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1.
Unfallchirurgie (Heidelb) ; 125(7): 553-558, 2022 Jul.
Article in German | MEDLINE | ID: mdl-34322719

ABSTRACT

According to the General Data Protection Regulation (GDPR 05/2018), anonymized data sets with a sufficiently high data density are classified as traceable and require a declaration of consent if they are evaluated centrally for research or quality control purposes. Quality assurance and further increases in the quality of care are, however, only possible with a nearly complete survey of seriously injured persons in the sense of health services research. The more than 600 German clinics that take part in the TraumaRegistry DGU® try to obtain the declarations of consent from this special patient population. The study clinic evaluated the rate of consent and the reasons for rejection or failure to obtain consent over a 12-month period. While using a resource-intensive workflow especially for patient education and obtaining the consent, a patient consent rate of 64.5% and an error rate of 35.5% were recorded. Of the 276 potential TraumaRegistry DGU® data records 98 could not be entered and were therefore neither available for quality control nor for multiple trauma research. In order to guarantee the quality control and the further improvement of the quality of care, an approximate total recording of the patient population is necessary; however, this cannot be achieved by requiring a declaration of consent. We therefore advocate creating the possibility of collecting the TraumaRegistry data set without consent, as this ultimately represents a standard data set, comparable to the Hospital Remuneration Act (§21-KHEntgG) data set but pseudonymised.


Subject(s)
Multiple Trauma , Computer Security , Health Services Research , Hospitals , Humans , Informed Consent
2.
Burns ; 46(5): 1013-1020, 2020 08.
Article in English | MEDLINE | ID: mdl-31843287

ABSTRACT

INTRODUCTION: Unplanned hospital readmissions in surgical areas account for high costs and have become an area of focus for health care providers and insurance companies. The aim of this systematic review is to identify the rate and common reasons for unplanned 30-day readmission following burns. METHODS: This study was performed following the PRISMA guidelines. Pubmed, Web of Science and CENTRAL databases were searched for publications without date or language restrictions. Extracted outcomes included 30-day readmission rate and reasons for readmission. Pooled 30-day readmission rate was estimated from weighted individual study estimates using random-effect models. Pooled estimates for risk factors are reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of eight studies were included into qualitative analysis and six (four adults, two children) into quantitative analysis. The overall readmission rate was 7.4% (95% CI 4.1-10.7) in adults and 2.7% (95% CI 2.2-3.2) in children. Based on two studies in 112,312 adult burn patients, burn size greater than 20% total body surface area (TBSA) was not a significant predictor of readmission rate (OR 1.75, 95% CI 0.64-4.75; NS). The most common reasons were infection/sepsis, wound healing complications, and pain in both adults and children. DISCUSSION: Unplanned readmissions following burns are generally low and appear more common in adults than in pediatric patients. However, only few studies are reporting on 30-day readmission rates following burns. Evidence is limited to support a significant association between greater burn size and higher readmission rates. Since cost effectiveness and utilized hospital capacity are becoming an area of focus for improvement in health care, future studies should assess the risk factors of unplanned readmission following burns. Follow-up assessments and outpatient resources, even if not underlined by this data, could reduce readmission rates. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42019117649.


Subject(s)
Burns/pathology , Infections/epidemiology , Pain/epidemiology , Patient Readmission/statistics & numerical data , Adult , Body Surface Area , Child , Humans , Risk Factors , Trauma Severity Indices , Wound Healing
4.
Handchir Mikrochir Plast Chir ; 52(2): 151-158, 2020 Apr.
Article in German | MEDLINE | ID: mdl-31724136

ABSTRACT

Human skin is an efficient barrier that protects the organism from noxious substances. Wounds destroy this barrier. Wound healing is a phased physiological regeneration of the destroyed tissue that ideally leads to occlusion of a wound, in particular by regeneration of connective tissue and capillaries. The Wnt signaling pathway is a highly conserved signal transduction cascade across the animal kingdom that controls basic cellular interactions in multicellular organisms. Accordingly, through the Wnt signaling path many processes, e. g. as the balance between proliferation and differentiation or apoptosis, coordinated. Wnt signaling is activated by a wound and participates in each subsequent phase of the healing process, beginning with inflammatory control and programmed cell death, to the mobilization of stem cells within the wound. Endogenous Wnt signaling is an attractive therapeutic approach to assist in the repair of skin wounds, as the complex mechanisms of the Wnt signaling pathway have become increasingly understood over the years. This review summarizes current data to clarify the role of Wnt signaling in the wound healing process of the skin.


Subject(s)
Skin Diseases , Wnt Signaling Pathway , Animals , Cell Differentiation , Humans , Skin , Wound Healing
5.
Orthop Traumatol Surg Res ; 104(6): 749-754, 2018 10.
Article in English | MEDLINE | ID: mdl-29581067

ABSTRACT

BACKGROUND: The acromioclavicular (AC) joint is of great importance for shoulder stability and one of the most frequently injured regions of the shoulder. HYPOTHESIS: AC joint reconstruction with the ligament augmentation & reconstruction system (LARS™) leads to a good-to-excellent outcome at long-term follow-up. PATIENTS AND METHODS: This study was performed as a retrospective single-centre data analysis of a level-I trauma centre. All patients treated operatively for an acute AC dislocation with the LARS™ between 2003 and 2013 were included. RESULTS: The study group consisted of three female (6%) and 44 male patients (94%) with an average age of 37 years and a minimum follow-up of two years. The overall mean clinical outcomes at latest follow-up were: Constant 93, DASH 2.64, ASES 96, SST 97, UCLA 34 and VAS 0.4-representing a good-to-excellent outcome in all patients. Overall, 45 patients (96%) reported to be very satisfied with the achieved result at latest follow-up. In five patients, (11%) complications occurred during the follow-up period, requiring surgical revision in four of the five patients (80%). CONCLUSION: AC joint reconstruction with the LARS™ achieves good-to-excellent clinical and functional outcomes at long-term follow-up with a surgical revision rate of 8.5%. LEVEL OF EVIDENCE: Retrospective follow-up study, case series, level IV.


Subject(s)
Acromioclavicular Joint/surgery , Joint Dislocations/surgery , Joint Instability/surgery , Plastic Surgery Procedures/methods , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Satisfaction , Postoperative Complications/etiology , Postoperative Complications/surgery , Plastic Surgery Procedures/adverse effects , Reoperation , Retrospective Studies , Young Adult
6.
J Psychiatr Res ; 97: 89-93, 2018 02.
Article in English | MEDLINE | ID: mdl-29223020

ABSTRACT

Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 ± 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.


Subject(s)
Blood Pressure/physiology , Depression/metabolism , Depression/physiopathology , Diabetes, Gestational/metabolism , Glucose Intolerance/metabolism , Intra-Abdominal Fat/metabolism , Adult , Biomarkers/metabolism , Cross-Sectional Studies , Depression/blood , Female , Glucose Intolerance/blood , Glucose Tolerance Test , Humans , Leptin/blood , Pregnancy , Resistin/blood
7.
Oper Orthop Traumatol ; 28(5): 392-401, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27484679

ABSTRACT

OBJECTIVE: Internal fixation of displaced fractures of the greater tuberosity allowing functional aftercare. INDICATIONS: Displaced fractures of the greater tuberosity >5 mm. Displaced fractures of the greater tuberosity >3 mm in athletes or overhead workers. Multiply fragmented fractures of the greater tuberosity. CONTRAINDICATIONS: Displaced 3­ or 4­part fractures of the proximal humerus. Nondisplaced fractures of the greater tuberosity. SURGICAL TECHNIQUE: Exposure of the fracture of the greater tuberosity by an anterolateral approach. Open reduction and temporary retention with a Kirschner wire or a "Kugelspieß" or reinforcement of the supraspinatus tendon and distal retention. Bending and positioning of the Bamberg plate and fixation by conventional or locking screws. Optional fixation of the rotator cuff to the plate. Exact monitoring of the implant position using the image intensifier to avoid inadequate distalization of the greater tuberosity. POSTOPERATIVE MANAGEMENT: Arm sling (e. g. Gilchrist) for 2 weeks. Start passive assisted exercise on postoperative day 1. Movement allowed up to the pain threshold. Physiotherapeutic treatment to prevent adhesions and capsular shrinking. RESULTS: In all, 10 patients with displaced fractures of the greater tuberosity underwent osteosynthesis using the Bamberg plate. After a follow-up of at least 6 months, a Constant-Murley score of 94.2  points (range 91-98 points) was achieved. The patients' average age was 45.6 years (range 29-68 years).


Subject(s)
Bone Plates , Fracture Fixation, Internal/instrumentation , Fractures, Comminuted/surgery , Minimally Invasive Surgical Procedures/instrumentation , Shoulder Fractures/surgery , Adult , Aged , Fracture Fixation, Internal/methods , Fracture Healing , Fractures, Comminuted/diagnosis , Humans , Middle Aged , Minimally Invasive Surgical Procedures/methods , Prosthesis Design , Shoulder Fractures/diagnosis , Treatment Outcome
8.
Am J Transplant ; 16(5): 1441-55, 2016 05.
Article in English | MEDLINE | ID: mdl-26607974

ABSTRACT

Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection.


Subject(s)
Calgranulin A/metabolism , Calgranulin B/metabolism , Graft Rejection/etiology , Graft Survival/immunology , Kidney Transplantation/adverse effects , Myeloid-Derived Suppressor Cells/immunology , T-Lymphocytes/immunology , Adult , Biomarkers/metabolism , Calgranulin A/immunology , Calgranulin B/immunology , Case-Control Studies , Cohort Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/metabolism , Graft Rejection/pathology , Humans , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Prognosis , Risk Factors
9.
Unfallchirurg ; 118(5): 476-8, 2015 May.
Article in German | MEDLINE | ID: mdl-25277729

ABSTRACT

Psychogenic polydipsia leading to severe hyponatremia is well documented in the literature. This electrolyte disorder can result in encephalopathy, cerebral edema and epileptic seizures. Another rare effect is rhabdomyolysis with all its well known complications (e.g. renal failure, hyperkalemia and cardiac arrhythmia) and even resulting in compartment syndrome due to severe muscle edema. We present the case of a patient with severe hyponatremia caused by psychogenic polydipsia leading to rhabdomyolysis and compartment syndrome.


Subject(s)
Compartment Syndromes/etiology , Compartment Syndromes/prevention & control , Polydipsia, Psychogenic/complications , Polydipsia, Psychogenic/therapy , Rhabdomyolysis/etiology , Rhabdomyolysis/prevention & control , Adult , Combined Modality Therapy/methods , Compartment Syndromes/diagnosis , Decompression, Surgical/methods , Diagnosis, Differential , Fluid Therapy/methods , Humans , Male , Polydipsia, Psychogenic/diagnosis , Rhabdomyolysis/diagnosis , Treatment Outcome
10.
J Cell Biochem ; 83(2): 326-41, 2001.
Article in English | MEDLINE | ID: mdl-11573249

ABSTRACT

The idea of a receptor reserve in mediating cellular function is well known but direct biochemical evidence has not been easy to obtain. This study stems from our results showing that L15 of epidermal growth factor (EGF) is important in both EGF receptor (EGFR) binding and activation, and the L15A analog of human EGF (hEGF) partially uncouples EGFR binding from EGFR activation (Nandagopal et al., [1996] Protein Engng 9:781-788). We address the cellular mechanism of mitogenic signal amplification by EGFR tyrosine kinase in response to L15A hEGF. L15A is partially impaired in receptor dimerization, shown by chemical cross-linking and allosteric activation of EGFR in a substrate phosphorylation assay. Immunoprecipitation experiments reveal, however, that L15A can induce EGFR autophosphorylation in intact murine keratinocytes by utilizing spare receptors, the ratio of total phosphotyrosine content per receptor being significantly lower than that elicited by wild-type. This direct biochemical evidence, based on function, of utilization of a receptor reserve for kinase stimulation suggests that an EGF variant can activate varying receptor numbers to generate the same effective response. L15A-activated receptors can stimulate mitogen-activated protein kinase (MAPK) that is important for mitogenesis. The lack of linear correlation between levels of receptor dimerization, autophosphorylation, and MAPK activation suggests that signal amplification is mediated by cooperative effects. Flow cytometric analyses show that the percentages of cells which proliferate in response to 1 nM L15A and their rate of entry into S-phase are both decreased relative to 1 nM wild-type, indicating that MAPK activation alone is insufficient for maximal stimulation of mitogenesis. Higher concentrations of L15A reverse this effect, indicating that L15A and wild-type differ in the number of receptors each activates to induce the threshold response, which may be attained by cooperative activation of receptor dimers/oligomers by van der Waal's weak forces of attraction. The maintenance of a receptor reserve underscores an effective strategy in cell survival.


Subject(s)
Epidermal Growth Factor/genetics , Epidermal Growth Factor/metabolism , ErbB Receptors/metabolism , Point Mutation/genetics , Alanine/genetics , Alanine/metabolism , Amino Acid Substitution/genetics , Animals , Binding Sites , Cell Division/physiology , Dimerization , Humans , Keratinocytes/cytology , Leucine/genetics , Leucine/metabolism , Ligands , Mice , Mitogen-Activated Protein Kinase 1/metabolism , Mitogens/pharmacology , Phosphorylation , Signal Transduction/drug effects , Signal Transduction/physiology
11.
J Nucl Med ; 42(8): 1243-50, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11483687

ABSTRACT

UNLABELLED: Acetate is preferentially transported into and metabolized by astrocytes, rather than synaptosomes or neurons, and labeled acetate is used as a glial reporter molecule to assess glial metabolism and glial-neuronal interactions. Because monocarboxylic acid transporter specificity might confer a phenotype to help localize, detect, and characterize brain tumors of glial origin, use of [2-(14)C]acetate and [(14)C]deoxyglucose (a glucose analog metabolized by all brain cells) was compared in rat and human brain tumors. METHODS: Cultured C6 glioma or U-373 glioblastoma/astrocytoma tumor cells were injected into the caudate nucleus of anesthetized CDF Fisher rats; 2--3 wk later, an intravenous pulse of [2-(14)C]acetate or [(14)C]deoxyglucose was given, and timed blood samples were drawn during the 5- or 45-min experiment, respectively. Local (14)C levels in the brain were assayed by quantitative autoradiography, and acetate uptake or glucose use was calculated. Uptake and metabolism of the [(14)C]acetate was also assayed in C6 glioma and human surgical tumor samples in vitro. RESULTS: [(14)C]Acetate uptake into rat brain C6 tumors was 9.9 +/- 2.1 mL/100 g/min, compared with 3.9 +/- 1.0 mL/100 g/min in contralateral tissue (n = 6; P < 0.001), and was much higher than that into other brain structures (e.g., 5:1 for white matter and 2:1 for cortical gray matter). Glucose use in C6 tumors was 111 +/- 34 micromol/100 g/min, versus 81 +/- 5 micromol/100 g/min in contralateral tissue (n = 6; P = 0.08); no left-right differences in glucose use or acetate uptake were seen in other brain structures. The tumor-to-contralateral-tissue ratio for acetate (2.3 +/- 0.3) exceeded that for deoxyglucose (1.4 +/- 0.5) (P < 0.05), indicating that acetate is a sensitive C6 glioma marker. [(14)C]Acetate uptake also demarcated a few 3-wk-old C6 tumors that had unlabeled necrotic cores. U-373 tumors were smaller than C6 tumors in rat brain and were detected equally well with [(14)C]acetate and [(14)C]deoxyglucose. In vitro uptake of [(14)C]acetate into human glioblastoma or meningioma tumors was higher than uptake into pituitary adenoma. Rat C6 and human tumors with high uptake metabolized acetate to acidic compounds and amino acids. CONCLUSION: Tumor imaging with radiolabeled acetate can help to localize and classify brain tumors. Transporter and metabolic substrate specificity are traits that can be exploited further for in vivo imaging of brain glial tumors.


Subject(s)
Acetic Acid , Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Meningioma/diagnostic imaging , Radiopharmaceuticals , Animals , Biotransformation , Brain/metabolism , Carbon Radioisotopes , Humans , Neoplasm Transplantation , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Rats , Transplantation, Heterologous , Tumor Cells, Cultured
12.
Eur J Pediatr ; 159(6): 412-5, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10867844

ABSTRACT

UNLABELLED: A neonate presented with clinical, biochemical, endocrine and radiographic features consistent with vitamin D deficiency rickets of maternal origin. Persistent hypocalcemia and subsequent development of pancytopenia, hemolysis and hepatosplenomegaly prompted further studies that led to the diagnosis of infantile osteopetrosis. CONCLUSION: Osteopetrosis is an important differential diagnosis of neonatal rickets and is not excluded by low vitamin D levels.


Subject(s)
Osteopetrosis/etiology , Vitamin D Deficiency , Female , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Complications
13.
J Biol Chem ; 274(12): 8208-16, 1999 Mar 19.
Article in English | MEDLINE | ID: mdl-10075725

ABSTRACT

The antineoplastic agent paclitaxel (TaxolTM), a microtubule stabilizing agent, is known to arrest cells at the G2/M phase of the cell cycle and induce apoptosis. We and others have recently demonstrated that paclitaxel also activates the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signal transduction pathway in various human cell types, however, no clear role has been established for JNK/SAPK in paclitaxel-induced apoptosis. To further examine the role of JNK/SAPK signaling cascades in apoptosis resulting from microtubular dysfunction induced by paclitaxel, we have coexpressed dominant negative (dn) mutants of signaling proteins of the JNK/SAPK pathway (Ras, ASK1, Rac, JNKK, and JNK) in human ovarian cancer cells with a selectable marker to analyze the apoptotic characteristics of cells expressing dn vectors following exposure to paclitaxel. Expression of these dn signaling proteins had no effect on Bcl-2 phosphorylation, yet inhibited apoptotic changes induced by paclitaxel up to 16 h after treatment. Coexpression of these dn signaling proteins had no protective effect after 48 h of paclitaxel treatment. Our data indicate that: (i) activated JNK/SAPK acts upstream of membrane changes and caspase-3 activation in paclitaxel-initiated apoptotic pathways, independently of cell cycle stage, (ii) activated JNK/SAPK is not responsible for paclitaxel-induced phosphorylation of Bcl-2, and (iii) apoptosis resulting from microtubule damage may comprise multiple mechanisms, including a JNK/SAPK-dependent early phase and a JNK/SAPK-independent late phase.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Microtubules/drug effects , Mitogen-Activated Protein Kinases , Ovarian Neoplasms/physiopathology , Paclitaxel/pharmacology , Female , Humans , JNK Mitogen-Activated Protein Kinases , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction , Transfection , Tumor Cells, Cultured
14.
Radiat Res ; 151(3): 244-56, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10073661

ABSTRACT

Monoclonal antibody 13A to murine CD44 was used to bind the alpha-particle emitter 213Bi to cell surfaces of cultured EMT-6 or Line 1 tumor cells. Data on kinetics and saturation of binding, cell shape and nuclear size were used to calculate the absorbed dose to the nuclei. Treatment of monolayer cells with [213Bi]MAb 13A produced a classical exponential survival curve with no apparent shoulder. Microdosimetry analyses indicated that 1.4-1.7 Gy produced a 37% surviving fraction (D0). Multicellular spheroids were shown to bind [213Bi]MAb 13A mainly on the outer cell layer. Relatively small amounts of activity added to the spheroids resulted in relatively large absorbed doses. The result was that 3-6-fold less added radioisotope was necessary to kill similar fractions of cells in spheroids than in monolayer cells. These data are consistent with the interpretation that the alpha particles from a single 213Bi atom bound to one cell can penetrate and kill adjacent cells. Flow cytometry was used to sort cells originating from the periphery or from the interior of spheroids. Cells from the outside of the [213Bi]MAb 13A exposed spheroids had a lower surviving fraction per administered activity than cells from the interior. Cells were killed efficiently in spheroids up to 20-30 cells in diameter. The data support the hypothesis that alpha-particle emitters should be very efficient at killing cells in micrometastases of solid tumors.


Subject(s)
Bismuth/therapeutic use , Immunoconjugates/therapeutic use , Radioisotopes/therapeutic use , Spheroids, Cellular/radiation effects , Alpha Particles/therapeutic use , Animals , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/therapeutic use , Cell Death/radiation effects , Cell Membrane/metabolism , Immunoconjugates/metabolism , Kinetics , Mice , Radiotherapy Dosage , Tumor Cells, Cultured , Tumor Stem Cell Assay
16.
Nervenarzt ; 69(11): 968-74, 1998 Nov.
Article in German | MEDLINE | ID: mdl-9859118

ABSTRACT

A number of observations including clinical manifestation, course, outcome, and family history, support the view that patients presenting with a major depression occurring first in late life should be treated as a nosological subgroup. In this study quantitative magnetic resonance imaging (MRI) was used to investigate volumes of different brain structures in 19 patients with late onset major depression (age of onset > 50) and 13 age matched controls. 3-D MRI sequences were acquired using a Siemens 1.5T scanner. Whole brain volume, CSF volume, volume of the frontal and temporal lobes and the volume of the amygdala-hippocampus complex were assessed using the software NMRWin. Compared to the controls, depressed patients showed a significantly lower whole brain volume and a significantly higher CSF volume, whereas volumes of the frontal and temporal lobes as well as the amygdala-hippocampus complex volumes were not significantly decreased. In addition, depressed patients exhibited a higher ventricle-brain ratio suggesting a higher degree of central atrophy compared to healthy individuals. Our results indicate that cerebral changes involving subcortical structures are of relevance in the pathogenesis of late-onset depression. Defining the aetiology of these lesions may be important for the development of preventive treatment of depression in the elderly.


Subject(s)
Brain/pathology , Dementia/diagnosis , Depressive Disorder, Major/diagnosis , Image Interpretation, Computer-Assisted/instrumentation , Magnetic Resonance Imaging/instrumentation , Aged , Aged, 80 and over , Atrophy , Brain Mapping/instrumentation , Female , Humans , Male , Mathematical Computing , Software
17.
Carcinogenesis ; 18(11): 2043-50, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9395200

ABSTRACT

A series of cells representing normal, non-tumorigenic cell lines, as well as differentiating neoplastic and undifferentiated neoplastic rat tracheal epithelial cell populations were evaluated for their ability to establish homologous and/or heterologous cell-cell gap junction communication in culture. Gap junction communication was evaluated by flow cytometric quantitation of the transfer of the fluorescent dye calcein from a donor to a recipient cell population via gap junctions. The data indicate that normal primary cultures of rat tracheal epithelial cells, as well as non-tumorigenic cell lines and squamous cell carcinomas cell populations, retain the ability to establish both homologous and heterologous gap junction communication. In all cases an average of >48% of recipient cells had acquired calcein label during a 5-h interval of co-culture of donor and recipient cells at confluent densities. Cells harvested directly from squamous cell carcinoma tumors exhibited similar levels of cell-cell communication. In contrast, cells giving rise to undifferentiated carcinomas, as well as cells harvested from undifferentiated carcinomas, exhibited very low levels or no homologous or heterologous cell-cell communication. Cell populations exhibiting distinctly different communication phenotypes were evaluated by Northern blot analysis for expression of connexins (Cx 26, 32 and 43) and E-cadherin. Neither communicating nor non-communicating cells expressed connexin 32. Those cell populations, which established functional gap junctions, expressed E-cadherin as well as connexin 26 and/or 43. In contrast, those cell populations that lacked the ability to communicate universally lacked expression of E-cadherin, and a quarter also lacked expression of detectable levels of connexin.


Subject(s)
Cadherins/analysis , Carcinoma, Squamous Cell/etiology , Cell Communication , Gap Junctions/physiology , Tracheal Neoplasms/etiology , Animals , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/ultrastructure , Connexins/analysis , Epithelial Cells/ultrastructure , Mice , Mice, Inbred ICR , Phenotype , Rats , Rats, Inbred F344 , Tracheal Neoplasms/chemistry , Tracheal Neoplasms/ultrastructure
18.
Blood ; 89(11): 4204-12, 1997 Jun 01.
Article in English | MEDLINE | ID: mdl-9166865

ABSTRACT

Hemoglobin (Hb) S Antilles is a naturally occurring form of sickling human Hb but causes a more severe phenotype than Hb S. Two homozygous viable Hb S Antilles transgene insertions from Tg58Ru and Tg98Ru mice were bred into MHOAH mice that express high oxygen affinity (P50 approximately 24.5 mm Hg) rather than normal (P50 approximately 40 mm Hg) mouse Hbs. The rationale was that the high oxygen affinity MHOAH Hb, the lower oxygen affinity of Hb S Antilles than Hb S (P50 approximately 40 v 26.5 mm Hg), and the lower solubility of deoxygenated Hb S Antilles than Hb S (approximately 11 v 18 g/dL) would favor deoxygenation and polymerization of human Hb S Antilles in MHOAH mouse red blood cells (RBCs). The Tg58 x Tg98 mice produced have a high and balanced expression (approximately 50% each) of h alpha and h beta(S Antilles) globins, 25% to 35% of their RBCs are misshapen in vivo, and in vitro deoxygenation of their blood induces 30% to 50% of the RBCs to form classical looking, elongated sickle cells with pointed ends. Tg58 x Tg98 mice exhibit reticulocytosis, an elevated white blood cell count and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.


Subject(s)
Anemia, Sickle Cell , Disease Models, Animal , Mice, Transgenic , Animals , Hemoglobin, Sickle/genetics , Humans , Mice
19.
J Affect Disord ; 42(1): 69-83, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9089060

ABSTRACT

Quantitative magnetic resonance imaging (MRI) was used to investigate volumes of different brain structures in 19 patients with late-onset major depression (DSM-III-R), 27 patients with Alzheimer's disease (NINCDS-ADRDA criteria) and 13 age matched controls. 3-D MRI sequences were acquired using a Siemens 1.5 T scanner. Whole brain volume, CSF volume, volume of the frontal and temporal lobes and the volume of the amygdala-hippocampus complex were assessed using the software NMR Win. Compared to the controls, depressed patients showed a significantly lower whole brain volume and a significantly higher CSF volume, whereas volumes of the frontal and temporal lobes as well as the amygdala-hippocampus complex volumes were not significantly decreased. In addition, depressed patients exhibited a higher ventricle-brain ratio suggesting a higher degree of central atrophy compared to healthy individuals. In contrast, Alzheimer patients showed significantly lower volumes than depressed patients and controls with respect to all volumetric parameters. Although the findings indicate the presence of brain atrophy in patients with late-onset depression, the pattern of volumetric changes in these patients differs markedly from that observed in patients with primary degenerative dementia.


Subject(s)
Brain/pathology , Dementia/diagnosis , Depressive Disorder/diagnosis , Magnetic Resonance Imaging , Neurocognitive Disorders/diagnosis , Aged , Aged, 80 and over , Amygdala/pathology , Atrophy , Brain Mapping , Cerebral Ventricles/pathology , Dementia/psychology , Depressive Disorder/psychology , Female , Frontal Lobe/pathology , Hippocampus/pathology , Humans , Male , Neurocognitive Disorders/psychology , Parietal Lobe/pathology , Reference Values
20.
Cell Immunol ; 173(1): 116-23, 1996 Oct 10.
Article in English | MEDLINE | ID: mdl-8871607

ABSTRACT

Interleukin-3 (Il-3) is a glycoprotein produced by a CD4+CD8- subpopulation of T-lymphocytes. Il-3 has been associated with the proliferation of bone marrow stem cells and their differentiation to granulocytes, macrophages, basophil/mast cells, megakaryocytes, erythroid cells, and neutrophils. The pBOR-Il-3 transgenic mice were developed by pronuclear microinjection to study how chemical insults modulate transcription of the Il-3 gene driven by a long-terminal repeat (LTR) of an endogenous retrovirus and to determine the biological consequences of interleukin-3 expression. We injected 5-azacytidine, a demethylating agent, to increase the LTR-driven expression of Il-3. Upon 5-azacytidine treatment, both the pBOR-Il-3 and the FVB/N nontransgenic controls developed thymic lymphomas. The pBOR-Il-3 mice developed thymic lymphomas at a higher frequency than the FVB/N mice. The thymic lymphoma cells were of a T-cell origin, as determined by T-cell receptor gene rearrangement analysis, and, in most cases, were of monoclonal origin. According to flow cytometric analysis of CD3, CD4, and CD8 cell surface markers, the thymic lymphoma cells did not lose their ability to differentiate, but the differentiation process was aberrant. Flow cytometric analyses also revealed that in pBOR-Il-3 mice the thymic lymphomas are mostly of a CD8+CD4- origin, whereas in the FVB/N group, the predominant type of thymic lymphoma is of a CD4+CD8- origin.


Subject(s)
Interleukin-3/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Thymus Neoplasms/immunology , Animals , Azacitidine/pharmacology , CD3 Complex/immunology , CD4 Antigens/immunology , CD8 Antigens/immunology , Carcinogens/pharmacology , Disease Models, Animal , Female , Gene Rearrangement, T-Lymphocyte , Incidence , Interleukin-3/pharmacology , Male , Mice , Mice, Transgenic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Thymus Neoplasms/genetics
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