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ABSTRACT: OBJECTIVE The relationship between depression and estrogen withdrawal remains controversial. The authors examined the effects of gonadotropin-releasing hormone agonist-induced ovarian suppression on mood, sleep, sexual function, and nighttime hot flushes. They focused on whether participating women experienced clinically significant depressive symptoms and whether specific symptoms associated with hypogonadism (nighttime hot flushes and disturbed sleep) increased susceptibility to depression. METHOD Participants were 72 healthy premenopausal women, ages 19-52 years, with no current or past axis I psychiatric diagnosis or gynecological or other medical illness. After 2 months of baseline screening, women received monthly injections of leuprolide acetate (3.75 mg) for 2-3 months. Outcomes were measured using the Beck Depression Inventory (BDI) and a daily rating scale measuring the severity of several affective and behavioral symptoms. Data were analyzed by repeated-measures analysis of variance using PROC MIXED (for mixed models). RESULTS BDI scores ≥10 were reported in four of the 72 women (5.6%). Relative to baseline, induced hypogonadism was associated with significantly decreased sexual interest, disturbed sleep, and more severe nighttime hot flushes, but no significant change in any mood-related symptom score. Hot flush severity was significantly correlated with disturbed sleep. CONCLUSIONS These data demonstrate that clinically significant depressive symptoms were rare accompaniments of short-term estradiol withdrawal and induced hypogonadism in healthy premenopausal women. Additionally, neither nighttime hot flushes nor disturbed sleep were sufficient to cause depressive symptoms in hypogonadal women.
American Journal of Psychiatry 04/2013; 170(4):426-33. · 12.54 Impact Factor
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ABSTRACT: A high prevalence of depressive symptoms is observed in women with primary ovarian insufficiency (POI) compared with women in whom the menopause is normally timed. Indeed, studies suggest that depression and/or its pharmacological treatment contribute to the onset of POI.
We characterize the prevalence of psychiatric disorders and the timing of onset of clinically significant depression relative to both the diagnosis of POI and the onset of menstrual irregularity in women with POI.
We conducted a cross-sectional clinic-based study at the National Institutes of Health Clinical Research Center.
A total of 174 women with spontaneous 46, XX POI and 100 women with Turner syndrome participated in the study.
The structured clinical interview for DSM-IV was performed.
Lifetime histories of depression in POI exceeded rates of depression reported in women with Turner syndrome and community-based samples of women (P < 0.001). The onset of depression frequently preceded the diagnosis of POI but occurred after the onset of menstrual irregularity. Analyses standardizing the periods of risk for depression showed that similar numbers of depressions occurred before and after these events.
POI is associated with an increased lifetime risk for major depression. Attention to the presence of depression in POI should become an important part of the care for these women. The onset of depression frequently occurs after signs of altered ovarian function but before the diagnosis of POI. Thus, in some women the association between POI and depression suggests an overlapping pathophysiology rather than a causal relationship.
The Journal of clinical endocrinology and metabolism 11/2010; 96(2):E278-87. · 6.50 Impact Factor
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Robert D Allison,
Antonios Katsounas, Deloris E Koziol,
David E Kleiner,
Harvey J Alter,
Richard A Lempicki,
Brad Wood,
Jun Yang,
Brandie Fullmer,
Karoll J Cortez,
Michael A Polis,
Shyam Kottilil
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ABSTRACT: Hepatic stellate cells (HSCs) mediate hepatitis C virus (HCV)-related liver fibrosis, and increased HSC activation in human immunodeficiency virus (HIV)/HCV coinfection may be associated with accelerated fibrosis. We examined the level of HSC activation in HIV/HCV-coinfected and HCV-monoinfected subjects and its relationship to the level of activation and gene expression of peripheral immune cells in coinfected subjects. HSC activation levels positively correlated with peripheral CD4+ and CD8+ T cell immune activation and were associated with enhanced interleukin-15 (IL-15) gene expression, suggesting a pathogenic role for IL-15-driven immunomediated hepatic fibrosis. Future strategies that reduce immune activation and HSC activation may delay progression of liver fibrosis.
The Journal of Infectious Diseases 09/2009; 200(4):619-23. · 6.41 Impact Factor
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ABSTRACT: To examine factors associated with emotional well-being in women with spontaneous primary ovarian insufficiency.
Cross-sectional and case-control study.
Clinical research center, national U.S. health research facility.
Women diagnosed with spontaneous 46,XX primary ovarian insufficiency (n = 100) at a mean age of 32.4 years and healthy control women of similar age (n = 60).
Administration of validated self-reporting instruments.
Illness uncertainty, stigma, goal disengagement/re-engagement, purpose in life, Positive and Negative Affect Schedule, Center of Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory.
Compared with controls, women with spontaneous primary ovarian insufficiency scored adversely on all measures of affect. Illness uncertainty and purpose in life were significant independent factors associated with anxiety (R(2) = 0.47), stigma and purpose in life were the significant independent factors associated with depression (R(2) = 0.51), and goal re-engagement and purpose in life were significantly and independently associated with positive affect (R(2) = 0.43).
This evidence supports the need for prospective studies. Our findings are consistent with the hypothesis that clinicians could improve the emotional well-being of their patients with primary ovarian insufficiency by [1] informing them better about their condition, [2] helping them to feel less stigmatized by the disorder, and [3] assisting them in developing alternative goals with regard to family planning as well as other goals.
Fertility and sterility 03/2009; 93(7):2321-9. · 3.97 Impact Factor
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ABSTRACT: To examine the relationship between spiritual well-being and functional well-being in women who have spontaneous premature ovarian failure.
Cross-sectional.
The Mark O. Hatfield Clinical Research Center at the US National Institutes of Health.
Women diagnosed with spontaneous premature ovarian failure (N = 138) at a median age of 28 years.
Administration of validated self-reporting instruments.
Functional Well-Being, Spiritual Well-Being, Meaning/Peace, and Faith scores.
We found a significant positive correlation between overall spiritual well-being and functional well-being scores. The Meaning/Peace subscale strongly correlated with functional well-being, explaining approximately 62% of the variance. In contrast, the Faith subscale was less strongly correlated with functional well-being, explaining only 7% of the variance. In multiple regression analysis evaluating the relative subscale contributions to functional well-being, only Meaning/Peace remained statistically significant. We found no significant associations between either spiritual well-being or functional well-being and age; age at diagnosis; time since diagnosis; or partner, children, or racial status.
This study provides cross-sectional data supporting the need for prospective controlled studies. Strategies to improve spiritual well-being in the domains of meaning, purpose, and inner peace may provide a therapeutic approach to reduce the emotional suffering that accompanies the life-altering diagnosis of premature ovarian failure.
Fertility and sterility 04/2007; 87(3):584-90. · 3.97 Impact Factor
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ABSTRACT: To determine whether the use of CD10 immunohistochemistry in addition to hematoxylin and eosin (H&E) staining would increase the sensitivity of surgically suspected endometriosis lesions.
Retrospective cohort study.
Tertiary care government research hospital.
Thirty-one women with chronic pelvic pain.
Immunohistochemical analysis for CD10 was performed on 108 possible endometriotic lesions and in the corresponding endometrial biopsy samples obtained during laparoscopy. When CD10 immunohistochemistry results were positive, the corresponding H&E section was reviewed to determine if the initial diagnosis should be revised.
Histologic diagnosis of endometriosis by adjunctive use of CD10 immunohistochemistry in conjunction with H&E-stained specimens.
In endometrial stroma, CD10 was consistently present. Of the 70 specimens judged negative initially by H&E staining, CD10 staining led to the diagnosis of endometriosis in 11. The addition of CD10 immunohistochemistry detected more positive endometriosis lesions than H&E staining alone (45% vs. 35%). In three women with minimal endometriosis at surgery but initially negative histopathology, CD10 immunohistochemistry changed the histologic diagnosis to endometriosis.
The adjunctive use of CD10 immunohistochemistry improves diagnostic sensitivity for endometriosis, especially for women with minimal disease.
Fertility and Sterility 08/2004; 82(1):86-92. · 3.56 Impact Factor
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ABSTRACT: To describe gait deficits and their association with lower-extremity muscle strength in children with juvenile idiopathic inflammatory myopathies (IIM).
Cross-sectional, descriptive study.
Clinical research center.
Consecutive sample of 25 ambulatory children diagnosed with juvenile IIM.
Not applicable.
Manual muscle test (MMT) of bilateral hip flexor, extensor, and abductor; knee extensor; and ankle plantarflexor strength, all measured on a 0- to 10-point scale and summary strength measures. Video-based movement analysis to determine walking speed; gait cycle time; right and left step time; stride length; right and left step length; and stance, swing, and double-limb support phase durations.
Walking speed (1.03+/-0.27 m/s) was reduced because of shortened stride lengths (1.03+/-0.21 m) more than prolonged gait cycle times (1.05+/-0.22s). Walking speed highly correlated with the number of muscle groups weaker than grade 7 out of 10 (r=-.89) and the strength of the hip flexors (r=.85).
Lower-extremity strength measures, including MMT scores of individual muscle groups and the number of weak muscle groups, were predictive of gait limitations in children with juvenile IIM.
Archives of Physical Medicine and Rehabilitation 06/2004; 85(5):767-71. · 2.28 Impact Factor
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Kittichai Promrat,
David H McDermott,
Carlos M Gonzalez,
David E Kleiner, Deloris E Koziol,
Matthew Lessie,
Maya Merrell,
Alejandro Soza,
Theo Heller,
Marc Ghany,
Yoon Park,
Harvey J Alter,
Jay H Hoofnagle,
Philip M Murphy,
T Jake Liang
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ABSTRACT: CCR5Delta32, a 32-base pair deletion of the CC chemokine receptor (CCR) 5 gene, is associated with slowed human immunodeficiency virus disease progression in heterozygotes and protection against infection in homozygotes. A recent study found a higher than expected frequency of CCR5Delta32/Delta32 in patients with hepatitis C virus infection. The roles of other disease-associated chemokine system polymorphisms have not been evaluated in hepatitis C virus infection.
Six chemokine system polymorphisms (CCR5Delta32, CCR5 promoter 59029-G/A, CCR2 -64I, RANTES [regulated upon activation, normal T cells expressed and secreted] -403 -G/A, and -28 -C/G and stromal derived factor 1 -3'A) were studied in 417 patients with liver diseases (339 with hepatitis C) and 2380 blood donors. The clinical parameters of hepatitis C virus infection were compared between carriers and noncarriers of each genetic variant.
The frequency of CCR5Delta32 homozygosity was 0.8% in whites with hepatitis C virus and 1.1% in controls (P = 0.75). The CCR5Delta32 allele was not associated with any of the clinical parameters of hepatitis C virus infection. Hepatitis C virus-seropositive whites with the RANTES -403-A allele were less likely to have severe hepatic inflammation compared with those without (odds ratio, 0.34; P = 0.03). In multivariate analysis, the CCR5 promoter 59029 -A allele was marginally associated with a sustained response to interferon therapy (odds ratio, 3.07; P = 0.048).
In this cohort, the frequency of CCR5Delta32 homozygosity in patients with hepatitis C was similar to controls. The high prevalence of CCR5Delta32 homozygosity in the hepatitis C virus patients of the earlier study likely reflects resistance to human immunodeficiency virus infection in hemophiliacs rather than a susceptibility to hepatitis C virus infection. Expression of CCR5 and RANTES may be important in the modulation of hepatic inflammation and response to interferon therapy in chronic hepatitis C.
Gastroenterology 02/2003; 124(2):352-60. · 11.68 Impact Factor
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ABSTRACT: Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-alpha, TGF-beta, and IFN-gamma) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-gamma genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-alpha. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.
American Journal of Transplantation 08/2002; 2(6):560-7. · 6.39 Impact Factor
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ABSTRACT: Background. Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein production. Furthermore, the functional consequence of a polymorphism at position -330 in the IL-2 gene has not been described. We associated in vitro protein production with cytokine gene polymorphic genotypes after costimulation of cultured peripheral blood lymphocytes.
Methods. PBL were isolated from forty healthy volunteers. Cytokine protein production was assessed by enzyme-linked immunosorbent assay. Polymorphisms in interleukin- (IL) 2, IL-6, IL-10, tumor necrosis factor (TNF-α), tumor growth factor (TGF-β), and interferon (IFN-γ) were determined by polymerase chain reaction (PCR).
Results. Statistical difference between protein production and cytokine polymorphic variants in the IL-10, IFN-γ, and TNF-α genes was not evident after 48-hour stimulation with concanavalin-A. In contrast, after anti-CD3/CD28 stimulation significant differences (P <0.05) were found among high and low producers for IL-2, IL-6, and among high, intermediate, and low producers for IFN-γ, and IL-10. Augmented levels of IL-2 in individuals that were homozygous for the polymorphic IL-2 allele were due to an early and sustained enhancement of IL-2 production. No association was found among TNF-α and TGF-β genotypes and protein production.
Conclusion. Polymorphisms in IL-2, IL-6, IL-10, and IFN-γ genes are associated with their protein production after anti-CD3/CD28 stimulation. The profound effect of the IL-2 gene polymorphism in homozygous individuals may serve as a marker for those that could mount the most vigorous allo- or autoimmune responses, or perhaps become tolerant more easily.
Transplantation 10/2001; 72(8):1444-1450. · 4.00 Impact Factor
