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Biomedical subjects

P Kinney

Publications and source records attributed to P Kinney.

10 recordsLinked to original sources
PubMed2000

Characterization of clinical tolerance to inhaled zinc oxide in naive subjects and sheet metal workers.

Clinical tolerance to the acute effects of zinc oxide inhalation develops in workers during periods of repeated exposure. The aims of this study were to determine whether clinical tolerance is accompanied by a reduction in the acute pulmonary inflammatory and cytokine responses to zinc oxide exposure and whether tolerance can be demonstrated in sheet metal workers who chronically inhale low levels of zinc oxide. Naive (never-exposed) subjects inhaled 5 mg/m3 zinc oxide on 1 or 3 days and underwent bronchoalveolar lavage 20 hours after the final exposure. Sheet metal workers inhaled zinc oxide on 1 day and control furnace gas on another day. Among naive subjects in whom tolerance was induced, bronchoalveolar lavage fluid percent neutrophils and interleukin-6 (IL-6) levels were significantly decreased compared with subjects who underwent only a single exposure. Sheet metal workers were much less symptomatic, but they still experienced a significant increase in plasma IL-6. The results indicate that clinical tolerance to zinc oxide is accompanied by reduced pulmonary inflammation and that chronically exposed sheet metal workers are not clinically affected by exposure to zinc oxide fume at the Occupational Safety and Health Administration Permissible Exposure Limit. The increase in IL-6 levels observed in the clinically responsive, and to a lesser extent, tolerant, states following zinc oxide inhalation is consistent with the dual role of IL-6 as a pyrogen and anti-inflammatory agent.

Administration, Inhalation↗
PubMed1997

Metal fume fever: characterization of clinical and plasma IL-6 responses in controlled human exposures to zinc oxide fume at and below the threshold limit value.

Results from animal and preliminary human exposure studies have called into question whether the 5 mg/m3 8-hour time-weighted average threshold limit value (TLV) for zinc oxide fume is sufficient to protect workers against metal fume fever. The objectives of this study were to determine the clinical effects of exposures to low concentrations of zinc oxide and to ascertain whether these exposures elevated circulating levels of specific cytokines, which could account for the symptoms of the metal fume fever syndrome. Thirteen resting naive subjects inhaled, on separate days, air and 2.5 and 5 mg/m3 of furnace-generated zinc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had blood drawn before and after each exposure. The mean (+/- SE) maximum rise in oral temperature at 6 to 12 hours after exposure was 1.4 +/- 0.3 degrees F after 5 mg/m3, compared with 0.6 +/- 0.5 degrees F after air exposure (P < 0.05). Mean temperature was also elevated after exposure to 2.5 mg/m3 zinc oxide (1.2 +/- 0.3 degrees F). In a parallel fashion, plasma levels of interleukin 6 (IL-6), a pyrogen, were significantly elevated after exposure to 5 mg/m3 zinc oxide. Mean IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9 (+/- 0.6), 2.8 (+/- 0.7), and 2.9 (+/- 0.6), respectively, on the air day and 1.6 (+/- 0.6), 4.4 (+/- 1.2), and 6.4 (+/- 1.1) on the 5 mg/m3 zinc oxide day. Zinc oxide exposure did not significantly affect plasma levels of tumor necrosis factor. Total symptom scores peaked 9 hours after the 5 mg/m3 zinc oxide exposure. Myalgias, cough, and fatigue were the predominant symptoms reported. Inhalation of zinc oxide for 2 hours at the current TLV of 5 mg/m3 produces fever and symptoms along with elevation in plasma IL-6 levels.

Adult↗
PubMed1997

The effect of a computer assisted instructional program on physical therapy students.

The purpose of this study was to assess the efficacy and efficiency of CAI for students learning evaluation and treatment skills for carpal tunnel syndrome (CTS). Ten volunteer physical therapy students were randomly assigned into either CAI or interactive lecture instructional groups. Each student completed a 36-item pretest on CTS. The CAI group used the Physical Therapy Patient Simulator CAI and the instructional group participated in lecture/discussion to complete the case studies. Following completion of instruction, an identical 36 item posttest was administered to all students. Individual start and finish times for the two groups were recorded by the instructor. A 2 x 2 ANOVA revealed no significant difference in pretest/posttest scores between CAI and interactive lecture. A t-test determined the CAI group completed the case assignment 30 minutes (24% faster than the interactive group. The findings suggest that using a CAI simulation program may be as effective and more efficient than traditional methods of instruction.

Carpal Tunnel Syndrome↗
PubMed1995

Increased DNA-protein crosslinks in lymphocytes of residents living in chromium-contaminated areas.

It has been known for a number of years that chromium-containing mine slags were used as landfill in residential areas of Hudson County, New Jersey. Since one of the major lesions induced in intact cells by chromate is the DNA-Protein crosslink, we have used this lesion as a biomarker of biological effect of chromium (Cr) exposure. We have previously developed a sensitive and easy-to-perform assay to detect DNA-Protein crosslinks, based on the selective K SDS precipitation of DNA associated with protein. We examined the levels of DNA-Protein crosslinks in peripheral blood mononuclear cells of 33 individuals determined to be at risk for chromium exposure by virtue of their residence in Hudson County and their urinary Cr levels. These data were compared to the levels of DNA-Protein crosslinks among 49 controls who resided in noncontaminated areas. A complete clinical examination and urine analysis did not show any Cr-related abnormalities among the exposed population. The mean DNA-Protein crosslink level in the lymphocytes of the exposed group was 1.3 +/- 0.5% (SD), whereas the unexposed group had 0.8 +/- 0.4% (p < 0.001), after adjustment for age, gender, race, smoking, and weight. Further studies in this population are needed to confirm the possible association between the high levels of DNA-Protein crosslink and Cr exposure.

Adult↗
PubMed1994

Application of reliability models to studies of biomarker validation.

We present a model of biomarker validation developed in our laboratory, the results of the validation study, and the impact of the estimation of the variance components on the design of future molecular epidemiologic studies. Four different biomarkers of exposure are illustrated: DNA-protein cross-link (DNA-PC), DNA-amino acid cross link (DNA-AA), metallothionein gene expression (MT), and autoantibodies to oxidized DNA bases (DNAox). The general scheme for the validation experiments involves n subjects measured on k occasions, with j replicate samples analyzed on each occasion. Multiple subjects, occasions, and replicates provide information on intersubject, intrasubject, and analytical measurement variability, respectively. The analysis of variance showed a significant effect of batch variability for DNA-PC and MT gene expression, whereas DNAox showed a significant between-subject variability. Among the amino acids tested, cysteine and methionine showed a significant contribution of both batch and between-subject variability, threonine showed between-subject variability only, and tyrosine showed between-batch and between-subject variability. The total variance estimated through the experiment was used to calculate the minimum sample size required for a future epidemiologic study including the same biomarkers used for the reliability study. Such validation studies can detect the various components of variability of a biomarker and indicate needed improvements of the assay, along with possible use in field studies.

Amino Acids↗
PubMed1993

Lack of significant changes in nutrition-related parameters with tumor necrosis factor treatment of cancer.

Cancer and its therapies frequently produce anorexia and cachexia. In this study, the acute (3 days) and chronic (4 wks) nutrition-related effects of cancer therapy with recombinant human tumor necrosis factor (rHuTNF) were investigated and described. Nutritional status, as measured by body weight and body composition (body fat and lean-to-fat ratio) with use of bioelectrical impedance, did not appear to deteriorate. None of the serum lipids changed significantly, but triglycerides did rise modestly over four weeks of therapy. Glucose and the peptide hormones (insulin, C-peptide, glucagon, and pancreatic polypeptide) thought to affect appetite did not change with rHuTNF therapy. Therefore, although TNF is thought to contribute to wasting in animal models, it had no negative effect on nutritional status in our small sample. The lack of adverse effect noted in this study is possibly due to the low dose level of rHuTNF or to adaptation.

Adult↗
PubMed1990

Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma.

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.

Adult↗
PubMedDate not supplied

Biologic effects of the adoptive transfer of cells depleted of monocytes with L-phenylalanine methyl ester.

Monocytes macrophages have negative regulatory effects on many immunologic responses. Depletion of monocytes from peripheral blood using the lysosomotropic agent, L-phenylalanine methyl ester (PME), has been shown to improve lymphokine activated killer (LAK) cell expansion in vitro. A pilot study of the adoptive transfer of LAK cells expanded with PME was performed in patients with metastatic renal cell carcinoma. Patients received interleukin-2 (IL-2) by continuous infusion for 5 days. Leukopheresis was performed daily for 4 days during the second week. Cells obtained from 8 patients were depleted of monocytes using PME in an one-step procedure; < or = 3% of the remaining cells were monocytes. All cells were expanded for 10 days in air-porous plastic bags with IL-2. Cells expanded 2.7-fold when depleted with PME and 1.7-fold when not depleted (P = 0.02). Expanded cells were administered together with IL-2. Patients received up to 60 x 10(10) PME-depleted cells (mean = 26 x 10(10)) with LAK activity (% lysis) of 60 +/- 12%. Lymphocyte phenotype and cytolytic activity were not modulated by PME-depletion, and clinical toxicities and systemic immunologic effects observed in patients receiving PME-depleted cells were similar to that of 5 patients receiving cells not expanded with PME. Thus, the use of PME to deplete monocytes ex vivo can result in the yield of large number of effectors that retain immunologic activity for potential clinical use. The process is convenient, efficient, and does not add clinical toxicity.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Tracking sources of bacterial contamination in stormwater discharges to Mission Bay, California.

Sources of the indicator bacteria total coliform, fecal coliform, and enterococcus were investigated in stormwater flows discharging to Mission Bay, a heavily used aquatic park in San Diego, California. Stormwater flows were targeted because long-term receiving water monitoring of the bay indicated that wet weather discharges were the predominant source of bacterial contamination. Exceedences in water quality objectives for body contact recreation established by the State of California most often occurred in the east bay, where the least amount of circulation and largest quantities of stormwater discharges occur. Unlike the wet weather results, almost all of the 89 storm drains that discharge to the bay either did not have flowing fresh water or did not contain exceedingly high bacteria densities during dry weather. Upstream tracking during multiple storm events on two of the largest watersheds draining to the bay showed that sources of indicator bacteria were diffuse and widespread. Densities were as high at the head of each watershed as they were at the mouth, where both discharged to the bay. Every reach in each creek exceeded State of California water quality objectives and had densities similar to surface flows measured before they entered the separate municipal storm sewer system from urban land uses, such as residential, commercial, and industrial, as well as open lands.

California↗