bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Holocene Landscape Archaeology in the Coso Basin, Northwestern Mojave Desert, California
Authors: Eerkens Jelmer W. , Rosenthal Jeffrey S. , Young D. Craig , King Jay
Published: June 2008

Early Holocene adaptations are still poorly understood in North America. The archaeological record of this period is often difficult to access and most studies have taken a site-based approach, focused on a small number of well-excavated sites. The archaeological record of the Coso Basin in the northwest Mojave Desert provides the unique opportunity to approach adaptations from a landscape, rather than a site-based, perspective. Large sections of land that were formed during the Pleistocene and Early Holocene, the landforms on which Early Holocene hunter-gatherers lived, are still exposed and easily accessible today. Previous studies have significantly under-represented these landforms in regional survey and excavation. Our analyses suggest that Early Holocene people made use of a wide range of environments, not primarily lakes and wetlands as has commonly been suggested. Furthermore, there is little indication that populations were more residentially mobile and lived in lower population densities than later in time. After accounting for survey, geological, and temporal biases, it is apparent that site densities equal or exceed those of later periods in time. These findings should challenge archaeologists to reconsider certain notions about the Early Holocene in the desert west and to, when possible, take a landscape approach in reconstructing prehistoric lifeways.
Effects on the Dental Arch Form Using a Preadjusted Appliance with Premolar Extraction in Class I Crowding
Authors: Miyake Hironao , Ryu Tatsuo , Himuro Toshihiko
Published: June 2008

Objective: To determine the dental arch form effects of treatment with a preadjusted appliance (0.022″ slot) performed concomitantly with extraction of premolars in Class I crowding.

Materials and Methods: Twenty-six patients (20.17 ± 12.15 years) with Class I crowding who attained a favorable occlusion after treatment were divided into nonextraction and extraction groups. The three-dimensional coordinates of the FA point of each tooth were determined. The dental arch form was expressed as a quartic polynomial expression with log F value used to represent the dental arch form and calculated using the quadratic and quartic coefficients. Changes in the dental arch form before and after treatment were compared between the groups.

Results: In the extraction group, log F value was significantly higher after treatment, and the upper dental arch became more tapered. The U1-APo was significantly lower after treatment. No change was observed in U1-FH. The anterior teeth demonstrated posterior movement due to sliding mechanics, and torque was controlled. The anterior length of the dental arch became significantly longer after treatment for the maxilla and mandible in both groups. Results demonstrated that the upper dental arch might become tapered after treatment used concomitantly with premolar extraction, as a result of the increase in anterior length while maintaining intercanine width for dealing with crowding of the anterior teeth.

Conclusion: It is necessary to anticipate that the upper dental arch form will become tapered during extraction treatment for Class I crowding and to select an appropriate arch form.
Cephalometric Superimpositions
Authors: Gu Yan , McNamara James A.
Published: June 2008

Objective: To test the hypothesis that there is no difference between the information produced by superimposition of serial lateral headfilms on anatomical structures and that produced by superimposition on metallic implants according to the protocols of Björk.

Materials and Methods: Serial cephalograms of 10 untreated subjects who had tantalum implants placed in the maxilla and mandible during childhood were analyzed. Headfilms taken at six consecutive stages of cervical vertebral maturation (CS1-CS6) for six female and four male subjects were used. Tracings were superimposed according to the methods of superimpositions advocated by the American Board of Orthodontics (ABO). In addition, superimpositions along the inferior border of the mandible were performed. Finally, superimpositions of serial tracings on stable intraosseous implants were made to determine the actual growth and remodeling patterns of the maxilla and mandible.

Results: The ABO maxillary superimposition method underestimates the vertical displacement and overestimates the forward movement of maxillary landmarks. Superimposing on the internal cortical outline of the symphysis and the inferior alveolar nerve canals generally approximates the mandibular superimposition on implants, although the lower anterior border of the symphysis may be a preferable area of superimposition. Superimposition on the lower border of the mandible does not reflect accurately the actual pattern of growth and remodeling of the mandible.

Conclusions: When analyzing serial headfilms, erroneous information concerning patterns of bone growth and remodeling can be obtained if convenient, but biologically incorrect superimposition protocols are used. In addition, tooth movements measured can be distorted significantly depending on the method of superimposition.
Tooth Positioner Effects on Occlusal Contacts and Treatment Outcomes
Authors: Park Yongjong , Hartsfield James Kennedy , Katona Thomas R. , Eugene Roberts W.
Published: June 2008

Objective: To determine if an increase in tooth contacts is the principal effect of tooth positioner wear.

Materials and Methods: Patient charts from a consecutive series were reviewed until a sample of 100 cases that used a tooth positioner was obtained. One hundred control cases were randomly selected from patients treated at the same period. Malocclusion severity and finished occlusion were assessed with the American Board of Orthodontics (ABO) Discrepancy Index (DI) and Objective Grading System (OGS) score, respectively. Finish casts for each patient were mounted on a Galleti articulator. Occlusal registrations were obtained with silicone-based impression material from casts fabricated from impressions taken at the time of fixed appliance removal (control) or at the end of the tooth positioner treatment (experimental). The number of the perforations and transparent areas on the occlusal registrations were quantified.

Results: There was no significant difference (P = .20) in the number of total occlusal contacts between the two groups. However, the OGS score of the tooth positioner group (16.7) was significantly (P = .0009) better than for the control group (19.9).

Conclusions: Tooth positioners were effective in improving the occlusal finish, but the effects were independent of an increase in occlusal contacts. Positioners primarily improved first order alignment by tipping teeth into an improved intercuspation.
Age-Related Changes of Periodontal Ligament Surface Areas during Force Application
Authors: Ren Yijin , Maltha Jaap C. , Stokroos Lets , Liem Robert S. B. , Kuijpers-Jagtman Anne Marie
Published: June 2008

Objective: To investigate the age-dependent morphology of the periodontal ligament (PDL) tissue and changes in its surface area (SA) during force application provided with a standardized orthodontic setup for a period of 12 weeks in young and adult rats.

Methods: Two groups of 30 rats, age 6 weeks and 9 to 12 months, were used. Orthodontic appliances were placed to move the maxillary molars mesially with the contralateral sides used as controls. At 1, 2, 4, 8, and 12 weeks, groups of animals were killed. The PDL SA and the PDL SA ratio between pressure and tension regions were determined.

Results: An age-related decrease in the PDL SA was noted at control sides. Significant changes during the experimental period occurred only at experimental sides: The PDL SA was smaller at pressure than at tension regions only at week 1 in young rats; in adult rats, the difference between the two regions was significant at week 8. These changes were confirmed by the morphologic disorganization of the PDL and alterations in the PDL SA ratio.

Conclusions: During force application, the PDL at the pressure regions became disorganized and subsequently was reorganized, as is shown by the histologic changes and SA of the PDL over time. This process occurred earlier and was more prominent in young rats; it occurred later and was more prolonged in adult animals.
Occlusal Hypofunction Induces Atrophic Changes in Rat Gingiva
Authors: Ishida Yuji , Kanno Zuisei , Soma Kunimichi
Published: June 2008

Objective: To clarify the influence of occlusal hypofunction on the integrity of gingival tissue and gingival extracellular matrix biosynthesis.

Materials and Methods: Thirteen-week-old male Wistar rats were divided into two groups. To eliminate occlusal forces, all the right maxillary molars were extracted in the hypofunctional group. The control group was anesthetized but not subjected to surgery. The rats were killed at 2 and 4 weeks after the procedure, and the lower right second molars were prepared for histological analysis. To investigate the effect of occlusal hypofunction on collagen biosynthesis, the expression of connective tissue growth factor (CTGF) and lysyl oxidase (LOX) was determined by immunohistochemistry as well as histological examination by hematoxylin and eosin staining.

Results: Disorientation of the collagen fibers, proliferation of the connective tissue fibroblasts, and enlargement of epithelial intercellular gaps were observed in gingival tissue of rat molars with experimental occlusal hypofunction. Immunohistochemically, the expression of CTGF and LOX was increased significantly (P < .05) in the hypofunctional group.

Conclusion: These results suggest that occlusal hypofunction can affect the structural integrity and the expression of CTGF and LOX in gingival tissue.
Anteroposterior Dental Arch and Jaw-Base Relationships in a Population Sample
Authors: Zhou Lei , Mok Chung-Wai , Hägg Urban , McGrath Colman , Bendeus Margareta , Wu John
Published: June 2008

Objective: To determine the association between the anteroposterior relationship of the dental arch and the anteroposterior relationship of the jaw-base in a Chinese population sample.

Materials and Methods: Orthodontic casts and lateral cephalograms were obtained from a random sample of 405 twelve-year-old Chinese children from a population survey in Hong Kong. Angle's classification was used to assess the dental arch relationship from orthodontic casts. The jaw-base relationship was assessed from the lateral cephalograms using angular (ANB angle) and linear (Wits analysis) measurements. The correlation between the anteroposterior dental arch and jaw-base relationships was assessed.

Results: The anteroposterior dental arch did coincide with the jaw-base relationships, as expressed by the ANB angle in 61%, the Wits analysis in 67%, and with both in 53%. The jaw-base relationship assessed with the Wits analysis was more significantly associated with the dental arch relationship (P < .001) than that assessed with the ANB angle (P < .01). The correlation coefficient between the ANB angle and the Wits appraisal was .65 for the combined sample, and .60, .64, and .67 for Class I, II, and III dental arch relationships.

Conclusion: In this population, the anteroposterior relationship of the dental arch and jaw-base fail to match in at least one out of every three individuals. Linear measurement of anteroposterior jaw-base relationships is a more valid reflection of the dental arch relationship than angular measurements.
Microleakage under Metallic and Ceramic Brackets Bonded with Orthodontic Self-Etching Primer Systems
Authors: Uysal Tancan , Ulker Mustafa , Ramoglu Sabri Ilhan , Ertas Huseyin
Published: June 2008

Objective: To compare the in vitro microleakage of orthodontic brackets (metal and ceramic) between enamel-adhesive and adhesive-bracket interfaces at the occlusal and gingival sides produced by self-etching primer system with that of conventional acid etching and bonding.

Materials and Method: Sixty freshly extracted human mandibular premolar teeth were used in this study. The teeth were separated into four groups of 15 teeth each and received the following treatments: Group 1, 37% phosphoric acid gel + Transbond XT liquid primer + stainless steel bracket; Group 2, Transbond Plus Self-Etching Primer (TSEP) + stainless steel bracket; Group 3, 37% phosphoric acid gel + Transbond XT liquid primer + ceramic bracket; Group 4, TSEP + ceramic bracket. After curing, specimens were further sealed with nail varnish, stained with 0.5% basic fuchsine for 24 hours, sectioned and examined under a stereomicroscope, and scored for microleakage for the enamel-adhesive and bracket-adhesive interfaces from both occlusal and gingival margins. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney U tests.

Results: The gingival sides in all groups exhibited higher microleakage scores compared with those observed in occlusal sides for both adhesive interfaces. Enamel-adhesive interfaces exhibited more microleakage than did the adhesive-bracket interfaces. Brackets bonded with self-etching primer system showed significantly higher microleakage at the enamel-adhesive interface of the gingival side.

Conclusions: TSEP causes more microleakage between enamel-adhesive interfaces, which may lead to lower bond strength and/or white-spot lesions.
Insertion Angle Impact on Primary Stability of Orthodontic Mini-Implants
Authors: Wilmes Benedict , Su Yu-Yu , Drescher Dieter
Published: June 2008

Objective: To analyze the impact of the insertion angle on the primary stability of mini-implants.

Materials and Methods: A total of 28 ilium bone segments of pigs were embedded in resin. Two different mini-implant sizes (Dual-Top Screw 1.6 × 8 mm and 2.0 × 10 mm) were inserted at seven different angles (30°, 40°, 50°, 60°, 70°, 80°, and 90°). The insertion torque was recorded to assess primary stability. In each bone, five Dual-Top Screws were used to compensate for differences in local bone quality.

Results: The angle of mini-implant insertion had a significant impact on primary stability. The highest insertion torque values were measured at angles between 60° and 70° (63.8° for Dual-Top 1.6 mm and 66.7° for Dual-Top 2.0 mm). Very oblique insertion angles (30°) resulted in reduced primary stability.

Conclusions: To achieve the best primary stability, an insertion angle ranging from 60° to 70° is advisable. If the available space between two adjacent roots is small, a more oblique direction of insertion seems to be favorable to minimize the risk of root contact.
Maxillary Molar Distalization with Noncompliance Intramaxillary Appliances in Class II Malocclusion
Authors: Antonarakis Gregory Stylianos , Kiliaridis Stavros
Published: June 2008

Objective: To use published data to evaluate quantitatively the dental effects of noncompliance intramaxillary appliances in individuals with Class II malocclusion.

Materials and Methods: A literature search was carried out identifing 13 prospective or retrospective clinical studies matching inclusion criteria. Only appliances with conventional anchorage designs were considered for the review. The data provided in these publications were grouped and analyzed in terms of molar distalization, tipping and vertical movements, and incisor and premolar mesialization, tipping, and vertical movements.

Results: Maxillary first molars showed distal crown movement and tipping greater than the mesial crown movement and tipping shown by incisors and premolars. Vertical movements of incisors and premolars were in general extrusive, but molars were intrusive or extrusive, depending on the study and the type of appliance used. Appliances that acted palatally seemed to display a smaller distal tipping movement, as well as smaller incisor and premolar mesial tipping movements, when compared with those that acted buccally. Friction-free appliances, namely the pendulum, produced a large amount of mesiodistal movement and tipping, if no therapeutic uprighting activation was applied.

Conclusions: Noncompliance intramaxillary molar distalization appliances all act by distalizing molars with a concomitant and unavoidable loss of anchorage, as revealed by incisor and premolar mesial movement. Buccal acting and palatal acting appliances demonstrate almost similar results, with palatal acting appliances showing less tipping. Friction-free palatal acting appliances appear to produce better molar distalizing effects, but with a concomitant notable loss of anchorage.
Stability Factors After Double-Jaw Surgery in Class III Malocclusion
Authors: Mucedero Manuela , Coviello Antonella , Baccetti Tiziano , Franchi Lorenzo , Cozza Paola
Published: June 2008

Objective: To identify the stability factors of skeletal Class III malocclusion after double-jaw surgery by a systematic review of the literature.

Materials and Methods: The survey covered the period from September 1959 to October 2007 and used the MeSH, Medical Subject Headings. The inclusion criteria were stability of bimaxillary surgery of the permanent dentition, adult patients with skeletal Class III malocclusion, a follow-up of at least 12 months, randomized and nonrandomized controlled clinical trials (RCCTs; CCTs), prospective and retrospective studies with and without concurrent untreated as well as normal controls, and clinical trials (CTs) comparing at least two treatment strategies without any untreated or normal control group.

Results: The search strategy resulted in 1783 articles. After selection according to the inclusion/ exclusion criteria, 15 articles qualified for the final review analysis. Quality was low in two studies, medium in twelve, and medium/high in one article, which was represented by a RCT (randomized clinical trial). Most of the studies had sufficient sample size, method error analysis, and adequate statistical methods. Thus, the quality level of the studies was sufficient to draw evidence-based conclusions.

Conclusions: Surgical correction of skeletal Class III malocclusion after combined maxillary and mandibular procedures appears to be stable for maxillary advancements up to 5 mm and for the correction of presurgical sagittal intermaxillary discrepancies smaller than 7 mm.
Perception of Profile among Laypeople, Dental Students and Orthodontic Patients
Authors: Tufekci Eser , Jahangiri Arousha , Lindauer Steven J.
Published: June 2008

Objective: To determine whether there are differences in self-awareness and perception of an individual's own profile among various groups.

Materials and Methods: Laypeople, orthodontic patients, and first (D1) and third-year dental (D3) students were surveyed (n = 75 each). The participants answered a questionnaire regarding how they felt about their own profile and teeth. They also chose from among various silhouettes the one that most resembled their own profile. Profile photos of participants were analyzed by two orthodontists who matched the individual to the depicted silhouettes. Agreement between participants and experts was evaluated using the Kappa statistic. Differences among groups in identifying their own profiles and differences among profile types in satisfaction with their appearance were compared using χ2.

Results: Overall agreement between the individuals' perceptions of their own profiles and evaluation by orthodontists was 53% (κ = .15). The four groups were different in their ability to recognize their own profile (P < .05). D3s were most accurate (64%, κ = .28), followed by D1s (57%, κ = .10), orthodontic patients (48%, κ = .19), and laypeople (43%, κ = .04). Individuals who considered themselves as having a Class II or III profile were less satisfied with the appearance of their profiles (P < .05). Those who considered themselves as having a Class III profile were also less happy with the appearance of their teeth (P < .05).

Conclusions: This study suggests that about half the population cannot characterize their own profile. However, subjects who perceived their own profiles as being different from average were more likely to be unhappy with their facial appearance.
Moments Generated during Simulated Rotational Correction with Self-Ligating and Conventional Brackets
Authors: Pandis Nikolaos , Eliades Theodore , Partowi Samira , Bourauel Christoph
Published: June 2008

Objective: To assess comparatively the magnitude of moments generated during rotational correction from different bracket systems during the late leveling and alignment stage of orthodontic treatment.

Materials and Methods: The three types of brackets assessed were Orthos2 (ORMCO, Glendora, CA), Damon2 (ORMCO), and In Ovation-R (GAC, Bohemia, NY). The brackets were bonded on replicas made of resin from models constructed from an aligned patient's mandibular arch, and a 0.014- × 0.025-inch CuNiTi (ORMCO) wire was inserted. Orthodontic rotational correction was simulated on the Orthodontic Measurement and Simulation System from −5° to +5° rotation in 0.25° increments on the distal and mesial direction. The moments generated at each increment of rotation throughout the full rotation path were statistically analyzed using a two-way analysis of variance and Tukey test at the .05 level of significance.

Results: Both bracket type and direction of rotation showed an effect on moment magnitude. The highest moment (27.2 Nmm) was observed for the Damon2 bracket assigned to its noncompliant slot wall door. Higher moments were found during distal premolar rotation. The In Ovation-R showed a magnitude of moment in the range of 9.0 Nmm in the same direction, whereas conventional brackets presented the lowest moments (5.0 Nmm).

Conclusions: A wide variation in magnitude of moments exerted by self-ligating and conventional brackets is noted in the simulated rotational correction of teeth, which relates to the geometry of the dental arch, the tooth position, and the rigidity of the closing component of the bracket slot.
Orthodontic Treatment Combined with Mandibular Distraction Osteogenesis and Changes in Stomatognathic Function
Authors: Maeda Aya , Soejima Kazuhisa , Ogura Mikinori , Ohmure Haruhito , Sugihara Kazumasa , Miyawaki Shouichi
Published: June 2008

We performed an orthodontic treatment combined with mandibular distraction osteogenesis in a 15-year-old patient who wanted a correction of a chin deficiency and a protruding upper lip. The patient had an Angle Class II division 1 malocclusion with mandibular retrusion, a low mandibular plane angle, and scissors bite. First, a quad-helix appliance was applied to the mandibular dentition to correct the scissors bite in the bilateral premolar region. Later, a preadjusted edgewise appliance was applied to the maxillary and mandibular teeth. After 3 days, a mandibular distraction osteogenesis was performed. During and after the distraction, the open bite between the upper and lower dental arches was corrected using up and down elastics. The total treatment time with the edgewise appliance was 14 months. A skeletal Class I apical base relationship, good facial profile, and optimum intercuspation of the teeth were achieved with the treatment. The jaw-movement pattern on the frontal view did not change during gum chewing. However, the maximum gap without pain increased. The electromyographic (EMG) activity of the masseter and anterior temporalis muscles, and maximum occlusal force increased. The present case report suggests that an orthodontic treatment combined with mandibular distraction osteogenesis in a patient with mandibular retrusion in the late growth period might be effective for improving stomatognathic function.
Root Resorption Following Treatment with Aligners
Authors: Brezniak Naphtali , Wasserstein Atalia
Published: June 2008

Can orthodontically induced inflammatory root resorption (OIIRR) be the result of Invisalign treatment? Since OIIRR was first described in the literature, orthodontists have been looking for a treatment procedure where no root shortening will occur. In the past decade, Invisalign orthodontic treatment has become very popular, and there is no description of OIIRR after this treatment. Therefore, it might be incorrectly concluded that the body is immune to this type of orthodontic treatment modality and no OIIRR appears as a result of this treatment. The following case report demonstrates an aspect of the complexity of OIIRR.
A New Premixed Self-Etch Adhesive for Bonding Orthodontic Brackets
Authors: Bishara Samir E. , Otsby Adam W. , Ajlouni Raed , Laffoon John , Warren John J.
Published: June 2008

Objective: To determine if a new premixed self-etch adhesive can be used to successfully bond orthodontic brackets to enamel.

Materials and Methods: Forty human molars were cleaned, mounted, and randomly divided into two groups. In group 1, 20 teeth were conditioned using the self-etching primer Transbond Plus (3M Unitek, Monrovia, Calif). In group 2, 20 teeth were conditioned using a new premixed self-etching adhesive, AdheSE One (Ivoclar Vivadent Inc, Amherst, NY). Both groups were bonded using brackets precoated with a composite adhesive. The teeth were debonded within half an hour following initial bonding using a universal testing machine. After debonding, the enamel surface was examined under 10× magnifications to determine the amount of residual adhesive remaining on the tooth. A Student's t-test was used to compare the shear bond strength (SBS) of the two groups, and the Chi-square test was used to compare the adhesive remnant index (ARI) scores for the two adhesive systems.

Results: The mean SBS of the brackets bonded to the teeth using AdhesSE One was 3.6 ± 1.3 MPa and was significantly lower (t = 2.80, P = .01) than the SBS of the brackets bonded using Transbond Plus (x̄ = 5.9 ± 3.2 MPa). The comparisons of the ARI scores between the two groups (χ2 = 19.26) indicated that bracket failure mode was also significantly different (P < .001), with more adhesive remaining on the teeth bonded using Transbond Plus.

Conclusions: The SBS of the new premixed self-etching adhesive needs to be increased for it to be successfully used for bonding orthodontic brackets.
Impact of Diabetes Susceptibility Loci on Progression From Pre-Diabetes to Diabetes in At-Risk Individuals of the Diabetes Prevention Trial–Type 1 (DPT-1)
Authors: Butty Vincent , Campbell Christopher , Mathis Diane , Benoist Christophe ,   the DPT-1 Study Group
Published: June 2008

OBJECTIVE—The unfolding of type 1 diabetes involves a number of steps: defective immunological tolerance, priming of anti-islet autoimmunity, and destruction of insulin-producing β-cells. A number of genetic loci contribute to susceptibility to type 1 diabetes, but it is unclear which stages of the disease are influenced by the different loci. Here, we analyzed the frequency of type 1 diabetes–risk alleles among individuals from the Diabetes Prevention Trial–Type 1 (DPT-1) clinical trial, which tested a preventive effect of insulin in at-risk relatives of diabetic individuals, all of which presented with autoimmune manifestations but only one-third of which eventually progressed to diabetes.

RESEARCH DESIGN AND METHODS—In this study, 708 individuals randomized into DPT-1 were genotyped for 37 single nucleotide polymorphisms in diabetes susceptibility loci.

RESULTS—Susceptibility alleles at loci expected to influence immunoregulation (PTPN22, CTLA4, and IL2RA) did not differ between progressors and nonprogressors but were elevated in both groups relative to general population frequencies, as was the INS promoter variant. In contrast, HLA DQB1*0302 and DQB1*0301 differed significantly in progressors versus nonprogressors (DQB*0302, 42.6 vs. 34.7%, P = 0.0047; DQB*0301, 8.6 vs. 14.3%, P = 0.0026). Multivariate analysis of the factors contributing to progression demonstrated that initial titers of anti-insulin autoantibodies (IAAs) could account for some (P = 0.0016) but not all of this effect on progression (P = 0.00038 for the independent effect of the number of DQB*0302 alleles). The INS-23 genotype was most strongly associated with anti-IAAs (median IAA levels in TT individuals, 60 nU/ml; AT, 121; and AA, 192; P = 0.000037) and only suggestively to the outcome of oral insulin administration.

CONCLUSIONS—With the exception of HLA, most susceptibility loci tested condition the risk of autoimmunity rather than the risk of failed immunoregulation that results in islet destruction. Future clinical trials might consider genotyping INS-23 in addition to HLA alleles as disease/treatment response modifier.
Neurological Features and Enzyme Therapy in Patients With Endocrine and Exocrine Pancreas Dysfunction Due to CEL Mutations
Authors: Vesterhus Mette , Ræder Helge , Aurlien Harald , Gjesdal Clara G. , Bredrup Cecilie , Holm Pål I. , Molven Anders , Bindoff Laurence , Berstad Arnold , Njølstad Pål R.
Published: June 2008

OBJECTIVE—To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy.

RESEARCH DESIGN AND METHODS—Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months.

RESULTS—Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P < 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common.

CONCLUSIONS—Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.
Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese
Authors: Cheung Bernard M.Y. , Wat Nelson M.S. , Tso Annette W.K. , Tam Sidney , Thomas G. Neil , Leung Gabriel M. , Tse Hung Fat , Woo Jean , Janus Edward D. , Lau Chu Pak , Lam Tai Hing , Lam Karen S.L.
Published: June 2008

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia.

RESEARCH DESIGN AND METHODS—We studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. We determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline.

RESULTS—Diabetes and hypertension were both related to age, obesity indexes, blood pressure, glucose, HDL cholesterol, and triglycerides. Of subjects with diabetes, 58% had raised blood pressure. Of subjects with hypertension, 56% had dysglycemia. BMI and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new-onset diabetes. Age, systolic blood pressure, and 2-h glucose were independent predictors of new-onset hypertension. BMI, systolic blood pressure, and 2-h glucose were independent predictors of the development of diabetes and hypertension together.

CONCLUSIONS—Diabetes and hypertension share common etiological factors. Patients with diabetes or hypertension should be screened and managed for the precursor of the other condition.
The Missed Patient With Diabetes
Authors: Zhang Xuanping , Geiss Linda S. , Cheng Yiling J. , Beckles Gloria L. , Gregg Edward W. , Kahn Henry S.
Published: June 2008

OBJECTIVE—This study examined the association between access to health care and three classifications of diabetes status: diagnosed, undiagnosed, and no diabetes.

RESEARCH DESIGN AND METHODS—Using data from the 1999–2004 National Health and Nutrition Examination Survey, we identified 110 “missed patients” (fasting plasma glucose >125 mg/dl but without diagnoses of diabetes), 704 patients with diagnosed diabetes, and 4,782 people without diabetes among adults aged 18–64 years. The population percentage undetected among adults with diabetes and the odds ratio of being undetected among adults who reported not having diabetes were compared between groups based on their access to health care.

RESULTS—Among those with diabetes, the percentages having undetected diabetes were 42.2% (95% CI 36.7–47.7) among the uninsured, 25.9% (22.9–28.9) among the insured, 49.3% (43.0–55.6) for those uninsured >1 year, 38.7% (29.2–48.2) for those uninsured ≤1 year, and 24.5% (21.7–27.3) for those continuously insured over the past year. Type of insurance, number of times receiving health care in the past year, and routine patterns of health care utilization were also associated with undetected diabetes. Multivariate adjustment indicated that having undetected diabetes was associated with being uninsured (odds ratio 1.7 [95% CI 1.0–2.9]) and with being uninsured >1 year (2.6 [1.4–5.0]).

CONCLUSIONS—Limited access to health care, especially being uninsured and going without insurance for a long period, was significantly associated with being a “missed patient” with diabetes. Efforts to increase detection of diabetes may need to address issues of access to care.
Acute Modulation of Toll-Like Receptors by Insulin
Authors: Ghanim Husam , Mohanty Priya , Deopurkar Rupali , Ling Sia Ching , Korzeniewski Kelly , Abuaysheh Sanaa , Chaudhuri Ajay , Dandona Paresh
Published: June 2008

OBJECTIVE—Low-dose insulin infusion has been shown to exert a prompt and powerful anti-inflammatory effect. Toll-like receptors (TLRs) are major determinants of the inflammatory response to viral and bacterial pathogens. We have now hypothesized that low-dose insulin infusion in obese type 2 diabetic patients suppresses TLR expression.

RESEARCH DESIGN AND METHODS—Ten type 2 diabetic patients were infused with a low dose of insulin (2 units/h) and dextrose to maintain normoglycemia for 4 h, while another 14 type 2 diabetic patients were infused with either dextrose or saline for 4 h and served as control subjects. Blood samples were collected before and at 2, 4, and 6 h. TLR expression was determined in mononuclear cells (MNCs).

RESULTS—Insulin infusion significantly suppressed TLR1, -2, -4, -7, and -9 mRNA expression in MNCs within 2 h of the infusion, with a maximum fall at 4 h by 24 ± 9%, 21 ± 5%, 30 ± 8%, 28 ± 5%, and 27 ± 10% (P < 0.05, for all), respectively, below the baseline. TLR2 protein was suppressed by 19 ± 7% (P < 0.05) below the baseline at 4 h. The DNA binding of PU.1, a major transcription factor regulating many TLR genes, was concomitantly suppressed by 24 ± 10% (P < 0.05) by 4 h in MNCs. There was no change in TLR expression or DNA binding by PU.1 following dextrose or saline infusion in the control groups.

CONCLUSIONS—Insulin suppresses the expression of several TLRs at the transcriptional level, possibly through its suppressive effect on PU.1.
A Murine Model of Infantile Neuronal Ceroid Lipofuscinosis—Ultrastructural Evaluation of Storage in the Central Nervous System and Viscera
Authors: Galvin Nancy , Vogler Carole , Levy Beth , Kovacs Attila , Griffey Megan , Sands Mark S.
Published: June 2008

Infantile neuronal ceroid lipofuscinosis (INCL), also known as Santavuori-Haltia disease, is an inherited neurodegenerative disorder caused by a mutation in the gene encoding the lysosomal enzyme palmitoyl-protein-thioesterase-1 (PPT1). Fatty acid–modified proteins are not degraded and accumulate as granular osmiophilic deposits in cells in the central nervous system; patients have blindness, seizures, progressive psychomotor deterioration, and die in early childhood. Although the disease manifests clinically primarily with neurological symptoms, visceral storage also accumulates. A murine model of INCL due to PPT1 deficiency exhibits clinical findings and pathology similar to those seen in patients with INCL. Homozygous PPT1-deficient mice have a shortened life span and neurological abnormalities including seizures, blindness, and mental and motor deficits. Widespread granular osmiophilic deposits (GRODs) accumulate in lysosomes in neurons and glia in the brain, retinal cells, kidney glomerular cells, aortic smooth muscle cells, and, in lesser amounts, in the fixed-tissue macrophage system. Accumulation of GRODs in aortic smooth muscle cells is accompanied by abnormalities in cardiac function and aortic root dilatation. This PPT1-deficient murine model is a well-defined genetic system that can be used to test potential therapies for lysosomal storage disease and to study the pathophysiology of INCL.
Aberrant Expression of β-HCG in Anaplastic Large Cell Lymphoma
Authors: Leong May Ying , English Martin , Mcmullan Dominic , Ramani Pramila
Published: June 2008

We report a case of anaplastic large cell lymphoma (ALCL) showing aberrant expression of β subunit of human chorionic gonadotrophin (β-HCG). The patient was a 14-year-old boy who presented with a right inguinal mass and a raised serum β-HCG level. Biopsy of the mass revealed a malignant neoplasm composed of large, pleomorphic cells with prominent nucleoli. These malignant cells showed positive staining with CD30, ALK, epithelial membrane antigen, and β-HCG. Chromosomal analysis showed t(2;5)(p23;q35) translocation, and polymerase chain reaction demonstrated T-cell receptor gene rearrangement. The patient did not respond well to chemotherapy, and he died 8 months after the diagnosis. To the best of our knowledge, this is the 1st case of ALCL showing aberrant expression of β-HCG and associated with a raised serum level of β-HCG. We report this case to bring awareness of this presumably rare occurrence to avoid the risk of misdiagnosis.
Expression of Hypoxia-Inducible Factors in Normal Human Lung Development
Authors: Rajatapiti Prapapan , van der Horst Irene W.J.M. , de Rooij Jessica D. , Tran Maxine G.B. , Maxwell Patrick H. , Tibboel Dick , Rottier Robbert , de Krijger Ronald R.
Published: June 2008

Pulmonary vascular development is essential for proper lung development, and its disturbance can lead to neonatal morbidity and mortality, as exemplified in congenital diaphragmatic hernia. Hypoxia-inducible factors (HIFs) appear to be key molecules in physiologic angiogenesis and in certain forms of lung pathology, such as bronchopulmonary dysplasia. Little is known about the qualitative and quantitative expression of HIFs in normal human fetal lung development. Therefore, we investigated the expression of HIF-1α, HIF-2α, and HIF-3α, along with their upstream regulators and downstream targets, von Hippel-Lindau protein, vascular endothelial growth factor A (VEGF-A), and its receptor, VEGFR-2, in 20 normal human fetal lungs (13.5 weeks in gestation until term) and 5 adult lungs. Quantitative polymerase chain reaction demonstrated a positive correlation between HIF-2α and VEGF-A expression and gestational age. Although there appeared to be a decreasing trend in HIF-3α expression during pregnancy, it did not reach statistical significance. Immunohistochemistry for HIF-1α and HIF-2α revealed that HIF-1α is expressed in the epithelium, while HIF-2α is expressed in both interstitium and epithelium. Our data indicate that HIFs, most notably HIF-2α, appear to exert an important role in angiogenesis during human fetal lung development, especially in the last phases of pregnancy, preparing the fetus for extrauterine life. As such, our results form the baseline data for the evaluation and interpretation of abnormal pulmonary vascular development.
The Role of the Pediatric Pathologist as Expert Witness in a Case of Neonatal Death
Authors: Krous Henry F. , Langston Claire
Published: June 2008

The pediatric pathology literature has given scant attention to expert testimony by physicians in medical malpractice actions that involve infants and children. We report the case of a neonate who died after a brief clinical course characterized by intermittent respiratory distress. The prosecting pathologist's erroneous postmortem diagnoses prompted the infant's mother to sue the attending physician for malpractice. During the course of the litigation, it became clear that the pathologist's testimony was evasive and misleading. After deliberating briefly, the jury ruled in favor of the defendant. Had the plaintiff's attorney obtained a 2nd opinion from another pathologist, preferably a pediatric pathologist, the legal proceedings in this case may have been avoided, thereby averting needless distress for both the plaintiff and defendant, aside from the costs involved. We discuss U.S. Supreme Court rulings pertaining to medical expert testimony and identify remedies to increase just outcomes in cases of medical malpractice.
Two Hyperplastic Esophagogastric Polyps in a Child with Neurofibromatosis Type 1 (NF-1)
Authors: Grynspan David , Lukacik Marek , Madani Shailender , Poulik Janet
Published: June 2008

Hyperplastic esophagogastric polyps usually occur in the distal esophagus or gastroesophageal junction and have been associated with damage to the esophageal mucosa. Histologically these polyps show hyperplastic gastric foveolar and/or squamous epithelium with inflamed stroma. Reports of esophagogastric polyps in the pediatric population are rare. Most of these reports only describe chronic inflammation within the lamina propria of the polyp, with only rare reports specifying the presence of epithelial hyperplasia. There have been 2 previous cases of hyperplastic esophagogastric polyps occurring in the context of neurofibromatosis type 1 (NF-1) in a single article. Here we report a 3rd case of hyperplastic esophagogastric polyps occurring in an 11-year-old male with NF-1. This case is unique in that there were 2 polyps in the same patient and in that the polyps showed hyperplastic gastric peptic glands in addition to foveolar-type and focal squamous epithelium. The case is discussed and literature reviewed.
Translocation (4;19)(q35;q13.1)–Associated Primitive round Cell Sarcoma: Report of a Case and Review of the Literature
Authors: Rakheja Dinesh , Goldman Stanton , Wilson Kathleen S. , Lenarsky Carl , Weinthal Joel , Schultz Roger A.
Published: June 2008

We report the 4th case of a primitive round cell sarcoma with the translocation (4;19)(q35;q13.1) as the primary cytogenetic abnormality. This undifferentiated sarcoma shows some features of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), including a diffuse reactivity for FLI1, but it shows only focal and weak reactivity for CD99 and is negative for a rearrangement of EWS, the molecular signature of ES/PNET. Recognition of the histopathologic and cytogenetic features of this entity is necessary to avoid its misdiagnosis as ES/PNET, especially in small biopsy samples.
Recurrent Placental Massive Perivillous Fibrin Deposition Associated with Polymyositis: A Case Report and Review of the Literature
Authors: Al-Adnani Mudher , Kiho Liina , Scheimberg Irene
Published: June 2008

We present a case of recurrent massive perivillous fibrin deposition (MPVFD) in a patient with polymyositis (PM). Massive perivillous fibrin deposition occurred in 2 consecutive pregnancies: the 1st ended in an intrauterine death at 34 weeks of gestation, while the 2nd pregnancy resulted in a live-born baby at 32 weeks of gestation. The association between MPVFD and PM has been rarely reported in the literature in the form of case reports of single pregnancies.
A Family with Atypical Cystic Fibrosis: Brother and Sister with Heterozygosity for Both G542X and R117H
Authors: Farez-Vidal M. Esther , Gómez-Llorente M. Amelia , Gómez-Llorente Carolina , Blanco Sonia , Casas-Maldonado Francisco , Campoy Cristina , Gómez-Capilla José Antonio
Published: June 2008

Clinical manifestations of cystic fibrosis (CF) are variable. Genetic and environmental factors that determine whether an individual will develop associated complications are still under investigation. The present study reports the genetic analysis of a family with different clinical forms of CF and addresses the difficulty of CF diagnosis in an individual with mutant alleles G542X and R117H because of the variable phenotype associated with R117H mutation. Both children in this family were heterozygous for G542X/R117H with the same thymine sequence (7T/9T) in intron 8 of CF transmembrane conductance regulator. The girl was diagnosed with CF, whereas the boy was diagnosed with azoospermia as the sole clinical manifestation. The possible implication of the hemochromatosis gene as a CF modifier locus was analyzed because the 2 children had the same genotype. No genetic differences were detected between brother and sister that explained the different clinical manifestations of CF.
Expression of Transforming Growth Factor-β 1, -β 2, and -β 3 in Human Developing Teeth: Immunolocalization According to the Odontogenesis Phases
Authors: Benedete Ana Paula Sassá , Sobral Ana Paula Veras , Lima Dirce Mary Correia , Kamibeppu Leonardo , Soares Fernando Augusto , Lourenço Silvia Vanessa
Published: June 2008

Transforming growth factor–β (TGF-β) is a multifunctional growth factor that has several biological effects in vivo, including control of cell growth and differentiation, cell migration, lineage determination, motility, adhesion, apoptosis, and synthesis and degradation of extracellular matrix, and TGF-β plays an important role in regulating tissue repair and regeneration. Our study analyzed the participation of TGF-β 1, -β 2, and -β 3 in the different stages of morphogenesis and differentiation of human developing dental organ using immunohistochemistry. The maxillae and mandibles of 10 human embryos ranging from 8 to 23 weeks of gestation were employed, according to the approval of the ethical committee. Our study revealed that the TGF-β subunits—β 1, β 2, and β 3—were present in the various stages of tooth development, but the expression varied according to the differentiation stage, tissue, and TGF-β subunit. Our results indicated that TGF-β 1 is closely related to differentiation of enamel organ and initiation of matrix secretion, TGF-β 2 to cellular differentiation, and TGF-β 3 to mineral maturation matrix.
Congenital Mesenteric Defects and Unexpected Death—A Rare Finding at Autopsy
Authors: Byard Roger W. , Wick Regula
Published: June 2008

Gastrointestinal causes of sudden and/or unexpected death in the young are uncommon and only rarely involve congenital anomalies of the mesentery. Two cases are reported of unexpected deaths following herniation of intestine through congenital mesenteric defects to illustrate the forensic issues that may arise. Case 1 involves a 2.5-year-old girl who collapsed on arrival to hospital following 18 hours of fever and apparently mildly nonspecific symptoms. Resuscitation was unsuccessful, and at autopsy a segment of gangrenous small intestine was found that had herniated through a congenital mesenteric defect. Case 2 involves a 23-year-old woman with a past history of severe mental and physical disabilities who was found dead in her bed. She had a recent history of mild diarrhea and vomiting, but had not appeared particularly ill. At autopsy the peritoneal cavity was filled with a very dilated and obstructed colon as a result of herniation of a segment of sigmoid colon through a distal small intestinal mesenteric defect. These cases demonstrate that symptoms and signs of intestinal ischemia may not be clearly manifested in early childhood and that developmental delay may also result in older individuals presenting in a nonspecific manner. Although rare, congenital mesenteric abnormalities with compromise of the intestinal vasculature remain a possibility to be considered at autopsy in all cases of unexpected death, despite the lack of a clear history of significant gastrointestinal disturbance. Death may relate to ischemic compromise of either the herniated portion of intestine (as in case 1) or to the stretched intestine bordering the hernial orifice (as in case 2).