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Biomedical subjects

L Clark

Publications and source records attributed to L Clark.

At least 37 records · Page 2Linked to original sources
PubMed1997

Risperidone dose and blood level variability: accumulation effects and interindividual and intraindividual variability in the nonresponder patient in the clinical practice setting.

Risperidone blood levels were measured every 2 weeks after initiation of therapy in 24 refractory chronic schizophrenic patients referred to a locked, skilled nursing facility for long-term treatment. Blood levels were assessed on 285 occasions over a 1- to 16-month treatment program. Drug plasma level increases peaked by 2 months for risperidone at 334% and by 6 months for 9-hydroxy-risperidone at 104% over the baseline levels. Total blood levels (risperidone plus 9-hydroxy-risperidone) peaked at 111% increase at 6 months and then declined 8% per month to 12 months, stabilizing at a value 31% higher than the initial value. Significant dose to blood level interindividual variation was noted. Considerable blood level variation was evident in single blood level sample determinations. The results suggest the value of risperidone blood levels, consideration of reduction of initial recommended starting dosages, and a need to optimize risperidone dosage approaches individually to patients.

Adult↗
PubMed1997

The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps.

Colorectal cancers continue as the second most common cause of death from cancer in the United States. Only a few prospective, randomized clinical trials have been performed to evaluate the potential preventive effects of dietary fiber or calcium in patients with an increased risk for the development or recurrence of colorectal cancer. We designed and conducted a double-blinded, placebo-controlled randomized trial involving supplementation of fiber and calcium intake and measurements of [3H]thymidine labeling index (LI) percentages in rectal mucosal biopsies obtained from patients with resected colorectal adenomas to examine the potential mechanisms by which dietary interventions might reduce colorectal cancer risk. We performed a randomized, double-blinded, Phase II study, using a factorial design to measure the effects of supplemental dietary wheat bran fiber (2.0 or 13.5 g/day) and calcium carbonate (250 or 1500 mg/day elemental calcium) supplementation on [3H]thymidine LI percentages in rectal mucosal crypts and 24-h in vitro outgrowth cultures. Measurements were made at baseline randomization (i.e., after a 3-month placebo run-in period using 2.0 g of wheat bran fiber plus 250 mg of calcium carbonate) and after 3 and 9 months on treatment in 100 randomized participants who had a history of colon adenoma resection. Neither the wheat bran fiber nor the calcium carbonate supplements significantly reduced [3H]thymidine LI percentages in rectal mucosal crypts (total or compartmental analysis) or 24-h in vitro outgrowth cultures at either 3 or 9 months of daily supplementation in the 93 evaluable participants. We conclude that 9 months of high-dose wheat bran fiber and calcium carbonate supplementation in study participants with a history of recently resected colorectal adenomas does not have a significant effect on cellular proliferation rates in rectal mucosal biopsies, comparing 3- and 9-month results to baseline results. Ultimately, there is great need for the evaluation of these two different nutrient interventions in the setting of Phase III studies wherein adenomatous polyp recurrence, rather than a rectal mucosal biomarker, serves as the primary end point.

Adenomatous Polyps↗
PubMed1996

Corneal infection with herpes simplex virus type 1 leads to autoimmune responses in rats.

Lewis rats were infected by corneal scarification with HSV type 1 type strain F virus. The animals showed symptoms of infection and inflammatory infiltrates of the eye but little mortality. After one month, immune responses to viral and autoantigens were examined. It was shown that lymph node cells proliferated to the myelin antigen, proteolipoprotein, and the HSV antigen, glycoprotein D, but showed depressed responses to antigens of the eye, specifically corneal and retinal antigens. Splenic cells showed small but significant responses to antigens of the eye, indicating immune deviation similar to that previously demonstrated in ACAID, where antigen had been injected into the anterior chamber of the eye.

Animals↗
PubMed1996

Randomized, double-blinded, placebo-controlled study of effect of wheat bran fiber and calcium on fecal bile acids in patients with resected adenomatous colon polyps.

BACKGROUND: Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. PURPOSE: We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. METHODS: In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. RESULTS: All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. CONCLUSIONS: High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. IMPLICATION: Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.

Adenomatous Polyposis Coli↗
PubMed1996

Postoperative use of pediatric pain scales: children's self-report versus nurse assessment of pain intensity and affect.

The purpose was to examine nurses' use of pediatric pain scales and to compare their estimate of the child's pain intensity and affect with the child's self-report. The Analog Chromatic Continuous Scale (ACCS) was used for pain intensity and the McGrath Affective Faces Scale (MAFS) for pain affect. Self-report of pain was obtained from 124 hospitalized postoperative children aged 5 to 17 years and compared with estimates of 44 pediatric nurses randomly assigned to either an experimental or control group. Experimental nurses used the ACCS and MAFS to obtain pain ratings whereas control nurses made estimates according to their customary method of assessment. Findings revealed that only 36% of the nurses had at any time used a pediatric pain scale. Correlations between the experimental nurses' ratings and the child's self-report were significantly higher than the control nurses' estimates and the child's self-report. The correlation between the child's self-report of pain intensity on the ACCS and of affect on the MAFS was r = .612, suggesting that nurses' use of both an intensity and affect pediatric pain scale would more accurately reflect the child's pain experience.

Affect↗
PubMed1996

Learning from patients: a discharge planning improvement project.

BACKGROUND: In 1991 Beth Israel Hospital (Boston) joined nine other hospitals in using the Picker/Commonwealth survey instrument to tap patients perceptions of their hospitalization experience. Beth Israel focused on one of the nine dimensions of the instrument-continuity and transition (discharge planning). FOUR WORK TEAMS: In 1992 four multidisciplinary work teams were formed-for cardiac surgical patients, stroke patients, patients on a medical unit, and patients on a medical and surgical unit. Each team conducted a patient/family discussion group, during which recently discharged patients and their families were asked about their preparation for discharge and asked for input on how to improve the process. INTERVENTIONS: Each work team developed interventions on the basis of information specific to their patients. The cardiac work team, for example, developed interdisciplinary practice guidelines for patient care management for the entire postoperative period; the guidelines include a patient education component on what patients and families can expect during hospitalization. OUTCOMES: Clinicians practice differently, inviting more patient feedback and other involvement in care, as a results of their involvement in the project. On the first annual patient survey, administered in 1994, only 6% of 1,179 randomly selected patients (versus 20% of the 100 patients first surveyed in 1993) indicated that they did not receive the information they needed to help themselves recover. CURRENT PROGRESS AND FUTURE DIRECTIONS: A standardized teaching packet containing material developed during the discharge planning improvement project is now distributed. In May 1995 the nursing department launched a patient and family learning center to better meet the health education needs of patients.

Aftercare↗
PubMed1996

Transfer of gametes into the fallopian tubes--is choice of side important?

The aim of this study was to define pregnancy rates for gamete intra-Fallopian transfer (GIFT) with respect to the ovary from which most oocytes were collected (i.e. a gross index of ovarian stimulation) and the Fallopian tube (ipsilateral or contralateral) into which gametes were replaced. The only inclusion criterion was the ability to transfer gametes into the Fallopian tubes at GIFT. No other factors that could influence outcome were considered. In this retrospective review of the clinic's database, no relationship was found between pregnancy rate and placement of gametes into the Fallopian tube coincident with the ovary from which most oocytes were collected. Thus when performing unilateral tubal transfer at GIFT gametes may be returned to the side most convenient to the operating surgeon without fear of compromising pregnancy potential.

Adult↗
PubMed1996

Changes in health after elective percutaneous coronary revascularization. A comparison of generic and specific measures.

OBJECTIVES: This study determines changes in health-related quality of life after elective percutaneous transluminal coronary angioplasty and compares generic and specific measures. METHODS: Changes in health-related quality of life were measured in consecutive, symptomatic patients undergoing elective percutaneous coronary revascularization using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Specific Activity Scale (SAS), and the Canadian Cardiovascular Society Classification (CCSC). The patients were interviewed as outpatients before admission and at least 6 months later. RESULTS: There were significant changes in the following SF-36 measures: physical functioning (postscore minus prescore = 19.1 +/- 24.1), role limitations due to physical-health problems (40.4 +/- 47.2), bodily pain (19.9 +/- 29.3), vitality (12.9 +/- 25.1), social functioning (20.0 +/- 33.1), role limitations due to emotional-health problems (26.7 +/- 49.0), and general mental health (7.1 +/- 21.2). General health perceptions did not change significantly. Internal-consistency reliability coefficients for these measures ranged from 0.73 to 0.91. There also was significant improvement in the CCSC class, but the SAS class did not change significantly. Overall, the SF-36 role-physical scale was the most responsive to changes after elective percutaneous coronary revascularization, followed by the CCSC and the SF-36 physical functioning scale. CONCLUSIONS: Although this study cannot determine the causal role of elective percutaneous coronary revascularization in these changes, it provides support for the usefulness of these measures in future evaluations of this intervention.

Activities of Daily Living↗
PubMed1996

Coronary restenosis.

Return of angina within 6 months of a catheter-based treatment of coronary artery disease usually reflects restenosis due to an overly aggressive local healing response to the procedure-related arterial injury. The restenotic lesion should be treated aggressively. Patients with preexisting diabetes mellitus, renal failure requiring hemodialysis, and left anterior descending artery lesions should be considered to be at exceedingly high risk for clinically significant restenosis. Exercise testing is indicated for all patients who experience a return of their angina within 6 months of an interventional procedure. Nurse practitioners in the primary care setting may be the first clinicians to hear of the return of angina. Patients should always be reassured that repeat intervention is almost always possible and is generally effective in providing long-term relief. New devices (in particular the Palmaz-Schatz stent) may help reduce the likelihood of restenosis, to the extent that they provide a large acute post-treatment lumen diameter that is more tolerant of intimal hyperplasia without producing significant narrowing. Until adjunctive drug therapy is found that effectively reduces the local tissue response to interventional therapy, all clinicians involved in caring for patients following such procedures will need to be vigilant and knowledgeable about recognizing and treating restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1996

Can caretakers of children with IDDM accurately measure small insulin doses and dose changes?

OBJECTIVE: To determine if caretakers of young children with IDDM could consistently reproduce small incremental measurements of insulin (U100). RESEARCH DESIGN AND METHODS: Fifteen caretakers of children with IDDM were asked to deliver repeated small doses of insulin, including doses separated by only 0.25 U of insulin. A sensitive gravimetric technique was used to determine the error in measurement of these low doses of insulin. Statistical analysis was used to evaluate accuracy and internal consistency of each caretaker at each dose. RESULTS: The means +/- SD at each dose level were as follows: 2.75 +/- 0.13 U at 2.5 U, 3.19 +/- 0.13 U at 3.0 U, 3.55 +/- 0.13 U at 3.25 U, and 3.70 +/- 0.11 U at 3.5 U. All doses were biased toward overadministration. There was as statistically significant difference in the dose delivered when the target doses were varied by only 0.25 U. The average differences and standard errors between 2.5 U and 3.0 U, 3.0 U and 3.25 U, and 3.25 U and 3.5 U were 0.44 +/- 0.20 U, 0.36 +/- 0.018 U, and 0.15 +/- 0.017 U, respectively. CONCLUSIONS: Participants were not accurate in measuring small insulin doses, consistently overdrawing insulin by an average of 0.22 U. Caretakers are reasonably internally consistent with a given dose, since participants were able to measure statistically significant differences in 0.25 U dose changes. The error in insulin measurement does not vary with the intended dose level. Caretakers in the same family deliver insulin doses as variable from each other as they are from the population as a whole; however, when two or more individuals are responsible for one insulin dose in a child with IDDM, they have a combined variability that is approximately 40% greater than a single individual's variability.

Caregivers↗
PubMed1995

Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis.

CD40 activation is critical for B-cell function, leading to activation and expression of cell surface markers, proliferation, immunoglobulin class switching and inhibition of programmed cell death (PCD). Germinal center B-cells, for example, can be prevented from undergoing PCD by CD40 activation. The mechanism by which PCD is inhibited has been an enigma. A potential role for A20, a novel zinc finger protein, in inhibiting B-cell apoptosis was suggested by our previous finding that it is induced by the Epstein-Barr virus LMP-1 gene product, a potent cell death inhibitor. We now show that CD40 activation induces A20 and that expression of A20 renders B-cell lines resistant to PCD. Additionally, we show that CD40 activation of A20 expression is mediated by inducible binding of NF-kappa B complexes to the A20 promoter and provide evidence for a critical role for Thr234 (in the CD40 cytoplasmic domain) in activating NF-kappa B.

Antigens, CD↗
PubMed1995

Haloperidol dose and blood level variability: toxicity and interindividual and intraindividual variability in the nonresponder patient in the clinical practice setting.

Haloperidol levels in blood were measured monthly in 43 refractory chronic schizophrenic patients referred to a locked skilled nursing facility for long-term treatment. Gross toxic side effects (seizures, catatonia, confusion) and Neuroleptic Induced Deficit Syndrome in conjunction with blood levels over 30 ng/ml were identified in 13 of our 43 patients. Blood level reductions contributed to a reduction of side effects and clinical improvement and led to the expedited discharge of 6 of these 13 patients of the toxic subgroup. Considerable blood level variation was evident in single samples, and four levels appeared necessary to develop confidence for accuracy. Significant dose to blood level interindividual variability was identified, thereby bringing into question fixed-dose approaches to patients. The results strongly suggest the utility of haloperidol blood levels in the clinical setting.

Administration, Oral↗
PubMed1995

Phase I clinical trial of serotherapy in patients with acute myeloid leukemia with an immunoglobulin M monoclonal antibody to CD15.

Sixteen patients with acute myeloid leukemia (AML) were treated with a continuous i.v. infusion of mAb PM-81, an IgM mAb directed against the cellular differentiation antigen CD15, which is expressed on leukemia cells of >95% of patients with AML. MAb PM-81, also referred to as MDX-11, is capable of activating human and rabbit complement and lysing CD15-positive AML cells. In this Phase I study, patients were treated with 0.5, 1.0, or 1.5 mg/kg MDX-11 delivered over a 24-h period followed by conventional chemotherapy. Transient decreases in circulating blast cells postinfusion (prior to chemotherapy) were observed at all doses. We were able to show MDX-11 binding to bone marrow blasts in those patients who achieved stable serum levels of MDX-11. Serum MDX-11 was detectable at the 1. 0- and 1.5-mg/kg doses. Doses of 0.5 and 1.0 mg/kg were generally well tolerated, with no toxicities greater than grade II (Eastern Cooperative Oncology Group) reported. However, two of five patients receiving the 1.5-mg/kg dose experienced grade IV toxicities that resolved with treatment (one of these patients completed the infusion). Common toxicities reported included fever, chills, and hypotension. Only one patient developed human antimouse antibodies at 4 weeks posttreatment. This study determined that 1.0 mg/kg is a biologically effective dose that can be administered safely with little toxicity. Based on these results, we are pursuing a Phase I/II study of MDX-11 infusion following chemotherapy for patients with relapsed AML.

Acute Disease↗
PubMed1994

Neuritogenic Lewis rat T cells use Tcrb chains that include a new Tcrb-V8 family member.

The P2 protein obtained from Schwann cells induces a population of T cells which, upon adoptive transfer, causes the disease experimental allergic neuritis (EAN), an animal model for Guillain-Barre syndrome. In this report, a truncated peptide, FR22, derived from a previously reported neuritogenic T-cell determinant, was used to generate from Lewis rats T cells that were shown to cause EAN. Since our previous studies showed that Tcrb-V8 was used by a majority of T-cell hybridomas specific for the neuritogenic peptide P26, which contains the FR22 sequence, we sequenced the Tcrb-V8+ mRNA from FR22-specific T-cell lines, and compared the sequences obtained with those obtained from similarly generated myelin basic protein (MBP) 68-88-specific Lewis rat T-cell lines. We found that in the EAN lines, several members of the Tcrb-V8 family were used, including a new family member, Tcrb-V8E. This was more diverse than the MBP-68-88-specific response in which only a single Tcrb-V8 family member was used. Also, in the EAN lines, the beta chain sequences did not show the same conserved junctional regions seen in the MBP lines. Thus, T-cell receptor beta chain usage in the response to this dominant neuritogenic peptide appears to be less restricted than the response to the dominant encephalitogenic determinant of MBP both in V region usage and in CDR3 usage.

Amino Acid Sequence↗
PubMed1994

Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts.

Epidermal growth factor receptor (EGFR) overexpression has been associated frequently with squamous cell carcinomas (SCC) and SCC cell lines. In most cases the level of EGFR on the tumours from which the cell lines were derived has not been determined, nor have EGFR levels been determined for xenograft tumours from the cell lines. In this study we determined EGFR expression on a new series of head and neck SCC (SCCHN)-derived cell lines, which were obtained from tumours representing a spectrum of malignant progression, and two cell strains derived from erythroplakia premalignant lesions. The level of EGFR on cell lines was determined by [125I]EGF competitive binding assays. EGFR levels on some of the original tumours and xenografts of the cell lines were determined on cryosections by a competitive binding assay based on [125I]EGFR1, an EGFR-specific monoclonal antibody. EGFR expression on the tumour cryosections was compared with expression on cryosections of skin and buccal mucosa. Eight of the ten tumour cell lines had elevated EGFR. Two of the tumour-derived cell lines and the two erythroplakia-derived cell strains expressed EGFR at levels similar to that detected on normal keratinocytes in tissue culture. Only two of the tumours overexpressed EGFR when compared with normal tissue. The other tumours had levels similar to that detected on the basal layers of skin or buccal mucosa. The xenografts expressed EGFR, as did the original tumours, even though they were derived from cell lines that displayed significant overexpression of EGFR. This study suggests that most tumours have a latent potential to overexpress EGFR which is realised in tissue culture.

Animals↗
PubMed1993

Induction of peripheral tolerance with peptide-specific anergy in experimental autoimmune neuritis.

Neuritogenic T cells specific for SP-26, a synthetic peptide (residue 53-78) of myelin P2 protein that causes experimental autoimmune neuritis (EAN), use the same T cell receptor (TCR) V gene family (V beta 8) that can induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Tolerance to autoregulatory T cells may be induced in rats by intravenous (iv) administration of antigen-coupled splenocytes; however, the mechanisms that lead to altered immune reactivity are not well understood. Here we demonstrate that SP-26, when coupled to syngeneic spleen cells and administered iv, either before or after disease induction, markedly inhibited development and expression of clinical signs and histological changes of EAN. The induction of tolerance by this method was peptide-specific and MHC-restricted. We showed previously that T cells involved in EAN utilize the T cell antigen receptor V beta 8, whereas less than 5% of normal rat peripheral T cells express V beta 8. We have examined T lymphocytes from tolerized rats to determine the presence or absence of V beta 8(+)-bearing cells in order to determine the mechanism of tolerance. V beta 8 cells were undetectable by Northern blot analysis in the lymph nodes of unimmunized animals but easily detected in SP-26-primed and tolerized rats. In addition, spleen cells isolated from tolerized animals were anergic and failed to proliferate in response to SP-26, but retained responsiveness to IL-2 and Con A stimulation. Thus, the peptide-specific unresponsiveness that can be induced in rats with EAN, a T-cell-mediated process that is MHC-restricted and utilizes the T cell receptor V beta 8, occurs while V beta 8 transcripts remain readily detectable in spleen and lymph node cells. The detection of V beta 8-bearing T cells requires the development of antibodies specific for this rat surface protein.

Amino Acid Sequence↗