Learning by doing virtually.

Selective reduction of bone without collateral damage (nerves, teeth) is essential in apicectomy. To test whether skills acquired on a virtual apicectomy simulator (VOXEL-MAN system with integrated force-feedback) are transferable from virtual to physical reality, two groups of trainees were compared. Group 1 received computer-based virtual surgical training before performing an apicectomy in a pig cadaver model. The probability of preserving vital neighboring structures was improved significantly, i.e. six-fold, after virtual surgical training (P<0.001). The average volume of the bony defects created by the trainees of Group 2 (mean: 0.47 ml) was significantly (P<0.001) larger than by the trainees of Group 1 (mean: 0.25 ml). Most importantly, the ability to objectively self-assess performance was significantly improved after virtual training. Training with a virtual apicectomy simulator appears to be effective, and the skills acquired are transferable to physical reality.

Innate immunity in human bone.

Bone has exceptional regenerative properties. Oral bone appears to be particularly resistant to infection despite exposure to oral flora, even in circumstances such as oral surgery where the thin mucosal layer covering the bone is disrupted. The goal of this study was to determine whether the innate immune system of antimicrobial peptides exists inside bone. Biopsies of non-infected and chronically infected mandibular bone were harvested from patients during maxillofacial surgical procedures. Bone biopsies from the iliac crest and fibula served as controls. Immunohistochemical staining was performed, directed against the human beta-defensin antimicrobial peptides (hBD) -1, -2 and -3. In addition, cultures of osteoblast-like cells were examined for the presence of each of the three beta-defensins and their mRNA transcripts. All three human beta-defensins were detected within the mineralized bone matrix of chronically infected mandibular bone in the vicinity of the endosteum and osteocytes. hBD-1, -2 and -3 were also found in the cytoplasm of osteocytes. Expression of all three beta-defensins was detected in each of the non-infected bone types including the controls, however, to a lesser degree than that found in the chronically infected mandibular bone. This may reflect upregulation of antimicrobial peptide expression in the presence of chronic infection. Cultures of non-infected osteoblast-like cells were found to express mRNA for each of hBD-1, -2 and -3. Immunohistochemical staining of the cultures was positive for hBD-1 and -2, but not for hBD-3. We provide the first evidence of a previously unrecognized innate immunological function of bone through the demonstration of the presence of the human beta-defensins hBD-1, -2 and -3 in bone.

Growth and transplantation of a custom vascularised bone graft in a man.

BACKGROUND: A major goal of research in bone transplantation is the ability to avoid creation of secondary bone defects. We aimed to repair an extended mandibular discontinuity defect by growth of a custom bone transplant inside the latissimus dorsi muscle of an adult male patient. METHODS: Three-dimensional computed tomography (CT) scanning and computer-aided design techniques were used to produce an ideal virtual replacement for the mandibular defect. These data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 and 20 mL of the patient's bone marrow. Thus prepared, the transplant was implanted into the latissimus dorsi muscle and 7 weeks later transplanted as a free bone-muscle flap to repair the mandibular defect. FINDINGS: In-vivo skeletal scintigraphy showed bone remodelling and mineralisation inside the mandibular transplant both before and after transplantation. CT provided radiological evidence of new bone formation. Postoperatively, the patient had an improved degree of mastication and was satisfied with the aesthetic outcome of the procedure. INTERPRETATION: Heterotopic bone induction to form a mandibular replacement inside the latissimus dorsi muscle in a human being is possible. This technique allows for a lower operative burden compared with conventional techniques by avoiding creation of a secondary bone defect. It also provides a good three-dimensional outcome.

Comparative analysis of serologic screening tests for the initial diagnosis of celiac disease.

OBJECTIVE: To prospectively evaluate and compare the sensitivity, specificity, and positive and negative predictive values of serum antigliadin (AGA) and antiendomysium antibodies (EMA) in predicting the initial diagnosis of celiac disease. DESIGN: Sera were tested prospectively for IgA and IgG AGA by enzymed-linked immunosorbent assay and IgA EMA by immunofluorescence techniques on monkey esophagus and human umbilical cord sections in 95 pediatric patients referred for duodenal biopsies. PATIENTS: Ninety-five pediatric patients were referred for duodenal biopsies, with a clinical suspicion of celiac disease; 24 of those patients had celiac disease by criteria of the European Society for Pediatric Gastroenterology and Nutrition. SETTING: A pediatric gastroenterology clinic of a tertiary care pediatric university hospital. RESULTS: EMA testing on human umbilical cords was the most specific but was also the least sensitive. All the patients with biopsy-proven celiac disease were identified by either one or both serologic tests (100% combined sensitivity). The combination of AGA and EMA on monkey esophagus resulted in a negative predictive value of 100% accuracy. CONCLUSIONS: A combination of AGA and EMA tests resulted in 100% sensitivity and 100% negative predictive value, useful in selecting patients for duodenal biopsy.

An unusual histiocytoid proliferation in infancy.

A 2 1/2-month-old female infant was admitted to the Hôpital Ste-Justine for investigation of marked hepatosplenomegaly. The pregnancy and neonatal period were uneventful and the child had exhibited normal growth. There were no skin or osseous lesions. Investigations revealed a coagulopathy with hypoproteinemia, but normal liver enzymes. An open liver biopsy revealed widespread infiltration of portal veins and hepatic sinusoids by large histiocyte-like cells, exhibiting protein S-100 and Ia antigen, but negative for OKT6, peanut agglutinin, and T and B cell and macrophage markers. Ultrastructural examination failed to reveal Birbeck granules. After a 4-month course of chemotherapy, liver and spleen size decreased, the biochemical profile returned to baseline levels, and the child has remained well. A repeat liver biopsy, performed at the end of the therapeutic trial, was normal. This patient presents an unusual pattern of infiltration of liver and spleen not readily classifiable within the present scheme of histiocytic disorders.

A two-tier polymerase chain reaction direct sequencing method for detecting and typing human papillomaviruses in pathological specimens.

An in-house polymerase chain reaction direct sequencing (PCR-DS) approach for HPV detection and typing was developed, taking advantage of two widely used pairs of human papillomavirus (HPV)-specific PCR primers, MY09/MY11 and GP5/GP6, and 33P-labeled dideoxynucleotides. In this study, 105 pathological specimens were examined: 89% were diagnosed as cervical intraepithelial neoplasia (CIN) grade I-III, 76.2% were HPV-positive by PCR-DS. The PCR using GP5/GP6 (first tier) and MY09/MY11 primers (second tier for the GP5/GP6-negative samples) detected additional 15%-25% HPV-positive samples compared with each pair used separately. Direct sequencing was then used to type the HPV. A readout of a sequence as short as 34 nucleotides within a specific region in the L1 gene is sufficient to type known or novel sequences. Because of its high sensitivity and cost-effectiveness, the two-tier PCR-DS was adopted by the authors as the current method of choice for HPV diagnosis with ultimate sequence precision.

Staged repair of pentalogy of Cantrell with tetralogy of Fallot.

We report a successful two-stage repair of tetralogy of Fallot associated with pentalogy of Cantrell. The first stage, performed in the neonatal period, consisted of repairing the omphalocele, separating the peritoneal from the pericardial cavities, and covering the heart. The second stage, performed at 6 years of age, consisted of complete intracardiac repair and placing the heart in the chest. The patient is alive and well 18 months after the operation.

Chronic alterations in cardiac mechanics after fetal closed heart operation.

Pulmonary artery banding was performed in 8 fetal sheep at 125 days' gestation to evaluate the feasibility of fetal closed cardiac operation. At 135 days' gestation, the fetuses were delivered and the cardiac mechanics were evaluated using a modified Langendorff isolated heart preparation. Two of the 8 fetuses aborted spontaneously 2 and 7 days after operation. Six fetuses (75%) survived the 10 days after delivery. The left ventricular cardiac mechanics in the banded fetuses (group I) were compared with those in 8 control fetuses (group II). All fetal hearts in both groups displayed a significant volume-pressure relationship. The volume-pressure curve was found to be shifted upward and to the left in the fetal hearts after pulmonary artery banding. The left ventricles subjected to increased in utero preload secondary to pulmonary artery banding were capable of generating greater peak systolic and developed pressures. Because the fetal heart manifests a Starling type of preload reserve, as such, it demonstrates that the possibility exists for subsequent fetal development to be altered by intrauterine intervention.

Operative creation of left to right cardiac shunts: pulmonary functional sequelae.

The creation of left to right cardiac shunts in neonates is frequently complicated by pulmonary morbidity in the immediate postoperative course. To elucidate the pattern, severity, and cause of lung dysfunction, pulmonary function testing was performed preoperatively and 1, 3, and 7 days postoperatively on 7 neonates undergoing Blalock-Taussig shunting. Pulmonary mechanics (compliance, conductance) were determined with esophageal manometry and pneumotachography, and functional residual capacity was measured by the helium dilution technique. The infants had pulmonary function preoperatively that was similar to that of healthy term neonatal controls. Significant decreases in compliance, conductance, and functional residual capacity were found on the first postoperative day (57%, 21%, and 53% of predicted, respectively). Alterations in conductance were more severe than those in compliance, but both were low through postoperative day 3. Functional residual capacity was the least affected parameter and recovered by postoperative day 3. All parameters were normal by postoperative day 7. These data indicate that shunting is associated with pulmonary morbidity through the third postoperative day that affects the airways more than the lung parenchyma. Pulmonary function studies of these infants may clarify the etiology of pulmonary dysfunction and have an impact on therapeutic strategies used in neonates undergoing cardiac operations.

Effects of halothane on the immature lamb heart.

The choice of anesthesia during pregnancy and fetal operations is controversial. Halothane frequently is used, but its direct effects on fetal cardiac performance are unknown. The effects of halothane on fetal cardiac mechanics were studied in 8 fetal lamb hearts (135 days' gestation) using a modified Langendorff model connected to a membrane oxygenator. The perfusate consisted of oxygenated maternal blood at a constant flow temperature, hematocrit value, and glucose level. Coronary blood flow, left ventricular systolic pressure, left ventricular end-diastolic pressure, and the developed left ventricular pressure at a fixed volume were evaluated at baseline and after the addition of incremental concentrations of halothane to the perfusate through the oxygenator. Perfusate halothane levels were maintained in a clinical range. Systolic and diastolic cardiac function were adversely affected by the administration of even low doses of halothane, despite a concomitant increase in coronary blood flow. Because of the immaturity of their calcium transport system, fetal hearts may be particularly sensitive to the known calcium channel-blocking properties of halothane.

High-frequency jet versus conventional ventilation in infants undergoing Blalock-Taussig shunts.

Nine infants undergoing modified Blalock-Taussig shunts were randomized to both high-frequency jet ventilation (HFJV) and conventional ventilation (CV). Vital signs, blood gases, mean airway pressure, lung mechanics, functional residual capacity, and lung movement were compared on both modes of ventilation keeping peak inspiratory and expiratory pressures constant. The mean airway pressure was lower on HFJV than on CV (8.5 versus 10.9 cm H2O). Arterial partial pressure of oxygen was greater on HFJV than on CV (55 versus 46 mm Hg), arterial partial pressure of carbon dioxide was lower on HFJV than on CV (28 versus 37 mm Hg), whereas compliance (0.54 versus 0.56 mL.cm H2O-1.kg-1). resistance (110 versus 95 cm H2O/L.s), and functional residual capacity (23 versus 22.5 mL/kg) remained the same. Lung movement and degree of retraction necessary for surgical exposure as evaluated by an independent observer was less with HFJV compared with CV. Compared with CV during the creation of Blalock-Taussig shunts, HFJV provides better gas exchange at lower mean airway pressure with similar lung function, lung volume, and hemodynamics.

Pressure-volume relationship of the fetal lamb heart.

In contrast to the adult heart, the fetal heart reportedly has little functional reserve. With increased clinical emphasis on fetal cardiac diagnosis, neonatal surgery, and the potential for future fetal cardiac intervention, it is essential that we better understand fetal cardiac function. Therefore, to demonstrate the extent of fetal cardiac preload reserve, we studied 10 fetal lambs using an isolated, isovolumic, blood-perfused heart preparation. We maintained constant afterload, inotropic state, coronary blood flow, heart rate, and perfusate blood gas values. As left ventricular (LV) volume (preload) was incrementally increased, LV end-diastolic pressure and LV peak systolic pressure were recorded. Linear regression analysis demonstrated that increases in LV developed pressures were predicted by the LV volume, demonstrating the presence of the Frank-Starling mechanism in each case. The plateau of the Starling pressure-volume curve occurred at an LV end-diastolic pressure of 12.5 +/- 4.79 mm Hg (95% confidence interval, 9.07 to 15.9 mm Hg), lower than the plateau expected in the adult heart. This implies that, in the management of fetal and immature neonatal hearts, preload reserve plays an important but limited role in cardiac reserve.

Effect of inhibitors of oxygen radical and nitric oxide formation on UV radiation-induced erythema, immunosuppression and carcinogenesis.

We investigated whether supplementation of a sunscreen containing the UVB absorber 2-ethyl-hexyl-methoxycinnamate (cinnamate) with oxygen radical inhibitors (ORI) would improve protection from sunburn, immunosuppression and carcinogenesis. Mice were exposed to solar-simulated UV radiation (ssUV) containing a mixture of UVB and UVA. In initial studies, the ORI 2,2'-dipyridyl and N(G)-monomethyl-L-arginine acetate (L-NMMA) were shown to prevent UVA-induced suppression of contact sensitivity (CS) in mice. Addition of these inhibitors to the sunscreen did not affect the sun protection factor (SPF), but lowered the level of edema when mice were exposed to ssUV. Combination of both inhibitors with the sunscreen, however, increased the SPF from 5 to 5.5. The immune protection factor (IPF) of the sunscreen was only 1.18, but addition of neither dipyridyl nor L-NMMA singly or in combination measurably improved immune protection. However, the ORI improved the ability of the sunscreen to prevent carcinogenesis. The results indicate that reactive oxygen or nitrogen species produced in response to UV radiation are important for erythema, immunosuppression and carcinogenesis, and addition of inhibitors improves the protective capacity of sunscreens.

Wheat starch intolerance in patients with celiac disease.

OBJECTIVE: Evaluate in patients with celiac disease the tolerance of prolonged consumption of small amounts of gliadin contained in products containing wheat starch. DESIGN: Open 1-year trial of the addition of wheat starch to a gluten-free diet in a cohort of adult patients with biopsy-proven celiac disease who had never consumed wheat starch. The control group consisted of patients with celiac disease who tolerated wheat starch. SUBJECTS: Seventeen patients with celiac disease and 14 control patients, all diagnosed according to criteria of the European Society of Pediatric Gastroenterology and Nutrition, were recruited from the Canadian Celiac Association and the Quebec Celiac Foundation. SETTING: The study was conducted in the outpatient clinic of the Gastroenterology and Nutrition Service of Ste Justine Hospital, Montreal, Quebec, Canada. INTERVENTIONS: Patients were asked to consume four to six portions daily of a wheat starch-containing product, mainly bread, for up to 1 year. MAIN OUTCOME MEASURES: The gliadin content of the wheat starch product used in this trial was quantified by enzyme-linked immunosorbent assay. Patient outcome measures included symptoms, nutritional parameters (anthropometric data, complete blood count, serum folate and iron levels), and immunologic parameters (antigliadin antibody and antiendomysium antibody titers). RESULTS: A quantifiable amount of immunoreactive gliadin (0.75 mg/100 g) was found in the wheat starch. The majority of the patients with celiac disease (11 of 17) who had never consumed wheat starch previously developed symptoms, which resolved within weeks of discontinuing the product. Relapse of skin lesions was seen in two of three patients with coexisting dermatitis herpetiformis. No weight loss or biochemical changes were observed. Despite the presence of symptoms, antigliadin antibody and antiendomysium antibody determinations were not useful to detect the clinical intolerance. APPLICATIONS: The innocuousness of the long-term ingestion of "gluten-free" products containing wheat starch is still unproven, and prolonged use of such products by patients with celiac disease cannot be recommended.

The economic burden of congestive heart failure in a managed care population.

OBJECTIVE: To examine the economic burden of and treatment patterns for congestive heart failure (CHF) in a managed care population. STUDY DESIGN: Retrospective review of medical and pharmacy claims. PATIENTS AND METHODS: We reviewed integrated medical and pharmacy claims data from 6 independent-practice-association model health maintenance organizations to identify patients diagnosed with CHF. Of the approximately 1.4 million people enrolled in these managed care plans during the study period (January through December 1994), a total of 2777 patients (mean age, 56.9 years) met the study criteria, which included diagnostic codes for CHF and claims eligibility of at least 1 year. We reviewed the charges incurred by patients diagnosed with CHF for the 6 months after the initial CHF medical claim. We also examined the treatment received by each of these patients. RESULTS: During the study period, 378 of the 2777 patients with CHF (14%) were admitted to the hospital at a cost of almost $3 million (an average of $7863 per hospitalized patient). Seventy-eight percent of the study population received prescription drugs, at an average per-patient cost of $942. The most commonly prescribed drug class was angiotensin-converting enzyme inhibitors, prescribed for 38% of patients. Calcium channel blockers were prescribed for 33% of patients, but beta-blockers were prescribed for only 18% of patients. Hospitalization accounted for 54% of the total cost for CHF treatment, with prescription drugs accounting for 38%. CONCLUSION: Congestive heart failure represents a significant financial burden within a non-elderly managed care population. Improved management of the condition is needed to reduce the morbidity and mortality, as well as the costs of treatment, associated with CHF. Considerable data indicate that drugs such as beta-blockers and angiotensin-converting enzyme inhibitors can significantly decrease the morbidity and mortality of CHF. Further investigation is needed into whether increased use of prescription pharmaceuticals may reduce hospitalization rates and overall costs for CHF in this setting.

Use of mental health services by persons with a mental illness in nursing facilities: initial impacts of OBRA87.

OBJECTIVE: To identify mental health service use patterns in nursing facilities subsequent to nursing home reforms in the Omnibus Budget Reconciliation Act of 1987. METHODS: The study involves a retrospective analysis of Medicare Part B claims for mental health care for persons in a nursing facility in 1992 (N = 692) using the Medicare Current Beneficiary Survey. Mental health service use was described and analyzed using logistic regression. RESULTS: Only 26% of nursing facility residents and 36% of residents with a mental illness had a mental health visit in 1992. Logistic regression confirms analyses prior to 1987 showing older residents and those in rural areas remain less likely to receive mental health visits. DISCUSSION: Claims data collected after the passage of The Nursing Home Reform Act (NHRA) of 1987 indicate continued low levels of mental health treatment in nursing homes.

Low-resolution gamma-ray measurements of process hold-up.

This tool, consisting of software with a compact detector, an M3CA, and an Intermec datalogger: 1. acquires and manages several hundred spectra in an hour; 2. produces prompt and reliable quantitative analyses; 3. is self-powered, easily carried and operated by a single user; 4. accomodates varying degrees of user expertise; 5. corrects for the effects of equipment geometry; 6. corrects for the effects of equipment attenuation; 7. tolerates facility variables such as temperature fluctuations and equipment accessibility; 8. has been subjected to quality testing under field conditions; and 9. does not require extensive specialized training for the operators.

Transmission and persistence of Actinobacillus actinomycetemcomitans in twins with advanced periodontitis.

The arbitrarily primed polymerase chain reaction technique (AP-PCR) was used to fingerprint Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis isolates in 44-year-old African American male and female twins who had not lived in the same household for 26 years. Both twins exhibited severe loss of periodontal attachment on several maxillary and mandibular teeth. All isolates of A. actinomycetemcomitans yielded the same AP-PCR banding pattern, whereas the P. gingivalis isolates from each twin showed different AP-PCR profiles. The finding of the same amplitype of A. actinomycetemcomitans in both twins suggests a single source of the organism and possibly a persistence of the organism in each twin for at least 26 years.

Mirror, mirror on the wall : self-perception of facial beauty versus judgement by others.

In 1878, Margaret Wolfe Hungerford published a simple but insightful phrase in her novel 'Molly Bawn' that was to be quoted so often it has almost become cliché: "Beauty is in the eye of the beholder". While many questions regarding the perception and neural processing of facial attractiveness have been resolved, it became obvious to us that study designs have been principally based on either facial self-perception or perception by others. The relationship between these however, remains both crucial and unknown. Standardized images were taken of 141 subjects. These 141 subjects were asked to complete the adjective mood scale (AMS) and to rank specific issues related to their looks on a visual analogue scale. The images were then shown to independent judges to rank specific issues related to their looks on a visual analogue scale. Our results show proof for a strikingly simple observation: that individuals perceive their own beauty to be greater than that expressed in the opinions of others (p < 0.001). This observation provides insight into our basic behavioural patterns and suggests that there are strong psychological mechanisms in humans supporting self-identification and thereby encouraging the self-confidence and resilience necessary to maintain one's social standing. While the psychological basis of self-confidence is multifactorial, our finding provides critical objective insight. We prove here for the first time that nothing more than the beauty of the beholder is in the eyes of the latter.

Endocultivation: the influence of delayed vs. simultaneous application of BMP-2 onto individually formed hydroxyapatite matrices for heterotopic bone induction.

When bone morphogenetic protein (BMP) is delivered to matrices in vivo may affect tissue engineered bone constructs for jaw reconstruction after cancer surgery. This study compared the effects of BMP application at different times after matrix implantation for heterotopic bone induction in a rat model. Hydroxyapatite blocks were implanted unilaterally onto the surface of the latissimus dorsi muscle. A second block was implanted onto the contralateral muscle after 1, 2 or 4 weeks and 200 µg rhBMP-2 was injected into the blocks on both sides. Bone formation and density inside the blocks was analysed by CT and histology. 8 weeks after BMP application increases in bone density within the scaffolds were most pronounced in the simultaneous application group (179 HU). Less pronounced increases were observed for the 1 (65 HU), 2 (58 HU) and 4 (31 HU; p<0.0001) week delay group. Homogeneous bone induction started from the central channel of the blocks. Capillaries and larger vessels were seen in all constructs, samples receiving delayed BMP treatment demonstrated significantly greater neovascularization. Delayed application of BMP was less effective for heterotopic bone formation than simultaneous application. A central channel allows homogeneous bone induction directly from the centre of the blocks.