An anti-CD44 antibody does not enhance engraftment of DLA-identical marrow after low-dose total body irradiation

920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings.     

The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

Prevalence of traumatic injuries to the permanent incisors in candidates for orthodontic treatment

Abstract  – The dental records made on presentation of 1367 consecutive patients (731 females and 636 males) for orthodontic treatment at a private orthodontic practice between 1998 and 2002 were examined for data relating to trauma to the permanent incisors. The results showed that 10.3% of these patients had suffered from dental trauma before the onset of orthodontic treatment. The highest prevalence of dental trauma was determined in the 11–15 years age group, corresponding to the dental developmental stage of the late mixed dentition. The most frequently affected teeth were the maxillary central incisors (79.6%), and the most common types of trauma were fracture of enamel–dentin without pulpal involvement (42.7%) and fracture of enamel (33.8%). Compared to patients with normal overjet and adequate lip coverage, the frequency of dental trauma was significantly higher in patients with increased overjet and adequate lip coverage ( P  = 0.028) or with increased overjet and inadequate lip coverage ( P  = 0.003). The results of the present study indicate that a significant percentage of candidates for orthodontic treatment, and especially those with increased overjet and inadequate lip coverage, suffer trauma to their permanent incisors before the onset of orthodontic treatment. It might also be concluded that preventive orthodontic treatment of such patients should be initiated and completed before the age of 11, i.e. in the early to middle mixed dentition.     

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.     

Bildgebende Diagnostik bei Verletzungen des Ellbogengelenks

Trauma und Berufskrankheit - Zusammenfassung Der Nachweis oder Ausschluss ossärer Verletzungen am Ellbogengelenk wird primär mit der Projektionsradiographie in 2 Ebenen geführt....