Employers confront violence in the workplace of the '90s.
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Employee Grievances↗
Biomedical subjects
K McCormick
Publications and source records attributed to K McCormick.
Wavelet variations on the Shannon sampling theorem.
The Shannon sampling theorem asserts that a continuous square-integrable function on the real line which has a compactly supported Fourier transform is uniquely determined by its restriction to a uniform lattice of points whose density is determined by the support of the Fourier transform. This result can be extended to the wavelet representation of functions in two ways. First, under the same type of conditions as for the Shannon theorem, the scaling coefficients of a wavelet expansion will determine uniquely the given square-integrable function. Secondly, for a more general function, there is a unique extension from a given set of scaling coefficients to a full wavelet expansion which minimizes the local obstructions to translation invariance in a variational sense.
Fourier Analysis↗
Osteomalacia with hypophosphatemia and hypercalciuria: a possible new variant of osteomalacia.
A 12-year-old girl had a severe genu valgum deformity and osteomalacia with hypophosphatemia, hypercalciuria, and modestly elevated levels of 1,25-dihydroxyvitamin D3 and intact parathyroid hormone. This patient seems to have a different type of hypophosphatemic osteomalacia from that previously described.
Calcitriol↗
Photon-assisted tunneling through a quantum dot.
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Journal Article↗
Bipolar surface electrical stimulation of the vertebrate retina.
BACKGROUND: Retinitis pigmentosa with attendant photoreceptor loss can cause a profound visual handicap. We have postulated that an intraocular prosthesis that could electrically stimulate the inner retina might provide vision to some of these patients. For such a prosthesis to be feasible, electrical stimulation of the inner retina must elicit a focal retinal response. The stimulating current densities required to elicit such a response must not result in irreversible toxic reactions at the electrode-tissue interface. METHODS: To test the feasibility of this approach, we used bipolar platinum wire electrodes to electrically stimulate the inner retinal surface in bullfrog eyecup preparations and, using similar methods, we electrically stimulated rabbit eyes after injecting intravenous sodium iodate (40 mg/kg), a retinal pigment epithelial toxin with secondary effects on the photoreceptors. RESULTS: Surface electrical stimulation of the inner retina in normal eyes and in eyes with outer retinal degeneration can elicit a localized retinal response. The threshold stimulating currents resulted in charge densities of 2.98 microcoulombs per square centimeter (bullfrog), 8.92 microC/cm2 (normal rabbit), and 11.9 microC/cm2 (rabbit retinas with outer retinal degenerations). These charge densities are within the previously delineated safe limits for long-term electrical stimulation of neural tissue using platinum microelectrodes (100 microC/cm2). CONCLUSION: Multifocal electrical stimulation of the retina might be a viable approach to provide some vision to patients who have profound visual loss due to outer retinal degenerations.
Animals↗
Enhancing clinical practice. The role of practice guidelines.
Health service researchers believe that significant practice variations occur, in part, because there is no strong consensus on best practices for managing a specific condition. The Agency for Health Care Policy and Research (AHCPR) supports the development of science-based clinical guidelines, performance measures, and standards of quality. Since 1992, it has published 6 clinical guidelines and is supporting development of more than 20 others. Each has a consumer version, in English and Spanish, to educate patients and describe care options. Widespread use of these guidelines will improve the quality of health care by assisting providers in making more informed decisions, thereby reducing unnecessary health care practices; will reduce some costs; and will provide feedback on knowledge gaps that merit the attention and support of researchers and policymakers.
Humans↗
Multimodality management of recurrent adult malignant gliomas: results of a phase II multiagent chemotherapy study and analysis of cytoreductive surgery.
Fifty-one adult patients with recurrent malignant gliomas were treated in a Phase II trial of multidrug chemotherapy (6-thioguanine, dibromodulcitol, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 5-fluorouracil, and hydroxyurea). Thirty-one patients underwent radical tumor debulking, before the administration of chemotherapy. Fifty-seven percent of all patients had either an objective radiographic response or stabilization of disease after the institution of therapy. The overall median survival time (MST) was 40 weeks; it was 79 and 33 weeks for anaplastic astrocytoma and glioblastoma patients, respectively. The overall median time to tumor progression (MTP) was 19 weeks--32 weeks for anaplastic astrocytoma patients and 13 weeks for glioblastoma patients. Serious chemotoxicity occurred in 35% of patients without permanent morbidity or mortality. The factors that affected response (including disease stabilization), MTP, and MST were identified through a multivariate statistical analysis. A longer MTP was associated with higher Karnofsky scores, lower grade initial histology, lack of prior chemotherapy, greater degree of myelotoxicity, smaller postoperative tumor volumes, greater extent of surgical resection, and a local versus diffuse recurrence pattern. A longer MST was associated with higher Karnofsky scores, lower grade histology at the time of recurrence, greater degree of myelotoxicity, and lobar versus deep tumor location. Response (including disease stabilization) correlated with higher Karnofsky scores, lower grade histology (initial and current), prior lower grade histology, smaller preoperative tumor volume, longer intervals from the time of initial diagnosis, and absence of prior chemotherapy. These results suggest that, in addition to established prognostic factors such as Karnofsky scores, other factors including prior chemotherapy administration, patterns of tumor recurrence, and tumor location may be important variables to consider in future Phase II-III clinical trials. Of the treatment variables analyzed, greater surgical debulking and smaller postoperative tumor volumes were associated with prolonged MTP but not MST, and greater myelotoxicity had a positive association with all outcomes. The significance of this latter relationship and its relevance to chemotherapy dosing will require further study. Standardization in the design and reporting of clinical trials and the use of computer-assisted tumor volume calculations to assess the extent of surgical resection and the response to therapy are advocated.
Adult↗
H mode of the W 7-AS stellarator.
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Journal Article↗
Hypothalamic-pituitary dysfunction after radiation for brain tumors.
BACKGROUND: Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon. METHODS: We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation. RESULTS: Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients, (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes. CONCLUSIONS: Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present.
Adolescent↗
Associations of HLA-DR and HLA-DQ types with anti-GBM nephritis by sequence-specific oligonucleotide probe hybridization.
Twenty-three patients from the United States with anti-glomerular basement membrane nephritis (Goodpasture's syndrome) were HLA class I and class II typed by serology and HLA-DR and HLA-DQB typed using sequence-specific oligonucleotide (SSO) probes. Protocols used were those of the 11th International HLA Workshop. We were able to confirm the strong association of DR2 with the disease and, using the molecular techniques, showed that all DR2 patients were restricted to DRB1-1501 and DQB1-0602 alleles. We also found highly significant associations between disease and the alleles of DRB1-0301 and DQB1-0201. DR4 alleles as a group were not significantly more frequent among patients, but the allele DRB1-0404 did appear to be associated with the disease. The use of SSO typing provides an expanded opportunity for refined analysis of HLA and disease associated alleles.
Base Sequence↗
An annotated algorithm approach to clinical guideline development.
The Urinary Incontinence in Adults Guideline Panel facilitated the ready elucidation of its guideline's management recommendations through the use of an annotated algorithm approach. The algorithms created as part of this guideline differ from previous algorithms in two ways: (1) they employ systematic annotation to link explicitly the algorithms' recommendations to the literature, and (2) they contain patient counseling and decision nodes to depict the major preference-dependent decision or branch points in the algorithm. We believe that these two innovations can help ensure the clinical validity of guidelines' algorithms while preserving appropriate clinical flexibility and respecting patient preferences.
Algorithms↗
Antiepileptic drug disposition during pregnancy.
A significant proportion of women with epilepsy have an increase in their seizure frequency during pregnancy. Multiple factors may be involved in this phenomenon, but changes in antiepileptic drug (AED) concentration appear to be the most significant. AED concentration declines as pregnancy progresses, due primarily to dynamic changes in plasma protein binding. Total concentrations of all first-line AEDs (carbamazepine, phenytoin, phenobarbital, and valproic acid) fall significantly during pregnancy, compared to baseline. Free or unbound drug concentrations, however, fall significantly only for phenobarbital. Valproate free concentrations actually increase by 25% by delivery. Women taking carbamazepine, phenytoin, or valproate may be relatively protected by adequate free concentrations of these compounds. When managing pregnant women with epilepsy, measurement of free AED concentrations and appropriate dose adjustment to maintain therapeutic ranges will permit more effective clinical management than using total concentration values.
Adult↗
The role of testosterone in trichloroethylene penetration in vitro.
Sex differences are known to exist in the metabolism and bioavailability of trichloroethylene (TCE). This study revealed that dermal penetration of [14C]TCE in vitro was twofold greater in untreated female than in untreated male Sprague-Dawley rats. Since testosterone has been shown to mediate a wide variety of sex differences, its role in dermal penetration of [14C]TCE was investigated. Penetration was measured by using an in vitro evaporation-penetration cell with a 10-hr collection period. Depriving male rats of testosterone (by castration) resulted in increased values for total penetration, area under the curve (AUC), and penetration slopes compared to those for male control animals. The values for male animals deprived of testosterone approached those found in the female control group. Administration of testosterone to female animals produced values for total penetration, AUC, and penetration slopes significantly lower than those of the female control group.
Analysis of Variance↗
Psychophysiologic correlates of quality of life in chronic bronchitis and emphysema.
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Activities of Daily Living↗
Chemoprotective effects of recombinant human IL-1 alpha in cyclophosphamide-treated normal and tumor-bearing mice. Protection from acute toxicity, hematologic effects, development of late mortality, and enhanced therapeutic efficacy.
In this study, recombinant human IL-1 alpha (rhIL-1 alpha) was used to protect normal and tumor-bearing BALB/c mice from the acute toxicity caused by lethal doses of cyclophosphamide (Cy) and 5-fluorouracil. Pretreatment of mice for 7 days with 10,000 U/day of rhIL-1 alpha protected 70 to 100% of mice from the acute death induced by lethal doses of both Cy (380 mg/kg) and 5-fluorouracil (250 mg/kg). In contrast, post-treatment of mice with single or multiple doses of rhIL-1 alpha was not chemoprotective. Pretreatment of mice with rhIL-1 alpha increased the acute LD90 of Cy from 380 mg/kg to greater than 500 mg/kg in normal mice, an LD90 dose-modifying effect of at least 1.25, was accompanied by a more rapid recovery from neutropenia and a less severe reduction in the number of bone marrow single lineage monocyte, myeloid, or myelomonocytic colonies. Some of the mice (10 to 50%) that were successfully protected by pretreatment with rhIL-1 alpha died after day 50. These mice consistently presented with extensive pulmonary inflammation and fibrosis at death. Mice bearing murine renal cancer (Renca) were also protected from the acute toxic effects of Cy (450 mg/kg) by pretreatment with rhIL-1 alpha. Renca-bearing mice pretreated with rhIL-1 alpha and either sublethal (300 mg/kg) or lethal (450 mg/kg) doses of Cy exhibited enhanced survival times over those of untreated Renca-bearing mice. Interestingly, the cause of death in Renca-bearing mice that ultimately failed treatment with rhIL-1 alpha plus 300 mg/kg Cy was recurrent tumor, whereas most mice treated with rhIL-1 alpha plus 450 mg/kg Cy had no detectable tumor, although several died from late pulmonary inflammation and fibrosis. Thus, the dose escalation of Cy in rhIL-1 alpha-pretreated mice results in greater antitumor effects of Cy. However, the dose escalation of some cytotoxic agents allowed by the use of myelostimulatory agents can result in late fatal complications not detected in acute toxicity testing.
Animals↗
Antitumor effects of alpha-interferon and gamma-interferon on a murine renal cancer (Renca) in vitro and in vivo.
Previous studies have shown that established murine renal cancer (Renca) can be successfully treated with the investigational drug flavone acetic acid (FAA) used in combination with recombinant interleukin 2 (IL-2). Additional experiments demonstrated that the in vivo administration of FAA rapidly induced the expression of the genes, as well as the biologically active proteins, for alpha- and beta-interferons (IFNs) as well as tumor necrosis factor alpha. Both IFN-alpha and IFN-gamma have been shown to have direct antiproliferative effects against some tumors, as well as being potent immunodulators for the induction of antitumor effector cells. Thus, the present study was designed to investigate the ability of IFN-alpha and/or IFN-gamma to mediate direct antiproliferative effects against Renca in vitro as well as to cause regression of Renca in vivo. The present study confirms that RAA and/or IL-2 are inactive against Renca in vitro, further suggesting an indirect mechanism for FAA-induced antitumor effects in vivo. However, the exposure of Renca in vitro to recombinant human IFN-alpha A/D, murine IFN-alpha or murine IFN-beta resulted in a dose dependent growth inhibition of Renca as assessed by the microculture tetrazolium dye incorporation assay. Very little growth inhibition was induced by recombinant murine IFN-gamma. Interestingly, IFN-alpha (100-1000 units/ml) when combined with very low doses of recombinant murine IFN-gamma (1-10 units/ml) yielded significantly more pronounced growth inhibition than either cytokine alone. This effect was most evident by 5 days of culture where combinations of 100-1000 units/ml recombinant human IFN-alpha A/D with 1-5 units/ml recombinant murine IFN-gamma yielded growth inhibition in the range of 45-99%. In order to determine whether the mechanisms for the antitumor activity of recombinant human IFN-alpha A/D and recombinant murine IFN-gamma was due to their direct antiproliferative effects, we also studied the efficacy of these combinations against i.p. Renca in athymic mice. In contrast to the potent antitumor effects observed in euthymic mice, the combination of IFN-alpha and IFN-gamma only slightly increased mean survival times in athymic mice and no long term survivors were obtained. Subsequent studies demonstrated that most mice (77%) cured of peritoneal Renca by recombinant human IFN-alpha A/D plus recombinant murine IFN-gamma were immune to rechallenge. Therefore the combination of IFN-alpha and IFN-gamma may directly inhibit the growth of Renca, but a major effect of IFNs in vivo must be to contribute to the induction of an anti-Renca immune response.
Adjuvants, Immunologic↗
Disease and symptom severity, functional status, and quality of life in chronic bronchitis and emphysema (CBE).
A path analysis model examined interrelationships among variables significantly associated with chronic dyspnea in chronic bronchitis and emphysema (CBE) and the relative influence of these variables on each other and on functional status and quality of life. Results from the 45 adults (mean age, 61) with moderate CBE disease severity showed that dyspnea severity has a sizable effect on functional status and quality of life. Disease severity was more strongly related to functional status than to quality of life. Depression and mastery had the strongest total effects on quality of life. Dyspnea severity had strong but separate effects on functional status and quality of life. From these preliminary results, it is suggested that a direct focus on psychologic interventions to ameliorate depression and improve mastery is likely to improve quality of life with some resultant positive effect on functional status.
Adaptation, Psychological↗
Pharmacokinetics of anticonvulsants in pregnancy: alterations in plasma protein binding.
Anticonvulsant levels decline as pregnancy progresses, even in the face of constant and, in some cases, increased dosages of medications. It has been suggested that this decline is responsible for the increase in seizure frequency seen in approximately one-third of the women with epilepsy who become pregnant. Changes in plasma protein binding may explain the declines in anticonvulsant concentrations during pregnancy. A prospective cohort study was designed to test this hypothesis. Carbamazepine, phenytoin and phenobarbital were studied. The mean total concentrations of all 3 drugs declined as pregnancy progressed, rising in the postpartum period. Free concentrations also declined, but did so significantly only for phenobarbital. The free fraction for all anticonvulsants studied rose significantly throughout pregnancy. Protein binding is significantly altered during pregnancy for all 3 drugs studied and appears to account for much of the decline in anticonvulsant concentrations seen in this condition. It is suggested that free rather than total drug concentrations be monitored in pregnant women with epilepsy.
Adult↗