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PubMed2004

Identification of a novel mechanism of NF-kappaB inactivation by progesterone through progesterone receptors in Hec50co poorly differentiated endometrial cancer cells: induction of A20 and ABIN-2.

OBJECTIVE: Nuclear factor kappa B (NFkappaB) is a strong anti-apoptotic factor, which is constitutively active in human endometrial cancer cells. Progesterone is the principal growth inhibitory hormone in the endometrial epithelium and promotes apoptosis. To identify the pathways through which progesterone controls NFkappaB function, we explored its genomic and non-genomic effects in endometrial cancer cells. METHODS: PR-negative Hec50co endometrial cancer cells were engineered to express high levels of the A or B isoform of PR (PRA or PRB) by adenoviral infection. Cells were treated with progesterone or vehicle alone, and RNA was isolated. Affymetrix microarrays were performed and transcriptional control of the genes of highest interest was confirmed by semi-quantitative RT-PCR. To assess the non-genomic effects of PR on inflammation associated with NF-kappaB, electromobility shift assays (EMSAs) were performed. RESULTS: Expression analysis demonstrated a significant effect of progesterone after 12- and 24-h treatment on several genes; in particular, A20 and ABIN-2 were induced through PRB. These factors bind in a complex and inhibit NFkappaB transcriptional activity. In addition, EMSAs revealed the complete inhibition of NFkappaB dimer binding to DNA by both PRA and PRB. CONCLUSIONS: Progesterone is the principal differentiating hormone in the endometrium. We have now identified several down-stream pathways of action, one of which is the control of genes involved in NFkappaB activity. The tumorigenic inflammatory and anti-apoptotic effects of NFkappaB are inhibited by progesterone/PRB through the transcriptional control of binding proteins A20 and ABIN-2. This pathway offers interesting targets for future therapeutic development.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Phenotypic and genotypic characterization of fecal Escherichia coli isolates with decreased susceptibility to fluoroquinolones: results from a large hospital-based surveillance initiative.

BACKGROUND: The prevalence of fecal colonization with Escherichia coli that has reduced susceptibility to fluoroquinolones is unknown. A detailed characterization of such isolates is limited. METHODS: We conducted 3 annual fecal surveillance initiatives at 2 hospitals from 2002 to 2004. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] to levofloxacin, > or = 0.125 microg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance (OST). Isolates were compared using pulsed-field gel electrophoresis. RESULTS: Of 789 fecal samples, 149 (18.9%) revealed E. coli with reduced susceptibility to fluoroquinolones. Of 149 isolates, 102 (68.5%) had a MIC > or = 8 microg/mL, 138 (92.6%) had > or = 1 gyrA mutation, 101 (67.8%) had > or = 1 parC mutation, and 59 (39.6%) demonstrated OST. Isolates with a MIC > or = 8 versus <8 microg/mL had more target mutations (median, 3 vs. 1; P<.001) and more often exhibited OST (51% vs. 15%; P<.001). Of 149 isolates, 144 (96.6%) demonstrated a MIC > or = 16 microg/mL to nalidixic acid. The prevalence of OST differed across study years (P = .01). There was no clonal spread of isolates. CONCLUSIONS: Colonization by E. coli with reduced fluoroquinolone susceptibility is common, and fluoroquinolone-resistance characteristics differ significantly over time. Resistance to nalidixic acid may be useful in the identification of E. coli with early resistance mutations.

Anti-Bacterial Agents↗
PubMed2002

Changes in integrin expression are associated with altered homing properties of Lin(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) hematopoietic stem cells following mobilization by cyclophosphamide/granulocyte colony-stimulating factor.

OBJECTIVE: Although migration of hematopoietic stem cells (HSC) is essential for normal hematopoiesis and successful hematopoietic cell transplantation, little is known about the mechanisms that underlie this movement. We have sought to characterize the factors that regulate HSC migration by analyzing changes in expression of particular adhesion receptors associated with cyclophosphamide/granulocyte colony-stimulating factor (Cy/G-CSF)-induced HSC mobilization. METHODS: Expression by Lineage(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) HSC of members of the beta1 integrin family of adhesion molecules was assessed in untreated or Cy/G-CSF-treated mice by multiparameter flow cytometry. In parallel, the in vivo homing properties of normal and mobilized HSC were compared following intravenous transfer of fluorescently marked HSC. RESULTS: Normal adult HSC express high levels of several beta1 integrin family members. Following Cy/G treatment, bone marrow HSC selectively downregulate alpha 2 integrin expression and upregulate alpha 5 expression. HSC found in the blood following Cy/G-CSF treatment express significantly lower levels of multiple integrins than their bone marrow and/or splenic counterparts. Changes in integrin expression by blood-borne HSC correlate with a 50% decrease in their ability to home to the bone marrow in short-term assays, and with previously observed defects in competitive engraftment by these HSC. Similar reductions in bone marrow (BM) homing are observed for BM HSC treated with alpha 4 integrin function blocking mAb prior to injection. Modulation of integrin expression induced by mobilization was not associated with cell-cycle progression. CONCLUSION: Changes in integrin expression and function are associated with HSC mobilization and likely significantly affect the engraftment potential of hematopoietic stem cells.

Animals↗
PubMed2005

Hypoxia activates MAPK activity in rat nucleus pulposus cells: regulation of integrin expression and cell survival.

OBJECTIVE: The aim of the present study was to investigate whether activation of MAPK subtypes ERK and p38 influences integrin expression and promotes nucleus pulposus cell survival in hypoxia. SUMMARY OF BACKGROUND DATA: We have recently shown that in a low oxygen environment, rat nucleus pulposus cells activate phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. However, the role of these signaling pathways in regulating cell matrix interactions is not known. METHODS: Rat nucleus pulposus cells were cultured in hypoxia (2% O2) or normoxia (20% O2). Western blotting and kinase assay were used to analyze expression of MAPK signaling molecules. Cell attachment to collagen was studied using an adhesion assay, whereas flow cytometry and RT-PCR were performed to quantify integrin receptor expression. RESULTS: In a hypoxic environment (2% O2), rat nucleus pulposus cells showed a persistent phosphorylation of p38 and ERK proteins; pERK catalyzed the phosphorylation of Elk1-Gst fusion protein. When ERK activity was blocked, cell adhesion to Type II collagen, one of the major extracellular matrix proteins in the nucleus pulposus tissue, was impaired. A similar inhibitory effect on collagen adhesion was observed when nucleus pulposus cells were treated with an antibody to alpha2 integrin. Furthermore, when ERK activity was inhibited, there was a decrease in alpha2 integrin mRNA expression. In contrast to ERK, inhibition of p38 activity did not modulate alpha2 integrin subunit mRNA expression. Likewise, inhibition of ERK, but not p38, resulted in downregulation of nucleus pulposus alpha2 integrin protein levels and blocked cell survival in hypoxia. CONCLUSIONS: Hypoxia activated MAPK signaling pathway activity in nucleus pulposus cells. ERK, but not p38, regulated alpha2 integrin expression and cell survival.

Animals↗
PubMed2006

Horizontal saccade dynamics across the human life span.

PURPOSE: To investigate saccade dynamics as a function of age to determine whether they follow the pattern of development and decline predicted by Weale's model of aging. METHODS: One hundred ninety-five participants between the ages of 3 and 86 years made visually guided horizontal prosaccades ranging in size from 1 degrees to 60 degrees in response to dot stimuli. Eye movements were recorded binocularly with a video-based eye tracker, sampling at 120 Hz. Saccadic latency, accuracy, and velocity were measured and analyzed as a function of age. RESULTS: Mean saccadic latency decreased from 439 ms at 3 years to 172 ms at 14 years, followed by a period of relative stability to age 50 and finally, gradually increased to 264 ms at >or=80 years. For saccadic accuracy (amplitude gain), there was a statistically significant (P<0.05) interaction between saccade size and age. Participants made increasingly hypometric saccades as age and saccade size increased. Average age group saccadic asymptotic peak velocity (Vmax) increased during childhood from 446 deg/s at age 3, to a peak of 610 deg/s at 14 years and then gradually declined with age to approximately 345 deg/s for participants>or=80 years. CONCLUSIONS: Age affected saccadic latency, accuracy, and velocity. For each parameter there was a different pattern of development and decline probably related to the way in which the portion of the brain that controls each function develops and ages.

Adolescent↗
PubMed2005

The influence of the Internet on decision making in acoustic neuroma.

OBJECTIVE: To determine the access to and the use of the Internet by acoustic neuroma patients as a medical information source, and the influence of the Internet on decision-making, as well as the patients' views on the quality of particular sites. MATERIALS AND METHODS: A retrospective 27-item questionnaire was sent to 138 consecutive acoustic neuroma patients diagnosed between 1997 and 2002. The study included patients treated by conservative, radiotherapeutic and surgical modalities. MAIN OUTCOME MEASURES: Patient demographics, the extent of Internet use as well as quality and quantity of available information. RESULTS: There were 86.95 per cent questionnaires available for analysis. Twenty-four per cent accessed the Internet to obtain information about acoustic neuromas. Ninety-seven per cent of patients said that the information provided in the clinic matched with the information obtained from the websites, 49 per cent said that the information obtained from the Internet did not influence decision making regarding acceptance of treatment of their tumour. Some patients said the Internet information was depressing, devastating, and they would never look up the Internet again for medical information. CONCLUSION: A significant proportion of our patients accessed the Internet for information. Caution should be exercised when advising patients regarding websites as the information on the Internet is often not controlled or checked for accuracy. Acoustic neuroma specialists and ENT surgeons in general should familiarize themselves with related websites so that patients can then be directed to high-quality sites.

Attitude to Health↗
PubMed2006

Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial results of a novel optical biopsy technique.

BACKGROUND: Biopsy and polypectomy frequently are performed for lesions that carry a low risk of malignant transformation in the colon. Elastic scattering spectroscopy (ESS) is a novel optical biopsy technique that can distinguish, almost instantaneously, between normal and abnormal tissue in vivo, without the need to remove tissue. We assessed the diagnostic potential of ESS in the colon to differentiate normal colonic mucosa, chronic colitis, hyperplastic polyps, adenomatous polyps (with dysplasia), and adenocarcinoma. METHODS: ESS spectra were obtained from 138 sites in 45 patients at colonoscopy. They were then compared with conventional biopsy specimens taken from the same site, including normal colonic mucosa, hyperplastic polyps, adenomatous polyps, chronic colitis, and colon cancer. Spectral analysis was carried out with a validated computerized model that used principal component analysis followed by linear discriminant analysis. Cross validation was carried out by using 60% of the data as a "training set" and the remaining 40% of the data as a "test set." RESULTS: A total of 483 spectra were analyzed (290 normal, 19 hyperplastic, 69 adenomatous polyps, 74 chronic colitis, and 31 colorectal cancer). The sensitivity and the specificity of differentiating adenomas from hyperplastic polyps was 84% and 84%, respectively; for cancer from adenomatous polyps, 80% and 75%, respectively; for colitis from normal tissue, 77% and 82%, respectively; and for dysplastic mucosa (from polyps) from colitis, 85% and 88%, respectively. CONCLUSIONS: ESS holds promise for differentiating colonic lesions with good accuracy and, therefore, is a potentially useful tool to make an instantaneous diagnosis during colonoscopy. It could prove a valuable aid for targeting biopsies in dysplasia surveillance in inflammatory bowel disease and for deciding which small polyps should be removed.

Biopsy↗
PubMed2004

Decellularized vein as a potential scaffold for vascular tissue engineering.

PURPOSE: Current strategies to create small-diameter vascular grafts involve seeding biocompatible, compliant scaffolds with autologous vascular cells. Our purpose was to study the composition and strength of decellularized vein to determine its potential as a vascular tissue-engineering scaffold. METHODS: Intact human greater saphenous vein specimens were decellularized by using sodium dodecyl sulfate (SDS). Residual cellular and extracellular matrix composition was studied with light and electron microscopy as well as immunohistochemistry. Burst and suture-holding strength was measured in vitro by insufflation and pull-through techniques. To assess initial handling and durability of decellularized vein in vivo, a canine model was developed wherein decellularized canine jugular veins were implanted as carotid interposition grafts in recipient animals. After two weeks of arterial perfusion, these grafts were studied with duplex imaging and histologic methods. RESULTS: Human saphenous vein decellularized by using SDS was devoid of endothelial cells and >94% of the cells resident within the vein wall. Collagen morphology appeared unchanged, and elastin staining decreased only slightly. Basement membrane collagen type IV remained intact. Compared with fresh vein, decellularized vein had similar in vitro burst (2480 +/- 460 mm Hg vs 2380 +/- 620 mm Hg; P >.05) and suture-holding (185 +/- 30 gm vs 178 +/- 66 gm; P >.05) strength. Decellularized canine vein functioned well in vivo without dilation, anastomotic complication, or rupture over 2 weeks of arterial perfusion. CONCLUSIONS: Vein rendered acellular with SDS has well-preserved extracellular matrix, basement membrane structure, and strength sufficient for vascular grafting. These properties suggest proof of concept for its use as a scaffold for further vascular tissue engineering. CLINICAL RELEVANCE: The following research examines the creation of a new small-diameter bypass graft. It is clinically relevant to patients who need distal arterial bypass, coronary artery bypass, or hemodialysis access, but who do not have adequate autologous vein for their surgeries. Future investigations will involve further tissue engineering of this vascular scaffold (eg, autologous endothelial seeding of its lumen) and testing the clinical usefulness of the completed graft.

Antigens, Surface↗
PubMed2006

A survey of Canadian websites providing information about female urinary incontinence.

OBJECTIVE: Urinary incontinence (UI) is a prevalent health issue that has significant detrimental effects on quality of life. The Internet offers a unique vehicle for incontinent women to access information that could facilitate conservative self-help therapy. An evaluation of Canadian websites offering female UI information was conducted to determine their quality and readability. METHODS: We evaluated websites using published general quality criteria for health sites and a quality assessment tool compiled by the authors for specific UI information derived from published, peer-reviewed clinical practice guidelines. Three health care professionals reviewed sites for quality, Canadian content, and interactivity. The readability of health information was also evaluated. RESULTS: Fifty-six Canadian sites (18 professional, 22 organizational, 16 commercial) were evaluated. Significant agreement was found among the raters' evaluations on all measures. For all sites, the mean scores were general quality, 9/14; specific UI quality, 30/122; reading ease, 37/100; grade level, 10.9. The median score for Canadian content was high, but for interactivity it was low. The only significant difference between site types was for general quality (F [2,165]=3.38, P=0.036). Post hoc Tukey's tests showed a significant difference between organizational and commercial sites, with organizational sites having higher general quality. CONCLUSION: Canadian websites providing female UI information have moderately high general quality, low specific UI information quality, minimal interactivity, and more than minimal Canadian content. The reading level of most sites is too high for average consumers. A webliography of the best sites has been developed to guide patients.

Canada↗
PubMed1996

Serum HCV RNA levels assessed by quantitative NASBA: stability of viral load over time, and lack of correlation with liver disease. The Trent HCV Study Group.

BACKGROUND/AIMS: We used the hepatitis C virus quantitative NASBA technique to evaluate the stability of viral load within individuals with chronic hepatitis C, to determine the range of viraemic load between individuals, and to assess the usefulness of hepatitis C virus RNA quantitation in predicting the severity of underlying hepatitis C virus-induced liver disease. METHODS: Hepatitis C virus RNA was determined, using the quantitative NASBA assay, in multiple serum samples from 11 individuals with chronic hepatitis C over an average time period of 11 months (range = 3-23 months), and in single serum samples from a further 10 individuals. RESULTS: In 10/11 individuals the hepatitis C virus RNA titres were within one log10 copies/ml of each other during this time period. In the eleventh, there was a rise of 1.36 log10 copies/ml in two serum samples taken 8 months apart. The viraemic load varied by 2.79 log10 copies/ml serum between individuals. There were no correlations between mean RNA levels and total biopsy scores (either Knodell or Sheffield scores), or the individual components of the biopsy scoring systems, except the sinusoidal infiltration component of the Sheffield score. There was also no difference in viral RNA levels between those infected with type 1 as compared to type 3 virus, with a mean level in both groups of 7.2 log10 copies/ml. CONCLUSIONS: Hepatitis C virus serum RNA level is stable within individuals within the studied time period. Viral load varies between infected individuals but is not a useful prognostic indicator of the severity of virus-induced liver disease.

Adult↗
PubMed2001

Patient quality of life after successful restorative proctocolectomy is normal.

OBJECTIVE: To measure quality of life (QoL), using validated health status instruments, of patients with functioning IPAA for CUC. PATIENTS AND METHODS: Between 1986 and 1997, a total of 77 patients had an IPAA. Thirteen patients were excluded [6 excised, 3 awaiting ileostomy closure, 2 lost to follow up, 2 serious unrelated illnesses]. Postal survey using SF36 and EuroQol questionnaires. Age, sex, year of pouch construction and stool frequency were documented. RESULTS: Fifty-six patients (87.5%) replied. Male:female ratio; 3:2. Median age; 34 years (range 13-64). Median time since pouch construction; 4 years (range 1-10 years). Median SF36 scores (range); physical function 86.6 (0-100), physical role 81.6 (0-100), body pain 78.4 (22-100), general health 61.6 (5-100), vitality 57.6 (5-100), social function 75.4 (25-100), emotional role 83.5 (0-100), mental health 70.7 (16-100). All the SF36 scores were within the normal range, as were the EuroQol scores. Median EuroQol score (range); 0.85 (-0.07-1.0). Median EuroQol thermometer score (range); 83.3 (20-100). There was no correlation between objective QoL score and age, gender, stool frequency and year of pouch construction. CONCLUSION: The QoL for patients with a functioning IPAA for CUC measured using validated health status instruments is normal. Age, gender, stool frequency and year of construction do not affect QoL outcome after the IPAA for ulcerative colitis.

Journal Article↗
PubMed2006

Lung transplantation in patients 60 years and older: results, complications, and outcomes.

BACKGROUND: Advanced recipient age is reported to negatively affect survival after lung transplantation (LTX). We hypothesized that LTX in patients aged > or = 60 years could be performed with acceptable outcomes. METHODS: We identified 182 consecutive LTX recipients from 1995 to 2005. Outcomes were analyzed and survival compared with results in recipients aged < 60, as well as with United Network for Organ Sharing (UNOS) registry outcomes for the same age and study period. Actuarial survivals were calculated by the Kaplan-Meier method. RESULTS: During the study period, 29% (52/182) of LTX recipients were > or = 60 years old (range, 60 to 69 years). Median follow-up was 2.9 years (range, 0 to 10 years). All patients but one received a single lung. Indications included chronic obstructive pulmonary disease in 63% (33/52), idiopathic pulmonary fibrosis in 27% (14/52), and other in 10% (5/52). In-hospital mortality was 12% (6/52) for those aged > or = 60 compared with 7% (9/130) for those aged < 60 (p = NS). Complications included reoperation in 10% (5/52), requirement for extracorporeal membrane oxygenation in 6% (3/52), renal failure in 12% (6/52), and stroke in 4% (2/52). Actuarial survivals at 30 days, and 1, 3, and 5 years were 90% (82, 98), 86% (76, 96), 71% (56, 85), and 55% (37, 73), respectively. No significant difference in survival was observed between age cohorts for our institutional data by Kaplan-Meier analysis (p = 0.34) or by Cox proportional hazard model (p = 0.15). A significant survival advantage was noted for our institution compared with UNOS for this cohort (p = 0.018). CONCLUSIONS: In carefully selected recipients > or = 60 years of age, LTX offers acceptable outcomes and survival.

Adolescent↗
PubMed2006

Dissociated hypotropia: clinical features and surgical management of two cases.

BACKGROUND: Dissociated vertical deviation (DVD), which almost always shows a hypertropia of the affected eye, occasionally can manifest as a hypotropia, either unilaterally or bilaterally. Two patients are presented who had this rare variant of DVD, which has been termed "dissociated hypotropia," both of whom underwent surgery and had good outcomes. METHODS: Two patients, ages 13 and 14, with unilateral dissociated hypotropia underwent large inferior rectus muscle recessions on their affected eyes. In one case, a video-based eye tracker was used to record the dissociated hypotropic drifts in the eye to plot the changes in the drift amplitudes in response to increasing density filters over the fixating eye (Bielschowsky phenomenon) and to confirm whether the deviation changed in the light versus the dark. RESULTS: In case 1, the hypotropia drift measured up to 18(Delta), and it was reduced to zero with a 6 mm inferior rectus recession in the affected eye. In case 2, the drift measured up to 20(Delta). Eye movement recordings showed a time course of the downward drift that mirrored that of upward drift of hypertropic DVD and confirmed the presence of a Bielschowsky phenomenon. The drift amplitude did not change in bright versus dark conditions. An 8 mm inferior rectus recession on the affected eye reduced the hypotropia to 5(Delta). CONCLUSIONS: Dissociated hypotropia is a rare form of the dissociated strabismus complex. The downward drift has a time course similar to the upward drift of hypertropic DVD and shows the Bielschowsky phenomenon. It responds to a large inferior rectus muscle recession.

Adolescent↗
PubMed2006

Functional and cytoarchitectural spinal cord protection by ATL-146e after ischemia/reperfusion is mediated by adenosine receptor agonism.

BACKGROUND: ATL-146e protects the spinal cord from ischemia/reperfusion injury, presumably via adenosine A(2A) receptor activation, but this relationship remains unproven. We hypothesized that spinal cord functional and cytoarchitectural preservation from ATL-146e would be lost with simultaneous administration of the specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine A(2A) receptor activation is responsible for the protective effects of this compound. METHODS: New Zealand White rabbits underwent 45 minutes of infrarenal aortic cross-clamping. Groups (n = 10) included sham, ischemia, ischemia plus ATL-146e (ATL-146E), ischemia plus ZM, or ischemia with both compounds (agonist-antagonist). Tarlov scores were recorded every 12 hours. After 48 hours, the spinal cord was fixed for histology and microtubule-associated protein 2 immunohistochemistry. RESULTS: Tarlov scores at 48 hours were significantly better in the sham and ATL-146E groups (5.0 and 3.9, respectively) compared with the other three groups (all < or =1.3; P < .001). On hematoxylin and eosin, neuronal viability was higher in the sham, ATL-146E, and agonist-antagonist groups compared with the control and ZM groups (P < .05). Microtubule-associated protein 2 expression was preserved in the sham and ATL-146E groups but was lost in the ATL + ZM, ZM241385, and control groups. CONCLUSIONS: ATL-146e preserves the spinal cord in terms of both cytoarchitecture and function after reperfusion of the ischemic spinal cord, but this preservation is not completely blocked by competitive adenosine A(2A) receptor antagonism. Although ATL-146e does seem to partially function through activation of the adenosine A(2A) receptor, the neuroprotective mechanism may not be limited to this particular receptor.

Adenosine A2 Receptor Agonists↗
PubMed2005

Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi.

BACKGROUND: To assess the effects of human immunodeficiency virus (HIV) infection on susceptibility to malaria, we compared the incidence rates of malaria by HIV type 1 (HIV-1) serostatus, baseline blood HIV-1 RNA concentration, and baseline CD4 cell count, over the course of a malaria season. METHODS: We followed a cohort of 349 adults in Malawi. For the 224 HIV-1-seropositive adults (64% of the cohort), we measured HIV-1 RNA concentration (n=187) and CD4 cell count (n=184) at baseline. Parasitemia was defined as presence of asexual parasites on a thick film of blood and was treated with sulfadoxine/pyrimethamine (SP), in accordance with national policy. Hazard ratios (HRs) of parasitemia were estimated using Cox regression. Demographics were adjusted for. RESULTS: HIV-1 seropositivity was associated with parasitemia (adjusted HR, 1.8 [95% confidence interval {CI}, 1.2-2.7] for a first parasitemia episode; adjusted HR, 2.5 [95% CI, 1.5-4.2] for a second parasitemia episode [> 14 days after the first episode]; adjusted HR, 1.9 [95% CI, 1.4-2.6] for parasitemia overall). Treatment failure (parasitemia < or = 14 days after SP treatment) did not differ by HIV-1 serostatus (risk ratio, 1.3 [95% CI, 0.5-3.2]). HIV-1 RNA concentrations and CD4 cell counts were moderately but inconsistently associated with parasitemia. A high parasite density with fever was associated with HIV-1 seropositivity and low CD4 cell count. CONCLUSION: HIV-infected adults in malaria-endemic areas are at increased risk for malaria. Where possible, additional malaria prevention efforts should be targeted at this population.

Adolescent↗
PubMed2005

Nutritional and cognitive relationships and long-term mortality in patients with various dementia disorders.

BACKGROUND: Subjects with dementia are at risk for protein-energy malnutrition. OBJECTIVE: To study the nutritional status, the short-term effects of adapted nutritional routines and the long-term mortality in subjects admitted for evaluation of cognitive dysfunction. DESIGN: prospective observational study. SETTING: University Hospital. SUBJECTS: A total of 231 patients (80 +/- 7 years, 65% women). METHODS: Body mass index (BMI, kg/m2), serum concentrations of albumin, ferritin, vitamin B12, folic acid and haemoglobin as well as Mini-Mental State Examination (MMSE, 0-30 p) results and co-morbidity were recorded at hospital admittance and before discharge. Seven years later, mortality was registered. RESULTS: Mean BMI was in the normal range (23.3 +/- 4) as were the biochemical indices, and they did not vary among patients with Alzheimer's disease (AD), vascular dementia (VaD), mild cognitive impairment, mixed dementia and other diagnoses. A BMI of <23 was found in 108 (52%) subjects. Weight and MMSE score correlated weakly (r = 0.18, P < 0.01) at inclusion. During a median hospital stay of 3 weeks, an average weight gain of 0.5 +/- 1.8 kg (P < 0.001) and an increase in MMSE score of 0.9 +/- 3 (P < 0.001) was observed. However, these changes did not correlate. A BMI of <23 was associated with an increased risk for 7-year mortality (OR 3, 95% CI = 1.3-6.7), which was independent of age, male gender, dementia diagnosis and co-morbidity. CONCLUSIONS: Nutritional status did not vary in patients with various dementia diagnoses. A BMI of <23 was related to reduced 7-year survival, but this result was independent of co-morbidity, male gender and age.

Aged↗
PubMed2006

Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact.

PURPOSE: Pseudomonas aeruginosa infections have been associated with considerable morbidity and mortality. Fluoroquinolones (FQ) are the only oral therapy available for P. aeruginosa infections, but resistance is increasingly prevalent. METHODS: We examined annual trends in FQ-resistant P. aeruginosa (FQRPA) from 1991 to 2000. Subsequently, inpatients with a clinical culture positive for P. aeruginosa between January 1, 1999 and December 31, 2000 were included in a case control study to identify risk factors for FQ resistance and a cohort study to examine the impact of FQ resistance on outcomes in P. aeruginosa. RESULTS: Annual prevalence of FQRPA increased from 15% in 1991 to 41% in 2000 (P <0.001 trend). Between 1999 and 2000, 332 P. aeruginosa isolates were FQ resistant and 540 were FQ susceptible. Prior FQ use was the only independent risk factor for FQRPA (adjusted OR = 3.43; 95% confidence interval [CI] 2.37, 4.96). Subjects with FQRPA had greater median hospital charges (62,325 dollars vs 48,734 dollars) (P =.007) and higher mortality (47.5% vs 35.5%) (P =.004). However, in a multivariate model, only imipenem resistance of the isolate was significantly associated with mortality. FQ resistance was not an independent risk factor. CONCLUSIONS: FQRPA has increased significantly and is associated with prior FQ use. Limiting FQ use may curb the emergence of resistance among P. aeruginosa. FQRPA is associated with increased hospital charges, but other resistance patterns may have a more significant impact on mortality.

Academic Medical Centers↗
PubMed2006

Effect of random seed placement error in permanent transperineal prostate seed implant.

BACKGROUND AND PURPOSE: Random seed placement error may adversely effect dose distribution in transperineal prostate seed implants. In this study, we investigated the extent to which individual seed activity influences dose-distribution degradation due to random seed placement error. PATIENTS AND METHODS: Separate initial treatment plans were prepared for three prostate sizes, 27.3, 43.2 and 48.9 cc, using 0.35, 0.55 and 0.75 mCi iodine-125 seeds. All stated activities are understood to be apparent activities. The combinations produced a total of nine treatment plans. Each initial treatment plan was subjected to 1000 stochastic three-dimensional Gaussian perturbations of seed location, with a standard deviation of 4mm for a total of 9000 treatment plans. The resulting plans were evaluated for target coverage and urethra involvement. RESULTS: Satisfactory initial treatment plans were prepared for all prostate sizes and seed activities. All 9000 perturbed treatment plans showed acceptable target coverage under the D90/90 criterion. Some of the perturbed plans for the 27.3 and 43.2 cc prostates with 0.55 and 0.75 mCi seeds failed the V100/90 criterion. Some of the randomly perturbed seed distributions showed significantly increased doses to the urethra relative to the unperturbed treatment plan. This effect was more pronounced with greater seed activity. CONCLUSIONS: There may be a higher probability of unfavorable target coverage due to random seed placement error when performing transperineal iodine-125 prostate seed implants using seeds with activity greater than 0.35 mCi. There may also be a higher probability of unfavorable urethra involvement when using higher activity seeds.

Brachytherapy↗