Effect of allogenic freeze-dried demineralized bone matrix on guided tissue regeneration in dogs

This randomized, split-mouth study was designed to evaluate the adjunctive effect of allogenic, freeze-dried, demineralized bone matrix (DBM) to guided tissue regeneration (GTR). Contralateral fenestration defects (6 x 4 mm) were created 6 mm apical to the buccal alveolar crest on maxillary canine teeth in 6 beagle dogs. DBM was implanted into one randomly selected fenestration defect. Expanded polytetrafluoroethylene (ePTFE) membranes were used to provide bilateral GTR. Tissue blocks including defects with overlying membranes and soft tissues were harvested following a four-week healing interval and prepared for histometric analysis. Differences between GTR+DBM and GTR defects were evaluated using a paired t-test (N = 6). DBM was discernible in all GTR+DBM defects with limited, if any, evidence of bone metabolic activity. Rather, the DBM particles appeared solidified within a dense connective tissue matrix, often in close contact to the instrumented root. There were no statistically significant differences between the GTR+DBM versus the GTR condition for any histometric parameter examined. Fenestration defect height averaged 3.7+/-0.3 and 3.9+/-0.3 mm, total bone regeneration 0.8+/-0.6 and 1.5+/-0.8 mm, and total cementum regeneration 2.0+/-1.3 and 1.6+/-1.7 mm for GTR+DBM and GTR defects, respectively. The histologic and histometric observations, in concert, suggest that allogenic freeze-dried DBM has no adjunctive effect to GTR in periodontal fenestration defects over a four-week healing interval. The critical findings were 1) the DBM particles remained, embedded in dense connective tissue without evidence of bone metabolic activity; and 2) limited and similar amounts of bone and cementum regeneration were observed for both the GTR+DBM and GTR defects.     

Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases

Extracellular signal-regulated kinases (ERK, also known as mitogen-activated protein kinases) are serine-threonine kinases transducing signals elicited upon ligand binding to several tyrosine kinase-associated receptors. We have reported that ERK2 phosphorylation and activation follows engagement of the low affinity receptor for the Fc portion of IgG (CD16) on NK cells, and is necessary for CD16-induced TNF-alpha mRNA expression. Here, we analyzed the involvement of ERK in NK cell-mediated cytotoxicity and IFN-gamma expression induced upon stimulation with targets cells, coated or not with Abs. Our data indicate that, as with immune complexes, ERK2 phosphorylation occurs in human primary NK cells upon interaction with target cells sensitive to granule exocytosis-mediated spontaneous cytotoxicity, and that this regulates both target cell- and immune complex-induced cytotoxicity and IFN-gamma mRNA expression. A specific inhibitor of mitogen-activated protein kinase kinase reduced both spontaneous and Ab-dependent cytotoxicity in a dose-dependent manner involving, at least in part, inhibition of granule exocytosis without affecting effector/target cell interaction and rearrangement of the cytoskeleton proteins actin and tubulin. Involvement of ERK in the regulation of Ca2+-dependent cell-mediated cytotoxicity was confirmed, using a genetic approach, in primary NK cells infected with a recombinant vaccinia virus encoding an ERK inactive mutant. These data indicate that the biochemical pathways elicited in NK cells upon engagement of receptors responsible for either spontaneous or Ab-dependent recognition of target cells, although distinct, utilize ERK as one of their downstream molecules to regulate effector functions.     

A study of replanted permanent teeth in different age groups

In the inpatient treatment of acute psychiatric episodes in children and adolescents, the psychiatrist must set up an initial treatment plan incorporating one or more psychotherapeutic modalities and adapt this plan to the patient's clinical course. This article summarises the clinical experience of a model unit at the University of Heidelberg, the result of a collaboration between the Department of General Psychiatry and the Department of Child and Adolescent Psychiatry at the Clinic of Psychiatry. A series of 116 adolescent admissions was reviewed for clinical diagnosis, the nature and frequency of psychotherapeutic modalities, and the role of family involvement in patient care. Differential and adaptative approaches to the selection of treatment modalities in the context of an acute care setting are emphasised.     

Chest radiographic data acquisition and quality assurance in multicenter studies

Dorsal fusion with the internal fixator has become the standard treatment of instabilities and deformities of the thoracolumbar spine. With our new device, the modular spine fixator (MSF), which has been specially designed for short-distance instrumentations, we have increasingly been treating unstable injuries of the thoracolumbar spine by one-level stabilization. Prerequisite is an accurate evaluation of the indication, including CT and MRI to assess the involvement of the intervertebral disc and the ligamental structures. The operative technique differs in some details from the procedure in more-multi-level instrumentations, especially concerning the application of the pedicle screws. The instrumentation is always combined with posterior allogenic bone grafting. Since the beginning of 1993 we also perform anterior autogenic transpedicular bone grafting. Between January 1991 and July 1995, 57 one-level stabilizations with the MSF were performed. Of the 57 patients operated on 39, 27 men and 12 women, with an average age of 41 years, have had a clinical and radiographic follow-up examination so far, on average, 27 months after the accident. Seventeen patients were completely free of pain and 17 patients (were only) sensitive to weather changes or had minor pain during great physical stress. Five patients had pain even during slight physical stress or at rest. The preoperatively measured Cobb angle was 15.1 degrees on average, after the operation 5.2 degrees, and at the time of the follow-up examination amounted to 8.1 degrees. The patients' range of motion was normal. Only five minor complications have been seen. No implant fatigue failure has been noted in this series. We derive from these results that, for correct indications, one-level stabilization can be performed successfully and should be firmly established in the operative treatment of unstable fractures of the thoracolumbar spine.     

My workplace: Intervention Center, Rikshospitalet. Expert gathering over children with heart disease

Intensity of vasopressin gene expression was compared in neurosecretory cells of supraoptic, postoptic, paraventricular and 6 accessory nuclei (extrahypothalamic included) of adult intact Wistar rats to study the morphofunctional specialization of magnocellular hypothalamic nuclei. Messenger RNA (mRNA) was revealed by radioautographic in situ hybridization, using 35S labelled exonic-intronic probe. By densitometry the amount of label was shown not to differ significantly in neurosecretory cells of all nuclei studied. The latter reflects similar basal level of vasopressin gene expression in all magnocellular nuclei of intact rats. The explanations of this fact as well as possible perspectives of studying molecular biological basis of functional specialization of different magnocellular hypothalamic formations are discussed.     

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

A genetic system to identify DNA polymerase beta mutator mutants

Hemagglutinins were determined in six species of mosquitoes that are susceptible and refractory to Brugia malayi (Filarioidea: Nematoda). High titers of hemagglutinins were found in the salivary gland extract and in the body fluid of a completely refractory species, Aedes taeniorhynchus, and in partially refractory species, Anopheles quadrimculatus but low levels of hemagglutinins were also present in the body fluid of Aedes aegypti (Black-eye, Liverpool strain), a susceptible species. Hemagglutinating activity was not found in the other three completely refractory species of mosquitoes, Culex quinquefasciatus, Culex nigripalpus, and Aedes albopictus in which blood coagulated rapidly after ingestion. High titers of hemagglutinins in the salivary glands of Ae. taeniorhynchus and An. quadrimaculatus facilitated rapid movement of sheathed microfilariae from the midgut to the hemocoel. It is suggested that high titers of hemagglutinins present in the hemocoel bound to the glycoconjugates with exposed carbohydrate moieties present on the microfilarial sheaths and developing abnormal larvae (L1) in the thoracic muscle cells. These hemagglutinin-bound glycoconjugates formed capsules that subsequently stimulated the immune response and resulted in melanization of microfilarial sheaths and sheathed microfilariae in the hemocoel and intracellularly developing abnormal L1 in the thoracic muscles. Only minimal encapsulation and melanization of B. malayi microfilariae was observed in the hemocoel of the other four species of mosquitoes that lacked hemagglutinins in the salivary glands. The results suggest that tissue specific hemagglutinins are one of several factors of vector susceptibility/refractoriness through immune reactions (encapsulation, activation of prophenoloxidases).     

Prediction of outcome and early vs. late improvement in OCD patients treated with cognitive behaviour therapy and pharmacotherapy

Several factors must be taken into account when deciding which specimen preparation technique(s) to use. These factors include the amount of material available, ease of preparing this material due to its properties and familiarity, location and size of the region of interest, amount of information sought, facilities accessible, and time available by the researcher to devote to the preparation of the specimen. The more popular specimen preparations for thin films, namely, electropolishing, cleaving, crushing, mechanical thinning followed by ion milling, and ultramicrotomy are discussed and the more unusual techniques such as extraction/replication, photochemical etching, lithography and reactive ion etching (RIE), chemically assisted ion beam etching (CAIBE), and precision polishing-based techniques are described. Their advantages and disadvantages in the context of the above factors are discussed. Suggestions for increasing one's success rate in preparing specimens are given. The role of transmission electron microscopy (TEM) analysis is considered since it rarely stands in isolation from other physical analytical techniques, nor is it often used as a quick diagnostic tool. Conservation of material by the minimization of the amount of material used (or destroyed) by TEM specimen preparation, and conservation of one's time by performing TEM analysis only on "worthy" samples should be given maximum consideration.     

Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: a decision analysis

BACKGROUND: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. OBJECTIVE: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. DESIGN: A markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. SETTING: Therapeutic decision at the time of diagnosis of CML. PATIENTS: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. INTERVENTION: Early transplantation, delayed transplantation, and no transplantation. MEASUREMENTS: Quality-adjusted, discounted life expectancy. RESULTS: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 53 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. CONCLUSIONS: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.