BDNF regulates the expression of fragile X mental retardation protein mRNA in the hippocampus

Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to NT-3, reduced FMR1 mRNA levels to 84.8% of control at 4 h and the levels were back to baseline by 24 h or 4 days. Furthermore, expression of FMR1 mRNA was reduced (82.4% of control) in vivo in the hippocampus of transgenic mice overexpressing TrkB receptors, and a small but significant (5.1%) decrease was also detected in FMRP protein levels. In contrast, the expression patterns of BDNF and TrkB mRNAs were not altered in FMRP-deficient mice compared to wild-type mice. Our data provide evidence that BDNF via TrkB signaling decreases FMRP expression and suggest a role for FMRP in BDNF-induced synaptic plasticity.     

Evidence of benefit from centralised treatment of ovarian cancer: a nationwide population-based survival analysis in Finland

To assess the effect of different hospital types or surgical volume on the survival of ovarian cancer patients, a nationwide and population-based analysis was carried out in Finland. The study included all 3,851 ovarian cancer patients operated from 1983-94. The patients were classified according to the hospital of the first surgery. The hospitals were categorized by type (university, central or other hospital) and, separately, into quartiles by the number of operated patients (surgical volume). The patients operated at university hospitals had better survival than those operated in central hospitals, the 5-year relative survival rates (RSR) being 45% (95% CI = 42-48%) and 37% (34-40%), respectively. RSR in the 'other hospital' category was 45% (42-48%). The RSR for the patients operated in the highest volume hospitals was 47% (43-50%), and by decreasing volume (quartile) the RSR was 40% (36-43%), 40% (36-43%) and 42% (38-45%), respectively. After controlling for potential confounding by stage and age using regression models, the results remained practically the same. The results indicate that further centralizing of operative treatment of ovarian cancer may still improve survival rates on a population level in Finland.     

Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease

BACKGROUND: Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use. METHODS: Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided. RESULTS: Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment. CONCLUSIONS: Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.     

p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer.

PURPOSE: Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used. EXPERIMENTAL DESIGN: Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing. RESULTS: Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion. CONCLUSIONS: p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues.     

Risk of cervical cancer subsequent to a positive screening cytology: follow-up study in Finland

BACKGROUND: The purpose of the study was to estimate subsequent incidence of cervical cancer among women with positive cytology followed by negative histology. METHODS: This was a longitudinal cohort study involving about 80,000 women with class II, III, IV or V cytology at the organized mass screening in Finland in 1971 1990. Follow-up through the Finnish Cancer Registry started from the fifth month following the initial screening and ended on December 31, 1995. RESULTS: Standardized incidence ratios (SIR) of invasive cervical cancer varied from 2.2 (class II) to 19 (class V), and SIRs of preinvasive lesion varied from 3.0 (class II) to 20 (class V) compared to the risk among the total Finnish female population of same age and calendar period. The relative risk was greatest during first years of follow-up for both preinvasive and invasive cervical lesions, and it remained significantly high over 5 years of follow-up. For women with class II cytology there were peaks in relative risk in the years of subsequent rescreenings. CONCLUSION: Women with positive cytology have a high relative risk of cervical cancer even when excluding the cancers found at screening; the high relative risk is persistent for more than 5 years, and therefore these women should be kept under close surveillance and repeated smears should be taken with relatively short intervals.     

The Need for Treatment and Satisfaction with Dental Appearance among Young Finnish Adults with and without a History of Orthodontic Treatment

The aim of this investigation was to evaluate orthodontic treatment need and patient satisfaction among young adults living in a city where free-of-charge orthodontic treatment was provided. A total of 281 18- to 19-year-old subjects randomly selected from the population register of the city of Vantaa took part in the study. The drop-out rate was 30%. Treatment need was clinically assessed according to the Index of Orthodontic Treatment Need (IOTN), consisting of a Dental Health Component (DHC) and an Aesthetic Component (AC). Information on previous orthodontic treatment was based on the patient records. Satisfaction of the subjects with their dental appearance and with the orthodontic treatment received was obtained using a questionnaire. The rate of orthodontic treatment among the subjects was 46% (54% for the females and 37% for the males, p < 0.05). 4% had discontinued treatment. A definite need for treatment (DHC 4 to 5/AC 8 to 10) was assessed in 15% of the subjects, and borderline/moderate need (DHC 3/AC 5 to 7) in 36%. No difference in IOTN scores between the treated and untreated subjects was found. Females had significantly more often no treatment need (DHC 1 to 2/AC 1 to 4) compared with males (p < 0.05). The majority of subjects (89%) reported that they were very or quite satisfied with their dental appearance. The odds of being satisfied were significantly higher for the treated subjects (OR = 2.71, p < 0.05) and lower for those at the non-attractive end of the AC scale (OR = 0.14, p < 0.01). Neither gender nor DHC grade significantly affected the odds of being satisfied among the subjects. The results indicate that the majority of young adults in this study were satisfied with their dental appearance regardless of objective treatment need of various degrees. The high treatment rate in relation to unnoticed treatment need calls for reevaluation of priorities in patient selection. Zusammenfassung: Ziel dieser Untersuchung war es, den kieferorthopädischen Behandlungsbedarf und die Zufriedenheit junger Erwachsener zu bewerten, die in einer Stadt leben, in der eine kostenlose kieferorthopädische Behandlung angeboten wurde. Insgesamt nahmen an dieser Studie 281 18- bis 19-jährige Personen teil, die nach dem Zufallsprinzip aus dem Bevölkerungsverzeichnis der Stadt Vantaa ausgewählt wurden. Die Ausfallsrate betrug 30%. Der Behandlungsbedarf wurde gemäß dem "Index of Orthodontic Treatment Need" (IOTN) bewertet, der sich aus dem "Dental Health Component" (DHC) und einem "Aesthetic Component" (AC) zusammensetzt. Anamnestische Daten der Patienten gaben Aufschluss über eine vorangegangene kieferorthopädische Behandlung. Die Zufriedenheit der Personen mit dem ästhetischen Erscheinungsbild ihrer Zähne und mit der kieferorthopädischen Behandlung wurde mittels eines Fragebogens festgestellt. Der Anteil der Personen mit kieferorthopädischer Behandlung betrug 46% (54% Frauen und 37% Männer, p < 0,05). 4% hatten die Behandlung abgebrochen. Ein eindeutiger Behandlungsbedarf (DHC 4 bis 5/AC 8 bis 10) wurde bei 15% der Untersuchten festgestellt, ein grenzwertiger/mäßiger Behandlungsbedarf (DHC 3/AC 5 bis 7) bestand bei 36%. Bei den behandelten und unbehandelten Personen stellte man keinen Unterschied bei den IOTN-Kriterien fest. Bei Frauen bestand wesentlich seltener Behandlungsbedarf (DHC 1 bis 2/AC 1 bis 4) als bei Männern (p < 0,05). Die Mehrheit der Untersuchten (89%) sagte aus, dass sie mit dem ästhetischen Erscheinungsbild ihrer Zähne sehr oder ziemlich zufrieden wären. Die Zufriedenheitsrate war bei den behandelten Personen deutlich höher (OR = 2,71, p < 0,05) und niedriger bei denen, die am unattraktiven Ende der AC-Skala standen (OR = 0,14, p < 0,01). Weder das Geschlecht noch der DHC-Grad beeinflusste signifikant die Zufriedenheitsrate der Untersuchten. Das Ergebnis deutet darauf hin, dass die Mehrheit der jungen Erwachsenen dieser Studie, unabhängig von einem objektiven Behandlungsbedarf verschiedenen Ausmaßes, mit ihrer dentalen Ästhetik zufrieden war. Die hohe Behandlungsquote in Beziehung zu einem nicht begründeten Behandlungsbedarf erfordert eine Neueinschätzung der Prioritäten bei der Auswahl der Patienten.     

Comparison of Swanson and Sutter metacarpophalangeal arthroplasties in patients with rheumatoid arthritis: a prospective and randomized trial

PURPOSE: To perform a prospective and randomized comparison of the clinical outcome of patients with rheumatoid arthritis who had Swanson or Sutter implant replacement arthroplasty of the metacarpophalangeal joints. METHODS: There were 45 patients (3 men, 42 women) and 49 hands; a total of 75 Swanson and 99 Sutter implants were inserted. The mean time between surgery and the final follow-up control visit was 58 months (range, 37-80 mo). Preoperative and postoperative measurements were performed including active extension and flexion, correction of ulnar deviation, and strength. RESULTS: There was no statistically significant difference between groups with regard to active extension deficit correction. Mean active flexion decreased less in the Sutter group than in the Swanson group but difference between the groups was statistically significant in only the index finger. At the final follow-up examination no significant differences existed between the groups in the correction of ulnar deviation or arc of motion. Grip strengths, chuck pinch, and thump-to-fingertip grip strengths did not improve in either of the groups. CONCLUSIONS: In this study clinical results showed no significant difference between the groups with the single exception of the amount of index finger metacarpophalangeal joint flexion.