Basic principles of magnetic resonance imaging

We have come full circle from spinning quarks to 3D medical images. The bulk of MRI is now performed using slice-selective gradients, during which RF energy is applied to excite the hydrogen nuclei. By stepping a phase-encoding gradient during each TR and using a frequency-encoding gradient as the data are sampled, the 3D human object can be reduced to many individual points or voxels. By acquiring multiple slices at once, the time efficiency of imaging can be vastly improved. Many newer strategies use variations of this technique to acquire multiple lines of data during a single echo, enshrining spin warp imaging as the most important method of signal acquisition for MRI.     

Physiological response to organophosphate residues in field workers

The physiologic response of 21 male agricultural field workers exposed to foliage-borne Guthion residues was monitored during routine peach-thinning operations in a northern California orchard. Surveillance included daily venipuncture and urine collection to determine whole blood cholinesterase (CHE) activity and level of dialkylphosphate excretion for 3 baseline (nonexposed) and 5 normal work days. Foliage samples were obtained to measure dislodgeable and total Guthion residues. A decrease in group-mean CHE activity by 15% over the surveillance period was found. Apart from one worker who showed a consistent decrease in CHE activity, reaching a maximum of 30% below baseline at the end of the work week, daily changes in individual CHE activity were erratic. Group-mean dialkylphosphate excretion levels provided a semiquantitative indication of exposure to Guthion. Medical examination before and after the exposure period revealed an absence of clinical signs of organophosphate intoxication.     

Orientation of the manubrium mallei: inexplicably widely variable

BACKGROUND: There is no consensus why the manubrium of the malleus, as viewed clinically through the external ear canal, generally points downward and posteriorly. OBJECTIVES: To depict the alignment of the handle of the malleus, viewed clinically through the external auditory canal, relative to the zygomatic arch, the Frankfort plane, and a visual plane proxy and relative to the horizontal semicircular canal. Also, to assess bilateral symmetry and manubrium alignment relative to mastoid pneumatization. STUDY DESIGN: Postmortem anatomic dissection of 41 bequeathed adult crania without clinical otitis. METHODS: The line of the manubrium as viewed through the external ear canal was measured relative to the Frankfort plane, to a proxy of the visual plane, and to the zygomatic arch. Mastoid sizes were determined radiographically. In a subset of 10 crania additionally studied by computed tomography, the manubrium position was checked relative to the horizontal semicircular canal. RESULTS: Relative to the zygomatic arch and Frankfort and visual planes, the range of manubrium angles was at least 45 degrees. Bilateral symmetry was found, each r 0.38 or greater (P < .05). Relative to the horizontal canals, the range of manubrial angles was 30 degrees, with symmetry suggested. Alignment did not correlate with mastoid pneumatization. CONCLUSION: Manubrium orientation as viewed through the external auditory canal is not obviously explicable. The wide variety of manubrium orientations may explain the manubrium-stapes offset that perplexes manubrium-stapes surgical constructions.     

The Los Angeles Lift Off: a sociocultural environmental change intervention to integrate physical activity into the workplace

PURPOSE: To present the development and feasibility testing of a sociocultural environmental change intervention strategy aimed at integrating physical activity into workplace routine. DESIGN: Randomized, controlled, post-test only, intervention trial. Setting. Los Angeles County Department of Health Services' worksites. PARTICIPANTS: Four hundred forty-nine employees, predominantly sedentary, overweight, middle-aged women of color, distributed across 26 meetings. INTERVENTION: A single 10-min exercise break during work time involving moderate intensity, low-impact aerobic dance and calisthenic movements to music. MEASURES: Primary-level of participation, particularly among sedentary staff; secondary-self-perceived health status, satisfaction with current fitness level, and mood/affective state. RESULTS: More than 90% of meeting attendees participated in the exercises. Among completely sedentary individuals, intervention participants' self-perceived health status ratings were significantly lower than controls' (OR = 0.17; 95% CI = 0.05, 0.60; P = 0.0003). Among all respondents not regularly physically active, intervention participants' levels of satisfaction with fitness were more highly correlated with self-ranked physical activity stage of change (r = 0.588) than the control participants' (r = 0.376, z = -2.32, p = 0.02). Among the completely sedentary, control participants reported significantly higher levels of energy than did intervention participants (P < 0.01). CONCLUSIONS: Captive audiences may be engaged in brief bouts of exercise as a part of the workday, regardless of physical activity level or stage of change. This experience may also appropriately erode sedentary individuals' self-perception of good health and fitness, providing motivation for adoption of more active lifestyles.     

The Edpm5 locus prevents the 'angiogenic switch' in an estrogen-induced rat pituitary tumor

Edpm5 is one member of a group of quantitative trait loci that are responsible for the difference in susceptibility to estrogen-induced prolactinoma between the Fischer 344 (F344) and Brown Norway (BN) strains. Upon chronic estrogen treatment F344 rats develop large, hemorrhagic and invasive pituitary tumors, which exhibit both tumor angiogenesis and neoplasia. In contrast, BN rats do not develop a tumor despite an estrogen-induced increase in lactotroph density. To investigate the role of Edpm5 in the development of these tumors, we have generated a novel congenic rat strain F344.BN-Edpm5BN by introgressing the segment of rat chromosome bearing Edpm5 from BN into the F344 strain background. Phenotypic differences between F344 and F344.BN-Edpm5BN must be due to a gene(s) within the chromosomal interval encompassing Edpm5. Through use of these strains, we find that Edpm5 specifically regulates the switch to angiogenic phenotype, independent of neoplasia. The F344.BN-Edpm5BN rats developed tumors, which exhibited significant growth, 7-fold greater mass than the pituitary of untreated rats, and neoplasia indistinguishable from that of the F344 strain. However, the F344.BN-Edpm5BN rat tumor had a non-angiogenic phenotype. After chronic estrogen treatment, there was no increase in microvessel count over untreated controls in F344.BN-Edpm5BN tumors, whereas F344 rat tumors showed a significant increase (P < 0.0005). The ultrastructural morphology of the pituitary blood vessels also did not show significant angiogenesis associated changes in F344.BN-Edpm5BN rat pituitary tumors. In contrast the parental strain F344 had pronounced angiogenic activity. The F344.BN-Edpm5BN strain also fails to express VEGF at the high levels seen in the F344 rat pituitary after estrogen treatment. Hence at least one gene that has a large impact, directly or indirectly, on the switch to angiogenic phenotype must reside within the chromosomal interval that is the Edpm5 quantitative trait locus.     

The ARF-p16 gene locus in carcinogenesis and therapy of head and neck squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: We have identified families with a high incidence of tumors including head and neck squamous cell carcinoma (HNSCC). The occurrence of melanoma in these kindreds suggested that the ARF-p16 gene may be involved in carcinogenesis. We wished to determine the gene defect associated with the familial predisposition to HNSCC and to determine whether restoration of the gene may have therapeutic benefit. STUDY DESIGN: Translational molecular research. METHODS: Molecular techniques were used to identify mutations of the ARF-p16 gene from the affected families and to test the activity of p16 and ARF mutants. In additional, HNSCC tumor tissue was analyzed to determine whether the wild-type p16 allele was lost or maintained. ARF-expressing adenoviruses were created, and their effect on HNSCC cell lines and normal head and neck epithelial cells was determined. RESULTS: Mutation of the ARF-p16 gene was found in two families with predisposition to develop HNSCC. Independent mutations detected in the germline DNA of both families inactivated p16, but not ARF, and the inactive mutant p16 allele segregated with disease within both families. The wild-type p16 allele was lost in HNSCC tumor tissue from both families. The efficacy of ARF in treatment of HNSCC was found to depend on retention of p53 activity within HNSCC tumor cells. Remarkably, ARF expression was found to kill cells, depending on loss of retinoblastoma activity. Because loss of retinoblastoma activity is nearly universal in tumors, ARF killed tumor cells that retained p53, but ARF spared normal cells. CONCLUSIONS: Our results support the recognition of a new clinical entity of familial head and neck cancer. We have shown that this syndrome is associated with inactivating mutations of the p16 gene that these mutations segregate with disease in two described families. Loss of the wild-type p16 allele in HNSCC tissue from both families strongly supports the role of the mutant p16 in carcinogenesis. We have also investigated the therapeutic utility of the alternate reading frame product of the p16 gene, ARF. The finding that ARF kills cells depending on loss of retinoblastoma activity and retention of p53 suggests that ARF may be effective in treatment of roughly 50% of head and neck cancers while sparing normal cells. Recognition of p16 mutations as an etiological factor in familial HNSCC provides an accessible tool for diagnosis of this syndrome. Clinical acceptance of familial head and neck cancer will ensure that patients are appropriately diagnosed and managed.