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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 91 records · Page 5Linked to original sources
PubMed1994

Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer.

A case report of a hypertensive crisis resulting from the ingestion of tap beer in a patient on an irreversible monamine oxidase inhibitor (MAOI; phenelzine) stimulated the investigation of different kinds of beer for tyramine concentration. The objective was to determine the tyramine concentration in tap and bottled beers. A total of 98 beer samples (79 different brands of beer) were analyzed by high-performance liquid chromatography for tyramine. Of these 98 beers, 49 were bottled or canned beers and 49 were beers on tap. All of the bottled beers analyzed had safe tyramine concentrations (< or = 10 mg/liter; range, 0 to 3.16 mg/liter) and, thus, do not require restriction in patients receiving MAOIs. Therefore, the consumption of canned or bottled beer, including dealcoholized beer, in moderation (fewer than four bottles or cans; 1.5 liters within a 4-hour period) appears to be safe and does not require restriction in patients receiving MAOIs. Only 4 of 98 beer samples studied were found to have a dangerous (> 10 mg/liter) tyramine concentration, one of which was the index beer. The tyramine concentration in these four beers ranged from 26.34 to 112.91 mg/liter. All four of these beers were tap beers produced by bottom fermentation (lagers) and brewed by a secondary fermentation process. Although we did not find any visible bacterial growth in the tap beers with high tyramine content, this finding does not preclude the possibility that bacterial contamination, bacterial growth, production of tyramine, and eventually bacterial death occurred at some earlier time. Therefore, to err on the side of caution, it is recommended that patients on irreversible MAOIs avoid beers on tap.

Adult↗
PubMed1993

Relationship of pain behavior to disease activity and health status in rheumatoid arthritis.

The purpose of the study was to investigate the contributions of disease activity, health status, and self-efficacy to the pain behavior exhibited by patients with rheumatoid arthritis. Measures included the Arthritis Impact Measurement Scales, the Arthritis Self-Efficacy Scale, a visual analogue scale for pain, and the McGill Pain Questionnaire. Joint counts and ratings of pain behavior also were obtained. All measures were collected at both baseline and 6 months. Hierarchical multiple regression analyses revealed that disease activity, as measured by joint count, was significantly related to a modified pain behavior index at both time intervals. With joint count entered into the regression model, no other variable consistently increased the predictive accuracy of the model. There were no significant correlations between the modified pain behavior index and either the visual analogue scale for pain or the McGill Pain Questionnaire scores. The results suggest that pain behavior in male rheumatoid arthritis patients is more closely related to disease activity than to self-reported pain, health status, or perceived self-efficacy.

Adaptation, Psychological↗
PubMed1993

C57BL/6 mice are resistant to tumor promotion by full thickness skin wounding.

The present study demonstrates that C57BL/6 mice, previously shown to be relatively resistant to skin tumor promotion by phorbol esters as well as several other classes of tumor promoters, are resistant to skin tumor promotion by full thickness skin wounding. Two separate experiments were performed comparing female SENCAR and C57BL/6 mice for their sensitivity to skin tumor promotion by skin wounding following initiation with 7,12-dimethylbenz[a]anthracene (DMBA). In the first experiment, groups of mice were initiated with 25 nmol DMBA and then received full thickness skin wounds in the initiated skin 2 weeks later. Neither SENCAR nor C57BL/6 mice developed skin tumors during the 26 weeks following initial wounding. However, these groups were rewounded in week 27 and 14 weeks later the SENCAR mice had developed a significant tumor response (0.75 papillomas per mouse, 55% incidence). At this time, the C57BL/6 mice still did not have a tumor response significantly different from the acetone-initiated controls. A second experiment was performed using a 100 nmol initiating dose of DMBA. Fifteen weeks after initial wounding in this experiment, the group of SENCAR mice had 0.76 papillomas per mouse (41% incidence) whereas no tumors were present in the group of C57BL/6 mice, even 31 weeks after the initial wounding. The results demonstrate that C57BL/6 mice are resistant to an endogenous skin tumor promotion mechanism and strongly support a link between skin tumor promotion by several classes of chemical promoters and full thickness wounding.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Comparison of 12-O-tetradecanoylphorbol-13-acetate and teleocidin for induction of epidermal hyperplasia, activation of epidermal PKC isozymes and skin tumor promotion in SENCAR and C57BL/6 mice.

The present study compared the ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin to induce sustained epidermal hyperplasia, activate partially purified epidermal protein kinase C (PKC) isozymes and promote skin tumors in SENCAR and C57BL/6 mice. Teleocidin was less effective than TPA on a molar basis for inducing sustained epidermal hyperplasia, promoting skin tumors and activating partially purified epidermal PKC isozymes in vitro when examined using SENCAR mice. In contrast, teleocidin was more effective than TPA on a molar basis for inducing sustained epidermal hyperplasia, approximately equi-effective for promoting skin tumors and significantly less effective for activating PKC isozymes in vitro when examined using C57BL/6 mice. Despite the differences in response of C57BL/6 mice to TPA and teleocidin, this mouse strain was still highly resistant to skin tumor promotion by both types of promoters when compared with SENCAR mice. The current results, when considered in light of our recent studies (Cancer Res., 51, 1398-1405, 1991), indicate that C57BL/6 are generally resistant to a variety of classes of skin tumor promoters, including the teleocidins. In addition, except for the phorbol esters, the induction of sustained epidermal hyperplasia does not appear to be as good a marker for overall promotion responsiveness between SENCAR and C57BL/6 mice with other classes of tumor promoters; although the induction of a significant sustained hyperplasia in the latter mouse strain did yield a weak tumor response. Taken together, the current data suggest that factors in addition to the induction of sustained epidermal hyperplasia, control responsiveness of C57BL/6 mice to skin tumor promotion by diverse promoting stimuli.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Further studies on the influence of initiation dose on papilloma growth and progression during two-stage carcinogenesis in SENCAR mice.

The present study was designed to further evaluate the growth and progression of papillomas to squamous cell carcinomas (SCCs) in groups of animals receiving initiating doses of 7,12-dimethylbenz[a]anthracene (DMBA) producing relatively low papilloma yields following long term promotion (60 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA). For comparison, groups of animals were initiated with various doses of DMBA and then promoted with mezerein (MEZ), benzoyl peroxide (BzPo) and chrysarobin (CHRY). Following initiation, groups of female SENCAR mice received the following promoter doses: TPA (1.0 or 2.0 micrograms per mouse); MEZ (2.0 micrograms per mouse); BzPo (20.0 mg per mouse); and CHRY (52.8 micrograms per mouse). The maximum papilloma to SCC conversion ratio obtained with TPA in the current study was 0.32. This value was in the range of maximum conversion ratios obtained with the other compounds: MEZ, 0.40; CHRY, 0.32 and BzPo, 0.19. In general, the highest papilloma to SCC conversion ratios observed with TPA as the promoter were obtained in groups that received the lowest doses of DMBA and had relatively low papilloma burdens. A comparison of papilloma to SCC conversion in groups of mice promoted with TPA, MEZ or CHRY and having similar papilloma yields, revealed very similar conversion ratios. Comparison of the BzPo group with a similar papilloma yield indicated that the conversion ratio was slightly lower with this promoter. The present results indicate that in mice promoted with TPA and having relatively low papilloma numbers, a larger proportion of these papillomas progress to SCCs during continued promoter treatment. Furthermore, the results suggest that papillomas behave similarly in their ability to progress to SCCs regardless of the promoter used when comparing groups of mice with similar tumor numbers. The data are discussed in terms of possible mechanisms for the observed results.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Effects of parturition, suckling and pseudopregnancy on variables of disease activity in the B/W mouse model of systemic lupus erythematosus.

OBJECTIVE: The pituitary hormone, prolactin, accelerates systemic lupus erythematosus in NZB/NZW F1 (B/W) mice. Our study evaluated disease activity in B/W females experiencing the physiologic hyperprolactinemia of mating, pregnancy, suckling, and pseudopregnancy. METHODS: Nonsuckling postpartum, suckling and pseudopregnant mice were compared to virgin females. Serum prolactin, anti-DNA antibodies (anti-DNA), gp70-anti-gp70 immune complexes, IgM, IgG, albuminuria, and renal function were monitored serially. RESULTS: Females that whelped 2 litters had apparent stimulation of anti-DNA; those that suckled their young had similar premature appearance of anti-DNA as well as delayed, but marked, hypergammaglobulinemia. Pseudopregnant mice, which characteristically secrete repeated surges of prolactin, had significant acceleration of multiple variables of disease activity. CONCLUSIONS: Pregnancy, parturition and suckling did not immediately accelerate lupus in B/W dams, and longevity was not affected in females that had borne litters. Pseudopregnancy was the most effective stimulator of variables of autoimmunity.

Albuminuria↗
PubMed1993

New Zealand white mice: an experimental model of exencephaly.

This is the initial report of an unusually high incidence of exencephaly in inbred New Zealand White (NZW) mice and the congenic NZW-xid strain, in which animals are homozygous for the recessive X-linked immune deficiency (xid) gene. The predominant expression of exencephaly in female pups and a disproportionate decrease in numbers of female pups in litters suggested that exencephaly was part of a continuum of lethal defects expressed preferentially in females. Genetic influence in the expression of exencephaly in NZW mice was postulated because environmental cohort controls did not express this defect. NZW mice are an additional model for studying the pathogenesis of neural tube defects.

Animals↗
PubMed1992

Premature death with bladder outlet obstruction and hyperprolactinemia in New Zealand black X New Zealand white mice treated with ethinyl estradiol and 17 beta-estradiol.

OBJECTIVE: To determine causes of death, estrogen toxicity, and hyperprolactinemia in a murine model of systemic lupus erythematosus (SLE). METHODS: Female New Zealand Black x New Zealand White (NZB x NZW) mice were implanted with ethinyl estradiol, 17 beta-estradiol, or empty capsules (controls). RESULTS: Estrogen-treated mice developed striking hyperprolactinemia and died prematurely with genitourinary complications. CONCLUSION: Implanted estrogens, including 17 beta-estradiol in a dose reported previously to stimulate SLE, contribute to premature death in NZB x NZW mice, through toxic effects. Estrogen therapy increases the level of prolactin, an immunostimulatory hormone.

Animals↗
PubMed1992

Psychological factors, immunologic activation, and disease activity in rheumatoid arthritis.

The purpose of this study was to use structural equation modeling techniques to examine potential interrelationships among psychological factors, immunologic activation, and disease activity in rheumatoid arthritis (RA). The subjects were 80 male patients with a diagnosis of classic or definite RA. Measures included the Beck Depression Inventory, the Arthritis Helplessness Index, and the Arthritis Impact Measurement Scales (AIMS) pain score. Joint counts and immunophenotypic analyses of peripheral blood lymphocytes also were collected. Path analysis showed that percentage of HLA-DR+ cells in the peripheral blood and helplessness were related to join count. In addition, joint count had an effect upon depression. Depression had an effect upon pain, but there was no reciprocal effect of pain upon depression. This study describes a preliminary path model of interrelationships among psychological factors, immunologic activation, and disease activity in RA.

Aged↗
PubMed1992

Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites.

The intent of this study was to identify pharmacokinetic and pharmacodynamic characteristics for spironolactone (SP) and its metabolites (canrenone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone, 7 alpha-thiomethylspirolactone) in cirrhotics under steady state conditions. Nine cirrhotics with ascites participated in the study. Serial blood samples were drawn and urine was collected over a 26-hour period. Using a reverse-phase high performance liquid chromatography (HPLC) method, all samples were analyzed for SP, canrenone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone, and 7 alpha-thiomethylspirolactone concentrations. Parent compound and metabolite urinary excretion rates as well as maximal concentrations and time at which these are observed were calculated. The apparent median terminal elimination rate constants (associated half-lives) were 0.0767 h-1 (9.04 hours) for SP, 0.0055 h-1 (126 hours) for 6 beta-hydroxy-7 alpha-thiomethylspirolactone, 0.029 h-1 (23.9 hours) for 7 alpha-thiomethylspirolactone and 0.012 h-1 (57.8 hours) for canrenone. SP metabolism is impaired in cirrhosis; terminal half-lives of SP and metabolites appear to be increased when compared with values reported in the literature for normals. When assuming a linear model, clearance-effect relationship estimates are best correlated with 7 alpha-thiomethylspirolactone and canrenone. Further research is required to identify specific pharmacokinetic and pharmacodynamic parameters for SP and its metabolites in this patient population.

Adult↗
PubMed1992

A controlled study of lymphocyte subsets in rheumatoid arthritis.

The purpose of this study was to determine if patients with rheumatoid arthritis (RA) exhibited unique patterns of peripheral blood lymphocyte (PBL) subsets in comparison to patients with osteoarthritis (OA) and, further, if such differences related to disease activity or nondisease factors. Data from 63 RA patients and 47 OA patients revealed that the RA patients had lower absolute numbers of CD2+ and CD4+ lymphocytes. Small differences also were found in selected B-cell subsets and subsets of lymphocytes expressing CD16 and/or CD57 antigens. Further analysis revealed that these differences were due primarily to the effects of cytotoxic medications in the RA group. However, there were also alterations in some subsets independent of medication groups. PBL subsets in RA patients did not relate to chronic low-dose prednisone or measures of disease activity. This study demonstrated the need to control carefully for variables such as age and medication in immunophenotypic investigations of RA.

Aging↗
PubMed1992

Further genetic analyses of skin tumor promoter susceptibility using inbred and recombinant inbred mice.

To explore further the genetics of susceptibility to skin tumor promotion in inbred mice, several aspects of responsiveness to 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined in C3H/He mice and segregating crosses between this mouse strain and C57BL/6 mice as well as BXD and BXH recombinant inbred (RI) strains. Dose-response relationships were established for skin tumor promotion by TPA following initiation with 7,12-dimethylbenz[a]anthracene in C3H/He and B6C3F1, as well as several other mouse stocks and strains included for comparison. The relative responsiveness to TPA skin tumor promotion was: SENCAR much greater than DBA/2 greater than C3H/He approximately B6D2F1 greater than B6C3F1 much greater than C57BL/6. Analyses of the susceptibility of B6C3F2 and B6C3F1 x C57BL/6 backcross mice suggested that a minimum of two dominant genetic loci control responsiveness to phorbol ester promotion in these mice. Further analysis of BXH and BXD RI strains suggested the presence of four distinct promotion-responsive phenotypes controlled by a minimum of two genetic loci. The existence of a 'hyper-responsive' phenotype in the sets of RI strains, however, suggests that a third, recessive locus also may play a role in controlling responsiveness to TPA promotion. At 48 h after the last of four applications of TPA, marked hyperplasia and an increase in dark basal keratinocytes were observed in C3H/He mice, whereas in B6C3F1 mice the response in these parameters was intermediate between C3H/He and C57BL/6 mice. A marked dermal inflammation, as determined by infiltration of polymorphonuclear cells, was observed in C3H/He and B6C3F1 mice, whereas little was noted in C57BL/6 mice. Furthermore, histological evaluations of selected BXD RI strains revealed a significant correlation between the magnitude of the hyperplasia response and the percentage of mice bearing tumors. The present data, in conjunction with our previous studies, confirm that the major gene(s) controlling susceptibility to tumor promoter induced by TPA in two sensitive strains (i.e. DBA/2 C3H/He) are similar or closely linked to those for induction of sustained hyperplasia. In addition, the present data provide new evidence for a model where allelic differences at a minimum of three loci contribute to gene differences in susceptibility to phorbol ester promotion DBA/2 and C3H/He versus C57BL/6 mice.

Animals↗
PubMed1992

Induction of epidermal ornithine decarboxylase activity in mouse skin exposed to biogenic silica fibers.

The present study demonstrates that biogenic silica fibers (BSF), previously shown to promote skin tumors in mice and more recently to promote the induction of mesotheliomas when injected into the pleural cavity of rats, rapidly induces epidermal ornithine decarboxylase (ODC) activity in SENCAR mice following topical application. The time course for induction of epidermal ODC by BSF was very similar to that observed following topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). Maximal ODC activity was observed 4-6 h following treatment with BSF. Cycloheximide (70 mg/kg i.p.) partially inhibited (61%) the induction of ODC by BSF at 5 h. In addition, retinoic acid (RA, 5 micrograms per mouse given 30 min before BSF) effectively inhibited BSF-induced ODC by 68%, while indomethacin (100 micrograms per mouse 2 h before BSF) had little or no effect. Copper(II) bis(diisopropylsalicylate) (2 mumol 30 min before BSF), an effective inhibitor of TPA-induced ODC activity and tumor promotion, also had little or no effect on BSF-induced ODC. The work described in this paper suggests that BSF induces epidermal ODC by a very specific mechanism that exhibits both similarities and differences with that of the phorbol ester, TPA. Nevertheless, this response strongly supports the conclusion that BSF is an effective tumor promoter in mouse skin and that ODC induction is an integral part of the mechanism of action of this environmental promoter.

Animals↗
PubMed1992

The effect of food or sucralfate on the bioavailability of S(+) and R(-) enantiomers of ibuprofen.

This randomized, multiple cross-over pharmacokinetic study was undertaken to determine if food or sucralfate alter the bioavailability of the active S(+) enantiomer of ibuprofen. Eleven healthy adult male volunteers were given three single 600-mg doses of ibuprofen (separated by 1 week) administered either in a fasting state, after a standardized breakfast, or with sucralfate 1 g. The main outcome measures were area under the concentration (AUC), maximum peak plasma concentration (Cmax), and time to reach peak concentration (tmax) for total, S(+), and R(-) enantiomer serum ibuprofen levels, drawn up to 10 hours after dosing. The AUC for R(-) ibuprofen was significantly lower than S(+) ibuprofen in all three treatment groups. The treatments had no different effects on AUC for S(+), R(+), or total ibuprofen. There was no difference in the ratio of S(+):R(-) enantiomers across different treatment groups, but the intersubject variability was significant (P < .05). The S(+) ibuprofen Cmax was greater than the R(-) ibuprofen Cmax for all treatment groups (P < .05). Sucralfate reduced the peak concentration of both S(+) and R(-) enantiomers when compared with fasting (P < .05). There was a slight but nonsignificant increase in the mean time to achieve peak concentration of both S(+) and R(-) enantiomers. Neither food nor sucralfate has a significant effect on ibuprofen enantiomer pharmacokinetics, but interindividual variability contributes significantly to the variability of enantiomer bioavailability.

Adult↗
PubMed1991

Prolactin influences autoimmune disease activity in the female B/W mouse.

Prolactin, an anterior pituitary hormone, stimulates humoral and cell-mediated immunity. This study investigated effects of manipulating prolactin levels in the autoimmune B/W mouse model of SLE. A group of B/W females was treated with daily injections of the prolactin-suppressing drug, bromocriptine. These mice had delayed elevation of anti-DNA antibodies and serum IgG; longevity was increased compared to control mice. Functioning syngeneic pituitary glands, implanted under the renal capsule, produced prolonged hyperprolactinemia in a separate group of female B/W mice. Hyperprolactinemic animals were characterized by premature albuminuria, elevated circulating gp70IC and IgG, and accelerated mortality. Analyses of thymic and splenic lymphocytes revealed no differences in lymphocyte subpopulations in mice with altered prolactin levels. This is the first report to substantiate an immunomodulatory role for prolactin in B/W mice. Further evaluation of this model may identify specific means of intervening clinically with immunosuppressive hormone-modulating therapy in SLE.

Albuminuria↗
PubMed1991

Biopsychosocial parameters of disease activity in rheumatoid arthritis.

The purpose of this study was to examine the applicability of a biopsychosocial model for estimating disease activity in rheumatoid arthritis (RA). Sixty-three patients with RA were evaluated at baseline, 3 months, and 6 months. Joint counts were collected as the measure of disease activity. Peripheral blood immunophenotypic subsets, demographic characteristics, and psychological measures were obtained and entered into hierarchical regression analyses, with the joint count as the dependent variable. Immunophenotypic subsets (that is, CD57+/CD16-, HLA-DR+) were predictive of disease activity at all three time intervals. At baseline and 3 months, psychological variables (that is, helplessness and depression) were significantly related to joint counts, and the full model was highly significant. The conclusion was that the biopsychosocial perspective is useful for estimating RA disease activity.

Aged↗