Biomedical subjects

A M Davis

Publications and source records attributed to A M Davis.

At least 55 records · Page 3Linked to original sources

PubMed2000

Antisense oligodeoxynucleotides as a tool in developmental neuroendocrinology.

Antisense oligodeoxynucleotides have been highly successful agents at modulating gene expression in the adult brain and widely exploited in the field of neuroendocrinology. We have also used this technique in the developing brain to explore the role of select proteins during sensitive periods of development, particularly those influenced by steroid hormones. Presented here are the technical details of using antisense oligodeoxynucleotides in the neonatal brain, as well as a review of some of our successes and failures. Our goal is to illustrate the relative ease of use of this technique in neonates and demonstrate the power such an approach offers so that other investigators will also begin to take advantage of this useful tool.

Animals↗

PubMed2000

Genetic technologies and courts of law.

Human genetic testing, and its next logical technological plateau, gene therapy, are largely unregulated in the United States and much of the world. Since the basic science and some of the technological know-how related to such tests and therapeutic regimes cross national boundaries, the disputes that follow in the wake of popular response to such technological advances could arise in virtually any court of the world. For much of the post-industrial world, this pits the unfettered processes of medical decision-making against standards of the rule of law enforced by independent courts of law. For a substantial portion of the developing world, courts are not independent and the rule of law is precariously standardized. There the proponents of unbounded genetic test development and experimentation have greatest opportunities for mischief that can create civil, criminal and military strife. In this paper we propose and discuss methods to forecast case scenarios. We will emphasize the globalization of civil and criminal conflicts that may be spurred by the use of genetic testing. Extra-judicial dispute resolution is likely to fail in the case of genetic tests. We finally propose an international means of judicial discourse that has potential to bring objectivity and even-handedness to the just resolution of issues spurred by genetic testing and engineered evolution.

Genetic Testing↗

PubMed2000

MDR1 gene expression and outcome in osteosarcoma: a prospective, multicenter study.

PURPOSE: Increased expression of the multidrug resistance gene (MDR1) has been implicated in osteosarcoma prognosis. This study represents the first prospective assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma. PATIENTS AND METHODS: A series of patients with high-grade, nonmetastatic extremity osteosarcoma were enrolled from six tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 30 months). All patients were treated with (neo)adjuvant chemotherapy and surgery. Tumors from 123 patients were analyzed for MDR1 mRNA expression. The association of the level of MDR1 expression with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Using the highest MDR1 value for each patient, a dose-response relationship was not identified between the level of MDR1 expression and systemic relapse (relative risk, 1.15; P =.44). Analyses based on biopsy or resection values alone gave similar results (P =.11 and.41, respectively, log rank test). In multivariate analysis, large tumor size (> 9 cm) was the only significant independent predictor of systemic outcome (relative risk, 2.8; P =.002). CONCLUSION: We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma. It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease.

Adolescent↗

PubMed2000

Periprosthetic bone remodelling around a prosthesis for distal femoral tumours. Measurement by dual-energy X-ray absorptiometry (DEXA).

We used dual-energy x-ray absorptiometry (DEXA) to evaluate the extent of periprosthetic bone remodelling around a prosthesis for distal femoral reconstruction, the Kotz modular femoral tibial replacement (KMFTR; Howmedica, Rutherford, New Jersey). A total of 23 patients was entered into the study which had four parts: 1) 17 patients were scanned three times on both the implant and contralateral legs to determine whether the precision of DEXA measurements was adequate to estimate bone loss surrounding the anchorage piece of the KMFTR; 2) in 23 patients the bone mineral density (BMD) in different regions of interest surrounding the diaphyseal anchorage was compared with that of the contralateral femur at the same location to test whether there was consistent evidence of loss of BMD adjacent to the prosthetic stem; 3) in 12 patients sequential studies were performed about one year apart to compare bone loss; and 4) bone loss was compared in ten patients with implants fixed by three screws and in 13 without screws. The mean coefficients of variation (SD/mean) for the 17 sets of repeated scans ranged from 2.9% to 7.8% at different regions of interest in the KMFTR leg and from 1.4% to 2.5% in the contralateral leg. BMD was decreased in the KMFTR leg relative to the contralateral limb and the percentage of BMD loss in general increased as the region of interest moved distally in the femur. Studies done after one year showed no consistent pattern of progressive bone loss between the two measurements. The ten patients with implants fixed by screws were found to have a mean loss of BMD of 42% in the most distal part of the femur, while the 13 without screw fixation had a mean loss of 11%. DEXA was shown to have adequate precision to evaluate loss of BMD around the KMFTR. This was evident relative to the contralateral leg in all patients and generally increased in the most distal part of the femur. In general, it stabilised between two measurements taken one year apart and was greater surrounding implants fixed by cross-locking screws.

Absorptiometry, Photon↗

PubMed2000

Robust assessment of statistical significance in the use of unbound/intrinsic pharmacokinetic parameters in quantitative structure-pharmacokinetic relationships with lipophilicity.

The optimization of pharmacokinetic properties remains one of the most challenging aspects of drug design. Key parameters, clearance and volume of distribution, are multifactorial, which makes deriving structure-pharmacokinetic relationships difficult. The correction of clearance and volume of distribution for the unbound fraction in plasma is one approach taken that has enabled quantitative structure-pharmacokinetic relationships to be derived. Three published data-sets where unbound parameters have been correlated with lipophilicity have been reanalyzed. The reanalysis has shown that high correlation coefficients can be achieved without any true correlation in the data and can lead to misinterpretation of the ways in which lipophilicity influences pharmacokinetics. Randomization procedures are proposed as a more robust method of assessing significance.

Algorithms↗

PubMed2000

Acquired segmental megacolon in an adult patient with cystic fibrosis.

Cystic fibrosis (CF) is characterized by symptoms related to pulmonary dysfunction and pancreatic insufficiency. Constipation, though a frequent complaint of patients with CF, receives less attention. We report a case of acquired segmental megacolon and constipation necessitating surgical colonic resection in an adult patient with CF. The differential diagnosis and possible causes of megacolon in this setting are discussed.

Adult↗

PubMed2000

Decreasing GAD neonatally attenuates steroid-induced sexual differentiation of the rat brain.

During development, exposure to gonadal steroids results in brain sexual differentiation. Postnatally, hypothalamic gamma-aminobutyric acid (GABA) levels are almost double in males versus females. We hypothesized that increased GABA neonatally results in masculinization. Males, females, and androgenized females were infused intrahypothalamically with antisense oligonucleotides against glutamic acid decarboxylase (GAD) mRNA at birth to reduce GABA synthesis. GAD protein and GABA levels were reduced 24 hr later without obvious toxic effects, as determined by histological examination. As adults, neonatally antisense-treated, androgenized females showed reduced intromission-like behavior and lordosis quotients compared with vehicle and scrambled controls. Lordosis quotients were reduced about 50% in nonandrogenized females versus vehicle and scrambled controls. These data suggest that GABA is involved in mediating brain sex differentiation and may act in both males and females.

Adrenal Cortex Hormones↗

PubMed1999

A comparison of osteopathic spinal manipulation with standard care for patients with low back pain.

BACKGROUND: The effect of osteopathic manual therapy (i.e., spinal manipulation) in patients with chronic and subchronic back pain is largely unknown, and its use in such patients is controversial. Nevertheless, manual therapy is a frequently used method of treatment in this group of patients. METHODS: We performed a randomized, controlled trial that involved patients who had had back pain for at least three weeks but less than six months. We screened 1193 patients; 178 were found to be eligible and were randomly assigned to treatment groups; 23 of these patients subsequently dropped out of the study. The patients were treated either with one or more standard medical therapies (72 patients) or with osteopathic manual therapy (83 patients). We used a variety of outcome measures, including scores on the Roland-Morris and Oswestry questionnaires, a visual-analogue pain scale, and measurements of range of motion and straight-leg raising, to assess the results of treatment over a 12-week period. RESULTS: Patients in both groups improved during the 12 weeks. There was no statistically significant difference between the two groups in any of the primary outcome measures. The osteopathic-treatment group required significantly less medication (analgesics, antiinflammatory agents, and muscle relaxants) (P< 0.001) and used less physical therapy (0.2 percent vs. 2.6 percent, P<0.05). More than 90 percent of the patients in both groups were satisfied with their care. CONCLUSIONS: Osteopathic manual care and standard medical care had similar clinical results in patients with subacute low back pain. However, the use of medication was greater with standard care.

Adult↗

PubMed1999

A simple biofeedback digital data collection instrument to control ventilation during autonomic investigations.

Autonomic evaluation using the heart rate spectrum is sensitive to changes in breathing parameters, but few studies using this technique have controlled both the rate and depth of breathing. Fewer still have also measured or controlled inspiration and expiration times, or end-tidal carbon dioxide. This study describes the development of a digital instrument that can be used to alter tidal volume, ventilation rate and the time of inspiration and expiration with paced breathing visual templates displayed on a computer monitor. The digital instrument runs during data acquisition and displays the ventilatory signal from the subject superimposed on the paced breathing templates. Thus, adjustment of ventilatory parameters is achieved by matching the actual breathing signal to the target template. By regulating the ventilation rate and the tidal volume, end-tidal carbon dioxide could be increased or decreased in small increments. This instrument provided ventilatory control to investigate the effects on the heart rate spectrum of breathing depth, ventilation rate, end-tidal carbon dioxide and the time of expiration.

Biofeedback, Psychology↗

PubMed1999

Bmp4 is required for the generation of primordial germ cells in the mouse embryo.

In many organisms the allocation of primordial germ cells (PGCs) is determined by the inheritance of maternal factors deposited in the egg. However, in mammals, inductive cell interactions are required around gastrulation to establish the germ line. Here, we show that Bmp4 homozygous null embryos contain no PGCs. They also lack an allantois, an extraembryonic mesodermal tissue derived, like the PGCs, from precursors in the proximal epiblast. Heterozygotes have fewer PGCs than normal, due to a reduction in the size of the founding population and not to an effect on its subsequent expansion. Analysis of beta-galactosidase activity in Bmp4(lacZneo) embryos reveals that prior to gastrulation, Bmp4 is expressed in the extraembryonic ectoderm. Later, Bmp4 is expressed in the extraembryonic mesoderm, but not in PGCs. Chimera analysis indicates that it is the Bmp4 expression in the extraembryonic ectoderm that regulates the formation of allantois and primordial germ cell precursors, and the size of the founding population of PGCs. The initiation of the germ line in the mouse therefore depends on a secreted signal from the previously segregated, extraembryonic, trophectoderm lineage.

Allantois↗

PubMed1999

Comparison between a 2- and 3-grade system in predicting metastatic-free survival in extremity soft-tissue sarcoma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether a histologic grading system consisting of 2 or 3 categories had better discrimination for predicting metastasis-free survival in extremity soft-tissue sarcoma. METHODS: One hundred thirty patients with nonmetastatic soft-tissue sarcoma were identified and the histologic grade (3-grade system) for each tumor was determined. For the 2-grade system, grade was determined by collapsing 3 grades into 2. The Kaplan-Meier method was used to estimate disease free survival. RESULTS: By use of a 3-grade system, grade 2 tumors showed a 5.2-fold and grade 3 tumors a 9-fold increased risk of systemic relapse when compared with grade 1 tumors. When grade 2 and 3 tumors were combined, they had a 2.6-fold increased risk of systemic relapse compared with grade 1 tumors. When grade 1 and 2 tumors were combined, grade 3 tumors had an 8.4-fold risk of relapse. After data were controlled for size and depth of tumor, each increase in grade in the 3-grade system showed a successive 2.3-fold increase in risk of systemic relapse. CONCLUSIONS: A 3-grade system may be more appropriate for predicting systemic relapse than 2 grades. A prospective study is required to confirm this.

Adolescent↗

PubMed1999

Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: a matched case-control study.

OBJECTIVE: To quantify the differences in physical disability and handicap experienced by patients with lower extremity sarcoma who required amputation for their primary tumor as compared with those treated by limb-sparing surgery. DESIGN: Matched case-control study. Twelve patients with amputation were matched with 24 patients treated by limb-sparing surgery on the following variables: age, gender, length of follow-up, bone versus soft-tissue tumor, anatomic site, and treatment with adjuvant chemotherapy. PATIENTS: Patients who underwent above-knee amputation (AKA) or below-knee amputation (BKA) for primary soft-tissue or bone sarcoma, who had not developed local or systemic recurrence, and who had been followed up for at least 1 year since surgery. MAIN OUTCOME MEASURES: The Toronto Extremity Salvage Score (TESS), a measure of physical disability; the Shortform-36 (SF-36), a generic health status measure; and the Reintegration to Normal Living (RNL), a measure of handicap. RESULTS: Mean TESS score for the patients with amputations was 74.5 versus 85.1 for the limb-sparing patients. (p = .15). Only the physical function subscale of the SF-36 showed statistically significant differences, with means of 45 and 71.1 for the amputation versus limb-sparing groups, respectively (p = .03). The RNL for the amputation group was 84.4 versus 97 for the limb-sparing group (p = .05). Seven of the 12 patients with amputations experienced ongoing difficulty with the soft tissues overlying their stumps. CONCLUSIONS: There was a trend toward increased disability for those in the amputation group versus those in the limb-sparing group, with the amputation group showing significantly higher levels of handicap. These data suggest that the differences in disability between amputation and limb-sparing patients are smaller than anticipated. The differences may be more notable in measuring handicap.

Adult↗

PubMed1999

Excellent long-term functional outcome after an operation for anomalous left coronary artery from the pulmonary artery.

OBJECTIVE: The aim of this study was to review the results of operations for anomalous left coronary artery from the pulmonary artery and the late outcome for exercise capacity, left ventricular function, and mitral regurgitation. METHODS: Twenty-one patients underwent operations over an 18-year period (median age, 9 months; range, 6 weeks-26 years) with a median follow-up of 6.5 years (range, 2 months-18 years). In addition to clinical and echocardiographic follow-up, patients at our institution were also investigated with radionuclide scans (n = 10) and treadmill exercise testing (n = 8). RESULTS: There were no operative or late deaths (0%; 95% confidence interval [CI], 0% and 16%). Five patients required support with a left ventricular assist device. Eighteen patients are currently in New York Heart Association class I, and 3 patients are mildly symptomatic. On nuclear gated scan at a mean of 6 years after the operation, the left ventricular ejection fraction was 64% (SD, 3%) at rest and increased to 74% (SD = 3%) on exercise (95% CI for the difference, 6%, 14%; P =.001). Treadmill endurance was normal for age (9.8-14.5 minutes) in those old enough to exercise. On echocardiography (n = 18), the current fractional shortening was 34% (SD, 4%) in the 15 patients with normal or only mildly abnormal ventricular septal motion. Three patients have undergone mitral valve operations. The left ventricular end-diastolic dimension fell from 48 mm (SD, 5.8 mm) before surgery to 35.1 mm (SD, 5.2 mm) at 1 year after the operation, and the fractional shortening increased over the first year from 19.6% (SD, 9.3%) to 32.8% (SD, 5.9%; both P <.001). CONCLUSIONS: Long-term clinical outcome and left ventricular function are good, despite severe left ventricular dysfunction at presentation.

Adolescent↗

PubMed1999

Developmental sex differences in amino acid neurotransmitter levels in hypothalamic and limbic areas of rat brain.

GABA, glutamate and aspartate are the predominant amino acid neurotransmitters in the mammalian brain. We have previously reported a developmental sex difference in messenger RNA levels of glutamate decarboxylase, the rate-limiting enzyme in GABA synthesis [Davis A. M. et al. (1996) Horm. Behav. 30, 538-552]. Males were found to have significantly higher levels of messenger RNA in many steroid-concentrating regions of the hypothalamus and limbic system on day 1 of life. Therefore, in this study, we have examined levels of amino acid neurotransmitters during early postnatal development in many of the same or related brain areas. We found that levels of all three transmitters change as animals age. While both GABA and aspartate concentrations increase, glutamate levels decrease. In addition, there are sex differences in neurotransmitter levels in several areas examined, including the ventromedial and arcuate nuclei of the hypothalamus, and the CA1 region of the hippocampus. Sex differences for GABA occur only on postnatal days 1 and 5. However, sex differences in aspartate occur later in development (postnatal day 20). The CA1 region of males has a significantly greater concentration of GABA, glutamate and aspartate than females on postnatal day 1. In addition, treatment of females with testosterone propionate on the day of birth results in increased GABA levels, suggesting that these sex differences may be the result of hormone exposure during development. We hypothesize that these hormonally mediated sex differences in amino acid transmitters early in development contribute to the establishment of sexually dimorphic neuronal architecture in the adult.

Aging↗

PubMed1999

Functional outcome in extremity soft tissue sarcoma.

The studies reporting functional outcome for patients undergoing limb preservation surgery for extremity soft tissue sarcoma (STS) have evaluated mainly impairments, that is, deficits at an anatomic structure level, such as joint range of motion and strength. Disability, activities of daily living, self-care, and mobility have been less frequently evaluated. Review of the literature suggests that approximately 50% of patients treated for STS have significant impairments, whereas the frequency of disability is less. Synthesis of the results is difficult because of the heterogeneity of patient samples, treatment, and the outcomes used to evaluate function. Future studies require the use of standardized definitions and reliable and valid functional outcome measures. Improved patient outcomes can be achieved only by understanding the determinants of these outcomes and by introducing interventions to improve patient functional outcome.

Activities of Daily Living↗

PubMed1999

Providers' smoking cessation attitudes and practices for older patients.

A mail survey of 136 providers in a health maintenance organization in the Chicago metropolitan area examined smoking cessation attitudes and performance of the 4As protocol (asking, advising, assisting, arranging) for patients aged 50 years or older. Asking about smoking was most frequent, followed by arranging, advising, and assisting. Physicians and nurse practitioners performed each of the 4As more often than did registered and licensed practical nurses. In multiple logistic regression analyses, provider type was the only significant predictor of asking about smoking. Advising, assisting, and arranging follow-ups were more likely to be performed by providers who perceived a sense of professional responsibility about older patients' smoking; advising was more likely for providers who perceived that they had enough time to advise older patients about smoking; and assisting and arranging were more likely for providers with a stronger sense of self-efficacy for helping older patients stop smoking.

Aging↗

PubMed1999

Gender issues in patients with extremity soft-tissue sarcoma: a pilot study.

Soft-tissue sarcoma (STS) affects men and women with equal frequency and commonly presents as an asymptomatic mass in patients 40 to 50 years of age. Recent study has identified physical, emotional, and psychological factors associated with a diagnosis of malignancy, but the tissues affecting the STS patient population may differ from those of more common cancers due to physical disability secondary to treatment. Research to date has not dealt specifically with gender differences in the reaction and adaptation to the cancer diagnosis. This pilot study was designed to evaluate the treatment experiences of five males and five females treated with surgery and radiation for STS of the thigh and followed posttreatment for at least 2 years. The open-ended interview was used to collect data, which was then subjected to a constant comparative analysis technique. The STS patients shared many concerns of cancer patients, with additional physical complaints. Physical symptoms were common to men and women, but women adapted more easily with explanation. Women feared losing life, family role, and relationships. Along with men, they also feared the losses of limb and career. For women, support included faith and sharing stories with others, whereas men preferred to deal with their illnesses individually and concealed emotions from loved ones. The perception of disease time frame was also distinct, with men adopting a fatalistic attitude and regarding their disease as an isolated episode. Women believed their condition was ongoing. Women need repeated information from several sources along with reassurance and increased social support, whereas men prefer the minimum of social support, requiring instead independence and extra attention to physical limitations. These results can improve STS patient treatment by increasing awareness in the patient, family, and medical team of the psychosocial issues that can be expected to arise.

Adaptation, Psychological↗

PubMed1999

Physician assistants as partners in physician-directed care.

1998 marked the acceptance of Physician Assistants (PAs) as members in the Southern Medical Association. We review the history of the PA profession and, more importantly, the physician/PA relationship. We also provide an overview of PA education and certification requirements. Variations in state law regarding PA utilization, including the delegation of prescribing privileges, are discussed. Current American Medical Association guidelines regarding physician/PA practice are provided.

Certification↗