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Biomedical subjects

G L White

Publications and source records attributed to G L White.

At least 19 recordsLinked to original sources
PubMed1999

Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice.

We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP695SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients.

Aging↗
PubMed1999

Diabetes in the managed care setting: a prospective plan.

BACKGROUND: As managed care organizations (MCOs) continue to expand into the care of the chronically ill, the concept of providing cost-effective care with a preventive approach is vital for primary care providers (PCPs) to embrace. Diabetes is an ideal disease to incorporate this concept. METHODS: We reviewed the literature using MEDLINE. We used the American Diabetes Association (ADA) Provider Recognition Program guidelines as the foundation for MCOs to establish a diabetes disease management program. RESULTS: The implementation of disease management protocols, the use of computerized management systems, and the team approach can provide cost-effective diabetic care. CONCLUSIONS: To compete in the managed care market, it is vital for providers to link with their Independent Practice Associations (IPA), the ADA, and MCOs to implement standard protocols and negotiate for adequate reimbursement.

Diabetes Mellitus↗
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↗
PubMed1998

Cellular and molecular effects of a pulse butyrate regimen and new inducers of globin gene expression and hematopoiesis.

Cooley's anemia is characterized by a deficiency of beta-globin chains, a relative excess of alpha-globin chains, and consequent accelerated programmed death of developing erythroid cells in the bone marrow. Increasing expression of the gamma-globin genes to adequately balance excess alpha-globin chains can ameliorate this disorder. Butyrates induce gamma-globin experimentally, but can also cause cell growth arrest with prolonged exposure or high concentrations, which in turn can accelerate apoptosis. To determine if these potentially opposing effects can be balanced to enhance therapeutic efficacy, an intermittent "pulsed" regimen of butyrate was evaluated. Following induction of gamma-globin mRNA and protein synthesis, total hemoglobin increased in beta-thalassemia patients by more than 2 g/dl above baseline, and Hb F increased above 20% in 5/8 sickle cell patients from baseline levels of 2% Hb F. Specific regulatory regions were identified in the gamma- and beta-globin gene promoters to which new binding of transcription factors, including alpha CP2 (an activator of gamma globin) occur during therapy solely in the butyrate-responsive patients. Other compounds which induce gamma globin, derivatives of acetic, phenoxyacetic, propionic, and cinnamic acids, and dimethylbutyrate, are under investigation. Some of these newer gamma-globin inducers (designed hemokines) provide better potential as therapeutics by also acting to increase hematopoietic cell viability and proliferation. Pharmacologic induction of expression of the endogenous gamma-globin genes is a realistic approach to therapy of the beta-globin disorders for many patients, with some effective agents available now and new therapeutics, with enhanced activities, under development.

Adult↗
PubMed1998

Shedding and transmission of baboon Herpesvirus papio 2 (HVP2) in a breeding colony.

Baboons in a captive breeding colony were monitored twice a year, and new additions were screened on arrival for shedding of Herpesvirus papio 2 (HVP2) and serologic reactivity to the agent. For 128 individual animals tested over a period of 1.5 years, shedding of infective virus was detected in 13 of 342 swab specimens (3.8%), each of these incidents representing shedding by a different animal. Among long-term colony animals, infective virus was recovered on only two occasions (5 of 236 swab specimens from five individuals). In all but one instance, animals shedding virus were infants, not adults, and all animals were shedding virus in the oral cavity. One of these five instances was an isolated case, but four (three infants and one adult) were clustered within a single breeding group. Molecular analyses of the HVP2 isolates from this cluster indicated that they likely arose from a single common source, probably the mother of one of the infants. None of 31 wild-caught baboons added to the colony during this period were found to be shedding infective virus, despite 93.5% of them being seropositive for HVP2. In contrast, 6 of 18 adult baboons (all seropositive) transferred into the colony from another breeding colony were found to be shedding HVP2 either orally (3 of 6) or genitally (3 of 6). In addition, 2 of 8 juvenile baboons in this shipment were found to be shedding virus in the oropharynx. Overall, 10 of 13 instances of HVP2 isolation were from the oropharynx rather than the genital tract, and 6 of 13 baboons shedding virus were infants or juveniles rather than adults. These results suggest that, although venereal transmission of HVP2 occurs among adult animals, oral infection of young, sexually immature baboons is not uncommon.

Aging↗
PubMed1998

A generic drug primer: regulatory aspects and scientific concepts.

The regulatory aspects of generic drug substitution and the scientific concepts that serve as the basis for generic drug approval are discussed, with emphasis on the source of therapeutic equivalence information compiled by the Food and Drug Administration in Approved Drug Products with Therapeutic Equivalence Evaluations. The Food and Drug Administration's determination of bioequivalence for immediate-release and extended-release dosage forms is summarized, with a discussion of the underlying assumptions and current issues regarding bioequivalence testing. Medical practitioners must comply with the regulations stated in each state's Pharmacy Practice Act when allowing generic substitution and should ensure that the substituted product is therapeutically equivalent to the prescribed product.

Drugs, Generic↗
PubMed1998

Attenuation of tissue thrombosis and hemorrhage by ala-TFPI does not account for its protection against E. coli--a comparative study of treated and untreated non-surviving baboons challenged with LD100 E. coli.

This study was designed to determine the effect of a delayed infusion (T+120 min) of alanyl tissue factor pathway inhibitor (ala-TFPI) on the response to LD100 E. coli. We hypothesized that baboons treated with a low dose of TFPI (5 mg/kg) which did not survive would exhibit thrombosis, infarction and hemorrhage of target tissues such as that seen in untreated animals infused with LD100 E. coli. Eight baboons were infused with 5 mg/kg of ala-TFPI over a 10 h period beginning immediately after a 2 h infusion of LD100 E. coli (experimental group). Four baboons were infused with E. coli followed by a 10 h infusion of saline (control group). Of the 12 baboons, the 11 non-survivors (TFPI = 7 out of 8; controls = 4 out of 4) were evaluated for the extent of thrombosis, necrosis, hemorrhage, and congestion of target tissues and for changes in clinical chemical parameters. We expected that failure to protect would correlate with failure to inhibit thrombosis of target tissue (8). Surprisingly ala-TFPI significantly inhibited thrombosis, hemorrhage and necrosis of adrenal and renal tissues and attenuated the rise in creatinine in the 7 treated non-survivors. The lungs of these non-survivors, however, exhibited intra-alveolar fibrin and a mild degree of hemorrhage and edema. We concluded that low doses of ala-TFPI begun as late as T+120 in minutes failed to protect against the lethal effects of LD100 E. coli in spite of completely preventing thrombosis and hemorrhage in target organs, and that thrombosis, infarction and hemorrhage of adrenal and renal tissue are not part of the lethal chain of events in this IV model of E. coli sepsis.

Animals↗
PubMed1998

Prostate cancer: clinical perspectives.

1. When obtaining a screening history for prostate cancer, important risk factors include age, family history, and ethnicity. The digital rectal examination remains the "gold standard" physical examination screening technique. 2. If prostate cancer is detected at an early stage, it is potentially curable. It is incumbent upon occupational health care providers to afford those constituents who fall into a high risk category, or who are > or = 40 years of age, every opportunity for prostate cancer screening. 3. Education is the "sine-qua-non" of complete health care provision for prostate cancer clients. The occupational health care provider can play a pivotal role in allaying a client's fear and misconception of this disease. 4. Providing appropriate assessment and advocacy for clients returning to the workplace following diagnosis and treatment of prostate cancer is crucial.

Adult↗
PubMed1997

Purification and characterization of secretory IgA from baboon colostrum.

In this report, we describe a method for purifying secretory immunoglobulin A (sIgA) from baboon (Papio anubis) colostrum. The colostrum was first clarified by centrifugation and then analyzed with various anti-human Ig-specific immunologic reagents. Cross-reactive IgA in the baboon colostrum was identified by ELISA. Western blot analysis also demonstrated cross-reactive epitopes associated with human IgA1, IgA2, secretory component (SC), and joining (J) chain. To purify the sIgA, colostrum was separated into 4 distinct fractions by gel filtration chromatography. Analysis of the individual fractions by ELISA indicated that the IgA elutes over one peak. The IgA fraction was compared with purified human sIgA on SDS-PAGE, and exhibited heavy (H) chains, light (L) chains, SC, and J chain. The baboon colostrum was also analyzed by ELISA for specific IgG H and L chain epitopes utilizing monoclonal antibodies (MAbs). No significant quantity of IgG was detected in the baboon colostrum or in the individual 4 fractions, while L chain reactivity was observed in the sIgA fraction. The sIgA fraction was pooled, concentrated, and was found to contain approximately 7 mg/ml sIgA. To determine if the baboon sIgA was dimeric like human sIgA, the purified sIgA was sized by molecular sieve chromatography. The molecular size of the sIgA preparation (350 kDa) was determined empirically by comparison to known molecular species used to calibrate the column. In addition, native SDS-PAGE indicated that baboon sIgA, like human sIgA, migrates between IgG and IgM, suggesting it has a dimeric form. The purified baboon sIgA preparation should prove useful in the future study of mucosal immune responses induced in non-human primate species and for the generation of sIgA-specific immunological reagents.

Animals↗
PubMed1997

Abrogation of IL-3 requirements and stimulation of hematopoietic cell proliferation in vitro and in vivo by carboxylic acids.

Short-chain fatty acids, such as butyrate and propionate, induce fetal globin gene expression and are under clinical investigation in the beta-hemoglobinopathies. Limitations of the short-chain fatty acids as therapeutics include their rapid metabolism and a tendency to induce cell growth arrest if administered for prolonged periods. In studies described here, the cellular effects of other inducers of fetal globin, phenoxyacetic acid and derivatives of short-chain fatty acids and cinnamic acids, were investigated in the human erythroid cell line K562, the IL-3 dependent multi-lineage cell line (32D), and in mice and primates. Several test compounds supported 32D cell proliferation despite a 50-fold depletion of IL-3, which resulted in growth arrest and apoptotic death in control cells. The degree of proliferation induced by certain test compounds was similar to the degree of proliferation induced by Erythropoietin and G-CSF in the cells. Eight of ten compounds induced gamma globin mRNA in K562 cells. A 2.5 to 6-fold increase in reticulocytosis was observed in vivo in mice treated with two prototype compounds. Pharmacokinetic studies of three prototype compounds demonstrated millimolar plasma concentrations after single oral doses for many hours in primates. These findings identify orally bioavailable compounds which induce gamma globin gene expression and hematopoietic cell proliferation through an activity which partially abrogates requirements for IL-3. Such compounds provide potential for oral therapeutics which stimulate proliferation of hematopoietic cells of multiple lineages, as well as inducing fetal globin.

Animals↗
PubMed1997

Prevalence of Herpesvirus papio 2 in baboons and identification of immunogenic viral polypeptides.

The prevalence of Herpesvirus papio 2 (HVP2) in several groups of captive and wild-caught baboons was determined by detection of anti-HVP2 antibodies in 133 sera of adult baboons. Over 90% of newly imported (wild-caught) adult olive baboons (Papio anubis) from Kenya and chacma baboons (P. ursinus) from South Africa were found to have anti-HVP2 titers. Similarly, approximately 85% of captive breeding colony baboons (P. anubis and P. cynocephalus) were seropositive for HVP2. Infected animals were generally easily identifiable by enzyme-linked immunosorbent assay because anti-HVP2 IgG titers in immune animals were usually high (16,000 to 64,000). There was little variation in the relative reactivity patterns of individual HVP2-immune sera when tested against herpes simplex viruses 1 and 2, monkey B virus, H. cercopithecus 2, and HVP2, or against different HVP2 strains. Also, differences were not detected between reactivity of olive and chacma baboon immune sera. Analysis of the polypeptide specificity of immune sera by western blot identified four viral antigens that were consistent targets of immune sera. These antigens were the gB glycoprotein, a pair of unidentified glycoproteins of 80 to 100 kDa, the gD glycoprotein, and a series of smaller capsid proteins. Additional viral proteins were variably recognized by individual immune sera. The results of this study indicate that HVP2 is a common infection of baboons; there is little antigenic variation among HVP2 strains; and there are several HVP2 antigens that represent consistent targets of the anti-HVP2 immune response of baboons.

Animals↗
PubMed1997

Allied health and physician assistants: a progressive partnership.

The recently published report of the National Commission on Allied Health stressed the perceived need for the development of more multi-skilled, generalist Allied Health professionals as a means of responding to the primary care focus of health care in the United States. There are many significant barriers to the development of such a professional in terms of educational requirements and licensing among other issues. Physician assistants have fulfilled this role in health care for nearly 30 years. The relationship between Allied Health and physician assistant education is not always clear although many Allied Health professionals pursue further education as physician assistants. Further development and clarification of this relationship presents an opportunity for Allied Health to participate in the training of generalist practitioners without complicating the educational requirements of other Allied Health professional programs.

Allied Health Personnel↗
PubMed1996

Corneal transplantation.

Corneal transplantation is a highly successful procedure for restoring sight in patients with corneal disease. The most common indication for transplantation is corneal edema following cataract extraction. A common problem following corneal transplantation is astigmatism, which often requires thick lenses for correction. The excimer laser holds promise for correcting postoperative astigmatism but is not yet in wide use. Rejection is a life-long risk and is most likely to occur during the first year. Topical corticosteroids are commonly used to decrease this risk. Frank corneal rejection must be recognized early and treated with intensive topical therapy.

Corneal Diseases↗
PubMed1995

Tuberculosis: a health education imperative returns.

The ominous resurgence of tuberculosis after many years of containment necessitates a review of the various factors responsible. An intense collaborative effort is needed to avoid potentially catastrophic consequences of the new epidemic. To provide a basis for health education recommendations, the factors contributing to the resurgence of tuberculosis, the nature of the current epidemic, and past health education efforts are reviewed. Further, an expanded Health Belief Model is offered as a foundation to guide educational campaigns.

AIDS-Related Opportunistic Infections↗
PubMed1995

Clinical comparison of Provisc and Healon in cataract surgery.

This prospective, randomized, multicenter clinical trial compared the safety and efficacy of the Provisc and Healon viscoelastics. Sixty-one eyes of 61 patients had an extracapsular cataract extraction with implantation of a posterior chamber intraocular lens with the aid of Provisc (n = 32) or Healon (n = 29). Mean changes in preoperative versus postoperative corneal thickness and intraocular pressure and the incidence and magnitude of postoperative corneal edema and iritis were not significantly different between the two groups. Observed complications were considered consequences of the surgery and unrelated to viscoelastic use. No adverse medical events occurred. These results indicate Provisc and Healon are clinically equivalent in terms of safety and efficacy when used as surgical aids.

Cataract Extraction↗