A key requirement for CD300f in innate immune responses of eosinophils in colitis.

Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f-/- mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f-/- mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer.

PURPOSE: We determine if histopathological factors of the primary penile tumor can stratify the risk of the development of inguinal lymph node metastases. MATERIALS AND METHODS: Clinical records of 48 consecutive patients with squamous cell carcinoma of the penis who underwent resection of the primary lesion and either inguinal lymph node dissection or were observed for signs of recurrence (median followup 59 months) were reviewed. Parameters examined included pathological tumor stage, quantified depth of invasion and tumor thickness, histological and nuclear grade, percentage of poorly differentiated cancer in the primary tumor, number of mitoses and presence or absence of vascular invasion. Variables were compared in 18 lymph node positive and 30 lymph node negative cases. RESULTS: Pathological tumor stage, vascular invasion and presence of greater than 50% poorly differentiated cancer were the strongest predictors of nodal metastasis on univariate and multivariate regression analyses. None of 15 pT1 tumors exhibited vascular invasion or lymph node metastases. Of 33 patients with pT2 or greater tumors 21 (64%) had vascular invasion and 18 (55%) had metastases. Only 4 of 25 patients (15%) with 50% or less poorly differentiated cancer in the penile tumor had metastases compared with 14 of 23 patients (61%) with greater than 50% poorly differentiated cancer (p = 0.001). No other variables tested were significantly different among the patient cohorts. CONCLUSIONS: Pathological stage of the penile tumor, vascular invasion and greater than 50% poorly differentiated cancer were independent prognostic factors for inguinal lymph node metastasis. Prophylactic lymphadenectomy in compliant patients with pT1 lesions without vascular invasion and 50% or less poorly differentiated cancer does not appear warranted.

Involuntary disenrollment from a Medicare managed care plan at an academic medical center: effect on patients.

OBJECTIVES: Little is known about the impact of mandatory (involuntary) disenrollment of patients from Medicare managed care organization (MCO) plans. We hypothesized that involuntary disenrollment raises significant concerns for patients, that younger enrollees (aged less than 65, "Medicare disabled") have different concerns than older patients, and that younger patients respond to termination of their plan within the MCO differently from older patients. We also examined other factors associated independently with enrollee decisions to stay in the MCO or return to Medicare fee-for-service. DESIGN: A cross-sectional telephone questionnaire. SETTING: A Medicare managed care plan at two outpatient clinics at an academic medical center in Denver, Colorado. PARTICIPANTS: Four hundred fifty enrollees recently notified of termination of their clinic's contract with a Medicare managed care plan were surveyed. MEASUREMENTS: Survey questions on demographics, patient concerns about disenrollment, and factors associated with staying at the academic medical center or switching to another clinic or plan associated with the MCO. RESULTS: Of 371 respondents, 57% switched to another plan within the MCO, including 65% of the Medicare disabled enrollees and 57% of the Medicare nondisabled enrollees. More than 60% of both Medicare disabled and older patients who switched felt that it was a significant problem for them. By multivariate analysis, age was not associated with switching, but a distant relationship with one's physician was associated with switching (odds ratio (OR) = 10.2; confidence interval (CI), 1.13-91.09) and having received care at the academic medical center for 1 year or longer (OR = 0.35, 95% CI, 0.17-0.69), postcollege education (OR = 0.34; CI, 0.16-0.69), and black race (OR = 0.29; CI, 0.13-0.68) were independently associated with not switching. Older and younger patients cited similar concerns raised by switching, but financial issues were identified as a major concern by more younger patients than older patients (P = .001). CONCLUSIONS: Involuntary disenrollment raised significant concerns for patients in a Medicare managed care plan.

A comparison of functional outcomes after hip fracture in group/staff HMOs and fee-for-service systems.

CONTEXT: Previous studies examining differences in the quality of care between capitated and fee-for-service payment systems have focused on the care delivered in a single setting. No study to date has compared outcomes over an entire episode of care delivered across multiple settings. OBJECTIVE: To compare outcomes of care for patients receiving institutional rehabilitation for hip fracture in fee-for-service and group/staff HMO delivery systems. DESIGN: One-year prospective inception cohort. SETTING: Six hospital-based, integrated care systems paid on a traditional fee-for-service model and five group/staff HMOs (paid fixed capitation rate by Medicare). The 11 delivery systems were selected because of their commitment to geriatric rehabilitation. PATIENTS: 196 fee-for-service and 140 group/staff HMO patients with acute hip fracture were identified on admission to inpatient rehabilitation. MEASURES: Four primary outcomes--recovery of activities of daily living, improvement in ambulation, return to community living, and mortality--were measured at 3, 6, 9, and 12 months. Service utilization was assessed in the acute-care hospital setting, rehabilitation setting, and at each 3-month follow-up interval. Risk adjustment was performed by using multiple and logistic regression. RESULTS: Overall, no differences were found between patients in group/staff HMOs and fee-for-service patients. Group/staff HMO patients experienced improved functional recovery at 6 months (P < 0.01) and improved ambulation at 12 months (P = 0.05) compared with fee-for-service patients, although these were isolated findings. With regard to utilization, group/staff HMO delivery systems used physician services less intensively and substituted less-skilled allied health personnel. CONCLUSION: Compared with fee-for-service delivery systems, with a similar commitment to excellence in geriatric rehabilitation, group/staff HMOs can achieve equivalent outcomes in older patients recovering from hip fracture with less-intense service utilization.

Tolterodine use for symptoms of overactive bladder.

OBJECTIVE: To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder. DATA SOURCES: Published articles and abstracts were identified from a MEDLINE search (January 1980-October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration-approved product labeling and the manufacturer were also used in the absence of published data. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of tolterodine involving human subjects were evaluated. DATA SYNTHESIS: Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents. CONCLUSIONS: Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.

Methods and prevalence of ADL limitations in Hispanic and non-Hispanic white subjects in rural Colorado: the San Luis Valley Health and Aging Study.

PURPOSE: The Hispanic population in the United States is the fastest growing minority group, yet there is little understanding of the disability patterns that occur as this population ages. We conducted a cross-sectional study to define the prevalence of limitations of activities of daily living (ADL) and measures of observed function. METHODS: We censussed two rural counties in southern Colorado and selected a stratified sample of both Hispanic and non-Hispanic white (NHW) residents; 81.6% completed the protocol. RESULTS: Among the 1250 subjects aged 65 years and older, Hispanic elderly living in the community had greater ADL disability than NHW subjects, both for any difficulty (p = 0.006), and for needing assistance (p = 0.002). Hispanic persons were less likely to reside in nursing homes (3.4%) compared with NHW persons (9.3%). Hispanic elderly had excess prevalence of dependent ADL tasks (needs assistance or unable to do), (age, gender-adjusted odds ratio = 1.39, 95% CI = 1.01-1.92) in community dwelling and nursing home residents combined. There was no Hispanic excess of less severe difficulty compared with NHW persons, and there was a similar prevalence of limitation on observed functional tasks (timed walk, stooping, rising from a chair) in both groups. CONCLUSIONS: There was a modest Hispanic excess of reported dependent ADL limitation, and no excess of observed functional difficulties. Hispanics enter older age with much less income and education, yet they do not have a marked excess prevalence of limitations in activities of daily living when compared with NHW persons living in the same area.

Indicators of nutritional risk in a rural elderly Hispanic and non-Hispanic white population: San Luis Valley Health and Aging Study.

OBJECTIVE: To describe the prevalence of nutritional risk factors among elderly residents in a rural Hispanic and non-Hispanic white population. DESIGN: A geographically based survey of community-dwelling elderly adults. SUBJECTS/SETTING: From July 1993 to July 1995, all Hispanic persons older than 65 years and an age-stratified, random sample of 69% of non-Hispanic white persons, from 2 Colorado counties, were invited to participate in a study of functional impairment and disability (81% responded). After exclusion of 184 respondents who required a surrogate respondent and 8 with missing diet data, the study consisted of 1,006 subjects. Interviews included questions similar to the Nutrition screening Initiative checklist, a 21-item food frequency questionnaire, and anthropometric measures. STATISTICAL ANALYSES PERFORMED: Gender- and ethnicity-specific, age-adjusted prevalence for each risk factor was estimated by use of logistic regression. RESULTS: Hispanic participants were more likely than non-Hispanic whites to report inadequate intake of vegetables, problems with teeth or dentures that limited the kinds and amounts of food eaten, difficulty preparing meals, and lack of money needed to buy food. Hispanic women reported nutritional risk factors more often than Hispanic men, although anthropometric markers indicated that Hispanic men may be at higher risk of nutritional deficiency. APPLICATIONS/CONCLUSIONS: Hispanic men and women had a higher prevalence of nutritional risk factors than non-Hispanic whites. Intervention programs targeting rural, elderly Hispanics should aim to ensure that basic nutrition needs (access to food, help preparing meals, and adequate dental care) are being met. Community programs to increase activity levels and consumption of nutrient-dense foods are recommended.

Cognitive functioning and impairment among rural elderly Hispanics and non-Hispanic whites as assessed by the Mini-Mental State Examination.

We conducted a cross-sectional study to determine the distribution of cognitive functioning as measured by the Mini-Mental State Examination (MMSE) among a sample of Hispanic and non-Hispanic White (NHW) residents from two counties in rural, southern Colorado. Residents aged 60 years and older (N = 1,360) were administered the full MMSE, a sociodemographic and medical interview. Protocols were developed to administer the MMSE equitably in both ethnic groups. Younger Hispanics tended to be categorized as severely impaired more than similarly aged NHWs (OR at age 70 = 4.14), however, older Hispanics and NHWs performed similarly after adjusting for education and gender (OR at age 90 = 1.00). The use of a modified MMSE scale that removed the ethnic bias demonstrated that NHWs and Hispanics had similar levels of severe impairment after full adjustment (OR = 0.93). Given the widespread use of the MMSE, these findings indicate the need for further validation of this instrument.

Higher instrumental activities of daily living disability in Hispanics compared with non-Hispanic whites in rural Colorado. The San Luis Valley Health and Aging Study.

This study examined Hispanic versus non-Hispanic white patterns of needing assistance with instrumental activities of daily living (IADL). The authors interviewed 798 Hispanic and 614 non-Hispanic white residents of rural Colorado, who were aged 60 years and older between 1993 and 1995. Seventy-five participants were nursing home residents at the time of the interview. Community-dwelling Hispanics were 1.6 times as likely as non-Hispanic whites to need assistance with at least one IADL task (95% confidence interval 1.25-2.13). A larger proportion of disabled non-Hispanic whites were in nursing homes but, after including nursing home residents, Hispanics remained significantly more likely to need assistance on at least one IADL task (odds ratio = 1.49, 95% confidence interval 1.16-1.93). Hispanics were also more likely to have difficulty on observed performance tasks. The Hispanic excess was not removed by adjusting for chronic disease, reported difficulty walking, or income. English language proficiency adjustment lowered the Hispanic excess, but adjusting for years of education or Mini-Mental State Examination scores more completely removed the ethnic differences. Higher education was protective for both Hispanic and non-Hispanic white elderly. Efforts to further investigate what facets or correlates of education are operating may offer useful insights into limiting IADL difficulties in future cohorts.

Evaluation of esophageal cytology using a neural net-based interactive scanning system (the PAPNET system): its possible role in screening for esophageal and gastric carcinoma.

A neural net-based, semiautomated, interactive computerized cell analysis system (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells from 138 esophageal smears obtained by lavage, brushings, or balloon from as many patients. From each smear, trained human observers examined 128 cell images selected by the machine. Abnormal cells were identified in all 35 patients with cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears, the displayed images allowed the recognition of effects of radiotherapy and, in 14 smears, the diagnosis of a specific tumor type, such as squamous cell carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the diagnosis of "carcinoma, not further specified," was established. One case of esophageal carcinoma in situ, not previously recognized on a smear or in the biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the smear, were identified in PAPNET-generated images. The possible application of the apparatus to the triage of smears and population screening for esophageal and gastric carcinoma precursors is discussed.

Physiologic changes in the elderly.

A variety of age-related changes in the oral cavity and throughout the aging body can affect dental care and treatment plans. Some of these changes may be unavoidable features of senescence. Others, previously thought to be part of "normal aging," may be modifiable with lifestyle choices or may represent subclinical pathological processes. The ability to compensate for losses in system capacity varies among individuals and may result in functional changes ranging from substantial to unmeasurable. An appreciation of the intricacy of these relationships, and coordinated treatment with the primary care physician, can enhance the dental care of the aged patient.

Geriatric care approaches in health maintenance organizations.

The objective of this project was to describe geriatric care provided under Medicare-risk contracts in HMOs with established Medicare programs. These findings provided the basis for an invitational workshop, sponsored by the National Institute on Aging and the Robert Wood Johnson Foundation, to formulate a research agenda for geriatric care in HMOs. The case study method involved site visits to seven HMOs by a physician with expertise in geriatrics, a managed care specialist, and a program development specialist. Representatives from the HMOs included senior executive officials, physicians recognized for providing and promoting geriatric care, research and program development staff, and various clinical staff including pharmacists, geriatric nurse practitioners, nurses, and social workers. The most frequently encountered geriatric care programs were categorized by the following six objectives: (1) identifying high risk patients, (2) assessing multi-problem patients, (3) treating multi-problem patients, (4) rehabilitating patients following acute events, (5) reducing medication problems, and (6) providing long-term care and home health care. Unique programs identified from these site visits included screening methods for new enrollees, approaches to comprehensive geriatric assessment, use of skilled nursing facilities for intensive rehabilitation and postacute care, and drug profiling and review. Utilization of geriatric nurse specialists and programs aimed at coordination with social services were pervasive in many of these HMOs. Workshop participants proposed several research and demonstration projects in all six areas. Overall consensus emerged that HMOs with Medicare-risk contracts provide a valuable setting for experimentation in geriatric care. Given the current health policy emphasis on managed care and capitated payment methodologies, geriatric care research in HMOs should be a high priority.

Epidemiology of hypertension in the elderly.

Epidemiological studies confirm that hypertension, particularly systolic hypertension, is a major cardiovascular and cerebrovascular risk factor in the elderly. Clinical trials convincingly demonstrate the benefits of treating both diastolic hypertension in persons up to age 80 years, and isolated systolic hypertension in persons over age 60. The European Working Party on Hypertension in the Elderly (EWPHE) trial showed that reducing elevated blood pressure resulted in a 27% reduction in overall cardiovascular mortality, as well as significant reductions in severe congestive heart failure, strokes and deaths from myocardial infarction. The Systolic Hypertension in the Elderly Program (SHEP) also reported a 36% reduction in the incidence of stroke and decreases in cardiovascular events, including myocardial infarctions, when hypertension was treated. Additional EWPHE data suggest that the optimal level of systolic blood pressure control is between 146 and 158mm Hg, while patients in the SHEP trial with isolated systolic hypertension derived benefits at an average treated systolic blood pressure of 143mm Hg. Elderly study populations comply well with antihypertensive treatment, and blood pressure can be safely lowered with simple drug regimens. Nonpharmacological treatment is recommended for initial treatment of mild diastolic hypertension and isolated systolic hypertension, and as adjuvant treatment with medication. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be chosen based on its potential for side effects, drug interactions and effects on concomitant disease states.

Factors associated with actinomyces-like organisms on Papanicolaou smear in users of intrauterine contraceptive devices.

To determine the factors associated with the presence of actinomyces-like organisms on cervicovaginal Papanicolaou smears in users of the intrauterine contraceptive device (IUD), we carried out a case-control study. Among about 80,000 Papanicolaou smears examined in one year in a large cytology laboratory, actinomyces-like organisms were identified on 107 smears; all but three smears were from IUD users. Compared with IUD users who did not have actinomyces-like organisms on Papanicolaou smears, those with actinomyces-like organisms had used the IUD for more years. An increased risk of actinomyces-like organisms on Papanicolaou smear was not apparent until 7 years of IUD use, however. No significant association of actinomyces-like organisms with the type of IUD was found after controlling for differences in duration of use between users of various IUDs. The percentage of women reporting gynecologic symptoms (vaginal discharge, pelvic pain, abnormal bleeding) also did not differ significantly between IUD users with and without actinomyces-like organisms on Papanicolaou smear (p = 0.5).

Assigning normal blood glucose values by probability plot analysis.

Blood glucose results for 2,601 specimens obtained at multiphasic health examination, divided into three age groups, were analyzed using probability plot paper. Two straight lines could be fitted to each distribution. The assumption was made that the lower lines correspond to "normal-healthy" persons, whereas the upper lines correspond to persons with defective control of blood sugar. It was concluded that the mean of the presumed normal-healthy subgroups rises only a few mg/dl per decade.

Analysis of tympanometry of a severe to profound hearing-impaired population of school-age children.

Impedance audiometry provides a reliable technique for identifying undetected middle ear pathologies in children with severe to profound sensorineural hearing loss. In this study, tympanograms were obtained on 104 children with sensorineural hearing losses of 60 dB or more. The tympanograms were classified according to type and were compared for bilateral similarity. A high percentage of the younger children had abnormal tympanograms, with almost half of these children having the same type of abnormal tympanogram bilaterally. The use of impedance audiometry as a screening technique for hearing-impaired school-age children is discussed.

Chronic mastopathy and breast cancer. A follow-up study.

Over an average period of seven years 2,9000 cases of benign breast lesions diagnosed by biopsy between 1948 and 1973 in the Department of Pathology, Kaiser Foundation Hospital, Oakland, were followed for breast cancer development. When classified according to traditional diagnostic categories, the cancer incidence per 1,000 person-years varies between 2.7 and 7.9 and appears to be elevated in comparison to expectations obtained from the Third National Cancer Survey, San Francisco Bay Area. Two thousand four hundred biopsies were also scored by the Black-Chabou method. There is an upward trend in the breast cancer incidence as the atypia score rises, a finding which confirms conclusions from a retrospective case-control study by Black et al.