bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Anatomical Features on the Outcome of Gingival Recessions Treated With Coronally Advanced Flap and Enamel Matrix Derivative: A 1‐Year Prospective Study
Authors: Berlucchi Ignazio , Francetti Luca , Fabbro Massimo Del , Basso Matteo , Weinstein Roberto L.
Published: June 2005

Background: Coronally advanced flap (CAF) is one of the most effective treatments of Miller Class I and II recessions. Even if excellent outcomes are reported in the literature, complete root coverage is not always predictable, since many surgical and host‐related factors may affect the percentage of root coverage obtained. The aim of this clinical study was to evaluate if some anatomical features such as tissue thickness, papillae height and width, recession depth, and vestibular bone height may influence defect coverage of Miller Class I and II gingival recessions treated with CAF in combination with enamel matrix derivative (EMD).

Methods: Thirty healthy, non‐smoking patients (13 men and 17 women; mean age 32.8 ± 6.2 years) were enrolled. Each patient was treated for one single recession using a CAF with the adjunct of EMD. Clinical parameters at baseline and 6 and 12 months were recorded and compared by using paired Student t test. Data were subdivided in two groups according to the baseline recession depth (REC): REC <4 mm (group 1) and REC ≥4 mm (group 2). The relation between the anatomical parameters (papilla height, papilla width, crestal bone height, and flap thickness) and percent of root coverage was evaluated by multiple linear regression analysis.

Results: At 12 months, 91.7% of root coverage was obtained with a mean attachment gain of 3.23 mm. Better results in terms of percentage of root coverage were obtained when the baseline REC was <4 mm compared to defects ≥4 mm (96.5% versus 83.5%). Flap thickness was positively correlated to the percentage of root coverage. For gingival recessions ≥4 mm, 100% root coverage was achieved only when tissue thickness was ≥1 mm. Root coverage percentage was slightly related to papilla width in both groups, while it was associated with papilla height only in group 1 (P = 0.004). Only in patients in group 1 was the height of bone on the vestibular side related to the percentage of root coverage obtained (P = 0.003).

Conclusions: The results of the present study suggest that baseline recession depth and flap thickness may influence the outcome of marginal tissue recession therapy with CAF plus EMD at 12 months. There is not a clear relation between root coverage and other anatomical features as papilla width, papilla height, and the amount of bone on the vestibular side. J Periodontol 2005;76:899‐907.
Healing of Dehiscence Defects Following Root Surface Demineralization With Tetracycline: A Histologic Study in Monkeys
Authors: Nagata Maria J.H. , Bosco Alvaro F. , Leite Cristiane M. , Melo Luiz G.N. , Sundefeld Maria L.M.M.
Published: June 2005

Background: The purpose of this study was to histologically evaluate the healing of experimental dehiscence defects after surface demineralization with tetracycline hydrochloride.

Methods: Six adult male monkeys (Cebus apella) were used in this study. Dehiscence defects were surgically created on the buccal aspect of the mandibular lateral incisors in all animals. The root surfaces were debrided and planed. In a split‐mouth design, a 10% tetracycline hydrochloride solution was applied to one tooth for 4 minutes (T group), followed by irrigation with saline. The contralateral tooth served as a control (C group). The flaps were repositioned and sutured. The animals were sacrificed at 6 months postoperatively and histological sections were processed. Computer‐assisted histomorphometric analysis was used to evaluate the formation of new cementum, new bone, new connective tissue attachment, and length of the epithelium (junctional and sulcular).

Results: Bone regeneration was similar in both groups (1.5 ± 0.3 mm for the T group and 1.5 ± 0.6 mm for the C group). The C group showed more new cementum than the T group (2.3 ± 0.3 mm versus 2.2 ± 0.3 mm) as well as a longer epithelium (1.0 ± 0.3 mm versus 0.9 ± 0.2 mm). The T group presented more new connective tissue attachment (3.1 ± 0.2 mm) than the C group (2.9 ± 0.6 mm). However, no statistically significant differences were detected between the two groups.

Conclusions: The amount of new attachment was similar in both groups. Root conditioning with 10% tetracycline solution did not produce any additional new attachment in comparison to the controls. J Periodontol 2005;76:908‐914.
Effect of Cyclosporin A on the Mineral Apposition Rate of Cementum and Dentin in Growing Rats
Authors: Shen E‐Chih , Fu Earl , Gau Ching‐Hwa , Hsieh Yao‐Dung , Chiang Cheng‐Yang
Published: June 2005

Background: Since there is no direct information to verify whether cyclosporin A (CsA) can affect the mineralization of dental hard tissue, the formation of dentin and cementum in growing rats was recorded by labeling the mineral phase of these tissues with fluorochrome marker in this study.

Methods: After the extraction of the right maxillary molars, 30 male 3‐week‐old Sprague‐Dawley rats were assigned to two groups. Following a 2‐week healing period, the experimental rats received 30 mg/kg CsA daily for 7 weeks, while the control rats received only mineral oil. The fluorescent markers, calcein and alizarin red, were given on alternate weeks for 7 weeks. At the end of study, the mandibles were obtained and undemineralized sections were processed. Serial sections, 8 µm thick, were cut for the entire distal roots of the first molars. Five central sections were selected to determine the mineral apposition of cellular cementum and dentin at the apex and middle of root, respectively.

Results: The apposition rates of apical cellular cementum were significantly influenced by CsA therapy, occlusal function, and observation duration. However, the dentin apposition rates were significantly influenced by the observation intervals only.

Conclusions: In this study, CsA therapy and occlusal function significantly influenced the apposition rates of apical cementum, but not the rates of mid‐root dentin. Our hypothesis that CsA can induce oral hard tissue alterations, as well as gingival overgrowth, is demonstrated. J Periodontol 2005;76:936‐940.
Impaired Degradation of Matrix Collagen in Human Gingival Fibroblasts by the Antiepileptic Drug Phenytoin
Authors: Kato Takahiro , Okahashi Nobuo , Kawai Shinji , Kato Takafumi , Inaba Hiroaki , Morisaki Ichijiro , Amano Atsuo
Published: June 2005

Background: Gingival overgrowth (GO) is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT‐induced GO characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF).

Methods: HGFs were cultured with various concentrations of PHT and viable cell numbers and collagen amounts were determined. Gene and protein expressions of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP) were quantified with reverse transcription‐polymerase chain reaction (RT‐PCR) analyses and Western blotting, respectively. Cellular endocytosis of collagen was assayed using flow‐cytometric analysis. The effects of PHT on extracellular signal‐regulated kinase 1/2 (ERK1/2) and inhibitor κB‐α (IκB‐α) were assayed.

Results: The proliferation of HGFs was not affected by PHT, whereas it significantly increased collagen accumulation. Further, the expressions of MMP‐1, ‐2, and ‐3 were markedly suppressed by PHT, whereas that of TIMP‐1 was induced in a dose‐ and timedependent manner. PHT also markedly prevented collagen endocytosis by HGFs, which was associated with the suppression of α2β1‐integrin expression. In addition, the phosphorylation of ERK1/2 and IκB‐α degradation were suppressed by PHT.

Conclusions: These results suggest that PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP‐1 and α2β1‐integrin‐mediated endocytosis. Those alterations are likely mediated through the cellular signaling pathways of ERK1/2 and nuclear factor κB. These synergistic effects may cause collagen accumulation, leading to GO. J Periodontol 2005;76:941‐950.
Aberrant Neutrophil Reactions in Periodontitis
Authors: Figueredo C.M.S. , Fischer R.G. , Gustafsson A.
Published: June 2005

Background: The aim of this study was to compare the activity of neutrophilic granulocytes in patients with severe periodontitis and patients with gingivitis alone.

Methods: The study population comprised 22 patients with gingivitis and 44 with periodontitis. Samples of gingival crevicular fluid (GCF) were collected from untreated patients with gingivitis and from shallow and deep pockets in untreated patients with periodontitis. GCF samples were analyzed for lactoferrin, elastase, matrix metalloproteinase‐8 and ‐9, and collagenolytic activity.

Results: The free elastase activity and the neutrophil activity, estimated as the ratio between elastase and lactoferrin, were significantly higher in the samples from the periodontitis patients. These differences were also observed in shallow pockets in periodontitis patients compared to similar pockets in patients with gingivitis.

Conclusion: This study shows higher levels of free elastase in untreated patients with periodontitis, relative to inflammation‐matched controls, which may explain the tissue destruction seen in periodontitis. J Periodontol 2005;76:951‐955.
Nitric Oxide Synthase Inhibition Prevents Alveolar Bone Resorption in Experimental Periodontitis in Rats
Authors: Leitão R.F.C. , Ribeiro R.A. , Chaves H.V. , Rocha F.A.C. , Lima V. , Brito G.A.C.
Published: June 2005

Background: Periodontitis is the most frequent cause of tooth loss in adults. Nitric oxide (NO) has been linked to bone resorption mechanisms during inflammation processes. The aim of this study was to investigate the effect of NOS (NO synthase) inhibitors in the alveolar bone loss in an experimental periodontitis disease (EPD) model.

Methods: Wistar rats were subjected to a ligature placement around the second upper left molars and were sacrificed at 11 days. Alveolar bone loss was evaluated by the sum of distances between the cusp tips and the alveolar bone along the axis of each molar root, subtracting from the contralateral side. Histopathological analysis was based on cell influx, alveolar bone, and cementum integrity. Leukogram was performed at 6 hours and 1, 7, and 11 days after the EPD induction. Groups were treated with the NOS inhibitors, aminoguanidine (AG) (2.5 to 10 mg/kg/d), or L‐arginine methyl ester (L‐NAME, 5 to 20 mg/ kg/d) intraperitoneally (i.p.), 1 hour before the EPD induction and daily for 11 days. Controls received only saline (EPD group). As controls for L‐NAME specificity, groups were co‐treated with either L‐arginine (150 to 600 mg/kg/d) or D‐arginine (600 mg/ kg/d) and L‐NAME (20 mg/kg/d). Different groups were used for morphometric and histopathological analysis.

Results: Both L‐NAME and AG significantly and dose‐dependently inhibited the alveolar bone loss as compared to EPD group. L‐NAME (20 mg/kg/d) reduced the alveolar bone loss by 50%, whereas AG (5 mg/kg/d) reduced it by 47% compared to EPD. This result was coupled to a significant reduction of cell influx to the periodontium, as well as to the preservation of alveolar bone and cementum, seen at histopathology, for both compounds. The co‐administration of L‐arginine, but not of D‐arginine reversed L‐NAME effects.

Conclusion: These data provide evidence that NOS inhibitors prevent inflammatory bone resorption in experimental periodontitis. J Periodontol 2005;76:956‐963.
Effect of Neutrophil Apoptosis on Monocytic Cytokine Response to Porphyromonas gingivalis Lipopolysaccharide
Authors: Berker Ezel , Kantarci Alpdogan , Hasturk Hatice , Van Dyke Thomas E.
Published: June 2005

Background: Neutrophil apoptosis may play a critical role in the resolution of inflammation by stimulating anti‐inflammatory cytokine generation from monocytes. In this study, we investigated the effect of apoptotic neutrophils on interleukin (IL)‐10 and IL‐1β production from monocytes in response to Porphyromonas gingivalis lipopolysaccharide.

Methods: Peripheral blood neutrophils from healthy individuals were isolated by sodium diatrizoate density gradient centrifugation. In order to induce apoptosis, neutrophils were cultured for 24 hours in modified Dulbecco's medium supplemented with 10% autologous serum. Cell apoptosis was quantified by Annexin V positivity and loss of CD16 expression on the cell surface. Peripheral blood mononuclear cells were isolated from the same subjects; monocytes were purified by magnetic cell sorting and cultured with or without apoptotic or fresh neutrophils. Lipopolysaccharide from Porphyromonas gingivalis was used for cell stimulation. IL‐1β and IL‐10 levels in supernatants were determined by enzyme‐linked immunosorbent assay (ELISA).

Results: IL‐10 generation was significantly increased in monocytes cultured with apoptotic neutrophils compared to monocytes alone or cocultured with fresh neutrophils (P <0.05). IL‐1β was suppressed both in resting and lipopolysaccharide‐stimulated monocytes in the presence of apoptotic neutrophils compared to monocytes alone or monocytes cultured with fresh neutrophils at all time points (P <0.05).

Conclusion: Neutrophil apoptosis provides a signal to monocytes, changing the phenotype of the monocyte resulting in the production of anti‐inflammatory cytokines and suppression of proinflammatory cytokines in response to lipopolysaccharide. J Periodontol 2005;76:964‐971.
Outer Membrane Vesicles From Porphyromonas gingivalis Affect the Growth and Function of Cultured Human Gingival Fibroblasts and Umbilical Vein Endothelial Cells
Authors: Bartruff Jeffrey B. , Yukna Raymond A. , Layman Don L.
Published: June 2005

Background: The purpose of this study was to examine the effects of outer membrane vesicles (OMV) obtained from Porphyromonas gingivalis (Pg) on the growth and function of human gingival fibroblasts (HGF) and human umbilical vein endothelial cells (HUVEC).

Methods: OMV were obtained from a cell‐free growth medium of Pg ATCC 33277 by 40% NH2SO4 precipitation and ultracentrifugation. Cell proliferation was measured by 3H‐thymidine incorporation into growing HGF and HUVEC. Endothelial cell function was determined by their capacity to form a network of capillary tubes on an extracellular matrix (ECM).

Results: Proliferating HGF and HUVEC demonstrated a significant dose‐dependent inhibition of 3H‐thymidine uptake when cultured with 0 to 40 µg/ml of OMV protein. HGF and HUVEC showed an IC50 of growth of about 9.0 µg/ml and 4.5 µg/ml of OMV protein, respectively. Capillary tube formation by HUVEC cultured on an ECM was suppressed by 70% to 80% with 5 µg/ml OMV protein after 18 hours of incubation. The presence of proteolytic enzymes in the OMV did not contribute to capillary tube disruption, since blocking enzyme activity with specific inhibitors did not reduce the suppression of capillary tube formation. After heating at 90°C for 5 minutes, OMV significantly lost their capacity to suppress capillary tube formation.

Conclusions: OMV significantly inhibit the proliferation of cultured HGF and HUVEC in a dose‐dependent manner. OMV suppressed the capillary tube formation by cultured HUVEC. The factor(s) appeared to be a protein and not endotoxin because its inhibitory activity was markedly reduced by heat inactivation. These studies suggest that OMV contribute to chronic periodontitis by suppressing cell proliferation and revascularization in periodontal tissues. J Periodontol 2005;76:972‐979.
Pain Experienced by Patients During Periodontal Recall Examination Using Thinner Versus Thicker Probes
Authors: Hassan Mohamed A. , Bogle Gary , Quishenbery Mary , Stephens Denise , Riggs Matt , Egelberg Jan
Published: June 2005

Background: The aim of the present study, performed during periodontal recall visits, was to compare the levels of pain experienced by patients during periodontal probing using probes with tip diameters of either 0.40 mm or 0.63 mm.

Methods: Three groups of 20 adult patients were examined by three different therapists. Diagonal maxillary/mandibular quadrants were probed with a 0.40 mm and a 0.63 mm probe, respectively. At the completion of probing of each quadrant, the patients were asked to describe their pain using a visual analog scale (VAS).

Results: Most patients showed low VAS pain scores for both probes. However, using an arbitrary threshold of VAS ≥40 mm to indicate significant pain, some patients had a painful experience. Lower median pain responses following probing with the 0.63 mm probe compared to the 0.40 mm probe were observed for patients of therapist 1, and for the quartile of all 60 patients that showed the highest VAS scores. For therapist 2 and 3 groups, no differences were found. The pain levels expressed by the three groups of patients varied, confirming results of our previous studies, which also observed differences in patients' pain experiences following probing by different therapists.

Conclusions: The ability to deliver dental care with a minimum of patient discomfort would seem to be an essential part of the skills of individual clinicians. We would like to suggest that dental therapists periodically evaluate this part of their skill by asking patients to express their pain experiences following various procedures using VAS scales. J Periodontol 2005;76:980‐984.
Effect of Topical Cimetidine Rinse on Gingival Crevicular Neutrophil Leukocyte Function
Authors: Van Dyke Thomas E. , Cutler Christopher W. , Kowolik Michael , Singer Robert S. , Buchanan William , Biesbrock Aaron R.
Published: June 2005

Background: Three coordinated mechanism‐of‐action clinical studies were conducted to examine the effects of topical cimetidine rinse on neutrophil function in the gingival crevice.

Methods: The first study was a randomized, double‐blind, placebo‐controlled, 28‐day experimental gingivitis study involving 21 healthy adults, in which subjects rinsed twice a day with placebo or 0.5% cimetidine rinses. At baseline and days 14, 21, and 28, neutrophils were harvested from prespecified gingival sulcular sites, purified, stained, and examined by trifluorochrome phagocytosis and killing microassay. The second and third studies were placebo‐controlled, 9‐week, three‐period (each of 3 weeks’ duration), longitudinal studies involving seven and nine adults with moderate periodontitis, respectively. Subjects rinsed twice a day during periods 1 and 3 with placebo and during period 2 with 0.5% cimetidine. At baseline and weekly intervals, neutrophils were harvested from prespecified periodontal pockets, purified, stained, and examined by trifluorochrome phagocytosis and killing microassay in the second study. In the third study, neutrophils were examined spectrophotometrically for superoxide production and in a luminol‐enhanced chemiluminescence assay.

Results: In the first study, the mean number of phagocytosing neutrophils was statistically significantly increased (P = 0.016) in the cimetidine group (31.1 cells/subject) versus the placebo group (13.7 cells/subject) at day 28. In addition, a statistically significant increase (P = 0.036) in bacterial killing was observed in the cimetidine rinse group; in the cimetidine group, 63.4% of bacteria in the neutrophils were killed compared to 46.2% in the placebo group. Additional data from the other two studies support these findings.

Conclusion: Collectively, these studies provide evidence that topical 0.5% cimetidine oral rinse enhances the antibacterial function of crevicular neutrophils. J Periodontol 2005;76:998‐1005.
An equation‐of‐state contribution for polar components: Quadrupolar molecules
Authors: Gross Joachim
Published: June 2005

An equation‐of‐state (EOS) contribution for quadrupolar interactions is developed based on a third‐order perturbation theory. Model constants are adjusted to comprehensive molecular simulation data for vapor–liquid equilibria of the two‐center Lennard–Jones (2CLJ) plus pointquadrupole fluid from the literature. Molecular elongations L* from 0 (spherical) to 0.8 are covered by the simulation data. The EOS is suited for both, the 2CLJ fluid and the tangent‐sphere Lennard–Jones framework. It is applied to pure components and mixtures of real substances with the perturbed‐chain statistical associating fluid theory (PC‐SAFT) EOS. It is possible to use tabulated values of quadrupolar moments (independently determined) directly in the EOS, so that no additional pure component parameter is introduced. Compared with the case where quadrupolar interactions are not specifically accounted for, the proposed model gives a systematic improvement of pure component properties and of mixture phase equilibria of strong quadrupolar components, such as carbon dioxide, and the absolute value of the required binary interaction parameter is significantly reduced. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Magnetic resonance imaging velocimetry of fluid flow in a clinical blood filter
Authors: Heese Frank , Robson Philip , Hall Laurie
Published: June 2005

Multislice spin echo (SE) pulsed‐field gradient phase‐contrast (PFG‐PC) magnetic resonance imaging (MRI) velocimetry has been used to determine the complex three‐dimensional (3‐D) recirculatory flow pattern of a simple, single‐phase blood analogue fluid (glycerol–water solution 70–30 vol%) in a commercially available blood filter (PALL AL8 arterial line blood filter), whose inlet and outlet ports are about 0.95 cm in diameter. The maximum shear stress measured in the fluid is 10 Pa, which is significantly lower than the value for the onset of red blood cell hemolysis. The flow field is in agreement with computational flow modeling (Fluent 4.3) and is reminiscent of the hydrocyclone flow in industrial separation devices. The development of this flow pattern is demonstrated for three different volume flow rates (1, 2, and 3 L/min). © 2005 American Institute of Chemical Engineers AIChE J, 2005
Raymond Pearl memorial lecture, 1989: Cultural practices as determinants of clinical pathology and epidemiology of venereal infections: Implications for predictions about the AIDS epidemic
Authors: Gajdusek D. Carleton
Published: June 2005

Sexually transmitted diseases newly introduced into diverse primitive and isolated populations have behaved differently in clinical severity and seriousness of the epidemics they have caused, because of culturally different sexual practices. Epidemic interstitial plasma cell pneumonia in the 1930s–1950s in eastern and northern Europe, caused by Pneumocystis carinii and accompanied by cytomegalovirus infection, was an unexpected AIDS‐like epidemic which spread slowly, then quickly and inexplicably disappeared. Newly recognized endemic HTLV‐I and epidemic HIV human retrovirus infections are behaving in a fashion similarly difficult to anticipate and predict.
Preterm infants born to women who had an elevated prepregnancy body mass index appear to be at increased risk of germinal matrix hemorrhage
Authors: Leviton Alan , Pagano Marcello , Kuban Karl C. K. , Fenton Terence , Wolff Mildred , Strassfeld Ruth
Published: June 2005

In a sample of 449 infants of birthweight ≤ 1.5 kg, the risk of germinal matrix hemorrhage increased monotonically with increases in maternal body mass index (BMI, wt/ht2). This relationship was repeated in many strata of the sample, including those defined by the occurrence of labor, maternal preeclampsia, route of delivery, intubation of the baby and acidosis, as well as strata defined by birthweight and gestational age. Even though the dose‐response relationship is prominent, caution is advised in drawing inferences from these findings until confirmation is provided that preterm infants born to mothers of high BMI are at increased risk of germinal matrix hemorrhage. © 1992 Wiley‐Liss, Inc.
Linked loci in chromosome 1 (FXIIIB, HF, PEPC) and their variability in Brazilian Indians
Authors: Kömpf J. , Luckenbach Ch. , Krczal D. , Salzano F. M. , Callegari‐Jacques S. M.
Published: June 2005

A total of 352 individuals living in seven localities of two Brazilian Indian groups (Macushi and Içana River Indians) were variously studied for coagulation factor XIIIB, human factor H, and a new polymorphism of peptidase C. No significant inter‐ or intra‐tribal differences were found for the FXIIIB alleles, the frequencies varying around 95% for F13B*3 and 5% for F13B*1. Results for HF were heterogeneous, HF*A presenting a much higher frequency among the Macushi (32%) than among the Içana River Indians (9%). Intratribal differences were also found among both groups. Linkage disequilibrium exists between alleles of these two systems (0.03 ± 0.01). These are the first results for human factor H obtained among Amerindians. The data for PEPC were limited to the Içana River Indians. There is heterogeneity among the three localities sampled and evidence of moderate linkage disequilibrium between markers in this locus and in F13B (0.02 ± 0.01). © 1992 Wiley‐Liss, Inc.
Sexual behavior and Down syndrome: The biological mechanism
Authors: Martin‐DeLeon Patricia A. , Williams Mary B. , Reynolds James F.
Published: June 2005

Sufficient evidence of a correlation between infrequent coitus and Down syndrome (DS) has now accumulated to warrant reevaluation of the suggested biological mechanisms. The evidence provides no support for delayed fertilization as the mechanism responsible for this correlation, as was originally proposed by German [Nature 217:516–519, 1968]. A better explanation of this association is provided by the sperm aging hypothesis, which gains its support from both animal studies and chromosomal findings of a paternal contribution to DS. The animal studies supporting this hypothesis show an increased incidence of sperm‐derived trisomies resulting from sperm stored for prolonged periods in the male tract. The chromosomal findings show a paternal origin in 20% of DS infants; the sperm aging hypothesis concerns the biological mechanism in this 20%. In addition to explaining the excess of DS for older mothers, the sperm aging hypothesis explains the excess for teenaged unwed mothers and indicates that sperm aging from decreased ejaculatory frequency may be a cause of DS in all age groups. Testable directly in humans against German's delayed fertilization hypothesis, the sperm aging hypothesis has immediate clinical implications. It suggests (1) an approach to reduce the incidence of DS and miscarriages and (2) clinical research that will increase knowledge of the circumstances indicating a need for antenatal monitoring.
The bingo model IV. The statistics of survivorship in the bingo‐gamma model
Authors: Murphy Edmond A. , Trojak Joseph E. , Berger Kenneth R. , Foster Ella C. , Opitz John M.
Published: June 2005

The survivorship (time to death or failure) of a bingo‐gamma (BG) model is defined as the minimum among the waiting times for completion among k independent gamma processes. The ith process is of order ni, with a mean rate for the occurrence of hits of ai, In this paper we address the case where, for all competing processes, the order and the rate at which hits occur are the same but both they and k are unknown. We denote by k the multiplicity, by n the order or the number of hits to failure, and by a the transition parameter. The joint maximum likelihood estimator (MLE) of the three paramters of this BG process is developed. An algorithm for calculating it has been devised and a computer program in BASIC has been written. The properties of the MLE: have been explored systematically, mainly by Monte Carlo simulation. The distributions, means, variances, covariances, and correlation coefficients of the three parameters are explored for samples of size 25 and samples of size 100. Also, the simple average of the observed survival times (which gives a method of moments estimator of the mean survival) is compared with the MLE of the mean survival; the two estimators seem to be unbiased and about equally efficient.
The bingo model of survivorship V. The problems of conformation to the empirical evidence
Authors: Murphy Edmond A. , Berger Kenneth R. , Trojak Joseph E. , Pyeritz Reed E. , Opitz John M.
Published: June 2005

We discuss the statistical and biological problems of adapting the theoretical bingo model to the analysis of empirical data. A distinction is made between an idealized pathogenetic model, which aims to represent the disease in as much authentic detail as the present state of knowledge allows and in components that have literal interpretation, and an empirical model, which deals with those effects of the pathogenetic model that one may hope to observe clinically. We review a variety of empirical models distinguishable by the amount of data available on intermediate degrees of damage short of total destruction. The relationship of damage to time is explored, and we consider the criteria and usefulness of linearization of this relationship where the diachronic (“longitudinal”) data are few and extend over a comparatively short time. Every time a patient is examined, the degree of cumulative damage is assessed in each of the body systems of interest. Thus the examination will furnish a set of measurements, which is obtained on each of several examinations, taken over a period that for preference is long relative to the survival of the system. Specific disorders discussed include dentition and enlargement of the aorta with age in the Marfan syndrome.
Unique mosaicism in Prader‐Labhart‐Willi syndrome—a contiguous gene or aneuploidy syndrome?
Authors: Kousseff BG , Diamond T , Essig Y , Miller K , Tedesco T , Opitz John M. , Reynolds James F. , Ledbetter David H.
Published: June 2005

A 16‐year‐old boy with Prader‐Labhart‐Wi11i syndrome (PLWS) had hypotonia, feeding difficulties, failure to thrive, strabismus and bilateral inguinal hernias with cryptorchidism during infancy followed by hyperphagia, marked early‐onset obesity with insulin‐dependent diabetes mellitus and necrobiosis lipoidica diabeticorum, short stature, hypogonadotropic hypogonadism and some of the facial characteristics of the individuals with the PLWS. IQ is estimated around 90.

Cytogenetic studies showed mosaicism: 45,X, t(Y;15) with partial deletion 15 (15pter → 15ql2); 46,X, t(Y;15), dic(15)(15pter → 15ql2::15ql2 → 15pter) and 47,X,t(Y;15), dic(15), dic(15). The dic(15) was bisatel1ited, NOR‐positive on both arms and represented inv dup(15). Thus, the 2 lines with the dic(15) showed partial trisomy 15 (15pter → 15q 12) and partial pentasomy 15 (15pter → 15ql2), respectively. The cell line ratios were different in lymphocyte and fibroblast cultures.

The unique cytogenetic findings in this patient, the reports of a variety of chromosome 15 aberrations in PLWS; as well as aberrations of other chromosomes, suggest that the condition is a contiguous gene syndrome rather than an aneuploidy syndrome.
Penetrance in the presence of genetic susceptibility to environmental factors
Authors: Khoury Muin J. , Flanders W. Dana , Beaty Terri H. , Optiz John M. , Reynolds James F.
Published: June 2005

Many single‐gene disorders (especially dominant traits) are known to exhibit “incomplete penetrance,” a term often criticized as reflecting our ignorance of genetic and environmental factors that may interact with the genotype to determine the ultimate phenotype of the individual. We explore the effects of an environmental factor on penetrance for a simple model of single gene‐mediated susceptibility to environmental factors. We show that penetrance of the susceptible genotype increases with increasing frequency of exposure to the factor and the strength of interaction between the factor and the genotype (relative risk). For disorders with disease frequency of 0.001 or less (as seen with many congenital malformations), penetrance is generally low (<10%) if the exposure frequency is low (<10%) even in the face of strong gene‐environment interaction. Such low penetrance can lead to low recurrence risks. Single‐gene effects could easily be overlooked in genetic analysis unless specific environmental factors are considered.
Prenatal diagnosis of the fragile X – The Australasian experience
Authors: Purvis‐Smith Stuart G. , Laing Sue , Sutherland Grant R. , Baker Elizabeth
Published: June 2005

Identification of increasing numbers of females heterozygous for fragile X linked mental retardation together with improved genetic counselling is creating a growing demand for prenatal diagnosis of fra(X). However, present cytogenetic techniques are somewhat unreliable and our collaborative approach has endeavoured to improve quality of cell culture systems and the sensitivity of fra(X) detection.

Since 1985 we have exchanged cell cultures between our laboratories for verification of diagnostic results and comparison of induction techniques and have benefitted from larger numbers of cells scored for fra(X). Our 50 cases represent almost all of such studies undertaken in Australasia (Australia and New Zealand). Ten cases were unequivocally fra(X) positive; there was discrepancy between laboratories in 4 cases and one false‐negative case.

We propose a protocol to enhance fra(X) detection and conclude that, provided care is exercised, couples at risk of a fra(X) pregnancy can benefit from prenatal cytogenetic diagnosis.
Prenatal diagnosis of fragile X syndrome by placental (chorionic villi) biopsy culture
Authors: McKinley Mark J. , Kearney Lyndal U. , Nicolaides Kypros H. , Gosden Christine M. , Webb Tessa P. , Fryns Jean P.
Published: June 2005

Second trimester ultrasound‐guided fetal blood sampling and placental biopsy were performed on 10 pregnancies at risk for fra(X)‐linked mental retardation (Martin‐Bell syndrome). Three cases were diagnosed as affected after cytogenetic analysis of fetal blood and placental cultures. The fra(X)(q27.3) and common fragile sites were shown to be expressed at a lower level in placenta than in fetal blood. Induction methods included methotrexate, 5‐fluoro‐2‐deoxyuridine, and excess thymidine. Excess thymidine may give the best expression of fra(X)(q27.3). Enhancement of fra(X)(q27.3) expression was not shown with caffeine or 5‐methoxybenzamide.
Prenatal exclusion of Norrie disease with flanking DNA markers
Authors: Gal Andreas , Uhlhaas Siegfried , Glaser Dieter , Grimm Tiemo , Neri Giovanni , Reynolds James F.
Published: June 2005

Three polymorphic DNA markers linked to the locus of Norrie disease were used for indirect genotype analysis in a ten‐wk‐old fetus at risk for the disease. When haplotypes of the family members and the estimated recombination frequency between Norrie gene and each of the DNA marker loci DXS7, DXS84, and DXS146 were taken into account, the risk that the fetus had inherited the mutation was about 1%.
Osteogenesis imperfecta type I with unusual dental abnormalities
Authors: Levin L. Stefan , Young Richard J. , Pyeritz Reed E. , Opitz John M. , Reynolds James F.
Published: June 2005

A large kindred with dominantly inherited osteogenesis imperfecta was evaluated. Affected individuals had bone fractures, blue sclerae, and hearing loss. In addition, all had dental abnormalities distinct from those previously described in other families with this syndrome. Deciduous teeth were normal in color or blue‐grey. On radiographs of an early developing deciduous dentition, pulps were larger than normal. In patients with mixed dentitions, pulp chambers of deciduous teeth were partially obliterated. Increased constriction at the junctions of the crowns and roots was found in some deciduous teeth. One patient had large pulp stones in the pulp chambers of all maxillary deciduous molars. Permanent teeth were normal in color but had oval pulp chambers with apical extensions into the coronal portions of the roots, large coronal pulp stones, narrow root canals, and thin roots. Individuals in this family who did not have osteogenesis imperfecta had normal teeth. In addition, a well circumscribed radiolucency without a sclerotic periphery, involving the apices of all permanent mandibular incisors, was found in the anterior mandible in one patient. These findings support the hypothesis that this family has yet another type I osteogenesis imperfecta “syndrome”.
Genetic aspects of artificial insemination with donor semen: The French CECOS federation guidelines
Authors: Jalbert Pierre , Leonard Claude , Selva Jacqueline , David Georges
Published: June 2005

The genetic problems raised by assisted reproduction using donor gametes (AID) are numerous and often complex. They concern the legitimacy and the appropriate forms of genetic screening for both gamete donors and recipients; the identification of genetic indications justifying the use of this method of reproduction; and ascertainment of the state of health of the conceptus at birth. The experience and guidelines of the French CECOS Federation, which comprises 20 AID treatment centers, are described. The discussion emphasizes the need for an international exchange of view on this subject.
Hypothesis: Familial Mediterranean fever—A genetic disorder of the lipocortin family?
Authors: Shohat M. , Korenberg J. R. , Schwabe A. D. , Rotter J. I.
Published: June 2005

Familial Mediterranean fever is an autosomal recessively inherited disorder of unknown cause characterized by recurrent attacks of inflammation, involving mainly the peritoneum, pleura, synovia, and skin. Based on a phenotype analysis, we propose that its manifestations may be related to a genetic defect in one of the family of lipocortin proteins. Evidence is presented supporting an abnormality in the first step of prostaglandin/leukotriene synthesis.
Chromosome abnormalities in selected newborn infants with malformations in Brazil
Authors: Borovik Cleide L. , Brunoni Décio , Sato Aurea E. , Barletta Horácio , Dualibi‐Casanova Luci , Hironaka Hideaki C. , Brunoni Leila R. , Brock Roger , Carvalho Laura A. , Costa Egle De Campos
Published: June 2005

Between 1982 and 1985, 109 infants were referred for cytogenetic examination out of a population of 73,192 liveborn infants from eight maternity hospitals surveyed by the ECLAMC/MONITOR program. Thirty‐one of the children had a chromosome abnormality different from trisomy 21.

Considering the total population surveyed, trisomy 18 was detected in 1:6,099; trisomy 13 was seen in 1:24,397 and unbalanced rearrangements were found in 1:7,319 infants. Those rates were not significantly different from the expected ones, as compared to previous cytogenetic surveys of consecutive births.

We concluded that most chromosome abnormalities associated with congenital malformations can be detected at low cost, provided there is a high accuracy of clinical examination and referral criteria, as well as close cooperation between pediatricians and geneticists.
Paracentric inversion of chromosome 19 in three generations
Authors: Phelan Mary C. , Schroer Richard J. , Krug Ernest F.
Published: June 2005

We observed a paracentric inversion of 19p in a 15‐month‐old white boy with developmental delay and mild facial anomalies. The inversion of 19p was also present in his phenotypically normal mother and maternal grandfather.
Decisions following the intrauterine diagnosis of sex chromosome aneuploidy
Authors: Robinson Arthur , Bender Bruce G. , Linden Mary G.
Published: June 2005

This is a report of 327 phone calls to our center concerning the intrauterine diagnosis of sex chromosome abnormalities (SCA). The first author (A.R.) responded to each by counseling either the parents or the referring professional. Sixty‐two percent continued the pregnancy. When the parents were counseled directly, the percentage continuing the pregnancy was significantly higher than when the information was transmitted through the professionals. Our results are different from most reports in these situations, and suggest that well‐informed couples, counseled by geneticists, are more likely to continue these pregnancies. The possible occurrence of SCA should be considered in preamniocentesis counseling.
Comparison of education and occupation of adults with achondroplasia with same‐sex sibs
Authors: Roizen Nancy , Ekwo Edem , Gosselink Carol
Published: June 2005

We compared the education and occupation of 20 adults with achondroplasia with their same‐sex sibs. While the mean number of years of formal education reported by affected males and females was comparable to that of their same‐sex sib, we found differences in the level of occupation between the groups. In general, affected females had a significantly lower occupational level compared to their unaffected sisters. In males and females the number of years of formal education and whether or not individuals had achondroplasia were the 2 most important factors determining occupational level when contrasting affected persons with their unaffected sibs. Education alone accounted for 28 and 42% of the observed variance in occupational level, respectively, for females and males.
DNA polymerase alpha defect in the N syndrome
Authors: Floy Kimberly M. , Hess Russell O. , Meisner Lorraine F.
Published: June 2005

The N syndrome is characterized by mental retardation, malformations, chromosome breakage, and development of T‐cell leukemia (Opitz et al.: Proceedings of the II International Congress IASSMD pp 115–119, 1971; Hess et al.: Clinical Genetics 6:237–246, 1974b, American Journal of Medical Genetics [supplement] 3:383–388, 1987). N syndrome fibroblasts were studied to see if the high chromosome breakage rate associated with this apparently X‐linked syndrome could be related to a deficiency of DNA polymerase alpha, a product of a gene localized to the X chromosome. Bleomycin, which is known to break double‐stranded DNA, produced increased chromosome breakage in normal control, Fanconi anemia, and N syndrome fibroblasts. When aphidicolin was used to inhibit repair mediated by DNA polymerase alpha, both normal control and Fanconi anemia fibroblasts showed significantly more chromosome breakage than was produced by bleomycin alone, but there was no increase in the amount of breakage seen in the N syndrome fibroblasts over that seen with bleomycin alone. This suggests that the N syndrome is due to a mutation affecting the region of the X chromosome on which the gene for DNA polymerase alpha is located, and that the high risk of T‐cell leukemia observed in the hemizygote is due to this DNA repair defect.
Model identifying the reproductive decision after genetic counseling
Authors: Frets Petra G. , Duivenvoorden Hugo J. , Verhage Frans , Ketzer Eva , Niermeijer Martinus F.
Published: June 2005

To assess the identifiability of reproductive planning after genetic counseling, a model was designed to study 8 relevant factors influencing reproductive decisions after genetic counseling. Altogether, 164 couples were interviewed at home 2 to 3 years after genetic counseling. The factors were arranged in a flow chart distinguishing 3 groups: reproductive outcome prior to genetic counseling, desire to have children, and interpretation of information gained from genetic counseling. The model based upon these retrospective data showed that reproductive decisions were identified correctly in 91% of the cases. The model consisted of 8 factors and documented the urgency of the desire to have children and the interpretation of the genetic risk. In addition, linear discriminant analysis of the 8 relevant factors enabled identification of the reproductive decision in 96% of the cases. This model may prove helpful to counselors and counselees by showing what other couples have decided in comparable circumstances and for which reasons.
Autosomal dominant Polycystic Kidney Disease: A linkage evaluation of heterogeneity in Italy
Authors: Mandich P. , Restagno G. , Novelli G. , Bellone E. , Potenza L. , Varetto O. , Dallapiccola B. , Carbonara A. , Ajmar F.
Published: June 2005

A survey of 29 families with Adult Polycystic Kidney Disease (ADPKD) was performed to evaluate the genetic heterogeneity of the disease in Italy. The approach was through the linkage between the disease and 2 polymorphic DNA fragments as detected by the probes 3′HVR and 24.1. Linkage between the polymorphic markers and the disease was confirmed, with the following lod scores: between 3′HVR and ADPKD1 = 12.974 at θ = 0.02; between 24.1 and ADPKD = 1.716 at θ = 0.07; between 3′HVR and 24.1 = 2.738 at θ = 0.09. No evidence of significant genetic heterogeneity in the examined Italian regions was detected.
Gene of type II autosomal dominant retinitis pigmentosa maps on the long arm of chromosome 3
Authors: Olsson J. E. , Samanns Ch. , Jimenez J. , Pongratz J. , Chand A. , Watty A. , Seuchter S. A. , Denton M. , Gal A.
Published: June 2005

Linkage analysis has been performed on a large Australian family segregating for the autosomal dominant form of retinitis pigmentosa (ADRP). The majority of patients had no subjective symptoms of night blindness until their second decade and good visual acuity until late in life. The disease in this family has been classified as Type II ADRP according to the subdivisions provided by both Massof and Finkelstein and Fishman and colleagues. Linkage (θmax:0.08 at zmax:4.78) is here demonstrated between the disease locus and D3S47 (a marker locus on the long arm of chromosome 3), which showed in an earlier study very close linkage without recombination to the disease locus in an Irish pedigree with a clinically more severe and early onset (Type I) ADRP.
Fibular hypoplasia and complex brachydactyly (Du Pan Syndrome) in an inbred Pakistani kindred
Authors: Ahmad Mahmud , Abbas Hasan , Wahab Abdul , Haque Sayedul
Published: June 2005

A Pakistani kindred comprising 7 generations contained 7 men and 2 women with fibular hypoplasia and complex brachydactyly (syn: Du Pan syndrome). Analysis of the pedigree is strongly suggestive of autosomal recessive inheritance. The average inbreeding coefficient (F) for the affected persons was found to be significantly greater than that for unaffected persons in the pedigree and consanguineous loops could account for all affected persons being homozygous for the abnormal allele.
Bilateral complete polysyndactyly (type IV Haas)
Authors: Gillessen‐Kaesbach Gabriele , Majewski F.
Published: June 2005

We describe complete cutaneous syndactyly of all fingers and polydactyly in a 2‐month‐old girl. Based on 3 previous reports, this constitutes a separate entity (McKusick 18620) with probable autosomal dominant inheritance.
Reproductive behavior of thalassemic couples segregating for Cooley anemia
Authors: Gamberini Maria Rita , Canella Rita , Lucci Marco , Vullo Calogero , Barrai Italo
Published: June 2005

The reproductive behavior in 1984 of families segregating for Cooley anemia in Ferrara was compared with that of a control group of families, matched for some biological variables which affect fertility. At the resolution power of the sample, it was found that there is no significant difference in these variables due to segregation for Cooley anemia, and it appears that there is no longer significant reproductive compensation in thalassemic couples, although a tendency to compensate does still exist. The increased life span of children affected by Cooley anemia, due to improvements in treatment in the past decade, is probably the main reason why the compensatory reproductive behaviour of the past has almost disappeared.