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Biomedical subjects

R W Johnson

Publications and source records attributed to R W Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Treatment of postherpetic neuralgia: an update.

Postherpetic neuralgia (PHN) is a chronic pain syndrome that is often refractory to treatment and can last for years, causing physical and social disability, psychological distress, and increased use of the healthcare system. In this paper we provide an update on recent developments in the treatment of PHN. We emphasise the results of recent studies that provide an evidence-based approach for treating PHN that was not available until very recently. In randomised, controlled clinical trials, the topical lidocaine patch, gabapentin, and controlled release oxycodone have been shown to provide superior pain relief in patients with PHN when compared with placebo. It has also recently been demonstrated that the tricyclic antidepressant nortriptyline provides equivalent analgesic benefit when compared with amitriptyline, but is better tolerated. Based on these results, nortriptyline can now be considered the preferred antidepressant for the treatment of PHN, although desipramine may be used if the patient experiences unacceptable sedation from nortriptyline. The topical lidocaine patch, gabapentin and controlled release oxycodone all appear to be as effective as tricyclic antidepressants in the treatment of patients with PHN, and the results of these recent studies suggest that each of these treatments should be considered early in the course of treatment. Additional controlled trials are needed to compare the efficacy and tolerability of these 4 treatments- tricyclic antidepressants, gabapentin, the topical lidocaine patch and controlled release opioid analgesics--used singly and in various combinations in the treatment of patients with PHN.

Herpes Zoster↗
PubMed2000

Uninsured status and out-of-pocket costs at midlife.

OBJECTIVE: To investigate how baseline health insurance coverage affects subsequent out-of-pocket costs and utilization of health services over a two-year period. DATA SOURCE: The first two waves of the Health and Retirement Study, a nationally representative survey of the noninstitutionalized population, ages 51 to 61 at baseline. Interviews were conducted in 1992 and 1994. Our sample consisted of 7,018 respondents who did not report public insurance as their sole source of coverage at baseline. STUDY DESIGN: We compared self-reports of physician visits, hospitalizations, and out-of-pocket health care costs, measured as payments to physicians, hospitals, and nursing homes, by type of insurance coverage at the beginning of the period. We estimated multivariate models of costs and service use to control for individual health, demographic, and economic characteristics and employed instrumental variable techniques to account for the endogeneity of insurance coverage. PRINCIPAL FINDINGS: Controlling for personal characteristics and accounting for the endogeneity of insurance coverage, persons at midlife with job-related health benefits went on to spend only about $50 per year less in out-of-pocket payments for health services than persons who lacked health insurance at the beginning of the period. However, they spent about $650 more per year in insurance premiums than the uninsured. The uninsured used relatively few health services, except when they were seriously ill, in which case they were likely to acquire public insurance. CONCLUSIONS: The medically uninsured appear to avoid substantial out-of-pocket health care costs by using relatively few health services when they are not seriously ill, and then relying upon health care safety nets when they experience medical problems. These results suggest that the main impact of non-insurance at midlife is not to place the locus of responsibility for costly health care upon individuals. Instead, it discourages routine care and transfers the costs of care for severe health events to other payers. Our findings on the high cost of employment-based coverage are consistent with evidence that the proportion of workers accepting health benefits from employers has been declining in recent years.

Age Factors↗
PubMed1999

Comparison of microemulsion and conventional formulations of cyclosporine A in preventing acute rejection in de novo kidney transplant patients. The U.K. Neoral Renal Study Group.

BACKGROUND: The microemulsion preconcentrate formulation of cyclosporine A (CsA) (Neoral) exhibits more uniform pharmacokinetics than the conventional formulation (Sandimmun; SIM). This randomized, open-label, U.K. multicenter study compared the efficacy, safety, and tolerability of Neoral and SIM in preventing acute rejection in de novo renal transplant recipients. METHODS: Adult cadaveric kidney recipients (n=293) received Neoral or SIM twice daily for 12 months. Initially identical Neoral and SIM doses were titrated, maintaining trough CsA levels within locally defined therapeutic limits. RESULTS: In the year after transplantation, acute rejection occurred in 34% of the Neoral and 47% of the SIM recipients (P=0.037). In the intent-to-treat population, fewer treatment failures (defined as acute rejection, graft loss, withdrawal, or death) occurred in the Neoral (45%) than the SIM recipients (58%) (P=0.015) and therapeutic CsA levels (> or =250 microg/L) were reached faster with Neoral than SIM (P=0.0017). Antibody treatment of refractory rejection was used slightly less in the Neoral group (Neoral: 10%; SIM: 12%). One-year patient and graft survival rates (excluding deaths with functioning grafts) were 95% and 88%, respectively, for Neoral and 96% and 89% for SIM. Both formulations were well tolerated. No differences were observed between therapies in the nature, frequency, or severity of adverse events. Neoral use was not associated with increased nephrotoxicity or excessive immunosuppression. CONCLUSIONS: Neoral reduced the incidence of acute rejection compared with SIM, without significant increases in adverse events. This was achieved without altering existing SIM protocols and was attributed to improved absorption of CsA from Neoral and less variability in whole blood CsA concentrations.

Acute Disease↗
PubMed1999

Central administration of insulin-like growth factor-1 inhibits lipopolysaccharide-induced sickness behavior in mice.

To assess the possible modulatory effects of insulin-like growth factor-1 (IGF-1) on the brain effects of proinflammatory cytokines, male CD-1 mice were injected into the lateral ventricle of the brain with a behaviorally depressing dose (100 ng) of the cytokine inducer lipopolysaccharide (LPS) and their response to various doses of IGF-1 (0, 100 and 1000 ng) was measured during behavioral tests carried before and at various time intervals after treatment. LPS induced a profound behavioral depression that was abrogated by the higher dose of IGF-1 tested. Since the behavioral effects of LPS are mediated by the local synthesis and results of proinflammatory cytokines, these results indicate that IGF-1 interferes with the production and/or action of proinflammatory cytokines in the brain.

Animals↗
PubMed1999

Intracerebroventricular injection of lipopolysaccharide increases plasma leptin levels.

Leptin regulates adiposity by reducing caloric intake and increasing energy expenditure. Because loss of body weight is common during infectious, neoplastic, and autoimmune diseases of the central nervous system, we examined whether an injection of lipopolysaccharide (LPS) into the lateral cerebral ventricle increases circulating leptin levels in fasted mice. Centrally injected LPS (100 ng) induced a two-fold elevation in plasma leptin 6, 12, and 18 h post-injection. Peripheral injection of the same dose of LPS did not affect leptin secretion. This suggests that inflammatory stimuli localized in the CNS are sufficient to induce leptin secretion in the periphery. The induction of leptin by inflammatory stimuli in the brain may be part of a feed-back loop that contributes to anorexia and cachexia in many CNS-oriented diseases.

Analysis of Variance↗
PubMed1999

Increased interleukin-6 expression by microglia from brain of aged mice.

Over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative disease. Because the occurrence of certain neurodegenerative diseases increases with age, in the present study we examined the expression of the inflammatory cytokine, interleukin-6 (IL-6), in the brain of aged mice. In an initial experiment, IL-6 was measured in crude protein extracts from brains of juvenile (1-month-old), adult (3-month-old), and aged (24-month-old) male BALB/c mice. The concentration of IL-6 in crude protein extracts from the cerebellum, cerebral cortex, and hippocampus increased with age. The increase in IL-6 was discrete, as levels in the hypothalamus were not age-dependent. To begin evaluating spontaneous IL-6 production in aging, glial cells were cultured from brains of neonate, adult, and aged mice. An age-associated increase in IL-6 mRNA and supernatant IL-6 concentration was evident, indicating glia from aged mice spontaneously express high levels of IL-6 relative to glia from adult and neonate mice. Flow cytometric analysis revealed that cultures established from aged brain compared to either adult or neonate brain comprised more microglia (i.e., MAC-1-positive cells). Furthermore, the proportion of microglia that was positive for IL-6 increased with age, whereas the proportion of astrocytes that were positive for IL-6 was not age-dependent. The present results suggest that IL-6 increases in the mouse brain with age, and that microglia cultured from aged mice spontaneously produce more IL-6 than those from neonate or adult mice. Therefore, microglia may contribute to the increased level of IL-6 present in aged brain.

Aging↗
PubMed1999

Participants' judgements of the European Donor Hospital Education Programme (EDHEP): an international comparison.

The European Donor Hospital Education Programme (EDHEP) is a one-day workshop, aimed at providing guidelines for breaking the news of the death of a relative and for raising the issue of organ donation with bereaved relatives. Participants' judgements of the workshop in the Netherlands and in the United Kingdom were compared to determine whether EDHEP meets doctors' and nurses' training needs in breaking bad news and requesting organ donation. In both countries EDHEP appears to be greatly appreciated by intensive care medical and nursing staff; the judgements are more positive in the United Kingdom than in the Netherlands. It seems that, irrespective of their professional experience, intensive care staff consider EDHEP a valuable teaching programme that increases confidence in communicating with bereaved relatives about death and organ donation.

Attitude of Health Personnel↗
PubMed1999

Behavior of adult and aged mice before and after central injection of interleukin-1beta.

The level of locomotor activity, body temperature (T(B)), and feeding for adult (3-5-month old) and aged (22-24-month old) male BALB/c mice was determined and the sensitivity of the two age groups to the anorectic, febrile, and behavioral properties of interleukin-1beta (IL-1beta) in the brain was examined. Baseline locomotor activity and T(B) were markedly lower in aged mice than in adults and the circadian rhythm for both activity and T(B) were disrupted in the aged. Adult and aged mice consumed similar amounts of food during the daytime and nighttime, but aged mice made longer, less frequent visits to the feed cup. To determine if aging affects the responsiveness to central IL-1beta, adult and aged mice were injected intracerebroventricularly with PBS or IL-1beta. Compared to age-matched PBS controls, IL-1beta increased T(B) in both adult and aged mice. The peak deltaT(B) was greater in aged mice than in adults, but because of a lower baseline T(B) in aged mice, peak T(B) after IL-1beta was not different between groups. Locomotor activity of aged mice receiving PBS was about half that of PBS-injected adults and was not depressed further by IL-1beta. However, compared to age-matched PBS controls, centrally administered IL-1beta depressed food intake more in aged mice than in adults. These data indicate that even though feeding, locomotor activity, and T(B) are affected by aging, the central component of the inflammatory response mediated by IL-1beta is retained.

Aging↗
PubMed1999

Gender differences in pension wealth: estimates using provider data.

Information from pension providers was examined to investigate gender differences in pension wealth at midlife. For full-time wage and salary workers approaching retirement age who had pension coverage, median pension wealth on the current job was 76% greater for men than women. Differences in wages, years of job tenure, and industry between men and women accounted for most of the gender gap in pension wealth on the current job. Less than one third of the wealth difference could not be explained by gender differences in education, demographics, or job characteristics. The less-advantaged employment situation of working women currently in midlife carries over into worse retirement income prospects. However, the gender gap in pensions is likely to narrow in the future as married women's employment experiences increasingly resemble those of men.

Female↗
PubMed1999

Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide.

Interleukin-1beta (IL-1beta) is expressed in the mouse brain after intracerebroventricular injection of lipopolysaccharide (LPS) and is thought to be responsible for many of the behavioral and neuroendocrine changes that occur during inflammation. In this study we show that LPS in the brain also induces expression of interleukin-1beta converting enzyme (ICE) and that ICE is important for the characteristic anorectic response of mice to intracerebroventricular LPS. Specifically, mice that were deficient in ICE (ICE(-/-)) resisted the anorexia caused by intracerebroventricular injection of LPS but were sensitive to the anorectic properties of recombinant IL-1beta. The typical anorectic response seen in wild-type (WT) mice after LPS was restored in ICE(-/-) mice by intracerebroventricular administration of the ICE analog cathepsin G. Conversely, anorexia induced by intracerebroventricular injection of LPS in WT mice was blocked by prior intracerebroventricular injection of the ICE antagonist YVAD. CMK. Furthermore, in situ hybridization immunohistochemistry revealed intense expression of ICE mRNA in the hippocampus and dorsomedial hypothalamus of WT mice after intracerebroventricular injection of LPS. Thus ICE mRNA is expressed in brain after intracerebroventricular injection of LPS and is important for induction of anorexia, presumably because it generates mature IL-1beta. These results suggest that preventing generation of mature IL-1beta can inhibit anorexia induced by LPS in the brain and, therefore, reveal ICE as a potential target for regulating food intake during brain inflammation.

Amino Acid Chloromethyl Ketones↗
PubMed1999

A comparison of pulmonary arterial occlusion algorithms for estimation of pulmonary capillary pressure.

Using the arterial occlusion method, we compared five literature-based estimates of pulmonary capillary pressure (Ppc) with the corresponding double occlusion pressures (Pdo) in anesthetized dogs whose chests had been closed after sternotomy for instrumentation. Arterial occlusions were performed with a balloon-tipped pulmonary artery catheter that housed pressure transducers immediately proximal and distal to the balloon. Separation of the proximal and distal pressure waveforms during balloon inflation allowed us to precisely define the moment of occlusion. We fit a monoexponential curve to pressure data beginning 200 ms after the onset of occlusion and a biexponential curve to data beginning at the instant of occlusion, with data obtained over a range of vascular states (control, serotonin infusion, histamine infusion). In addition, we investigated the use of sampling of the raw data to estimate capillary pressure. Three of the five literature-based estimates of Ppc yielded values similar to Pdo. The optimal (least average difference from Pdo) interpolation/extrapolation time points of the curve fits varied, depending on the type of curve fitting and the state of the pulmonary vasculature. We also determined that a close approximation of Pdo may be derived from the raw data, as an alternative to exponential curve fitting.

Algorithms↗
PubMed1998

Domain structure analysis of elongation factor-3 from Saccharomyces cerevisiae by limited proteolysis and differential scanning calorimetry.

Elongation-factor-3 (EF-3) is an essential factor of the fungal protein synthesis machinery. In this communication the structure of EF-3 from Saccharomyces cerevisiae is characterized by differential scanning calorimetry (DSC), ultracentrifugation, and limited tryptic digestion. DSC shows a major transition at a relatively low temperature of 39 degrees C, and a minor transition at 58 degrees C. Ultracentrifugation shows that EF-3 is a monomer; thus, these transitions could not reflect the unfolding or dissociation of a multimeric structure. EF-3 forms small aggregates, however, when incubated at room temperature for an extended period of time. Limited proteolysis of EF-3 with trypsin produced the first cleavage at the N-side of Gln775, generating a 90-kDa N-terminal fragment and a 33-kDa C-terminal fragment. The N-terminal fragment slowly undergoes further digestion generating two major bands, one at approximately 75 kDa and the other at approximately 55 kDa. The latter was unusually resistant to further tryptic digestion. The 33-kDa C-terminal fragment was highly sensitive to tryptic digestion. A 30-min tryptic digest showed that the N-terminal 60% of EF-3 was relatively inaccessible to trypsin, whereas the C-terminal 40% was readily digested. These results suggest a tight structure of the N-terminus, which may give rise to the 58 degrees C transition, and a loose structure of the C-terminus, giving rise to the 39 degrees C transition. Three potentially functional domains of the protein were relatively resistant to proteolysis: the supposed S5-homologous domain (Lys102-Ile368), the N-terminal ATP-binding cassette (Gly463-Lys622), and the aminoacyl-tRNA-synthase homologous domain (Glu820-Gly865). Both the basal and ribosome-stimulated ATPase activities were inactivated by trypsin, but the ribosome-stimulated activity was inactivated faster.

Amino Acid Sequence↗
PubMed1998

Clinical response and temporal patterns of acute cellular rejection: relationship to chronic transplant nephropathy.

The association between acute cellular rejection (ACR) and the development of chronic rejection has been the subject of much debate. Studies have suggested that the two phenomena may be linked, or, conversely that there may be no association at all. In order to clarify this relationship the outcome of 284 renal allografts were examined. The transplants were all performed at a single institution between April 1989 and December 1991, allowing a minimum follow up of 5 years. ACR was classified into three clinical response groups: (1) fully responsive to therapy (type 1 ACR), (2) partially responsive (type 2) and (3) ACR requiring treatment with ATG or OKT3 (type 3). Acute and chronic rejection were determined by histological (Banff) criteria. Chronic transplant nephropathy (CTN) occurred significantly more frequently in those with late ACR after day 60 than in those who had early rejection (53.5% versus 17.3%, respectively, P < 0.00001). Acute rejection that was fully responsive to therapy (type 1) had no association with CTN, but partially responsive rejection and rejection requiring second-line treatment were both significantly associated with CTN (P < 0.0001 and P < 0.001, respectively). This study suggests that it is the clinical behaviour and response to treatment of ACR that is paramount in determining the onset of chronic rejection, and not hte mere presence or absence of the clinical phenomenon.

Acute Disease↗
PubMed1998

Neuroendocrine-immune interactions in the neonate.

Cytokine responses to lipopolysaccharides in neuroendocrine tissues are age- and tissue-dependent in neonatal pigs. Developmental differences in serum and tissue-specific responses are not necessarily equivalent. Lower levels of cytokine gene expression in neuroendocrine tissues of early neonates potentially could influence neuroendocrine and immune responses to infection. The limited information on neuroendocrine-immune responses and interactions in neonatal farm animals presents significant challenges, as well as opportunities for new discoveries and improvements of livestock production.

Acute-Phase Reaction↗
PubMed1998

Immune and endocrine regulation of food intake in sick animals.

To understand why sick animals do not eat, investigators have studied how the immune system interacts with the central nervous system (CNS), where motivation to eat is ultimately controlled. The focus has been on the cytokines secreted by activated mononuclear myeloid cells, which include interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Either central or peripheral injection of recombinant IL-1 beta, IL-6, and TNF-alpha reduce food-motivated behavior and food intake in rodents. Moreover, these cytokines and their receptors are present in the endocrine system and brain, and antagonism of this system (i.e., the cytokine network) has been shown to block or abrogate anorexia induced by inflammatory stimuli. Recent studies indicate that the same cytokines act on adipocytes and induce secretion of leptin, a protein whose activity has been neuroanatomically mapped to brain areas involved in regulating food intake and energy expenditure. Therefore, many findings converge to suggest that the reduction of food intake in sick animals is mediated by inflammatory cytokines, which convey a message from the immune system to the endocrine system and CNS. The nature of this interaction is the focus of this short review.

Adaptation, Physiological↗
PubMed1998

An association between antibodies specific for endothelial cells and renal transplant failure.

Human leucocyte antigen (HLA)-specific antibodies, present at the time of transplant, cause renal transplant rejection but cases of rejection of HLA-identical renal transplants indicate that antibodies to non-HLA antigens may also be detrimental. There is increasing evidence that antibodies to antigens present on endothelial cells and monocytes, and on endothelial cells alone, are associated with transplant rejection. We investigated 105 patients with failed renal transplants for the presence of endothelial cell reactive antibodies and compared them with 94 successful transplant patients to determine the role of non-HLA antibodies in transplant failure. Patient sera were tested by enzyme-linked immunoabsorbent assay (ELISA) using as a target fixed cells either from the endothelial/epithelial cell line EAHy.926 or primary cultures of human umbilical vein endothelial cells. Antibody binding was detected using an alkaline phosphatase-conjugated anti-human immunoglobulin G (IgG) antibody. Fourteen of the 105 failed transplant patients had endothelial cell-reactive antibodies as compared with only three of the 94 patients with successful transplants (Fisher's exact test, p = 0.02). Antibody-positive sera were absorbed with the epithelial cell line A549 to remove antibodies directed against the epithelial component of EAHy.926 and with a pool of lymphoblastoid cell line cells to remove HLA-specific antibodies. Absorption did not reduce antibody activity showing the antibodies to be directed against endothelial cell determinants. Antibody-positive sera were also tested by flow cytometry against the monocyte cell line THP-1 and 13 of the 14 patients were negative. In conclusion, we have demonstrated the presence of IgG antibodies directed against endothelial cell determinants in renal transplant recipients in association with renal transplant failure.

Absorption↗