Problems and needs for improving primary care of osteoarthritis patients: the views of patients, general practitioners and practice nurses

Background  

Osteoarthritis (OA) is highly prevalent and has substantial impact on quality of life as well as on healthcare costs. The general practitioner (GP) often is the first care provider for patients with this chronic disease. The aim of this study was to identify health care needs of patients with OA and to reveal possible obstacles for improvements in primary care management of OA patients.     

Über eine Epidemie der Heine-Medinschen Krankheit in den Niederlanden während des Jahres 1912

Ohne Zusammenfassung     

Dendrosome-based delivery of siRNA against E6 and E7 oncogenes in cervical cancer

Although small interfering RNA (siRNA) treatment holds great promise for the treatment of cancers, the field has been held back by the availability of suitable delivery vehicles. For cervical cancer the E6 and E7 oncogenes are ideal siRNA targets for treatment. The purpose of the present study was to explore the potential of dendrosomes for the delivery of siRNA targeting E6 and E7 proteins of cervical cancer cells in vitro. Optimization of dendrimer generation and nitrogen-to-phosphate (N/P) ratio was carried out using dendrimer–fluorescein isothiocyanate oligo complexes. The optimized N/P ratios were used in formulating complexes between dendrimers and siRNA targeting green fluorescence protein (siGFP). Although formulation 4D100 (dendrimer-siRNA complex) displayed the highest GFP knockdown, it was also found to be highly toxic to cells. In the final formulation 4D100 was encapsulated into dendrosomes so as to mask these toxic effects. The optimized dendrosomal formulation (DF), DF3 was found to possess a siGFP-entrapment efficiency of 49.76% ± 1.62%, vesicle size of 154 ± 1.73 nm, and zeta potential of +3.21 ± 0.07 mV. The GFP knockdown efficiency of DF3 (dendrosome) was found to be almost identical to that of 4D100, but the former was completely nontoxic to the cells. DF3 containing siRNA against E6 and E7 was found to knock down the target genes considerably, as compared with the other formulations tested. Our results imply that dendrosomes hold potential for the delivery of siRNA and that a suitable targeting strategy could be useful for applications in vivo.From the Clinical EditorsiRNA treatment holds great promise for the treatment of cancers, but overall, the availability of suitable delivery vehicles remains a major issue. The purpose of this study was to explore the potential of dendrosomes for the delivery of siRNA targeting specific proteins in cervical cancer cells in vitro. The results suggest that dendrosomes hold potential for the delivery of siRNA and a suitable targeting strategy could be useful for applications in vivo.     

Preclinical evaluation of coronary vascular function after cardioplegia with HTK and different antioxidant additives.

OBJECTIVE: Due to limited resources, improvement of preservation solutions is still of great importance in cardiac transplant surgery. New additives with antioxidant properties were tested with respect to coronary function of isolated rat hearts. METHODS: Bretschneider HTK solution containing none or an antioxidant additive (deferoxamine, trolox or LK 616) was used for 8h cold cardioplegia. After reperfusion with Krebs-Henseleit buffer (KHB), we assessed vascular dilator capacity (bradykinin, adenosine triphosphate, reactive hyperemia), myocardial function (left ventricular developed pressure, heart rate, oxygen consumption) and release of biochemical markers (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin, adenosine). RESULTS: Bradykinin- and adenosine triphosphate-induced vasodilations were largely reduced in hearts stored 8h in traditional HTK as compared to unstored controls. Storage in HTK+LK 616 significantly improved bradykinin-induced vasodilation. Vasodilation toward ATP was best preserved in hearts stored in HTK+deferoxamine. Deferoxamine and trolox, both improved reactive hyperaemic response during reperfusion. Left ventricular pressure development was significantly reduced after 8h cardioplegia, but no difference existed between different cardioplegia groups. Release of biochemical markers of tissue injury was similar in all cardioplegia groups. After storage in HTK+LK 616 (100 microM), however, heart marker release was slightly augmented as compared to HTK. CONCLUSIONS: Despite similar myocardial function and marker release, coronary vascular function after cardioplegic storage may profit by addition of iron chelators (or antioxidants) to traditional HTK solution.     

Einsatz einer Mischkultur in Acetat-Fermentationen

Bacterial cultures were selected from the native flora of liquid manure in order to metabolize liquid manure substances. The mixed culture used in the growth experiments is characterized by low growth rates when maximum degradation of acetate occurs. The biomass concentration reached 2.2 g/l.     

Evaluation and Treatment of Children with Primary Immune Deficiency in the Emergency Department

The potential for morbidity and mortality in patients who have PID with febrile and nonfebrile illness is extremely high. Familiarity with the clinical manifestations of PID and collaboration with a pediatric immunologist are prerequisites for optimal short-term care of these complex patients. Conservative management with empiric broad-spectrum antimicrobials, early and aggressive surgical debridement of abscesses, and admission at a tertiary pediatric care center are often indicated.     

Positive and negative symptoms covary during clozapine treatment in schizophrenia

Although negative symptoms were traditionally considered to be unresponsive to neuroleptic medication, recent studies have demonstrated that negative symptoms do improve during neuroleptic treatment and that such improvement tends to occur concurrently with improvement in positive symptoms. Clozapine is an atypical neuroleptic that is effective in a significant proportion of otherwise neuroleptic-nonresponsive schizophrenic patients; in contrast to conventional neuroleptics, clozapine is also purported to possess unique efficacy in the amelioration of negative symptoms. How clozapine-associated reduction in negative symptoms relates to change in positive symptoms is not clear. To study the relationship between change in positive and negative symptoms during clozapine treatment, we monitored symptomatology in 40 DSM-III-R schizophrenic patients before and about 8 weeks after a trial of clozapine. Both positive and negative symptoms improved significantly. There was a significant correlation (r = .63,p <.01) between change in positive symptoms and change in negative symptoms; as with conventional neuroleptics, negative symptoms improved concomitantly with positive symptoms during clozapine treatment. Clozapine's apparent greater efficacy on negative symptoms may be related to its greater efficacy on positive symptoms in otherwise neuroleptic-refractory patients and its lesser propensity to cause extrapyramidal side-effects.     

Coexistence of Neoplasia and Cortical Dysplasia in Patients Presenting with Seizures

Summary: Tumors and cortical dysplasia are associated with epilepsy, but few studies have examined the coexistence of neoplasia and dysplasia in these patients. We studied 13 patients (age 4–29 years) with recurrent seizures of 1 month to 21-year' duration (median 72 months). Ten patients were aged <21 years. Imaging studies localized the lesion to the temporal lobe (10 patients), parietal lobe (2 patients), and frontal lobe (1 patient). Tumors included ganglioglioma (8 patients), dysembryoplastic neuroepithelial tumor (DNT) (3 patients), and low-grade as- trocytoma (2 patients). Cortical dysplasia, including atypical aggregates of neurons (6 patients), multifocal loss of the cortical laminar architecture (7 patients), and neurons in the molecular layer of the cortex (3 patients) were observed near but separate from the tumor. Coexistence of certain tumors with cortical dysplasia, most frequently observed in the pediatric population, suggests a hamar-tomatous/dysplastic nature of the neoplasms.