Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single-dose and multiple-dose administration in healthy foals.

BACKGROUND: Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. OBJECTIVES: To evaluate the pharmacokinetic interactions and pulmonary distribution of rifampicin and gamithromycin in healthy foals, and to investigate the cellular uptake of gamithromycin in vitro. STUDY DESIGN: Controlled, four-period, consecutive, single-dose and multiple-dose study. METHODS: Pharmacokinetics and lung distribution of rifampicin (10 mg/kg) and gamithromycin (6 mg/kg) were measured in nine healthy foals using LC-MS/MS. Enzyme induction was confirmed using the 4ß-OH-cholesterol/cholesterol ratio. Affinity of gamithromycin to drug transport proteins was evaluated in vitro using equine hepatocytes and MDCKII-cells stably transfected with human OATP1B1, OATP1B3 and OATP2B1. RESULTS: Rifampicin significantly (P<0.05) increased the plasma exposure of gamithromycin (16.2 ± 4.77 vs. 8.57 ± 3.10 µg × h/mL) by decreasing the total body clearance. Otherwise, gamithromycin significantly lowered plasma exposure of single- and multiple-dose rifampicin (83.8 ± 35.3 and 112 ± 43.1 vs. 164 ± 96.7 µg × h/mL) without a change in metabolic ratio and half-life. Gamithromycin was identified as an inhibitor of human OATP1B1, OATP1B3 and OATP2B1 and as a substrate of OATP2B1. In addition, it was extracted by equine hepatocytes via a mechanism which could be inhibited by rifampicin. MAIN LIMITATIONS: Influence of gamithromycin on pulmonary distribution of rifampicin was not evaluated. CONCLUSION: The plasma exposure of gamithromycin is significantly increased by co-administration of rifampicin which is most likely caused by inhibition of hepatic elimination.

Biomechanical modelling of impact-related fracture characteristics and injury patterns of the cervical spine associated with riding accidents.

BACKGROUND: Horse-related injuries are manifold and can involve the upper and lower limbs, the trunk, spine or head. Cervical spine injuries are not among the most common injuries. However, they can be fatal and often result in neurological symptoms. This study investigated the influence of the posture of the cervical spine on the ultimate strength and the pattern of vertebrae failure with the aim to provide some guidance for protective clothing design. METHODS: Eighteen human cervical spines, each divided into two specimens (three vertebrae each), were subjected to a simulator test designed to mimic a spinal trauma in different postures of the specimen (neutral, flexion, extension). The stress-to-failure, the deformation at the time of fracture and the fracture patterns assessed based on CT scans were analysed. FINDINGS: Stress-to-failure of the superior specimens was lower for the flexion group compared to the others (P=0.027). The superior specimens demonstrated higher stress-to-failure in comparison to the inferior specimens (P<0.001). Compression in a neutral or flexed position generated mild or moderate fracture patterns. On the contrary, the placement of the spine in extension resulted in severe fractures mostly associated with narrowing of the spinal canal. INTERPRETATION: The results imply that a neutral cervical spine position during an impaction can be beneficial. In this position, the failure loads are high, and even if a vertebral fracture occurs, the generated injury patterns are expected to be mild or moderate.

[Osteoporotic fractures of the distal radius. What is new?]. / Osteoporotische Frakturen des distalen Radius. Was ist neu?

The demographic development will result in an increase of up to 30 % of distal radius fractures. There are various therapy options but what is new? Conservative therapy: conservative therapy is reserved for stable fractures only. Osteosynthesis by K-wires: due to low biomechanical stability in older patients, insufficient functional and radiological results were achieved. External fixator: external fixators are used in compound and complex fractures and show better results than K-wire osteosynthesis. Angular stable plate osteosynthesis: with angular stable plates it is possible to achieve good results with complex fractures and they are currently the method of choice. Intramedullary osteosynthesis: intramedullary nails result in a faster functional improvement than angular stable plates but have limitations. New is that 90% of osteoporotic distal radial fractures are treated with angular stable plates which have shown good results in single study groups.

[Medium-term results of surgical treatment for osteitis of the clavicle]. / Mittelfristige Ergebnisse der operativen Behandlung bei Claviculaosteitis.

AIM: Osteitis of the clavicle is rare and not well described in the international literature. We describe a concept of surgical treatment with medium-term observations. METHOD: A total of 22 patients (12 women, 10 men; BMI Ø 24.6 kg/m(2), age Ø 48 years) with osteitis of the clavicle were included in the series. The treatment regime consisted of a surgical approach. Data collection was prospective. Data gathered preoperatively and at follow-up included clinical examination, laboratory findings, radiographs and the Constant scoring system. The mean follow-up period was 13.3 (3-53) months. RESULTS: The described surgical concept was able to permanently eliminate infection in all cases studied. Surgical revisions were required in six patients. The average Constant score showed a significant increase from 66 to 84 at follow-up. Patients also showed good functional results after total resection of the clavicle. CONCLUSION: The reported treatment regime provides reliable results in terms of eliminating infection with good clinical results. Neighboring joints were frequently also involved in the infection and needed to be surgically addressed.

Hook plate for medial clavicle fracture.

Medial clavicle fractures are the least common type of clavicular fractures. Although rare, such injuries deserve rapid diagnosis and effective treatment to avoid future complications. An optimal, standardized operative treatment has not been yet established. We report a case of medial clavicle fracture, where primary operative treatment was indicated due to gross dislocation. An open reduction and osteosynthesis with a modified hook plate was performed, leading to an excellent postoperative outcome after a sixteen-month follow-up. The hook plate seems to be a promising approach for the operative treatment of medial clavicle fractures.