Scandinavian Fellowship for Oral Pathology and Oral Medicine: guidelines for oral pathology and oral medicine in the dental curriculum.

In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral pathology and oral medicine in the European Dental Curriculum.

BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD. METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD. RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation. PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.

Preoperative clinical evaluation, outline of surgical technique and outcome in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy. The mechanisms of epileptogenesis and seizure semiology of the mesial and neocortical temporal lobe epilepsy are discussed. The evaluation and selection of patients for TLE surgery requires team work: the different clinical aspects of neuropsychological evaluation, magnetic resonance and functional imaging (positron emission tomography, single photon emission computed tomography and magnetoenephalography) are reviewed. In our programme of epilepsy surgery at Kuopio University Hospital, Finland, we have performed 230 temporal resections from 1988 until 2002. Preoperative diagnostic EEG-videotelemetry often required intracranial monitoring and it has proved to be safe and efficient. The indications and technique for tailored temporal lobe resection with amygdalohippocampectomy used in our institution, as well as the complications, are described. Our analysis of outcome after temporal lobe surgery included 140 consecutive adult patients between 1988 and 1999; one year after the operation in unilateral TLE the Engel I-II outcome was observed in 68% of the patients. Outcome of surgery improved significantly after introduction of the standardised MR imaging protocol from 1993; 74% of patients with unilateral TLE achieved Engel I-II outcome.

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients.

OBJECTIVE: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. METHODS: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. RESULTS: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p < or = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome. CONCLUSIONS: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts.

BACKGROUND: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. OBJECTIVE: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. METHODS: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous for a loss-of-function mutation in the DAP12 gene. RESULTS: In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on T2-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. CONCLUSIONS: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.

Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses.

Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.

Human papillomavirus infections in children: the potential role of maternal transmission.

To date, more than 100 types of human papillomavirus (HPV) have been identified. In the past 20 years, there has been an increasing interest in HPVs because of their potential role in the pathogenesis of malignant tumors. HPV infections are known to affect predominantly adult, sexually active age groups, whereas skin warts, at various anatomic sites, are usually associated with younger individuals. The modes of viral transmission in children remain controversial, including perinatal transmission, auto- and hetero-inoculation, sexual abuse, and, possibly, indirect transmission via fomites. Recent studies on perinatal infection with HPV have been inconclusive. It is still unclear how frequently perinatal infection progresses to clinical lesions, whether genital, laryngeal, or oral. Conflicting reports have been published on the prevalence of HPV infections in children. The current consensus is, however, that newborn babies can be exposed to cervical HPV infection of the mother. The detection rate of HPV DNA in oral swabs of newborn babies varies from 4% to 87%. The concordance of HPV types detected in newborn babies and their mothers is in the range of 57% to 69%, indicating that the infants might acquire the HPV infection post-natally from a variety of sources. HPV antibodies have been detected in 10% to 57% of the children, and there is usually no correlation between seropositivity and the detection of HPV DNA in either the oral or the genital mucosa. There is also evidence that transmission in utero or post-natal acquisition is possible. The mode of in utero transmission remains unknown, but theoretically the virus could be acquired hematogenously, by semen at fertilization, or as an ascending infection in the mother. The understanding of viral transmission routes is important, particularly because several vaccination programs are being planned worldwide. The serologic response to HPV detected in different populations of young women or women at risk of cervical cancer might be due to genital infections, but the possibility that HPV infection has been acquired earlier in life through the oral mucosa or respiratory tract cannot be ruled out.

Risk of harboring an unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: The purpose of the present study was to calculate the prevalence and relative risk of unruptured incidental intracranial aneurysms (IAs) among families with IA case(s) compared with the general population in one geographically defined area in East Finland and to identify the risk group that could benefit most from screening for IAs. We compared these results with our earlier study results of familial IA (FIA) cases, with two or more known IA cases in the same family. METHODS: The study groups were collected from the catchment area of the University Hospital of Kuopio in East Finland. The inclusion criteria were age 30 to 70 years and unruptured incidental IAs > or =3 mm. Patients with previous subarachnoid hemorrhage or in whom a ruptured IA was found to be the cause of death were excluded from all study groups. During routine forensic autopsies the circle of Willis was studied for IAs to estimate the number of IAs in the general population. In the families with one known IA case and in FIA families, MR angiography was used as a preliminary screening method for IAs, followed by intra-arterial angiography to verify suspected IAs. Study populations were age and sex adjusted for the statistical calculations. RESULTS: The relative risk for IAs among first-degree relatives in FIA families was 4.2 (95% confidence interval, 2.2 to 8.0) and among first-degree relatives in families with only one affected family member was 1.8 (95% confidence interval, 0.7 to 4.8) compared with the general population in East Finland. CONCLUSIONS: First-degree relatives in FIA families constitute a high-risk group for incidental IAs, and this group would benefit from screening studies for IAs. Screening for IAs in families with only one affected member or in the general population is not recommended.

Exposure of an infant to cervical human papillomavirus infection of the mother is common.

OBJECTIVE: The purpose of this study was to determine the potential of exposure of an infant to cervical human papillomavirus infection of the mother. STUDY DESIGN: Cervical scrapes of the mothers and nasopharyngeal aspirate fluids of their infants were analyzed at the time of delivery. The study included 106 infants born by vaginal delivery or by cesarean section and their 105 mothers. Positive results were confirmed and typed by direct deoxyribonucleic acid sequencing or single-strand conformation polymorphism of the polymerase chain reaction product. RESULTS: Both the mother's and her infant's samples were positive for the same type of human papillomavirus in 29 mother-infant pairs. Interestingly, five infants born by cesarean section were found to be human papillomavirus deoxyribonucleic acid positive for the same human papillomavirus type as their mother. The overall concordance between human papillomavirus types in the mother and her newborn was 69% (29/42). Regardless of match in types found in the mother's and her infant's sample, human papillomavirus deoxyribonucleic acid positivity was found in 39 of all the 106 infants (37%). CONCLUSIONS: Our results indicate that the infant of the human papillomavirus-infected mother is exposed to infection even when the cervical infection of the mother is subclinical. The possibility of transplacental exposure has to be considered as well.

Familial intracranial aneurysms.

BACKGROUND: We set out to determine the prevalence of incidental intracranial aneurysms in first-degree relatives aged 30 years or more of people with intracranial aneurysms, and to see if polycystic kidney disease contributes to the aggregation of familial intracranial aneurysms. METHODS: 91 families with two or more affected members had previously been identified from a 14 year series of 1150 intracranial aneurysm patients treated at the University Hospital of Kuopio, Finland. Magnetic resonance angiography was used as a preliminary screening method, followed by conventional four-vessel angiography to verify suspected aneurysms. Participants were also screened for polycystic kidneys by ultrasonography. FINDINGS: Incidental aneurysms were detected in 40 individuals: 38 of 438 individuals from 85 families without polycystic kidney disease or other diagnosed heritable disorders, and two of 22 individuals from six families known to have polycystic kidney disease. The crude and age-adjusted prevalence of incidental intracranial aneurysms among screened first-degree relatives was 8.7 (SE 1.3)% (95% CI 6.2-11.7) and 9.1 (1.4)% (6.2-11.7), respectively, for the familial group and the crude prevalence for the polycystic kidney group was 9.1 (6.1)% (1.1-29.2). INTERPRETATION: Our results demonstrate a high prevalence of incidental intracranial aneurysms among first-degree relatives aged 30 years or older of patients with the condition and indicate that the risk of having an aneurysm is about four times higher for a close relative than for someone from the general population. Also, polycystic kidney disease families are a small fraction of the familial intracranial aneurysm families.

Wooden foreign particles in the orbit--spontaneous recovery.

A six-year-old boy consulted an ophthalmologist, because another boy had hit his right eye with a tree branch. There were slight corneal erosions, and a superficial small wound in the oedematous upper lid. The erosions healed in 2 days, but the lid showed progressive ptosis and oedema. Computed tomography revealed a hyperdense, tight structure, which was suspected to be a foreign particle. An orbital exploration was made three times, but the foreign body was not found. After prolonged suppuration, two wooden particles appeared spontaneously 4 and 5.5 months after the trauma. After that, the suppuration subsided and the wound healed.

Polymerase chain reaction amplification of human papillomavirus DNA from archival, Papanicolaou-stained cervical smears.

OBJECTIVE: To test the applicability of four protocols in recovering DNA suitable for amplification with the polymerase chain reaction (PCR) in archival, Papanicolaou-stained cervical smears. STUDY DESIGN: The most efficient method was used to isolate DNA from 11 archival, Papanicolaou-stained smears with cytopathic changes due to human papillomavirus (HPV) infection to confirm the presence of HPV DNA. RESULTS: beta-Globin was successfully amplified in all smears, while HPV DNA was detected in 6 of 11. Four of the four HPV DNA-negative smears were classified as high grade squamous intraepithelial lesions. Failure to detect HPV DNA might have been due to the low copy number of HPV DNA or deletion of the L1 region. CONCLUSION: High cellularity and the method of recovering DNA from the smear are important determinants of successful amplification of HPV DNA in archival cervical smears.

Magnetic resonance angiographic screening for asymptomatic intracranial aneurysms: the problem of false negatives: technical case report.

To emphasize the limitations of magnetic resonance angiographic screening for intracranial aneurysms, we present the case of a patient with a false-negative screening result, unfortunately advancing to rupture of the aneurysm. An asymptomatic woman underwent magnetic resonance angiographic screening in an investigational setting. Three years later, she had an onset of sudden headache, after which her condition rapidly deteriorated. Severe subarachnoid hemorrhage and an intracerebral hematoma were diagnosed. Conventional angiography detected a small ruptured middle cerebral artery trifurcation aneurysm and two very small aneurysms. There are still limitations in the ability of magnetic resonance angiography to detect small or very small aneurysms. Even small-probability findings should always be confirmed or excluded by conventional angiography.

Vertical transmission of human papillomavirus from infected mothers to their newborn babies and persistence of the virus in childhood.

OBJECTIVE: The purpose of this study was to determine the potential for human papillomavirus to be transmitted vertically. STUDY DESIGN: We started a systematic study of children 0.3 to 11.6 years old born to mothers included in the cohort of 530 women prospectively followed up for genital human papillomavirus infections in Kuopio since 1981. So far 98 children have been examined. The examinations included medical history, clinical examination of the oral cavity and hand warts, and cytologic samples from the oral mucosa for detection of human papillomavirus deoxyribonucleic acid with polymerase chain reaction with subsequent Southern blot hybridization. RESULTS: Human papillomavirus deoxyribonucleic acid was found in 31 of the 98 (31.6%) oral scrapings. with MY09 and MY11 human papillomavirus primers, 12 of the 98 were positive for human papillomavirus deoxyribonucleic acid in the electrophoresis gel and in subsequent hybridization. Nineteen of the positive samples were not visible in the gel but become positive when hybridized. At delivery, 5 mothers had genital human papillomavirus infection with the same virus type found in her child. In the additional 11 mothers genital human papillomavirus infection with the same virus type as in the child was diagnosed a few months before or after delivery. Mothers of the 25 children shown to be negative for oral human papillomavirus were also human papillomavirus deoxyribonucleic acid negative at delivery. Minor hyperplastic growths of the oral mucosa were found in 21 of the 98 children (21%). One child had a papilloma where human papillomavirus 16 deoxyribonucleic acid was detected, as was also found in her mother's genital area at delivery. CONCLUSIONS: Our results support the concept that an infected mother can transmit human papillomavirus to her child.

Transmission of genital human papillomavirus infections is unlikely through the floor and seats of humid dwellings in countries of high-level hygiene.

To evaluate the transmission of genital human papillomavirus (HPV) through the floor and seats of humid dwellings, samples were collected with a toothbrush from the floor and seat surfaces of humid dwellings; showers, saunas and dressing rooms. The survey included 3 bathing resorts, 1 indoor swimming pool, 2 schools and 2 private homes. Polymerase chain reaction (PCR) was used to amplify the human beta-globin gene and HPV DNA. The results for HPV DNA amplification were confirmed by Southern blot hybridization under low stringency using a probe mixture of HPV types 6, 16, 18 and 31. beta-globin could be amplified only from 3 sample taken from a dressing room of and indoor public swimming pool. No HPV DNA-positive samples were found. These results indicate that transmission of genital HPV infection via floor or seat surfaces in the above dwellings in general or family use is highly unlikely.

Intracranial aneurysms: MR angiographic screening in 400 asymptomatic individuals with increased familial risk.

PURPOSE: To evaluate the accuracy and limitations of magnetic resonance (MR) angiographic screening for incidental intracranial aneurysms (IAs) in healthy individuals with a family history of IA. MATERIALS AND METHODS: Four hundred asymptomatic individuals in 68 families with a history of aneurysmal subarachnoid hemorrhage underwent MR angiography. Six families also had a history of polycystic kidney disease. A multislab, three-dimensional, time-of-flight sequence was used. Conventional angiography was performed to confirm positive MR angiographic findings. RESULTS: IAs were detected with MR angiography in 37 individuals, 32 of whom underwent conventional angiography. Intraobserver consistency was excellent (kappa = 0.96), and interobserver reproducibility was good to excellent (kappa = 0.59-0.82). Both techniques showed similar results in the evaluation of size, localization, and orientation of aneurysms and visibility of the aneurysm neck. CONCLUSION: MR angiography is an accurate and feasible method of noninvasive screening for IAs in individuals at high risk. Conventional angiography is still necessary before operative treatment.

Multiple intracranial aneurysms in a defined population: prospective angiographic and clinical study.

Multiple intracranial aneurysms (MIA) have been detected in up to one-third of patients with cerebral aneurysms. Three main external factors influence these figures as follows: the quality of angiographies, the quantity of vessels studied, and referral policy. In a 1-year prospective study, we determined the incidence of MIA in a defined catchment area in East Finland by investigating all of the patients with intracranial aneurysms with panangiography. In 114 unselected patients, a total of 170 intracranial aneurysms were detected, and, of these, 39 (34%) harbored MIA. In contrast to most other reports, there was a male predominance in patients with MIA, and half of these men had hypertension. Intracavernous carotid and pericallosal aneurysms were more frequent in patients with MIA. The number of asymptomatic vertebrobasilar aneurysms was extremely low, and most of the nonruptured aneurysms were found in bilateral carotid angiograms. In spite of the active search, the proportion of vertebrobasilar aneurysms remained at 6%. Although our surgical policy was most active, one-third of the asymptomatic aneurysms remained untreated, mainly because of the poor condition of the patient.