Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

Bone density and microarchitecture in hepatitis C and HIV-coinfected postmenopausal minority women.

We found that HIV+/HCV+ women had 7-8% lower areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) at the spine, hip, and radius (p < 0.01) and 5-7% lower volumetric BMD (vBMD) by central quantitative computed tomography (cQCT) at the spine and hip (p < 0.05). These data suggest that true deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women. INTRODUCTION: aBMD by DXA is lower in persons coinfected with HIV and HCV (HIV+/HCV+) than with HIV monoinfection (HIV+). However, weight is often also lower with HCV infection, and measurement of aBMD by DXA can be confounded by adiposity; we aimed to determine whether true vBMD is also lower in HIV+/HCV+ coinfection. METHODS: We measured aBMD of the lumbar spine (LS), total hip (TH), femoral neck (FN), and ultradistal radius (UDR) by DXA and vBMD of the spine and hip by cQCT and of the distal radius and tibia by high-resolution peripheral QCT (HRpQCT) in 37 HIV+/HCV+ and 119 HIV+ postmenopausal women. Groups were compared using Student's t tests with covariate adjustment by multiple regression analysis. RESULTS: HIV+/HCV+ and HIV+ women were of similar age and race/ethnicity. HIV+/HCV+ women had lower body mass index (BMI) and trunk fat and were more likely to smoke and less likely to have a history of AIDS. In HIV+/HCV+ women, aBMD by DXA was 7-8% lower at the LS, TH, and UDR (p < 0.01). Similarly, vBMD by cQCT was 5-7% lower at the LS and TH (p < 0.05). Between-group differences in LS aBMD and vBMD remained significant after adjustment for BMI, smoking, and AIDS history. Tibial total vBMD by HRpQCT was 10% lower in HIV+/HCV+ women. CONCLUSION: HIV+/HCV+ postmenopausal women had significantly lower spine aBMD and vBMD. These deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women.

Frailty in Postmenopausal African American and Hispanic HIV-Infected Women.

Studies suggest frailty occurs earlier in HIV-infected individuals, but data in postmenopausal HIV-infected women are lacking. We assessed the prevalence of frailty and association with anthropometric measures in HIV-infected and uninfected postmenopausal women. Fried's frailty phenotype was measured in HIV-infected and uninfected Hispanic and African American postmenopausal women participating in a study of bone metabolism; fat and lean mass were measured by whole body dual energy x-ray absorptiometry (DXA). Multivariable logistic regression evaluated frailty risk factors. The study was conducted at Columbia University Medical Center between 2002 and 2007. The participants were 61 HIV-infected and 27 uninfected Hispanic and African American postmenopausal women. The study compared prevalence and predictors of frailty in HIV-infected and uninfected postmenopausal women. Prevalence of frailty tended to be higher among HIV-infected than uninfected controls (11.5% vs 0% p=0.07). Surprisingly, among HIV-infected women, total body fat, not lean mass, was associated with frailty in multivariate analysis. Higher prevalence of frailty in African American and Hispanic HIV-infected postmenopausal women (11.5%) was similar to the 11% prevalence reported in minority women who were 10 years older in the general population. Our data suggest that frailty occurs earlier in HIV-infected postmenopausal women, but larger longitudinal studies are necessary to confirm whether musculoskeletal aging is accelerated by HIV infection.

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women.

UNLABELLED: We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. INTRODUCTION: To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. METHODS: In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. RESULTS: The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART. CONCLUSIONS: In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.

Sildenafil citrate and Torsade de pointes

Sildenafil citrate is a drug used in the treatment of erectile dysfunction. It is an inhibitor of the enzyme phosphordiesterase-5; it slows down the breakdown of c-GMP and nitrous oxide. The cardiac effects associated with Sildenafil citrate have been extensively studied in medical literature, especially its potent vasodilatory effect when combined with nitrate-based medications, producing intractable hypotension, but a lesser known and potentially lethal side effect is prolonged cardiac repolarization when used at dosage greater than recommended, leading to QT prolongation that could theoretically lead to dangerous cardiac dysrrhythmias and sudden death in men with coronary artery disease. The authors present the case of a 49-year-old hypertensive Hispanic man who arrived to our emergency department with the chief complaint of acute epigastric pain for 3 hours of evolution after ingestion of Sildenafil citrate 50 milligrams (mg). The patient was found to have an acute ST elevation inferior myocardial infarction (STEMI). Shortly after diagnosis the patient developed a polymorphic ventricular tachycardia (Torsade de pointes) before thrombolytic administration. We present this case followed by a brief discussion, to heighten awareness of the possible association of acute inferior STEMI and the development of Torsade de Pointes after the use of Sildenafil citrate.

Outcome of pregnancies complicated by systemic sclerosis and mixed connective tissue disease.

Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are rare autoimmune diseases which share the common feature of non-inflammatory vasculopathy. Studies evaluating pregnancy outcomes in these patients have yielded conflicting results. We sought to describe the outcomes of pregnancies associated with SSc and MCTD followed at our center utilizing a retrospective review of all pregnant women with SSc and MCTD followed at Stanford University from 1993 to 2003. We identified 20 pregnancies occurring in 13 women with SSc or MCTD. Twelve pregnancies occurred in seven women with SSc and eight pregnancies occurred in six women with MCTD. The overall preterm delivery rate was 39% and small for gestational age infants occurred in 50% and 63% of pregnancies associated with SSc and MCTD, respectively. Fetal loss complicated two pregnancies in women with severe diffuse SSc and the antiphospholipid antibody syndrome. There were no cases of congenital heartblock among infants, and only one case of pre-eclampsia was observed. Maternal flares of disease during pregnancy were generally mild. Most pregnancies in women with SSc and MCTD in this cohort were uncomplicated. The high rates of prematurity and small for gestational age infants underscore the risk for growth restriction consistent with the vasculopathy associated with these diseases.

A novel fibronectin binding site required for fibronectin fibril growth during matrix assembly.

Fibronectin (FN) assembly into a fibrillar extracellular matrix is a stepwise process requiring participation from multiple FN domains. Fibril formation is regulated in part by segments within the first seven type III repeats (III1-7). To define the specific function(s) of this region, recombinant FNs (recFNs) containing an overlapping set of deletions were tested for the ability to assemble into fibrils. Surprisingly, recFN lacking type III repeat III1 (FNDeltaIII1), which contains a cryptic FN binding site and has been suggested to be essential for fibril assembly, formed a matrix identical in all respects to a native FN matrix. Similarly, displacement of the cell binding domain in repeats III9-10 to a position close to the NH2-terminal assembly domain, as well as a large deletion spanning repeats III4-7, had no effect on assembly. In contrast, two deletions that included repeat III2, DeltaIII1-2 and DeltaIII2-5, caused significant reductions in fibril elongation, although binding of FN to the cell surface and initiation of assembly still proceeded. Using individual repeats in binding assays, we show that III2 but not III1 contains an FN binding site. Thus, these results pinpoint repeat III2 as an important module for FN-FN interactions during fibril growth.

Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development.

Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.

Resistance to a residential AIDS home: an empirical test of NIMBY.

OBJECTIVE: This study is designed to evaluate the NIMBY (not-in-my-back-yard) syndrome regarding a proposed residential home for HIV-positive individuals. Hypotheses attempted to explain support of the home and fear of loss in real estate values. These variables were analyzed in terms of value of homes, distance to site, fear of AIDS and homophobia. METHOD: A survey of New Hope, Pennsylvania employed a 10% probability cluster sample. This resulted in 106 responses and a response rate of 70.7%. Correlational and multiple regression analyses were used to test hypotheses. FINDINGS: Support of the home and fear of loss in real estate values were not found to be related to distance from one's home to the site or to value of one's home. Bath were related to fear of AIDS and homophobia. CONCLUSIONS: NIMBY opposition in the case of an AIDS residence was found to be primarily related to fear of AIDS and homophobia. This situation, an AIDS residence, appears to be different from other instances of NIMBY.

Effects of interleukin-1alpha, interleukin-1 receptor antagonist, and neutralizing antibody on proinflammatory cytokine expression by human squamous cell carcinoma lines.

Proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been detected in tumor specimens and primary cell cultures from patients with head and neck squamous cell carcinoma. IL-1alpha has been reported to play an important role in inducing the expression of cytokines IL-6, IL-8, and GM-CSF during inflammation. We examined whether these cytokines are expressed together in five primary and seven established UM-SCC cell lines, and we also examined the effects of IL-1alpha, IL-1 receptor antagonist or neutralizing antibody (Ab) upon expression of this repertoire of proinflammatory cytokines in established UM-SCC lines. Secretion of proinflammatory cytokines IL-1alpha, IL-6, IL-8, and GM-CSF was detected by ELISA in both the primary and established UM-SCC lines. Constitutive expression of specific mRNAs for these cytokines was confirmed in the UM-SCC lines by reverse transcriptase-PCR and Northern blot analysis. Addition of recombinant IL (rIL)-1alpha but not rIL-6 induced a dose-dependent increase in IL-8 and GM-CSF production. IL-1 receptor antagonist (IL-RA) or anti-IL-1 neutralizing Ab could completely inhibit the rIL-1alpha-inducible increase in IL-8 and GM-CSF expression, but the inhibitors had a negligible effect on the constitutive level of production of the cytokines. Transfer and expression of the IL-1alpha gene in a low-cytokine-producing cell line, UM-SCC-38, induced IL-8 and GM-CSF expression, but this expression was also not inhibited by IL-1RA or anti-IL-1 neutralizing Ab. We conclude that IL-1alpha can enhance the expression of cytokines IL-8 and GM-CSF in UM-SCC cell lines but that constitutive expression of these cytokines by UM-SCC is not inhibited by exogenous IL-1RA or neutralizing Ab.

A novel opioid mechanism seems to modulate phagocytosis in Tetrahymena.

We have previously reported that a beta-endorphin-like substance inhibits phagocytosis in Tetrahymena perhaps by a mu-like opioid receptor. We now report a further characterization of the elements involved in the signal transduction mechanism of this opioid. Affinity chromatography followed by immunoblots of both intracellular extracts and extracellular medium reveal the presence of two main proteins of 64 and 75 kDa. These molecular weights are much higher than that of any known opioid peptide or precursor protein and suggest that we may be dealing with either a novel opioid or with proteins that by chance cross-react with anti-beta-endorphin antibody. Nevertheless, when the biological activity of these proteins was tested it was found that they had an effect similar to that of mammalian beta-endorphin, namely inhibition of phagocytosis by a naloxone-reversible mechanism. We have probed a size-selected Tetrahymena library with a pro-opiomelanocortin probe and have obtained several positive clones; the sequencing of their inserts should establish whether we are dealing with a bona fide member of the opioid family. Another aspect we have been studying is the G-proteins which appear to be involved in the modulation of phagocytosis. We have found, by means of Western blotting (using an antibody against the conserved GTP-binding region of the alpha-subunit), two bands of 51 and 59 kDa; no alpha-subunit of 59 kDa had been reported previously and may represent a novel G-protein. In spite of these differences, the opioid signal transduction mechanism appears to remarkably resemble that present in more complex organisms.

Cholesterol 7 alpha-hydroxylase activity is increased by dietary modification with psyllium hydrocolloid, pectin, cholesterol and cholestyramine in rats.

Sources of dietary fiber known to alter cholesterol metabolism and/or bile acid pool size were fed to rats, and activity of the rate-limiting step in bile acid synthesis, cholesterol 7 alpha-hydroxylase, was measured. In the first experiment, semipurified diets containing 5% cellulose, psyllium hydrocolloid, pectin or oat bran as dietary fiber sources or 2% cholestyramine were fed to groups of 10 male Wistar rats for 4 wk. In the second experiment, groups of six rats were fed diets containing 5% cellulose, rice bran, oat bran or psyllium with and without 0.25% cholesterol. In the first experiment, the activity of cholesterol 7 alpha-hydroxylase (pmol.min-1.mg protein-1) was highest in the cholestyramine-treated group (95.6 +/- 3.6), followed by groups fed psyllium (35.5 +/- 3.5) or pectin (36.0 +/- 4.5), which exhibited more than twice the enzyme activity of groups fed cellulose (16.9 +/- 1.9) or oat bran (12.3 +/- 2.0). In the second experiment, feeding cholesterol resulted in significantly higher enzyme activity when cellulose (65%), oat bran (118%) and rice bran (60%) were fed, but no difference in activity was observed when cholesterol was added to the psyllium-containing diet. Higher activity of cholesterol 7 alpha-hydroxylase when pectin or psyllium rather than cellulose was fed may explain the almost twofold higher bile acid pool sizes previously reported in response to feeding either of these fibers. These data support the hypothesis that the hypocholesterolemic effect of soluble fibers is modulated through increased synthesis and therefore pool size of bile acids.

Homeland, gender and Chinese drinking.

Taiwan and Hong Kong represent areas of rapid industrial development and the attention of traditional Chinese attitudes toward drinking. To measure the influence of the different homelands on alcohol consumption, a survey of 150 foreign Chinese students (94 males and 56 females) was conducted. In terms of homeland, 95 participants (63.3%) were from mainland China, 29 (19.3%) were from Taiwan, and 26 (17.3%) were from Hong Kong. Both homeland and gender were found to be important predictors of alcohol consumption. Those from mainland China drank less than those from either Taiwan or Hong Kong. it is concluded that cultural values play an important role in explaining drinking among the Chinese.

The expression of neuropeptide Y immunoreactivity in the avian sympathoadrenal system conforms with two models of coexpression development for neurons and chromaffin cells.

We have studied the expression and development of neuropeptide Y-like immunoreactivity (NPY-LI) in the sympathoadrenal system of the chicken using single and double immunocytochemical techniques and radioimmunoassay. NPY-LI is expressed by neurons of the paravertebral sympathetic ganglia and by chromaffin cells of the adrenal gland in embryonic and adult chickens. The peptide is coexpressed with catecholaminergic properties in neurons. In chromaffin cells, it is also expressed with immunoreactivity to somatostatin and serotonin. We have used the expression of NPY-LI to analyze how cells that coexpress two or more neuroactive substances arrive at their final phenotype. Our results suggest that the ontogeny of coexpression in neurons of the avian paravertebral sympathetic ganglia occurs in a sequential pattern, where the expression of the peptide follows the initial expression of the "classical neurotransmitter". In contrast, in chromaffin cells, expression of the peptides occurs concomitantly with expression of catecholaminergic properties or soon after. Initially, coexpression of several neuroactive substances occurs, but this is followed by further specialization where the expression of one peptide prevails over the other. We believe that the two models of coexpression shown by our results can be used to describe the ontogeny of coexpression in other cells of the nervous system.

Race, belief in destiny, and seat belt usage: a pilot study.

A survey of 1063 individuals found that when belief in destiny was statistically controlled, differences in seat belt use by race disappeared. Thus, racial differences in seat belt use are statistically accounted for and might be explained by belief in destiny. Efforts to increase seat belt use should target minority groups rather than include them in broadbrush programs. Further, these efforts should take into account this important difference in motivation.

Prospective study about the incidence of B lactamase producing bacteriae in otitis media in the population of the emergency room of the University Pediatric Hospital.

The purpose of the study is to determine the incidence of beta-lactamase producing pathogens causing otitis media (O.M.) in the Emergency Room population of the University Pediatric Hospital. In our first four months of study, 22 patients, between the ages of 6 months to 13 y/o have been evaluated. Middle ear secretion cultures were obtained by tympanocentesis. The organisms recovered from cultures were S. epidermidis 3 (14%), S. pneumoniae 2 (9%) H. influenzae 1 (5%), mix flora 1 (5%) and 13 (59%) with no growth. None of these organisms were beta-lactamase producers. Up to 64% of the patients had history of 2 to 5 OM episodes during the last six months. Interesting is the association of bronchial asthma, sinusitis and allergy history with OM. Final study results will be presented in a near future.

The role of tourism in alcohol-related highway fatalities.

Tourism and fatal single motor vehicle accidents, an index of alcohol-related motor accidents, are examined in a cross-sectional analysis of the 50 states of the Union and the District of Columbia. A multiple regression model is employed in which average mileage driven, percent of metropolitan residents, and number of licensed drivers are statistically controlled. Tourism is found to be positively associated with the single motor vehicle fatality rate. Further research and policy implications are discussed.