72 research outputs found
Postoperative spinal infection mimicking systemic vasculitis with titanium-spinal implants
<p>Abstract</p> <p>Background</p> <p>Secondary systemic vasculitis after posterior spinal fusion surgery is rare. It is usually related to over-reaction of immune-system, to genetic factors, toxicity, infection or metal allergies.</p> <p>Case Description</p> <p>A 14 year-old girl with a history of extended posterior spinal fusion due to idiopathic scoliosis presented to our department with diffuse erythema and nephritis (macroscopic hemuresis and proteinuria) 5 months post surgery. The surgical trauma had no signs of inflammation or infection. The blood markers ESR and CRP were increased. Skin tests were positive for nickel allergy, which is a content of titanium alloy. The patient received corticosteroids systematically (hydrocortisone 10 mg) for 6 months, leading to total recess of skin and systemic reaction. However, a palpable mass close to the surgical wound raised the suspicion of a late infection. The patient had a second surgery consisting of surgical debridement and one stage revision of posterior spinal instrumentation. Intraoperative cultures were positive to Staphylococcus aureus. Intravenous antibiotics were administered. The patient is now free of symptoms 24 months post revision surgery without any signs of recurrence of either vasculitis or infection.</p> <p>Literature Review</p> <p>Systemic vasculitis after spinal surgery is exceptionally rare. Causative factors are broad and sometimes controversial. In general, it is associated with allergy to metal ions. This is usually addressed with metal on metal total hip bearings. In spinal surgery, titanium implants are considered to be inert and only few reports have presented cases with systemic vasculitides. Therefore, other etiologies of immune over-reaction should always be considered, such as drug toxicity, infection, or genetic predisposition.</p> <p>Purposes and Clinical Relevance</p> <p>Our purpose was to highlight the difficulties during the diagnostic work-up for systemic vasculitis and management in cases of posterior spinal surgery.</p
The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter
Nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH), a rare hereditary condition resulting in elevated levels of fetal hemoglobin (Hb F) in adults, is associated with promoter mutations in the human fetal globin (HBG1 and HBG2) genes. In this paper, we report a novel type of nd-HPFH due to a HBG2 gene promoter mutation (HBG2:g.-109G>T). This mutation, located at the 3′ end of the HBG2 distal CCAAT box, was initially identified in an adult female subject of Central Greek origin and results in elevated Hb F levels (4.1%) and significantly increased Gγ-globin chain production (79.2%). Family studies and DNA analysis revealed that the HBG2:g.-109G>T mutation is also found in the family members in compound heterozygosity with the HBG2:g.-158C>T single nucleotide polymorphism or the silent HBB:g.-101C>T β-thalassemia mutation, resulting in the latter case in significantly elevated Hb F levels (14.3%). Electrophoretic mobility shift analysis revealed that the HBG2:g.-109G>T mutation abolishes a transcription factor binding site, consistent with previous observations using DNA footprinting analysis, suggesting that guanine at position HBG2/1:g.-109 is critical for NF-E3 binding. These data suggest that the HBG2:g-109G>T mutation has a functional role in increasing HBG2 transcription and is responsible for the HPFH phenotype observed in our index cases
Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease
Background:
Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61h/h) called ‘HypoE’ when fed an atherogenic, ‘Paigen’ diet develop occlusive, atherosclerotic coronary arterial disease (CHD), myocardial infarctions (MI), and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet). Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals.
Methodology/Principal Findings:
HypoE mice were maintained on a standard lab chow diet (control) until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western) or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented.
Conclusions/Significance:
HypoE mice provide a powerful, surgery-free, diet-‘titratable’ small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation) on a variety of features of cardiovascular disease.National Institutes of Health (U.S.)National Heart, Lung, and Blood Institut
Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients
Genetic factors are thought to influence the risk for lung cancer. Since pulmonary surfactant mediates the response to inhaled carcinogenic substances, candidate genes may be among those coding for pulmonary surfactant proteins. In the present matched case–control study a polymorphism within intron 4 of the gene coding for surfactant specific protein B was analysed in 357 individuals. They were divided into 117 patients with lung cancer (40 patients with small cell lung cancer, 77 patients with non small cell lung cancer), matched controls and 123 healthy individuals. Surfactant protein B gene variants were analysed using specific PCR and cloned surfactant protein B sequences as controls. The frequency of the intron 4 variation was similar in both control groups (13.0% and 9.4%), whereas it was increased in the small cell lung cancer group (17.5%) and the non small cell lung cancer group (16.9%). The gene variation was found significantly more frequently in patients with squamous cell carcinoma (25.0%, P=0.016, odds ratio=3.2, 95%CI=1.24–8.28) than in the controls. These results indicate an association of the surfactant protein B intron 4 variants and/or its flanking loci with mechanisms that may enhance lung cancer susceptibility, especially to squamous cell carcinoma of the lung
Susceptibility of β-thalassemia heterozygotes to COVID-19
Background: β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomed-ical priority. Methods: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), consecutively recruited during the last trimester of 2020. Patient characteristics including age, sex, current smoking status, atrial fibrillation, chronic respiratory disease, coronary disease, diabetes, neoplasia, hyperlipidemia, hypertension, and β-thalassemia heterozygosity were assessed for COVID-19 severity, length of hospitalization, intensive care unit (ICU) admission and mortality from COVID-19. Results: We assessed patient characteristics associated with clinical symptoms, ICU admission, and mortality from COVID-19. In multivariate analysis, severe-critical COVID-19 was strongly associated with male sex (p = 0.023), increased age (p <0.001), and β-thalassemia heterozygosity (p = 0.002, OR = 2.89). Regarding the requirement for ICU care, in multivariate analysis there was a statistically significant association with hypertension (p = 0.001, OR = 5.12), while β-thalassemia heterozygosity had no effect (p = 0.508, OR = 1.33). Mortality was linked to male sex (p = 0.036, OR = 2.09), increased age (p < 0.001) and β-thalassemia heterozygosity (p = 0.010, OR = 2.79) in multivariate analysis. It is worth noting that hyperlipidemia reduced mortality from COVID-19 (p = 0.008, OR = 0.38). No statistically significant association of current smoking status with patient characteristics studied was observed. Conclusions: Our pilot observations indicate enhanced mortality of β-thalassemia heterozygotes from COVID-19. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
Vulnerability of β-Thalassemia Heterozygotes to COVID-19: Results from a Cohort Study
Background: The assignment of mortality risk from SARS-CoV-2 virus (COVID-19) to vulnerable patient groups is an important step toward containment of the pandemic. Methods: A total of 760 patients with a positive molecular test for SARS-CoV-2 who were unvaccinated against COVID-19 were recruited between 1 January and 30 June 2021. Patients were grouped by age; sex; and common morbidities, such as atrial fibrillation, chronic respiratory disease, coronary disease, diabetes type II, neoplasia, hypertension and β-Thalassemia heterozygosity. As a primary endpoint, we assessed mortality risk from COVID-19, and as secondary endpoints, we considered clinical severity and need for Intense Care Unit (ICU) admission. Results: In multivariate analysis, male sex (p < 0.001, OR = 2.59), increasing age (p < 0.001, OR = 1.049), β-Thalassemia heterozygosity (p = 0.001, OR = 2.41) and chronic respiratory disease (p = 0.018, OR = 1.84) were identified as risk factors associated with mortality due to COVID-19. Moreover, male sex (p < 0.001, OR = 1.98), increasing age (p < 0.001, OR = 1.052) and β-Thalassemia heterozygosity (p = 0.001, OR = 2.59) were associated with clinical severity in logistic regression. Regarding ICU admission, the risk factors were identified as male sex (p = 0.002, OR = 1.99), chronic respiratory disease (p = 0.007, OR = 2.06) and hypertension (p < 0.001, OR = 5.81). Conclusions: An increased mortality risk from COVID-19 was observed for older age, male sex, β-Thalassemia heterozygosity and respiratory disease. Carriers of β-Thalasse-mia were identified as more vulnerable for severe clinical symptomatology, but there was no increased possibility for ICU admission. Readjustment of these findings to consider impacts of variant strains prevailing during the latest viral outbreak among vulnerable patient groups may offer timely relief from the pandemic. © 2022 by the authors. Licensee MDPI, Basel, Switzerland
Estradiol and leptin as conditional prognostic IVF markers
We studied the concentration of serum estradiol and serum and follicular
fluid leptin in 200 women undergoing their first in vitro fertilization
with embryo transfer (IVF-ET) program at the time of human chorionic
gonadotrophin administration and oocyte retrieval, in an attempt to
assess their concerted role on embryo quality and the prognosis of IVF
outcome. Low serum (46.49 +/- 8.4 ng/ml) and follicular fluid (52 +/-
9.8 ng/ml) leptin levels were associated with a high number of
‘good-quality’ embryos (73.6%) and high implantation (11.2%) and
pregnancy (35.8%) rates and were observed in women with normal peak
estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin
and estradiol interact coordinately in a concentration-dependent manner
to control IVF outcome. Further studies will be required to substantiate
and clarify the mechanism of proposed conditional interaction between
the two hormonal systems
Estradiol and leptin as conditional prognostic IVF markers
We studied the concentration of serum estradiol and serum and follicular fluid leptin in 200 women undergoing their first in vitro fertilization with embryo transfer (IVF-ET) program at the time of human chorionic gonadotrophin administration and oocyte retrieval, in an attempt to assess their concerted role on embryo quality and the prognosis of IVF outcome. Low serum (46.49 +/- 8.4 ng/ml) and follicular fluid (52 +/- 9.8 ng/ml) leptin levels were associated with a high number of 'good-quality' embryos (73.6%) and high implantation (11.2%) and pregnancy (35.8%) rates and were observed in women with normal peak estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin and estradiol interact coordinately in a concentration-dependent manner to control IVF outcome. Further studies will be required to substantiate and clarify the mechanism of proposed conditional interaction between the two hormonal systems
Only three of the seven human chorionic gonadotropin beta subunit genes can be expressed in the placenta.
Human chorionic gonadotropin (hCG) is a placental hormone essential for the maintenance of pregnancy. While the alpha subunit of this hormone is encoded by a single gene, the beta subunit is encoded by a complex family of seven very similar genes or pseudogenes. Two approaches have been taken to establish which of these genes are functional. First, we have used two restriction enzyme site polymorphisms to correlate 15 independently isolated beta hCG cDNA clones with their corresponding genes. Second, we have used transient expression in COS cells to assay for correctly-initiated transcription from six of the seven beta hCG gene promoters. From these data, we conclude that, at most, only three of the seven beta hCG genes are expressed in the placenta. Comparison of the sequences of a functional and a non-functional beta hCG gene reveals no obvious differences, such as promoter changes, that could account for this differential expression
Association of maternal angiotensin II type 1 and type 2 receptor combination genotypes with susceptibility to early-onset preeclampsia
Allelic variations affecting the activity of the maternal renin-angiotensin system may play a role in the development of hypertensive disorders of pregnancy like preeclampsia, its more severe early-onset form, and intrauterine growth restriction. We examined the association of common allelic variants of angiotensin II type 1 and type 2 receptor genes (AT1R and AT2R) sorted in five AT1R/AT2R receptor combination genotype groups with susceptibility to early-onset preeclampsia (EOP). The occurrence of AT1R (A1166C) and A2TR (C3123A) alleles in wild type (AA, CC), heterozygous (A/C, C/A), and homozygous (C/C, A/A) states was recorded in 84 women with a history of EOP and 84 age-matched controls sorted in five AT1R/AT2R receptor combination genotype (wild type: AA/CC, one mutant: AA/CA, AC/CC, two mutant: AC/CA, AA/AA, CC/CC, three mutants: AC/AA, CC/CA and four mutant: CC/AA) groups, by polymerase chain reaction-RFLP analysis. Three mutant receptor combination genotype carriers were more common in women with a history of EOP than in controls (26.18% vs. 4.76%, p = 0.003, OR = 8.25). Receptor combination genotyping may be of clinical value in: (a) maternal prediction of susceptibility to EOP, (b) disease subtyping for directed studies with receptor signaling antagonists, (c) the broader study of hypertension. © 2021, The Author(s), under exclusive licence to Springer Nature Limited
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