Frail older patient care by interdisciplinary teams: a primer for generalists

Frail older patients-unlike younger persons in the health care system or even well elders-require complex care. Most frail older patients have multiple chronic illnesses. Optimum care cannot be achieved by following the paradigm of ongoing traditional health care, which emphasizes disease and cure. Because no one health care professional can possibly have all of the specialized skills required to implement such a model of health care delivery, interdisciplinary team care has evolved. This paper describes the roles of the participating team members in the context of interdisciplinary care for frail older adults. In addition, the challenges that occur when Geriatric Interdisciplinary (ID) Teams involved in providing care to frail older patients are identified and discussed.     

Sequence variations in the public human genome data reflect a bottlenecked population history

Single-nucleotide polymorphisms (SNPs) constitute the great majority of variations in the human genome, and as heritable variable landmarks they are useful markers for disease mapping and resolving population structure. Redundant coverage in overlaps of large-insert genomic clones, sequenced as part of the Human Genome Project, comprises a quarter of the genome, and it is representative in terms of base compositional and functional sequence features. We mined these regions to produce 500,000 high-confidence SNP candidates as a uniform resource for describing nucleotide diversity and its regional variation within the genome. Distributions of marker density observed at different overlap length scales under a model of recombination and population size change show that the history of the population represented by the public genome sequence is one of collapse followed by a recent phase of mild size recovery. The inferred times of collapse and recovery are Upper Paleolithic, in agreement with archaeological evidence of the initial modern human colonization of Europe.     

Breast radiotherapy with inclusion of internal mammary nodes: a comparison of techniques with three-dimensional planning

PURPOSE: To compare the partially wide tangent (PWT) technique of breast and internal mammary chain irradiation with photon/electron (P/E) and standard tangent (ST) techniques in terms of dose homogeneity within breast and the dose to critical structures such as the heart and lung. METHODS AND MATERIALS: Sixteen left breast cancer patients underwent CT simulation. The breasts, lungs, heart, and internal mammary chain were contoured and treatment plans generated on a three-dimensional planning system (Helax-TMS). RESULTS: The mean dose to the left breast volume with the ST, P/E, and PWT techniques was 94.7%, 98.4%, and 96.5%, respectively (p = 0.029). The left lung received the lowest mean dose with the ST technique (13.9%) compared with PWT (22.8%) and P/E (24.3%). The internal mammary chain volume was most consistently treated with the PWT (mean dose 99%) vs. P/E (86%) and ST (38.4%) techniques. The heart received the least dose with ST (mean dose 6.7%) vs. PWT (10.3%) and P/E (19%). The PWT treated the greatest amount of contralateral breast (mean dose 5.8%) vs. ST (3.2%) vs. P/E (2.8%). CONCLUSION: The PWT technique treats the internal mammary chain with acceptable toxicity to major organs, especially the heart, and with reasonable dose homogeneity in patients with mastectomy or intact breasts.     

Successful treatment of extramammary Paget's disease with imiquimod

Extramammary Paget's Disease (EMPD) is an uncommon neoplasm found in the genital, anorectal, or axillary area. Surgical excision is considered the standard treatment, although possible loss of tissue function and disease recurrence are seen. Other treatment modalities such as radiotherapy, topical chemotherapy, and photodynamic therapy are associated with varying degrees of effectiveness, but the search for an effective, safe treatment with minimal side effects proves to be challenging. We report a case where complete clinical and histological resolution of non-invasive EMPD of the penis was achieved with minimal adverse effects after six weeks of imiquimod (Aldara) application. As an immune system modifier that stimulates cytokine and interferon production, imiquimod may be a useful alternative or adjuvant in the treatment of EMPD.     

Drugs of abuse and the elicitation of human aggressive behavior

The drug-violence relationship exists for several reasons, some direct (drugs pharmacologically inducing violence) and some indirect (violence occurring in order to attain drugs). Moreover, the nature of that relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. This paper reviews the existing literature regarding the extent to which various drugs of abuse may be directly associated with heightened interpersonal violence. Alcohol is clearly the drug with the most evidence to support a direct intoxication-violence relationship. The literatures concerning benzodiazepines, opiates, psychostimulants, and phencyclidine (PCP) are idiosyncratic but suggest that personality factors may be as (or more) important than pharmacological ones. Cannabis reduces likelihood of violence during intoxication, but mounting evidence associates withdrawal with aggressivity. The literature on the relationship between steroids and aggression is largely confounded, and between 3,4-methylenedioxymethamphetamine (MDMA) and aggression insufficient to draw any reasonable conclusions. Conclusions and policy implications are briefly discussed.     

Recombinant fowlpox viruses encoding the anchor-modified gp100 melanoma antigen can generate antitumor immune responses in patients with metastatic melanoma.

PURPOSE: The purpose of this study was to evaluate the immunological responses and therapeutic effectiveness of immunization with fowlpox vaccines encoding the gp100 melanoma antigen in patients with metastatic melanoma. Experimental Design: In three consecutive clinical trials, patients were immunized with recombinant fowlpox viruses encoding three different forms of the melanoma/melanocyte-associated antigen gp100: (a) the native, full-length gp100 molecule; (b) the gp100 molecule with two amino acids modified to increase binding to HLA-A*0201 molecules; and (c) a "minigene" construct encoding a single, modified epitope gp100:209-217(210M) targeted to the endoplasmic reticulum. The immunogenicity of these constructs was studied using peripheral blood mononuclear cells to measure epitope-specific release of IFN-gamma. RESULTS: Reactivity against gp100 was not seen in any patient before receiving fowlpox immunization. Whereas just one of seven patients developed reactivity after receiving fowlpox encoding native gp100, 10 of 14 patients who received fowlpox encoding the anchor modified full-length gp100 exhibited reactivity against the native gp100 molecule, and 12 of 16 patients were successfully immunized after inoculation with the modified minigene construct (p2 = 0.02). There was no difference in the latter group between those randomized to vaccination by i.v. or i.m. routes. There was one partial cancer regression in the group of 46 patients receiving virus in the absence of interleukin (IL)-2. Once patients showed evidence of progressive disease, they were eligible for "cross-over" treatment to IL-2 alone or with the fowlpox virus. None of the 13 patients receiving the full-length or modified full-length forms of gp100 responded when receiving IL-2, whereas 6 of 12 patients who received the fowlpox containing the minigene construct and then received IL-2 showed objective cancer regressions, including three patients with complete regression. CONCLUSIONS: These data underscore the importance of modifying anchor residues of nonmutated self-antigen peptides to generate cellular immune responses after immunization and support the further investigation of recombinant fowlpox viruses encoding modified epitopes administered in combination with IL-2.     

Changes in youth smoking participation in California in the 1990s

OBJECTIVE: To identify which key transitions in the adolescent smoking uptake process changed during periods of increasing and decreasing adolescent smoking participation in California. METHODS: Age groups (12-14 and 15-17 years) from longitudinal surveys of California adolescents, conducted in 1993-1996 (prevalence increasing) and in 1996-1999 (prevalence declining), allowed comparisons of transition rates across these periods for: never smokers (committed and susceptible) to any smoking, experimenters to established smokers, and current established smokers to former smokers (15-17-year-olds only). Analyses adjusted for demographics and other baseline environmental influences on adolescents to smoke, with a variable for 'time period' included to test for differential period transition rates. RESULTS: Adjusted analyses indicated a time period effect (1993-1996 versus 1996-1999) on all transitions examined for 12-14-year-olds. For 15-17-year-olds, the time period effect was significant for the transition from committed never smoker to any smoking, but only marginally significant for experimenter to established smoker and from current established to former smoker. CONCLUSION: Adolescent smoking participation appeared to decline at all phases in the smoking uptake process, with generally larger declines in younger adolescents. Intensified public health measures to curb adolescent smoking beginning in the mid 1990s may have been responsible.     

Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2

Methionine aminopeptidase (MetAP)-2 has been suggested as a novel target for cancer therapy because the anticancer agent TNP-470 irreversibly inactivates the catalytic activity of this enzyme. However, the importance of MetAP2 in cell growth and tumor progression was uncertain because previous data were based on the chemically reactive TNP-470. Here we show that a rationally designed reversible MetAP2 inhibitor, A-357300, suppresses tumor growth preclinically without the toxicities observed with TNP-470. We have synthesized this bestatin-type MetAP2 inhibitor with the aid of crystal structures of the enzyme-inhibitor complexes and parallel synthesis. A-357300 induces cytostasis by cell cycle arrest at the G(1) phase selectively in endothelial cells and in a subset of tumor cells, but not in most primary cells of nonendothelial type. A-357300 inhibits angiogenesis both in vitro and in vivo and shows potent antitumor efficacy in carcinoma, sarcoma, and neuroblastoma murine models. These data affirm that MetAP2 plays a pivotal role in cell growth and establish that reversible MetAP2 inhibitors are promising novel cancer therapeutic agents.     

Positron emission tomography in the initial staging of esophageal cancer

OBJECTIVE: To assess the value of positron emission tomography (PET) compared with computed tomography (CT) in the initial staging of esophageal cancer. DESIGN: Case series. SETTING: Tertiary care veterans hospital. PATIENTS: Patients with newly diagnosed esophageal cancers from January 1996 through May 2001 who underwent both CT and PET scanning within 4 weeks were included in the study (n = 24). Only patients who underwent pathological or radiographic follow-up were included. MAIN OUTCOME MEASURES: The sensitivity, specificity, and negative and positive predictive values of CT and PET were determined based on a criterion standard of pathological staging in 16 patients (67%) and follow-up imaging in 8 patients (33%). RESULTS: For staging regional lymph node involvement, CT and PET scans showed no statistically significant difference in sensitivity (57% and 71%, respectively) and specificity (71% and 86%, respectively). For detection of metastatic disease, CT and PET showed no significant difference in sensitivity (83% and 67%, respectively) and specificity (75% and 92%, respectively). There was no significant difference in clinical decision making when the results of both tests were discordant. CONCLUSIONS: There was no significant difference between the 2 imaging modalities in the initial staging of esophageal cancer. The CT scan was a sensitive indicator of distant metastases, whereas PET was more specific. It is unclear what additional role PET scanning should have in the initial screening of patients.