OBJECTIVE: To follow the clinical course of patients with the mitochondrial DNA mutation 3243A>G for 3 years. METHODS: Thirty-three adult patients with the 3243A>G mutation entered a 3-year follow-up study. They were clinically evaluated annually, audiometry was performed, and samples were drawn for the analysis of blood chemistry and mutation heteroplasmy in leukocytes. Holter recording was performed three times during the follow-up and echocardiography, neuropsychological assessment, and quantitative EEG and brain imaging conducted at entry and after 3 years. RESULTS: The incidence of new neurologic events was low during the 3-year follow-up. Sensorineural hearing impairment (SNHI) progressed, left ventricular wall thickness increased, mean alpha frequency in the occipital and parietal regions decreased, and the severity of disease index (modified Rankin score) progressed significantly. The rate of SNHI progression correlated with mutation heteroplasmy in muscle. The increase in left ventricular wall thickness was seen almost exclusively in diabetic patients. Seven patients died during the follow-up, and they were generally more severely affected than those who survived. CONCLUSIONS: Significant changes in the severity of disease, sensorineural hearing impairment, left ventricular hypertrophy, and quantitative EEG were seen in adult patients with 3243A>G during the 3-year follow-up.
Comment In: Neurology. 2007 Jan 9;68(2):163-417210904
To compare men with prostate disease with those from the general population regarding polymorphisms in the androgen receptor gene and in the 5alpha-reductase II (SRD5A2) gene.
The SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n=89), benign prostate hyperplasia (n=45) and healthy military conscripts (n=223).
The SRD5A2 high-activity allele variants A49T AT and V89L LL were more frequent in CaP-patients compared to general population, p=0.026 and p=0.05, respectively. CaP progression was, however, independent of SRD5A2 variants. In contrary, men with GGN
The prospects for the treatment of metastatic melanoma are improving. Whereas previous scientific meetings dedicated to the treatment of metastatic melanoma patients were overshadowed by our inability to improve overall survival or lengthen the time to progression, the results presented at the most recent meetings are hopeful. The 5th Canadian Melanoma Conference held on 24-27 February in Banff (AB, Canada) was nothing short of optimistic. This year's meeting was divided into three themes: basic science and pathology, dermatology and surgery, and immunology and systemic treatment. In addition, dermoscopy case studies were presented, and Hoffmann la Roche sponsored a symposium on the evaluation of treatment for advanced melanoma. It underscored the importance of early detection and patient stratification, based upon the molecular profile of the tumor, in order to optimize the response to targeted therapy.
To investigate, in a population-based cohort of patients with juvenile chronic arthritis (JCA), onset characteristics, progression, outcome, and prognostic factors longitudinally for 5 years.
This cohort consisted of 132 incidence cases identified between 1984 and 1986 in southwestern Sweden followed for 5 years with annual reports of subgroup, joint assessment, disease activity, eye examinations, laboratory measurements, and medication. At the 5-year follow-up, the Childhood Health Assessment Questionnaire (Child-HAQ) was evaluated. European League Against Rheumatism (EULAR) criteria for diagnosis and disease activity were used.
During the 5 years only four patients were lost to follow-up, 34% changed subgroup and 8% developed uveitis. At the 5-year follow-up the disease was active in 12% of the patients, stable in 28%, inactive in 25%, and in remission in 34%. Among those examined, 24% had radiological changes, of whom half had advanced changes. The Child-HAQ median score at the 5-year follow-up was 0.13 (range 0.0-1.9). The number of involved joints at inclusion correlated positively with active disease at the 5-year follow-up. Age at disease onset, the number of involved joints, and the number of joints with arthritis correlated positively with continuous disease and Child-HAQ score. CONCLUSION. Our study shows a diverse disease course during the first 5 years of JCA where one-third changed subgroup and two-thirds did not reach remission. Age of disease onset, the number of involved joints, and the number of joints with arthritis at inclusion were associated with poor outcome at the 5-year follow-up.
PURPOSE: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T(1-4p)N(0)M(0) prostate cancer patients provided by a single institution between 1989 and 1996. METHODS AND MATERIALS: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. RESULTS: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T(3-4) or Gleason score (GS) > or =7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T(1-2) and GS or =7B.
PURPOSE: To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss. DESIGN: Population-based cohort study. PARTICIPANTS: Nine hundred forty-six residents (age range, 60-80 years) of Copenhagen participated in the study from 1986 through 1988. Excluding participants who had died since baseline, 359 persons (97.3% of survivors) were reexamined from 2000 through 2002. METHODS: Participants underwent extensive ophthalmologic examinations. Age-related maculopathy lesions were determined by grading color fundus photographs from the examinations using a modified Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Incidence of drusen type and size, pigmentary abnormalities, pure geographic atrophy, exudative ARM, visual impairment, and blindness. RESULTS: The 14-year incidences of early and late ARM were 31.5% and 14.8%, respectively. Individuals 75 to 80 years of age at baseline had significantly (P or =125 microm; 34.2% vs. 12.8%, respectively), soft drusen (45.2% vs. 21.4%), pigmentary abnormalities (31.4% vs. 17.0%), pure geographic atrophy (17.4% vs. 1.0%), and exudative ARM (23.3% vs. 5.7%). Severe drusen type, large drusen, and retinal pigmentary abnormalities at baseline were important predictors of incident late ARM. The 14-year incidences of visual impairment (20/200) or legal blindness from late ARM were 6.0% and 3.4%, respectively. Late ARM caused 35.7% of all visual impairment and 66.7% of all blindness. CONCLUSIONS: There is a high incidence of ARM lesions in this elderly white population. Severe drusen type and size or a combination of drusen and pigmentary abnormalities significantly increases the risk of developing late ARM, the most frequent cause of legal blindness in this population.
The 16-year incidence, progression and regression of diabetic retinopathy in a young population-based Danish cohort with type 1 diabetes mellitus: The Danish cohort of pediatric diabetes 1987 (DCPD1987).
The aim was to investigate the long-term incidence of proliferative diabetic retinopathy (PDR), and progression and regression of diabetic retinopathy (DR) and associated risk factors in young Danish patients with Type 1 diabetes mellitus. In 1987-89, a pediatric cohort involving approximately 75 % of all children with Type 1 diabetes in Denmark
17 beta-Hydroxysteroid dehydrogenases (17HSDs) catalyze the interconversions between active 17 beta-hydroxysteroids and less-active 17-ketosteroids thereby affecting the availability of biologically active estrogens and androgens in a variety of tissues. The enzymes have different enzymatic properties and characteristic cell-specific expression patterns, suggesting differential physiological functions for the enzymes. Epidemiological and endocrine evidence indicate that estrogens play a key role in the etiology of breast cancer while androgens are involved in mechanisms controlling the growth of prostatic cells, both normal and malignant. Recently, we have developed, using LNCaP prostate cancer cell lines, a cell model to study the progression of prostate cancer. In the model LNCaP cells are transformed in culture condition to more aggressive cells, able to grow in suspension cultures. Our results suggest that substantial changes in androgen and estrogen metabolism occur in the cells during the process. These changes lead to increased production of active estrogens during transformation of the cells. Data from studies of breast cell lines and tissues suggest that the oxidative 17HSD type 2 may predominate in human non-malignant breast epithelial cells, while the reductive 17HSD type 1 activity prevails in malignant cells. Deprivation of an estrogen response by using specific 17HSD type 1 inhibitors is a tempting approach to treat estrogen-dependent breast cancer. Our recent studies demonstrate that in addition to sex hormone target tissues, estrogens may be important in the development of cancer in some other tissues previously not considered as estrogen target tissues such as colon. Our data show that the abundant expression of 17HSD type 2 present in normal colonic mucosa is significantly decreased during colon cancer development.
The objective was to perform a long-term follow-up study of patients that had received high cost dental care within the Swedish National Dental Insurance System in 1977-1978 with special focus on remaining teeth, periodontal disease progression, change in the prevalence of root-filled teeth and teeth with apical periodontitis as well as the survival of fixed prosthetic reconstructions. All 262 patients who had had their treatment plans sent for approval for high-cost dental care in 4 local health insurance districts and who were sampled for base-line studies in 1977-1978, were offered a free clinical examination including radiographs in 1998. 177 patients (68 % of the original sample) could be reached for telephone interview and 104 of them (40 % of the original sample) were examined clinically and radiographically. Comparisons were made with records and radiographs from 1977-1978. The analyses were performed with the individual patient as the studied unit. The low progression of severe periodontal disease during the 20-23 year follow-up period and the decrease in number of teeth with apical periodontitis among a majority of the patients examined, indicated that the dental care received resulted in a limitation of dental disease on the individual level. Furthermore 63 % of the patients had the fixed prosthetic reconstructions, received after approval 1977-1978, in full extention after 20-23 years. However, more tooth losses were observed among the patients in this study than in similar studies in Swedish general populations over the same decades. Furthermore multiple tooth extractions were significantly more frequent in patients with severe periodontitis at baseline and in patients with less apical periodontitis at follow-up in this study. Thus it seems that tooth extraction not seldom was a treatment choice for teeth with severe periodontitis and apical periodontitis among the patients examined clinically in this study.