The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.

Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.     

The need for cellular elements during axonal regeneration in the sea lamprey spinal cord.

Spinal axons in the larval sea lamprey regenerate following a complete spinal transection. It is not known whether regenerating growth cones require contact with cellular elements or whether the basement membrane and collagenous meninx primitiva which surround the spinal cord are sufficient for neurite out-growth. To determine this, a freeze lesion was made which severed axons, destroyed neuronal perikarya, and greatly reduced the number of glial cells. After at least 10 weeks of recovery, 50 neurites from 31 Müller and Mauthner axons were labeled by intracellular injection of HRP. Eighty-six percent of these neurites did not regenerate into the lesion site. No neurites grew through the lesion. No animals recovered coordinated swimming. These results suggest that glial and/or neuronal surfaces are required for axonal regeneration. Moreover, a monolayer of glial cells appears to be suboptimal and a three-dimensional matrix of cells may be necessary to promote regeneration in the lamprey spinal cord.     

Retrolisthesis and lumbar disc herniation: a preoperative assessment of patient function.

BACKGROUND CONTEXT: Retrolisthesis is relatively rare but when present has been associated with increased back pain and impaired back function. Neither the prevalence of this condition in individuals with lumbar disc herniations nor its possible relation to preoperative back pain and dysfunction has been well studied. PURPOSE: The purposes of this study were as follows: (1) to determine the prevalence of retrolisthesis (alone or in combination with other degenerative conditions) in individuals with confirmed L5-S1 disc herniation who later underwent lumbar discectomy; (2) to determine if there is any association between retrolisthesis and degenerative changes within the same vertebral motion segment; and (3) to determine the relation between retrolisthesis (alone or in combination with other degenerative conditions) and preoperative low back pain, physical function, and quality of life. STUDY DESIGN/SETTING: Cross-sectional study. PATIENT SAMPLE: A total of 125 individuals were identified for incorporation into this study. All patients had confirmed L5-S1 disc herniation on magnetic resonance imaging (MRI) and later underwent L5-S1 discectomy. All patients were enrolled in the Spine Patient Outcomes Research Trial (SPORT) study; data were obtained from the multi-institutional database comprised of SPORT patients from across the United States. OUTCOME MEASURES: Retrolisthesis, degenerative change on MRI, and Modic changes. METHODS: MRI scans of the lumbar spine were assessed at spinal level L5-S1 for all 125 patients. Retrolisthesis was defined as posterior subluxation of 8% or more. Disc degeneration was defined as any loss of disc signal on T2 imaging. Modic changes were graded 1 to 3 and collectively classified as vertebral endplate degenerative changes. The presence of facet arthropathy and ligamentum flavum hypertrophy was classified jointly as posterior degenerative changes. RESULTS: The overall incidence of retrolisthesis at L5-S1 in our study was 23.2%. Retrolisthesis combined with posterior degenerative changes, degenerative disc disease, or vertebral endplate changes had incidences of 4.8%, 16%, and 4.8% respectively. The prevalence of retrolisthesis did not vary by sex, age, race, smoking status, or education level when compared with individuals with normal sagittal alignment. However, individuals with retrolisthesis were more likely to be receiving workers' compensation than those without retrolisthesis. Increased age was found to be associated with individuals having vertebral endplate degenerative changes (both alone and in conjunction with retrolisthesis) and degenerative disc disease. Individuals who had retrolisthesis with concomitant vertebral endplate degenerative changes were more often smokers and had no insurance. The presence of retrolisthesis was not associated with an increased incidence of having degenerative disc disease, posterior degenerative changes, or vertebral endplate changes. No statistical significance was found between the presence of retrolisthesis on the degree of patient preoperative low back pain and physical function. Patients with degenerative disc disease were found to have increased leg pain compared with those patients without degenerative disc changes. CONCLUSIONS: We found no significant relationship between retrolisthesis in patients with L5-S1 disc herniation and worse baseline pain or function. It is possible that the contribution of pain or dysfunction related to retrolisthesis was far overshadowed by the presence of symptoms caused by the concomitant disc herniation. It remains to be seen whether retrolisthesis will affect outcome after discectomy in these patients.     

Increased glucose excursion in cystic fibrosis and its association with a worse clinical status

BACKGROUND: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. METHODS: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. RESULTS: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV(1)). CONCLUSION: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.     

Patient experience with, and use of, an electronic monitoring system to assess vaccination responses

OBJECTIVE: To evaluate the user experience and acceptability of an electronic patient monitoring system. SETTING AND PARTICIPANTS: 822 Military and civilian personnel at a health clinic at a major US military headquarters used an Internet and telephone-based electronic monitoring system to report vaccination-site responses and symptoms after receiving the smallpox vaccination. Focus groups of vaccinees were conducted to help develop a survey about the experience that was distributed to 379 vaccinees (96% completion rate). RESULTS: Users of the electronic monitoring system reported that it was fast and easy to use and reported they would use a system like this again and recommend an electronic monitoring system to a friend or relative. Most users (84%) were comfortable with a physician tracking their vaccine reaction using their electronic reports, but only half (51%) were comfortable with eliminating the post-vaccination follow-up visit with their health-care provider based on their electronic reports. CONCLUSIONS: This electronic monitoring system was well received by vaccinees and allowed health-care providers to track the status of vaccinees. However, vaccinees were not comfortable replacing a physician visit with electronic monitoring, at least for the smallpox vaccination. A monitoring system like this may be useful in public health settings, such as mass vaccination or prophylaxis during a bioterrorism event, a pandemic influenza outbreak, or another public health emergency.     

Effect of Bupivacaine and Levobupivacaine on Exocytotic Norepinephrine Release from Rat Atria

Background: The cardiotoxic mechanism of local anesthetics may include interruption of cardiac sympathetic reflexes. The authors undertook this investigation to determine if clinically relevant concentrations of bupivacaine and levobupivacaine interfere with exocytotic norepinephrine release from cardiac sympathetic nerve endings.

Methods: Rat atria were prepared for measurements of twitch contractile force and 3[H]-norepinephrine release. After nerve endings were loaded with 3[H]-norepinephrine, the tissue was electrically stimulated in 5-min episodes during 10 10-min sampling periods. After each period, a sample of bath fluid was analyzed for radioactivity and 3[H]-norepinephrine release was expressed as a fraction of tissue counts. Atria were exposed to buffer alone during sampling periods 1 and 2 (S1 and S2). Control atria received saline (100 [mu]l each, n = 6 atria) in S3-S10. Experimental groups (n = 6 per group) received either bupivacaine or levobupivacaine at concentrations (in [mu]M) of 5 (S3-S4), 10 (S5-S6), 30 (S7-S8), and 100 (S9-S10).

Results: Bupivacaine and levobupivacaine decreased stimulation-evoked fractional 3[H]-norepinephrine release with inhibitory concentration 50% values of 5.1 +/- 0.5 and 6.1 +/- 1.3 [mu]m. The inhibitory effect of both local anesthetics (~70%) approached that of tetrodotoxin. Local anesthetics abolished the twitch contractions of atria with inhibitory concentration 50% values of 12.6 +/- 5.0 [mu]m (bupivacaine) and 15.7 +/- 3.9 [mu]m (levobupivacaine). In separate experiments, tetrodotoxin inhibited twitch contractile force by only 30%.