Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

Image fusion of bone SPECT and CT - a specific diagnostic method in oral and maxillofacial surgery]

OBJECTIVE: The aim of this study was to evaluate the benefit of image fusion of CT (computertomography) and bone SPECT (single photon emission computed tomography) in diagnosis of head and neck cancer. METHODS AND PATIENTS: Computer based image fusion has been applied in 39 patients with suspected cancer in the oromaxillofacial region following CT and SPECT without any further hazard for the patients. Afterwards image fusion was set in comparision to simultaneously evaluation of CT and SPECT and histological findings. RESULTS: In 5 out of 39 patients SPECT/CT image fusion obtained more precise anatomical findings in tumour expansion than simultaneously evaluation of CT and SPECT. CONCLUSION: For planning of surgical and radiation therapy of oral and maxillofacial cancer, image fusion of CT/SPECT provides efficient and plastical diagnostic imaging. Particularly in complex anatomical regions like maxilla or base of the skull image fusion could be an additional device, if simultaneous evaluation of CT and SPECT is not clear.     

Bone-ligament transfer of coracoacromial ligament for acromioclavicular dislocation: A new fixation method used in 6 cases

We treated 6 grade III acromioclavicular injuries with a new fixation method using a bone-ligament transfer of the coracoacromial ligament into a clavicular tunnel. After an average of 16 months, function and cosmesis were excellent in all patients.     

Predictors of poliomyelitis case confirmation at initial clinical evaluation: implications for poliomyelitis eradication in the Americas.

In 1985, the Pan American Health Organization adopted the goal of eradication of poliomyelitis from the Americas by 1990. Strategies to accomplish this included high vaccination coverage, aggressive outbreak control, and active surveillance for acute flaccid paralysis (AFP). Although the sensitivity of AFP surveillance for detecting paralytic poliomyelitis cases is high, studies have shown the specificity to be low. In 1990, 2497 notified cases of AFP were investigated in the Americas of which 2146 had stool specimens collected. However, only 18 were confirmed as poliomyelitis by isolation of wild poliovirus from stool specimens, 71 were classified as being compatible with poliomyelitis. Cases of AFP due to causes other than poliomyelitis result in extensive but unnecessary outbreak control measures. To predict, at initial clinical evaluation, the likelihood of future confirmation as a case of poliomyelitis, likelihood ratios (LR) were calculated for different combinations of clinical characteristics of AFP cases (249) from Mexico in 1989 and 1990. The best predictors in a child with AFP were proximal muscle involvement which progressed '4 days together with fever at onset of paralysis, and proximal and unilateral involvement with either fever at onset or paralysis which progressed '4 days. The odds would increase by 12 that the child would eventually be confirmed as poliomyelitis (19), based on a stool culture positive for wild poliovirus (95% confidence interval (CI) 2.6-55.9). A guide for use in the field is proposed whereby local health officials, often with little training in neurological evaluation, can predict at initial clinical examination the likelihood that an AFP case will subsequently be confirmed as poliomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Energy spectra of poly(arylenevinylene)s containing different aromatic units

The energy gaps of poly(p-arylenevinylene)s with phenylene, naphthylene and anthrylene subunits are determined by extrapolating the UV/VIS spectroscopic data of the oligomers. The band structure of the three polymers was theoretically investigated. The topology-, geometry- and correlation-factors were determined upon which the energy spectra of this class of one-dimensional π-electron systems depend.     

Thrombin Inhibition in discordant xenograft rejection

Abstract: Microvascular thrombosis and the associated platelet and endothelial cell activation are prominent observations in xenograft rejection. This pathological picture could be related to the excessive generation of thrombin in the context of either inflammation or putative inter-species molecular incompatibilities between activated coagulation factors and their natural anticoagulants. Relatively selective thrombin Inhibition with the serine protease inhibitor SDZ MTH 958 (MTH-958) are independent of heparinoids and anti-thrombin III. MTH-958 has been shown to significantly prolong porcine cardiac function during perfusion with human blood in an ex vivo model. The aim of this study was to validate the role of thrombin generation in a rodent model of discordant xenograft rejection in vivo. The effect of thrombin inhibition with MTH-958 was tested in both hyperacute rejection (HAR) and delayed xenograft rejection (DXR) after decomplementation with cobra venom factor (CVF) in normal Lewis (Lew) rats and Intrinsic C6 deficiency In PVG (C6-/PVG) recipient rats. Recipient rats received heterotopic guinea pig cardiac xenografts and were treated with titrated doses of MTH-958 until the time of graft rejection. Plasma samples at selected time points were examined to confirm effective thrombin inhibition, and rejected grafts were analyzed by immunohistology. MTH-958 significantly improved graft survival in HAR albeit the extent of prolongation was not marked, but the agent failed to prolong survival In CVF-treated Lew rats. In C6-/PVG rats receiving MTH-958, a significantly reduced graft survival time was observed when compared with C6-/PVG controls. The grafts from MTH-958-treated animals showed dense deposits of C3, IgM, and IgG with fibrin levels similar to controls. The thrombin antagonist tested could prolong xenograft survival during HAR but had no benefit in DXR. The relative non-specificity of the serine protease inhibitor MTH-958 with the potential activation of alternative pathway of complement via the inhibition of factor I could account for the failure to prolong xenograft survival in DXR. The pathogenetic significance of thrombin generation in this situation remains to be determined by the use of more selective and pharmacologically acceptable I anti-thrombin agents.     

Aktuelle und effektive bildgebende Diagnostik von Sprunggelenk und Fuß

Projection radiographic techniques have been used in a standardized manner for decades for the diagnosis of conditions of the foot and ankle; the indications for them and the pattern of findings useful in the initial diagnosis and monitoring of the course are generally known to clinical radiology staff. Computed tomography has been introduced as an extension of the basic procedures performed for diagnosis in the ankle and the hindfoot. In the case of complex fractures, however, specialist experience is essential. CT is an easily accessible investigative procedure and is meanwhile economical and very powerful. Magnetic resonance imaging supplements the range of investigations in special cases when there are particular problems. Microfractures, findings indicative of inflammation and/or dystrophy and, in particular questions concerning the musculoligamentous support system are the situations in which such investigations are needed. Ultrasound has an additive value vis-à-vis magnetic resonance imaging and is an easily accessible and highly effective examination procedure both for the primary diagnosis and for serial monitoring. Financial constraints in the healthcare sector are increasingly limiting purely medical indications. Regardless of this development, the retention of projection radiography, computer tomography, and magnetic resonance imaging must be demanded for the initial diagnosis in the care of foot and ankle injuries. The earliest possible implementation of all these techniques for the initial diagnosis is the first step towards effective treatment. Cafrefully chosen and, if appropriate, complementary strategies are needed for monitoring of the course and for assessment.