Idiopathic fetal growth restriction: a pathophysiologic approach

Known causes of fetal growth restriction (FGR) can be traced in up to 40 percent of the cases. In the remainder of cases, FGR is idiopathic in origin. Evidence from experimental studies, antenatal findings at Doppler velocimetry of the uterine and umbilical arteries, and placental pathology studies suggests that idiopathic FGR can be divided into three groups: 1) primary abnormality in the uteroplacental perfusion; 2) primary abnormality in the fetoplacental perfusion; and 3) abnormal villous structure at the interface between fetal and maternal circulation. An improved understanding of the pathophysiology of idiopathic FGR is crucial to gain insight into its pathogenesis.     

Epilepsy in older adults: causes, consequences and treatment

OBJECTIVES: Seizures and epilepsy are common problems in older adults. Although, the highest incidence of seizures and epilepsy occurs in individuals more than 65 years of age, the magnitude of this public health problem, and its consequences on the quality of life of older adults, are not appreciated. Moreover, there is no consensus on the most appropriate way to diagnose or manage epilepsy in this population. This report reviews the current literature on all aspects of epilepsy in older people. DESIGN/METHODS: The medical literature was reviewed for all articles pertaining to pathophysiology, diagnosis, and treatment of epilepsy in older people. RESULTS: Epidemiology, etiology, diagnosis, use of diagnostic tests including EEG and imaging, new medical and surgical treatments, and psychosocial issues as they relate to older epilepsy patient are discussed. Several questions that merit future systematic investigation are presented. CONCLUSION: Seizures and epilepsy in older people are much more common than is generally known. There are unique issues related to this population with regard to diagnosis and treatment. Several new medical and surgical therapies are now available for all epilepsy patients, some of which may be helpful for the older epilepsy patient.     

Introducing Critical Appraisal to studies of animal models investigating novel therapies in sepsis

OBJECTIVES: To discuss theoretical and practical aspects relating to the design of animal studies investigating the efficacy of novel therapeutic agents for the treatment of sepsis, and to make explicit the process whereby these studies can be evaluated for the purpose of designing clinical trials in humans. DATA SOURCES: Relevant articles from the pertinent literature were reviewed. STUDY SELECTION: Studies relevant to an evidence-based assessment of clinical studies on therapeutic efficacy, and studies relevant to the design of animal models of sepsis were selected. DATA EXTRACTION: Concepts relevant to an evidence-based assessment of the animal literature were extracted. DATA SYNTHESIS: Articles were reviewed and an evidence-based framework for the assessment of animal studies was developed. In this process, we discuss the steps that are necessary to assess the internal validity of an individual study and review topics relevant to the application of animal data to the design of clinical trials. CONCLUSIONS: The success of clinical trials of sepsis therapies is predicated on the generation and interpretation of sound preclinical data. In this review, we have attempted to outline an evidence-based approach to the assessment of preclinical animal studies evaluating novel therapeutic interventions in sepsis.     

Treatment and prophylaxis of disseminated Mycobacterium avium complex in HIV-infected individuals

OBJECTIVE: To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals. DATA SOURCES: A MEDLINE (January 1966-July 1997) and AIDSLINE (January 1980-July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background. A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics. CONCLUSIONS: The incidence of disseminated MAC has increased dramatically with the AIDS epidemic. The infection can lead to increased morbidity and mortality in HIV-infected patients. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3.     

Introduction to special section: Relapse to substance abuse: Recent findings from basic and clinical research.

A series of 6 articles concerning relapse to substance abuse and its treatment is introduced. Two articles review animal models of relapse and the potential role of drug priming effects, 2 articles present new data from experimental human research on cognitive and contextual determinants of relapse, while 2 articles describe clinical approaches and review the effectiveness of relapse prevention treatment. The series integrates clinical and basic research around a common theme and demonstrates that various types of research representing diverse perspectives are needed to understand this important feature of substance dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the relation between abilities, learning, and human performance.

Describes the author's research efforts to link basic and applied psychology concepts in each of the following areas: aptitude measurement, learning and training, and human task performance. Several studies are described in detail to illustrate a number of broad issues, particularly the possibility of using combinations of experimental and correlational methods for studying complex human behavior, and the need to develop concepts that allow more dependable generalization of research findings to new situations (particularly to new tasks). A taxonomy of human perceptual-motor abilities is described and related to more complex tasks. Other studies investigated the relationship between abilities and skill acquisition; individual differences in various learning phenomena (e.g., transfer of training); and whether the taxonomic categories are useful for standardizing laboratory tasks and for generalizing results of these tasks to new tasks. Results suggest that (a) experimental-correlational studies can be used to develop a body of principles relating task dimensions to ability requirements; (b) kinesthetic ability factors become more important than spatial ones as psychomotor learning progresses; and (c) it should be possible to develop a data base about human performance, indexed by type of task. (37 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Has high-frequency ventilation been inappropriately discarded in adult acute respiratory distress syndrome?

OBJECTIVES: To review the basic physiologic principles that support the role for high-frequency ventilation (HFV) in acutely lung-injured patients, to critically assess clinical trial data in this area, and discuss why a metasummary is not feasible and a large-scale clinical trial is needed. DATA SOURCES: We searched a computerized database (MEDLINE) from 1976 to January 1997 using the text words "high-frequency ventilation" and "acute respiratory distress syndrome" to retrieve all relevant candidate articles. STUDY SELECTION: We retrieved all English language clinical studies conducted in tertiary care centers that employed HFV in adult acute respiratory distress syndrome (ARDS) patients. DATA EXTRACTION: Only prospective, randomized trials, cohort/case-control studies, and case series evaluating HFV vs. conventional mechanical ventilation in adult ARDS patients were included. DATA SYNTHESIS: We independently screened 3,166 articles on ARDS and 494 papers on HFV in our computer search. We checked reference lists and contacted experts in the field of mechanical ventilation in ARDS to ensure that no relevant studies had been missed. Only four articles met our inclusion criteria and were evaluated in detail. CONCLUSIONS: Current clinical studies are statistically under-powered and a metasummary is not feasible because of study quality, as well as lack of similar clinical end points and measures of magnitude of benefit. A large, multicenter trial should be initiated to define the role of HFV in the treatment of adult ARDS.     

Use of mivacurium in orthopedic surgery: comparison of 2 different-dose inductions

OBJECTIVE: To evaluate the postnatal growth of full-term infants with fetal growth retardation (FGR) syndrome and their subgroups (disproportionate and proportionate) after six months of delivery. METHODS: This is a prospective follow-up study of 200 full-term gestations. We compare 100 FGRs (34 cases of FGR-disproportionate and 66 FGR-proportionate) infants against 100 normal infants/controls. At the sixth months of postnatal life, the infants were subjected to a standard paediatric evaluation and examination. RESULTS: At the sixth months of postnatal life, the infant weight was 7.183 g +/- 727 in the FGR group vs. 8.019 g +/- 823 in the control group, p < 0.001. 31% of FGR infants were found under the 10th percentile value as read for the 6th months standard, whereas the same value was detected in only 3% of control infants, p < 0.001. Likewise, 38% of FGR cases were under the 10th percentile of height versus 7% of control cases, p < 0.001. Proportionate FGR infants showed a higher increase of height in comparison to those from a disproportionate group (17.3 cm +/- 1.4 vs. 15.5 cm +/- 3.4, p < 0.05). A negative correlation was found between neonatal ponderal index (NPI) and weight gain (R = -0.16, p < 0.05). CONCLUSIONS: Six months after delivery, weight and height were lower in FGR infants than in controls. At that age, disproportionate and proportionate FGR infants had similar weight and height, being the height catch-up more significant in proportionate ones.     

Gene therapy of cancer

OBJECTIVE: To provide a review of the basic concepts and terminology of human genetics, the clinical application and risks of gene therapy, and ethical and societal issues. DATA SOURCES: Review articles, research studies, and book chapters related to genetics and human gene therapy. CONCLUSIONS: The genetic changes that play a role in the development of cancer have begun to be elucidated, and these discoveries have led to strategies to destroy cancers by correcting genetic defects or manipulating genes to induce tumoricidal activities. Gene therapy is a novel investigational intervention that is constantly evolving. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses will need an increased understanding of cellular biology, genetics, and genetics engineering. Major considerations for nursing practice include patient and family education, informed consent, side effects, and ethical and societal issues.     

ACE inhibitor- versus angiotensin II blocker-induced cough and angioedema

OBJECTIVE: To compare the tolerability of angiotensin-converting enzyme (ACE) inhibitors with that of angiotensin II (AII)-receptor blockers and the incidence of cough and angioedema associated with their use through review of published data. DATA SOURCES: References were identified through a MEDLINE search of articles published between January 1975 and April 1997. Bibliographies of pertinent references were also reviewed. RESULTS: Results of placebo-controlled and comparative trials of the AII blockers demonstrate that they are at least as effective as ACE inhibitors for hypertension, but exhibit an incidence of cough and absent or rare angioedema like that of placebo. CONCLUSIONS: In the 10 comparative trials described, all reported a lower incidence of cough with AII blockers than with ACE inhibitors. Angioedema was not reported in the comparative trials described.     

Effects of growth hormone and estrogen on T lymphocytes in older women

OBJECTIVE: To assess the effect on peripheral blood T lymphocytes of recombinant human growth hormone administered to healthy older women. DESIGN: Prospective, open study. SETTING: Veterans Administration clinical research unit and community surrounding Palo Alto, California. PARTICIPANTS: Thirty-three women were recruited in two age groups: 20 to 40 years (n = 13) and 70 years or older (n = 24). Subjects were healthy, community-dwelling volunteers. INTERVENTIONS: Recombinant human growth hormone at a dose of 0.025 mg/kg body weight/day was administered to the older subjects by daily subcutaneous injection over a 6-month study period. MAIN OUTCOME MEASURES: Mean percentage and number of peripheral blood CD45RA + ("naive") T cells, mean counts per minute (CPM) of [3H]-thymidine incorporation following stimulation of peripheral blood mononuclear cells with phytohemaglutinin (T cell proliferation). RESULTS: Before therapy, mean percentage and number of peripheral blood CD45RA + T cells and T cell proliferative responses were significantly reduced in older compared with younger women. The fraction of older women with CD45RA + T cell levels or T cell proliferative responses in the young range was significantly decreased in those who were receiving estrogen (1/10) compared with those who were not (9/14). After treatment with growth hormone, there were no significant changes in the mean CD45RA + T cell levels or proliferative responses of the older women. CONCLUSIONS: The results suggest that T cell changes associated with the age-related decline in secretion of growth hormone cannot be reversed by growth hormone therapy during the eighth decade.     

Factors to consider for predictable post and core build-ups of endodontically treated teeth. Part II: Clinical application of basic concepts

Post and core build-ups represent an important pre-prosthetic procedure prior to the restoration of an endodontically treated tooth. The dental practitioner is presented with the dilemma of selecting from an ever increasing variety of materials, techniques and designs related to this procedure, many of which are harmful and mired in controversy. Part II of this paper will review some basic theoretical concepts related to post and core build-ups with the objective of applying these concepts to address a number of pertinent clinical questions related to the above selection process. This review should provide the dentist with a reference to produce a more predictable post and core build-up.     

Pathogenesis of human leukocyte antigen B27-positive arthritis. Information from clinical materials

In the spondyloarthropathies human leukocyte antigen (HLA) B27 confers a strong genetic predisposition to the development and to the chronicity of disease after extra-articular infection with certain gram-negative bacteria. The close relationships between infection, HLA-B27, other genetic factors, and the host immune system, however, still are unexplained. HLA-B27-positive arthritis continues to be an area of intensive investigation in basic and clinical research. New animal models with HLA-B27 transgenic mice and rats, as well as recent developments in understanding the processes involved in signal transduction, cytokine production, and human T-lymphocyte activation, contribute to the development of new pathogenic models of the spondyloarthropathies. This article summarizes the current concepts of the cause and pathogenesis of the spondyloarthropathies resulting from studies of clinical materials. The host-microbial interplay in human disease, namely in bacteria-induced reactive arthritis, may eludicate principle disease mechanisms in acute disease and in the development of chronic autoimmune arthritis or ankylosing spondylitis.     

Tissue culture assays using Caco-2 cell line differentiate virulent from non-virulent Listeria monocytogenes strains

OBJECTIVE: Fibroblast growth factor 9 (FGF-9) is a relatively new member of the FGF family isolated from the conditioned medium of a human glioblastoma cell line as a secreting type factor that exhibits a growth-stimulating effect on primary glial cells. To elucidate the roles of FGF-9 in human brain tumors, the expression and biological activities of FGF-9 were studied using culture cells and surgically obtained tumor specimens. METHODS: Measurement of FGF-9 and basic FGF in conditioned media of cell cultures was performed by using a sandwich enzyme immunoassay. The mitogenic effect of FGF-9 was evaluated by cell growth studies. FGF-9 expression in vivo was demonstrated by immunohistochemistry. RESULTS: One of 4 glioma cell lines and 4 of 16 human meningiomas examined actually secreted detectable amounts of FGF-9 proteins. In comparison, basic FGF production was detected from 3 of 4 glioma cell lines and 11 of 16 human meningiomas. Similarly to basic FGF, recombinant human FGF-9 significantly stimulated the in vitro cell proliferation in three of four glioma cell lines investigated in a dose-dependent manner. A time course growth study using U87 MG cells revealed an accelerated growth stimulation by FGF-9 after Day 4. The growth stimulatory activity was also shown in three of four human meningiomas studied. Moderate to strong immunoreactivity for FGF-9 was observed in 40 (82%) of 49 human brain tumors examined irrespective of origin, tumor type, grade of malignancy, or whether initial or recurrent. In contrast, strong immunostaining was localized in neurons in the normal human cerebral cortex. CONCLUSION: The present findings suggest that FGF-9 may be involved in the biology of human brain tumors with a possible importance in tumor cell growth. Whether the growth factor is more generally involved in oncogenesis of human tumors awaits further investigation.     

Construction of a vein-pouch aneurysm at a surgically created carotid bifurcation in the rat

Currently available animal models for the study of treatment of aneurysms are either expensive or yield unreliable results. An animal series was devised to address both of these problems by creating a new animal model. Twelve Sprague-Dawley rats were used to demonstrate that a vein-pouch aneurysm could be constructed at a surgically created carotid bifurcation. Patency rates, growth dynamics, and histologic morphology were studied at three time intervals. A 100% patency rate at the aneurysm orifice was achieved with one-third of the aneurysms showing varying degrees of partial apical thrombosis. A growth pattern was established over the study period. Magnetic resonance angiography and digital subtraction angiography were successfully employed to study a small number of additional aneurysms. Our conclusion is that a bifurcation aneurysm can be constructed in the rat with high patency rates and predictable saccular morphology which resembles most human intracranial aneurysms. This inexpensive animal model can be used to study novel modalities for the treatment of aneurysms.     

Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: pathophysiology and management

The clinicopathological spectrum of Creutzfeldt-Jakob disease has recently been extended by the identification of an apparently new variant of this disorder in the UK. The hypothesis that this new disorder is causally related to the transmissible agent responsible for bovine spongiform encephalopathy has prompted re-evaluation of the relationships between human and animal transmissible spongiform encephalopathies, and reinforced the need for adequate experimental models to investigate this field. Recent experimental transmission studies of bovine spongiform encephalopathy into primates have supported the hypothesis, and reinforced the central role of neuropathology in the investigation of this group of diseases. Whilst clearly of distinctive etiology, Creutzfeldt-Jakob disease shares both clinical and neuropathological features with other human dementias; renewed evaluation of potentially similar disease mechanisms in these devastating conditions might provide new information of both scientific and therapeutic value.     

Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance

OBJECTIVE: To review the mechanisms and clinical significance of adverse interactions between warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) and discuss how these interactions can be avoided. DATA SOURCES: Previous studies of interactions between warfarin and NSAIDs or reports of adverse interactions were identified from a MEDLINE search (1976 to present) and from the reference lists of pertinent articles. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for inclusion in the review. Pertinent information was selected for discussion. DATA SYNTHESIS: All NSAIDs can prolong bleeding time by inhibiting platelet function. High-dose aspirin has a direct hypoprothrombinemic effect. Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of warfarin through a pharmacokinetic interaction by inhibiting the hepatic metabolism of warfarin. Mefenamic acid also enhances the anticoagulant effect of warfarin, but the mechanism is not known. The clinical relevance of protein binding displacement in the interaction between warfarin and NSAIDs has been overstated, although a significant one may be more likely in the presence of high concentrations of NSAIDs in patients with slow elimination of warfarin (e.g., those with severe heart failure or impaired liver function). NSAIDs can induce gastrointestinal bleeding, which is likely to be more severe if warfarin is also given. CONCLUSIONS: The combined use of warfarin and NSAIDs is generally discouraged because of the increased risk of bleeding in these patients. In patients receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, and NSAIDs that are associated with a higher risk of bleeding peptic ulcers should be avoided. Patients should be closely monitored for anticoagulant control and bleeding complications during the combined use of warfarin and NSAIDs.     

Small molecule inhibitors of the platelet-derived growth factor receptor, the fibroblast growth factor receptor, and Src family tyrosine kinases

The inhibition of tyrosine kinases involved in growth factor signal transduction pathways represents an attractive strategy for controlling aberrant cellular growth. Over the last 4-5 years, there have been numerous reports on the discovery of small molecule inhibitors for potential therapeutic applications to a number of proliferative diseases, principally cancer and restenosis, where the over-expression of certain tyrosine kinases has been demonstrated. These include, amongst others, the platelet-derived growth factor receptor, the fibroblast growth factor receptor, and the nonreceptor c-Src tyrosine kinase. This review compiles published reports and patent filings from 1995 to mid-1997 that include data directly related to inhibition of the platelet-derived growth factor receptor, fibroblast growth factor receptor, and Src family tyrosine kinases. Potential clinical applications for selected classes of tyrosine kinase inhibitors reviewed herein will likely depend on the demonstration of meaningful activity in a variety of therapeutic targets in animal models.