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Biomedical subjects

K McCormick

Publications and source records attributed to K McCormick.

16 recordsLinked to original sources

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

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

A descriptive analysis of nursing staff behaviors in a teaching nursing home: differences among NAs, LPNs, and RNs.

Various staff behaviors in a nursing home were sampled seven times a day, 5 days a week over 37 months and were coded separately for LPNs, RNs, and NAs. The behavior most frequently observed was patient care, which occurred during 56.9% of the samples. We observed staff interacting with patients during 10.7% and with other staff during 19.5% of the samples. The LPNs displayed significantly more patient care behaviors and NAs significantly more nonwork behaviors than other nursing staff. RNs displayed the least nonwork behavior. We conclude that nursing staff devote most of their time to patient needs and relatively little time to nonproductive activities.

Behavior

A staff management system for maintaining improvements in continence with elderly nursing home residents.

We developed a staff management system for maintaining treatment gains achieved on a specialized continence unit located in a geriatric nursing home. Geriatric assistants learned to use a prompted voiding procedure to maintain improved dryness for 4 elderly residents. The staff management system included self-monitoring and recording of prompted voiding activities and supervisory monitoring and feedback based on group performance of these activities. Results show that the system was effective in maintaining prompted voiding activities with corresponding maintenance of improved patient continence. However, a gradual decline in staff performance was noted 4 to 5 months after the initiation of the system. During a subsequent phase of the study, provision of individual feedback restored staff performance to previous levels. Results are discussed in relation to the practicality of prompted voiding interventions in nursing home environments and the applicability of staff management systems in this setting.

Aged

Valproic acid disposition and protein binding in pregnancy.

Nine epileptic women were followed prospectively through pregnancy on a monthly basis. At each visit, total and free serum valproic acid levels and albumin levels were obtained. Assays were done by gas-liquid chromatography, and free drug was separated by ultrafiltration. Despite an upward dose adjustment in four patients, total valproic acid levels declined as pregnancy proceeded, but free levels did not. Plasma free fractions and clearances increased, but intrinsic clearances, which were adjusted for changes in body weight, remained unchanged.

Adult

Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels.

We have developed a method for embedding cells within a collagen matrix which allows sustained growth of mouse mammary tumor epithelial cells in primary culture. A characteristic and reproducible pattern of organization and growth occurs: the cells rearrange themselves and produce duct-like structures extending into the matrix, resulting in a three-dimensional outgrowth. Autoradiography showed continuous [3H]thymidine incorporation during 8 weeks in culture. An increase in DNA content of the cultured cells as a function of time was observed. Mouse mammary tumor cells cultured in the conventional monolayer system failed to show any significant increase in cell number during a culture period of 6 weeks. In addition, in such monolayer systems, cells progressively became detached from the dishes in long-term culture. The mammary epithelial cell origin of the collagen gel cell outgrowths was shown by electron microscopic demonstration of polarized cells containing tight junctions and budding mammary tumor virus particles. In addition, in vivo transplantation of collagen gel outgrowths resulted in the development of mammary adenocarcinoma histologically similar to the donor tumor. Cellular outgrowth patterns resembling those from tumor cells were also seen in similar collagen gel cultures of normal mammary cells from mouse and human and of hyperplastic alveolar nodule cells from mouse. The significance and usefulness of this system in comparison to the conventional monolayer system are discussed.

Animals

Glucocorticoid regulation of prolactin receptors on mammary cells in culture.

Mouse mammary epithelial cultures were examined for the ability to specifically bind [125I]PRL after cultivation on floating collagen gels. Corticosterone, particularly hydrocortisone, were effective in increasing the ability of mouse mammary cells to bind [125I]PRL. The absence of a glucocorticoid in the medium resulted in a loss of PRL binding during the 3 days in culture. 17 beta-Estradiol, progesterone, and aldosterone at equal molar concentration had no or only a small effect in increasing [125I]PRL binding.

Aldosterone

Evaluating the appropriateness of a nurse expert system's patient assessment.

The Urological Nursing Information System (UNIS) is an expert-system prototype designed to help nurses perform patient assessments on elderly nursing home residents known to be incontinent of urine. A study was conducted to evaluate the appropriateness of the patient-assessment parameters stored in the knowledge base of UNIS. These parameters were stored as objects--a kind of template for holding related clusters of data, facts, rules, hypotheses, or any knowledge in a single conceptual unit. Each object was rated for its appropriateness by 14 nurse experts. Resulting scores ranged from +14 to -14. The effect of the nurse experts' educational backgrounds and work settings on their ratings were also analyzed. The results indicated that 95.6% of the objects received favorable ratings from the nurse experts. Educational background was not a significant factor chi 2 = 5.2, but work settings did have a significant affect chi 2 = 21.07, p = 0.01.

Aged