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Biomedical subjects

F Hefti

Publications and source records attributed to F Hefti.

At least 19 recordsLinked to original sources
PubMed1999

[Foot pain].

Foot pain is a relatively common problem in children and adolescents. Most frequently the pain is localized at the heel, the mid- and forefoot are less common sites of discomfort. In this article we discuss the etiology of pain in those cases, where the foot has a normal clinical aspect. Sever's disease is most common in adolescents with strenuous athletic activity or with obesity. The calcaneal apophysis is overloaded. Usually the radiologic aspect of the calcis is normal. Treatment consists in reduction of the athletic activity, soft bedding of the heel in the shoes and reduction of weight. Avascular necrosis of the metatarsal head II or III (Freiberg's disease) is also relatively common, while necrosis of the navicular bone (Köhler's disease) is very rare. Treatment in these cases is always conservative. Pain can also originate from tarsal coalition. While in the beginning the foot has a normal aspect, lateron a rigid flatfoot can develop. In unclear cases stress fractures of the metatarsal bones, infections and tumors also have to be considered.

Adolescent↗
PubMed1999

[Osteotomy of the hind-foot in children and adolescents].

The position of the talus and the os calcaneum has consequences for the architecture of the forefoot. Medial tilting of the talus with vertical position provokes flattening of the medial arch and abduction of the forefoot. Varus position of the calcis and lateral direction of the talus (as in residual clubfoot), however, causes supination and adduction of the forefoot. Repair of deformities in the hindfoot therefore also influences the forefoot. A large number of various osteotomies have been proposed at both bones. The most popular ones are Dwyer's osteotomy at the corpus of the calcis and its modification described by Mitchell at the same location for correction of the cavus foot and the residual clubfoot, and the lengthening osteotomy at the neck of the calcaneum according to Evans. Indication and operative technique of these three procedures are described in detail. The closing wedge osteotomy according to Dwyer is indicated in cases of cavus feet. In clubfeet the os calcis is usually too short and the medial opening wedge osteotomy provokes skin problems. In these cases an osteotomy according to Mitchell with lateral displacement of the tuber calcanei is more suitable. In flat- and skew-feet a lengthening osteotomy at the neck of the calcaneum according to Evans can be indicated, especially when the load of the foot is bigger medially under the talus rather than at the lateral margin of the foot. If these procedures are carried out carefully, they have low complications rates.

Adolescent↗
PubMed1999

[Osteotomies of the mid- and back-foot in recurrent club foot].

There are no clear guidelines on the treatment of relapsed clubfoot, which is a relatively frequent and difficult problem in paediatric orthopaedics. Numerous operative interventions are mentioned in the literature as suitable for correction of a residual deformity of the food. There are numerous soft tissue procedures (release operations, tendon extensions, tendon transfers and redressement by means of a fixateur externe) and osseous interventions (osteotomies, arthrodeses) that can be carried out in isolation or in combination. In the present article two types of osteotomy are described that make it possible to correct the most frequent forms of relapsed clubfoot: combined closing wedge cuboid and opening wedge cuneiform osteotomy for correction of adductus and supination of the forefoot and the calcaneal osteotomy after Dwyer for correction of varus position of the calcaneal part of the foot. The combined osteotomy in the midfoot involves shortening of the lateral ray with simultaneous lengthening of the medial ray, with the wedge out of the cuboid bone inserted into the medial cuneiform bone, which leads mainly to correction of the adductus, but does also make it possible to achieve partial correction of the supination with an osteotomy right through the cuneiform bone. In the case of rigid foot deformities it is advisable to carry out preliminary stretching by means of a fixateur externe, while in the case of a bean-shaped foot a combination of osteotomy and medial and lateral release is recommended. Results of a follow-up study of our own patients treated with this operation have shown that no revision operations were necessary in any of the patients with idiopathic clubfoot. Other types of osteotomy described in the literature as suitable for correction of residual forefoot adductus and supination are also mentioned in this paper. Thecalcaneal osteotomy after Dwyer, for which a lateral approach is always used, generally leads to satisfactory correction of varus position of the calcaneal part of the foot. It the calcaneus is found to have a short posterior part this osteotomy is modified so that instead of taking the form of a wedge osteotomy with lateral closing it is followed by a lateral displacement. In this way it is possible to prevent making the already short posterior calcaneus even shorter. Both the combined midfoot osteotomy and the calcaneal osteotomy after Dwyer can be performed alone or in combination with each other or with different operative interventions.

Bone Malalignment↗
PubMed1999

[Flatfoot].

Many parents are anxious because of the insufficient arch of the feet of their children. A true congenital deformity (congenital vertical talus) is extremely rare. In children the arch is physiologically flattened with a hypervalgus of the hindfoot. Those feet do not need treatment. If there is no medial recess in the footprint in a child over 3 years of age, then we are talking about a flexible flatfoot. When the load of the foot is more pronounced at the medial rather than at the lateral side, operative treatment can be indicated, such as a lengthening osteotomy of the calcaneum. If the flatfoot is rigid, the reason for it is usually a tarsal coalition. Operative transection of the osseous bridge with fat interposition can solve the problem. Flatfeet may also occur in neuromuscular diseases. Depending on the severity of the deformity, splints can be effective, or--in the more severe cases--operative treatment such as a triple arthodesis can be indicated.

Adolescent↗
PubMed1999

Analysis of the neurotrophic effects of GPI-1046 on neuron survival and regeneration in culture and in vivo.

The putative neurotrophic effects of the immunophilin ligand GPI-1046 were evaluated in established experimental systems of neuron survival and axon growth in vitro and in vivo. GPI-1046 marginally increased neurite outgrowth of chick dorsal root ganglia in culture under conditions where a very robust effect of nerve growth factor was seen. GPI-1046 failed to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium in culture or to protect cultured cortical neurons from experimentally induced apoptosis in vitro. In adult rats in vivo, daily administration of GPI-1046 (10 mg/kg, s.c.) for three days enhanced the maximal regeneration distance of both motor and large myelinated sensory axons measured using an electrophysiological assay. However, detailed morphometric analysis of these animals failed to provide evidence for an increase in axon numbers in GPI-1046-treated animals. The ability of GPI-1046 to promote the recovery of dopaminergic function following unilateral 6-hydroxydopamine lesions of the substantia nigra was also tested in rats. In the first study, the duration of amphetamine (3 mg/kg, s.c.)-induced circling, but not the maximal number of rotations, was significantly reduced in animals treated with GPI-1046 for five days (10 mg/kg/day). In a second study, testing the effects of delayed GPI-1046 administration, chronic treatment with GPI-1046 (10 mg/kg/day) for two weeks, beginning one month after surgery, did not alter circling responses. Morphometric analysis failed to reveal any changes in either the density of tyrosine hyroxylase-positive fibres in dopaminergic target areas or in cell numbers in the substantia nigra in both experiments. Thus, while GPI-1046 produced marginal effects on neurite outgrowth in dorsal root ganglia cultures and on functional paramaters of nerve regeneration in vivo, we failed to obtain evidence in support of the notion of a general neuroprotective effect of the compound or for an effect on morphologic nerve regeneration in vivo.

1-Methyl-4-phenylpyridinium↗
PubMed1999

The staurosporine-like compound L-753,000 (NB-506) potentiates the neurotrophic effects of neurotrophin-3 by acting selectively at the TrkA receptor.

K-252b, a member of the staurosporine family of protein kinase inhibitors, selectively potentiates the activation of the nerve growth factor receptor, TrkA, by a nonpreferred ligand, neurotrophin-3 (NT-3), in a variety of cell types. At higher (micromolar) concentrations of K-252b, an inhibitory effect occurs because of the inhibitory action of K-252b on the Trk kinase. By examining analogs of K-252b, we identified the compound L-753,000 (NB-506), which potentiates the action of NT-3 on TrkA but is devoid of the inhibitory action of K-252b. L-753,000 was effective at nanomolar concentrations in a Chinese hamster ovary cell line that expressed TrkA but was devoid of p75, the low-affinity neurotrophin receptor. L-753,000 also potentiated the activation of mitogen-activating protein kinase signaling (downstream from Trk activation) by NT-3 in this cell line. Although L-753,000, like K-252b, had a negligible effect in the absence of NT-3, the compound was found to potentiate NT-3-induced survival in both rat and chick primary cultures of dissociated dorsal root ganglia (DRG) and on neurite outgrowth of chick DRG explants. Unlike K-252b, which at micromolar concentrations inhibits the survival response of NT-3 in dissociated rat DRG, L-753,000 continued to potentiate the actions of NT-3 up to a concentration of 10 microM. Furthermore, the compound, unlike K-252b, did not inhibit an unrelated protein kinase, protein kinase C, at concentrations up to 10 microM. Because L-753, 000 selectively potentiates the NT-3-induced stimulation of TrkA without inhibiting Trks and other protein kinases, it represents a novel class of selective modifiers of neurotrophin actions.

Analysis of Variance↗
PubMed1999

Osteochondritis dissecans: a multicenter study of the European Pediatric Orthopedic Society.

To assess of the value of conservative and operative treatment of osteochondritis dissecans of the knee, a multicenter study was performed. In 12 European countries, 798 cases of osteochondritis of the knee have been collected from 44 hospitals. Results were based on 452 patients with 509 affected knees with minimum follow-up was 1 year (mean follow-up, 3 years and 11 months) and sufficient data for evaluation: 61% were male patients; 39% female patients; 318 affected knees were found in juvenile patients; 191 affected knees were in adult or premature patients. The localization was the medial femoral condyle on the lateral side in 51% (typical site) of patients. Various other sites were involved. Of the 509 affected knees, 154 were treated conservatively, 355 were treated surgically (many with multiple operations). For evaluation, the initial situation (at the time of the diagnosis) was favorable in 198 patients (no effusion, diameter of the lesion < 20 mm and no gross dissection on imaging) and unfavorable (one of the parameters did not meet these prerequisites) in 311 patients. The results were better in young patients than in adult patients. However, in the adolescent group, 22% of patients had abnormal knee at follow-up. The classical localization has a better prognosis than an unusual one. Patients with a favorable situation at diagnosis have significantly better results after conservative treatment than those who have undergone operation. When there are signs of dissection, the results are better after operative than after conservative treatment.

Adolescent↗
PubMed1998

Distinct mechanism for antidepressant activity by blockade of central substance P receptors.

The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.

Adolescent↗
PubMed1998

Cerebellar brain-derived neurotrophic factor-TrkB defect associated with impairment of eyeblink conditioning in Stargazer mutant mice.

In the spontaneous ataxic mutant mouse stargazer, there is a selective reduction of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebellum. BDNF protein levels in the cerebellum are reduced by 70%. Despite normal levels of full-length and truncated TrkB receptor, constitutive and neurotrophin-4/5-induced tyrosine phosphorylation was significantly reduced in several signal transduction molecules, including phospholipase-Cgamma1, erk1, and erk2. Morphological examination revealed an increased number of external granule cells at postnatal day 15 and the presence of abnormal neurons resembling immature granule cells in the adult. These abnormalities are associated with a severe impairment in the acquisition of classical eyeblink conditioning, indicating cerebellar malfunction. Our data suggest that normal BDNF expression and TrkB signal transduction in the cerebellum are necessary for learning and plasticity in this model.

Animals↗
PubMed1998

Regionally specific induction of BDNF and truncated trkB.T1 receptors in the hippocampal formation after intraseptal injection of kainic acid.

The septo-hippocampal cholinergic and GABAergic systems were lesioned with single unilateral injections of kainic acid (KA) into the septum to further characterize the role of these afferents in the regulation of hippocampal brain-derived neurotrophic factor (BDNF) expression. Nearly all cells expressing choline acetyltransferase, trkA or glutamic acid decarboxylase mRNA disappeared in the medial septum 7 days after the neurotoxin administration. The lesion resulted in a complete loss of CA3 pyramidal cells, and robust increases in BDNF mRNA levels in hippocampal granular dentate cells and in the amygdala. There were rapid transient increases of BDNF mRNA levels in the hippocampal formation and cortex. In addition, we found a strong induction of truncated trkB.T1 mRNA receptors in the stratum radiatum and stratum oriens of the CA3 subfield. The prolonged induction of BDNF mRNA levels suggests an important role of this neurotrophin, possibly mediated by truncated trkB receptors, in the regulation of hippocampal plasticity following injury.

Animals↗
PubMed1998

Discoid lateral meniscus in children. Long-term follow-up after total meniscectomy.

We retrospectively reviewed the long-term results of total meniscectomy performed in seventeen knees (fourteen children) to treat a discoid lateral meniscus. The mean duration of follow-up was 19.8 years (range, 12.5 to 26.0 years). On the basis of the rating system of the International Knee Documentation Committee, seven knees were normal (grade A), six were nearly normal (grade B), three were abnormal (grade C), and one was severely abnormal (grade D) at the latest follow-up evaluation. Ten of the seventeen knees had clinical symptoms of osteoarthrosis. Radiographs were available for fifteen of the knees at the latest follow-up evaluation. Eleven of the treated knees could be compared with the uninvolved, contralateral knee. Ten knees had osteoarthrotic changes, such as flattening of the lateral femoral condyle, formation of a ridge along the lateral femoral condyle, and spurring and sclerosis of the tibial plateau. Osteochondritis dissecans developed in two knees, nine and twenty years after the initial meniscectomy.

Adolescent↗
PubMed1997

[Injury of the dens axis in early childhood. Clinical case report and discussion].

Because of the special features of the subdental synchondrosis, fractures of the odontoid process in childhood can be seen as a separate entity. The subdental synchondrosis must be regarded as sort of an intervertebral disc and not as a growth plate. Among the generally rare fractures of the cervical spine in children this type ist the most common. Usually conservative treatment with a cast-fixation like the halo fixateur or the minerva jacket leads to consolidation. We report on the case of a 2-year-old girl with a fracture of the odontoid process who developed a unilateral syndrome hours after the accident. The treatment was conservative with a halo-like cast fixation. Nine weeks after the fixation bony consolidation was achieved and the cast could be removed. In the first days after fixation full neurological recovery had occurred. In early childhood (till the 7th year of life) according to the literature, patterns of neurologic dysfunction are incomplete injuries of the spinal cord and have the potential for recovery [4, 5, 7, 9, 10, 12].

Child, Preschool↗
PubMed1997

[Open reduction technique].

Closed reduction of a hip dislocation will prove even more difficult if the dislocation has existed over a longer period of time. The indication is based on several principles: An open reduction may be carried out only after an unsuccessful attempt to perform a closed reduction or at a fixed age limit (12 or 24 months) or based upon arthrographic findings. In our department, for babies up to the age of 12 months, we always try to perform a closed reduction. Between 12 to 24 months, arthrographic findings will determine the choice of method. After the age of two, as a rule, we use an open reduction. The preliminary treatment consists of longitudinal traction. Current methods of approach to the hip joint are the medial approach according to Ludloff or the frontal approach by means of an inguinal incision. With the medial approach, there is greater risk of damaging the circumflex artery; also, a higher rate of avascular necrosis of the femoral head has been observed. Therefore, we only practice the ventral approach. Mainly for cosmetic reasons, however, instead of using the Smith-Petersen procedure, we apply a pure inguinal incision proximal to the inguinal ligament. The approach is found by detaching the muscle tissue at the anterior and interior iliac spine. Medially and laterally of the pelvic ridge, though, the tissue may be left. The joint capsule may be opened in the shape of a T or a V. A t-shape incision offers a better survey, whereby the risk of damaging a vessel is somewhat higher. In addition to resection of the teres ligament, it is necessary to indent the transverse acetabular ligament. Often, aponeurotic recession of the psoas tendon must be performed as well and the labrum indented and pushed outwards before reduction. The risk of insufficient development of the acetabulum can be minimized only if the femoral head is optimally centered. If the femoral head is in a high position (i.e., if the upper ridge of the femoral metaphysis lies higher than the triradiate cartilage), a shortening osteotomy of the femur should always be performed. This is the only possibility of repositioning the femoral head without exercising exaggerated pressure. On the other hand, we are rather reticent to perform a pelvic osteotomy at the time of repositioning. For children under 2 years of age, we recommend to that the acetabulum be allowed to develop and that a pelvic osteotomy be performed at a lager period if necessary. Postoperative treatment is given for a period of 12 weeks in a hip-leg cast in the Fettweis position, followed by another 3 months in a splint. Possible complications are redislocations, avascular necrosis of the femoral head and persistent acetabular dysplasia. An optimal technique will considerably reduce the risks of such complications.

Acetabulum↗
PubMed1997

Ligand-induced down-regulation of Trk messenger RNA, protein and tyrosine phosphorylation in rat cortical neurons.

Chronic exposure of brain neurons to nerve growth factor in vitro and in vivo results in increased levels of the nerve growth factor receptor TrkA. In contrast, in the present study, we have found that chronic exposure of rat embryonic cortical neurons to brain-derived neurotrophic factor (BDNF) leads to a pronounced reduction of the levels of protein and messenger RNA for the full-length but not the truncated BDNF receptor TrkB. Similar effects were observed with the other TrkB ligands neurotrophin-3 and neurotrophin-4/5. After pretreatment with BDNF, neurotrophin-3 or neurotrophin-4/5, subsequent tyrosine phosphorylation responses of the remaining Trks to the same factors were greatly reduced. Three days exposure of rat embryonic cortical neurons to BDNF induced an absolute refractory period of several hours, with no subsequent response to the same factor. Similar but less pronounced refractory effects were observed with neurotrophin-3 and neurotrophin-4/5. Our results suggest a negative regulatory effect of BDNF and other TrkB ligands on TrkB receptors. Down-regulation of the TrkB response by its ligands might play a role in the control of BDNF action during early development, when BDNF levels significantly increase. Our findings are also of potential clinical relevance, since the possibility of ligand-induced down-regulation of the receptor response needs to be addressed when considering BDNF or other neurotrophins for the therapy of neurodegeneration.

Animals↗
PubMed1997

Axotomized septal cholinergic neurons rescued by nerve growth factor or neurotrophin-4/5 fail to express the inducible transcription factor c-Jun.

The inducible transcription factor c-Jun increases in neurons in response to axotomy by unknown mechanisms, and it has been postulated that c-Jun may regulate genes involved in promoting either degeneration or regeneration of axotomized neurons. In this report, we investigated the effect of daily or twice daily intraventricular administration of the neurotrophins nerve growth factor or neurotrophin-4/5 on the decrease in choline acetyltransferase expression and the increase in c-Jun expression in rat medial septum/diagonal band neurons three, seven and 14 days following unilateral, complete, fornix fimbria lesion. We also examined whether medial septum/diagonal band neurons might die by apoptosis within two weeks of fornix fimbria lesion using terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labelling. Our results show that both nerve growth factor and neurotrophin-4/5 maintain the phenotype of basal forebrain cholinergic neurons following axotomy. Furthermore, using double-labelling immunofluorescence, we found that while c-Jun was expressed in cholinergic neurons in control-treated rats seven days following fornix fimbria lesion, cholinergic neurons rescued by either nerve growth factor or neurotrophin-4/5 in neurotrophin-treated rats failed to express c-Jun. At no time-point (three, seven or 14 days post-axotomy) did any neurons in the medial septum/diagonal band stain positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling, suggesting that medial septum/diagonal band neurons do not undergo apoptosis within the first two weeks following axotomy at the time-points observed by us. Therefore, these results show that both nerve growth factor and neurotrophin-4/5 rescue the phenotype of axotomized cholinergic neurons and that these rescued neurons fail to express c-Jun in response to axotomy. In addition, since neither nerve growth factor nor neurotrophin-4/5 induced c-Jun in medial septum/diagonal band cholinergic neurons, it seems unlikely that the neurotrophic effects of nerve growth factor and neurotrophin-4/5 on cholinergic neurons are mediated via c-Jun expression. Furthermore, since axotomy failed to increase terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labelling in septal neurons, it appears unlikely that c-Jun expression in these axotomized neurons is related to neuronal degeneration via apoptosis.

Animals↗
PubMed1997

Protective effects of neurotrophin-4/5 and transforming growth factor-alpha on striatal neuronal phenotypic degeneration after excitotoxic lesioning with quinolinic acid.

Lesioning of the mammalian striatum with the excitotoxin quinolinic acid results in a pattern of neuropathology that resembles that of post mortem Huntington's disease brain. Certain neurotrophic factors can rescue degenerating cells in a variety of lesion types, including those produced by neurotoxins. Several neurotrophic factors promote the survival of striatal neurons and/or are localized within the striatum. Of these factors, neurotrophin-4/5 and transforming growth factor-alpha were chosen for administration to rats lesioned with quinolinic acid. Adult rats received a single unilateral intrastriatal injection of quinolinic acid (120 nmol) and either trophic factors or the control protein cytochrome c for seven days thereafter. The pattern of phenotypic degeneration was assessed by immunocytochemical labeling of various striatal neuronal populations at five rostrocaudal levels. Quinolinic acid produced a preferential loss in the number of cells immunoreactive for glutamate decarboxylase, with a relative sparing of the number of choline acetyltransferase-immunoreactive cells and, to a lesser degree, calretinin-immunoreactive cells. None of these phenotypic populations was protected by either neurotrophin-4/5 or transforming growth factor-alpha. In contrast, when glutamate decarboxylase cells were alternatively identified by calbindin immunolabeling, both factors were found to have partially reversed the loss in the number of calbindin-positive cells induced by excitolesioning. In addition, the loss in the number of parvalbumin-immunopositive cells due to quinolinic acid was partially reversed by neurotrophin-4/5, while the loss in the number of NADPH-diaphorase-stained cells was partially reversed by transforming growth factor-alpha. These findings reveal a new population of striatal cells, calretinin neurons, that are relatively resistant to quinolinic acid toxicity and that neurotrophin-4/5 and transforming growth factor-alpha partially protect against the phenotypic degeneration of striatal cell populations in an in vivo animal model of Huntington's disease.

Animals↗