Tc-99m HMPAO labeled leukocytes superior to bone scan in the detection of osteomyelitis in children.

Seven children (aged 7 to 16 years) with confirmed osteomyelitis underwent imaging with Tc-99m HMPAO labeled leukocytes and with Tc-99m diphosphonates. The patients were scanned at 1/2 hour and at 3 hours. The scans were evaluated visually, and the lesion-to-normal bone ratios were quantitated. All the lesions on leukocyte scans and six out of seven lesions in bone scans were readily detectable 1/2 hour after injection of the radiopharmaceutical, but 3 hours is the better imaging time. In quantitative analysis, the lesion-to-normal bone ratio increased with leukocytes significantly higher than with the bone scans (P less than 0.05). When the scintigraphic findings were compared with surgical and radiologic results, the leukocyte images detected and localized lesions better than the bone scans. According to these preliminary results, Tc-99m HMPAO labeled leukocytes seem to offer a rapid and accurate method for detecting bone infections.     

Effect of litter quality on foot pad dermatitis,hock burns and breast blisters in broiler breeders during the production period

Foot pad dermatitis and hock burn lesions are a form of contact dermatitis, a condition affecting skin areas in contact with unsuitable or irritating material. Contact dermatitis is a common problem, reducing the welfare of broilers, and is believed to also affect broiler breeders. However, there is very little research on contact dermatitis in breeders. This study followed the severity of foot pad lesions in broiler breeders throughout the production period. At slaughter the presence of hock burns and breast blisters was also determined. In addition, changes in litter condition over time and the impact of litter quality on foot pads were evaluated. The study was performed on 10 broiler breeder farms, including altogether 18 flocks. Foot pads of 100 hens per flock were assessed at the end of rearing period, three times during the production period, and at slaughter. Foot pad and hock lesions, as well as litter condition were scored on a 5-point scale. Litter quality was evaluated as pH, moisture and ammonia content. The condition of foot pads deteriorated towards slaughter age, with the occurrence of severe lesions reaching a maximum of 64% on average at slaughter. Hock lesions and breast blisters were rare. The litter layer became drier over time. Although poorer litter condition and wetness influenced foot pad health negatively, the effect on severe lesions was not significant. We also observed a negative effect on foot pad condition of larger slat areas. In conclusion, maintaining good litter quality alone is not enough to ensure healthy foot pads in broiler breeders.     

Evaluation of cocktail approach to standardise Caco-2 permeability experiments.

The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein.     

Fixation of syndesmotic ruptures in 38 patients with a malleolar fracture: a randomized study comparing a metallic and a bioabsorbable screw

OBJECTIVES: To compare the performance of a metallic and a biodegradable screw in the fixation of tibia-fibula syndesmotic ruptures. DESIGN: A randomized, prospective, and blinded study. SETTING: Central hospital, Department of Surgery. PATIENTS: Forty consecutive patients with a clinically verified syndesmotic rupture in association with a malleolar fracture, of whom 38 completed the study. INTERVENTION: After syndesmosis rupture was diagnosed, implant selection was performed intraoperatively by a strict randomization with sealed envelopes. Eighteen patients were treated with a metallic screw, and 20 with a bioabsorbable polylevolactic acid screw. The metallic screws were removed in a second operation at 8 weeks postoperatively. All patients had a treatment-blinded clinical and radiographic control after a mean follow-up of 35 (range 17-51) months. MAIN OUTCOME MEASURES: Return to previous physical activity level, evaluation of ankle stability, range of motion, circumference of the ankle, and a radiographic evaluation of both ankles including a measure of the talocrural, medial joint, and syndesmotic space widths. RESULTS: More patients with a polylevolactic acid screw returned to their previous activity level, and there was less swelling in the ankles of these patients, but joint motion was similar between the groups. The mean values of syndesmotic and medial joint spaces were significantly higher in the radiographs of the operated ankles when compared to the uninjured ankle, but there was not a correlation to the type of screw used. CONCLUSIONS: Polylevolactic acid screws worked as well, or slightly better than, metallic ones in syndesmosis fixation in patients with an ankle fracture.     

Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: studies with halofantrine

The relative oral bioavailability (BA) of halofantrine base (Hf) was assessed in male beagle dogs after administration of a medium chain triglyceride (MCT), a long chain triglyceride (LCT), and a blended LCT/MCT lipid solution formulation of Hf (Study 1) and after administration of suspensions of Hf base and Hf. HCl in LCT (Study 2). A series of in vitro lipid digestion experiments were also performed in an attempt to clarify the data obtained. In vitro drug solubilization profiles were markedly dependent on the mass of lipid employed in lipid digestion experiments. At high lipid masses ( approximately 25 mg triglyceride/mL), MCT formulations gave maximal benefit, whereas at low lipid concentrations ( approximately 5 mg triglyceride/mL), LCT formulations provided improved solubilization capacity. The in vitro digestion and solubilization data at lower lipid masses were consistent with the in vivo data where the BA of Hf after oral administration of the LCT solution > LCT/MCT blend > MCT solution. The second BA study showed similar, albeit variable, exposure after oral administration of a suspension of Hf base or Hf. HCl in LCT and this trend was broadly consistent with in vitro results. This study demonstrates the potential utility of in vitro digestion models to assess and rank order the in vivo performance of lipid solution and suspension formulations of poorly water-soluble drugs such as Hf.     

Simple end-to-end suture versus augmented repair in acute Achilles tendon ruptures: a retrospective comparison in 98 patients

We retrospectively compared the results in 98 patients with an acute Achilles tendon rupture treated with an augmented tendon repair (n = 59) to patients with an end-to-end suture (n = 39) after an average follow-up of 44 (22-69) months. 7 patients were operated on more than 2 weeks after the rupture, all with augmention. The complication rates in the augmention group were 0.1 and in the end-to-end suture group 0.2. We found no differences in subjective outcome or rerupture rate between the groups. In the augmentation group, the rate of complications was higher in those operated on after 2 weeks than in those operated on before. A simple end-to-end suture seems sufficient.     

Diseases caused by nuclear genes affecting mtDNA stability

Diseases caused by nuclear genes that affect mitochondrial DNA (mtDNA) stability are an interesting group of mitochondrial disorders, involving both cellular genomes. In these disorders, a primary nuclear gene defect causes secondary mtDNA loss or deletion formation, which leads to tissue dysfunction. Therefore, the diseases clinically resemble those caused by mtDNA mutations, but follow a Mendelian inheritance pattern. Several clinical entities associated with multiple mtDNA deletions have been characterized, the most frequently described being autosomal dominant progressive external ophthalmoplegia (adPEO). MtDNA depletion syndrome (MDS) is a severe disease of childhood, in which tissue-specific loss of mtDNA is seen. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients may have multiple mtDNA deletions and/or mtDNA depletion. Recent reports of thymidine phosphorylase mutations in MNGIE and adenine nucleotide translocator mutations in adPEO have given new insights into the mechanisms of mtDNA maintenance in mammals. The common mechanism underlying both of these gene defects could be disturbed mitochondrial nucleoside pools, the building blocks of mtDNA. Future studies on MNGIE and adPEO pathogenesis, and identification of additional gene defects in adPEO and MDS will provide further understanding about the mammalian mtDNA maintenance and the crosstalk between the nuclear and mitochondrial genomes.     

Alvik's glenoplasty for humeroscapular dislocation. 6-year follow-up of 52 shoulders

In Alvik's modification of the Eden-Hybbinette operation, an iliac crest bone graft is inserted in a groove in the glenoid rim of the scapula. In this retrospective study, 52 shoulders in 46 patients operated on using the modified Alvik's method were reviewed. The mean age of the patients at the time of the operation was 32 years, and the average follow-up time was 6 years. There were no operative complications, and two thirds of the patients were satisfied with the operation. Spontaneous redislocation occurred postoperatively in only one shoulder. In addition, there were 10 traumatic redislocations. Postoperative arthrosis was found in nine shoulders; the arthrosis had more correlation with the patient's age at the time of the operation than with the follow-up time. In 41 shoulders, there was bony healing of the transplant.     

A modification of the Hammett equation for predicting ionisation constants of p-vinyl phenols

Currently there are several compounds used as drugs or studied as new chemical entities, which have an electron withdrawing group connected to a vinylic double bond in a phenolic or catecholic core structure. These compounds share a common feature – current computational methods utilizing the Hammett type equation for the prediction of ionisation constants fail to give accurate prediction of pK_a's for compounds containing the vinylic moiety. The hypothesis was that the effect of electron-withdrawing substituents on the pK_a of p-vinyl phenols is due to the delocalized electronic structure of these compounds. Thus, this effect should be additive for multiple substituents attached to the vinylic double bond and quantifiable by LFER-based methods. The aim of this study was to produce an improved equation with a reduced tendency to underestimate the effect of the double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19 para-substituted vinyl phenols was used. The ionisation constants were measured potentiometrically, and a training set of 10 compounds was selected to build a regression model (r² = 0.987 and S.E. = 0.09). The average error with an external test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0. Thus, we have been able to significantly improve the existing model for prediction of the ionisation constants of substituted p-vinyl phenols.