Citations

AbstractMultiple myeloma (MM) is a B-lineage malignancy characterized by diverse genetic subtypes and clinical outcomes. The recurrent immunoglobulin heavy chain (IgH) switch translocation, t(4;14)(p16;q32), is associated with poor outcome, though the mechanism is unclear. Quantitative reverse-transcription–polymerase chain reaction (RT-PCR) for proposed target genes on a panel of myeloma cell lines and purified plasma cells showed that only transcripts originating from the WHSC1/MMSET/NSD2 gene are uniformly dysregulated in all t(4;14)POS patients. The different transcripts detected, multiple myeloma SET domain containing protein (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein (RE-IIBP), are produced by alternative splicing and alternative transcription initiation events. Translation of the various transcripts, including those from major breakpoint region 4-2 (MB4-2) and MB4-3 breakpoint variants, was confirmed by transient transfection and immunoblotting. Green fluorescent protein (GFP)–tagged MMSET I and II, corresponding to proteins expressed in MB4-1 patients, localized to the nucleus but not nucleoli, whereas the MB4-2 and MB4-3 proteins concentrate in nucleoli. Cloning and localization of the Exon 4a/MMSET III splice variant, which contains the protein segment lost in the MB4-2 variant, identified a novel protein domain that prevents nucleolar localization. Kinetic studies using photobleaching suggest that the breakpoint variants are functionally distinct from wild-type proteins. In contrast, RE-IIBP is universally dysregulated and also potentially functional in all t(4;14)POS patients irrespective of fibroblast growth factor receptor 3 (FGFR3) expression or breakpoint type.

OBJECTIVE: To report a case of pulmonary hypersensitivity associated with furazolidone use and review the literature on this topic. CASE SUMMARY: A 43-year-old white female presented with fever and dyspnea. She had recently completed a course of furazolidone 125 mg 4 times daily for 10 days for enteritis. Investigations revealed bibasilar interstitial infiltrates on chest X-ray, hypoxia, and 21% eosinophilia. Her fever, hypoxia, and dyspnea rapidly abated following discontinuation of furazolidone and administration of corticoteroids. DISCUSSION: Furazolidone is a bactericidal agent used to treat infectious enteropathies. It is chemically similar to nitrofurantoin, which is well known to cause pulmonary hypersensitivity reactions. Application of the Naranjo probability scale suggests that a furazolidone adverse reaction in this patient was probable. A MEDLINE search from 1966 to October 2004 revealed 2 previously reported cases suggestive of furazolidone pulmonary hypersensitivity. All published reports closely resemble each other and descriptions of nitrofurantoin-associated pulmonary hypersensitivity reactions. CONCLUSIONS: Furazolidone may induce pulmonary hypersensitivity reactions; clinicians should be aware of this potentially serious adverse effect.

Estrogens play a crucial role in the causation and development of sporadic human breast cancer (BC). Chromosomal instability (CIN) is a defining trait of early human ductal carcinoma in situ (DCIS) and is believed to precipitate breast oncogenesis. We reported earlier that 100% of female ACI (August/Copenhagen/Irish) rats treated with essentially physiological serum levels of 17β-estradiol lead to mammary gland tumors with histopathologic, cellular, molecular, and ploidy changes remarkably similar to those seen in human DCIS and invasive sporadic ductal BC. Aurora-A (Aur-A), a centrosome kinase, and centrosome amplification have been implicated in the origin of aneuploidy via CIN. After 4 mo of estradiol treatment, levels of Aur-A and centrosomal proteins, γ-tubulin and centrin, rose significantly in female ACI rat mammary glands and remained elevated in mammary tumors at 5–6 mo of estrogen treatment. Centrosome amplification was initially detected at 3 mo of treatment in focal dysplasias, before DCIS. At 5–6 mo, 90% of the mammary tumor centrosomes were amplified. Comparative genomic hybridization revealed nonrandom amplified chromosome regions in seven chromosomes with a frequency of 55–82% in 11 primary tumors each from individual rats. Thus, we report that estrogen is causally linked via estrogen receptor α to Aur-A overexpression, centrosome amplification, CIN, and aneuploidy leading to BC in susceptible mammary gland cells.

Objective.To determine why people do or do not wear helmets while bicycling.Methods.A survey was conducted from August through October 1999. Two survey areas were chosen for this study: local public schools and paved bicycle trails. For the school arm of the study, 3 public elementary, middle, and high schools were selected from 3 different regions of Rochester, Minnesota, for participation in the study. For the bicycle arm of the study, 3 paved trails located in southeastern Minnesota were selected. A total of 2970 surveys were distributed to the public school system, and 463 surveys were collected from bicyclists on the paved bicycle trails. The survey population was split into 3 age categories for analysis: child (7–10), adolescent (11–19), and adult (older than 19).Results.Of the 2970 surveys distributed to Rochester public schools, 2039 (69%) were returned for analysis. Seventy-eight of the surveys that were completed in the public school system were discarded for the following reasons: age <10 years (35), insufficient completion (24), and selection of every reason for not wearing a bicycle helmet (19). A total of 463 surveys were completed on the 3 paved bicycle trails. One survey from the paved bicycle trail arm of the study was discarded because of insufficient completion. The total number of surveys used for statistical analysis was 2424. The distribution of male (52.7%) and female (47.3%) participants was similar. No significant difference in bicycle helmet use was found between genders.The age groups with the highest rate of bicycle helmet use were 50 to 59 years (62%) and older than 59 years (70%). The age groups with the lowest rate of bicycle helmet use were 11 to 19 years (31%) and 30 to 39 years (30%). The most common reasons given for not wearing a bicycle helmet were “uncomfortable,” “annoying,” “it's hot,” “don't need it,” and “don't own one.” Bicycle helmet use was significantly influenced by peer helmet use in all 3 age groups. Children also were more likely to wear a bicycle helmet when their parents wore bicycle helmets.A majority of respondents in all 3 age groups indicated that bicycle helmets provided either “moderate” or “great” protection from head injury, although significantly more adults (65.9%) than adolescents (43.9%) believed that the protection afforded by bicycle helmets was “great.” Despite this belief, a majority of adolescents and adults indicated that there was only a “slight risk” of head injury when bicycling without a helmet. Participants in all 3 categories were more likely to wear a bicycle helmet when they indicated either that there was a “great risk” of head injury when bicycling without a helmet or that helmets provided “great protection” from head injury. Adolescents and adults who believed that bicycling without a helmet put one at “great risk” for head injury also were more likely to indicate that helmets provided “great protection” from head injury.Conclusions.The prevalence of bicycle helmet use remains low despite research indicating the high level of head injury risk when bicycling without a helmet and the significant protection afforded by bicycle helmets. With the information provided by this survey, a well-designed intervention to increase the use of bicycle helmets can be implemented. Suggestions for a campaign to promote an increase in bicycle helmet use include focusing efforts on males and females between 11 and 19 years and 30 and 39 years of age; educating the public on new bicycle helmet designs that address comfort, ventilation, and fashion; educating adolescents on the significant protection from head injury afforded by bicycle helmets; and educating the public on the risk and severity of head injury associated with bicycling without a helmet. The influence of parents and peers on bicycle helmet use may be targeted through education and statements such as, “If you wear a bicycle helmet, you are not only protecting yourself, you are also helping to protect your friends and/or children.” bicycle, helmet, injury, accident, prevention.

Abstract OBJECTIVE AND IMPORTANCE Cerebellar hemorrhage remote from the site of surgery may complicate neurosurgical procedures. We describe our experience with two cases of cerebellar hemorrhage after spinal surgery and review the three cases previously reported in the literature to determine whether these cases provide insight regarding the pathogenesis of remote cerebellar hemorrhage. CLINICAL PRESENTATION One of our patients developed cerebellar hemorrhage in the vermis and right hemisphere after transpedicular removal of a partially intradural T9–T10 herniated disc with the patient in the prone position. The other patient developed cerebellar hemorrhage in the vermis and bilateral hemispheres after L3–S1 decompression and instrumentation with the patient in the prone position, during which the dura was inadvertently opened. INTERVENTION The first patient was treated conservatively and had mild residual dysarthria and gait ataxia 2 months after surgery. The second patient underwent exploration and revision of the lumbar wound with primary dural repair. The cerebellar hemorrhage was treated conservatively, and the patient had mild dysarthria and ataxia 1 month after surgery. CONCLUSION Cerebellar hemorrhage must be considered in patients with unexplained neurological deterioration after spinal surgery. Dural opening with loss of cerebrospinal fluid has occurred in every reported case of cerebellar hemorrhage complicating a spinal procedure, supporting the hypothesis that loss of cerebrospinal fluid is central to the pathogenesis of this condition. Because remote cerebellar hemorrhage can occur after procedures with the patient in the supine, sitting, and prone positions, patient positioning seems unlikely to play a causative role in its occurrence.

ABSTRACT OBJECTIVE Remote cerebellar hemorrhage (RCH) is an infrequent and poorly understood complication of supratentorial neurosurgical procedures. We retrospectively compared 42 patients who experienced RCH with a case-matched control cohort, to delineate risk factors associated with the occurrence of this complication. METHODS Between 1988 and 2000, 42 patients experienced RCH after supratentorial neurosurgical procedures at our institution. Diagnoses were made on the basis of postoperative computed tomographic or magnetic resonance imaging findings in all cases. The medical records for these patients were reviewed and compared with those for a control cohort of 43 patients, matched for age, sex, surgical lesion, and type of craniotomy, who were treated during the same period. RESULTS RCH most commonly occurred after frontotemporal craniotomies for unruptured aneurysm repair or temporal lobectomy and was frequently an incidental finding on postoperative computed tomographic scans. However, some cases of RCH were associated with significant morbidity, and two patients died. Preoperative aspirin use and elevated intraoperative systolic blood pressure were significantly associated with RCH (P = 0.026 and P = 0.036, respectively). Pathological findings for two cases demonstrated hemorrhagic infarctions in both. CONCLUSION RCH most commonly follows supratentorial neurosurgical procedures, performed with the patient in the supine position, that involve opening of cerebrospinal fluid cisterns or the ventricular system (such as unruptured aneurysm repair or temporal lobectomy). Preoperative aspirin use and moderately elevated intraoperative systolic blood pressure are potentially modifiable risk factors associated with the development of RCH. Although RCH can cause death or major morbidity, most cases are asymptomatic or exhibit a benign course. Cerebellar “sag” as a result of cerebrospinal fluid hypovolemia, causing transient occlusion of superior bridging veins within the posterior fossa and consequent hemorrhagic venous infarction, is the most likely pathophysiological cause of RCH.