Aseptic bone necroses as a late complication following successful treatment of leukemias and severe aplastic anemia

Aseptic bone necrosis is a well known complication after corticosteroid treatment in adults and several hundred cases have been reported. Alterations in fat metabolism with vascular occlusion due to fat embolization, as well as microtraumata and osteoporosis are discussed as etiologic factors. In contrast, aseptic bone necrosis in relation to corticosteroid treatment is rare in children and adolescents. We therefore report 3 patients, aged from 10 to 18 years, suffering from severe aplastic anemia, meningeal relapse after acute lymphocytic leukemia and acute myelocytic leukemia respectively, who developed aseptic bone necrosis 6, 11, and 20 months following the onset of corticoid therapy. The patients survive from 28+ to 50+ months after diagnosis of their initial hematologic disease, as it can be expected today for increasing numbers of patients. We therefore believe, that aseptic bone necrosis may represent a serious therapy related complication and suggest that, diagnostic examination in patients with suspicious complaints of the hip, shoulder or knee should also exclude the possibility of a bone necrosis after leucemic relapse has been ruled out. Since radiological changes only develop several weeks to months after the onset of the clinical symptoms and because of the disabling consequences for patients, misdiagnosed at the beginning, a 99 technetium bone scan should be done as early as possible. Corticosteroids, despite their serious side effects are still being considered as a important part of hematologic therapy and are not being omitted in the near future, so that the earliest possible diagnosis of bone necrosis will remain of great importance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular endothelial growth factor expression and bone formation in posterior glenoid fossa during stepwise mandibular advancement.

This study assessed the amount of vascular endothelial growth factor (VEGF) expression and related the findings to new bone formation in the posterior glenoid fossa during stepwise mandibular advancement. A total of 250 female Sprague-Dawley rats, 35 days old, were randomly divided into 10 groups, each including 5 control and 20 experimental rats. Within each group, 10 experimental rats were fitted with functional appliances with a 1-step advancement of 3.5 mm. Another 10 were fitted with stepwise appliances with an initial advancement of 2 mm and a subsequent increase to 3.5 mm on day 30. The rats in the experimental groups were killed on days 3, 7, 14, 21, 30, 33, 37, 44, 51, and 60, respectively. The matched controls were killed on the same time points. Sections (7 microm) were cut through the glenoid fossa sagittally and stained with anti-VEGF antibody. VEGF expression in the posterior glenoid fossa was evaluated with a computer-assisted image-analyzing system. Both VEGF expression and new bone formation were greater in the experimental rats than in the controls. During stepwise advancement, initial VEGF expression was less than that of 1-step advancement, but the second advancement elicited another peak on day 44. New bone formation was also less than that of 1-step advancement during early stages of stepwise advancement but then began to increase from day 37 onward. The maximum increase was observed on day 60. Stepwise advancement of the mandible delivers mechanical stimuli that produce a series of tissue responses that lead to increased vascularization and bone formation.     

Effects of short-term stimulation of serotoninergic pathways on the pulsatile secretion of luteinizing hormone in the absence and presence of acute opiate-receptor blockage

To investigate the role of the serotoninergic system in regulating pulsatile gonadotropin secretion in man, we tested the influences of a novel selective serotonin re-uptake inhibitor (fluoxetine HCl) on episodic LH release in men. Spontaneous LH pulsatility was assessed by computerized analysis of serial LH concentrations measured in blood samples withdrawn at 10 min intervals for 24 h. Possible alterations in pituitary responsiveness were tested by administering three consecutive two-hourly intravenous pulses of GnRH (10 micrograms, 10 micrograms, and 100 micrograms). The effects of fluoxetine (20 mg orally three times daily for one wk) were assessed in a double-blind, placebo-controlled design. Compared with the placebo, fluoxetine elicited no changes in 24 h mean serum LH concentrations, LH pulse characteristics (Cluster analysis), or LH secretion and clearance parameters assessed in response to exogenous GnRH administration (deconvolution analysis) in the presence of normal opiatergic tone (nine healthy young men), and during acute blockade of the opiatergic system (seven young men treated with the mu-opiate receptor antagonist, naltrexone). In summary, a selective enhancer of serotoninergic activity (fluoxetine HCl) does not affect pulsatile LH release basally or in the presence of acute inhibitory opiatergic tone. Since this probe does modify prolactin secretion in man, we conclude that stimulation of the serotoninergic system by this selective neuroendocrine probe shows no demonstrable coupling between the serotoninergic and the opiatergic pathways that modulate pulsatile LH release in man.     

An Evolutionarily Conserved Region in the Second lntron of the Human Nestin Gene Directs Gene Exmession to CNS Progenitor Cells and to Early Neural Ciest Cells

Central nervous system (CNS) progenitor cells transiently proliferate in the embryonic neural tube and give rise to neurons and glial cells. A characteristic feature of the CNS progenitor cells is expression of the intermediate filament nestin and it was previously shown that the rat nestin second intron functions as an enhancer, directing gene expression to CNS progenitor cells. In this report we characterize the nestin enhancer in further detail. Cloning and sequence analysis of the rat and human nestin second introns revealed local domains of high sequence similarity in the 3' portion of the introns. Transgenic mice were generated with the most conserved 714 bp in the 3' portion of the intron, or with the complete, 1852 bp, human second intron, coupled to the reporter gene lacZ. The two constructs gave a very similar nestin-like expression pattern, indicating that the important control elements reside in the 714 bp element. Expression was observed starting in embryonic day (E)7.5 neural plate, and at E10.5 CNS progenitor cells throughout the neural tube expressed lacZ. At E12.5, lacZ expression was more restricted and confined to proliferating regions in the neural tube. An interesting difference, compared to the rat nestin second intron, was that the human intron at E10.5 mediated lacZ expression also in early migrating neural crest cells, which is a site of endogenous nestin expression. In conclusion, these data show that a relatively short, evolutionarily conserved region is sufficient to control gene expression in CNS progenitor cells, but that the same region differs between rodents and primates in its capacity to control expression in neural crest cells.     

Integration of radiology and hospital information systems (RIS, HIS) with PACS: requirements of the radiologist.

PACS development has now reached a stage where it can clearly be stated that the technology for storage, networking and display in a fully digital environment is available. This is reflected by an already large and rapidly increasing number of PACS installations in USA, Western Europe and Japan. Such installations consist of a great variety of information systems, more or less interconnected, like PACS, HIS, RIS and other departmental systems, differing in both hardware and software. Various data - even if they only concern one person - are stored in different systems distributed in the hospital. The integration of all digital systems into a functional unit is determined by the radiologist's need of quick access to all relevant information regardless where it is stored. The interconnection and functional integration of all digital systems in the hospital determine the clinical benefits of PACS. This paper (1) describes the radiologist's requirements concerning this integration, and (2) presents some realistic solutions such as the Siemens ISI (Information System Interface), and a mobile viewing station for the wards (visitBox).     

In vivo biological validation and biophysical modeling of the sensitivity and positive accuracy of endocrine peak detection. II. The follicle-stimulating hormone pulse signal

Despite interest in the in vivo control of gonadotropin release, valid assessment of the physiological regulation of the pulsatile secretion of the gonadotropin FSH has been hampered by the uncertain validity and reliability of available FSH peak detection algorithms. Difficulties in identifying FSH peaks accurately are believed to arise in part because of the slow metabolic clearance of this glycoprotein hormone. Here, we have used two complementary strategies to test the validity of FSH pulse detection. First, by means of a computer-assisted mathematical model for simulating episodic hormone secretion, we evaluated the effects of various putative FSH secretory pulse amplitudes and half-lives on the sensitivity and positive accuracy of peak detection. Secondly, we used an in vivo primate animal model, in which presumptively true FSH pulses were evaluated independently by continuous electrophysiological monitoring of mediobasal hypothalamic multiunit activity. These two approaches allowed us to define optimal pulse analysis parameters that yield maximal sensitivity and positive accuracy for detecting FSH peaks in synthetic and biological time series. We found (as predicted intuitively) that increasing half-times of hormone disappearance decrease both the sensitivity and positive accuracy of peak detection for any given peak detection thresholds and hormone secretory amplitudes. However, adequately sampled episodic FSH time series could be analyzed for FSH pulsatility by an appropriately constrained, objective computerized algorithm with reasonable (less than 10-15%) false negative and false positive errors, such that resultant sensitivity and positive accuracy exceed 85-90%. Of interest, computer simulations and the in vivo animal model exhibited similar discriminative capabilities. We conclude that increasing half-times of hormone (e.g. FSH) removal do impair hormone peak detection sensitivity and positive accuracy. Nevertheless, gonadotropin time series can be analyzed for FSH pulsatility in a valid manner with adequately constrained false negative and false positive error rates.     

Multimodale Behandlung einer Alopecia universalis

Alopecia universalis is characterized by total loss of body hair and can occur at any age, causing significant psychological morbidity in most cases. Though there is evidence to suggest that alopecia universalis is an autoimmune disease, the cause of the disease is still not known with certainty. Spontaneous recovery is unusual (<10%), and the long-term prognosis in cases not responding to therapy is poor, despite the variety of therapies available. Experience of immunosuppressive treatment in children with alopecia universalis is limited. We report on a 4-year-old boy, who was successfully treated for refractory alopecia universalis with prednisolone and cyclosporine A by mouth combined with topical application of tacrolimus. Our case report shows that systemic immunosuppression may be a promising treatment option for some children with alopecia universalis who are badly distressed by their condition. However, potential treatment-related risks have to be weighed against the psychosocial stress experienced by these patients and their families.     

Efficacy of autograft and freeze-dried allograft to enhance fixation of porous coated implants in the presence of interface gaps.

Autogenous cancellous bone and freeze-dried allogeneic cancellous bone were tested in a total of 41 adult male mongrel dogs. In each humerus, an implant with a commercially pure titanium fiber metal porous coating was placed in an overreamed cavity so that a uniform 3-mm gap was present between the implant and host cancellous bone. Graft material was placed in the gap of one humerus while the gap of the other humerus was left empty and served as a paired negative control. Histologically, both autograft and allograft appeared to aid repair of the defect, but quantitatively only autograft enhanced new bone formation within the defect. Treatment with autograft significantly increased the amount of bone ingrowth within the implants by nearly three-fold at 4 weeks and eight-fold at 8 weeks. The enhancing effect was recognizable as early as 2 weeks. The strength of fixation was increased by nearly seven-fold at 4 weeks and two-fold at 8 weeks in the autograft group, but this was only statistically significant at 4 weeks. Treatment with allograft did not enhance bone ingrowth at any time period, but had a small positive effect on strength of fixation at 4 weeks.