Showing papers by "Loma Linda University published in 2003"

Clinical complications with implants and implant prostheses.

Abstract: The purpose of this article is to identify the types of complications that have been reported in conjunction with endosseous root form implants and associated implant prostheses. A Medline and an extensive hand search were performed on English-language publications beginning in 1981. The searches focused on publications that contained clinical data regarding success/failure/complications. The complications were divided into the following 6 categories: surgical, implant loss, bone loss, peri-implant soft tissue, mechanical, and esthetic/phonetic. The raw data were combined from multiple studies and means calculated to identify trends noted in the incidences of complications. The most common implant complications (those with a greater than a 15% incidence) were loosening of the overdenture retentive mechanism (33%), implant loss in irradiated maxillae (25%), hemorrhage-related complications (24%), resin veneer fracture with fixed partial dentures (22%), implant loss with maxillary overdentures (21%), overdentures needing to be relined (19%), implant loss in type IV bone (16%), and overdenture clip/attachment fracture (16%). It was not possible to calculate an overall complications incidence for implant prostheses because there were not multiple clinical studies that simultaneously evaluated all or most of the categories of complications. Although the implant data had to be obtained from different studies, they do indicate a trend toward a greater incidence of complications with implant prostheses than single crowns, fixed partial dentures, all-ceramic crowns, resin-bonded prostheses, and posts and cores.

Practice parameter: Evaluation of the child with global developmental delay Report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society

Abstract: Objective: To make evidence-based recommendations concerning the evaluation of the child with a nonprogres- sive global developmental delay. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. Results: Global developmental delay is common and affects 1% to 3% of children. Given yields of about 1%, routine metabolic screening is not indicated in the initial evaluation of a child with global developmental delay. Because of the higher yield (3.5% to 10%), even in the absence of dysmorphic features or features suggestive of a specific syndrome, routine cytogenetic studies and molecular testing for the fragile X mutation are recommended. The diagnosis of Rett syndrome should be considered in girls with unexplained moderate to severe developmental delay. Additional genetic studies (e.g., subtelomeric chromosomal rearrangements) may also be considered in selected children. Evaluation of serum lead levels should be restricted to those children with identifiable risk factors for excessive lead exposure. Thyroid studies need not be undertaken (unless clinically indicated) if the child underwent newborn screening. An EEG is not recommended as part of the initial evaluation unless there are historical features suggestive of epilepsy or a specific epileptic syndrome. Routine neuroimaging, with MRI preferred to CT, is recommended particularly if abnormalities are found on physical examination. Because of the increased incidence of visual and auditory impairments, children with global developmental delay may undergo appropriate visual and audiometric assessment at the time of diagnosis. Conclusions: A specific etiology can be determined in the majority of children with global developmental delay. Certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed. NEUROLOGY 2003;60:367-380

Dimensions of peri-implant mucosa: an evaluation of maxillary anterior single implants in humans.

Abstract: Background: Attempts have been made to evaluate the biologic dimension of osseointegrated implants; however, most are histologic studies in animals, and the effect of soft tissue support from adjacent teeth on the interproximal dimension of the peri-implant mucosa for anterior single implants has not been addressed. This study clinically evaluated the dimensions of the periimplant mucosa around 2-stage maxillary anterior single implants in humans after 1 year of function. The influence of the peri-implant biotype was also examined Methods: Forty-five patients (20 males and 25 females) with a mean age of 47.3 years were included in this study. A total of 45 maxillary anterior single implant crowns with a mean functional time of 32.5 months (range, 12 to 78) were evaluated. The dimensions of peri-implant mucosa were measured by bone sounding using a periodontal probe at the mesial (MI), mid-facial (F), and distal (DI) aspects of the implant restoration and the proximal aspects (MT, DT) of adjacent natural t...

Clinical complications in fixed prosthodontics

Abstract: The purpose of this article is to identify the incidence of complications and the most common complications associated with single crowns, fixed partial dentures, all-ceramic crowns, resin-bonded prostheses, and posts and cores. A Medline and an extensive hand search were performed on English-language publications covering the last 50 years. The searches focused on publications that contained clinical data regarding success/failure/complications. Within each type of prosthesis, raw data were combined from multiple studies and mean values calculated to determine what trends were noted in the studies. The lowest incidence of clinical complications was associated with all-ceramic crowns (8%). Posts and cores (10%) and conventional single crowns (11%) had comparable clinical complications incidences. Resin-bonded prostheses (26%) and conventional fixed partial dentures (27%) were found to have comparable clinical complications incidences. The 3 most common complications encountered with all-ceramic crowns were crown fracture (7%), loss of retention (2%), and need for endodontic treatment (1%). The 3 most common complications associated with posts and cores were post loosening (5%), root fracture (3%), and caries (2%). With single crowns, the 3 most common complications were need for endodontic treatment (3%), porcelain veneer fracture (3%), and loss of retention (2%). When fixed partial denture studies were reviewed, the 3 most commonly reported complications were caries (18% of abutments), need for endodontic treatment (11% of abutments), and loss of retention (7% of prostheses). The 3 most common complications associated with resin-bonded prostheses were prosthesis debonding (21%), tooth discoloration (18%), and caries (7%). (J Prosthet Dent 2003;90:31-41.) A complication has been defined 1 as “a secondary disease or condition developing in the course of a primary disease or condition.” Although complications may be an indication that clinical failure has occurred, this is not typically the case. It is also possible that complications may reflect substandard care. But once again, this is usually not true. Most of the time, complications are conditions that occur during or after appropriately performed fixed prosthodontic treatment procedures. Knowledge regarding the clinical complications that can occur in fixed prosthodontics enhances the clinician’s ability to complete a thorough diagnosis, develop the most appropriate treatment plan, communicate realistic expectations to patients, and plan the time intervalsneededforpost-treatmentcare.Althoughaplethora of articles present clinical complications data, none provide a comprehensive comparison of the complications associated with the most commonly used restorations/

Immediate placement and provisionalization of maxillary anterior single implants: 1-year prospective study.

Abstract: Purpose This 1-year prospective study evaluated the implant success rate, peri-implant tissue response, and esthetic outcome of immediately placed and provisionalized maxillary anterior single implants. Materials and methods Thirty-five patients (8 men, 27 women) with a mean age of 36.5 years (range 18 to 65) were included in this study. Thirty-five threaded, hydroxyapatite-coated implants were placed and provisionalized immediately after each failing tooth had been removed. The definitive restoration was placed 6 months later. The patients were evaluated clinically and radiographically at implant placement and at 3, 6, and 12 months after implant placement. Results At 12 months, all implants remained osseointegrated. The mean marginal bone change from the time of implant placement to 12 months was -0.26 +/- 0.40 mm mesially and -0.22 +/- 0.28 mm distally. No significant differences in the Plaque Index scores were noted at different time intervals. The mean midfacial gingival level and mesial and distal papilla level changes from pretreatment to 12 months were -0.55 +/- 0.53 mm, -0.53 +/- 0.39 mm, and -0.39 +/- 0.40 mm, respectively. All patients were very satisfied with the esthetic outcome and none had noticed any changes at the gingival level. Discussion Although marginal bone and gingival level changes were statistically significant from pretreatment to 12 months of follow-up, they were well within clinical expectations. Conclusion The results of this study suggest that favorable implant success rates, peri-implant tissue responses, and esthetic outcomes can be achieved with immediately placed and provisionalized maxillary anterior single implants.

Is It Time for Clinicians to Routinely Track Patient Outcome? A Meta‐Analysis

Abstract: Empirically supported psychotherapies, treatment guidelines, best practices, and treatment manuals are methods proposed to enhance treatment outcomes in routine practice. Patient-focused research systems provide a compatible and contrasting methodology. Such systems monitor and feed back information about a patient's progress during psychotherapy for the purpose of enhancing outcomes. A meta-analytic review of three large-scale studies is summarized and suggests that formally monitoring patient progress has a significant impact on clients who show a poor initial response to treatment. Implementation of this feedback system reduced deterioration by 4% to 8% and increased positive outcomes. Our interpretation of these results suggests that it may be time for clinicians routinely and formally to monitor patient treatment response.

Television watching and soft drink consumption: associations with obesity in 11- to 13-year-old schoolchildren.

Abstract: Objectives: To determine the prevalence of obesity among sixth- and seventh-grade students in a schoolbased setting, and to identify lifestyle parameters associated with obesity. Methods: Sixth- and seventh-grade students (n=385, 186 boys and 199 girls) from 3 schools participated in a school-based screening study, and 319 completed a short questionnaire. Height and weight were measured, and body fat as a percentage of body weight was obtained using a Tanita bioelectrical impedance scale. Results: Overall, 35.3% of students had a body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) at or above the 85th percentile, and half these students (17.4%) had a BMI at or above the 95th percentile. Rates were higher among Latino and lower among Asian than non-Hispanic white students. Significant associations were found between BMI and hours of television watched per evening and daily soft drink consumption. The mean (SE) BMI z score for those watching less than 2 hours per night (0.34 [0.09]) was lower than for those watching 2 or more hours per night (0.82 [0.08];P.001). The mean (SE) BMIz score for those consuming less than 3 soft drinks per day (0.51 [0.07]) was lower than for those consuming 3 or more soft drinks per day (1.02 [0.13]; P=.003). Latino students watched more television (2.4 hours per night) than did non-Hispanic white or Asian students (1.3 hours per night;P.001 for each) and consumed more soft drinks (1.6 per day) than non-Hispanic white students (1.1 per day; P=.004) or Asian students (0.7 per day; P.001). Conclusions: Time spent watching television and the number of soft drinks consumed were significantly associated with obesity. Latinos spent more time watching television and consumed more soft drinks than did non-Hispanic white or Asian students. These findings will be beneficial in developing preventive measures for these children.

Hemorrhagic Shearing Lesions in Children and Adolescents with Posttraumatic Diffuse Axonal Injury: Improved Detection and Initial Results

Abstract: PURPOSE: To compare the effectiveness of a high-spatial-resolution susceptibility-weighted (SW) magnetic resonance (MR) imaging technique with that of a conventional gradient-recalled-echo (GRE) MR imaging technique for detection of hemorrhage in children and adolescents with diffuse axonal injury (DAI). MATERIALS AND METHODS: Seven young patients with a mean Glasgow Coma Scale score of 7 ± 4 (SD) at admission were imaged a mean of 5 days ± 3 after injury. High-spatial-resolution three-dimensional GRE imaging performed with postprocessing by using a normalized phase mask was compared with conventional GRE MR imaging. The total and mean values of lesion number and apparent hemorrhage volume load determined with both examinations were compared. Mean values were compared by using paired t test analysis. Differences were considered to be significant at P ≤ .05. RESULTS: Hemorrhagic lesions were much more visible on SW MR images than on conventional GRE MR images. SW MR imaging depicted 1,038 hemorrhagic DAI l...

Microduplication 22q11.2, an Emerging Syndrome: Clinical, Cytogenetic, and Molecular Analysis of Thirteen Patients

Abstract: Chromosome 22, particularly band 22q11.2, is predisposed to rearrangements due to misalignments of low-copy repeats (LCRs). DiGeorge/velocardiofacial syndrome (DG/VCFS) is a common disorder resulting from microdeletion within the same band. Although both deletion and duplication are expected to occur in equal proportions as reciprocal events caused by LCR-mediated rearrangements, very few microduplications have been identified. We have identified 13 cases of microduplication 22q11.2, primarily by interphase fluorescence in situ hybridization (FISH). The size of the duplications, determined by FISH probes from bacterial artificial chromosomes and P1 artificial chromosomes, range from 3–4 Mb to 6 Mb, and the exchange points seem to involve an LCR. Molecular analysis based on 15 short tandem repeats confirmed the size of the duplications and indicated that at least 1 of 15 loci has three alleles present. The patients’ phenotypes ranged from mild to severe, sharing a tendency for velopharyngeal insufficiency with DG/VCFS but having other distinctive characteristics, as well. Although the present series of patients was ascertained because of some overlapping features with DG/VCF syndromes, the microduplication of 22q11.2 appears to be a new syndrome.

ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses

Abstract: Exposure to genotoxic agents is a major cause of human cancer, and cellular responses to genotoxic stress are important defense mechanisms. These responses are very complex, involving many cellular factors that form an extensive signal transduction network. This network includes a protein kinase cascade that connects the detection of DNA damage to the activation of transcription factors, which in turn regulate the expression of genes involved in DNA repair, cell cycle arrest and programmed cell death (apoptosis). The mitogen-activated protein kinases are the best-studied members of the kinase cascade with an acknowledged role in the genotoxic stress response. However, the initial activation of the protein kinase cascade is not fully understood, although several protein kinases, such as ataxia telangiectasia, mutated (ATM), ATM- and Rad3-related (ATR), and DNA-dependent protein kinase (DNA-PK) in humans, are increasingly recognized for their potential roles in the sensing of DNA damage and initiating the subsequent protein kinase cascade. In this review, the properties of these three kinases are discussed and their functions in the initiation of the genotoxic stress response are explored.

Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens.

Abstract: Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs) This study determines whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach to cancer detection and diagnosis The mini-array of TAAs comprised full-length recombinant proteins expressed from cDNAs encoding c-myc, p53, cyclin B1, p62, Koc, IMP1, and survivin Enzyme immunoassay was used to detect antibodies in 527 sera from six different types of cancer Antibody frequency to any individual TAA was variable but rarely exceeded 15-20% With the successive addition of TAAs to a final total of seven antigens, there was a stepwise increase of positive antibody reactions up to a range of 44-68% Breast, lung, and prostate cancer patients showed separate and distinct profiles of reactivity, suggesting that uniquely constituted antigen mini-arrays might be developed to distinguish between some types of cancer Distinct antibody profiles were not observed in gastric, colorectal, and hepatocellular carcinomas with this set of seven TAAs Detection of autoantibodies in cancer can be enhanced by using a mini-array of several TAAs as target antigens Additional studies in early cancer patients and high-risk individuals and the design of unique antigen panels for different cancers would help to determine whether multiple antigen mini-arrays for the detection of autoantibodies might contribute a clinically useful noninvasive approach to cancer detection and diagnosis

Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor.

Abstract: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal proliferation of transformed myofibroblasts, with a prominent inflammatory cell component, that can mimic other spindle cell processes such as nodular fasciitis, desmoid tumor, and gastrointestinal stromal tumor. Genetic analyses have recently demonstrated rearrangements of anaplastic lymphoma kinase (ALK), located at 2p23, in a subset of IMTs. Molecular characterizations have identified ALK fusions involving tropomyosin-3 and -4 (TPM-3 and -4), the clathrin heavy chain (CLTC), and the cysteinyl-tRNA synthetase (CARS) genes as fusion partners. Here we describe two IMTs with a novel ALK fusion that involves the Ran-binding protein 2 (RANBP2) gene at 2q13, which normally encodes a large (358-kDa) nucleopore protein localized at the cytoplasmic side of the nuclear pore complex. The N-terminal 867 residues of RANBP2 are fused to the cytoplasmic segment of ALK in the 1,430-amino acid RANBP2-ALK chimeric protein. Myofibroblasts that express RANBP2-ALK exhibit nuclear membrane-associated ALK staining that is unique compared to the subcellular localization observed with other ALK fusions in IMT, presumably attributable to heteroassociation of the fusion with normal RANBP2 at the nuclear pore. These findings expand the spectrum of ALK abnormalities observed in IMT and further confirm the clonal, neoplastic nature of these lesions.

Understanding soft drink consumption among female adolescents using the theory of planned behavior

Abstract: This study identified factors that influence regular soda consumption among 707 female students, aged 13-18 years, attending North Los Angeles County public high schools. Participants completed a group-administered Theory of Planned Behavior-based questionnaire. Almost all of the participants, 96.3%, reported that they currently drink soda; 50.1% reported drinking 2 glasses of soda or more per day during the past year. Students reported drinking regular soda more than diet soda and reported drinking phosphoric acid-containing soda more than non-phosphoric acid-containing soda. Attitude, subjective norm and perceived behavioral control had statistically significant positive associations with intention, and were each significant predictors of intention to drink regular soda and together explained 64% of its variance. The strongest predictor was attitude, followed by perceived behavioral control and subjective norm. Our results suggest that efforts to reduce soda consumption among female adolescents should include parents and friends. It is also important that soda should not be excessively available at home or widely accessible to teenagers at schools. Healthy eating messages for adolescents need to be developed and incorporated into existing and future campaigns to reinforce the perception that there are other healthier drinks that quench thirst and that taste good as well.

Possible mechanisms underlying pregnancy-induced changes in uterine artery endothelial function

Abstract: The last 10 years has seen a dramatic increase in our understanding of the mechanisms underlying the pregnancy-specific adaptation in cardiovascular function in general and the dramatic changes that occur in uterine artery endothelium in particular to support the growing fetus. The importance of these changes is clear from a number of studies linking restriction of uterine blood flow (UBF) and/or endothelial dysfunction and clinical conditions such as intrauterine growth retardation (IUGR) and/or preeclampsia in both humans and animal models; these topics are covered only briefly here. The recent developments that prompts this review are twofold. The first is advances in an understanding of the cell signaling processes that regulate endothelial nitric oxide synthase (eNOS) in particular (Govers R and Rabelink TJ. Am J Physiol Renal Physiol 280: F193-F206, 2001). The second is the emerging picture that uterine artery (UA) endothelial cell production of nitric oxide (NO) as well as prostacyclin (PGI2) may be as much a consequence of cellular reprogramming at the level of cell signaling as due to tonic stimuli inducing changes in the level of expression of eNOS or the enzymes of the PGI2 biosynthetic pathway (cPLA2, COX-1, PGIS). In reviewing just how we came to this conclusion and outlining the implications of such a finding, we draw mostly on data from ovine or human studies, with reference to other species only where directly relevant.

An evidence-based medicine approach to the evaluation of the role of exogenous risk factors in sporadic amyotrophic lateral sclerosis.

Abstract: An evidence-based medicine approach was applied to evaluate analytic studies of exogenous risk factors for amyotrophic lateral sclerosis (ALS) published since 1991. Classification systems for evaluating the literature and for drawing conclusions based on the class of available evidence were developed, modeled on those used by national societies. Considerations regarding the impact on the general public of confirming a role for putative risk factors were made explicit. There was evidence in support of smoking being a probable (‘more likely than not’) risk factor for ALS. Smoking has broad public health impact, no redeeming features, and is a modifiable risk factor. Evidence supported the conclusion that the following were probably not risk factors for ALS: trauma, physical activity, residence in rural areas and alcohol consumption. Evidence-based medicine methodology does not permit calculation of the magnitude of type I or type II errors in drawing these conclusions. New evidence may change these conclusions. Recommendations for future research include: draw on clinical trial methodology in designing future, confirmatory, case-control studies; consider utilizing cohort studies, recognizing the longer timelines for these to come to fruition; accord priority to investigating putative risk factors with greatest public health impact. Advances in study methodology may lead to development of finite research cycles for individual putative risk factors for sporadic ALS.

Almonds vs complex carbohydrates in a weight reduction program.

Abstract: OBJECTIVE: To evaluate the effect of an almond-enriched (high monounsaturated fat, MUFA) or complex carbohydrate-enriched (high carbohydrate) formula-based low-calorie diet (LCD) on anthropometric, body composition and metabolic parameters in a weight reduction program. DESIGN: A randomized, prospective 24-week trial in a free-living population evaluating two distinct macronutrient interventions on obesity and metabolic syndrome-related parameters during weight reduction. SUBJECTS: In total, 65 overweight and obese adults (age: 27–79 y, body mass index (BMI): 27–55 kg/m2). INTERVENTION: A formula-based LCD enriched with 84 g/day of almonds (almond-LCD; 39% total fat, 25% MUFA and 32% carbohydrate as percent of dietary energy) or self-selected complex carbohydrates (CHO-LCD; 18% total fat, 5% MUFA and 53% carbohydrate as percent of dietary energy) featuring equivalent calories and protein. MAIN OUTCOME MEASUREMENTS: Various anthropometric, body composition and metabolic parameters at baseline, during and after 24 weeks of dietary intervention. RESULTS: LCD supplementation with almonds, in contrast to complex carbohydrates, was associated with greater reductions in weight/BMI (−18 vs −11%), waist circumference (WC) (−14 vs −9%), fat mass (FM) (−30 vs −20%), total body water (−8 vs −1%) and systolic blood pressure (−11 vs 0%), P=0.0001–0.05. A 62% greater reduction in weight/BMI, 50% greater reduction in WC and 56% greater reduction in FM were observed in the almond-LCD as compared to the CHO-LCD intervention. Ketone levels increased only in the almond-LCD group (+260 vs 0%, P<0.02). High-density lipoprotein cholesterol (HDL-C) increased in the CHO-LCD group and decreased in the almond-LCD group (+15 vs −6%, P=0.05). Glucose, insulin, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and LDL-C to HDL-C ratio decreased significantly to a similar extent in both dietary interventions. Homeostasis model analysis of insulin resistance (HOMA-IR) decreased in both study groups over time (almond-LCD: −66% and CHO-LCD: −35%, P<0.0001). Among subjects with type 1 diabetes, diabetes medication reductions were sustained or further reduced in a greater proportion of almond-LCD as compared to CHO-LCD subjects (96 vs 50%, respectively). CONCLUSION: Our findings suggest that an almond-enriched LCD improves a preponderance of the abnormalities associated with the metabolic syndrome. Both dietary interventions were effective in decreasing body weight beyond the weight loss observed during long-term pharmacological interventions; however, the almond-LCD group experienced a sustained and greater weight reduction for the duration of the 24-week intervention. Almond supplementation of a formula-based LCD is a novel alternative to self-selected complex carbohydrates and has a potential role in reducing the public health implications of obesity.

Fruits, vegetables and lung cancer: a pooled analysis of cohort studies.

Abstract: Inverse associations between fruit and vegetable consumption and lung cancer risk have been consistently reported. However, identifying the specific fruits and vegetables associated with lung cancer is difficult because the food groups and foods evaluated have varied across studies. We analyzed fruit and vegetable groups using standardized exposure and covariate definitions in 8 prospective studies. We combined study-specific relative risks (RRs) using a random effects model. In the pooled database, 3,206 incident lung cancer cases occurred among 430,281 women and men followed for up to 6-16 years across studies. Controlling for smoking habits and other lung cancer risk factors, a 16-23% reduction in lung cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of consumption for total fruits (RR = 0.77; 95% CI = 0.67-0.87 for quintile 5; p-value, test for trend < 0.001) and for total fruits and vegetables (RR = 0.79; 95% CI = 0.69-0.90; p-value, test for trend = 0.001). For the same comparison, the association was weaker for total vegetable consumption (RR = 0.88; 95% CI = 0.78-1.00; p-value, test for trend = 0.12). Associations were similar between never, past, and current smokers. These results suggest that elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk, which is mostly attributable to fruit, not vegetable, intake. However, we cannot rule out the possibility that our results are due to residual confounding by smoking. The primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation. © 2003 Wiley-Liss, Inc.

pKa Values of Guanine in Water: Density Functional Theory Calculations Combined with Poisson-Boltzmann Continuum-Solvation Model

Abstract: It has long been postulated that rare tautomeric or ionized forms of DNA bases may play a role in mispair formation. To investigate the role this phenomenon plays in the mispairing of guanine and to develop a calculation methodology that can be extended to mutagenic DNA damage products, we used first principles quantum mechanics (density functional theory (B3LYP) with the Poisson−Boltzmann continuum−solvation model) to calculate the relative stabilities of tautomers of guanine in various environments and their pK_a values in aqueous solution. This method allows us to calculate site specific pK_a values — information that is experimentally inaccessible — as well as overall pK_a values for each stage, wherein our numbers are in agreement with experimental values. We find that neutral guanine exists in aqueous phase as a mixture of two major keto tautomers, the N_9H form (1) and a N_7H form (3). These keto forms are also major species present in the gas phase, as well as the O_6H enol tautomer (7a). These results show that tautomeric configurations can be drastically different depending on the environment. Here, we discuss the reasons for this environmental variability and suggest some possible implications. Finally, we estimate that the relative population of deprotonated guanine is 0.2−2% in the range of pH 7−8, a significant enough population to potentially play a role in mispair formation.

Multimodality treatment of giant intracranial arteriovenous malformations.

Abstract: OBJECTIVE Giant arteriovenous malformations (AVMs) (ie, those greater than 6 cm at maximum diameter) are difficult to treat and often carry higher treatment morbidity and mortality rates than do smaller AVMs In this study, we reviewed the treatment, angiographic results, and clinical outcomes in 53 patients with giant AVMs who were treated at Stanford between 1987 and 2001 METHODS The patients selected included 20 males (38%) and 33 females (62%) Their presenting symptoms were hemorrhage (n = 20; 38%), seizures (n = 18; 34%), headaches (n = 8; 15%), and progressive neurological deficits (n = 7; 13%) One patient was in Spetzler-Martin Grade III, 9 were in Spetzler-Martin Grade IV, and 43 were in Spetzler-Martin Grade V The mean AVM size was 68 cm (range, 6-15 cm) AVM venous drainage was superficial (n = 7), deep (n = 20), or both (n = 26) At presentation, 31 patients (58%) were graded in excellent neurological condition, 17 were graded good (32%), and 5 were graded poor (9%) RESULTS The patients were treated with surgery (n = 27; 51%), embolization (n = 52; 98%), and/or radiosurgery (n = 47; 89%) Most patients received multimodality treatment with embolization followed by surgery (n = 5), embolization followed by radiosurgery (n = 23), or embolization, radiosurgery, and surgery (n = 23) Nineteen patients (36%) were completely cured of their giant AVMs, 90% obliteration was achieved in 4 patients (8%), less than 90% obliteration was achieved in 29 patients (55%) who had residual AVMs even after multimodality therapy, and 1 patient was lost to follow-up Of the 33 patients who either completed treatment or were alive more than 3 years after undergoing their most recent radiosurgery, 19 patients (58%) were cured of their AVMs The long-term treatment-related morbidity rate was 15% The clinical results after mean follow-up of 37 months were 27 excellent (51%), 15 good (28%), 3 poor (6%), and 8 dead (15%) CONCLUSION The results in this series of patients with giant AVMs, which represents the largest series reported to date, suggest that selected symptomatic patients with giant AVMs can be treated successfully with good outcomes and acceptable risk Multimodality treatment is usually necessary to achieve AVM obliteration

Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms.

Abstract: To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25-40%, 15-17%, and 8-10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40-55%, 11-18%, and 25-32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms.

Defining the Sudden Infant Death Syndrome

Abstract: Sudden infant death syndrome (SIDS) is a term that was first proposed in 1969 for a distinctive subgroup of unexpected infant deaths that occur during the postneonatal period with relatively consistent clinical, epidemiological, and pathological features. This term played an important role by focusing attention on a major category of postneonatal infant death, providing support to grieving families, and diminishing the guilt and blame characteristic of these deaths. Unfortunately, the application of this term has become increasingly controversial. Some have applied it too liberally, and others not at all. According to the definition proposed in 1969, despite slight changes suggested in 1989, SIDS remains a diagnosis of exclusion. Although this syndrome has several distinctive features, including age distribution and apparent occurrence during sleep, there has been reluctance to include these features in the definition. The problems created by the lack of an adequate definition are discussed. A 2-tiered approach is suggested, with a more general definition intended primarily for case management and death administration, and a more restrictive one intended primarily for research purposes, which distinguishes those deaths closely fitting the classic SIDS profile from those with one or more less typical features.