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Biomedical subjects

J H Carter

Publications and source records attributed to J H Carter.

At least 37 records · Page 2Linked to original sources
PubMed1996

Apparent inhibition of apoptosis by polyamines and aminothiols in DNA fragmentation assays is artifactual.

We report that, in commonly used DNA fragmentation assays, polyamines and the radioprotective aminothiol WR1065 artifactually depress the degree of spontaneous or induced cellular apoptosis in two distinct ways. Firstly, in assays utilizing Hoechst 33258 dye to measure apoptotic DNA, both amines quench the fluorescence of low affinity dye/DNA binding resulting in preferential underestimation of DNA in the apoptotic DNA fraction and a resultant underestimation of the extent of DNA fragmentation. Secondly, these amines can cause aggregation and condensation of apoptotic DNA, causing anomalous sedimentation under conditions universally employed to separate apoptotic from intact DNA in cell lysates. This anomalous sedimentation of apoptotic DNA leads to underestimation of fragmentation in fluorescence assays as well as in agarose gel assays. We demonstrate that manipulation of the ionic strength of the lysis buffer or lowering the dye concentration ameliorates the effects of dye quenching in the Hoechst assay. Alternatively, this effect is alleviated by substituting DAPI for Hoechst in this assay. Inclusion of a polyanion to the lysis buffer antagonizes the condensation and anomalous sedimentation of apoptotic DNA observed regardless of which dye is used in the assay. These studies call into question the validity of previously reported studies suggesting that polyamines and the radioprotective aminothiol, WR1065, inherently suppress the apoptotic process and underline the need to consider alternative endpoints of apoptosis such as morphology in order to assess effects on cellular apoptosis of exogenously added agents, particularly di- or polycations.

Journal Article↗
PubMed1996

Alcoholism and African-American women: a medical sociocultural perspective.

Today's research explaining women's usage of alcohol is inaccurate. Researchers have failed to include the powerful variable of race. African-American females are increasing their use of alcohol, yet the literature fails to tell why. To understand alcoholism among African-American women, it is necessary to conceive their culture, values, and role in society. This article highlights the biopsychosocial issues impacting female African Americans, and the need for unbiased research and treatment. Women who have the dual status of addiction and are members of a racial minority face a special range of stressors. Therefore, clinicians who serve them must possess more than generalized clinical skills.

Black or African American↗
PubMed1995

In vivo administration of dichloroacetic acid suppresses spontaneous apoptosis in murine hepatocytes.

Spontaneous apoptosis in hepatocytes of male B6C3F1 mice that received dichloroacetic acid (DCA) in their drinking water for 5-30 days (28-58 days of life) was examined as part of ongoing studies to determine the molecular basis of the hepatocarcinogenicity of this nongenotoxic water chlorination by-product. DCA at 0.5 and 5.0 g/liter, significantly reduced apoptosis relative to untreated controls in a dose-dependent fashion. Regression analysis indicated that apoptosis declined over the 30-day period in the livers of control, age-paired animals receiving no drug. Animals receiving low-dose DCA exhibited a similar, although quantitatively depressed, trend line, whereas animals receiving high-dose DCA showed maximal depression of apoptosis at 5 days, which was sustained throughout the course of the 30-day period. These studies suggest that DCA has the ability to down-regulate apoptosis in murine liver. When taken together with previous data demonstrating DCA-dependent decrease in labeling index in these same livers, these data further support the hypothesis that the carcinogenic mechanism of DCA may involve suppression of the ability of the liver to remove initiated cells by apoptosis rather than by induction of selective proliferation of initiated cells.

Animals↗
PubMed1995

Immunohistochemical analysis of dichloroacetic acid (DCA)-induced hepatocarcinogenesis in male Fischer (F344) rats.

We examined the incidence of proliferative lesions, hyperplastic nodules and altered hepatic foci, in male F344 rat liver, to determine their preneoplastic potential during dichloroacetic acid (DCA)-induced hepatocarcinogenesis. Immunohistochemical and image analysis methods were used to detect the expression of 6 histochemical markers of neoplastic cells; p21 ras, p39 c-jun, p55 c-fos, aldehyde dehydrogenase (ALDH), glutathione s-transferase (GST-p), and alpha fetoprotein (AFP) during DCA-induced hepatocarcinogenesis. Our results were consistent with our previous data and suggested that the hyperplastic nodules, rather than altered hepatic foci, is a putative preneoplastic lesion during DCA-induced hepatocarcinogenesis in the male F344 rat.

Aldehyde Dehydrogenase↗
PubMed1995

Mood and anxiety fluctuation in Parkinson's disease associated with levodopa infusion: preliminary findings.

Pilot data on mood and anxiety changes in 15 Parkinson's disease patients with motor fluctuations are described based on ratings every 30 min for 5 h bracketing a 2-h constant-rate levodopa infusion. Robust mood and anxiety effects slightly preceded but temporally paralleled fluctuations in motor tapping scores. Research nurse ratings blind to patient ratings corroborated the changes. The magnitude of changes in mood and anxiety scores did not correlate with the magnitude of changes in tapping scores. The findings of this uncontrolled study suggest mood and anxiety fluctuations may be a common and potentially important component of levodopa-induced fluctuations.

Affect↗
PubMed1995

Race/ethnicity and other sociocultural influences on alcoholism treatment for women.

This chapter discusses sociocultural influences on the availability, access, diagnosis, and treatment of alcoholism for women, particularly those in minority groups. Race/ethnicity and other sociocultural influences are presented in terms of the societal context and the counselor-client relationship. The latest data on heavy drinking, alcohol-induced mortality, and alcoholism treatment utilization are presented on African-American, Hispanic, and white women. Data also are presented on the ability to pay for treatment through insurance or earnings. Information on Native Americans and Asian/Pacific Islanders is included whenever possible.

Alcoholism↗
PubMed1995

Biochemical, pathologic and morphometric alterations induced in male B6C3F1 mouse liver by short-term exposure to dichloroacetic acid.

Dichloroacetic acid (DCA) is a complete hepatocarcinogen and tumor promoter in the male B6C3F1 mouse. Published reports indicate that the compound is non-genotoxic. This study examines possible non-genotoxic (epigenetic) mechanisms by which DCA elicits its carcinogenic response. Correlative biochemical, pathologic and morphometric techniques are used to characterize and quantify the acute, short-term response of hepatocytes in the male B6C3F1 mouse to drinking water containing DCA. Cellularity, [3H]thymidine incorporation, DNA concentration, nuclear size, and binuclearity are evaluated in terms of level of exposure (0, 0.5 and 5 g/l) and length of exposure to DCA. The dose-related alterations in hepatocytes of animals exposed to DCA for 30 days or less indicate that short-term exposure to DCA results in inhibition of mitoses, alterations in cellular metabolism and a shift in ploidy class. Thus, DCA carcinogenesis may involve cellular adaptations, development of drug resistance and selection of phenotypically altered cells with a growth advantage.

Analysis of Variance↗
PubMed1995

Using the Nursing Interventions Classification to implement Agency for Health Care Policy and Research guidelines.

The mandate for establishing guidelines for assessing effectiveness has been given to the Agency for Health Care Policy and Research (AHCPR). This agency has published 10 practice guidelines for practitioners to use. The present task for practitioners is to establish how effectively use these guidelines. Nurse researchers at the University of Iowa have provided a practical standardized language of nursing interventions that will help nurses demonstrate and communicate current nursing practice. This Nursing Interventions Classification (NIC) will allow nurses to implement the guidelines, demonstrate nursing input for patient care, and make nursing visible to consumers and other health care providers.

Clinical Nursing Research↗
PubMed1995

Dapiprazole's effect upon accommodative recovery: is it due entirely to changes in depth of field?

We conducted a study to evaluate the ability of dapiprazole 0.5% ophthalmic solution to reverse accommodative loss brought about by mydriatic drugs having mild cycloplegic effects. To accomplish this, we analyzed data from several earlier randomized, masked clinical studies. Our composite data include over 90 subjects dilated with tropicamide. Tropicamide was used alone in 1% concentration, as well as in combination with phenylephrine, 2.5% and in the proprietary preparation, Paremyd (Allergan Pharmaceuticals). Accommodative amplitude and pupillary diameter were measured before instilling dilating drops and then again one-half hour later, immediately before instilling either dapiprazole or a placebo. Accommodative amplitude and pupil diameter measurements were then repeated four more times, on both the treatment and control eyes and at 30, 60, 120, and 180 min after instillation of the last drop of dapiprazole or placebo. We found accelerated "accommodative" recovery with dapiprazole for each of the three tropicamide-containing drugs used in our study. This is not surprising because some recovery of accommodative amplitude after dapiprazole's administration is expected. This is because dapiprazole accelerates pupillary recovery and a narrowing of the pupil gives rise to an increase in ocular depth of field. Rate of accommodative recovery with dapiprazole was found not to be significantly different for all three tropicamide-containing preparations tested (p > 0.05). Does dapiprazole produce improvement in amplitude of accommodation beyond that attributable to increased depth of field?(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1995

Long-duration response to levodopa.

We measured the long-duration response to levodopa by changes in tapping rate in 16 patients with Parkinson's disease undergoing 3 to 5 days of levodopa withdrawal. "Off" tapping rates deteriorated 22% over the course of this holiday, the decline beginning 24 hours after levodopa withdrawal. Deterioration was more pronounced in the more affected hand in asymmetrically affected patients. A 2-hour infusion of levodopa after the levodopa holiday did not restore the long-duration response, although it produced a greater short-duration response than before the holiday. These observations indicate that the long-duration response is an important component of the therapeutic benefit of levodopa and is separable from the short-duration response.

Female↗
PubMed1995

Dose-response relationship of levodopa with mood and anxiety in fluctuating Parkinson's disease: a double-blind, placebo-controlled study.

We investigated the effect of levodopa on mood and anxiety in eight Parkinson's disease patients with motor fluctuations. Each patient received 0.0-, 0.5-, and 1.0-mg/kg/hr levodopa infusions in randomly assigned order under double-blind conditions on consecutive days. Mood elevation and anxiety reduction based on half-hourly patient rating and a corresponding increase in tapping speed occurred with active drug infusion but not placebo infusion. The effects were dose related. The higher-dose infusion rate produced more rapid onset, greater magnitude, and longer duration of response. We conclude that mood and anxiety fluctuations related to levodopa dosing are robust pharmacologic, and not placebo, effects.

Affect↗
PubMed1995

Psychosocial/cultural issues in medicine and psychiatry: treating African Americans.

In general, we are raised in a specific cultural environment, and consequently, we have a common sense of identity, shared standards, and religion. The effects of this commonality carries over into health-care situations, including health maintenance and disease prevention. This article provides an overview of how psychosocial/cultural issues have been used with insensitivity to race, culture, and the value orientations of African Americans. It is concluded that the training of all health-care practitioners should include psychosocial/cultural aspects of illnesses.

Black or African American↗
PubMed1994

Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients.

Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. In an open-label trail, we examined the effects of entacapone, a peripheral inhibitor of COMT, administered acutely or for 8 weeks, on the pharmacokinetics and pharmacodynamics of levodopa in 15 parkinsonian subjects with a fluctuating response to levodopa. Acutely and chronically administered entacapone similarly decreased the plasma elimination of orally and intravenously administered levodopa. Absorption of levodopa was minimally affected. During chronic entacapone treatment, daily levodopa dosages were reduced by 27% yet mean plasma levodopa concentrations were increased by 23%. Plasma 3-O-methyldopa concentrations were decreased by 60%. Entacapone increased the duration of action of single doses of levodopa by a mean of 56%. The percent of the day "on" after 8 weeks of entacapone treatment was 77%; it dropped to 44% upon withdrawal of entacapone. We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa.

Aged↗
PubMed1994

Effect of brief levodopa holidays on the short-duration response to levodopa: evidence for tolerance to the antiparkinsonian effects.

To determine whether tolerance to the antiparkinsonian actions of levodopa develops during longterm levodopa therapy, we compared the response to 2-hour levodopa infusions before and after 2- to 4-day levodopa holidays using tapping and walking speeds and tremor/dyskinesia scores as measures of response in 17 parkinsonian patients with a fluctuating response to levodopa. As expected, motor function deteriorated during the levodopa holiday, but the maximum motor tapping and walking speeds and dyskinesia scores produced by the levodopa infusion before the holiday were the same as those produced by the infusion after the holiday. Because the baseline motor function was lower after the holiday, the increment in tapping and walking speeds (ie, the difference between the baseline and the maximum response) was larger with the postholiday infusion (p < 0.01). The postholiday infusion produced a longer response than did the preholiday infusion as measured by tapping score (p = 0.047), walking speed (p = 0.02), and tremor or dyskinesia scores (p = 0.02). The prolongation of the response was greater in patients receiving larger daily doses of levodopa (r = 0.55; p = 0.03). These changes in the duration of response suggest that progressive shortening of the response to levodopa during long-term therapy is partially caused by development of tolerance to levodopa and not just by loss of dopamine storage sites. Tolerance to levodopa should be considered in establishing oral dosing regimens and in developing new strategies for drug delivery.

Adult↗
PubMed1994

Provider and subscriber education: the key to survival.

Any employer's demand for a 20-percent reduction in price is unrealistic and unreasonable. A new mindset is required and can only be achieved through intensive subscriber and physician education about the reality of health care costs.

Capitation Fee↗
PubMed1993

Does tolerance develop to levodopa? Comparison of 2- and 21-H levodopa infusions.

To determine if acute tolerance to levodopa develops, we compared the response to 2- and 21-h levodopa infusions with the rate adjusted during the long infusion to yield the same plasma concentration as at the end of the 2-h infusion. The duration of response after discontinuing the long infusions was briefer than after discontinuing the short infusion, suggesting the development of tolerance. Furthermore, dyskinesia severity was greater during long infusions. We conclude that continuous dopaminergic stimulation with levodopa may not offer optimal control of parkinsonism in patients with response fluctuations.

Aged↗