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2.
HNO ; 66(Suppl 1): 1-6, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28667388

ABSTRACT

BACKGROUND: Tufted angiomas (TAs) are uncommon benign vascular tumors mostly located cutaneously or subcutaneously in the skin of the neck and upper trunk, which appear during childhood and grow slowly. TAs are a variant of lobular capillary hemangiomas. This is the first study to provide an overview of the current literature in combination with the authors' own clinical experience on this rare entity in the head and neck area with non-dermatological localization. METHODS: A selective Medline and Google Scholar database search was performed. Additionally, we conducted an ICD-10-based database search on hemangiomas (D18.0) in the Charité SAP patient records. RESULTS: We identified 13 reports in the literature consisting of 16 cases of TA of the head and neck. Males were predominantly affected by TAs (70.6%). The mean age of the patients at the time of surgery was 31.5 years; the mean maximum diameter of the tumors was 16.3 mm. Additionally, we report on one case of TA in our Department of Head and Neck Surgery. A male patient presented with swelling and redness of the left upper eyelid. Radiological examination with computed tomography showed a suprabulbar tumor with a diameter of 13 mm. The tumor was surgically removed via a transcutaneous blepharoplasty approach with the patient under general anesthesia. DISCUSSION: There is only one other case report on the surgical excision of an intra-orbital TA described to date. Here, we present an epidemiological overview, therapeutic considerations, and differential diagnoses.


Subject(s)
Hemangioma , Skin Neoplasms , Adult , Child , Female , Hemangioma/diagnosis , Hemangioma/therapy , Humans , Male , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy
3.
HNO ; 65(12): 981-986, 2017 Dec.
Article in German | MEDLINE | ID: mdl-28761971

ABSTRACT

BACKGROUND: Tufted angiomas (TAs) are uncommon benign vascular tumors mostly located cutaneously or subcutaneously in the skin of the neck and upper trunk, which appear during childhood and grow slowly. TAs are a variant of lobular capillary hemangiomas. This is the first study to provide an overview of the current literature in combination with the authors' own clinical experience on this rare entity in the head and neck area with non-dermatological localization. METHODS: A selective Medline and Google Scholar database search was performed. Additionally, we conducted an ICD-10-based database search on hemangiomas (D18.0) in the Charité SAP patient records. RESULTS: We identified 13 reports in the literature consisting of 16 cases of TA of the head and neck. Males were predominantly affected by TAs (70.6%). The mean age of the patients at the time of surgery was 31.5 years; the mean maximum diameter of the tumors was 16.3 mm. Additionally, we report on one case of TA in our Department of Head and Neck Surgery. A male patient presented with swelling and redness of the left upper eyelid. Radiological examination with computed tomography showed a suprabulbar tumor with a diameter of 13 mm. The tumor was surgically removed via a transcutaneous blepharoplasty approach with the patient under general anesthesia. DISCUSSION: There is only one other case report on the surgical excision of an intra- orbital TA described to date. Here, we present an epidemiological overview, therapeutic considerations, and differential diagnoses.


Subject(s)
Hemangioma , Skin Neoplasms , Adult , Child , Diagnosis, Differential , Female , Hemangioma/diagnostic imaging , Hemangioma/surgery , Humans , Male , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/surgery , Tomography, X-Ray Computed
4.
Skin Res Technol ; 23(4): 452-458, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28271554

ABSTRACT

BACKGROUND: The multiphoton tomography (MPT) has evolved into a useful tool for the non-invasive investigation of morphological and biophysical characteristics of human skin in vivo. Until now, changes of the skin have been evaluated mainly by using clinical and histological techniques. In this study, the progress of wound healing was investigated by MPT over 3 weeks with a final examination after 24 months. Especially, the collagen degradation, reepithelization and tissue formation were examined. As specific parameter for wound healing and its course the second-harmonic generation-to-autofluorescence aging index of dermis (SAAID) was used. METHODS: About 10 volunteers aged between 25 and 58 years were examined. Acute wounds were scanned with three Z-stacks taken per visit. The stacks were taken up to a depth of 225 µm at increments of 5 µm and a scan time for 3 seconds per scan. Subsequently, the SAAID was evaluated as an indicator for wound healing. Furthermore, single scans were taken for morphological investigations. RESULTS: The evaluation revealed a distinct difference in the SAAID behavior between the Z-stacks taken at each visit. Furthermore, the degradation of collagen and cells and their reappearance could be shown in the course of the visits. CONCLUSIONS: Clear differences in the curve behavior of the SAAID at every visit were shown in this study. The SAAID curves and morphological images could be correlated with findings of the clinical examination of different wound healing phases. Therefore, SAAID curves and morphological MPT imaging could provide a non-invasive tool for the determination of wound healing phases in patients in vivo.


Subject(s)
Wound Healing/physiology , Adult , Collagen/physiology , Curettage , Epidermis/diagnostic imaging , Humans , Microscopy, Fluorescence, Multiphoton/methods , Middle Aged , Postoperative Care , Tomography/methods
5.
J Steroid Biochem Mol Biol ; 169: 176-188, 2017 05.
Article in English | MEDLINE | ID: mdl-27163393

ABSTRACT

Stored platelet concentrates (PLCs) for therapeutic purpose, develop a platelet storage lesion (PSL), characterized by impaired platelet (PLT) viability and function, platelet extracellular vesicle (PL-EV) release and profound lipidomic changes. Whereas oxidized low-density lipoprotein (oxLDL) activates PLTs and promotes atherosclerosis, effects linked to oxidized high-density lipoprotein (oxHDL) are poorly characterized. PLCs from blood donors were treated with native (nHDL) or mildly oxidized HDL (moxHDL) for 5days under blood banking conditions. Flow cytometry, nanoparticle tracking analysis (NTA), aggregometry, immunoblot analysis and mass spectrometry were carried out to analyze PL-EV and platelet exosomes (PL-EX) release, PLT aggregation, protein expression, and PLT and plasma lipid composition. In comparison to total nHDL, moxHDL significantly decreased PL-EV release by -36% after 5days of PLT storage and partially reversed agonist-induced PLT aggregation. PL-EV release positively correlated with PLT aggregation. MoxHDL improved PLT membrane lipid homeostasis through enhanced uptake of lysophospholipids and their remodeling to corresponding phospholipid species. This also appeared for sphingomyelin (SM) and d18:0/d18:1 sphingosine-1-phosphate (S1P) at the expense of ceramide (Cer) and hexosylceramide (HexCer) leading to reduced Cer/S1P ratio as PLT-viability indicator. This membrane remodeling was associated with increased content of CD36 and maturation of scavenger receptor-B1 (SR-B1) protein in secreted PL-EVs. MoxHDL, more potently than nHDL, improves PLT-membrane lipid homeostasis, partially antagonizes PL-EV release and agonist-induced PLT aggregation. Altogether, this may be the result of more efficient phospho- and sphingolipid remodeling mediated by CD36 and SR-B1 in the absence of ABCA1 on PLTs. As in vitro supplement in PLCs, moxHDL has the potential to improve PLC quality and to prolong storage.


Subject(s)
Blood Platelets/cytology , Coagulants/chemistry , Lipoproteins, HDL/chemistry , Platelet Aggregation , Blood Platelets/metabolism , Flow Cytometry , Homeostasis , Humans , Lipids/chemistry , Lipoproteins, LDL/chemistry , Lysophospholipids/chemistry , Mass Spectrometry , Nanoparticles/chemistry , Oxidation-Reduction , Oxygen/chemistry , Sphingosine/analogs & derivatives , Sphingosine/chemistry
6.
HNO ; 65(Suppl 1): 68-72, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27995276

ABSTRACT

BACKGROUND: It is a known fact that bacterial or viral acute otitis media occurs more frequently in the winter months. Only a few older studies on seasonal differences in middle ear findings are available. These studies are based solely on tympanography, without correlation to intraoperative middle ear findings. This study addresses the question of whether seasonal differences can be found in the preoperative tympanogram and in the corresponding intraoperative findings in children with chronic middle ear problems. PATIENTS AND METHODS: This retrospective study included patients who had undergone myringotomy with or without tympanostomy tube insertion at the Charité-Universitätsmedizin Berlin between January and December 2011. Corresponding to the catarrhal phases, winter months were defined as those from November to April; summer months from May to October. The preoperative tympanogram and the documented intraoperative middle ear finding were statistically analyzed for seasonal differences. RESULTS: A total of 654 ears from 206 male and 127 female patients with mean age 3.7 ± 2.5 years were analyzed. In the majority of cases, a type B tympanogram was found (n = 376; 57.5%), whereas the middle ear was filled with air in 19.1% of cases. No significant seasonal differences were found for either the intraoperative middle ear findings or the preoperative tympanograms (p > 0.05). CONCLUSION: For children with a typical history of chronic otitis media without effusion and chronic tube ventilation dysfunction, myringotomy with or without tympanostomy tube insertion is indicated independently of the season. The results indicate that a wait-and-see approach with hope of improvement during the summer months is not rational.


Subject(s)
Acoustic Impedance Tests/statistics & numerical data , Audiometry/statistics & numerical data , Otitis Media/diagnosis , Otitis Media/epidemiology , Seasons , Acoustic Impedance Tests/methods , Adolescent , Age Distribution , Child , Child, Preschool , Diagnosis, Differential , Female , Germany/epidemiology , Humans , Infant , Infant, Newborn , Male , Otitis Media/physiopathology , Prevalence , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Sex Distribution
7.
HNO ; 65(8): 651-656, 2017 Aug.
Article in German | MEDLINE | ID: mdl-27904919

ABSTRACT

BACKGROUND: It is a known fact that bacterial or viral acute otitis media occurs more frequently in the winter months. Only a few older studies on seasonal differences in middle ear findings are available. These studies are based solely on tympanography, without correlation to intraoperative middle ear findings. This study addresses the question of whether seasonal differences can be found in the preoperative tympanogram and in the corresponding intraoperative findings in children with chronic middle ear problems. PATIENTS AND METHODS: This retrospective study included patients who had undergone myringotomy with or without tympanostomy tube insertion at the Charité-Universitätsmedizin Berlin between January and December 2011. Corresponding to the catarrhal phases, winter months were defined as those from November to April; summer months from May to October. The preoperative tympanogram and the documented intraoperative middle ear finding were statistically analyzed for seasonal differences. RESULTS: A total of 654 ears from 206 male and 127 female patients with mean age 3.7 ± 2.5 years were analyzed. In the majority of cases, a type B tympanogram was found (n = 376; 57.5%), whereas the middle ear was filled with air in 19.1% of cases. No significant seasonal differences were found for either the intraoperative middle ear findings or the preoperative tympanograms (p > 0.05). CONCLUSION: For children with a typical history of chronic otitis media without effusion and chronic tube ventilation dysfunction, myringotomy with or without tympanostomy tube insertion is indicated independently of the season. The results indicate that a wait-and-see approach with hope of improvement during the summer months is not rational.


Subject(s)
Middle Ear Ventilation , Otitis Media with Effusion , Child , Child, Preschool , Ear, Middle/physiology , Female , Humans , Infant , Male , Otitis Media with Effusion/epidemiology , Otitis Media with Effusion/therapy , Retrospective Studies , Seasons
8.
Laryngorhinootologie ; 94(7): 437-40, 2015 Jul.
Article in German | MEDLINE | ID: mdl-26125291

ABSTRACT

BACKGROUND: Bone removal during mastoidectomy and cochleostomy or round window enlargement prior to electrode insertion is typically performed with a drill. The present work is a review of alternate methods of mastoidectomy and cochleostomy/round window enlargement that may reduce the risk of acoustic inner ear trauma associated with use of surgical drills during cochlear implant surgery. MATERIALS AND METHODS: MEDLINE database search was conducted using PubMed and Google Scholar search engines. Inclusion criteria for this study was the use of a laser to ablate the bone respectively the opening of Cochlear in terms of Cochleostomy. RESULTS: For the experimental studies, a total number of 4 papers were found, which deal with the application of the widely used CO2 laser. A comparison of the works could only partially under the above criteria, since no single study protocol was used and not always the sound pressure levels were determined occurring or evidence of damage to the inner ear missing. But for all that, a comparison of the work has been attempted because it is the authors' opinion about a promising approach to the atraumatic opening of the inner ear. CONCLUSION: There are promising approaches, using a laser to realize the erosion of bone and perform the opening of the inner ear. Nevertheless, there is a significant need for further investigations and in particular, the acoustic injury is not well enough understood here.


Subject(s)
Cochlea/surgery , Cochlear Implantation/methods , Laser Therapy/methods , Ostomy/methods , Cochlear Implantation/instrumentation , Laser Therapy/instrumentation , Lasers, Gas/therapeutic use , Mastoid/surgery , Round Window, Ear/surgery
9.
HNO ; 63(8): 552-6, 2015 Aug.
Article in German | MEDLINE | ID: mdl-26160005

ABSTRACT

BACKGROUND: Head and neck tumors are rare entities in neonates. Hamartomas are benign congenital neoplasms. To date, there is a lack of sufficient epidemiological data concerning hamartomas in the field of otorhinolaryngology. MATERIALS AND METHODS: We retrospectively analyzed experiences at the Charité over the past 10 years in an ICD-10-based manner. Our otorhinolaryngology department maintains close cooperation with the level 1 perinatal center on our campus. RESULTS: The authors identified 3 patients suffering from fibrous hamartomas. This corresponds to an incidence of 2-3/30,000 newborns. The clinical aspects and courses are described in detail. Experiences with the management of hamartomas obstructing the upper aerodigestive tract are described. CONCLUSION: Head and neck hamartomas are very rare malformations. They possess the ability to cause otorhinolaryngological emergencies in newborns. Interdisciplinary management and histological assessment are mandatory. Anmerkung.


Subject(s)
Academic Medical Centers/statistics & numerical data , Hamartoma/epidemiology , Hamartoma/pathology , Head and Neck Neoplasms/epidemiology , Head and Neck Neoplasms/pathology , Child, Preschool , Female , Germany/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Male , Risk Assessment
10.
Eur J Cancer ; 51(4): 514-521, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25623438

ABSTRACT

BACKGROUND: Increases in incidence of oropharyngeal squamous cell carcinoma (OPSCC) in countries with falling tobacco use have been attributed to a growing role of human papilloma virus (HPV) in the carcinogenesis. Trends of HPV prevalence in populations with persistently high portions of smokers are poorly characterised. PATIENTS AND METHODS: Registry data from East Germany were used to determine incidence trends between 1998 and 2011. Data from patients treated at the Charité University Medicine Berlin between 2004 and 2013 (cohort 1, N=436) were used for estimation of trends in HPV prevalence, smoking and survival. HPV prevalence was prospectively confirmed in cohort 2 (N=213) comprising all primary HNSCC cases at the Charité in 2013. RESULTS: Between 1998 and 2011 incidence of both OPSCC and non-OPSCC increased. An increase in HPV prevalence (% of HPV+ cases in 2004-2006 versus 2012-2013: 27% versus 59%, P=0.0004) accompanied by a moderate decrease in the portion of current smokers was observed in OPSCC but not in non-OPSCC. The change in disease epidemiology in OPSCC was associated with significant improvement in overall survival. Increased HPV prevalence in OPSCC (48%) compared to non-OPSCC (11%) was confirmed in cohort 2. CONCLUSIONS: Despite clear differences to the United States in terms of tobacco use, the increase in OPSCC incidence in a European population was also mainly attributed to HPV, and the HPV status significantly affected prognosis. For clinical trial design it is important to consider the large group of smokers within HPV-induced OPSCC.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Head and Neck Neoplasms/epidemiology , Papillomaviridae/isolation & purification , Smoking/adverse effects , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/virology , Europe/epidemiology , Female , Head and Neck Neoplasms/etiology , Head and Neck Neoplasms/virology , Humans , Incidence , Male , Smoking/epidemiology , Squamous Cell Carcinoma of Head and Neck
11.
J Comp Pathol ; 151(1): 19-24, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24813152

ABSTRACT

Feline lung tumours are currently subclassified according to the criteria of the World Health Organisation, but this scheme contains overlap in the tumour phenotype. The aims of the present study were to re-evaluate the histological features of feline lung tumours and to correlate these with expression of the markers thyroid transcription factor (TTF)-1 and Ki67. TTF-1 was found to be a highly specific marker for neoplastic and non-neoplastic lung tissue and thyroid tissue, but was expressed only weakly in invasive lung tumours. A combined semiquantitative score for Ki67 and TTF-1 expression correlated well with differentiation and invasive behaviour of the tumours and may thus be of potential value for evaluation of feline lung tumours.


Subject(s)
Biomarkers, Tumor/analysis , Cat Diseases/pathology , Lung Neoplasms/veterinary , Nuclear Proteins/biosynthesis , Transcription Factors/biosynthesis , Adenoma/pathology , Adenoma/veterinary , Animals , Carcinoma/pathology , Carcinoma/veterinary , Cats , Immunohistochemistry , Lung Neoplasms/pathology , Thyroid Nuclear Factor 1
12.
HNO ; 61(2): 159-60, 162-5, 2013 Feb.
Article in German | MEDLINE | ID: mdl-23223919

ABSTRACT

We report on a rare case of an exon 16 mutation of the MYH9 gene in a 23-year-old woman. This gene encodes for non-muscular myosin IIA, which acts as a cytoskeletal contractile protein in diverse cell types. This disorder led to sensorineural hearing loss, macrothrombocytopenia, and proteinuria. MYH9 gene mutation can lead to diverse organ manifestation like pre-senile cataract or renal failure which are progressive in course. Due to the current lack of causal treatment, diagnostic steps, advice for follow-up examinations and symptomatic therapy approaches are presented.


Subject(s)
Genetic Predisposition to Disease/genetics , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Molecular Motor Proteins/genetics , Myosin Heavy Chains/genetics , Thrombocytopenia/diagnosis , Thrombocytopenia/genetics , Female , Hearing Loss, Sensorineural/therapy , Humans , Mutation/genetics , Thrombocytopenia/therapy , Young Adult
13.
Dtsch Med Wochenschr ; 137(43): 2201-6, 2012 Oct.
Article in German | MEDLINE | ID: mdl-23076666

ABSTRACT

BACKGROUND: Psychoeducation and professional support of family caregivers are regarded as important aspects in dementia care. In the context of a general practitioner's (GP) based dementia care project we investigated if professional counselling after making a diagnosis of dementia can reduce the development of depression in family caregivers. METHODS: 42 patients with dementia and their family caregivers took part in the prospective, randomized study with a follow-up after 18 months. 29 families received psychosocial counselling, the control group was provided an information brochure about dementia including helpful contact addresses. Counselling included education about the illness. Additionally, the current individual needs were identified and assistance was administered if necessary. RESULTS: The counseling was rated as "very helpful" or "helpful" by most of the caregivers as well as by the partaking GPs. While depression rate between counseling and control group did not differ significantly at baseline, the depression rate was significantly increased in the control group after 18 month as compared to the intervention group. CONCLUSION: Despite the small study size we provide first strong evidence that early psychosocial counselling can reduce the development of depression in family caregivers. Early, professional counselling improves the quality of dementia care within a GP-based dementia care setting and it might stabilize and extend the home care duration of dementia patients.


Subject(s)
Alzheimer Disease/nursing , Alzheimer Disease/psychology , Caregivers/psychology , Cost of Illness , Counseling/methods , General Practice , Home Nursing/psychology , Activities of Daily Living/classification , Activities of Daily Living/psychology , Aged , Aged, 80 and over , Consumer Behavior , Depressive Disorder/prevention & control , Depressive Disorder/psychology , Follow-Up Studies , Humans , Male , Mental Status Schedule , Middle Aged , Pamphlets , Personality Inventory , Prospective Studies , Quality of Life/psychology , Risk Factors , Social Support
15.
HNO ; 59(10): 1063-6, 2011 Oct.
Article in German | MEDLINE | ID: mdl-21735278

ABSTRACT

We report on a very rare case of iceberg tumor. A giant lipoma arising from the deep lobe of the parotid gland led to an infraauricular mass and tonsil protrusion. After appropriate imaging (ultrasound and MRI) surgical resection was performed. Tonsil protrusions require differential diagnostic evaluation. Apart from the most prevalent parotid gland tumors, like pleomorphic adenoma and cystadenolymphoma, one must consider rare lipomas. Malignancy (e.g. liposarcoma) can only be excluded by histological examination of the whole specimen.


Subject(s)
Lipoma/diagnosis , Palatine Tonsil/pathology , Parotid Neoplasms/diagnosis , Facial Paralysis/diagnosis , Facial Paralysis/prevention & control , Humans , Lipoma/pathology , Lipoma/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Invasiveness , Parotid Gland/pathology , Parotid Gland/surgery , Parotid Neoplasms/pathology , Parotid Neoplasms/surgery , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Skull Base/pathology , Submandibular Gland/pathology , Submandibular Gland/surgery , Tumor Burden , Ultrasonography
17.
Clin Microbiol Infect ; 16(7): 934-44, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19686277

ABSTRACT

Long-term-care facilities (LTCFs) are reservoirs of resistant bacteria. We undertook a point-prevalence survey and risk factor analysis for specific resistance types among residents and staff of a Bolzano LTCF and among geriatric unit patients in the associated acute-care hospital. Urine samples and rectal, inguinal, oropharyngeal and nasal swabs were plated on chromogenic agar; isolates were typed by pulsed-field gel electrophoresis; resistance genes and links to insertion sequences were sought by PCR; plasmids were analysed by PCR, restriction fragment length polymorphism and incompatibility grouping. Demographic data were collected. Of the LTCF residents, 74.8% were colonized with ≥1 resistant organism, 64% with extended-spectrum ß-lactamase (ESBL) producers, 38.7% with methicillin-resistant Staphylococcus aureus (MRSA), 6.3% with metallo-ß-lactamase (MBL) producers, and 2.7% with vancomycin-resistant enterococci. Corresponding rates for LTCF staff were 27.5%, 14.5%, 14.5%, 1.5% and 0%, respectively. Colonization frequencies for geriatric unit patients were lower than for those in the LTCF. Both clonal spread and plasmid transfer were implicated in the dissemination of MBL producers that harboured IncN plasmids bearing bla(VIM-1), qnrS, and bla(SHV-12). Most (44/45) ESBL-producing Escherichia coli isolates had bla(CTX-M) genes of group 1; a few had bla(CTX-M) genes of group 9 or bla(SHV-5); those with bla(CTX-M-15) or bla(SHV-5) were clonal. Risk factors for colonization of LTCF residents with resistant bacteria included age ≥86 years, antibiotic treatment in the previous 3 months, indwelling devices, chronic obstructive pulmonary disease, physical disability, and the particular LTCF unit; those for geriatric unit patients were age and dementia. In conclusion, ESBL-producing and MBL-producing Enterobacteriaceae and MRSA were prevalent among the LTCF residents and staff, but less so in the hospital geriatric unit. Education of LTCF employees and better infection control are proposed to minimize the spread of resistant bacteria in the facility.


Subject(s)
Bacteria/isolation & purification , Drug Resistance, Multiple, Bacterial , Hospital Units , Long-Term Care , Patients , Personnel, Hospital , Bacteria/drug effects , Cross Infection/diagnosis , Cross Infection/epidemiology , Cross Infection/microbiology , Electrophoresis, Gel, Pulsed-Field , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Enterococcus/drug effects , Enterococcus/isolation & purification , Health Services for the Aged , Hospitals , Humans , Inguinal Canal/microbiology , Italy , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Nose/microbiology , Oropharynx/microbiology , Plasmids , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Rectum/microbiology , Risk Factors , Urine/microbiology , Vancomycin Resistance
18.
Horm Metab Res ; 36(8): 531-7, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15326562

ABSTRACT

The aim of this study was to establish a diabetic model of primary human adipocytes for investigating potential defects in early insulin signalling. Specimens of human subcutaneous adipose tissue were obtained during orthopaedic surgical procedures. Preadipocytes were isolated and differentiated to adipocytes. Western blot analysis and immunoprecipitation were performed to determine protein content of IRS-1, IRS-2, p85, phosphorylation of IRS-1, IRS-2, Akt and MAPK as well as association between p85 and IRS-1/IRS-2. In addition to short-term insulin stimulation, the effect of hyperinsulinaemia was investigated by treating cells with insulin over a period of 36 hours. We found a significantly reduced basal expression of IRS-1 (54 +/- 15%) in adipocytes from type 2 diabetic subjects compared to controls with a further significant reduction in expression after long-term treatment (30 +/- 12%) compared to short-term treatment. IRS-2 expression also showed a significant reduction under hyperinsulinaemic conditions (20 +/- 2%) in diabetics vs. controls. Furthermore, long-term treatment with insulin in diabetic adipocytes led to a significant reduction in the phosphorylation of IRS-1(68 +/- 11%), IRS-2 (82 +/- 11%), Akt (42 +/- 2%), and MAPK (92 +/- 12%) and in the subsequent association between p85 to IRS-1 and IRS-2 (100 +/- 16% and 96 +/- 12%) in comparison to controls. Investigating glucose uptake diabetic adipocytes revealed a significant reduction of 90 +/- 2%. In this study, we were able to establish a new diabetic model of primary human adipocytes. A defect in early insulin signalling in type 2 diabetic patients under hyperinsulinaemic conditions was determined. These results might help to give further insights in early insulin action; additionally, this human model represents a useful target for the study of new therapeutic approaches.


Subject(s)
Adipocytes/metabolism , Diabetes Mellitus, Type 2/metabolism , Insulin/metabolism , Signal Transduction , Adipocytes/pathology , Aged , Case-Control Studies , Cell Differentiation , Cells, Cultured , Deoxyglucose/pharmacokinetics , Diabetes Mellitus, Type 2/pathology , Female , Humans , Hyperinsulinism/chemically induced , Hyperinsulinism/metabolism , Insulin/pharmacology , Insulin Receptor Substrate Proteins , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Mitogen-Activated Protein Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphoproteins/metabolism , Phosphorylation/drug effects , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt , Time Factors
19.
Vasa ; 31(2): 75-80, 2002 May.
Article in English | MEDLINE | ID: mdl-12099148

ABSTRACT

OBJECTIVES: Oxidative modification of low-density-lipoprotein (LDL) increases its atherogenic potential to induce the accumulation of lipids and cells in the vascular wall. Patients have different lipoprotein profiles according to their LDL-subgroup pattern. The subgroup of LDL, which is most susceptible to oxidation, is most likely the dense LDL3 subfraction. In order to study an assumed association between hypertension, LDL subgroup distribution and the susceptibility of LDL to oxidation, 14 normotensive patients without family histories of hypertension (NT), 13 normotensive patients with family histories of hypertension (NT-FH), 10 hypertensive patients without family histories of (HT) and 11 hypertensive patients with family histories of hypertension (HT-FH) were evaluated. PATIENTS AND METHODS: LDL was oxidatively modified by incubation with copper ions (1.6 microM/L). The course of LDL-oxidation was measured in vitro by continuous photometric monitoring and the quantitative distribution of 3 LDL-subgroups by capillary isotachophoresis (ITP). RESULTS: The lag-phases of NT-FH and hypertensive patients were shorter than those of the control group (NT: 116 +/- 36 minutes; NT-FH 92 +/- 32 minutes, p < 0.05; HT: 95 +/- 41 minutes; HT-FH: 76 +/- 33 minutes, p < 0.05). Compared to NT a significant difference in the relative preponderance of LDL3 subgroup was observed for HT-FH (23.5 +/- 4.6% versus NT: 19.3 +/- 6.6%), additionally, statistical analysis showed a similar trend amongst the other patient groups (NT-FH: 20.4 +/- 7.4%, HT: 21.4 +/- 4.6%). CONCLUSIONS: The increased occurrence of the LDL3 subgroup might contribute to a higher susceptibility to LDL oxidation and therefore create an increased risk of vascular disease in the genotypic and phenotypic hypertensive patient population.


Subject(s)
Hypertension/genetics , Lipoproteins, LDL/blood , Adult , Female , Genetic Predisposition to Disease , Genotype , Humans , Hypertension/blood , Male , Middle Aged , Oxidation-Reduction , Phenotype , Risk
20.
Eur J Immunol ; 31(11): 3153-64, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11745332

ABSTRACT

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.


Subject(s)
Ceramides/metabolism , Drosophila Proteins , Lipopolysaccharide Receptors/metabolism , Lipopolysaccharides/pharmacology , Membrane Microdomains/metabolism , Membrane Proteins , Monocytes/metabolism , Antigens, CD/metabolism , CD47 Antigen , Carrier Proteins/metabolism , Humans , Inflammation/metabolism , Ligands , Macrophage-1 Antigen/metabolism , Membrane Glycoproteins/metabolism , Receptors, Cell Surface/metabolism , Tetraspanin 28 , Toll-Like Receptor 4 , Toll-Like Receptors
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