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Biomedical subjects

E Langer

Publications and source records attributed to E Langer.

At least 19 recordsLinked to original sources

Drug interactions and cytotoxic effects of paclitaxel in combination with carboplatin, epirubicin, gemcitabine or vinorelbine in breast cancer cell lines and tumor samples.

The purpose of this study was to analyze the drug interactions of paclitaxel (PTX) with epirubicin (EPI), carboplatin (CBDCA), gemcitabine (GEM) and vinorelbine (VIN) in human breast cancer cells and compare the cytotoxic activity of each drug combination in primary breast cancer samples. These experiments were intended to identify the most active agents in combination with PTX, and to provide a preclinical rational for future clinical investigations in breast cancer. Multiple drug effect/combination index (CI) isobologram analysis was applied to combinations of PTX with either CBDCA, EPI, GEM or VIN in MCF-7, MDA-MB-231 and SK-BR-3 human breast cancer cell lines. Drug concentrations were limited to the ranges achievable in humans in vivo, and the drugs were applied simultaneously at fixed molar ratios for each drug combination. Interactions were assessed at multiple effect levels (IC10-IC90). Additionally, the cytotoxic activity of these combinations was assessed in tumor samples of 50 primary breast cancer patients, utilizing the ATP-tumorchemosensitivity assay (ATP-TCA). Drug interactions were shown to be strongly dose-related in the human breast cancer cell lines investigated. At clinically relevant concentrations, CBDCA/PTX demonstrated synergistic (MCF-7) or additive (MDA-MB-231, SK-BR-3) interactions, and EPI/PTX showed additive (SK-BR-3, MCF-7) and antagonistic (MDA-MB-231) interactions. GEM/PTX and VIN/PTX, however, demonstrated antagonism over multiple dose effect levels at clinically relevant drug concentrations in all three cell lines tested. At plasma peak concentrations, EPI/PTX, CBDCA/PTX, GEM/PTX and VIN/PTX achieved > or = 90% tumor growth inhibition in 93, 86, 63 and 50%, respectively, of primary breast cancer samples investigated with the ATP-TCA. Cumulative dose-response plots of primary breast cancer tumor cells responding in vitro with > or = 90% growth inhibition showed a strong dose dependence for both EPI/PTX and CBDCA/PTX. In conclusion, the current data indicate favorable drug interactions for CBDCA/PTX at clinically relevant drug concentrations in breast cancer cells, and demonstrate superior in vitro cytotoxicity of EPI/PTX and CBDCA/PTX compared to GEM/PTX and VIN/PTX in primary breast cancer cultures.

Antineoplastic Agents↗

Mortality following isolation of various respiratory viruses in nursing home residents.

OBJECTIVE: To compare mortality following isolation of influenza A to mortality following isolation of other respiratory viruses in a nursing home. SETTING: The Wisconsin Veterans Home, a 688-bed skilled nursing facility for veterans and their spouses. PARTICIPANTS: All residents with respiratory viral isolates obtained between 1988 and 1999. DESIGN: Thirty-day mortality was determined following each culture-proven illness. RESULTS: Thirty-day mortality following isolation of viral respiratory pathogens was 4.7% (15/322) for influenza A; 5.4% (7/129) for influenza B; 6.1% (3/49) for parainfluenza type 1; 0% (0/26) for parainfluenza types 2, 3, and 4; 0% (0/26) for respiratory syncytial virus (RSV); and 1.6% (1/61) for rhinovirus. CONCLUSIONS: Mortality following isolation of certain other respiratory viruses may be comparable to that following influenza A (although influenza A mortality might be higher without vaccination and antiviral agents). The use of uniform secretion precautions for all viral respiratory illness deserves consideration in nursing homes.

Aged↗

Evolution of gilled mushrooms and puffballs inferred from ribosomal DNA sequences.

Homobasidiomycete fungi display many complex fruiting body morphologies, including mushrooms and puffballs, but their anatomical simplicity has confounded efforts to understand the evolution of these forms. We performed a comprehensive phylogenetic analysis of homobasidiomycetes, using sequences from nuclear and mitochondrial ribosomal DNA, with an emphasis on understanding evolutionary relationships of gilled mushrooms and puffballs. Parsimony-based optimization of character states on our phylogenetic trees suggested that strikingly similar gilled mushrooms evolved at least six times, from morphologically diverse precursors. Approximately 87% of gilled mushrooms are in a single lineage, which we call the "euagarics." Recently discovered 90 million-year-old fossil mushrooms are probably euagarics, suggesting that (i) the origin of this clade must have occurred no later than the mid-Cretaceous and (ii) the gilled mushroom morphology has been maintained in certain lineages for tens of millions of years. Puffballs and other forms with enclosed spore-bearing structures (Gasteromycetes) evolved at least four times. Derivation of Gasteromycetes from forms with exposed spore-bearing structures (Hymenomycetes) is correlated with repeated loss of forcible spore discharge (ballistospory). Diverse fruiting body forms and spore dispersal mechanisms have evolved among Gasteromycetes. Nevertheless, it appears that Hymenomycetes have never been secondarily derived from Gasteromycetes, which suggests that the loss of ballistospory has constrained evolution in these lineages.

Basidiomycota↗

Perception of body shape by underweight average, and overweight men and women.

Using figure drawings, perception of body shape was evaluated by underweight, average, and overweight men and women. Body-shape dissatisfaction was greatest for 60 overweight women, and about the same in 151 average weight women as it was for 102 overweight men. Average weight men (n = 107) and underweight women (n = 31) were fairly satisfied with their current shapes. Both men and women had distorted views of the shape the opposite sex found most attractive. Women guessed that men would prefer a thinner shape than they actually did, and men guessed that women would prefer a larger shape than they actually did. The distortion was larger for men as their own size increased but not for women.

Adult↗

Risk factors for bacteriuria in men.

OBJECTIVE: To identify risk factors for bacteriuria in a selected group of institutionalized men. METHODS: A total of 99 men, mean age seventy-one years, range forty-eight to one hundred four years, living in a nursing home were evaluated for diagnoses of benign prostatic hyperplasia (BPH) and diabetes mellitus (DM), symptoms of bladder outlet obstruction, and postvoid residual urine volume (PVR). At the time of evaluation urine cultures were performed for all subjects. Urinalyses had been performed in all men within the two years prior to initiation of the study. Residents unable to give informed consent, with a history of cancer of the prostate or bladder, previous urethral or prostate surgery, or inability to void in the standing position were excluded. RESULTS: Prior to or during the study 30 residents had bacteriuria, which was not correlated with age, PVR, previous diagnoses of BPH or DM, or with obstructive or irritative urinary symptoms consistent with bladder outlet obstruction. CONCLUSIONS: Competent, institutionalized residents with higher functional levels meeting the inclusion criteria were not at a high risk of bacteriuria. The concept that increased PVR per se predisposes to bacteriuria cannot be substantiated.

Age Factors↗

Aging free from negative stereotypes: successful memory in China and among the American deaf.

This study explores whether negative stereotypes about aging contribute to memory loss in old age. The research participants consisted of old and young Chinese hearing, American Deaf, and American hearing individuals. Members of the mainland Chinese and the American Deaf cultures were recruited on the basis of the belief that they would be less likely than hearing Americans to be exposed to and accept negative stereotypes about aging. The expected results were (a) an interaction in which the 3 groups of younger Ss would perform similarly on the memory tasks, whereas the older Deaf and older Chinese participants would outperform the older American hearing group and (b) a positive correlation between view toward aging and memory performance among the old Ss. The data supported both hypotheses. The results suggest that cultural beliefs about aging play a role in determining the degree of memory loss people experience in old age.

Adolescent↗

Efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine in elderly nursing home subjects during an influenza outbreak.

OBJECTIVE: To compare the efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. DESIGN: A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. SETTING: Fourteen Wisconsin nursing homes. PARTICIPANTS: Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. INTERVENTIONS: Participants received, by intramuscular injection, 0.5 mL of a trivalent influenza vaccine containing 15 micrograms each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mL of an influenza vaccine containing the same antigens conjugated to diphtheria toxoid (HA-D). MEASUREMENTS: Blood was obtained pre- and 1 month post-vaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. RESULTS: 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). CONCLUSIONS: HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HA-D's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers.

Aged↗

[Myiasis in female travelers to the tropics].

Myiasis is a rare disease in Europe and the USA; it is defined by the development of parasitic, mostly tropical maggots in the human body. They are best identified by the pattern of their terminal spiracles and the shape of their stigmal plates. In spite of the size of the larvae of Cordylobia anthropophaga, there is only low-grade inflammation; the clinical course is benign.

Aged↗

Golgi-Kopsch silver study of the brain of a patient with untreated phenylketonuria, seizures, and cortical blindness.

This report describes the morphological changes observed in the brain of an untreated 27-year-old man with phenylketonuria, cortical blindness, and seizures. Golgi-Kopsch silver, cresyl violet, and hematoxylin and eosin stains were used to study cell structure and organization of the cerebellum, the lateral geniculate nuclei, the visual cortex, frontal cortex, and hippocampus. Extensive neuronal losses occurred in the right lateral geniculate nucleus (LGN), the visual cortex, and hippocampus. The left LGN, cerebellum, and frontal cortex retained neuronal components; there was a reduction in the number of dendritic processes on the Purkinje cells of the PKU subject. The loss of neurons in the LGN and occipital cortex is related to the blindness and the neuronal loss in the hippocampus is related to seizure activity.

Blindness↗

Thyroid stimulating hormone elevation without antithyroid antibody elevation in nursing home patients.

OBJECTIVES: To investigate the relationship between antithyroid antibody elevation and thyrotropin (TSH) elevation. SETTING: Large state veterans home. METHODS: Seven hundred seventy-six residents were screened for TSH elevation. Seventy-two residents with TSH elevation and no history of thyroid disease or recent iodine exposure later had determinations of antithyroglobulin and antimicrosomal antibodies. The relationship between TSH levels and antibody titers was explored. RESULTS: Eleven percent of the residents had TSH elevation. Thirty-two percent of men and 64% of women with TSH elevation had elevation of antithyroid antibodies. Those residents with the highest antithyroid antibody titers had significantly greater TSH elevation. CONCLUSION: Previous investigators have found similar percentages of individuals with TSH elevation who lack antithyroid antibody elevation. We hypothesize that TSH elevation without elevated antibody titers may be the result of a previously described involutional histologic lesion of the thyroid.

Aged↗

Readmissions and acuity in the nursing home--how will the nursing homes manage?

Decreased hospital length of stay and the shift of location of death from the hospital to the nursing home have increased the burden of care that must be provided by nursing home staff. Complex interaction of multiple disease states was the dominant factor in the readmission of nursing home residents to hospitals within 30 days of their previous discharge. Advanced nursing practice provided by gerontological nurse practitioners can monitor acute and chronic illnessess and decrease rates of hospitalization, as well as provide educational expertise to improve the nursing assessment and planning skills of the nursing home staff.

Aged↗

Misleading elevation of the free thyroxine index in nursing home residents.

The significance of an elevated free thyroxine index (FTI) as an indicator of hyperthyroidism was studied while screening 651 elderly nursing home residents. Eleven subjects had FTI elevations. Most of these patients were chronically ill and/or malnourished. Clinical assessment, repeated FTI determinations, and subsequent measurements of levels of triiodothyronine, free thyroxine by equilibrium dialysis, and thyrotropin (thyroid-stimulating hormone) by sensitive assay showed that all subjects with FTI elevation were euthyroid. The FTI elevation in the chronically ill institutionalized elderly patient is not necessarily an expression of hyperthyroidism.

Aged↗

[Generalized argyrosis].

For many years a 52-year-old patient suffering from duodenal ulcer had taken a silver-containing preparation, the total quantity of silver ingested in this manner amounting to about 35 g. 18 years after the first manifestation of duodenal ulcer a dermatologist diagnosed argyria and confirmed this by biopsy. After acute coronary failure with marked nicotine abuse autopsy revealed granulated deposits of silver in the corium, particularly on elastic fibres, at the sweat glands, sebaceous glands and hair follicles. There were no deposits in the epidermis. Dense silver deposits were also seen in the walls of most of the blood vessels, in the basal membranes of the renal glomeruli, of the choroid plexus and of the seminiferous tubules, as well as in the portal fields. Definite intracellular deposits occurred in macrophages only. The metal was found only rarely in epithelial basal membranes. Generalised argyria does not entail any pathological implications and is considered to be intractable.

Anti-Ulcer Agents↗

Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome.

Two non-alcoholic homosexual patients with acquired immunodeficiency syndrome (AIDS) are reported who developed acute Wernicke's encephalopathy in the terminal stage of their illness. The first patient presented with vascular congestion, minute haemorrhages, proliferation of microglia and of the vessel walls at the predilection sites of the Wernicke-Korsakoff process. In the second patient only the mamillary bodies were involved. Besides Wernicke's encephalopathy, a primary cerebral immunoblastoma and cerebral toxoplasmosis were found in the first patient, whereas the second showed severe encephalitis with numerous microglial and multinucleated giant cells reacting positively with anti-HIV antibody. Just as in the development of Wernicke's encephalopathy in malignant diseases, the catabolic trend of the metabolism of the immunodeficient patients with consecutive thiamine deficiency must be considered the principal pathogenetic mechanism.

Acquired Immunodeficiency Syndrome↗

Do the elderly sue physicians?

We reviewed malpractice data from the state of Wisconsin for 1983 and 1984 to determine the frequency and the outcome of malpractice litigation by the elderly. Research data were obtained from court dockets filed with Wisconsin's Patients Compensation Panel and from 281 attorneys who provided the age for 431 claimants. The results showed that 10.0% of malpractice suits in Wisconsin were filed by the elderly during the study years. When we compared the frequency of litigation with the use of the health care system (number of hospitalizations and inpatient days), the elderly were significantly less likely than younger persons to initiate malpractice litigation despite greater exposure to potential negligence. However, once a malpractice suit was filed, there was no significant difference between older and younger litigants in the disposition of the case or in the likelihood of being the prevailing party when a finding or award was made. These findings suggest that the elderly are less likely to file malpractice claims against health care providers than would be expected given their use of the health care system. This finding may be related to social, economic, and legal barriers to malpractice litigation by older adults.

Adult↗