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1.
J Clin Med ; 12(16)2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37629244

ABSTRACT

To develop effective dementia prevention strategies, it is necessary to understand risk factors, associated factors and early signs of dementia. Subjective cognitive decline (SCD) is the earliest form of dementia. The aim of this study is to assess depression as a factor that is significantly associated with SCD. The data of 1030 general practitioner patients from the AgeWell.de-study (60-77 years; CAIDE dementia risk score ≥ 9) were analysed. A descriptive analysis was conducted using validated instruments like the Geriatric depression scale (GDS), Lubben social network scale (LSNS-6) and education classes according to CASMIN (Comparative Analysis of Social Mobility in Industrial Nations). A multivariate regression model with the dependent variable SCD was calculated. Of the 1030 participants, 5.9% had depressive symptoms and 31.3% SCD. The group with depressive symptoms showed significantly higher body-mass-index (p = 0.005), lower education class (p = 0.022), lower LSNS-6 score (p < 0.001), higher sports activity (p < 0.001), and more sleeping problems (p = 0.026). In the regression model a higher GDS-score [Odds ratio (OR): 1.219 (p < 0.001)], more sleeping problems [OR: 1.550 (p = 0.017)] and higher education class [middle/high: OR: 1.474/1.875 (p = 0.037/0.004)] were significantly associated with SCD. This study identified depressive symptoms, sleeping problems, and higher education classes as factors associated with SCD, which can represent an early form of dementia.

2.
BMJ Case Rep ; 14(6)2021 Jun 29.
Article in English | MEDLINE | ID: mdl-34187795

ABSTRACT

A 52-year-old woman with HIV and recent antiretroviral therapy non-adherence presented with a 5-day history of widespread painful vesicular skin lesions. Direct fluorescent antibody testing of the skin lesions was positive for varicella zoster virus (VZV). On day 3, she developed profound right upper extremity weakness. MRI of the brain and cervical spine was suggestive of VZV myelitis. Lumbar puncture was positive for VZV PCR in the cerebrospinal fluid (CSF) and CSF HIV viral load was detected at 1030 copies/mL, indicating 'secondary' HIV CSF escape. She was treated with intravenous acyclovir for 4 weeks and subsequent oral therapy with famciclovir then valacyclovir for 6 weeks. She also received dexamethasone. The patient had an almost full recovery at 6 months. Myelitis is a rare complication of reactivated VZV infection that can have atypical presentation in immunocompromised patients. Such 'secondary' HIV CSF escape should be considered in immunosuppressed patients with concomitant central nervous system infection.


Subject(s)
Central Nervous System Infections , HIV Infections , Herpes Zoster , Myelitis , Acyclovir/therapeutic use , Female , HIV Infections/complications , HIV Infections/drug therapy , Herpesvirus 3, Human , Humans , Middle Aged , Myelitis/diagnosis , Myelitis/drug therapy , Myelitis/etiology
3.
Clin Infect Dis ; 73(8): 1404-1411, 2021 10 20.
Article in English | MEDLINE | ID: mdl-34050746

ABSTRACT

BACKGROUND: Synaptic injury is a pathological hallmark of neurological impairment in people living with human immunodeficiency virus (HIV, PLWH), a common complication despite viral suppression with antiretroviral therapy (ART). Measurement of synaptic density in living humans may allow better understanding of HIV neuropathogenesis and provide a dynamic biomarker for therapeutic studies. We applied novel synaptic vesical protein 2A (SV2A) positron emission tomographic (PET) imaging to investigate synaptic density in the frontostriatalthalamic region in PLWH and HIV-uninfected participants. METHODS: In this cross-sectional pilot study,13 older male PLWH on ART underwent magnetic resonance imaging (MRI) and PET scanning with the SV2A ligand [11C]UCB-J with partial volume correction and had neurocognitive assessments. SV2A binding potential (BPND) in the frontostriatalthalamic circuit was compared to 13 age-matched HIV-uninfected participants and assessed with respect to neurocognitive performance in PLWH. RESULTS: PLWH had 14% lower frontostriatalthalamic SV2A synaptic density compared to HIV-uninfected (PLWH: mean [SD], 3.93 [0.80]; HIV-uninfected: 4.59 [0.43]; P = .02, effect size 1.02). Differences were observed in widespread additional regions in exploratory analyses. Higher frontostriatalthalamic SV2A BPND associated with better grooved pegboard performance, a measure of motor coordination, in PLWH (r = 0.61, P = .03). CONCLUSIONS: In a pilot study, SV2A PET imaging reveals reduced synaptic density in older male PLWH on ART compared to HIV-uninfected in the frontostriatalthalamic circuit and other cortical areas. Larger studies controlling for factors in addition to age are needed to determine whether differences are attributable to HIV or comorbidities in PLWH. SV2A imaging is a promising biomarker for studies of neuropathogenesis and therapeutic interventions in HIV.


Subject(s)
HIV Infections , Positron-Emission Tomography , Aged , Cross-Sectional Studies , HIV , HIV Infections/complications , HIV Infections/drug therapy , Humans , Male , Pilot Projects
4.
PLoS One ; 16(3): e0248025, 2021.
Article in English | MEDLINE | ID: mdl-33657167

ABSTRACT

INTRODUCTION: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. METHODS AND FINDINGS: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.


Subject(s)
Anosmia/epidemiology , COVID-19/diagnosis , Health Personnel/trends , Adult , Anosmia/diagnosis , Anosmia/virology , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , Female , Health Personnel/statistics & numerical data , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2/pathogenicity , Self Report , Smell/physiology , United States/epidemiology
5.
Blood Rev ; 47: 100736, 2021 05.
Article in English | MEDLINE | ID: mdl-32771228

ABSTRACT

While most clinicians recognize adult therapy-related leukemias following cytotoxic chemotherapy and radiation, environmental regulatory agencies evaluate exposure to "safe levels" of leukemogenic compounds. Benzene represents the most notorious leukemogenic chemical. Used in the production of ubiquitous items such as plastics, lubricants, rubbers, dyes, and pesticides, benzene may be responsible for the higher risk of acute myeloid leukemia (AML) among automobile, janitorial, construction, and agricultural workers. It is possible that ambient benzene may contribute to many cases of "de novo" AML not arising out of germline predispositions. In this appraisal of the available literature, we evaluate and discuss the association between chronic, low-dose and ambient exposure to environmental benzene and the development of adult AML.


Subject(s)
Benzene/toxicity , Environmental Exposure/adverse effects , Leukemia, Myeloid, Acute , Occupational Exposure/adverse effects , Adult , Humans , Leukemia, Myeloid, Acute/chemically induced , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Risk Factors
6.
Clin Endocrinol (Oxf) ; 94(2): 183-192, 2021 02.
Article in English | MEDLINE | ID: mdl-33037656

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in young adults with obesity. Obesity is associated with relative growth hormone (GH) deficiency, and data from animal studies and from humans with pituitary GH deficiency suggest a role for GH deficiency in the pathogenesis of NAFLD. The effects of GH on NAFLD in those with obesity are unknown, however, prompting this pilot study to assess effects of GH administration on measures of NAFLD in young adults. METHODS: Twenty-four men and women aged 18-29 years with BMI ≥ 30 kg/m2 , hepatic fat fraction (HFF) ≥ 5% on proton magnetic resonance spectroscopy (1 H-MRS) and insulin-like growth factor 1 (IGF-1) z-score ≤ 0 were randomized to treatment with recombinant human GH (rhGH) versus no treatment for 24 weeks. The primary endpoint was change in HFF. RESULTS: Compared to no treatment, the effect size of rhGH on absolute HFF over 24 weeks was -3.3% (95% confidence interval: -7.8%, 1.2%; p = .14). At 24 weeks, HFF < 5% was achieved in 5 of 9 individuals receiving rhGH versus 1 of 9 individuals receiving no treatment (p = .04). rhGH did not significantly reduce ALT, AST or GGT. Serum IGF-1 increased as expected with rhGH treatment, and there were no changes in fasting lipids, C-reactive protein, fasting glucose or 2-h glucose following an oral glucose tolerance test. CONCLUSION: Data from this pilot study suggest that rhGH treatment in young adults with obesity and NAFLD may have benefits to reduce liver fat content, although larger studies are needed to confirm this effect.


Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Non-alcoholic Fatty Liver Disease , Female , Growth Hormone , Humans , Insulin-Like Growth Factor I , Male , Non-alcoholic Fatty Liver Disease/drug therapy , Pilot Projects , Young Adult
7.
Blood Rev ; 47: 100760, 2021 05.
Article in English | MEDLINE | ID: mdl-32988660

ABSTRACT

Myeloid neoplasms like acute myeloid leukemia (AML) originate from genomic disruption, usually in a multi-step fashion. Hematopoietic stem/progenitor cell acquisition of abnormalities in vital cellular processes, when coupled with intrinsic factors such as germline predisposition or extrinsic factors such as the marrow microenvironment or environmental agents, can lead to requisite pre-leukemic clonal selection, expansion and evolution. Several of these entities have been invoked as "leukemogens." The known leukemogens are numerous and are found in the therapeutic, occupational and ambient environments, however they are often difficult to implicate for individual patients. Patients treated with particular chemotherapeutic agents or radiotherapy accept a calculated risk of therapy-related AML. Occupational exposures to benzene, dioxins, formaldehyde, electromagnetic and particle radiation have been associated with an increased risk of AML. Although regulatory agencies have established acceptable exposure limits in the workplace, accidental exposures and even ambient exposures to leukemogens are possible. It is plausible that inescapable exposure to non-anthropogenic ambient leukemogens may be responsible for many cases of non-inherited de novo AML. In this review, we discuss the current understanding of leukemogens as they relate to AML, assess to what extent the term "de novo" leukemia is meaningful, and describe the potential to identify and characterize new leukemogens.


Subject(s)
Bone Marrow , Carcinogenesis , Carcinogens/toxicity , Environmental Exposure/adverse effects , Leukemia, Myeloid, Acute , Occupational Exposure/adverse effects , Tumor Microenvironment/drug effects , Bone Marrow/metabolism , Bone Marrow/pathology , Carcinogenesis/chemically induced , Carcinogenesis/metabolism , Carcinogenesis/pathology , Humans , Leukemia, Myeloid, Acute/chemically induced , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Risk Factors
8.
medRxiv ; 2020 Sep 10.
Article in English | MEDLINE | ID: mdl-32935121

ABSTRACT

BACKGROUND: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals, like HCW. METHODS: We performed a prospective cohort study, tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, novel behavioral at-home assessment of smell function with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and RT-qPCR testing to identify SARS-CoV-2 infection. RESULTS: SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. Among the 17 infected HCW, 53% reported smell loss, and were more likely to report smell loss than COVID-negative HCW on both the at-home assessment and the screening questionnaire (P < .01). 67% reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among COVID-positive HCW who reported smell loss (P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of COVID-19 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

9.
Article in English | MEDLINE | ID: mdl-32692703

ABSTRACT

Objective Basal (unstimulated) LH levels and leuprolide stimulation tests are used to define pubertal status of children presenting with signs of early puberty. The primary aims of this study were to (i) confirm utility of detectable basal LH levels in precluding the need for leuprolide stimulation testing, and, (ii) determine whether duration of testing could be abbreviated from usual 3 h test without compromising sensitivity. Methods We reviewed morning basal and leuprolide-stimulated LH levels in 105 children, aged 1-9 years (mean 6.9 years, SD 1.8) who were seen for concerns of precocious puberty and received a leuprolide stimulation test between June 2006 and March 2017. Results A pubertal basal LH level had high specificity and poor sensitivity for the following outcome measures: (1) peak stimulated LH≥5 mIU/mL (2) treatment with GnRHa; and (3) a composite outcome of (1) and/or (2). Following leuprolide stimulation, LH response was highest at 180 min in most children (n=78, 74.3%). Using a single cutoff of LH≥5 mIU/mL at any timepoint, 25% of children would have been misdiagnosed with an abbreviated 60 min test. A single sample at 180 min would have correctly identified 97% of patients. Conclusions A pubertal basal LH level is sufficient to distinguish children with precocious puberty without stimulation testing. However, prepubertal basal LH had relatively poor negative predictive value to refute CPP, necessitating clinical follow-up and/or a leuprolide stimulation test. For a cutoff of LH≥5 mIU/mL at any timepoint, test duration of 180 min maximizes sensitivity.

10.
J Nutr ; 149(1): 78-87, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30624677

ABSTRACT

Background: People with HIV (PWH) are at risk for developing metabolic comorbidities driven, in part, by immune activation/inflammation. Little is known about diet quality, a potential modifiable factor in PWH. Objectives: This study aimed to explore diet quality in terms of conformance with US dietary guidelines by calculating Healthy Eating Index-2010 (HEI) scores among adults with and without HIV in Boston, MA, and determine associations with HEI and markers of immune activation/inflammation. Methods: One-hundred and three HIV-infected [50 women, 53 men; mean ± SD age: 47 ± 7 y; body mass index (BMI, in kg/m2): 26 ± 5] and 38 uninfected adults (17 women, 21 men; age: 46 ± 7 y; BMI: 28 ± 4) were included in this cross-sectional analysis. Participants who completed a 4-d food record from which HEI could be calculated were included. HEI was compared between participants with and without HIV, within HIV-infected participants stratified by sex, and by HIV serostatus and sex. In the HIV group, predictors of HEI were determined in multivariable modeling. Univariate associations with diet quality and inflammation/immune markers were assessed. Results: The HEI score was 51.3 in the HIV-infected participants and 57.3 in the HIV-uninfected participants (P = 0.052). In the comparison by HIV serostatus and sex, HIV-infected women had significantly lower HEI (49.2) compared with HIV-infected men (55.7) (P = 0.005) and HIV-uninfected men (61.8) (P = 0.002). Adjusting for potential confounding factors, sex remained an independent predictor of HEI in HIV (P = 0.02). In the HIV group, higher log HEI was associated with lower concentration of the immune activation marker sCD14 (P = 0.009). Conclusions: Diet quality tended to be lower in HIV-infected individuals compared with HIV-uninfected individuals and was lower among HIV-infected women compared with HIV-infected men, and HIV-uninfected men. There may also be an association with diet quality and sCD14 in PWH. Future prospective studies are needed to confirm these findings and determine whether improving diet quality is a useful strategy to reduce metabolic abnormalities in this population. This study was registered at clinicaltrials.gov as NCT00455793.


Subject(s)
Diet/standards , HIV Infections , Adult , Boston/epidemiology , Cross-Sectional Studies , Diet Surveys , Diet, Healthy , Female , HIV Infections/epidemiology , Humans , Male , Middle Aged , Nutrition Policy , Prospective Studies , Sex Factors
11.
J Clin Endocrinol Metab ; 103(11): 4176-4186, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30239757

ABSTRACT

Context: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are widely prescribed. Statins may have important metabolic effects on insulin sensitivity and liver fat, but limited studies have assessed these effects by using euglycemic hyperinsulinemic clamp, stable isotopes, and 1H magnetic resonance spectroscopy (MRS) for liver fat quantification. Objective: To study the effects of pitavastatin on hepatic fat and insulin sensitivity. Design: Six-month, double-blind, randomized, placebo-controlled trial. Setting: Academic clinical research center in Boston, Massachusetts. Participants: Overweight, insulin-resistant men aged 40 to 65 years who had not received statin therapy for ≥1 year. Interventions: Pitavastatin 4 mg or placebo daily. Outcome: The primary endpoints were changes in insulin sensitivity measured by euglycemic hyperinsulinemic clamp and liver fat measured by 1H MRS. Results: Pitavastatin showed no effect on endogenous glucose production (ΔRa glucose 0.07 ± 0.07 vs 0.04 ± 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin-stimulated glucose uptake during "low dose" (ΔM 0.1 ± 0.1 vs -0.3 ± 0.2 mg/kg/min, P = 0.11) and "high dose" (ΔM -0.5 ± 0.3 vs -0.7 ± 0.4 mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose challenge. There was also no change in liver fat fraction (-1 ± 1 vs -0 ± 1%, P = 0.56). Conclusion: Compared with placebo, pitavastatin did not affect hepatic or whole-body insulin sensitivity, and it did not reduce liver fat.


Subject(s)
Fatty Liver/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Insulin Resistance , Overweight/metabolism , Quinolines/administration & dosage , Adult , Blood Glucose/analysis , Blood Glucose/drug effects , Blood Glucose/metabolism , Double-Blind Method , Fatty Liver/diagnostic imaging , Fatty Liver/etiology , Fatty Liver/pathology , Glucose Clamp Technique , Humans , Insulin/metabolism , Liver/diagnostic imaging , Liver/drug effects , Liver/pathology , Male , Middle Aged , Overweight/blood , Overweight/complications , Proton Magnetic Resonance Spectroscopy , Treatment Outcome
12.
J Clin Endocrinol Metab ; 103(6): 2376-2384, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29659888

ABSTRACT

Context: HIV-infected individuals demonstrate increased renin-angiotensin-aldosterone system activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV. Objective: To investigate effects of eplerenone on insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV. Design: Six-month, double-blind, randomized, placebo-controlled trial. Setting: Academic clinical research center. Participants: HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis. Intervention: Eplerenone 50 mg or placebo daily. Outcome: The primary end point was change in insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique. Secondary end points included change in body composition and inflammatory markers. Results: Forty-six individuals were randomized to eplerenone (n = 25) vs placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (-1.28 to 1.48) vs 0.43 (-1.95 to 2.55) mg/min/µIU/mL insulin; P = 0.71, eplerenone vs placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1 (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs placebo-treated group, demonstrating expected physiology. MR antagonism with eplerenone was well tolerated among the HIV population, with no considerable changes in blood pressure or potassium. Conclusion: MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.


Subject(s)
Adiposity/drug effects , Eplerenone/therapeutic use , HIV Infections/metabolism , Inflammation/drug therapy , Insulin Resistance/physiology , Mineralocorticoid Receptor Antagonists/therapeutic use , Adult , Aged , Blood Pressure/drug effects , Double-Blind Method , Eplerenone/administration & dosage , Female , Glucose Clamp Technique , HIV Infections/complications , Humans , Inflammation/complications , Inflammation/metabolism , Lipids/blood , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/administration & dosage , Renin-Angiotensin System/drug effects , Treatment Outcome
13.
Physiol Rep ; 5(19)2017 Oct.
Article in English | MEDLINE | ID: mdl-29038352

ABSTRACT

HIV-infected patients commonly experience changes in central and peripheral fat content as well as ectopic fat accumulation. However, whether hepatic and epicardial fat stores relate differentially to body composition or how these associations are modified by HIV status has not been well explored. A previously recruited sample of 124 HIV-infected patients and 58 healthy controls had undergone dual energy X-ray absorptiometry (DEXA) and computed tomography (CT) from which body composition measures, liver-spleen ratio, and epicardial fat volume were obtained. Unique to the HIV-infected group, there was a parabolic association between abdominal subcutaneous adipose tissue (SAT) area and liver-spleen ratio (P = 0.03, inflection point 324 cm2) such that hepatic fat content was greatest at the extremes of low and high SAT A quadratic model also closely described the relationship between mean leg fat and liver-spleen ratio among patients with HIV (P = 0.02, inflection point 4.7 kg), again suggesting greater liver fat content with both low and high leg fat. Notably, an analogous relationship of epicardial fat with SAT was not evident among HIV-infected individuals or healthy controls. In contrast, visceral adipose tissue (VAT) linearly related to both liver-spleen ratio in HIV and epicardial fat volume irrespective of HIV status in multivariable models. In conclusion, our analyses implicate both low and high SAT as risk factors for hepatic fat accumulation in HIV These findings add to growing evidence of SAT dysfunction in the setting of HIV infection, and highlight key physiologic differences between hepatic and epicardial fat depots.


Subject(s)
Adiposity , HIV Infections/epidemiology , Heart/diagnostic imaging , Liver/diagnostic imaging , Adult , Case-Control Studies , Female , HIV Infections/diagnostic imaging , Humans , Male , Middle Aged , Spleen/diagnostic imaging
14.
AIDS ; 31(16): 2253-2259, 2017 10 23.
Article in English | MEDLINE | ID: mdl-28832410

ABSTRACT

OBJECTIVE: Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). DESIGN AND METHODS: We utilized data from two multicenter Phase III trials of tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT. In the current analysis, we sought to examine the impact of VAT reduction on ALT and AST among patients participating in the Phase III trials with baseline elevated ALT or AST. Within this group, we compared changes in ALT and AST in VAT responders vs. nonresponders after 26 weeks of treatment, and then assessed the effects of drug discontinuation on these endpoints over a subsequent 26-week period. RESULTS: At baseline, VAT was positively associated with ALT (P = 0.01). In study participants assigned to tesamorelin with baseline ALT or AST more than 30 U/l, VAT responders experienced greater reductions in ALT (-8.9 ±â€Š22.6 vs. 1.4 ±â€Š34.7 U/l, P = 0.004) and AST (-3.8 ±â€Š12.9 vs. 0.4 ±â€Š22.4 U/l, P = 0.04) compared with nonresponders over 26 weeks. This improvement among VAT responders persisted over 52 weeks even in those switched to placebo despite a partial reaccumulation of VAT. CONCLUSION: A clinically significant VAT reduction with tesamorelin was associated with improved liver enzymes among HIV-infected patients with abdominal obesity and elevated baseline transaminases.


Subject(s)
Alanine Transaminase/blood , Anti-Obesity Agents/therapeutic use , Aspartate Aminotransferases/blood , Fatty Liver/pathology , Growth Hormone-Releasing Hormone/analogs & derivatives , HIV Infections/complications , Obesity/complications , Adolescent , Adult , Aged , Clinical Trials, Phase III as Topic , Female , Growth Hormone-Releasing Hormone/therapeutic use , Humans , Intra-Abdominal Fat/pathology , Male , Middle Aged , Obesity/drug therapy , Placebos/administration & dosage , Treatment Outcome , Young Adult
15.
J Orthop Surg (Hong Kong) ; 25(2): 2309499017716252, 2017.
Article in English | MEDLINE | ID: mdl-28656874

ABSTRACT

BACKGROUND: Total knee arthroplasty (TKA) has been established as a successful surgical treatment in the late stages of rheumatoid joint destruction. The purpose of this study was to review the clinical outcome and survivorship in rheumatoid arthritis (RA) patients undergoing TKA in hybrid technique with a cementless fixation of the femoral component. METHODS: We analysed retrospectively 66 RA patients who underwent 72 TKAs (P.F.C. Sigma®). Mean follow-up time was 124 ± 41 months. To evaluate postoperative clinical outcome, knee injury and osteoarthritis outcome score (KOOS) and Oxford knee score (OKS) were assessed. Kaplan-Meier analysis was used to calculate survivorship. The primary outcome was revision for any reason. RESULTS: Thirty-four patients (36 knees) died and two patients (2 knees) were lost to follow-up. Three patients (four knees) did not agree to participate. Twenty-seven patients (30 knees) were available for assessing clinical scores. The average scores were 85 ± 14 for KOOS and 34 ± 10 for OKS. In three patients (three knees), revision was necessary, including restricted range of motion ( n = 1), instability ( n = 1), and infection ( n = 1). There were no cases of loosening in this cohort study. The survival rates were 100% at 5 years, 97.1% at 10 years (95% CI 89.0-99.2%) and 95.6% at 15 years (95% CI 86.9-98.5%). CONCLUSIONS: This study confirms that excellent clinical results and a good 10-year survivorship can be obtained with hybrid fixation technique in TKA in the unique population of RA patients.


Subject(s)
Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement, Knee/methods , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/physiopathology , Arthroplasty, Replacement, Knee/instrumentation , Cementation , Female , Femur/surgery , Humans , Kaplan-Meier Estimate , Knee Prosthesis , Male , Middle Aged , Range of Motion, Articular , Retrospective Studies , Survivorship , Treatment Outcome
16.
PLoS One ; 11(12): e0168335, 2016.
Article in English | MEDLINE | ID: mdl-28006008

ABSTRACT

During vertebrate embryonic development, early skin, muscle, and bone progenitor populations organize into segments known as somites. Defects in this conserved process of segmentation lead to skeletal and muscular deformities, such as congenital scoliosis, a curvature of the spine caused by vertebral defects. Environmental stresses such as hypoxia or heat shock produce segmentation defects, and significantly increase the penetrance and severity of vertebral defects in genetically susceptible individuals. Here we show that a brief exposure to a high osmolarity solution causes reproducible segmentation defects in developing zebrafish (Danio rerio) embryos. Both osmotic shock and heat shock produce border defects in a dose-dependent manner, with an increase in both frequency and severity of defects. We also show that osmotic treatment has a delayed effect on somite development, similar to that observed in heat shocked embryos. Our results establish osmotic shock as an alternate experimental model for stress, affecting segmentation in a manner comparable to other known environmental stressors. The similar effects of these two distinct environmental stressors support a model in which a variety of cellular stresses act through a related response pathway that leads to disturbances in the segmentation process.


Subject(s)
Embryo, Nonmammalian/pathology , Heat Stress Disorders/etiology , Heat-Shock Response , Hot Temperature/adverse effects , Osmosis , Somites/pathology , Zebrafish/embryology , Animals , Heat Stress Disorders/pathology
17.
Alcohol Clin Exp Res ; 31(6): 950-4, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17433008

ABSTRACT

BACKGROUND: A role of appetite-regulating peptides like leptin and ghrelin in the neurobiology of alcohol craving has been proposed by several studies. Aim of this analysis was to search for differences regarding an association between these peptides and alcohol craving with respect to different subtypes and beverage consumption patterns in patients with alcohol dependence. METHODS: We analyzed a sample of 188 patients at admission for alcohol detoxification regarding leptin and ghrelin (n=117) serum levels. Craving was measured using the Obsessive Compulsive Drinking Scale (OCDS). Patients were classified according to Lesch's typology of alcohol dependence and according to their preferred type of alcoholic beverage (beer, wine, spirits). RESULTS: Using general linear models to analyze a possible interaction between subtypes and leptin/ghrelin levels with respect to craving, we found a significant positive association for leptin in patients of Lesch's types 1 and 2, and in patients consuming beer or wine. Ghrelin levels showed a significant trend regarding an association with craving in patients of Lesch's type 1. In the other subgroups we found no significant results. CONCLUSIONS: Our findings show that appetite-regulating peptides may be of special importance regarding alcohol craving in subtypes of patients. This may explicate at least in part previous contradictory findings.


Subject(s)
Alcohol Drinking/physiopathology , Alcoholism/physiopathology , Leptin/physiology , Peptide Hormones/physiology , Adult , Alcoholism/classification , Appetite Regulation/physiology , Female , Ghrelin , Humans , Linear Models , Male , Middle Aged
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