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1.
Chirurg ; 90(11): 905-912, 2019 Nov.
Article in German | MEDLINE | ID: mdl-31359113

ABSTRACT

BACKGROUND: Radical en bloc resection of the tumor with ipsilateral hemithyroidectomy and central lymphadenectomy (PTX+HTX) is currently the generally recommended treatment strategy for parathyroid carcinoma (PC) in Germany; however, it remains unclear whether the en bloc resection leads to a prognostic benefit compared to parathyroidectomy (PTX) alone, especially considering disease-free and overall survival. OBJECTIVE: This study analyzed the survival of patients with PC after PTX+HTX compared to patients with PTX. METHODS: Patients with PC were identified from a prospective database and retrospectively analyzed regarding clinicopathological features, surgical treatment, disease-free interval and overall survival. RESULTS: Out of 1705 patients who were operated on because of primary hyperparathyroidism (pHPT), 18 (1.1%) had histologically confirmed PC. In nine patients PTX+HTX was initially performed and the other nine patients received only PTX. After PTX, all of the nine patients developed a recurrence after a median of 18 months (range 7-84 months), while only one patient had a recurrence after PTX+HTX. After PTX a median three (range 2-18) reoperations were indicated for relapse but after PTX+HTX only one patient had to undergo two relapse surgeries (p < 0.001). The recurrence-free survival after PTX+HTX was significantly longer than after PTX (143 vs. 18 months, p = 0.01), while the overall survival of both groups after a median follow-up of 107.5 months did not significantly differ. DISCUSSION: If there is any clinical suspicion of PC, an en bloc resection should be performed to prolong recurrence-free survival and avoid reoperations.


Subject(s)
Parathyroid Neoplasms , Parathyroidectomy , Germany , Humans , Neoplasm Recurrence, Local , Parathyroid Neoplasms/surgery , Prognosis , Prospective Studies , Retrospective Studies
2.
Transl Psychiatry ; 6(12): e974, 2016 12 06.
Article in English | MEDLINE | ID: mdl-27922638

ABSTRACT

Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory.


Subject(s)
Dopamine/physiology , Extinction, Psychological/physiology , Fear/physiology , Histone Acetyltransferases/physiology , Signal Transduction/physiology , Amygdala/physiology , Animals , Benzamides/pharmacology , Combined Modality Therapy , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Extinction, Psychological/drug effects , Fear/drug effects , Implosive Therapy , Levodopa/pharmacology , Male , Mice , Prefrontal Cortex/physiology , Pyridines/pharmacology , Signal Transduction/drug effects
3.
Nature ; 531(7594): 371-5, 2016 Mar 17.
Article in English | MEDLINE | ID: mdl-26958833

ABSTRACT

Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.


Subject(s)
Insulin-Like Growth Factor I/metabolism , Neural Inhibition , Neurons/metabolism , Vasoactive Intestinal Peptide/metabolism , Visual Cortex/cytology , Visual Cortex/physiology , Animals , Female , Male , Mice , Mice, Inbred C57BL , Neural Pathways , Neuronal Plasticity , Neurons/cytology , Pyramidal Cells/metabolism , Synapses/metabolism , Vision, Ocular/physiology
4.
Org Lett ; 3(24): 3955-7, 2001 Nov 29.
Article in English | MEDLINE | ID: mdl-11720578

ABSTRACT

Vinylsilanes are converted into enamides by a sequence comprising epoxidation, nucleophilic ring opening of the resulting epoxysilanes with NaN(3), and reduction of the azide, followed by a "one-pot" N-acylation/Peterson elimination process. This method is distinguished by its wide applicability and stereoselective course. [reaction: see text]

5.
J Cardiothorac Vasc Anesth ; 12(4): 390-2, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9713724

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the incidence of cardiopulmonary resuscitation (CPR) after cardiac surgery and to find predictors of survival. DESIGN: A retrospective study with data obtained by chart review. SETTING: A university hospital 24-bed cardiac surgical intensive care unit (ICU). PARTICIPANTS: Between 1993 and 1994, 4,968 consecutive adult patients who underwent cardiac surgery at the authors' hospital were studied. INTERVENTIONS: None. MAIN RESULTS: One hundred thirteen of these patients (2.3%) were resuscitated. Seventy-nine patients (70%) survived to be discharged from the hospital. Significant predictors of survival were the time between admission to the ICU and initiation of CPR, CPR time, and creatine kinase (CK) and CK-MB values. CONCLUSIONS: The incidence of CPR after cardiac surgery was 2.3% with no difference between valve surgery and CABG. Best results were achieved when arrhythmias or bleeding were the predisposing causes. Further studies have to be undertaken concerning long-term results and quality of life of the discharged patients.


Subject(s)
Cardiac Surgical Procedures , Cardiopulmonary Resuscitation , Adult , Aged , Aged, 80 and over , Arrhythmias, Cardiac/complications , Cardiac Surgical Procedures/adverse effects , Coronary Artery Bypass/adverse effects , Creatine Kinase/blood , Critical Care , Female , Forecasting , Heart Valves/surgery , Humans , Incidence , Isoenzymes , Longitudinal Studies , Male , Middle Aged , Patient Admission , Patient Discharge , Postoperative Hemorrhage/complications , Quality of Life , Retrospective Studies , Risk Factors , Survival Rate , Time Factors
6.
J Interferon Cytokine Res ; 16(4): 283-7, 1996 Apr.
Article in English | MEDLINE | ID: mdl-9162521

ABSTRACT

We compared the antiviral activities of three recombinant human interferons (IFN-alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.


Subject(s)
Antiviral Agents/therapeutic use , Carrier State , Coxsackievirus Infections/drug therapy , Enterovirus B, Human/drug effects , Heart/drug effects , Interferons/therapeutic use , Cells, Cultured , Fibroblasts/drug effects , Fibroblasts/virology , Heart/virology , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Interferon-beta/therapeutic use , Interferon-gamma/therapeutic use , Myocardium/cytology , Recombinant Proteins/therapeutic use
7.
J Mol Cell Cardiol ; 27(10): 2199-208, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8576936

ABSTRACT

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population. Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml, whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (< 50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy.


Subject(s)
Antiviral Agents/pharmacology , Enterovirus B, Human/drug effects , Fibroblasts/drug effects , Heart/virology , Interferon-alpha/pharmacology , Myocardium/cytology , Virus Replication/drug effects , Cell Division/drug effects , Cells, Cultured , Child, Preschool , Enterovirus B, Human/physiology , Fibroblasts/virology , Humans , Infant , Interferon alpha-2 , Myocarditis/virology , Recombinant Proteins , Virus Latency
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