A nationwide, retrospective analysis of symptoms, comorbidities, medical care and autopsy findings in cases of fatal pulmonary embolism in younger patients.

OBJECTIVE: Our objective was to provide a comprehensive description of fatal pulmonary embolism (PE) in younger persons. Specifically, we recorded information on symptoms, comorbidity, medical contact, if this had been required, and subsequent autopsy findings. METHODS: We reviewed all death certificates from persons aged 0-35 years who had died between 1 January 2000 and 31 December 2006, and retrospectively identified all cases of fatal PE. Additional information was retrieved from the National Patient Registry, autopsy reports, and clinical charts. RESULTS: Sixty-one cases of fatal PE were included; 38% of these were in males. The median age was 29 years. The predominant symptoms were dyspnea, syncope, leg pains, and chest pains. Sixty-three per cent of patients reportedly experienced symptoms for days, weeks, or months. More than half of the patients had sought medical care, and at the time of medical evaluation the majority of the patients were not hemodynamically compromised. In 21% cases, the correct diagnosis was reached before death; however, in only 5% of cases was this accomplished before clinical deterioration. Furthermore, clinical history and subsequent postmortem examinations showed that approximately half of younger persons dying from PE were otherwise healthy, and in no case was occult cancer diagnosed. CONCLUSIONS: Our data show that a substantial proportion of younger victims of fatal PE had experienced symptoms for an extended period of time. Furthermore, the correct diagnosis remained elusive in the majority of cases, even though approximately half of the subjects had sought medical evaluation for symptoms that, in retrospect, were most likely caused by a venothrombotic event.

Differential G protein receptor kinase 2 expression in compensated hypertrophy and heart failure after myocardial infarction in the rat.

The onset of heart failure is associated with characteristic changes in myocardial expression of G protein receptor kinase 2 (GRK2). Although, GRK2 significantly contributes to the regulation of myocardial function in the failing heart, the GRK2 expression during cardiac hypertrophy without heart failure remains to be explored. We here report a differential expression of GRK2 in cardiac hypertrophy with or without heart failure in response to a myocardial infarction in the rat. Postmyocardial infarction animals were divided into two groups depending on the absence or presence of pulmonary edema, which is a manifestation of heart failure. Remarkably, cardiac GRK2 expression and activity were inhibited in animals with cardiac hypertrophy without heart failure, whereas animals with heart failure had elevated GRK2. Thus, three weeks after the infarction cardiac GRK2 expression in animals with hypertrophy alone was decreased to 0.34 of control, whereas in the group of animals with heart failure GRK2 expression was 1.89-fold higher than in sham-operated animals. GRK2 activity was affected in a similar way, three and nine weeks after the infarction cardiac GRK2 activity was reduced to 0.58 and 0.62 in animals with hypertrophy without heart failure when compared to sham operated animals. By contrast, GRK2 activity was increased by 1.32- and 1.21-fold three and nine weeks postinfarction in animals with heart failure when compared to sham animals. These data suggest that GRK2 expression is differentially regulated in hypertrophic, non-failing and hypertrophic, failing hearts.

G protein-coupled receptor kinase 2--a feedback regulator of Gq pathway signalling.

G protein coupled receptors or serpentine receptors work as signalling switches that turn extracellular signals into activation of multiple molecules at the intracellular face of the plasma membrane. Serpentine receptors are the targets of around 70% of all current drugs in clinical medicine. We suggest that these receptors can be pharmacologically targeted by modification of their unique internal inhibitors the G protein coupled receptor kinases (GRKs). The GRKs constitute a family of serine/threonine kinases that specifically bind to and phosphorylate agonist-activated serpentine receptors. The phosphorylated receptors are recognized by arrestins that bind to the receptor and uncouple them from attached G proteins thereby terminating G protein signalling. This review focuses on a ubiquitously expressed GRK family member dubbed GRK2 (previously called beta-adrenergic receptor kinase 1) that regulates cellular signalling at multiple levels. In Gq-coupled signalling modules GRK2 may function as a feedback inhibitor molecule that monitors, inhibits and re-directs the information flow. GRK2 acts as a negative feedback protein by interacting with at least six key signalling molecules in the Gq pathway including; receptors, free G beta gamma subunits, activated G alpha q subunits, phosphatidylinositol-4, 5-bisphosphate (PIP2), protein kinase C (PKC) and calmodulin (CaM). GRK signalling is important for immune, endocrine and cardiovascular function manifesting itself in disorders such as heart failure and lymphocyte activation especially in chronic inflammation. This review summarizes the advances made in understanding the many actions of GRKs and addresses their potential as novel therapeutic targets.

The regenerative potential of oxytalan fibers. An experimental study in the monkey.

Although a number of studies have described the oxytalan fibers as being a natural component of the periodontal ligament, little information exists about the regenerative potential of these connective tissue fibers. The aim of the present study was to examine whether oxytalan fibers have the capacity to reform after regenerative periodontal therapy. Intrabony defects were produced surgically at the mesial aspects of teeth 37, 35, 45, 47 and at the distal aspects of teeth 11, 21, 31, 41 in one monkey (Macaca fascicularis). After 3 months, the defects were exposed using a full-thickness flap procedure. The root surfaces were debrided and subsequently PDGF-growth factors were placed in the defects. 4 of the 8 sites were covered with a bioresorbable membrane before closure of the wound. Post-surgically, antibiotics were given systemically for 1 week, and tooth cleaning was carried out 1x a week during the entire experimental period. After 5 months, the animal was sacrificed and the oral tissues were fixed by perfusion with 10% buffered formalin. Specimens containing the defects and surrounding tissues were dissected free and histological sections were cut in the mesio-distal direction, parallel to the long axes of the teeth. The sections were stained with hematoxylin and eosin or with the oxone-aldehyde-fuchsin-Halmi staining method and subsequently examined in the light and in the electron microscope. The results revealed that new oxytalan fibers oriented mainly in an apico-occlusal direction had developed in the regenerated periodontal ligament. Many of the newly-formed fibers were inserted into the new cementum, thus suggesting a strong relationship between this tissue and the oxytalan fibers. It is concluded that the regenerated periodontal ligament connective tissue formed after surgery contains oxytalan fibers similar to those present in the original tissue. These results demonstrate that oxytalan fibers develop de novo in the newly-formed periodontal ligament.

The microvasculature of human oral mucosa using vascular corrosion casts and India ink injection. I. Tongue papillae.

The microvasculature of human tongue papillae originating from 9 males and 6 females, aged 0.5 to 2 years was studied by scanning electron microscopy (SEM) of vascular corrosion casts and by light microscopy (LM) of India ink injected specimens. All papillae showed a microvasculature characterized by primary, secondary and tertiary capillary loops. In the filiform papillae the loops were generally arranged in a corolla-like pattern with the tertiary loops demonstrating a hair-pin shape. The fungiform papillae showed basically a similar architectural pattern although the loops were somewhat more compact and complex in structure. A small, shallow depression of the tertiary loops at the top of these papillae was found to be occupied by a prominent rete ridge of the surface epithelium. There was a gradual transition from filiform to foliate papillae, the latter appearing as rows of coalesced filiform papillae. The circumvallate papillae easily identified by the surrounding furrow showed a rather complex and compact pattern of capillary loops of which typical hair-pin shaped tertiary loops dominated the periphery of the papilla. Small grooves or depressions in the vascular network were found to be occupied by rete ridges of the overlying mucosal epithelium.

Scanning electron microscopy of black stain on human permanent teeth.

Black stain may develop on the coronal surfaces of human teeth, and this type of stain is common in the Hong Kong Chinese population. The present study was undertaken to ascertain if the deposit conforms in composition to the black stain found elsewhere, and to describe its ultrastructure using the scanning electron microscope. Gram-stained smears were made from black stain on the teeth of 11 adult Hong Kong Chinese and studied microscopically. From another 15 persons extracted teeth exhibiting black stain were obtained and fixed. Two ground sections were made from each tooth, one was stained with toluidine blue, the other was dried and prepared for scanning electron microscopy. The gram-stained smears demonstrated predominantly gram-positive filamentous microorganisms with an admixture of gram-positive cocci and rods. The ground sections revealed a deposit on the outer surface of the enamel, which was clearly divided into two distinctly different layers: an inner yellow opaque layer, and an outer layer of microorganisms. Scanning electron microscopy demonstrated that the deposit consisted entirely of microorganisms, and that in portions close to the enamel they were often obscured by a substance indicative of calcification. Thus the black stain found on the teeth of Hong Kong Chinese is similar in composition and structure to that reported to occur in other populations. The black stain is a special type of dental plaque characterized by its simple flora and its tendency to calcify.

Ultrastructure of developing subgingival plaque in beagle dogs.

The aim of this study was to describe the ultrastructure of developing subgingival plaque. In 6 beagle dogs, healthy gingiva prevailed after a pre-experimental period of intensive plaque control. At the start of the experiment, all oral hygiene measures were withdrawn. Biopsies comprising buccal gingiva and adjacent dental tissues were obtained from premolars and molars on days 0, 4, 7, 21, and 28 and processed for electron microscopy. Sections of day 0 exhibited a junctional epithelium in close contact with the tooth and absence of subgingival aggregations of bacteria on the tooth surface. For each of the subsequent periods studied, some sections did not exhibit subgingival plaque. In the remaining sections with subgingival plaque, almost all bacteria appeared in aggregates attached to the tooth surface. The number of bacteria at the orifice of the gingival sulcus increased with time. Further apically, the micro-organisms formed either a continuous layer of even thickness or, more frequently, discrete microcolonies along the tooth surface. The bacteria comprised practically entirely Gram-negative cocci, rods or spirochetes. The latter were present either mixed with the other types in the discrete microcolonies or constituted the bulk of the continuous layer of plaque. In the apical part of the subgingival plaque, a shift from Gram-negative cocci and rod during the early stages of gingival inflammation, to a predominance of spirochetes in later stages was noted. The study shows that in dogs, starting from a plaque- and gingivitis-free baseline, a predominantly Gram-negative subgingival flora may form within a few days after withdrawal of all oral hygiene measures and that a shift in the bacterial composition of the subgingival plaque takes place during a 4-week period of no oral hygiene.

Formation and ecology of plaque at different locations in the mouth.

Some recent findings concerning microbial colonization of smooth surfaces of teeth, gingival crevices, occlusal fissures and removable dentures are reviewed considering the many ecologic factors of importance for the oral microbial communities. The oral microbiota is extremely complex comprising at least 200 taxa. In spite of interindividual and site-to-site variations, each oral habitat has a characteristic microbiota ranging from Gram-positive, facultatively anaerobic cocci and rods in occlusal fissures to predominance of Gram-negative, strictly anaerobic rods and spirochetes in deep periodontal pockets.

Effect of chlorhexidine rinses on the morphology of early dental plaque formed on plastic film.

The effect of chlorhexidine on early plaque formation was studied in vivo in order to assess potential structural and quantitative changes. 3 subjects with healthy gingiva were used. Plastic films were applied to the buccal surfaces of the maxillary right first premolars and plaque was allowed to form for either 4 or 24 h. A single 1-min rinse with 0.2% chlorhexidine digluconate was used for the 4-h experiments, 1 min after film placement, whereas, for the 24-h experiments, an additional 1 min rinse was used at 12 h. In total, 62 films were obtained, half treated and half controls. These were processed for light and transmission electron microscopy, using standardized techniques for area sampling and cell counting. All plastic films were covered by a surface coating of acellular material in or on which bacteria, epithelial cells and leukocytes were observed. In the controls, an important increase in bacterial count was seen between 4 and 24 h, whereas the increase with chlorhexidine was slight. There were fewer bacteria in the chlorhexidine as compared to the water specimens, for both time periods. Many microorganisms in the chlorhexidine samples appeared to be undergoing degeneration with coagulated cytoplasm and disrupted cell walls.

Quantitative relationship between yeast and bacteria in denture-induced stomatitis.

Quantitative cultural studies of yeasts and bacteria were made from 7-day-old denture plaque accumulate on pieces of self-adhesive tape stuck on the fitting surface of the maxillary denture in 17 edentulous subjects with healthy oral mucosa and in 27 patients affected with denture-induced stomatitis. Significantly higher numbers of yeasts and bacteria were cultured in the stomatitis patients than in the controls. This indicates that the rate of plaque formation is increased in patients with denture-induced stomatitis. Yeasts usually constituted less than 1% of the anaerobic bacterial counts, but the percentage of yeasts was significantly higher in the stomatitis patients than in the controls. There was a significant correlation between initially higher yeast counts and improvement of the clinical condition of the palatal mucosa following antimycotic treatment. In some patients only bacteria were grown and antimycotic treatment had no effect. The study supported the contention that yeast antigens and toxins of denture plaque are significant factors in initiation and maintenance of denture-induced stomatitis. However, bacteria may also be involved as pathogens.

Predominant cultivable microflora of plaque on removable dentures in patients with healthy oral mucosa.

Plaque from the fitting surface of upper full dentures in eight patients with healthy palatal mucosa was studied. To characterize the predominant cultivable flora, 916 isolates (100-128 from each sample) were subcultured from anaerobic roll-tubes. Streptococci constituted 0-81 per cent (median, 41 per cent) of the isolates with varying proportions of Streptococcus milleri, Streptoccus mutans, Streptococcus salivarius, Streptococcus mitior and Streptococcus sanguis. Staphylococcus aureus made up 0-13 per cent (median, 6 per cent). Gram-positive rods constituted 1-74 per cent (median, 33 per cent). Among these, Actinomyces israelii, Actinomyces naeslundii, Actinomyces viscosus and Actinomyces odontolyticus were the most common species, whereas lactobacilli were isolated only from two samples, constituting 21 and 48 per cent. Among Gram-negative bacteria, only Veillonella parvula was common, constituting 3-20 per cent (median, 10 per cent). Gram-negative rods were isolated only from three samples in small proportions making up 0-6 per cent (median, 0 per cent) of the flora. Forty-seven isolates (5 per cent) were lost. Cultures for yeasts on Sabouraud agar were positive for five samples and the yeast counts corresponded to 0-0.45 per cent (median, 0.002 per cent) of the total viable counts. The microflora of denture plaque is highly variable and is to a large extent similar to that of some forms of dental plaque.

Predominant cultivable microflora of human dental fissure plaque.

Plaque developed in 10 occlusal fissures from unerupted third molars during implantation for 200 to 270 days in lower molars of dental students was studied. To characterize the predominant cultivable flora, 592 isolates (51 to 67 from each fissure) were subcultured from anaerobic roll tubes. Twenty-eight of the isolates were lost. Streptococci constituted 8 to 86% (median, 45%) of the isolates, Streptococcus mutans constituted 0 to 86% (median, 25%) and S. sanguis constituted 0 to 15% (median, 1%). A few isolates of "S. mitior" and "S. milleri" were found, but no S. salivarius. Staphylococci made up 0 to 23% (median, 9%). Gram-positive rods constituted 6 to 59% (median, 35%). Of these, 0 to 46% (median, 18%) were Actinomyces naeslundii and A. viscosus, but no anaerobic actinomyces were isolated. Arachnia and propionibacteria made up small proportions, lactobacilli were isolated from two fissures, constituting 10 and 29%, and eubacteria were isolated from one fissure (27%). Gram-negative cocci made up 0 to 46% (media, 4%). Only two isolates of gram-negative rods were found, both facultative anaerobes. Although 8 of the 10 fissures had large proportions of S. mutans, lactobacilli, or both, no caries was found even with microradiography. The large individual variation probably reflects differences in initial colonization from saliva and in growth conditions in each fissure.

Method for studying the development, structure and microflora of denture plaque.

Pieces of sandblasted, self-adhesive tape were stuck to the fitting surface of maxillary dentures in 17 edentulous subjects with clinically normal palatal mucosa. After 1 week, during which the subjects abstained from denture hygiene, the tape samples were removed for cultural and microscopical examinations. The microorganisms were suspended in RTF by ultrasonic treatment and total viable anaerobic counts and viable counts of yeasts per cm2 of tape were calculated after inoculation of serial dilutions on nonselective medium and sabouraud agar. Total anaerobic viable counts ranged from 4 X 10(4) to 5 X 10(8). By repeated sampling the largest intra-individual variation was 10-fold, only. Yeast counts constituted less than 1% of the total viable counts in all but two of the subjects. Light and electron microscopy showed a bacterial plaque of predominantly cocci and rods.