Childhood Cancer and the Risk of ESKD

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.     

Treatment of an edentulous patient with a dry mouth

Dental health professionals are being asked to care for a growing number and range of medically compromised patients living with chronic health problems. Although tooth loss overall has declined in the United States, millions of persons, particularly those of more advanced age, still require treatment for the edentulous condition. Particular challenges are faced when this oral state is combined with a complex medical history. The primary learning objective for this case is to increase your general knowledge of and skills in the dental management of the complete denture patient with a dry mouth.     

Telomerase activity as a marker of breast carcinoma in fine-needle aspirated samples

BACKGROUND: Telomerase activity in breast fine-needle aspiration (FNA) samples may have diagnostic utility. The purpose of this study was to compare in FNA samples of breast tumor the diagnostic accuracy as correlated with histologic final diagnosis. METHODS: Fine-needle aspiration samples were obtained from 617 patients with palpable breast tumors. Slide preparation and cytology were performed according to a uniform approach. Extracts derived from 10(3) cells from the residual cells in the syringe were used for the telomeric repeat amplification protocol (TRAP) assay. Of the original 617 patients, 220 underwent open biopsy or surgery, and 93 cancers and 127 patients' benign diseases were diagnosed by histologic examination. RESULTS: All 62 tumors that were diagnosed as "malignant" or "probably malignant" by FNA cytology were cancerous, and 50 cases (81%) showed detectable telomerase activity. Among 17 "atypical" or "indeterminate" cases, all 10 tumors with detectable telomerase activity subsequently were diagnosed as breast carcinoma whereas 6 of 7 tumors without telomerase activity were diagnosed as benign. Among the 141 "benign" or "unsatisfactory" samples, 12 of 21 cases with detectable telomerase activity subsequently were diagnosed as cancer. CONCLUSIONS: The diagnostic accuracy of telomerase activity in FNA samples is considered to be equivalent or slightly higher to that of cytology (86% vs. 70%). Detection of telomerase activity should be considered an alert for false-negative results of FNA cytology and may be useful as a diagnostic marker for breast malignancy, especially in samples cytologically undetermined to be malignant. Cancer (Cancer Cytopathol) Copyright 2000 American Cancer Society.     

Mechanism-based combination telomerase inhibition therapy

Inhibition of telomerase is an exciting therapeutic target, since it is required for the long-term proliferation of most cancer cells but not present in most somatic cells. However, effective telomerase inhibitors have yet to be tested in clinical trials. In this issue of Cancer Cell, Seimiya and coworkers explore inhibiting tankyrase, an enzyme involved in making telomeres accessible to telomerase. Adding a partial inhibition of tankyrase to a partial inhibition of telomerase drove cancer cells into crisis and death. The combination of tankyrase and telomerase inhibitors may offer new opportunities for realizing the promise of telomerase inhibition therapy.     

Effectiveness of influenza vaccine during pregnancy in preventing hospitalizations and outpatient visits for respiratory illness in pregnant women and their infants

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends influenza vaccination for women who will be in the second or third trimester of pregnancy during the influenza season. We analyzed hospital admissions with principal diagnoses of influenza or pneumonia and influenza-like illness (ILI) outpatient visits to study the effectiveness of influenza vaccine during pregnancy in protecting women and infants from influenza-related morbidity. Estimates of influenza vaccine effectiveness across five flu seasons (Fall 1997 to Spring 2002) were calculated using Cox proportional hazards models for women and infant study populations in Kaiser Permanente Northern California. Outpatient utilization outcomes included physician visits with a diagnosis of upper respiratory infection, pharyngitis, otitis media, asthma, bronchial asthma, viral infection, pneumonia, fever, cough, or wheezing associated with respiratory illness. Inpatient outcomes included hospitalizations with principal diagnoses of influenza or pneumonia. Women who received influenza vaccine during pregnancy had the same risk for ILI visits compared with unvaccinated women, adjusting for women's age and week of delivery. When asthma visits were excluded from the outcome measure, we also found no difference in the risk of outpatient visits for vaccinated and unvaccinated women. Hospital admissions for influenza or pneumonia for women in the study population were quite rare and no women died of respiratory illness during pregnancy. Infants born to women who received influenza vaccination had the same risks for influenza or pneumonia admissions compared with infants born to unvaccinated women, adjusting for infant's gender, gestational age, week of birth, and birth facility. Maternal influenza vaccination was also not a significant determinant of risk of ILI (excluding otitis media) outpatient visits for infants, nor did it significantly affect the risk of otitis media visits. Influenza vaccination during pregnancy did not significantly affect the risk of cesarean section, adjusting for the woman's age. It also did not affect the risk of preterm delivery. Although the immunogenicity of influenza vaccination in pregnancy in mother and infant has been well documented, in this study, we were unable to demonstrate the effectiveness of influenza vaccination with data for hospital admissions and physician visits. One possible interpretation of these findings is that typical influenza surveillance measures based on utilization data are not reliable in distinguishing influenza from other respiratory illness. Hospitalizations for respiratory illness were uncommon in both vaccinees and nonvaccinees.     

Relationship between low back pain in post-menopausal women and mineral content of lumbar vertebrae

Until recently, chronic low back pain in post-menopausal women was commonly attributed to osteoporosis. This opinion has since been challenged on many counts, but controversy persists. The objective of this study was to examine this relationship. In 67 post-menopausal women, the mineral content of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry and the age-normalized bone mineral index (ANBMI), the Z-score, was determined. Mean ANBMI in 40 subjects who complained of chronic low back pain (Group 1) was compared with mean ANBMI in the 27 who did not (Group 2). Pain intensity and related disability were quantified using standard questionnaires. Their respective correlations with ANBMI index and age at onset of menopause were examined. Correlation coefficients and significance of group differences were examined by appropriate statistical methods. The results showed that the mean ANBMI in Group 1 subjects was 96.5 +/- 16.9%, in Group 2 subjects it was 88.6 +/- 10.0%. Neither pain intensity nor disability was correlated with ANBMI. A weak but significant positive correlation was noted between body mass index and intensity of low back pain (r = 0.37; P < 0.05). The occurrence and severity of chronic low back pain in post-menopausal women, and the disability thereof, appear to be unrelated to the mineral content of lumbar vertebrae.     

Disparate effects of telomere attrition on gene expression during replicative senescence of human mammary epithelial cells cultured under different conditions

Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (M0) by the inactivation of p16(INK4A) during cell culture on plastic dishes leads to a state of permanent replicative arrest termed senescence. While culture of HMECs on feeder layers abrogates M0 and p16(INK4A) inactivation, progressive telomere attrition in these cells also eventually results in permanent replicative arrest. Expression of telomerase prevents both senescence on plastic (S-P) and senescence on feeder layers (S-FL) in HMECs, as it does also in cultured primary human fibroblasts. We report here that the gene expression profiles of senescence in HMECs of the same lineage maintained under different culture conditions showed surprisingly little commonality. Moreover, neither of these senescence-associated profiles in HMECs resembles the profile for senescence in human fibroblasts. These results indicate that senescence-associated alterations in gene expression resulting from telomere attrition are affected by culture conditions as well as by cell origins, and argue that replicative senescence at the molecular level is a diverse rather than unique cellular process.