Colorectal cancer screening in HIV-infected patients 50 years of age and older: missed opportunities for prevention

OBJECTIVES: Although human immunodeficiency virus (HIV)-infected patients are now living longer, there are no published data on colorectal cancer (CRC) screening in this population. We hypothesized that HIV-infected patients were less likely to be screened for CRC compared to patients without HIV. METHODS: Consecutive HIV-infected patients > or =50 yr old seen in our outpatient clinic from 1/1/01 to 6/30/02 were identified. For each HIV-infected patient, we selected one age- and gender-matched control subject without HIV infection who was seen during the same time period. The electronic medical records were reviewed to determine the proportion of patients that had a fecal occult blood test (FOBT), flexible sigmoidoscopy, air-contrast barium enema (ACBE), or colonoscopy. RESULTS: During the 18-month study period, 538 HIV-infected outpatients were seen and 302 (56.1%) were > or =50 yr old. Despite significantly more visits with their primary care provider, HIV-infected patients were less likely to have ever had at least one CRC screening test (55.6%vs 77.8%, p < 0.001). The proportion of HIV-infected patients who ever had a FOBT (43.0%vs 66.6%, p < 0.001), flexible sigmoidoscopy (5.3%vs 17.5%, p < 0.001), ACBE (2.6%vs 7.9%, p= 0.004), or colonoscopy (17.2%vs 27.5%, p= 0.002) was significantly lower than in control subjects. In addition, HIV-infected patients were significantly less likely to be up-to-date with at least one CRC screening test according to current guidelines (49.3%vs 65.6%, p < 0.001). CONCLUSIONS: A substantial number of HIV-infected patients are > or =50 yr of age and CRC screening is underutilized in this population. Public health strategies to improve CRC screening in HIV-infected patients are needed.     

Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis

We studied the effects of long-term (i.e. 4 wk) voluntary exercise on the hypothalamic-pituitary-adrenocortical (HPA) axis in male mice. Voluntary exercise was provided by giving mice access to a running wheel, in which they indeed ran for about 4 km/d. Exercising mice showed similar body weights as control animals but presented less abdominal fat, lighter thymuses, and heavier adrenal glands. Exercise resulted in asymmetric structural changes in the adrenal glands. Whereas control mice had larger left than right adrenals, this condition was abolished in exercising animals, mainly because of enlargement of the right adrenal cortex. Tyrosine hydroxylase mRNA expression in the adrenal medullas of exercising mice was increased. In exercising mice, early-morning baseline plasma ACTH levels were decreased, whereas plasma corticosterone levels at the start of the dark phase were twice as high as those in control animals. To forced swimming and restraint stress, exercising mice responded with higher corticosterone levels than those of the control animals but with similar ACTH levels. However, if exposed to a novel environment, then exercising mice presented decreased ACTH responses. Interestingly, exercising mice showed a decreased corticosterone response to novelty only when the novel environment contained a functioning running wheel. Glucocorticoid receptor levels were unchanged, whereas mineralocorticoid receptor levels were decreased, in hippocampus of exercising animals. Corticotropin-releasing factor mRNA levels in the paraventricular nucleus were lower in exercising mice. Thus, voluntary exercise results in complex, adaptive changes at various levels within the HPA axis as well as in sympathoadrenomedullary and limbic/neocortical afferent control mechanisms. These changes seem to underlie the differential responsiveness of the HPA axis to physical vs. emotional challenges.     

Emerging Technologies to Increase Ligand Binding Assay Sensitivity

Ligand binding assays (LBAs) have been the method of choice for protein analyte measurements for more than four decades. Over the years, LBA methods have improved in sensitivity and achieved larger dynamic ranges by using alternative detection systems and new technologies. As a consequence, the landscape and application of immunoassay platforms has changed dramatically. The introduction of bead-based methods, coupled with single molecule detection standardization and the ability to amplify assay signals, has improved the sensitivity of many immunoassays, in some cases by several logs of magnitude. Three promising immunoassay platforms are described in this article: Single Molecule Counting (SMC™) from Singulex Inc, Single Molecule Arrays (Simoa™) from Quanterix Corporation, and Immuno-PCR (Imperacer®) from Chimera Biotec GmbH. These platforms have the potential to significantly improve immunoassay sensitivity and thereby address the bioanalytical needs and challenges faced during biopharmaceutical drug development.KEY WORDS: immunoassays, Immuno-PCR (Chimera Biotec GmbH), ligand binding assay (LBA), sensitivity, Single Molecule Array (Quanterix Corporation), Single Molecule Counting (Singulex Inc)     

Pediatric solid organ transplant recipients: Transition to home and chronic illness care

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high‐level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self‐managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty‐one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post‐discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post‐discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post‐discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self‐manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post‐discharge care.     

Characterization of P2x1 purinoreceptors on rat platelets: effect of clopidogrel

This study aimed to determine the binding characteristics of [³H]α,β-Me-ATP, a specific ligand of the P2x1 receptors to rat platelets, and to investigate the effect of clopidogrel, a thienopyridine compound which has been found to selectively inhibit ADP-induced platelet aggregation and adenylyl cyclase ex vivo . Binding of [³H]α,β-Me-ATP to rat platelets was time-dependent and saturable. Scatchard analysis of the saturation binding data indicated that [³H]α,β-Me-ATP bound to one population of specific binding sites with high affinity ( K _D  =  23.6 ± 1.6 n m ; B _max = 690 ± 24 fmole/10⁸cells) ( n= 3). Unlabelled α,β-Me-ATP as well as 2-MeS-ADP and ADP competitively inhibited the specific binding of [³H]α,β-Me-ATP with IC₅₀ values of 19.0 ± 6.6, 103 ± 20 and 1120 ± 80 n m respectively ( n= 3). Other nucleotide analogues such as ATP, ATP-γS, UTP and GTP also antagonized [³H]α,β-Me-ATP binding. When administered orally (10 mg/kg, p.o.), clopidogrel inhibited ADP- or 2-MeS-ADP-induced platelet aggregation but did not affect the binding of [³H]α,β-Me-ATP to rat platelets ex vivo. In vitro , α,β-Me-ATP did not induce the aggregation or shape change of rat platelets and did not interfere with ADP-induced platelet aggregation.     

Sensitivity to inhibition by β-chemokines correlates with biological phenotypes of primary HIV-1 isolates

Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by β-chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β. Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI) biological phenotypes recovered from patients at various stages of HIV-1 infection were assessed, and the results indicated that only the isolates with the NSI phenotype were substantially inhibited by the β-chemokines. More important to note, these data demonstrate that resistance to inhibition by β-chemokines RANTES, MIP-1α, and MIP-1β is not restricted to T cell line-adapted SI isolates but is also a consistent property among primary SI isolates. Analysis of isolates obtained sequentially from infected individuals in whom viruses shifted from NSI to SI phenotype during clinical progression exhibited a parallel loss of sensitivity to β-chemokines. Loss of virus sensitivity to inhibition by β-chemokines RANTES, MIP-1α, and MIP-1β was furthermore associated with changes in the third variable (V3) region amino acid residues previously described to correlate with a shift of virus phenotype from NSI to SI. Of interest, an intermediate V3 genotype correlated with a partial inhibition by the β-chemokines. In addition, we also identified viruses sensitive to RANTES, MIP-1α, and MIP-1β of NSI phenotype that were isolated from individuals with AIDS manifestations, indicating that loss of sensitivity to β-chemokine inhibition and shift in viral phenotype are not necessarily prerequisites for the pathogenesis of HIV-1 infection.     

Serum S-100B protein levels during and after successful carotid artery stenting or carotid endarterectomy.

PURPOSE: To characterize the course of S-100B serum levels, a reliable marker for cellular brain damage, in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA) for carotid artery stenosis compared to control groups undergoing hemithyroidectomy (HT) or coronary angiography (CA). METHODS: Forty-six consecutive patients scheduled for revascularization of internal carotid artery (ICA) stenosis were included in the study. Fourteen patients (11 men; median age 70 years, interquartile range [IQR] 63-74) were selected for treatment with CAS, while CEA was performed in 31 patients (24 men; median age 68 years, IQR 54-78) during the same time period. Fourteen consecutive patients (8 men; median age 60 years, IQR 48-70) undergoing CA for suspected coronary heart disease and 14 patients (10 women; median age 36 years, IQR 26-54) undergoing HT for a single thyroid nodule served as controls. RESULTS: All procedures were completed successfully. During ICA clamping in CEA patients without postoperative neurological deficits, median S-100B serum levels transiently increased from 0.04 to 0.26 ng/mL (p<0.01) and returned to baseline levels after declamping. Median S-100B serum levels of CAS patients without neurological impairment remained at baseline values. No increase in S-100B levels occurred in either control group. Three CEA patients who suffered from neurological deficits (1 transient ischemic attack and 1 major stroke) showed sustained elevation of S-100B serum levels 6 hours after extubation. CONCLUSION: In patients without neurological complications, CEA but not CAS was associated with a transient increase in the S-100B serum levels. Results indicate that the increase in S-100B does not originate from extracerebral sources, but rather appears to represent an impairment of the blood-brain barrier integrity or subtle brain cell damage probably due to hypoperfusion during clamping. Sustained elevation of S-100B serum levels corresponded to the development of postoperative neurological deficits.     

Preeclampsia enhances neuroglial marker expression in umbilical cord Wharton's jelly-derived mesenchymal stem cells

Objective: The aim of the study was to compare the neuroglial phenotype of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) from pregnancies complicated with preeclampsia and gestational age (GA)-matched controls.

Methods: WJ-MSC were isolated from umbilical cords from both groups and analyzed for the cell surface expression of MSC markers and the gene and protein expression of neuroglial markers.

Results: All WJ cells were highly positive for the MSC markers CD105, CD90 and CD73, but negative for markers specific for hematopoietic (CD34) and immunological cells (CD45, CD14, CD19 and HLA-DR). WJ-MSC from both groups expressed neuroglial markers (MAP-2, GFAP, MBP, Musashi-1 and Nestin) at the mRNA and protein level. The protein expressions of neuronal (MAP-2) and oligodendrocytic (MBP) markers were significantly increased in WJ-MSC from preeclampsia versus GA-matched controls.

Conclusions: WJ-MSC from preeclamptic patients are possibly more committed to neuroglial differentiation through the activation of pathways involved both in the pathophysiology of the disease and in neurogenesis.