Citations

Abstract Introduction: Limited information is available about the clinical features of Paget's disease of bone among unselected patients in the community. We examined morbidity and mortality associated with this condition in a large inception cohort of Olmsted County, MN, residents with a new diagnosis of Paget's disease from 1950 through 1994. Materials and Methods: Survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to assess the impact of various covariates on death. Results: Paget's disease of bone was diagnosed in 236 Olmsted County residents (mean age at diagnosis, 69.6 yr; 55% men). The majority were symptomatic at diagnosis (58%), and the proportion with symptoms did not change from the prescreening era (1950 to June 1974) to the postscreening era (July 1974–1994). Most patients had polyostotic disease (72%), and the pelvis (67%), vertebra (41%), and femur (31%) were the most common sites of involvement. Skeletal complications attributable to Paget's disease included bowing deformities (7.6%), fracture of pagetic bone (9.7%), and osteosarcoma (0.4%). Osteoarthritis was observed in 73% of patients, and 11% had a hip or knee replacement. Nonskeletal complications related to Paget's disease included cranial nerve (0.4%), peripheral nerve (1.7%), and nerve root (3.8%) compression, basilar invagination (2.1%), hypercalcemia (5.2%), and congestive heart failure (3.0%). Hearing loss, noted in 61%, was significantly higher than previously reported. Conclusions: Compared with white Minnesota residents, overall survival was slightly better than expected (p = 0.010). No clinical risk factors were identified that were associated with an increased risk of death.

AbstractWe analyzed the presenting features and survival in 1689 patients with multiple myeloma aged younger than 50 years compared with 8860 patients 50 years of age and older. Of the total 10 549 patients, 7765 received conventional therapy and 2784 received high-dose therapy. Young patients were more frequently male, had more favorable features such as low International Staging System (ISS) and Durie-Salmon stage as well as less frequently adverse prognostic factors including high C-reactive protein (CRP), low hemoglobin, increased serum creatinine, and poor performance status. Survival was significantly longer in young patients (median, 5.2 years vs 3.7 years; P < .001) both after conventional (median, 4.5 years vs 3.3 years; P < .001) or high-dose therapy (median, 7.5 years vs 5.7 years; P = .04). The 10-year survival rate was 19% after conventional therapy and 43% after high-dose therapy in young patients, and 8% and 29%, respectively, in older patients. Multivariate analysis revealed age as an independent risk factor during conventional therapy, but not after autologous transplantation. A total of 5 of the 10 independent risk factors identified for conventional therapy were also relevant for autologous transplantation. After adjusting for normal mortality, lower ISS stage and other favorable prognostic features seem to account for the significantly longer survival of young patients with multiple myeloma with age remaining a risk factor during conventional therapy.

Abstract Studies suggest that underglycosylation of the cell membrane mucin MUC1 may be associated with epithelial ovarian cancer. We identified 26 genes involved in glycosylation and examined 93 single nucleotide polymorphisms (SNP) with a minor allele frequency of ≥0.05 in relation to incident ovarian cancer. Cases were ascertained at the Mayo Clinic, Rochester, MN (n = 396) or a 48-county region in North Carolina (Duke University; n = 534). Ovarian cancer–free controls (n = 1,037) were frequency matched to the cases on age, race, and residence. Subjects were interviewed to obtain data on risk factors and a sample of blood for DNA and genotyped using the Illumina GoldenGate assay. We excluded subjects and individual SNPs with genotype call rates of &lt;90%. Data were analyzed using logistic regression, with adjustment for age and residence. We fitted dominant, log additive, and recessive genetic models. Among Caucasians, nine SNPs in eight genes were associated with risk at P &lt; 0.05 under at least one genetic model before adjusting for multiple testing. A SNP in GALNT1 (rs17647532) was the only one that remained statistically significant after Bonferroni adjustment for multiple testing but was not statistically significant in Hardy-Weinberg equilibrium among controls. Haplotype analyses revealed a global association of GALNT1 with risk (P = 0.038, under a recessive genetic model), which largely reflected a decreased risk of one haplotype (0.10 frequency; odds ratio, 0.07; P = 0.01) compared with the most common haplotype (0.39 frequency). These results suggest that genetic polymorphisms in the glycoslyation process may be novel risk factors for ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(2):397–404)

Abstract Background: Early adolescent weight may affect the risk of postmenopausal breast cancer, and this association may be modified by a family history of breast or ovarian cancer in a first-degree relative, and/or estrogen (ER) and progesterone (PR) receptor status of the disease. Methods: Relative weight at age 12 years (above, below, or average weight compared with peers) and family history were ascertained using a mailed questionnaire in 1986, in the Iowa Women's Health Study, a prospective cohort study of postmenopausal women. Incident breast cancer cases (including ER and PR status) were identified using the Iowa Surveillance, Epidemiology, and End Results Cancer Registry. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression, and were adjusted for breast cancer risk factors, including body mass index at age 18 years and body mass index at study baseline. Results: Through 2003, 2,503 cases of postmenopausal breast cancer were identified among 35,941 women in the analytic cohort. Compared with women with average weight at age 12 years, there was no association of below average weight with risk of breast cancer (RR, 1.02; 95% CI, 0.92-1.13), whereas women with above average weight had a lower risk (RR, 0.85; 95% CI, 0.74-0.98). There was no evidence of an interaction between weight at age 12 years and family history (P = 0.44). The inverse association of above average weight with risk of breast cancer was strongest for PR− tumors (RR, 0.62; 95% CI, 0.43-0.89), intermediate for ER+ (RR, 0.80; 95% CI, 0.67-0.96) and ER− (RR, 0.77; 95% CI, 0.50-1.19) tumors, and weakest for PR+ tumors (RR, 0.90; 95% CI, 0.74-1.09). These associations were not modified by a family history (all P &gt; 0.18). In a joint ER/PR analyses, the strongest inverse association with above average weight at age 12 years was seen for ER+/PR− (RR, 0.49; 95% CI, 0.29-0.85). Conclusion: Above average weight at age 12 years was inversely associated with risk of postmenopausal breast cancer, and was not modified by a family history of the disease. The inverse association was strongest for ER+/PR− tumors. (Cancer Epidemiol Biomarkers Prev 2008;17(2):374–8)

Background and Purpose— The extent of potential consent bias in observational studies elucidating genetic and environmental contributions to ischemic stroke is largely unknown. The purpose of this study was to assess differences in stroke cohort characteristics between those who provided informed consent and those whose enrollment was authorized by surrogate decision makers. Methods— The Ischemic Stroke Genetics Study (ISGS) is a prospective, 5-center, case-control study of first-ever ischemic stroke. Demographic, clinical, and stroke characteristics were compared between cases enrolled by self versus by surrogate. Data from one site that limits enrollment only to those able to self-consent were also analyzed to compare those who enrolled with those not able to consent. Results— Overall, 10% (54 of 517) were enrolled using surrogate authorization. Self-consented and surrogate-authorized cases did not differ significantly in age, sex, or conventional risk factors. Surrogate-authorized cases had significantly more severe stroke deficits, larger infarcts, and infarcts localizing to left supratentorial regions. Similarly, at the site restricting enrollment, stroke severity and characteristics differed between self-consented individuals and those otherwise eligible but unable to provide consent. Conclusions— Failure to permit surrogate authorization in genetic studies of ischemic stroke may skew enrollment toward less severe strokes caused by smaller infarcts. This potential consent bias may undermine the ability to identify genetic determinants of risk and severity and suggests that surrogate enrollment in these studies can be ethically justifiable.

✓ As a rule, normal human nerve does not contain glomus bodies. Nonetheless, rare examples of glomus tumors do arise in peripheral nerves of various sizes. Their pathobiological characteristics are poorly understood, but reported examples have been small and clinically benign. The authors identified in 1 patient each a glomus tumor and a glomangioma involving nerve. Clinical histories as well as imaging and surgical findings were reviewed. All available H & E–stained slides were examined in both cases. Immunohistochemical stains and electron microscopy, as appropriate, were also performed. The lesions were subtotally and completely resected, respectively. An uneventful postoperative recovery was noted in both patients. Glomus tumors and glomangiomas can involve major nerves on rare occasions. They seem to follow a favorable clinical course, and conservative resection can be of benefit.

✓ The authors report on a patient without neurofibromatosis Type 1 or 2 (NF1 or NF2) and without evidence of schwannomatosis, who was found to have an unusual combination of nerve sheath tumors—a large cellular schwannoma and multifascicular involvement of a plexiform neurofibroma arising from the same site within the radial nerve and posterior cord of the infraclavicular brachial plexus. This case broadens the spectrum of combined pathological features of nerve sheath tumors. Genetic studies revealed a combined loss of neurofibromin and merlin in both regions and chromosome arm 22q deletion within the neurofibroma component only. The latter finding supports the suggestion that these were two different clonal neoplasms, and is consistent with a collision tumor pattern.

✓Reconstruction of extensive nerve defects is hampered by the amount of autogenous nerve tissue available for transplantation and by donor site morbidity. Nerve allografts, being of foreign origin and potentially unlimited in supply, provide a solution to these problems. Studies have shown that nerve allotransplants require immunosuppression only until end-organ connections are made and that immunosuppressant therapy may be subsequently discontinued with no negative effect on functional outcome. Also, recent experimental and clinical focus has been on shorter periods of immunosuppression in order to reduce risk, even stopping immunosuppression after regeneration has reached the distal suture line rather than before recovery of end-organ connections. In the pediatric population, the increased disease burden and increased potential for nerve regeneration as well as the frequent availability of a living related donor make allografts all the more attractive as solutions to nerve reconstructive problems. Nevertheless, the risks of immunosuppression must not be underemphasized, and they deserve more attention in the current nerve transplantation literature. The authors report on a child who, at the age of 1 year, received a nerve allograft from a living related donor who was positive for Epstein–Barr virus (EBV). The child quickly developed a symptomatic EBV infection concurrent with immunosuppressant drug therapy. The immunosuppression regimen was stopped prematurely, and the patient suffered only a short illness, but the EBV infection could have developed into a life-threatening posttransplant lymphoproliferative disorder (PTLD). The patient is consequently predisposed to develop PTLD and will have to be monitored for the rest of his life. This case highlights the importance of considering the potentially fatal risks associated with this elective procedure. Future studies are needed to quantify and minimize this complication. Nevertheless, it should be weighed against the potential functional benefit from using nerve allografts.