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1.
Front Nutr ; 9: 921213, 2022.
Article in English | MEDLINE | ID: mdl-36211493

ABSTRACT

Background: Infection is associated with impaired nutritional status, especially for infants younger than 5 years. Objectives: We assessed the impact of infection indicated by both acute phase proteins (APP), C-reactive protein (CRP), and α-1-acid-glycoprotein (AGP), and as reported by maternal recall on the nutritional status of infants. Materials and methods: A total of 505 pregnant women were enrolled in a nested longitudinal cohort study of vitamin A (VA). Data from 385 children are reported here. The incidence and severity of respiratory infection and diarrhea (previous 14 days) were assessed by maternal recall; infant/child feeding practices were collected. Infant weight, recumbent length, and heel-prick capillary blood were taken at 9 months postpartum. Indicators of the VA status [retinol binding protein (RBP)], iron status (Hb, ferritin), and subclinical inflammation APP, CRP (>5 mg/L), and AGP (>1 g/L) were determined. Impacts of infection on the infant nutritional status were estimated using logistic regression models. Results: Infection prevalence, based on elevated CRP and AGP levels, was 36.7%. For diarrhea reported symptoms, 42.4% of infants at 9 months had no indication of infection as indicated by CRP and AGP; for acute respiratory reported symptoms, 42.6% had no indication of infection. There was a significant positive association with infection among VA-deficient (RBP < 0.83 µmol/L) infants based on maternal reported symptoms but not with iron deficiency (ferritin < 12 µg/L). The odds of having infection, based on increased CRP and AGP, in underweight infants was 3.7 times higher (OR: 3.7; 95% CI: 2.3, 4.5; P = 0.019). Infants with iron deficiency were less likely (OR: 0.40; 95% CI: 0.1, 0.7; P = 0.001) to have infection based on CRP and AGP, while infants with VA deficiency were five times more likely (OR: 5.06; 95% CI: 3.2, 7.1; P = 0.0001) to have infection. Conclusion: Acute phase proteins are more useful in defining infection in a population than reported symptoms of illness. Not controlling for inflammation in a population while assessing the nutritional status might result in inaccurate prevalence estimation.

2.
Osteoporos Int ; 29(3): 685-697, 2018 03.
Article in English | MEDLINE | ID: mdl-29260289

ABSTRACT

Abaloparatide, a novel PTH1 receptor agonist, increased bone formation in osteopenic ovariectomized cynomolgus monkeys while increasing cortical and trabecular bone mass. Abaloparatide increased bone strength and maintained or enhanced bone mass-strength relationships, indicating preserved or improved bone quality. INTRODUCTION: Abaloparatide is a selective PTH1R activator that is approved for the treatment of postmenopausal osteoporosis. The effects of 16 months of abaloparatide administration on bone formation, resorption, density, and strength were assessed in adult ovariectomized (OVX) cynomolgus monkeys (cynos). METHODS: Sixty-five 9-18-year-old female cynos underwent OVX surgery, and 15 similar cynos underwent sham surgery. After a 9-month period without treatments, OVX cynos were allocated to four groups that received 16 months of daily s.c. injections with either vehicle (n = 17) or abaloparatide (0.2, 1, or 5 µg/kg/day; n = 16/dose level), while Sham controls received s.c. vehicle (n = 15). Bone densitometry (DXA, pQCT, micro-CT), qualitative bone histology, serum calcium, bone turnover markers, bone histomorphometry, and bone strength were among the key measures assessed. RESULTS: At the end of the 9-month post-surgical bone depletion period, just prior to the treatment phase, the OVX groups exhibited increased bone turnover markers and decreased bone mass compared with sham controls. Abaloparatide administration to OVX cynos led to increased bone formation parameters, including serum P1NP and endocortical bone formation rate. Abaloparatide administration did not influence serum calcium levels, bone resorption markers, cortical porosity, or eroded surfaces. Abaloparatide increased bone mass at the whole body, lumbar spine, tibial diaphysis, femoral neck, and femoral trochanter. Abaloparatide administration was associated with greater lumbar vertebral strength, and had no adverse effects on bone mass-strength relationships for the vertebrae, femoral neck, femoral diaphysis, or humeral cortical beams. CONCLUSIONS: Abaloparatide administration was associated with increases in bone formation, bone mass and bone strength, and with maintenance of bone quality in OVX cynos, without increases in serum calcium or bone resorption parameters.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Resorption/prevention & control , Osteogenesis/drug effects , Parathyroid Hormone-Related Protein/therapeutic use , Absorptiometry, Photon/methods , Animals , Biomarkers/blood , Bone Density/drug effects , Bone Density/physiology , Bone Density Conservation Agents/pharmacology , Bone Resorption/physiopathology , Female , Lumbar Vertebrae/physiopathology , Macaca fascicularis , Osteogenesis/physiology , Ovariectomy , Parathyroid Hormone-Related Protein/pharmacology , Peptide Fragments/blood , Procollagen/blood , Receptor, Parathyroid Hormone, Type 1/agonists , X-Ray Microtomography/methods
3.
Strahlenther Onkol ; 192(3): 182-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26713323

ABSTRACT

BACKGROUND AND PURPOSE: For localized prostate cancer, treatment options include external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT). Erectile dysfunction (ED) is a common side-effect. Our aim was to evaluate penile erectile function (EF) before and after BT, EBRT, or RP using a validated self-administered quality-of-life survey from a prospective registry. MATERIAL AND METHODS: Analysis included 478 patients undergoing RP (n = 252), EBRT (n = 91), and BT (n = 135) with at least 1 year of follow-up and EF documented using IIEF-5 scores at baseline, 6 weeks, 6 months, 1 year, and annually thereafter. RESULTS: Differences among treatments were most pronounced among patients with no or mild initial ED (IIEF-5 ≥ 17). Overall, corrected for baseline EF and age, BT was associated with higher IIEF-5 scores than RP (+ 7.8 IIEF-5 score) or EBRT (+ 3.1 IIEF-5 score). EBRT was associated with better IIEF-5 scores than RP (+ 4.7 IIEF-5 score). In patients undergoing EBRT or RP with bilateral nerve sparing (NS), recovery of EF was observed and during follow-up, the differences to BT were not statistically significant. Overall age had a negative impact on EF preservation (corrected for baseline IIEF). CONCLUSION: In our series, EF was adversely affected by each treatment modality. Considered overall, BT provided the best EF preservation in comparison to EBRT or RP.


Subject(s)
Brachytherapy/statistics & numerical data , Erectile Dysfunction/epidemiology , Prostatectomy/statistics & numerical data , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/therapy , Radiotherapy, Conformal/statistics & numerical data , Adult , Age Distribution , Aged , Aged, 80 and over , Causality , Comorbidity , Erectile Dysfunction/prevention & control , Germany/epidemiology , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Radiation Injuries/epidemiology , Retrospective Studies , Risk Factors , Treatment Outcome
4.
Eur Arch Otorhinolaryngol ; 273(7): 1841-8, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26059208

ABSTRACT

The aim of the study was to assess regional control and survival in primary irradiated oropharyngeal cancer patients with advanced neck disease (≥cN2a) receiving planned neck dissection (PND) irrespective of the nodal response compared to salvage neck dissection (SND) in case of regional persistence or reccurence in relation to tumoral p16 overexpression. 96 consecutive patients treated at the University Hospital of Zurich, Switzerland were included. Tissue microarray-based scoring of p16 expression was obtained. 5 years overall (OS) and disease-specific survival (DSS) in the PND and SND cohort were 70 vs. 57 % (p = 0.20) and 80 vs. 65 % (p = 0.14), respectively. Regional control in PND and SND achieved 95 vs. 87 % (p = 0.29), respectively. There was no statistically significant impact of neck treatment (PND vs. SND) on regional control or survival among patients with p16-negative tumors (5 years OS 59 vs. 50 %, p = 0.66; 5 years DSS 59 vs. 57 %, p = 0.89) nor among patients with p16-positive tumors (5 years OS 84 vs. 67 %, p = 0.21; 5 years DSS 95 vs. 81 %, p = 0.24). The type of neck dissection after primary intensity-modulated radiotherapy (IMRT) had no impact on regional control and survival even in human papillomavirus (HPV)-associated disease. Therefore we are convinced that based on the accuracy of newer diagnostic modalities the surveillance of a radiologically negative neck after primary chemoradiation (CRT) is oncologically safe irrespective of p16 expression of the tumor.


Subject(s)
Carcinoma, Squamous Cell/therapy , Cyclin-Dependent Kinase Inhibitor p16/genetics , Gene Expression Regulation, Neoplastic , Neck Dissection/methods , Neoplasm Staging , Oropharyngeal Neoplasms/therapy , RNA, Neoplasm/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/secondary , Chemoradiotherapy , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/pathology , Radiotherapy, Intensity-Modulated , Survival Rate/trends , Switzerland/epidemiology
5.
Clin Rheumatol ; 34(1): 51-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25024096

ABSTRACT

New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of rheumatoid arthritis (RA) have recently been proposed. The aim of this cohort study was to examine whether fulfilling these 2010 ACR/EULAR criteria at the first visit has an impact on the clinical course and on the radiographic progression of the disease. For this observational cohort study, we included patients from the Swiss RA registry SCQM with early RA or undifferentiated arthritis (UA, disease duration ≤1 year), as defined by the treating rheumatologist, who had not received any previous disease modifying anti-rheumatic drugs (DMARDs). Patients were categorized into two groups depending on whether or not they fulfilled the 2010 ACR/EULAR criteria (≥6 points vs <6 points) at the first visit. The primary outcome measures were the evolution of the DAS 28 and of radiographic erosions as measured by the Ratingen score over time. Of the 592 patients fulfilling the inclusion criteria, 352 satisfied the 2010 ACR/EULAR criteria at baseline, whereas 240 were not classifiable as definite RA. The ACR/EULAR criteria scores correlated with disease activity at disease onset (R (2) = 0.31). DMARD treatment was subsequently initiated in all patients, mostly with methotrexate (MTX). There were no significant differences in the therapeutic strategies between patients fulfilling or not fulfilling the classification criteria. Six months after inclusion, patients fulfilling the ACR/EULAR criteria developed a 39.1 % reduction of DAS 28 scores, as compared to a 33.6 % reduction in patients not fulfilling the ACR/EULAR criteria (p = 0.0002), independently of their respective treatment strategy. Importantly, the DAS 28 scores were higher in those patients fulfilling the ACR/EULAR criteria (ACR/EULAR positive patients) throughout the observation, as compared to patients not fulfilling those (ACR/EULAR negative patients). Average radiographic progression was higher among ACR/EULAR positive than negative patients (progression of Ratingen score/year 0.50 vs 0.32, resp., p = 0.03) after 3 years of follow-up. Among early RA/UA patients, a score of the 2010 ACR/EULAR criteria sufficient to classify RA selects patients with worse clinical outcome and more radiographic progression.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Adult , Aged , Cohort Studies , Disease Progression , Female , Humans , Male , Middle Aged , Prospective Studies , Radiography , Rheumatology , Severity of Illness Index , Treatment Outcome
6.
HNO ; 62(8): 575-81, 2014 Aug.
Article in German | MEDLINE | ID: mdl-24906340

ABSTRACT

BACKGROUND: Anterior cervical spine surgery is a common procedure for fusions and/or discectomies. Postoperative dysphonia and dysphagia are known complications. In this study, we examined the frequency and outcomes of these complications in this patient population. MATERIALS AND METHODS: Patients planned to receive anterior cervical spine surgery between 01.03.2010 and 28.02.2011 at the Department of Neurosurgery, St. Gallen were prospectively included. Patients were evaluated using laryngoscopy, fiberoptic endoscopic evaluation of swallowing (FEES), voice field measurements and validated questionnaires. RESULTS: From the 53 patients included in the study, 40 had at least one complete follow-up examination. The frequency of postoperative dysphonia due to recurrent nerve palsy was 4/40 (10 %), although this was temporary in 3 patients. FEES revealed a pathological result in 18.9 % of patients. Postoperative Swallowing Quality of Life Questionnaire (Swal-QoL) scores were significantly lower. CONCLUSION: At a frequency of 10 %, dysphonia due to recurrent nerve palsy is a relevant complication in cervical spine surgery, albeit temporary in most cases. Postoperative dysphagia is common and should be evaluated and treated during follow-up.


Subject(s)
Cervical Vertebrae/surgery , Deglutition Disorders/etiology , Dysphonia/etiology , Laminectomy/adverse effects , Peripheral Nervous System Diseases/etiology , Adult , Aged , Deglutition Disorders/diagnosis , Dysphonia/diagnosis , Female , Humans , Male , Middle Aged , Peripheral Nervous System Diseases/diagnosis , Treatment Outcome
7.
Br J Cancer ; 110(10): 2420-6, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24736584

ABSTRACT

BACKGROUND: There are neither prospective data nor agreement on the optimal routine follow-up procedures in patients treated for soft tissue sarcoma of the limb. METHODS: Data on 174 consecutive patients with a soft tissue sarcoma of the limb undergoing follow-up by oncologists at a single centre from 2003 to 2009 were included in this analysis. The rate and site of recurrence and mode of detection were analysed. Outcome of the patients was assessed. RESULTS: Eighty-two patients (47%) experienced relapse of any type. Isolated local recurrence occurred in 26 patients and local relapse with synchronous pulmonary metastases in five patients. Local recurrences were detected clinically in 30 of these 31 patients; magnetic resonance imaging identified only one local recurrence. Twenty-eight patients developed isolated lung metastases; in nine patients these were amenable to resections, seven of whom are currently free of disease after treatment. Lung metastases were detected by chest x-ray (CXR) in 19 patients, computed tomography scanning in 3 patients, and clinically in 11 patients. Twenty-three patients developed non-pulmonary metastases. More than 80% of relapses occurred in the first 2 years of follow-up; however, later recurrences were also observed. CONCLUSIONS: Routine follow-up CXR can detect lung metastases suitable for surgical resection, although the optimal interval of imaging has yet to be defined. Local relapse is almost always detected by patients or physicians, and routine scanning of the primary site is of doubtful benefit. Patient and physician education to detect local relapse may be helpful. Prospective evaluation of follow-up is recommended.


Subject(s)
Extremities/pathology , Sarcoma/epidemiology , Soft Tissue Neoplasms/epidemiology , Adolescent , Adult , Aged , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Extremities/surgery , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Radiotherapy, Adjuvant , Retrospective Studies , Sarcoma/secondary , Sarcoma/therapy , Soft Tissue Neoplasms/therapy , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
8.
AIDS ; 27(13): 2163-6, 2013 Aug 24.
Article in English | MEDLINE | ID: mdl-23842136

ABSTRACT

We evaluated the University of North Carolina-Malawi Risk Screening Score (UMRSS) for detection of acute and early HIV-1 infection (AEHI) in a cohort of Kenyan MSM with approximately 8% annual HIV-1 incidence. Three components of the UMRSS (fever, diarrhea, and discordant rapid HIV tests) were also independent predictors of AEHI in our cohort. The predictive ability (area under the receiver operating characteristic curve, AUC) of the UMRSS was 0.79. A cohort-derived risk score consisting of six characteristics (fever, diarrhea, discordant rapid HIV tests, fatigue, age <30 years, and symptomatic sexually transmitted disease) had a higher AUC of 0.85. Screening for AEHI will have substantial transmission prevention benefits.


Subject(s)
HIV Infections/diagnosis , Homosexuality, Male , Adult , Area Under Curve , Cohort Studies , Female , HIV Infections/transmission , HIV Infections/virology , HIV-1/isolation & purification , Humans , Kenya , Male , Predictive Value of Tests , Risk Assessment/methods , Young Adult
9.
AIDS Behav ; 17(4): 1255-65, 2013 May.
Article in English | MEDLINE | ID: mdl-23494223

ABSTRACT

African men who have sex with men (MSM) face significant stigma and barriers to care. We investigated antiretroviral therapy (ART) adherence among high-risk adults, including MSM, participating in a clinic-based cohort. Survival analysis was used to compare attrition across patient groups. Differences in adherence, weight gain, and CD4 counts after ART initiation were assessed. Among 250 HIV-1-seropositive adults, including 108 MSM, 15 heterosexual men, and 127 women, patient group was not associated with attrition. Among 58 participants who were followed on ART, 40 % of MSM had less than 95 % adherence, versus 28.6 % of heterosexual men and 11.5 % of women. Although MSM gained less weight after ART initiation than women (adjusted difference -3.5 kg/year), CD4 counts did not differ. More data are needed on barriers to adherence and clinical outcomes among African MSM, to ensure that MSM can access care and derive treatment and prevention benefits from ART.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Heterosexuality/psychology , Homosexuality, Male/psychology , Medication Adherence/psychology , Risk-Taking , Adolescent , Adult , Black People/psychology , Black People/statistics & numerical data , CD4 Lymphocyte Count , Follow-Up Studies , HIV Infections/prevention & control , HIV Infections/psychology , HIV-1 , Heterosexuality/ethnology , Homosexuality, Male/statistics & numerical data , Humans , Kenya , Lost to Follow-Up , Male , Middle Aged , Prospective Studies , Risk Factors , Sex Workers/psychology , Sex Workers/statistics & numerical data , Social Stigma , Socioeconomic Factors , Surveys and Questionnaires , Treatment Outcome , Young Adult
10.
Gene Ther ; 20(4): 386-95, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22739387

ABSTRACT

The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFNγ. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector- and central memory T cells specifically recognized NY-ESO-1(157-165)/ HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo.


Subject(s)
Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/immunology , Immunotherapy , Multiple Myeloma/therapy , Neoplasm Proteins/immunology , Peptide Fragments/immunology , Receptors, Antigen, T-Cell/immunology , Animals , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/transplantation , Cell Line, Tumor , Genetic Therapy , Humans , Immunologic Memory , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-2/genetics , Interleukin-2/metabolism , Mice , Multiple Myeloma/immunology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Peptide Fragments/genetics , Peptide Fragments/metabolism , Receptors, Antigen, T-Cell/genetics , Receptors, CCR7/genetics , Receptors, CCR7/metabolism , Transduction, Genetic
11.
AIDS ; 27(3): 437-46, 2013 Jan 28.
Article in English | MEDLINE | ID: mdl-23079811

ABSTRACT

BACKGROUND: HIV-1 incidence estimates and correlates of HIV-1 acquisition in African MSM are largely unknown. METHODS: Since 2005, HIV-1-uninfected men who reported sex with men and women (MSMW) or sex with men exclusively (MSME) were followed at scheduled visits for collection of behavioural and clinical examination data and plasma for HIV-1 testing. Urethral or rectal secretions were collected from symptomatic men to screen for gonorrhoea. Poisson regression methods were used to estimate adjusted incidence rate ratios to explore associations between risk factors and incident HIV-1 infection. Plasma viral loads (PVLs) were assessed over 2 years following seroconversion. RESULTS: Overall HIV-1 incidence in 449 men was 8.6 [95% confidence interval (CI) 6.7-11.0] per 100 person-years. Incidence was 5.8 (95% CI 4.2-7.9) per 100 person-years among MSMW, and 35.2 (95% CI 23.8-52.1) per 100 person-years among MSME. Unprotected sex, receptive anal intercourse, exclusive sex with men, group sex, and gonorrhoea in the past 6 months were strongly associated with HIV-1 acquisition, adjusted for confounders. PVL in seroconverters was more than 4 log10 copies/ml at 230 (73.4%) of 313 visits in MSMW and 153 (75.0%) of 204 visits in MSME. CONCLUSION: HIV-1 incidence is very high among MSM in coastal Kenya, and many seroconverters maintain high PVL for up to 2 years after infection. Effective HIV-1 prevention interventions, including treatment as prevention, are urgently needed in this population.


Subject(s)
Condoms/statistics & numerical data , Gonorrhea/epidemiology , HIV Seropositivity/epidemiology , HIV-1 , Herpes Genitalis/epidemiology , Homosexuality, Male , Sexual Behavior/statistics & numerical data , Viral Load , Adolescent , Adult , Counseling , Gonorrhea/prevention & control , HIV Seropositivity/psychology , HIV Seropositivity/transmission , HIV-1/isolation & purification , Health Knowledge, Attitudes, Practice , Herpes Genitalis/prevention & control , Humans , Incidence , Kenya/epidemiology , Male , Needs Assessment , Prospective Studies , Risk Factors , Sexual Behavior/psychology , Social Stigma
12.
J Acquir Immune Defic Syndr ; 59(2): 185-93, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-22227488

ABSTRACT

OBJECTIVE: To identify and describe populations at risk for HIV in 3 clinical research centers in Kenya and South Africa. DESIGN: Prospective cohort study. METHODS: Volunteers reporting recent sexual activity, multiple partners, transactional sex, sex with an HIV-positive partner, or, if male, sex with men (MSM; in Kenya only) were enrolled. Sexually active minors were enrolled in South Africa only. Risk behavior, HIV testing, and clinical data were obtained at follow-up visits. RESULTS: From 2005 to 2008, 3023 volunteers were screened, 2113 enrolled, and 1834 contributed data on HIV incidence. MSM had the highest HIV incidence rate of 6.8 cases per 100 person-years [95% confidence interval (CI): 4.9 to 9.2] followed by women in Kilifi and Cape Town (2.7 cases per 100 person-years, 95% CI: 1.7 to 4.2). No seroconversions were observed in Nairobi women or men in Nairobi or Cape Town who were not MSM. In 327 MSM, predictors of HIV acquisition included report of genital ulcer (Hazard Ratio: 4.5, 95% CI: 1.7 to 11.6), not completing secondary school education (HR: 3.4, 95% CI: 1.6 to 7.2) and reporting receptive anal intercourse (HR: 8.2, 95% CI: 2.7 to 25.0). Paying for sex was inversely associated with HIV infection (HR: 0.2, 95% CI: 0.04 to 0.8). 279 (13.0%) volunteers did not return after the first visit; subsequent attrition rates ranged from 10.4 to 21.8 volunteers per 100 person-years across clinical research centers. CONCLUSIONS: Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials.


Subject(s)
HIV Infections/epidemiology , Homosexuality, Male , Risk-Taking , Sex Work , Adolescent , Adult , Aged , Female , Humans , Incidence , Kenya/epidemiology , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors , Sexual Behavior , South Africa/epidemiology , Young Adult
13.
AIDS ; 25(9): 1219-24, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21505300

ABSTRACT

BACKGROUND: Acute HIV-1 infection (AHI) may present with symptoms for which urgent healthcare is sought. However, little is known about healthcare seeking around the time of HIV-1 seroconversion in sub-Saharan Africa. METHODS: Review of clinical, counselling, treatment and laboratory records of previously HIV-1 seronegative at-risk adults, followed at monthly or 3-monthly visits, who seroconverted and enrolled in an AHI cohort. All HIV-seronegative plasma samples were tested for p24 antigen (p24) and stored preseroconversion samples for HIV-1 RNA (RNA). Factors associated with malaria treatment while acquiring HIV-1 were evaluated in multiple logistic regression. RESULTS: Sixty men and 12 women (95% of 75 seroconverters) were evaluated, including 43 (60%) with either p24-positive or RNA-positive or HIV-1 discordant rapid antibodies prior to seroconversion. Prior to diagnosis, 54 patients (75%) reported fever and 50 (69%) sought urgent care for symptomatic illness, including 23 (32%) who sought care in a nonresearch setting. Twenty-nine patients (40%) received presumptive malaria treatment. Only 24% of febrile patients were tested for malaria parasites. All documented smear results were negative. Malaria treatment was strongly associated with fever [adjusted odds ratio (aOR): 46, 95% confidence interval (CI): 3-725] and nonresearch setting (aOR: 5, 95% CI: 3-64). AHI was suspected in six (12%) patients who presented for urgent care during research evaluation. CONCLUSIONS: The majority of adults with AHI seek urgent healthcare. These individuals are often presumptively treated for malaria. Improved recognition of AHI in adults presenting for care may offer opportunities for optimizing HIV prevention strategies.


Subject(s)
Antimalarials/therapeutic use , Fever/drug therapy , HIV Seropositivity/drug therapy , HIV-1/drug effects , Adolescent , Adult , Female , Fever/diagnosis , Fever/immunology , HIV Seropositivity/diagnosis , HIV Seropositivity/immunology , Health Care Surveys , Homosexuality/statistics & numerical data , Humans , Kenya/epidemiology , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Prospective Studies , Sex Work/statistics & numerical data , Treatment Outcome , Young Adult
14.
Burns ; 37(6): 1010-4, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21470779

ABSTRACT

Function of the skin lymphatics as well as blood perfusion of a meshed transplant is crucial for the healing. The lymphatic regeneration and arterial perfusion of skin transplants after severe burns of the extremities had been studied in eight patients by microlymphography, laser doppler perfusion imaging and transcutaneous oxygen pressure measurements 1, 6 and 18 months after transplantation. One month after transplantation, only fragmented as well as many giant lymphatic skin vessels were present in the transplant. After 6 months a normal lymphatic network had developed in all grafts. The extension of the dye in the lymphatics decreased from 4.5 (0-16) at 1 month to 3.0 (1-6) mm after 18 months, indicating improved lymph drainage capacity. The permeability of the lymphatics in the graft was normal. After 1 month, median laser flux in the transplant was 155.6% (105-246%) of the normal skin but it normalised within 18 months. By contrast, transcutaneous oxygen measurement (TcPO(2)) increased from 44 (21-47) to 55 (50-76) mmHg. In meshed transplants used to cover severely burned skin morphological and functional normal lymphatics develop within 6 months and the initially increased laser flux due to inflammatory reaction normalises. Our results provide important insights into the healing process of skin transplants after burn.


Subject(s)
Burns/physiopathology , Lymphatic Vessels/physiology , Microvessels/physiology , Regeneration/physiology , Skin/anatomy & histology , Adult , Aged , Blood Gas Monitoring, Transcutaneous , Burns/diagnostic imaging , Burns/surgery , Female , Humans , Laser-Doppler Flowmetry , Lymphography/methods , Male , Microcirculation/physiology , Middle Aged , Perfusion Imaging/methods , Prospective Studies , Skin/blood supply , Skin Transplantation/methods , Wound Healing/physiology
15.
Ann Surg Oncol ; 18(7): 1924-31, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21207165

ABSTRACT

BACKGROUND: An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI). METHODS: Twenty-three patients who were pretreated with systemic (immuno)chemotherapy received FUDR-HAI alone or combined with systemic chemotherapy. We reviewed patient charts and our prospective patient database for survival and associated risk factors. RESULTS: Patients received FUDR-HAI for unresectable CRLM from January 2000 to September 2010. Twelve patients (52%) received concurrent systemic chemotherapy. Median overall survival (OS), progression-free survival (PFS), and hepatic PFS were 15.6 months (range, 2.5-55.7 months), 3.9 months (range, 0.7-55.7 months), and 5.5 months (range, 1.6-55.7 months), respectively. The liver resection rate after HAI was 35%. PFS was better in patients undergoing secondary resection than in patients without resection (hazard ratio [HR] 0.21; 95% confidence interval [95% CI] 0.07-0.66; P = 0.0034), while OS showed a trend toward improvement (HR 0.4; 95% CI 0.13-1.2; P = 0.09). No differences were observed in OS (P = 0.69) or PFS (P = 0.086) in patients who received FUDR-HAI alone compared with patients treated with combined regional and systemic chemotherapy. No statistically significant differences were seen in patients previously treated with one chemotherapy line compared with patients treated with two lines. Presence of extrahepatic disease was a negative risk factor for PFS (liver-only disease: HR 0.03; 95% CI 0.0032-0.28; P < 0.0001). Toxicities were manageable with dose modifications and supportive measures. CONCLUSIONS: FUDR-HAI improves PFS and results in a trend toward improved OS in selected patients able to undergo liver resection after tumor is downsized.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Hepatic Artery , Infusions, Intra-Arterial , Liver Neoplasms/drug therapy , Adult , Aged , Cohort Studies , Colorectal Neoplasms/pathology , Female , Floxuridine/administration & dosage , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Leucovorin/administration & dosage , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prospective Studies , Retrospective Studies , Survival Rate , Treatment Outcome
16.
Ann Oncol ; 21(8): 1694-1698, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20139151

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy. PATIENTS AND METHODS: DLBCL patients receiving FDG-PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence. RESULTS: Seventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041). CONCLUSIONS: FDG-PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG-PET/CT during follow-up is indicated for patients <60 years with clinical signs of relapse and in patients >60 years with and without clinical signs of relapse.


Subject(s)
Antineoplastic Agents/therapeutic use , Fluorodeoxyglucose F18 , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Risk Factors
17.
AIDS ; 21(18): 2513-20, 2007 Nov 30.
Article in English | MEDLINE | ID: mdl-18025888

ABSTRACT

BACKGROUND: The role of homosexuality and anal sex practices in the African HIV -1 epidemic is not well described. We aimed to assess the risk factors for prevalent HIV-1 infection among men who have sex with men (MSM) to guide HIV-1 prevention efforts. METHODS: Socio-behavioural characteristics, signs and symptoms of sexually transmitted diseases (STD), and serological evidence of HIV-1 were determined for 285 MSM at enrolment into a vaccine preparedness cohort study. We used multivariate logistic regression to assess risk factors for prevalent HIV-1 infection. RESULTS: HIV-1 prevalence was 43.0% [49/114, 95% confidence interval (CI), 34-52%] for men who reported sex with men exclusively (MSME), and 12.3% (21/171, 95% CI, 7-17%) for men who reported sex with both men and women (MSMW). Eighty-six (75%) MSME and 69 (40%) MSMW reported recent receptive anal sex. Among 174 MSM sexually active in the last week, 44% reported no use of condoms with casual partners. In the previous 3 months, 210 MSM (74%) reported payment for sex, and most clients (93%) were local residents. Prevalent HIV-1 infection was associated with recent receptive anal sex [odds ratio (OR), 6.1; 95% CI, 2.4-16], exclusive sex with men (OR, 6.3; 95% CI, 2.3-17), and increasing age (OR, 1.1 per year; 95% CI, 1.04-1.12). Only four MSM reported injecting drug use. CONCLUSIONS: The high prevalence of HIV-1 in Kenyan MSM is probably attributable to unprotected receptive anal sex. There is an urgent need for HIV-1 prevention programmes to deliver targeted risk-reduction interventions and STD services to MSM in Kenya.


Subject(s)
HIV Infections/transmission , HIV-1 , Homosexuality, Male , Adolescent , Adult , Anal Canal , Condoms/statistics & numerical data , Epidemiologic Methods , Female , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Kenya/epidemiology , Male , Risk-Taking , Sex Work/statistics & numerical data , Sexually Transmitted Diseases/epidemiology , Substance Abuse, Intravenous/complications , Unsafe Sex/statistics & numerical data
18.
Nature ; 410(6831): 910-3, 2001 Apr 19.
Article in English | MEDLINE | ID: mdl-11309611

ABSTRACT

Fuel cells are attractive alternatives to combustion engines for electrical power generation because of their very high efficiencies and low pollution levels. Polymer electrolyte membrane fuel cells are generally considered to be the most viable approach for mobile applications. However, these membranes require humid operating conditions, which limit the temperature of operation to less than 100 degrees C; they are also permeable to methanol and hydrogen, which lowers fuel efficiency. Solid, inorganic, acid compounds (or simply, solid acids) such as CsHSO4 and Rb3H(SeO4)2 have been widely studied because of their high proton conductivities and phase-transition behaviour. For fuel-cell applications they offer the advantages of anhydrous proton transport and high-temperature stability (up to 250 degrees C). Until now, however, solid acids have not been considered viable fuel-cell electrolyte alternatives owing to their solubility in water and extreme ductility at raised temperatures (above approximately 125 degrees C). Here we show that a cell made of a CsHSO4 electrolyte membrane (about 1.5 mm thick) operating at 150-160 degrees C in a H2/O2 configuration exhibits promising electrochemical performances: open circuit voltages of 1.11 V and current densities of 44 mA cm-2 at short circuit. Moreover, the solid-acid properties were not affected by exposure to humid atmospheres. Although these initial results show promise for applications, the use of solid acids in fuel cells will require the development of fabrication techniques to reduce electrolyte thickness, and an assessment of possible sulphur reduction following prolonged exposure to hydrogen.

19.
Acta Crystallogr B ; 56 ( Pt 5): 773-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11006552

ABSTRACT

Hydrothermal investigations in the high-silica region of the K(2)O-Nd(2)O(3)-SiO(2) system, carried out in a search for novel fast-ion conductors (FICs), yielded the new compound tripotassium neodymium heptasilicate, K(3)NdSi(7)O(17). Single-crystal X-ray methods revealed that K(3)NdSi(7)O(17) crystallizes in space group P3, has lattice constants a = 16.131 (2) and c = 7.7146 (19) A, Z = 4, and 22 atoms in the asymmetric unit. Refinement was carried out to a residual, R(F), of 0.0253 and a weighted residual, wR(F(2)), of 0.0702 using anisotropic displacement parameters for all atoms. The silicate anion forms an interrupted framework, within which both Nd octahedra and K polyhedra are situated. The structure is unusual in that it contains a symmetry-constrained Si-O-Si bond angle of 180 degrees. No isomorphs to K(3)NdSi(7)O(17) are known.

20.
Eur Respir J ; 13(5): 961-9, 1999 May.
Article in English | MEDLINE | ID: mdl-10414390

ABSTRACT

Eosinophils are recruited to the airways during allergic reactions, but animal models have shown that their mere presence is not sufficient for the development of bronchopulmonary hyperreactivity. Other factors, such as immunoglobulin (Ig)E, seem to be required. Using mice selected for the production of large amounts of IgE, the effects of antibody neutralization of IgE on antigen-induced lung recruitment of eosinophils and induction of bronchopulmonary hyperreactivity and of other indicators of inflammation were studied. A monoclonal non-anaphylactogenic rat anti-mouse IgE (mAb1-5), given within 24 h of the challenge with antigen, reduced tissue eosinophilia, the recruitment of IgE-bearing cells identified as basophils, mucous cell metaplasia, anaphylactic bronchoconstriction and bronchopulmonary hyperreactivity. mAb1-5 inhibited interleukin (IL)4 titres in the bronchoalveolar lavage fluid, but not those of I1-5. Inhibition by mAb1-5 may result from competitive displacement of immunoglobulin E from its different receptors, thus preventing cell stimulation. Moreover, the inhibition of the massive recruitment of immunoglobulin E-bearing basophils into the lungs within hours after challenge and of interleukin4 production by mAb1-5 may be important factors leading to the reduction of pulmonary eosinophilia and bronchopulmonary hyperreactivity. Thus, immunoglobulin (Ig)E and allergic IgE-bearing cells seem to play an essential role in the initial development of the late allergic airway responses.


Subject(s)
Antibodies, Anti-Idiotypic/immunology , Antibodies, Monoclonal/pharmacology , Asthma/immunology , Bronchial Hyperreactivity/immunology , Immunoglobulin E/immunology , Animals , Antibodies, Anti-Idiotypic/pharmacology , Asthma/physiopathology , Basophils/immunology , Bronchial Hyperreactivity/physiopathology , Eosinophils/immunology , Immunoglobulin E/physiology , Lung/immunology , Lung/physiopathology , Mice , Mice, Inbred BALB C , Mice, Inbred Strains , Ovalbumin/immunology , Rats , Time Factors
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