Practical approaches to incidental findings in brain imaging research.

A decade of empirical work in brain imaging, genomics, and other areas of research has yielded new knowledge about the frequency of incidental findings, investigator responsibility, and risks and benefits of disclosure. Straightforward guidance for handling such findings of possible clinical significance, however, has been elusive. In early work focusing on imaging studies of the brain, we suggested that investigators and institutional review boards must anticipate and articulate plans for handling incidental findings. Here we provide a detailed analysis of different approaches to the problem and evaluate their merits in the context of the goals and setting of the research and the involvement of neurologists, radiologists, and other physicians. Protecting subject welfare and privacy, as well as ensuring scientific integrity, are the highest priorities in making choices about how to handle incidental findings. Forethought and clarity will enable these goals without overburdening research conducted within or outside the medical setting.

History of medical ethics and perspectives on disparities in minority recruitment and involvement in health research.

The legitimate and successful recruitment of minorities as research participants in clinical trials should be addressed from an ethical and historical perspective. To gain an appreciation of the challenges, to develop strategies and to overcome the disparities of minority involvement in clinic trials, it is essential to be cognizant of previous violations and abuses of ethics and human rights. Also significant are major legislation, regulations and federal initiatives that resulted from those abuses. From history, we have learned we cannot generalize data and assume that, if we have the majority group in clinical trials, then we can accurately apply that data to minorities. There are cultural and environmental differences; thus, it is absolutely crucial that researchers approach recruitment of minority groups with cultural competence and cultural sensitivity. Federal regulations and legislation set the framework for protection of human participants in research.

Maxillary morphology in obstructive sleep apnoea syndrome.

The aim of this case-control study was to test the hypothesis that maxillary morphology differs between obstructive sleep apnoea (OSA) patients and non-snoring, non-apnoeic subjects. Forty randomly selected patients [36 M, 4 F; mean age 49 +/- 2 (SEM) years] with varying degrees of OSA (mean Apnoea/Hypopnoea Index 32 +/- 4/hour) were compared with 21 non-snoring, non-apnoeic control subjects (18 M, 3 F; mean age 40 +/- 2 years). An intra-oral assessment of the occlusion was carried out, particularly for the presence or absence of posterior transverse discrepancies. Maxillary dental arch width was assessed by standardized lateral inter-tooth measurements (inter-canine, inter-premolar, and inter-molar) from dental models. Palatal height and maxillary depth were also measured. The maxillary dental arch was described by a 4th order polynomial equation. The ratios of maxillary to mandibular width (max/mand) and maxillary to facial width (max/facial) were determined from standardized postero-anterior cephalometric radiographs in a subgroup of patients (n = 29) and all controls. Twenty patients (50 per cent) had evidence of posterior transverse discrepancies compared with one control subject (5 per cent; P < 0.01). All patients had significantly reduced inter-canine, inter-premolar, and inter-molar distances (P < 0.05). The maxillary depth was also shorter (P < 0.05), but palatal height was not different. The quadratic coefficient of the polynomial equation was greater in the patients than in the controls (P < 0.05), indicative of greater arch tapering. Patients had smaller maxillary to mandibular and maxillary to facial width ratios (P < 0.01). These results suggest that OSA patients have narrower, more tapered, and shorter maxillary arches than non-snoring, non-apnoeic controls. Further work is required to determine the relevance of these findings in the pathophysiology of OSA.

History of medical ethics and perspectives on disparities in minority recruitment and involvement in health research.

The legitimate and successful recruitment of minorities as research participants in clinical trials should be addressed from an ethical and historical perspective. To gain an appreciation of the challenges, to develop strategies and to overcome the disparities of minority involvement in clinic trials, it is essential to be cognizant of previous violations and abuses of ethics and human rights. Also significant are major legislation, regulations and federal initiatives that resulted from those abuses. From history, we have learned we cannot generalize data and assume that, if we have the majority group in clinical trials, then we can accurately apply that data to minorities. There are cultural and environmental differences; thus, it is absolutely crucial that researchers approach recruitment of minority groups with cultural competence and cultural sensitivity. Federal regulations and legislation set the framework for protection of human participants in research.

Absence of radiometric differentiation between periapical cysts and granulomas.

A recent study reported that the mean density of periapical cysts was greater than that of periapical granulomas. This study, which used a larger sample size and a robust method for standardization of density and contrast between images, found no difference between the radiographic density of cysts and granulomas classified by microscopic evaluation. Cysts tend to be larger than granulomas, but there was wide variation in size of both types of lesions. There was no significant correlation between the density of a lesion and its size.

Evaluation of ultrasonic and sonic instruments for intraradicular post removal.

Ultrasonic instruments are a valuable asset for removing intraradicular posts from root canals before nonsurgical endodontic therapy. The purpose of this study was to evaluate the relative efficacy of post removal by ultrasonic and sonic devices. Fifty extracted teeth were instrumented and obturated. The canals were prepared and Parapost #5 posts were cemented with zinc phosphate cement. The teeth were divided into five groups, subjected to ultrasonic or sonic instrumentation and the time measured until post removal. Median values in minutes for the post extractions in each group were: Cavitron = 6.0, Enac = 8.3, and Neosonic = 41.2. Sonic instruments were generally unable to remove the posts. The results of this experiment indicate that the Cavitron and Enac ultrasonic units are significantly more efficient for removing posts than the Neosonic. Sonic instruments were not useful for post removal.

Purification and properties of the Escherichia coli K-12 NAD-dependent nucleotide diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase.

The Escherichia coli K-12 NAD-dependent nucleotide-diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase, catalyzes the conversion of ADP-D-glycero-D-mannoheptose to ADP-L-glycero-D-mannoheptose. ADP-L-glycero-D-mannoheptose is a key intermediate of lipopolysaccharide inner core biosynthesis in several genera of Gram-negative bacteria. Sedimentation equilibrium and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified epimerase revealed that the native enzyme has a molecular mass of 240 kDa and a subunit molecular weight of 37,000 +/- 3,000. Lectin binding studies of the purified epimerase indicated that the protein is glycosylated. There was 1 mol of tightly bound NAD+ per enzyme subunit. Variable but small fractions of purified preparations of epimerase are highly fluorescent and contain NADH. The native enzyme can be resolved into apoenzyme and NAD+ by acidic ammonium sulfate precipitation. The catalytic activity can be reconstituted with the addition of NAD+ to the apoenzyme. Optimum pH range for enzyme activity is broad, between 5.5 and 9.5. It exhibits a temperature optimum at 42 degrees C. The Km and Vmax for the substrate is 0.1 mM and 46 mumol 30 min-1 mg-1, respectively. The native enzyme displays UV and fluorescence spectra that are consistent with the presence of enzyme bound NAD+. CD spectra of the holoepimerase indicate 11% alpha-helical and 36% beta-sheet structures.

Torsional properties of twisted and machined endodontic files.

The torsional properties of conventionally twisted K-type endodontic files and recently developed machined K-type endodontic files were compared. File sizes 10 through 40 were subjected to torsional load in clockwise and counterclockwise directions independently. Results showed that a statistically significant reduction in clockwise rotation occurred at failure with all of the machined files except size 10. Counterclockwise rotation at failure was also significantly lower for the machined files in sizes 10 through 30. There was no difference in torsional strength between the file types regardless of rotation direction. Therefore, machined files exhibit less ductility than twisted files prior to fracture and may be more susceptible to torsional failure clinically.

Enzymatic amplification of hepatitis B virus DNA in serum compared with infectivity testing in chimpanzees.

The in vivo infectivity titration of hepatitis B virus (HBV) has been biologically standardized in terms of chimpanzee infectious dose (CID50). The polymerase chain reaction (PCR) was used for in vitro enzymatic amplification of HBV DNA and comparison with CID50. Serial dilutions of human serum specimens containing HBV adw (CID50 10(-7] and ayw (CID50 10(-7.5] were tested to determine the reproducibility and sensitivity of PCR for the detection of HBV DNA. The detection limit of HBV DNA in serum using PCR was 10(-8) for either amplification of HBV DNA extracted from serum or direct amplification of HBV DNA in proteolyzed serum. The amplification efficiency of PCR in proteolysates was not significantly reduced by using a 0.25% concentration (vol/vol) of nonionic detergents and 2.5% concentration (vol/vol) of digested human serum. Thus, PCR is a specific and rapid method for in vitro detection of HBV DNA that is more sensitive than the in vivo infectivity titration of HBV by chimpanzee inoculation. Therefore, if HBV-related DNA cannot be detected by PCR in specimens or biologic products, they probably do not contain infectious HBV.

Antibodies to synthetic peptides from the preS1 region of the hepatitis B virus (HBV) envelope (env) protein are virus-neutralizing and protective.

Hepatitis B virus (HBV) envelope (env) proteins contain three antigenic domains designated S, preS2 and preS1. Studies with synthetic peptide immunogens demonstrated the role of preS2 epitopes in protection against HBV infection. The preS1 domain is implicated in virus-cell receptor interactions suggesting that anti-preS1-specific antibodies should neutralize the infectivity of HBV by blocking virus attachment to cells. We present here evidence that an antiserum to a peptide from the preS1 sequence, anti-preS(21-47), is virus-neutralizing and that active immunization of chimpanzees with a longer peptide derived from the preS1 sequence, preS(12-47), elicits antibodies protective against HBV infection. These results establish the role of the preS1 domain in the process of virus neutralization and the potential of synthetic preS1 analogues for hepatitis B vaccination.

Successful postexposure vaccination against hepatitis B in chimpanzees.

To study the effect of postexposure vaccination, four chimpanzees were vaccinated with hepatitis B (HB) vaccine 4, 8, 48, and 72 hr, respectively, after intravenous injection of an infectious hepatitis B virus (HBV) inoculum. The second and third vaccine inoculations were given 2 and 6 weeks later, i.e., at considerably shorter intervals than recommended either for ordinary prophylactic vaccination or for postexposure vaccination in combination with hepatitis B immune globulin (HBIG). The chimpanzees were followed for 1 year. None showed HBs-antigenemia, liver enzyme elevation (ALT), or histopathological alterations in liver biopsies. Late appearance of anti-HBc was observed only in the serum of the animal whose series of vaccination started 72 hr after HBV inoculation. An unvaccinated control chimpanzee, which received the HBV inoculum only, developed clinical hepatitis B with ALT-elevations and HBs-antigenemia within 2 months of the experimental HBV inoculation. These results indicate that postexposure vaccination against hepatitis B begun within 48 hr after HBV exposure, with short intervals between the vaccine injections, can protect against hepatitis B infection also when concomitant HBIG-prophylaxis is not given.

Photoelastic analysis of stresses in resin-bonded cingulum rest seats.

Two-dimensional photoelastic analysis of resin-bonded cingulum rest seats demonstrated improvement in stress distribution when the lingual surface of the tooth was prepared with a cingulum groove. This preparation is more important for teeth that are more vertically or lingually oriented and have flatter lingual surfaces, such as mandibular canines.

Morphology and immunohistochemistry of experimental and human non-A, non-B hepatitis.

The diagnosis of non-A, non-B hepatitis (NANBH) presently depends on the exclusion of hepatitis A, B and other causes of hepatitis, because no specific tests are available for diagnosis. Different approaches were used in order to detect NANBH infection in human and chimpanzee tissue. Endogenous interferon production was not detected in the weekly serum samples of 6 chimpanzees inoculated with a human agent of NANBH in contrast to the 5 HBV-infected animals. An antibody raised against a glycoprotein (GP77) associated with NANBH reacted immunohistochemically with liver biopsies obtained from NANBH-infected chimpanzees and with 11 out of 14 human liver biopsies from patients with NANBH. Two out of 12 human biopsies taken from patients with other liver diseases were positive. Diffuse reaction was noted in the cytoplasm of hepatocytes in chimpanzees. Three reaction patterns--diffuse, submembranous and perinuclear--were observed in human liver biopsies. A 35S radiolabeled DNA-probe of 780 base pairs--specific activity 5.4 x 10(4) cmp/micrograms DNA--isolated from NANBH-infected chimpanzees has been shown to hybridize in situ with liver sections from NANBH-infected chimpanzees. Data suggest that immunohistochemical and in situ hybridization methods can be successfully used for detection of NANBH infection in the liver of humans and chimpanzees.

Chronic osteomyelitis of mandible caused by penicillin-resistant Bacteroides ruminicola. Report of a case.

Osteomyelitis of the jaws caused by a Bacteroides species is uncommon. A case of osteomyelitis of the mandible caused by penicillin-resistant Bacteroides ruminicola is reported. The diagnosis was confirmed by isolation of the organism and bone scan (99mTc medronate disodium) of the mandible. Clindamycin and hyperbaric oxygen therapy resolved the infection.

Oral mucositis in patients undergoing bone marrow transplantation.

Thirty patients who received bone marrow transplantation treatment from HLA identical sibling donors for immunologic and malignant diseases were studied. In essentially all of the patients oral changes developed during the first 30 days following transplant. Oral symptoms frequently constituted the major complaints of the patients during the follow-up period. The oral changes included mucositis, xerostomia, pain, and bleeding. Mucositis was more severe and of longer duration when associated with herpes simplex infections and when optimal oral hygiene was not maintained. Xerostomia which accompanies engraftment was an early sign of acute graft-versus-host disease. A nonbrushing method of oral hygiene was effective in reducing the severity and duration of mucositis. This technique offers a short-term alternative to brushing in pancytopenic patients who are susceptible to bleeding or trauma.