Growth modulation of angular deformities with a novel constant force implant concept-preclinical results

PurposeVarus-valgus deformities in children and adolescents are often corrected by temporary hemi-epiphysiodesis, in which the physis is bridged by an implant to inhibit growth. With standard implant solutions, the acting forces cannot be regulated, rendering the correction difficult to control. Furthermore, the implant load steadily increases with ongoing growth potentially leading to implant-related failures. A novel implant concept was developed applying a controlled constant force to the physis, which carries the potential to avoid these complications. The study aim was to proof the concept in vivo by analyzing the effect of three distinct force levels on the creation of varus deformities.MethodsThe proposed implant is made of a conventional cerclage wire and features a twisted coil that unwinds with growth resulting in an implant-specific constant force level. The proximal medial tibial physes of 18 lambs were treated with the implant and assigned to three groups distinct by the force level of the implant (200 N, 120 N, 60 N).ResultsThe treatment appeared safe without implant-related failures. Deformity creation was statistically different between the groups and yielded on average 10.6° (200 N), 4.8° (120 N) and 0.4° (60 N) over the treatment period. Modulation rates were 0.51°/mm (200 N), 0.23°/mm (120 N) and 0.05°/mm (60 N) and were constant throughout the treatment.ConclusionBy means of the constant force concept, controlled growth modulation appeared feasible in this preclinical experiment. However, clinical trials are necessary to confirm whether the results are translatable to the human pathological situation.     

Interleukin-6 and selected plasma proteins in healthy persons of different ages

In the present study, interleukin-6(IL-6) and several acute phase proteins were measured in healthy participants (23–87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml(00.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.     

Effect of cyclosporin A,azathioprine, and prednisolone on carbohydrate metabolism of rat hepatocytes

The effect of different immunosuppressive drugs (prednisolone, azathioprine, cyclosporin A) on liver carbohydrate metabolism in the rat was investigated. Daily administration of prednisolone (3 mg/kg body weight) and azathioprine (2 mg/kg body weight) intraperitoneally for 2 weeks caused significantly lower liver glycogen content than that in NaCl-treated controls. Liver glucose and lactate content, as well as plasma glucose, glucagon, and serum insulin concentration of these animals, remained unchanged. There were no differences in any of these parameters between cyclosporin A (15 mg/kg body weight)-treated and vehicle (olive oil/ethanol)-treated animals. Prednisolone caused significantly lower glucose production in isolated rat hepatocytes using Na-pyruvate as the substrate, whereas glucose production was unchanged in hepatocytes of azathioprine-treated rats using pyruvate or l-serine as substrates. Glucose production from pyruvate or serine was significantly inhibited by cyclosporin A compared to the vehicle, but did not differ from the effects of azathioprine and prednisolone. Lactate production was significantly lower in cyclosporin-treated animals than in those given either the vehicle or azathioprine. Cyclosporin A completely reversed the inhibition of hepatocyte glycogen consumption caused by the vehicle. However, glycogen production in the presence of cyclosporin A was comparable to the effects of prednisolone and azathioprine. Finally, hepatocyte ketone body production using pyruvate as the substrate was higher in the presence of all immunosuppressive drugs. In the presence of serine, acetoacetate production increased in rats treated with 50 mg/kg body weight cyclosporin A, and -hydroxybutyrate production in animals receiving 15 and 50 mg/kg body weight cyclosporin A.This article is dedicated to Professor K. Kochsiek, Chief of the Medical Department, University of Würzburg, FRG, on the occasion of his 60th birthday     

Methods for in vivo haematoporphyrin derivative quantification: a review

Photodynamic therapy is a new treatment for early carcinomas. Although undergoing phase 1/2 clinical assays, clinical indications for this therapy remain rare mainly because of the approximate dosimetry of HPD uptake by tumour tissues in human beings.In this review we present the potential interest and limits of both direct fluorescence detection or dosimetry of HPD and in vivo measurements of singlet oxygen, produced during photodynamic therapy. Clinical applications of such measurements should represent one of the main conditions for the future development of photodynamic therapy.

---

Résumé La photochimiothérapie est un nouveau traitement des cancers débutants. Alors que des essais cliniques de phase 1–2 sont entrepris, les indications pour ce type de traitement demeurent rares, principalement du fait d'une dosimétrie approximative de la captation de l'hématoporphyrine dérivée par les tissus cancéreux humains. La fluorescence émise par l'HPD peut Être utilisée in-vivo pour un diagnostique topographique de la répartition de l'HPD, mais aussi le dosage quantitatif des espèces fluorescentes présentes dans le mélange HPD. Le dosage de l'oxygène singulet, généré lors de la réaction photochimique, est nettement plus difficile à réaliser mais a été proposé pour le dosage in-vivo des formes porphyriniques actives présentes dans le milieu. Les applications cliniques de telles mesures représentent une condition essentielle pour le developpement de la photochimiothérapie car à côté des possibilités de diagnotiques offertes par l'analyse de la répartition intratumorale de l'HPD, un dosage précis permettrait d'optimiser le moment du traitement, arbitrairement fixé aujourd'hui à 72 heures.

     

In situ dormancy of B lymphocytes programmed for an IgE antibody response and their sudden release from unresponsiveness under in vitro conditions

Priming of CBA/J mice with different doses of antigen has aprofound effect on the ratio of IgE versus IgG antibodies appearingupon Immunization. Repeated injections of minute doses induceIgG and high titers of IgE antibodies. Large doses elicit ahigh IgG but a very low IgE antibody titer. In order to studythe modalities for activation and inactivation of IgE-producingB cells, an in vitro culture system was established in whichspleen cells from animals primed with keyhole limpet hemocyaninwere re-stliulated with antigen. In contrast to the expectationfrom the in vivo situation, spleen cells from animals Immunizedwith large doses of antigen and virtually lacking IgE antibodiesproduce high amounts of IgE antibodies upon re-stimulation invitro. The titers in spleen cell cultures from mice primed withminute doses remain proportional to the response measured asserum antibodies. In accordance with the induction of high amountsof IgE antibodies in spleen cell cultures from mice primed withlarge doses, the frequency of IgE antibody-secreting cells wasraised drastically, 1000-fold. The in vitro response is a trueanamnestic response. The sudden appearance in high frequencyof IgE antibody-forming cells among spleen cells isolated fromprimed mice which have high IgG but virtually no IgE antibodytiters is as yet unexplained and the origin of the B memorycells has not yet been traced. The answer might be crucial forour understanding of the down-regulation of the IgE Immune responses.     

Cost comparison of sevoflurane with isoflurane anesthesia in arthroscopic menisectomy surgery

PURPOSE: To determine the "real world" cost of sevoflurane compared with isoflurane in balanced general anesthesia for daycare arthroscopic menisectomy, we prospectively investigated perioperative drug requirement and expense as well as recovery time. METHODS: Following intravenous induction, 40 consenting adult patients randomly received either sevoflurane- or isoflurane-based anesthesia with a standardized gas inflow rate of 3 l x min. Recovery was assessed in the postanesthetic recovery room (PARR) in a double-blind manner at 15 min intervals using the Aldrete scoring system until patients met discharge criteria. RESULTS: Patient demographics, anesthetic duration, volatile potency and adjunct drug requirements were similar in the two groups. Total perioperative drug cost per patient was CAN$38.10+/-10.13 (mean +/- SD) for the sevoflurane group and $23.87+/-6.59 for the isoflurane group (P<0.01). Although the nonvolatile drug cost was comparable between the two groups, the volatile drug cost per patient was $19.40+/-8.80 for sevoflurane and $4.50+/-1.90 for isoflurane (P<0.01). This four-fold sevoflurane-to-isoflurane cost difference was the product of two ratios, both based on the volume of liquid anesthetic: the ratio of consumption, 2.1; and the ratio of institutional price, 2.1. Intraoperative hemodynamic response, time until discharge from the PARR and incidences of postoperative nausea and vomiting did not significantly differ between the two groups. CONCLUSIONS: When used to maintain equipotent balanced general anesthesia for daycare arthroscopic menisectomy, volatile consumption and cost were greater for sevoflurane compared with isoflurane. Nonvolatile perioperative drug cost and recovery times were similar, however, in the two groups.     

MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease. Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999     

Red wine inhibits the cell-mediated oxidation of LDL and HDL

OBJECTIVE: We compared the in vitro effects of red wine, white wine and ethanol on the cell mediated oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) by three frequently-used assays. METHODS: LDL and HDL isolated from normolipidemic human serum were incubated with J774.A1 macrophages in DMEM with copper, with or without red wine, white wine or ethanol (equivalent to 0.2 mg ethanol/ml). Lipoprotein oxidation was assessed by conjugated diene formation as measured by changes in absorbance at 234 nm (deltaA234), thiobarbituric-acid-reactive-substance (TBARS) production and trinitrobenzene-sulfonic-acid (TNBS) reactivity. RESULTS: Red wine (0.2 mg ethanol/mL) inhibited LDL oxidation as indicated by an 85.7% decrease in absorbance at 234 nm, a 96.5% decrease in TBARS production and complete prevention of the decrease in TNBS reactivity. White wine and ethanol did not have any significant effect at 0.2 mg/mL. White wine at 1.0 mg ethanol/mL inhibited TBARS production from LDL by 84.1%. Red wine (0.2 mg ethanol/mL) inhibited HDL oxidation as indicated by a 78.9% decrease in deltaA234, an 81.7% decrease in TBARS production and by no change in TNBS reactivity. White wine and ethanol had no effect at 0.2 mg/mL. White wine at 1.0 mg ethanol/mL inhibited TBARS production from HDL by 66.4%. CONCLUSIONS: These results indicate that red wine inhibits the cell mediated oxidation of lipoproteins, that white wine is not as effective as red wine and that the effect of the red wine is not due to its ethanol content.     

Continent Cutaneous Urinary Diversion Using The Full-Thickness Bowel Flap Tube as Continence Mechanism: A Simplified Tunneling Technique

Purpose

We present a time and labor saving embedding technique for a full-thickness bowel flap tube used as a continent outlet.

Materials and Methods

In 17 patients the bowel flap tube was extramurally embedded instead of being submucosally tunneled. The reservoir was attached to the abdominal wall to reinforce the continence mechanism and prevent the tunnel from opening.

Results

All 17 patients are completely continent and 14 of 16 evacuate urine easily with a 14F catheter. Due to recurrent stomal stenosis 1 patient with severe diabetes has undergone incontinent diversion.

Conclusions

Our described tunneling procedure for the full-thickness bowel flap tube is easy to perform and provides excellent continence.