Temporary screw epiphyseodesis of the first metatarsal for correction of juvenile hallux valgus.

PURPOSE: Juvenile hallux valgus deformity (JHVD) is rare but may be associated with symptoms or deformities that require surgical treatment. Literature recommends waiting to perform surgical treatment until maturity. However, if conservative treatment is not sufficient and the children's psychological or physical suffering is particularly severe, earlier surgical treatment should be considered. The aim of this study was to evaluate the safety and efficiency of temporary screw epiphyseodesis of the lateral epiphyseal plate of the first ray metatarsal as a new treatment option for JHVD during growth age. METHODS: Between June 2011 and November 2017, 33 patients (24 girls, nine boys; 59 feet) with a JHVD were treated by temporary screw epiphyseodesis of the lateral epiphyseal plate of the first ray metatarsal. At the time of surgery mean age was 11.1 years SD 1.4 (8 to 15). Patients were followed clinically and with standing, weight-bearing radiographs of the feet in two planes. RESULTS: In all, 22 patients (39 feet) were included into this study. Mean follow-up was 27.8 months SD 9.9 (12 to 58). The hallux valgus angle changed from 26.5° SD 6.6° preoperatively to 20.2° SD 6.2° (p < 0.001) at time of follow-up. The intermetatarsal angle changed from 14.1° SD 5.4° to 10.5° SD 2.9° during this time (p < 0.01). In two patients (three feet) the screws were removed before the JHVD was fully corrected due to local tenderness over the screw head. In two patients screw migration away from the growth plate was observed, resulting in no further deformity correction in one patient and increasing deformity in the other patient. No other complications were seen. CONCLUSION: Temporary screw epiphyseodesis of the lateral epiphyseal plate of the first ray metatarsal seems to be an effective, safe, technically easy and minimally invasive early treatment option to correct JHVD in children with particularly severe suffering. Due to the individual correction rate, frequent follow-up visits are recommended until skeletal maturity. LEVEL OF EVIDENCE: IV.

Outcome After Combined Pelvic and Femoral Osteotomies in Patients with Legg-Calvé-Perthes Disease.

BACKGROUND: The aim of this study was to evaluate the outcome at skeletal maturity of combined pelvic and femoral varus osteotomies in children with Legg-Calvé-Perthes (LCP) disease. METHODS: From January 1998 to December 2009, 69 patients with LCP disease underwent combined osteotomies at our institution. Fifty-two children (19 girls and 33 boys) met the inclusion criteria and were enrolled in the study. The LCP disease was classified and the cases of all patients were reviewed at skeletal maturity. The mean age (and standard deviation) at the time of diagnosis was 6.9 ± 2.4 years, and the mean age at the time of surgery was 7.9 ± 2.3 years. The mean time to follow-up was 10.8 ± 3.5 years. The final follow-up radiographs were assessed according to the Stulberg classification and the sphericity deviation score. RESULTS: The mean Harris hip score at the time of follow-up was 90 ± 13.2. According to the Harris hip score grading system, 37 patients (71%) had an excellent outcome; 8 patients (15%), a good result; 3 patients (6%), a fair result; and 4 patients (8%), a poor result. Seven patients (13%) were classified as having a Stulberg class-I hip; 20 (38%), a class-II hip; 15 (29%), a class-III hip; 6 (12%), a class-IV hip; and 4 (8%), a class-V hip. The mean sphericity deviation score was 24.4 ± 14.4 at skeletal maturity. There was a strong relationship between a younger age at diagnosis and better functional and radiographic outcomes. CONCLUSIONS: In the absence of a randomized study design, conclusions have to be drawn with caution. Combined pelvic and femoral osteotomies in these children with LCP disease did not result in better functional or radiographic outcomes compared with the historic results of Salter osteotomy or proximal femoral osteotomy alone. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Multiple-dose pharmacokinetics of cefpirome in long-term hemodialysis with high-flux membranes.

Cefpirome is a cephalosporin eliminated primarily by kidneys that requires dosage reduction in patients with renal failure. The pharmacokinetic parameters were studied in 10 patients with end-stage renal disease who were receiving hemodialysis. Repeated intravenous administration of 2 gm cefpirome three times a week resulted in trough levels of 12.2 +/- 5.4 micrograms/ml and peak serum concentrations of 99.6 +/- 82.1 micrograms/ml. After 3 1/2 hours of hemodialysis with polysulfone high-flux membranes, 62.3% +/- 23.3% of cefpirome was removed. The interdialytic half-life was 9.35 +/- 0.99 hours, and the intradialytic half-life was 2.02 +/- 0.7 hours.

Management of serious staphylococcal infections in the outpatient setting.

Patients with serious staphylococcal infections, e.g. endocarditis and osteomyelitis, need prompt and prolonged parenteral antibiotic treatment to ensure eradication of the causative pathogen. The major cost in the treatment of these infections is the long period of hospitalisation required for the administration of intravenous antibiotics. To shorten the hospitalisation period, outpatient treatment can be given to some patients. In this study, patients with acute exacerbations of chronic osteomyelitis (n = 44) or endocarditis (n = 10) were treated with intravenous teicoplanin. The pathogens were Staphylococcus aureus (n = 41, 13 of which were methicillin resistant) and coagulase-negative staphylococci (n = 13, one of which was methicillin resistant). After a mean loading dose of 15 mg/kg for 3 to 10 days, patients received teicoplanin 3 times a week at a dose (mean 15 mg/kg) individualised to achieve serum trough concentrations of approximately 10 mg/L for osteomyelitis and 20 mg/L for endocarditis. Treatment duration ranged from 28 to 150 (mean 62) days for patients with osteomyelitis and from 28 to 88 (mean 49) days for patients with endocarditis. 37 (84%) patients with osteomyelitis and 8 (80%) patients with endocarditis were treated successfully. Adverse events were observed in 9 patients and included rash (n = 3), thrombocytopenia (n = 3), and drug fever, pseudomembranous colitis, nausea, leucopenia and transient hearing impairment (one patient each). In conclusion, this study demonstrates that teicoplanin can be administered successfully in an outpatient setting according to a 3-times weekly schedule for the treatment of patients with staphylococcal osteomyelitis and endocarditis.

In vitro evaluation of teicoplanin and other antimicrobials against streptococci group D bacteria.

In vitro activities of teicoplanin were compared with those of ampicillin, imipenem, rifampicin, coumermycin and vancomycin against clinical isolates of Streptococcus faecalis (n = 100) and Streptococcus faecium (n = 30). Against Str. faecalis, ampicillin and imipenem had an MIC90 and MBC90 of 3.9 micrograms/ml. Coumermycin and rifampicin had poor bactericidal activity with MBC90 values of 31.2 and 62.5 micrograms/ml. Teicoplanin was extremely active with an MIC90 of 0.95 microgram/ml and an MBC90 of 1.86 micrograms/ml.

Methicillin- and gentamicin-resistant Staphylococcus aureus: susceptibility to fosfomycin, cefamandole, N-formimidoyl-thienamycin, clindamycin, fusidic acid and vancomycin.

The in vitro activity of fosfomycin against 90 strains of methicillin- and gentamicin-resistant Staphylococcus aureus was studied in an in vitro microtitre system using Mueller-Hinton broth supplemented with glucose-6-phosphate. In parallel the antistaphylococcal activity of cefamandole, N-formimidoyl-thienamycin, clindamycin, fusidic acid and vancomycin was determined with the same organisms. The following MIC50 (MIC95) values were obtained: fosfomycin 8 (128) mg/l, cefamandole 8 (greater than 64) mg/l, clindamycin 0.25 (16) mg/l, fusidic acid less than 0.25 (less than 0.25) mg/l, vancomycin 1 (2) mg/l and N-formimidoyl-thienamycin 4 (16) mg/l. A high MIC/MBC ratio was noted for cefamandole, in contrast to fosfomycin.

A rare case of pancreatic lipoma.

During CT scanning, a pancreatic lipoma was diagnosed in a 70 year-old woman presenting with abdominal pain, elevated amylase and abnormal liver function tests. The patient underwent surgical excision of the lipoma located in the head of the pancreas. The postoperative course was uneventful. This is the third case of pancreatic lipoma described in the literature. It is a very rare neoplasm that should be included in the category of "non-ductal" tumors of the pancreas. The role of different diagnostic tools for the differential diagnosis of ductal pancreatic adenocarcinoma is discussed.

[Short review of pathophysiology and therapeutic possibilities in onchocerciasis with reference to a case report]. / Kurze Ubersicht über Pathophysiologie und Therapiemöglichkeiten der Onchozerkose anhand eines Fallberichtes.

We report the first case of onchocerciasis in Austria in a African patient who was admitted to hospital for psychiatric reasons initially. The clinical diagnosis was confirmed by skin-snip examination and staining of the microfilariae. Pathophysiology and therapeutic possibilities are discussed.

A case of visceral leishmaniasis in Austria.

We report a patient aged 41 years with fever of unknown origin. Notable aspects of his travel history were a trip to the Philippines and a sailing trip around Sicily. The patient presented with fever up to 40 degrees C since 4 weeks, weakness, headache, hepatosplenomegaly and night sweat. No specific cause could be found. Based on clinical findings tuberculosis was suspected and empirical tuberculostatic treatment was started. However, during the following 6 weeks the patient's condition deteriorated. A bone marrow biopsy performed to exclude a haematological malignancy revealed Leishmania sp. in macrophages. This histological diagnosis was confirmed retrospectively by re-examination of a previously performed liver biopsy and by an increased anti-leishmania serum antibody titer of 1:1280. The patient was treated with sodium stibogluconate (pentostam, 850 mg) for 30 days and recovered slowly.

[Mefloquine and sulfadoxine/pyrimethamine overdose in malaria tropica]. / Mefloquin- und Sulfadoxin/Pyrimethamin-Uberdosierung bei Malaria tropica.

A 39 year-old man with malaria due to Plasmodium falciparum received 3500 mg mefloquine over 3 days, in addition to 3250 mg chloroquine and 175/3500 mg sulfadoxine/pyrimethamine. He developed severe neuropsychiatric symptoms and had to be hospitalized. Treatment with diazepam, haloperidol and thioridazine achieved relief of the severe symptoms after 4 days. The patient was still suffering from discrete neuropsychiatric symptoms 8 months after treatment.

Single-dose pharmacokinetics of teicoplanin during hemodialysis therapy using high-flux polysulfone membranes.

Teicoplanin is a new glycopeptide antibiotic with potent activity against Gram-positive bacteria. It has been considered to be non-dialyzable due to its high molecular weight (1875-1891 d) and high protein binding (89%). Therefore, a reduced dose was recommended for patients on hemodialysis therapy, with the loading dose being followed by a considerably lower maintenance dose and/or extension of the interval between doses. The present study was performed to evaluate the pharmacokinetics of teicoplanin during hemodialysis therapy using high flux membranes. The pharmacokinetic parameters of teicoplanin were studied in 15 patients with chronic renal failure on hemodialysis. A high flux polysulfone membrane (ultrafiltration coefficient of 40 ml/h/mmHg) was used. Teicoplanin was administered at a dosage of 10 mg.kg-1 body weight in 100 ml isotonic saline solution during the first 10 minutes of hemodialysis therapy. Pharmacokinetic analysis was performed using a three compartment analysis. After a single dose of teicoplanin plasma peak levels were 26.4 +/- 12.0 micrograms/mL (mean +/- SD) after 30 minutes. Teicoplanin concentrations rapidly declined to a nadir of 6.1 +/- 2.5 micrograms/mL at the end of the 3.5-hour session dialysis. Extracorporeal clearance was 39.7 +/- 24.5 mL/min. Removal of 19.3 +/- 7.7% of the drug was estimated if infused during hemodialysis. T 1/2 alpha were 0.37 +/- 0.25 hrs, t 1/2 beta 20.1 +/- 7.1 hrs, and t 1/2 gamma 549.7 +/- 210.5 hrs. We conclude that teicoplanin levels are reduced to a subtherapeutic range during one single high-flux dialysis session if the drug is administered during hemodialysis. Thus, in contrast to previous suggestions relevant amounts of teicoplanin are removed during hemodialysis and thus teicoplanin cannot be viewed as non-dialyzable drug. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.

How do in-vitro release profiles of nanosuspensions from Alzet® pumps correspond to the in-vivo situation? A case study on radiolabeled fenofibrate.

In research and development sufficiently high and constant plasma levels of drug candidates are often requested, but simple solutions of hydrophobic drugs delivered from the commonly used micro-osmotic pumps cannot meet these demands. Nanosuspensions released from implanted osmotic devices can be a strategy to overcome this challenge but little is known about their pharmacokinetic behavior after subcutaneous application. In the current study, four different nanosuspension formulations containing iodinated fenofibrate were prepared, physicochemically characterized and investigated concerning their in-vitro release kinetics from osmotic pumps. One nanosuspension of lower viscosity exhibited thereby an unexpectedly first order release kinetics, whereas the higher viscous counterpart was released in the expected zero-order manner. To assess the relation of the in-vitro release kinetics to the in-vivo fate of nanosuspensions, various [(131)I] iodinated fenofibrate formulations were subcutaneously applied to mice. The biodistribution was followed by means of γ-scintigraphy and γ-scintillation. Two different nanosuspensions released from osmotic pumps were compared to bolus injections of a nanosuspension and an organic drug solution. The distribution and elimination of the bolus injected drug solution were almost completed within 48h. In contrast, a long lasting (>1week) depot at the injection site was formed by the bolus injected nanosuspension. Ex vivo examination of the organs showed a sustained, but exponential decrease of the radiolabel concentration. More constant drug levels in the organs were achieved within the nanosuspensions released from osmotic pumps. The organ levels of [(131)I] labeled fenofibrate were found to be more constant in case of the pump with the higher viscous nanosuspension in contrast to the lower viscous counterpart. However, the very different release profiles of the lower and higher viscous nanosuspension observed in-vitro were not observed in-vivo, as both pumps showed zero order release. In conclusion, nanosuspensions of poorly soluble compounds released from subcutaneously implanted osmotic pumps can be a suitable approach in pharmacokinetic studies. Although the in-vivo release of nanosuspensions differed in the expected release profile from the in-vitro test results, these in-vitro release tests present a valuable tool for the pre-selection of suitable nanosuspension candidates.

Modulation of doxorubicin activity in cancer cells by conjugation with fatty acyl and terpenyl hydrazones.

Doxorubicin N-acylhydrazones derived from saturated, unsaturated and terpene-terminated fatty acids were tested for anticancer activity in cells of human HL-60 leukaemia, 518A2 melanoma, MCF-7/Topo breast and KB-V1/Vbl cervix carcinomas. In the latter, the N-heptadecanoyl hydrazone was more cytotoxic than its unsaturated C18-fatty acyl analogues and even three times more than doxorubicin. The (menthoxycarbonyl)undecanoyl hydrazone was twice as active as doxorubicin in these multidrug resistant KB-V1/Vbl and in the 518A2 cells and also more efficacious in KB-V1 and MCF-7 cells that had been desensitised for doxorubicin. All hydrazones induced apoptosis albeit by slightly different mechanisms. While apoptosis induction by the menthoxymalonyl hydrazone was characterized by an upfront increase in caspase-8 activity, all other hydrazones elicited a hike in caspase-9 activity. Treatment of HL-60 and 518A2 cells with doxorubicin or its heptadecanoyl, linolenoyl, (menthoxycarbonyl)undecanoyl or menthoxymalonyl hydrazones also led to diverging increases of the ratio of bax to bcl-2 mRNA expression, of reactive oxygen species and of mitochondrial membrane damage.