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J C White

Publications and source records attributed to J C White.

At least 55 records · Page 3Linked to original sources
PubMed1995

Lesbian health care. What a primary care physician needs to know.

Many primary care physicians take care of lesbians and women sexually active with women without being aware of their patients' sexual orientation. These women have unique medical and psychosocial needs that each physician must consider. Lesbian identity or being sexually active exclusively with women influences care in areas such as sexually transmitted diseases, risk of human immunodeficiency virus infection, counseling, cancer risk, screening, parenting, depression, alcohol use, and violence. We review an approach to taking a history with all women that facilitates open, comfortable communication with lesbians. We also review specific medical and psychosocial areas of primary care in which caring for lesbians is different from caring for other women. Further research is needed on lesbian health issues to provide appropriate guidelines to clinicians.

Adolescent↗
PubMed1993

The transfer of patients' ethics information among cooperating institutions: a future function of ethics networks.

With increasing use of ethics resources by health care teams, the number of patients transferred from one care setting to another who may have had ethics consultations is rising rapidly. There has been virtually no discussion in the ethics literature and no experience in our community addressing questions concerning the continuity of ethics care and the transfer of ethics information. Our ethics committee faced the following questions during a recent consultation. Should there be continuity of ethics care between institutions? If so, what should be the nature of the communication? How is continuity best accomplished? Do ethics consultants or committees incur additional liability following the transfer of care? Where should the boundaries of confidentiality be drawn? How can existing health care ethics networks facilitate continuity of ethics care? We address these ethical and logistical questions and hope to encourage others to report their views on these issues.

Communication↗
PubMed1993

Gastrointestinal transit is not impaired by regional loss of myenteric neurons in rat jejunum.

Chronic absence of myenteric neurons from a 5-cm segment of rat jejunum causes alterations in myoelectric activity. Spike potentials characteristic of phase III activity of the migrating motor complex (MMC) are present; however, the number of propagating spike potentials through the myenterically denervated region is reduced. The objective of this study was to examine the effect of the regional loss of myenteric neurons on gastrointestinal transit of a solid marker in the fasted rat. The rate of gastric emptying was not affected by the absence of the myenteric plexus in a 5-cm segment of the jejunum. However, 15 days after either myenteric denervation or vehicle treatment of a segment of jejunum, a more cephalad distribution and decreased rate of intestinal propulsion of the solid marker was observed in the small intestine. This delay in small intestinal transit observed at 15 days was not seen at 48 and 120 days. The decrease in transit at 15 days can be attributed to the handling of the bowel during the surgical procedure. The mouth-to-cecum transit time (MCT) was also not affected by chronic absence of the myenteric plexus. Furthermore, the MCT indicated that bacterial overgrowth, a common manifestation when gut motility is disrupted, did not occur in the small intestine after the experimental destruction of the myenteric plexus. The results of this study indicate that the regional loss of the myenteric plexus does not impair gastrointestinal transit in the fasted rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Novel antagonists of the 5-HT3 receptor. Synthesis and structure-activity relationships of (2-alkoxybenzoyl)ureas.

A series of benzoylureas derived from bicycle amines were prepared and evaluated for 5-HT3 antagonist activity on the rat isolated vagus nerve. From among these compounds, those analogues which were ortho substituted by an alkoxy group on the benzoyl function were shown to be potent 5-HT3 antagonists with similar or greater potency than the standard agent ondansetron. NMR and X-ray crystallography studies showed these o-alkoxy compounds to exist as a planar, hydrogen-bonded, tricyclic ring system. In molecular modeling studies on endo-N-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl-amino] carbonyl]-2-(cyclopropylmethoxy)benzamide (30) the central hydrogen-bonded ring was able to mimic an aromatic ring present in previously reported 5-HT3 antagonists.

Animals↗
PubMed1992

Modulation of the cellular pharmacokinetics of ara-CTP in human leukemic blasts by dipyridamole.

The effect of dipyridamole (DP) on the cellular retention of 1-beta-D-arabinofuranosylcytosine (ara-C) and its metabolites was examined in leukemic blasts that had been isolated directly from bone marrow aspirates from patients afflicted with acute myeloid leukemia (AML). When AML cells were loaded for 2 h with 1 microM [3H]-ara-C and then transferred to ara-C-free medium, total intracellular concentrations of radiolabel and [3H]-ara-C 5'-triphosphate [3H]-ara-C-CTP rapidly declined. After 8 h, total intracellular levels of tritium were 4.4 times higher if 10 microM was included in the washout medium; however, the majority of this intracellular radiolabel corresponded to [3H]-uridine arabinoside ([3H]-ara-U) and [3H]-ara-C. DP significantly increased the mean t1/2 for [3H]-ara-CTP from 102 to 136 min (P less than 0.01), but this effect was much less pronounced than that obtained for total tritium and the increase was quite variable (0-70%; median, 19%). The presence of DP in the washout medium also increased the incorporation of ara-C into DNA and the formation of ara-CDP-choline. The level of ara-CDP-choline continued to increase in both DP-containing and DP-free media for the first 4 h following drug removal and the formation of ara-CDP-choline continued during the first few hours in ara-C-free medium. At the end of the 8-h wash in DP-containing medium, the cellular concentration of ara-CDP-choline was equivalent to that found at the beginning of the washout period. Although statistically significant, the effect of DP on ara-CTP retention in AML blasts was much less pronounced than that previously observed in L5178Y leukemia. The former cells exhibited only 10% as many nucleoside transport carriers as did the L5178Y cells as measured by their capacity to bind [3H]-nitrobenzylmercaptopurine riboside (NBMPR). The effect of DP in prolonging ara-CTP retention was proportional to the number of [3H]-NBMPR binding sites. This suggests that in patients cells that exhibit extremely low transport capacity, most of the net catabolism occurs via deamination, and further inhibition of transport by DP in an effort to improve cellular retention of ara-C has little effect on ara-CTP catabolism.

Biological Transport↗
PubMed1992

Age and sex as factors influencing spontaneous exploration and object investigation by preadult rats (Rattus norvegicus).

This study examined developmental and sex differences in the exploratory and investigatory behaviors of Long-Evans rats (Rattus norvegicus). Littermate sextuplets were divided into sex-matched groups (at 30, 60, and 90 days of age) and were individually videotaped on 2 consecutive nights in an arena that contained stimulus objects. Multiple measures of locomotor exploration and object investigation increased significantly with age but were not influenced by sex. Older rats entered more quickly, were more active, spent more time in the arena, and spent more time investigating inanimate stimulus objects than did younger rats. Sex did not significantly affect most measures of open-field behavior; however, the data suggest that the sexes may begin to diverge by 90 days. These results suggest that preadult rats of both sexes are equipped early in development with similar strategies and repertoires for exploration and investigation.

Age Factors↗
PubMed1992

Methylphenidate as a treatment for depression in acquired immunodeficiency syndrome: an n-of-1 trial.

BACKGROUND: Uncontrolled studies report that methylphenidate effectively treats depression in patients with acquired immunodeficiency syndrome (AIDS). Other studies report that methylphenidate improves cognition in patients with dementia stemming from human immunodeficiency virus (HIV). We performed a double-blind, placebo-controlled n-of-1 trial to learn whether methylphenidate was an effective treatment for depression in an outpatient with mild HIV dementia. METHOD: The patient received either placebo or drug in a double-blinded fashion in increasing doses in each of three 2-week phases (A = placebo, B = methylphenidate, C = placebo). Blinded outcomes of depression and cognition were measured initially and twice in each phase. Depression was measured using the Hamilton Rating Scale for Depression (HAM-D) and a mood self-assessment scale. Cognition was measured using the digit span (forward and backward subtest of the Wechsler Adult Intelligence Scale-Revised, Trail-Making Tests A and B, and the Symbol Digit Modalities Test (SDMT). RESULTS: HAM-D scores improved during the methylphenidate phase (initial = 33; A = 23, 25; B = 15, 10; C = 28, 27), as did the subjective mood assessment ratings. Digit span backward scores improved with the drug (initial = 4; A = 4, 3; B = 6, 8; C = 5, 4), as did Trail-Making Test B scores (initial = 125 seconds; A = 133, 103 seconds; B = 86, 82 seconds; C = 88, 96 seconds). Digit span forward, SDMT, and Trail-Making Test A, however, showed no drug-related trend. CONCLUSION: We conclude that methylphenidate was beneficial in the treatment of depression in this patient with AIDS.

AIDS Dementia Complex↗
PubMed1991

A critical role for uridine nucleotides in the regulation of deoxycytidine kinase and the concentration dependence of 1-beta-D-arabinofuranosylcytosine phosphorylation in human leukemia cells.

The intracellular concentration of 1-beta-D-arabinofuranosylcytosine (ara-C) for half-maximal phosphorylation by leukemic blasts obtained directly from patients was 2.1 +/- 2.5 microM (median, 1.3 microM, N = 25), and the rate of ara-C accumulation actually declined at concentrations above 20 microM in 35% of these cell populations. These apparent Km values for cellular phosphorylation were an order of magnitude lower than the Km of deoxycytidine (dCyd) kinase for ara-C with ATP as phosphate donor. dCyd kinase was purified from human leukemia cells and assayed for [3H]ara-C kinase activity with a mixture of 7 nucleotides at their approximate cellular concentrations or with a single nucleotide deleted. At low or high ara-C concentrations, ATP, GTP, CTP, or dTTP could be eliminated without significantly altering the rate. The only potential phosphate donor that was clearly important was UTP, since its deletion reduced the rate to only 25% of that with the complete mix. As anticipated, eliminating dCTP, the end product of this salvage pathway, moderately increased the rate by 50% at 0.4 microM ara-C or by 26% at 40 microM ara-C. At 40 microM ara-C, deleting UDP from the mix increased the rate more than deleting dCTP. dCTP was less inhibitory against 1 mM UTP (50% inhibitory concentration, 26 microM) than against 4 mM ATP (50% inhibitory concentration, 2.2 microM). In kinetic assays with 4 mM ATP and variable ara-C, UDP was a potent uncompetitive inhibitor with a Ki of 4 microM; the Ki for ADP was 1000-fold higher. Direct fit of kinetic data to the Michaelis equation yielded a Km for ara-C of 49 microM with 4 mM ATP as the phosphate donor; however, there was evidence of negative cooperativity with a Hill coefficient of 0.7. High ara-C Km values were also obtained with GTP and CTP, but with no evidence of cooperativity. With 1 mM UTP, the Km was 1.5 microM with moderate substrate inhibition; thus the kinetic data with UTP were similar to those for ara-C phosphorylation by intact cells. UDP was less potent versus UTP than versus ATP. It lowered the Vmax and enhanced the ara-C substrate inhibition without altering the Km. When 1 mM UTP and 4 mM ATP were mixed, the kinetic pattern was similar to that for UTP alone. The Km for UTP with [3H]dCyd as the phosphate acceptor of 0.8 microM was 25-fold lower than the Km for ATP of 20 microM.(ABSTRACT TRUNCATED AT 400 WORDS)

Blast Crisis↗
PubMed1991

The ubiquity of contraction enhanced H reflexes: normative data and use in the diagnosis of radiculopathies.

Surface recorded contraction enhanced H reflexes to single stimuli were obtained from muscles supplied by the C5, 6, 7, 8, L3, 4, 5, S1 and 2 nerve roots. For each of 12 such muscles, these reflexes were recorded from 25 control subjects as well as standard unenhanced H reflexes from the gastrocnemius muscles. Amplitude and latency criteria for normality were determined. Thirty-two patients with typical histories and physical findings of radiculopathy secondary to degenerative disease of the spine (C6 nerve root - 9 patients, C7 - 10, C8 - 4, L4 - 4, L5 - 4, S1 - 1) were studied with these H reflexes and the needle electrode. Thirty patients had H reflex abnormalities appropriate to the signs and symptoms. Eighteen had absent H reflexes and 16 had abnormalities to amplitude criteria. None were abnormal by latency criteria. Twelve patients had abnormal needle examinations and all also had abnormal H reflexes. These results indicate that contraction enhanced H reflexes are ubiquitous, readily obtainable and sensitive to the presence of clinically clear-cut radiculopathies.

Adolescent↗
PubMed1991

Antimetabolites.

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Antimetabolites, Antineoplastic↗
PubMed1991

Chemorepulsion of trichomonads by products of neutrophil oxidative metabolism.

To determine whether secreted neutrophil products affect the migration of motile microorganisms such as Trichomonas vaginalis, stimulated human neutrophils and cell-free oxygen metabolites were used as stimuli in a multiwell filter chemotaxis assay using tritiated T. vaginalis. When stimulated neutrophils were present on the opposite side of the filter, migration of T. vaginalis into the filter was significantly diminished, and this reduction varied with the dose of neutrophil stimulus. The reduction of movement was abrogated by the addition of catalase and superoxide dismutase to scavenge oxygen metabolites. Studies with cell-free hydrogen peroxide or hypochlorite preparations indicated that the reduction in trichomonal trapping in the filter was due to chemorepulsion and not to a nonspecific decrease in motility or adherence. These findings suggest that active migration away from neutrophil products might be a means by which trichomonads avoid the microbicidal functions of host phagocytes.

Animals↗
PubMed1991

Crossover comparison of maximum dose glyburide and glipizide.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) failing to respond to therapy with a maximum dose of glyburide (GB) or glipizide (GZ) are often given a trial of the alternate second-generation sulfonylurea (SGS) before insulin therapy is considered. The efficacy of this therapeutic maneuver has not been thoroughly tested. We studied 26 subjects with fasting serum glucose (FSG) levels greater than 8.3 mmol/L (150 mg/dL) despite maximum doses of either GB (20 mg/day) or GZ (40 mg/day). Group 1 consisted of 16 subjects taking GB (mean FSG = 12.7 mmol/L [228 mg/dL]) and group 2 included 10 subjects taking GZ (mean FSG = 13.0 mmol/L [234 mg/dL]). Subjects continued taking their original SGS for 8 weeks then switched to a maximum dose of the alternate agent for an additional 8 weeks. Values for FSG, hemoglobin A1c, and lipids were recorded before the study and after 8 weeks on each SGS trial. No significant changes were noted for any variable in either group. When maximum dose GB therapy was compared to maximum dose GZ therapy in the combined study group (n = 26), no advantage was noted for either agent. We conclude that metabolic control in NIDDM patients failing to respond to therapy with maximum dose GB or GZ is not improved by switching to the alternate SGS.

Blood Glucose↗
PubMed1991

Leukapheresis induced changes in cell cycle distribution and nucleoside transporters in patients with untreated acute myeloid leukemia.

Bone marrow leukemia cells from eight adults with untreated acute myeloid leukemia (AML) were evaluated before and after three daily leukaphereses to determine if mechanical cytoreduction can modulate the cell cycle distribution. The percentage of cells in S-phase and the proliferative fraction (PF = %S + %G2M) were determined by flow cytometry after dual labeling with bromodeoxyuridine and propidium iodide. Prior to pheresis the median %S and PF were 5.4 and 15.4%, respectively. The median change in %S was +2.5% (range -5.5 to +18.8) with increases greater than or equal to 3.7% in 4/8 patients. The median change in PF was +6.1% (range -13.8 to +25.3) with an increase of greater than or equal to 3.6% in 6/8 patients. The median absolute changes of 2.5 and 6.1% represent increases of 47% for %S and 40% for PF compared to the day 1 (pre-pheresis) median values. As the number of nucleoside transporters in the cell membrane [nitrobenzylmercaptopurine riboside (NBMPR) binding sites] has been related to the percentage of cells in S-phase and to cytosine arabinoside (ara-C) cellular pharmacology, these were also measured before and after leukapheresis. Changes in the number of NBMPR binding sites varied widely with a median increase of 365 sites per cell (range -26,061 to +10,396). The change in NBMPR sites was significantly and positively correlated with changes in %S (r = 0.829, p = 0.042). These data suggest that mechanical cytoreduction by leukapheresis can increase the fraction of leukemia cells in S-phase and the PF in some patients with AML. The increase in %S is accompanied by an increase in NBMPR binding sites per cell. These changes in leukemia cell characteristics would be expected to result in an increase in efficacy of ara-C or other S-phase specific agents.

Binding Sites↗
PubMed1991

Effect of dose on the pharmacokinetic and pharmacodynamic effects of cytarabine.

In summary, there are compelling laboratory and clinical data indicating that higher doses of ara-C than are currently used in SDaC protocols constitute optimal therapy. The cellular pharmacokinetics of ara-C are optimized at extracellular drug concentrations in the 10 to 15 mumol/L range. At these concentrations, transport rates are no longer rate-limiting, and ara-C phosphorylation capacity is saturated. The prime determinants of ara-C effect then shift to multiple intracellular events including anabolism to nucleotides, catabolism via deamination by Cyd-dCyd deaminase and dCMP deaminase, half-life of ara-CTP, the extent of incorporation into DNA, and the half-life of ara-CMP residues in DNA. It is postulated that at these high doses an additional effect of ara-C occurs on the cell membrane through affects on membrane phospholipid synthesis. This effect may contribute to the brisk cell lysis associated with HiDaC treatment. When administered as repetitive doses of 3 g/m2 over a 1- to 3-hour period, systemic deamination of ara-C gives rise to high plasma concentrations of ara-U. This metabolite has a long plasma half-life and, at least in the mouse, is concentrated in the liver and kidneys. High concentrations in these organs retard the further catabolism of ara-C and thus increase the systemic AUC providing a longer exposure period to the drug. A similar mechanism may obtain in patients treated with HiDaC. The observed decreased clearance of ara-C when administered in gram versus milligram doses and the long-terminal gamma-phase in plasma clearance of the drug associated with HiDaC usage quite probably reflects this effect of ara-U in patients. Additionally, by some as yet unknown mechanism, high concentrations of ara-U cause accumulation of leukemia cells in S-phase, the phase of the cell cycle wherein ara-C is maximally effective. This effect of ara-U may add to the cytokinetic effects initiated by rapid cytoreduction, which summate in the observed enhancement of the proliferative fraction of residual leukemia cells on day 8. The effect of a second course of therapy at this time is thereby enhanced. These dose-related and metabolite-drug interactions that occur when ara-C is given at high doses constitute a means for "self-potentiation" and may thus contribute to its overall therapeutic efficacy.

Animals↗
PubMed1991

Plasma glucagon concentration in cirrhosis is related to liver function but not to portal-systemic shunting, systemic vascular resistance, or urinary sodium excretion.

We tested the hypothesis that increased plasma glucagon concentration resulting from portal-systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis. Twenty-seven studies were performed in patients with alcoholic liver disease, 11 of whom had ascites. Liver function was quantitated as the elimination rate of antipyrine, caffeine, and stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and intravenously (24-13C). Portal-systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Cardiac output was measured by using Doppler echocardiography. Plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but was unrelated to urinary sodium excretion, heart rate, mean arterial pressure, cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18, and 0.22, respectively). Plasma glucagon concentration correlated with the half-lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r = 0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14). Increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance. However, increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention.

Glucagon↗
PubMed1991

S-phase fraction is not correlated with nucleoside transport in acute myeloid leukemia cells.

The expression of nucleoside carrier [nitrobenzylmercaptopurine riboside (NBMPR) binding] sites has been related to proliferative fraction in cell lines and in patient myeloid and lymphoid blasts. This correlation was examined in patients with untreated acute myeloid leukemia (AML). Bone marrow blasts were incubated with 8 microM bromodeoxyuridine (BrdUrd) and dual-labeled with propidium iodide and anti-BrdUrd monoclonal antibody. Flow cytometry was used to determine the percentage of cells with detectable BrdUrd incorporation into DNA (%S) and the proliferative fraction (PF = %S+%G2M) in 63 patients; NBMPR binding sites were quantitated in samples from 29 patients. The median %S was 6.1% (range 0.6-25.9%) and the median PF was 13.0% (range 2.4-36.1%), with a median of 7243 NBMPR binding sites per cell (range 1716-27247). In contrast to a previous report which included bone marrow and peripheral blood blasts, %S in marrow blasts did not correlate with NBMPR binding sites per cell (r = 0.005, p = 0.979). Similarly, PF did not correlate with NBMPR sites per cell (r = 0.190, p = 0.325). This lack of correlation between leukemia cell proliferation and NBMPR binding sites per cell suggests that DNA synthesis in AML blasts depends primarily on de novo nucleoside synthesis rather than the usage of salvage pathways.

Adult↗