Human papillomavirus (HPV) in an Icelandic population: correlation of HPV DNA to cyto- and histopathologic lesions and evaluation of treatment strategies

This study is based on 100 cases with cervical intra-epithelial neoplasia (CIN) smears referred for colposcopy and 200 controls with normal smears. The study analyses (a) the frequency of different grades of CIN and koilocytotic lesions among the cases based on cyto- and histopathologic findings; (b) the frequency of human papillomavirus (HPV) among the cases with Virapap/Viratype (V/V) in biopsies vs swabs and among the controls with V/V and polymerase chain reaction (PCR) in swabs; (c) the frequency of the HPV types according to the grade of CIN. Among the cases koilocytotic lesions were found in 98% of the biopsies and 27% of the smears. High-graded smears and high-risk viruses had at entry a positive predictive value (PPV) of 80% and 88% respectively and a sensitivity of 72% for histologically verified high-graded CIN lesions. Both tests combined increased the sensitivity to 88%. The false-negative rate of colposcopy was 3% and the undergraded rate of CIN I and unclassified CIN smears for histologically verified CIN II–III was 62%. Among the cases the rate of HPV positive tests increased with a higher CIN grade. Cytology and colposcopy are complementary for the diagnosis of CIN and the swabs and biopsies for the diagnosis of HPV. Among the cases the rate of HPV-positive tests with V/V was 62% (97% high-risk viruses) and among the controls 5.5% (78% high-risk viruses). Among the controls the frequency of HPV occurrence with PCR was 11.2% and decreased with older age. The therapeutic conclusions are that the high-graded CIN lesions should receive ablative treatment irrespective of HPV typing, whereas low-graded lesions with high-risk viruses should be treated or observed closely.     

Infantile spasms associated with theophylline toxicity

We report on a 6-month-old infant with asthma who developed spasms and hypsarrhythmia on the electroencephalogram (EEG) shortly after starting oral theophylline medication. Theophylline levels at that time were just above the upper normal range. The spasms stopped and the EEG normalized when theophylline was discontinued and nitrazepam therapy started. On follow-up over the next 3 years there was no recurrence of seizures and the chilďs neurodevelopment has been normal. Nitrazepam was stopped at 10 months and the waking and sleeping EEG were normal at 14 months. We believe that the infantile spasms were caused by theophylline.     

The Icelandic and Nordic cervical screening programs: trends in incidence and mortality rates through 1995.

BACKGROUND: The objective of cervical cancer screening is to lower the incidence and mortality rates of the disease. This study evaluates the effectiveness of cervical screening and the UICC and EC screening recommendations based on the Nordic screening experience. METHODS: The study analyzes the features of the Icelandic and the Nordic screening programs and the observed trends in the incidence and mortality rates in these countries through 1995. RESULTS: Organized screening started in all the Nordic countries soon after 1960 and had nation-wide coverage in all these countries, except in Denmark (45% coverage in 1991), by around 1973 but in Norway screening was only spontaneous up to late in 1994. Up to 1985 the target age group and screening interval were most intensive in Iceland, followed by Finland, Sweden and Denmark. All countries except Finland lowered the lower age limit and intensified the screening intervals after 1985. Through the period 1986-1995 the reduction in both the mortality and the incidence rates was greatest in Iceland (mortality: 76% and incidence: 67%) and Finland (73% and 75%, respectively), intermediate in Sweden (60% and 55%, respectively) and Denmark (55% and 54%, respectively), and lowest in Norway (43% and 34%, respectively). The age-specific incidence in the 20-29 age group has been increasing since 1971 in all the Nordic countries, except in Finland, where the yearly registered age-specific incidence has been increasing in the targeted 30-54 age group since 1991. In Iceland screening has greatly affected the rate of all stages of squamous cell carcinoma, but not the rate of adeno- and adenosquamous carcinomas. In fact the rate of adenocarcinoma has been increasing. CONCLUSIONS: Organized screening is more effective than spontaneous screening in reducing the risk of cervical cancer. Although differences in environmental, biological and ethnic factors may call for different screening strategies, screening should preferably start soon after age 20 with a screening interval of 2-3 years.     

Guidelines for the management of traumatic dental injuries. I. Fractures and luxations of permanent teeth

Abstract –  Crown fractures and luxations occur most frequently of all dental injuries. An appropriate treatment plan after an injury is important for a good prognosis. Guidelines are useful for delivering the best care possible in an efficient manner. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the current best evidence, based on literature research and professional opinion. In this first article of three, the IADT Guidelines for management of fractures and luxations of permanent teeth will be presented.     

Guidelines for the management of traumatic dental injuries. II. Avulsion of permanent teeth

Abstract –  Avulsion of permanent teeth is the most serious of all dental injuries. The prognosis depends on the measures taken at the place of accident or the time immediately after the avulsion. Replantation is the treatment of choice, but cannot always be carried out immediately. An appropriate emergency management and treatment plan is important for a good prognosis. Guidelines are useful for delivering the best care possible in an efficient manner. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases in which the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the current best evidence based on literature research and professional opinion. In this second article of three, the IADT Guidelines for management of avulsed permanent teeth are presented.     

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration

BACKGROUND: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1). METHOD: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis. RESULTS: Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm. CONCLUSIONS: The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.     

Intra-individual change over time in DNA methylation with familial clustering

Hans T. Bjornsson, MD, PhD; Martin I. Sigurdsson, MD; M. Daniele Fallin, PhD; Rafael A. Irizarry, PhD; Thor Aspelund, PhD; Hengmi Cui, PhD; Wenqiang Yu, PhD; Michael A. Rongione, BA; Tomas J. Ekström, PhD; Tamara B. Harris, PhD; Lenore J. Launer, PhD; Gudny Eiriksdottir, PhD; Mark F. Leppert, MD; Carmen Sapienza, PhD; Vilmundur Gudnason, MD, PhD; Andrew P. Feinberg, MD, MPH

JAMA. 2008;299(24):2877-2883.

Context  Changes over time in epigenetic marks, which are modifications of DNA such as by DNA methylation, may help explain the late onset of common human diseases. However, changes in methylation or other epigenetic marks over time in a given individual have not yet been investigated.

Objectives  To determine whether there are longitudinal changes in global DNA methylation in individuals and to evaluate whether methylation maintenance demonstrates familial clustering.

Design, Setting, and Participants  We measured global DNA methylation by luminometric methylation assay, a quantitative measurement of genome-wide DNA methylation, on DNA sampled at 2 visits on average 11 years apart in 111 individuals from an Icelandic cohort (1991 and 2002-2005) and on average 16 years apart in 126 individuals from a Utah sample (1982-1985 and 1997-2005).

Main Outcome Measure  Global methylation changes over time.

Results  Twenty-nine percent of Icelandic individuals showed greater than 10% methylation change over time (P < .001). The family-based Utah sample also showed intra-individual changes over time, and further demonstrated familial clustering of methylation change (P = .003). The family showing the greatest global methylation loss also demonstrated the greatest loss of gene-specific methylation by a separate methylation assay.

Conclusion  These data indicate that methylation changes over time and suggest that methylation maintenance may be under genetic control.