Sexual orientation and health: comparisons in the women's health initiative sample

CONTEXT: Little is known about older lesbian and bisexual women. Existing research rarely compares characteristics of these women with comparable heterosexual women. OBJECTIVE: To compare heterosexual and nonheterosexual women 50 to 79 years on specific demographic characteristics, psychosocial risk factors, screening practices, and other health-related behaviors associated with increased risk for developing particular diseases or disease outcomes. DESIGN: Analysis of data from 93,311 participants in the Women's Health Initiative (WHI) study of health in postmenopausal women, comparing characteristics of 5 groups: heterosexuals, bisexuals, lifetime lesbians, adult lesbians, and those who never had sex as an adult. SETTING: Subjects were recruited at 40 WHI study centers nationwide representing a range of geographic and ethnic diversity. PARTICIPANTS: Postmenopausal women aged 50 to 79 years who met WHI eligibility criteria, signed an informed consent to participate in the WHI clinical trial(s) or observational study, and responded to the baseline questions on sexual orientation. MAIN OUTCOME MEASURES: Demographic characteristics, psychosocial risk factors, recency of screening tests, and other health-related behaviors as assessed on the WHI baseline questionnaire. RESULTS: Although of higher socioeconomic status than the heterosexuals, the lesbian and bisexual women more often used alcohol and cigarettes, exhibited other risk factors for reproductive cancers and cardiovascular disease, and scored lower on measures of mental health and social support. Notable is the 35% of lesbians and 81% of bisexual women who have been pregnant. Women reporting that they never had sex as an adult had lower rates of Papanicolaou screening and hormone replacement therapy use than other groups. CONCLUSIONS: This sample of older lesbian and bisexual women from WHI shows many of the same health behaviors, demographic, and psychosocial risk factors reported in the literature for their younger counterparts, despite their higher socioeconomic status and access to health care. The lower rates of recommended screening services and higher prevalence of obesity, smoking, alcohol use, and lower intake of fruit and vegetables among these women compared with heterosexual women indicate unmet needs that require effective interactions between care providers and nonheterosexual women.     

Neurobiology of anxiety disorders and implications for treatment

The neurobiology of the anxiety disorders, which include panic disorder, post-traumatic stress disorder (PTSD), and specific phobias, among others, has been clarified by advances in the field of classical or Pavlovian conditioning, and in our understanding of basic mechanisms of memory and learning. Fear conditioning occurs when a neutral conditioned stimulus (such as a tone) is paired with an aversive, or unconditioned stimulus (such as a footshock), and then in the absence of the unconditioned stimulus, causes a conditioned fear response. Preclinical studies have shown that the amygdala plays a key role in fear circuitry, and that abnormalities in amygdala pathways can affect the acquisition and expression of fear conditioning. Drugs such as glutamate N-methyl-D-aspartate (NMDA) antagonists, and blockers of voltage-gated calcium channels, in the amygdala, may block these effects. There is also preliminary evidence for the use of centrally acting beta-adrenergic antagonists, like propranolol, to inhibit consolidation of traumatic memories in PTSD. Finally, fear extinction, which entails new learning of fear inhibition, is central to the mechanism of effective anti-anxiety treatments. Several pharmacological manipulations, such as D-cycloserine, a partial NMDA agonist, have been found to facilitate extinction. Combining these medication approaches with psychotherapies that promote extinction, such as cognitive behavioral therapy (CBT), may offer patients with anxiety disorders a rapid and robust treatment with good durability of effect.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line

Using specific radioimmunoassays, 8 day cultures of Hep G2 cells were shown to contain in their supernatants 16, 74, and 828 ng/mL and in their cell lysates, 8, 55, and 48 ng/2 X 10(8) cells of factor VII, protein C, and protein S, respectively. These proteins and the protein C inhibitor were functionally active, and each of these activities was neutralized by their respective polyclonal antibodies. Although vitamin K had a modest effect, warfarin decreased the activity of secreted factor VII, protein C, and protein S by 50% to 90%. Protein C and protein S antigens were reduced three- to fourfold by warfarin. The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment. Intrinsic labeling and immunoprecipitation indicated that factor VII, protein S, and the protein C inhibitor were secreted as 52,000, 77,000, and 58,000 molecular weight (mol wt) proteins, respectively. Protein C was secreted as a single-chain protein of about 65,000 mol wt, indicating that all of the vitamin K- dependent proteins are translated and secreted as single-chain molecules. Each of the four proteins studied represented their plasma protein counterparts structurally, functionally, and immunochemically. Thus, all of the known soluble components of the protein C pathway are produced by liver parenchymal cells.     

Ineffectiveness of clonidine in the treatment of the benzodiazepine withdrawal syndrome: report of three cases

The effectiveness of clonidine hydrochloride in the treatment of abrupt withdrawal from long-term, therapeutic doses of benzodiazepines was studied in three patients under double-blind, placebo-controlled conditions. The intensity, severity, and duration of the abstinence syndrome were not altered by clonidine at a dose sufficient to markedly reduce blood pressure and plasma free 3-methoxy-4-hydroxyphenylglycol. These results contrast with the established efficacy of clonidine in the opiate withdrawal syndrome and suggest that many of the symptoms of benzodiazepine withdrawal may not be caused by hyperactivity of the noradrenergic system.     

Abnormal regulation of noradrenergic function in panic disorders. Effects of clonidine in healthy subjects and patients with agoraphobia and panic disorder

Clonidine hydrochloride, an alpha 2-adrenergic receptor agonist that decreases noradrenergic function, was administered to 21 healthy subjects and 26 drug-free patients with agoraphobia and panic attacks. Clonidine produced significantly greater decreases in plasma MHPG levels and sitting and standing diastolic blood pressure and significantly smaller increases in growth hormone levels and self-rated drowsiness in the patients. These findings indicate that the regulation of noradrenergic activity is aberrant in some patients with panic disorder, since a previous study demonstrated that patients with panic disorder exhibit increased plasma MHPG levels, blood pressure, and behavioral responses to the alpha 2-adrenergic receptor antagonist yohimbine. The increased dynamic range of noradrenergic activity observed as an increased sensitivity to both clonidine and yohimbine may reflect abnormalities in the regulatory inputs to noradrenergic neurons, or dysfunction in the alpha 2-adrenergic receptor effector coupling mechanism or the intracellular effector system.     

Digital ischemia in clandestine intravenous drug users

Five young adults were seen initially with digital ischemia without a history of trauma or underlying systemic illness. After careful evaluation and treatment, inadvertent intraarterial drug injection was found to be the cause of the ischemia. The diagnosis was initially overlooked because the patients did not offer a history of drug abuse and did not appear like the stereotypical drug user. These patients may be seen early or several months after their accidental intraarterial injection. With the increase in drug abuse today, all segments of society can be affected. This diagnosis should be considered in any patient with unexplained digital ischemia.     

Nocardiosis of the lung: chest radiographic findings in 21 cases

Pulmonary manifestations of nocardial infection were present in 21 patients, with microbiologic proof in all and pathologic proof in 12. An analysis of the findings in these patients, combined with a review of previous reports of nocardiosis, suggests several important conclusions for radiologists. First, nocardiosis may occur in otherwise healthy persons but is most common in compromised patients, especially those being treated with anti-inflammatory agents, particularly corticosteroids, for chronic obstructive pulmonary disease and other systemic diseases. As pathologic manifestations are both suppurative and granulomatous, the chest radiographic manifestations are pleomorphic and not specific. Consolidations and large irregular nodules, often cavitary, are most common; nodules, masses, and interstitial patterns also occur. Pleural effusions are quite common, and lymph nodes may be enlarged. Difficulty and slowness of culture growth, along with the lack of a serologic test for nocardiosis, necessitate its inclusion in the differential diagnosis for both compromised and noncompromised patients in whom an apparent pulmonary infection cannot be rapidly diagnosed.     

Lithium treatment and serotoninergic function. Neuroendocrine and behavioral responses to intravenous tryptophan in affective disorder

Evidence suggests that lithium treatment alters serotoninergic (5-HT) function in laboratory animals and humans. Since 5-HT function may be abnormal in patients with affective disorders, we studied 23 such patients by measuring responses to intravenous infusion of the 5-HT precursor tryptophan before and during short-term (less than one week) or long-term (greater than three weeks) lithium treatment. The prolactin response to tryptophan was significantly enhanced after short-term lithium treatment; long-term lithium treatment had no effect. Other studies have shown that the prolactin response to tryptophan is also enhanced after long-term tricyclic antidepressant treatment in depressed patients and after short- and long-term lithium treatment in healthy subjects. The present findings suggest that lithium treatment enhances 5-HT function, but that homeostatic responses of the 5-HT system to long-term lithium treatment may differ in patients with affective disorder and healthy subjects.