Dentists' variability in restorative decisions, microscopic and radiographic caries depth

Restorative and dental caries depth decisions were recorded for 5168 un restored approximal tooth surfaces by 17 dentists who worked in the school dental clinics of the North York (Ontario) Public Health Department. Each dentist examined 15 pairs of experimental bitewing radiographs for which true caries depth had previously been determined by microscopy of the sectioned teeth following production of the radiographs. The dentists independently recorded their restorative decisions and radiographic caries depth perceptions. The relationship between the variation in the dentists' restorative decisions and their perceptions of caries depth based on a re-reading of the bitewings on the one hand, and true caries depth on the other was also examined. The percentages of total variability in each dentist's restorative decisions attributable to radiographic and to microscopic caries depth were estimated using regression analyses. Large variations were found among the 17 dentists' distributions of overall restorative and depth decisions. The relationship between microscopic caries depth and the dentists' restorative decisions was, understandably, less strong than that of the dentists radiographic perceptions of caries depth and restorative decisions. Relative to true caries depth, high numbers of false positive and false negative restorative decisions were made. Overall, 50% of the variability in the dentists' restorative decisions was explained by the perceptions of radiographic caries depth; however, among individual dentists, the range was from 29% for one dentist to 69% for another. A much lower percentage of the overall restorative variation was explained by microscopic depth, 18%. Like the finding of the only two previous European studies that quantified the role of radiographs on clinical decisions, this study demonstrated that dentists' perceptions of dental caries depth using bitewing radiographs play a major but variable role in their restorative decisions for approximal tooth surfaces.     

Pyogenic liver abscesses and acute schistosomiasis mansoni: report on 3 cases and experimental study

Three children with acute schistosomiasis mansoni developed pyogenic liver abscesses. The abscesses were diagnosed by ultrasonography and confirmed during laparotomy. Staphylococcus aureus were the sole bacteria isolated from the abscesses. An experimental study was carried out in mice to establish whether schistosomiasis is a predisposing cause for pyogenic liver abscesses. Seventeen mice (group 1) were infected with 40 Schistosoma mansoni cercariae (LE strain) and 60 d later inoculated intravenously with a strain of Staph. aureus, isolated from a patient with bacteraemia; 17 mice infected with Sch. mansoni (group 2), 19 infected with bacteria alone (group 3), and 18 uninfected mice (group 4), served as controls. Thirteen group 1 mice (77%) developed multiple liver abscesses while none was observed in the controls. These results indicate that acute schistosomiasis mansoni concurrent with Staph. aureus bacteraemia favours the colonization of the liver by bacteria and the development of pyogenic hepatic abscesses.     

Local intraluminal infusion of biodegradable polymeric nanoparticles. A novel approach for prolonged drug delivery after balloon angioplasty

BACKGROUND: Several perfusion balloon catheters are under investigation for local drug delivery; however, sustained tissue drug levels are difficult to achieve with these techniques. To overcome this problem, sustained-release, biodegradable nanoparticles represent a potential alternative for prolonged local delivery. METHODS AND RESULTS: A biodegradable polylactic-polyglycolic acid (PLGA) copolymer was used to formulate nanoparticles. Fluorescent-labeled nanoparticles were intraluminally administered in a single, 180-second infusion after balloon injury in the rat carotid model. Localization and retention at different time points and biocompatibility of nanoparticles were evaluated. To evaluate the potential of the system in the prevention of neointimal formation, dexamethasone was incorporated into the particles and delivered locally as above. Nanoparticles were seen in the three layers of the artery at 3 hours and 24 hours. At 3 days, they were mainly present in the adventitial layer, decreasing at 7 days, with no fluorescent activity at 14 days. The PLGA nanoparticles appeared to be fully biocompatible. In the dexamethasone nanoparticle study, a significant amount of dexamethasone was present in the treated segment for up to 14 days after a single infusion, with no plasma levels detected after the first 3 hours. There was a 31% reduction in intima-media ratio in animals treated with local dexamethasone nanoparticles compared with control. CONCLUSIONS: Nanoparticles successfully penetrated into the vessel wall and persisted for up to 14 days after a short, single intraluminal infusion. Local administration of nanoparticles with incorporated dexamethasone significantly decreased neointimal formation. This methodology appears to have important potential for clinical applications in local drug delivery.     

Histogenesis of the chequered pattern of ivory of the African elephant (Loxodonta africana)

This study aimed to propose a hypothesis on the events which lead to the development of the characteristic chequered pattern of elephant ivory. Twenty fragments of ivory and six elephant tusks were obtained through the National Parks Board of South Africa. Polished surfaces were prepared in sagittal and longitudinal planes and the characteristics of the distinctive chequered pattern described. Light- and electron-microscopical techniques and image analyses were employed to determine the morphological basis of the pattern and to describe the spatial distribution, density and morphology of the dentinal tubules. These investigations showed that the distinctive pattern was the result of the sinusoidal, centripetal course followed by dentinal tubules. The apical, slanted part of the sinusoidal curve is the result of the centripetally moving odontoblast, which, during formation of ivory, progresses towards the centre of the tusk on a decreasing circumference. It is suggested that this leads to cell crowding, increased pressure between odontoblasts and subsequent apical movement of their cell bodies, cell degeneration and fusion. Odontoblastic degeneration and fusion probably relieve the pressure between the crowded odontoblasts by reducing their numbers and the remaining odontoblasts now orientate their centripetal course towards the tip of the tusk, thereby forming the anterior-directed part of the sinusoidal path of the tubule. As odontoblasts progress centripetally the diameter of the pulpal cavity decreases further and the processes of apical movement, fusion and degeneration of odontoblasts are repeated. This occurs until the pulpal cavity is obliterated.     

Age-related deficits on the radial maze and in fear conditioning: hippocampal processing and consolidation

Young adult, middle-aged, and old male F-344 rats were assessed for their hippocampal ability. This was accomplished by examining the animals on two different paradigms, each incorporating a simultaneous measure of hippocampal-dependent and -independent processing. The animals were fear conditioned and then tested for retention of the conditioning context and tone. This was followed by an 8-arm radial maze task which combined spatial working and cued reference memory elements. The two paradigms are compared in terms of task demands, potential confounds, and validity for aging studies. The results indicate that the performance of the animals on the two tasks is correlated. Age-related deficits limited to the hippocampal aspects of the above tasks were found, with no deficits found in the analogous but hippocampus-independent aspects of these tasks. The function of the hippocampus in incorporating new memories is time-related. Therefore, the possibility of age-related changes in consolidation was examined. It has previously been shown on the fear conditioning paradigm that the hippocampus is involved in retention of the aversive context for approximately 28 days. In the present study, an attempt was made to test the animals for retention of the conditioning context both early into the period of consolidation (10 days) and after consolidation should have been completed (52 days). The results indicate that, initially, the old animals show comparable retention to young rats. When examined later, young animals showed a stronger retention of the conditioning context than they had previously. The aged rats, however, did not seem to benefit from this additional period of time and in fact showed a decrease in retention of the conditioning context. The data are interpreted in terms of consolidation, alternative explanations of the data are presented, and suggestions are given for future research. Finally, the implications of such age-related changes in hippocampal consolidation on learning and memory are discussed.     

Primary afferent tachykinins are required to experience moderate to intense pain

The excitatory neurotransmitter glutamate coexists with the peptide known as substance P in primary afferents that respond to painful stimulation. Because blockers of glutamate receptors reliably reduce pain behaviour, it is assumed that 'pain' messages are mediated by glutamate action on dorsal horn neurons. The contribution of substance P, however, is still unclear. We have now disrupted the mouse preprotachykinin A gene (PPT-A), which encodes substance P and a related tachykinin, neurokinin A. We find that although the behavioural response to mildly painful stimuli is intact in these mice, the response to moderate to intense pain is significantly reduced. Neurogenic inflammation, which results from peripheral release of substance P and neurokinin A, is almost absent in the mutant mice. We conclude that the release of tachykinins from primary afferent pain-sensing receptors (nociceptors) is required to produce moderate to intense pain.     

Loss of heterozygosity at 5q21-22 (adenomatous polyposis coli gene region) in oral squamous cell carcinoma is common and correlated with advanced disease

We determined the frequency of loss of heterozygosity (LOH) at chromosome 5q21-22 (adenomatous polyposis gene region) in oral SCC from 49 patients using PCR-based assays. Of 43 informative (heterozygous) tumors, 41.9% [95% confidence interval (CI)=27.0, 57.9] contained LOH at 5q21-22. LOH at 5q21-22 was strongly associated with stage at diagnosis: 100%, (3/3), 50% (13/26), and 14% (2/14) of tumors from patients with distant metastases, regional spread, and localized disease, respectively, contained this genetic alteration (P=0.01). There were no statistically significant associations between LOH at 5q21-22 and other patient or tumor characteristics, but LOH was more commonly found in the tumors of heavy smokers, infrequent alcohol consumers, and in tumors containing either p53 mutations or HPV-DNA. In univariate analyses, LOH at 5q21-22 was associated with poor prognosis (hazard ratio=1.8, 95%, CI 0.8, 4.5); this relationship did not persist after adjustment for stage of disease (hazard ratio=1.1, 95% CI=0.4, 3.1). These data provide further evidence that inactivation of the APC gene and/or other genes at 5q21-22 is common and may be involved in the development and/or progression of oral SCC. Larger studies are needed to determine whether LOH at 5q21-22 is linked to known oral SCC etiologic factors and/or the prognosis of oral SCC patients, as well as to genetic instability at other loci involved in these malignancies.     

Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis. Results of a controlled clinical trial of selective decontamination

OBJECTIVES: To establish, firstly, whether gram-negative (re)-colonization of the gut leads to an increased risk of gram-negative pancreatic infections and whether this event is time-related and, secondly, whether the difference in the quantity and quality of micro-organisms colonizing the digestive tract influences morbidity and mortality. DESIGN: Prospective analysis of the results of systematic semi-quantitative cultures of several body areas taken from patients with severe acute pancreatitis, during a controlled multicenter trial of adjuvant selective decontamination. SETTING: Surgical intensive care units of 16 hospitals. PATIENTS: A total of 2,159 semi-quantitative cultures from the oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed. Interventions: Surveillance cultures from the oropharynx and rectum were taken on admission and repeated twice weekly and from the (peri)-pancreatic devitalized tissues (i. e. necrosis) at every relaparotomy and from drainage. MEASUREMENTS AND RESULTS: All gram-negative pancreatic infections were preceded by intestinal colonization with the same micro-organisms. The risk of developing a pancreatic infection following gram-negative intestinal colonization (15/42 patients) was significantly higher as compared to patients without gram-negative colonization (0/10 patients) (p < 0.001) or to patients in whom E. coli was the only intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of intestinal E. coli did not increase the risk of pancreatic infection. Gram-negative colonization of the rectum and oropharynx significantly correlated with the later development of pancreatic infection: relative risks 73.7 (p < 0.001) and 13.6 (p < 0.001), respectively. However, when both areas were evaluated simultaneously, the rectum was more significant (p < 0.001). The severity of intestinal intestinal colonization until the moment of pancreatic infection showed an increase in time in all 15 patients. In 11 of 15 patients (73%) these infections occurred within 1 week following the first isolation from the digestive tract. Gram-negative intestinal colonization was associated with a 3.7 fold increased mortality risk (p = 0.004). CONCLUSIONS: Gram-negative intestinal colonization, E. coli excepted, is an early prognostic parameter in patients in whom pancreatic infection has not yet occurred and represents a significantly increased risk of pancreatic infections and mortality.     

Distinct patterns of NCAM expression are associated with defined stages of murine hair follicle morphogenesis and regression

Hair follicle development, growth (anagen), and regression (catagen) largely result from bidirectional epithelial-mesenchymal interactions whose molecular basis is still unclear. Because adhesion molecules are critically involved in pattern formation and because the fundamental importance of neural cell adhesion molecule (NCAM) for feather development has been demonstrated, we studied the protein expression patterns of NCAM during hair follicle development and regression in the C57BL/6 mouse model. During murine hair follicle development, NCAM immunoreactivity (IR) was first detected on epithelial hair placodes and later on selected keratinocytes in the distal outer root sheath. Mesenchymal NCAM immunoreactivity (IR) was noted on fibroblasts of the future dermal papilla (DP) and the perifollicular connective tissue sheath. Fetal hair follicle elongation coincided with strong, ubiquitous dermal NCAM IR, which remained strong until the follicles entered into their first neonatal catagen. At this time, the strong interfollicular dermal NCAM IR decreased substantially. During consecutive hair cycles, mesenchymal NCAM IR was seen exclusively on DP and perifollicular connective tissue sheath fibroblasts and on the trailing cells of regressing catagen hair follicles. These highly restricted and developmentally controlled expression patterns suggest an important role for NCAM in hair follicle topobiology during morphogenesis and cyclic remodeling of this miniorgan.     

Evaluation and comparison of three mobilization methods for the collection of granulocytes

BACKGROUND: Cancer chemotherapeutic regimens have become more potent and myeloablative. As a consequence, morbidity and mortality due to opportunistic infections have become a major challenge. The provision of adequate doses of viable granulocytes has thus become an important approach for circumventing the problem. A schedule for collecting therapeutic numbers of cells with minimal donor toxicity has yet to be established. STUDY DESIGN AND METHODS: An investigation of three mobilization schedules for the collection of granulocytes for transfusion--granulocyte-colony-stimulating factor (G-CSF) 5 micrograms per kg daily; G-CSF 5 micrograms per kg every other day, and prednisone 60 mg given orally (20 mg doses at 17 hours, 12 hours, and 2 hours before the collection). RESULTS: A total of 464 apheresis procedures involving 163 healthy donors were analyzed. Prednisone caused a small increase in the white cell (WBC) counts over the collection days, while G-CSF every other day and daily schedules improved WBC counts to 145 and 160 percent, respectively (p = 0.004). Similarly, administration of G-CSF daily and every other day mobilized higher yields of granulocytes over the collection days, compared to the prednisone schedule (170% and 180% vs. 105%; p = 0.02). CONCLUSION: Compared with prednisone, higher WBC yields were achieved by G-CSF stimulation; G-CSF given every other day is as effective as daily G-CSF administration for the recruitment of granulocytes, which makes the mobilization procedure more cost-effective.