Therapeutic vaccination for HPV induced cervical cancers

Cervical Cancer is the second leading cause of cancer-related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.     

Murine polyomavirus-like particles induce maturation of bone marrow-derived dendritic cells and proliferation of T cells

We analysed the effects of murine polyomavirus-like particles (PLPs) on bone marrow-derived dendritic cells (BMDCs) and T cells in vitro. BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines. Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells. Our results suggest that PLPs may be used as vaccine adjuvants priming dendritic cells to induce potent T cell responses.     

Suprakondyläre Femurosteotomien in Kniegelenknähe

Background

Similar to the reappreciation of high tibial osteotomy (HTO), supracondylar distal femur varus osteotomy (SCO) for lateral compartment osteoarthritis (OA) of the knee has gained renewed interest as new knowledge has become available on the influence of malalignment on the development, progression and symptoms of OA. Furthermore, the less than optimal results of total knee replacement (TKR) in younger patients have also led to renewed interest in joint-preserving treatment options.

Purpose

Varus SCO has not had the same success or widespread use as valgus HTO. The goal in SCO is similar to HTO, to shift the load from the diseased to the healthy ompartment, in order to reduce pain, improve function and delay placement of a TKR. Valgus OA however occurs much less frequently than varus OA and varus SCO is considered a technically more demanding procedure. In the past the surgical techniques for SCO were mainly dependent on difficult-to-use implants making the procedure more complex. Complication rates related to the failure of fixation up to 16 % have been reported.

Disussion

The new biplane osteotomy technique fixated with a locking compression plate is very stable; bone healing potential is optimal using this technique and takes 6–8 weeks. Full weight bearing before full bone healing is possible without loss of correction.

Conclusion

In this article patient selection, planning, surgical techniques, stability of fixation and bone healing for SCO are discussed. In the past the surgical techniques for SCO were mainly dependent on difficult to use implants making the procedure more complex. Complication rates related to the failure of fixation of up to 16 % have been reported.     

The past,present, and future of telemedicine for Parkinson's disease

Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinson's disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD. Historically, telemedicine has relied on expensive equipment to connect single patients to a specialist in pilot programs in wealthy nations. As the cost of video conferencing has plummeted, these efforts have expanded in scale and scope, now reaching larger parts of the world and extending the focus from care to training of remote providers. Policy, especially limited reimbursement, currently hinders the growth and adoption of these new care models. As these policies change and technology advances and spreads, the following will likely develop: integrated care networks that connect patients to a wide range of providers; education programs that support patients and health care providers; and new research applications that include remote monitoring and remote visits. Together, these developments will enable more individuals with PD to connect to care, increase access to expertise for patients and providers, and allow more‐extensive, less‐expensive participation in research. © 2014 International Parkinson and Movement Disorder Society     

Transcatheter electrosurgery in bipolar or monopolar modes

• Transcatheter electrosurgery has emerging value in a range of other new procedures that require traversing tissue (transcaval access, transcatheter Glenn Shunt) or slicing tissue (LAMPOON slicing of the mitral valve and BASILICA slicing of the aortic valve).
• This is the first report of bipolar radiofrequency wires used to cross lesions in humans, reported here in seven re‐entry CTO cases.
• The bipolar configuration may provide directionality to charge without need for wire alignment and advancement, but is theoretically disadvantageous for tissue “cutting” because of problems with charge concentration.

     

Phosphorylation of cytosolic proteins by resting and activated human neutrophils

A study was conducted on the phosphorylation of proteins in the neutrophil cytosol in response to phorbol myristate acetate (PMA) and N- formyl-methionyl-leucyl-phenylalanine (fMLP). Autoradiography of gel electrophoretograms prepared from neutrophils incubated with 32Pi in the presence and absence of the activators showed nine proteins whose state of phosphorylation was affected by neutrophil activation. 32P was gained by eight of these proteins and was lost by the ninth. For all but one of these proteins, the change in the extent of labeling appeared to reach completion by one to two minutes. It was possible to quantitate the changes in 32P content of three of the nine proteins. One of these was the 20-kD protein that lost label when the neutrophils were activated. Quantitation showed that over half the 32P present in this protein in the resting state was gone within 0.2 minutes after activation. The other two were proteins weighing 11 and 69 kD. The phosphorylation characteristics of these two proteins differed, depending on whether activation had been carried out with PMA or fMLP. These differences in protein phosphorylation support other evidence suggesting that PMA and fMLP do not activate neutrophils by identical biochemical pathways. Differences in phosphorylation between resting and activated cells were not affected by dibutyryl cyclic guanosine monophosphate (cGMP), dibutyryl cyclic adenosine monophosphate (cAMP), theophylline, aspirin, hydrocortisone, or colchicine. The differences were abolished, however, by 30 mumol/L trifluoperazine. This finding is consistent with the hypothesis that the calcium/calmodulin system plays a biochemical role in the activation of neutrophils.