhibitory concentration - PBS phosphate-buffered 0.9% saline - FBS fetal bovine serum - GSH glutathione - GST glutathione-S-transferase This work was supported by NIH grant PO1-38493, by a grant from the Mathers Foundation, by a grant from Bristol-Myers-Squibb, Inc., Wallingford, Connecticut, and by ACS grant CH-487