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Biomedical subjects

T P Moyer

Publications and source records attributed to T P Moyer.

At least 19 recordsLinked to original sources
PubMed1998

Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms.

Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n=29), active 4 mg nicotine gum (n=31), saline placebo nasal spray (n=16) or placebo gum (n=15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1=no withdrawal, 41=extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (+/-SD) age of the subjects was 38.6 (+/-10.1) years, 48% were females, smoking rate was 24.5 (+/-7.8) cigarettes per day, and years of smoking was 19.9 (+/-10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects.

Adult↗
PubMed1998

Silicon analysis of breast and capsular tissue from patients with saline or silicone gel breast implants: II. Correlation with connective-tissue disease.

The silicone breast implant controversy rages on. Recent work has demonstrated that normal or baseline breast tissue silicon levels in women who had had no prior exposure to any type of breast implant may be as high as 446 microg/gm of tissue. These data ranged from 4 to 446 microg/gm of tissue, with a median of 27.0 microg/gm of tissue. In addition, numerous other epidemiologic and rheumatologic studies have demonstrated no association between silicone breast implants and any connective-tissue diseases. Despite these reports, the use of silicone implants remains restricted. The present study measured breast and capsular tissue silicon levels from 23 breasts in 14 patients with saline implants, and from 42 breasts in 29 patients with silicone implants. No patient in the saline implant group presented with signs or symptoms of connective-tissue disease. Patients with silicone implants, however, were divided into three groups based on the presence or absence of signs or symptoms of connective-tissue disease: group I, no symptoms or signs; group II, + symptoms, no signs; and group III, + symptoms, + signs. Six patients in group III were diagnosed with a specific connective-tissue disease, including systemic lupus erythematosus, rheumatoid arthritis, or scleroderma. The most common indications for implant removal or exchange were capsular contracture and implant rupture, although 41 percent of patients with silicone implants expressed media-related concern over the implant issue. The most common symptoms described by patients in groups II and III were joint pain and stiffness, arm pain and numbness, and fatigue. In all groups, capsular tissue silicon levels were significantly greater than breast tissue levels. This finding may indicate that the capsule serves as a barrier to the distribution of silicone from the implant into adjacent breast tissue. Although breast tissue silicon levels in patients with silicone implants were not significantly greater than those in patients with saline implants (p = 0.48), capsular tissue levels in patients with silicone implants were, indeed, significantly greater than those in patients with saline implants (p < 0.001). However, no statistically significant differences in tissue silicon levels were observed with relation to the presence or absence of connective-tissue disease signs or symptoms in patients with silicone implants (groups I to III). Therefore, these data strengthen the conclusion that there is no association between tissue silicon levels and connective-tissue disease.

Breast↗
PubMed1998

Supporting pharmaceutical studies for FDA submissions: diversifying the drug monitoring laboratory.

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.

Clinical Trials as Topic↗
PubMed1997

Hemosiderosis in cirrhosis: a study of 447 native livers.

BACKGROUND & AIMS: Hemosiderosis may have a detrimental effect on some chronic liver diseases. The aim of this study was to determine the prevalence and diagnostic implications of hemosiderosis in cirrhosis. METHODS: Tissue iron in 447 cirrhotic livers was studied histologically and chemically. RESULTS: Positive iron staining was found in 145 cases (32.4%), and increased chemical hepatic iron concentration was found in 91 cases (20.3%), including 38 cases (8.5%) with hepatic iron overload in the hemochromatosis range, defined by an iron index of > or = 1.9 (iron index equals hepatic iron concentration in micromoles per gram divided by age). However, homozygous hemochromatosis seemed to have caused the cirrhosis in only 5 instances. Stainable iron was found in 22%-67% of the cases with nonbiliary cirrhosis but in only 7%-20% of cases with biliary cirrhosis. Most available pretransplant biopsy specimens failed to show evidence of homozygous hemochromatosis. CONCLUSIONS: Iron overload is very common in many types of nonbiliary cirrhosis but rare in biliary cirrhosis. The hemosiderosis of affected livers seems to be acquired and to occur rapidly once cirrhosis has developed; cirrhosis alone may cause iron accumulation. In the presence of cirrhosis, hepatic iron indices of >1.9 should not be interpreted as proof of homozygous hemochromatosis.

Adult↗
PubMed1997

Determination of silicon in breast and capsular tissue from patients with breast implants performed by inductively coupled plasma emission spectroscopy. Comparison with tissue histology.

A method for analysis of silicon in tissue was developed to determine silicon content in breast parenchymal and periprosthetic capsular tissues of patients with silicone or saline implants and to compare levels in tissues from normal (nonaugmented) breasts. It is of interest to determine whether increased silicon content in tissues can be associated with morbidity in patients who have received silicone implants. This manuscript addresses the issues involved in analysis of breast tissue samples for silicon and compares silicon levels with tissue histologic findings and patient morbidity. One hundred sixty tissue samples were obtained for silicon analysis from 72 patients during augmentation, capsulectomy with or without replacement mammoplasty, mastectomy, or biopsy procedures and were frozen in acid-washed polystyrene tubes at 220 degrees C until analysis. Samples were thawed, sectioned to approximately 0.1 g (dry weight), and digested in nitric acid before analysis by inductively coupled plasma emission spectroscopy, monitoring emission intensity at 251.6 nm. Tissue silicon levels (breast parenchymal and periprosthetic capsular tissue) in patients with silicone gel implants were much higher (mean, 9,287 micrograms/g, n = 106) than in patients with saline implants (mean, 196 micrograms/g, n = 37) or nonaugmented breasts (mean, 64 micrograms/g, n = 17). Histologic examination was performed on 54 tissue samples stained with hematoxylin-eosin. Tissue samples were rated as to degree of inflammation and calcification, and amount of giant cells, foamy histiocytes, and vacuoles containing a colorless refractory material. Vacuolization and foamy histiocyte ratings correlated significantly with tissue silicon concentration. No correlations were found between tissue silicon concentration and inflammation, calcification, or giant cell rating. Implant age (number of years an implant was in place before sampling) correlated with capsular tissue silicon concentration in patients with intact implants but not in those with ruptured implants. No difference in tissue silicon concentration was found between patients with or without signs or symptoms of morbidity. Using 0.1 g of tissue, the method was linear to 1,000 micrograms/g, and sensitivity was 3.7 micrograms/g. Precision between runs (mean, 5.1 micrograms/g; coefficient of variance, 13.7%; n = 13) was calculated from multiple analyses of a bovine liver standard (National Bureau of Standards, reference material 1577a). Significant biologic variability (21.4% to 52.5%) was seen in tissues with high silicon levels. Paraffin-embedded, formalin-fixed tissues are not amenable to silicon analysis by this method, because of leaching of silicone from the tissues during preparation. Thus only fresh frozen tissue samples were used.

Age Factors↗
PubMed1996

Silicon analysis of breast and periprosthetic capsular tissue from patients with saline or silicone gel breast implants.

The ubiquitousness of silicon is well known. Recent work has demonstrated measurable baseline levels of silicon in nonaugmented cadavers, subsequent to numerous reports of significant elevations of such levels within patients with silicone breast implants and even more reports alleging a causal relation between silicone gel prostheses and connective-tissue diseases. Despite the lack of scientifically substantiated data that such a relation exists, the calamitous silicone breast implant controversy has ensued. Saline-filled breast implants are constructed with a silicone elastomer envelope that remains in direct contact with periprosthetic capsular tissue following implantation. Although there is no evidence to link saline implants with any disorders, it is important to know if saline breast implants contribute any silicon to human body baseline silicon levels. The present study measured tissue silicon levels in 28 breasts of 16 patients with saline-filled implants to determine if the silicone envelope of these prostheses can contribute to the elevation of such levels. These data were compared with data from 116 breasts of 65 patients with silicone gel-filled prostheses as well as breast tissue from 17 patients (controls) who had never been exposed to either type of implant. Samples of breast tissue and periprosthetic capsular tissue were obtained from patients with both intact and ruptured implants. Silicon levels of breast tissue specimens from patients with saline-filled implants were within the range of the controls if the implants were intact. Silicon levels in periprosthetic capsular tissue from patients with intact saline-filled implants were significantly higher than controls (p < 0.02); however, they were still 100-fold less than capsular tissue levels from patients with intact gel-filled implants. Silicon levels measured in both types of tissue were significantly elevated in patients with silicone gel-filled implants compared with controls (p < 0.01). In the case of ruptured gel implants, breast tissue demonstrated higher silicon levels than did similar specimens from patients with intact implants (p < 0.054); periprosthetic capsular tissue levels also were elevated, although the differences were not statistically significant (p = 0.54). These findings are independent of the implant brand or length of exposure to the particular prosthesis. The finding of elevated levels of silicon in both breast and periprosthetic capsular tissue in patients with silicone gel-filled implants in no way implies or substantiates any claim of a causal relationship between silicone and any reported illnesses.

Adult↗
PubMed1996

The importance of urinary magnesium values in patients with gut failure.

OBJECTIVE: To determine whether urinary magnesium (Mg) values in patients with gut failure would be more helpful than serum Mg measurements in assessment of Mg deficiency. DESIGN: We compared serum and urinary Mg values in 16 patients with gut failure and 16 age- and sex-matched control subjects. MATERIAL AND METHODS: Sixteen patients with gut failure (nine women and seven men; mean age, 59 years) had serum and 24-hour urinary mg measured before Mg replacement therapy. Short bowel syndrome was present in 75%, and diffuse small bowel disease was present in 25%. RESULTS: The median value for serum Mg was 1.7 mg/dL for patients and 2.0 mg/dL for healthy control subjects (P < 0.001). The median values for urinary Mg were 19 mg and 127 mg per 24-hour specimen in patient and control groups, respectively (P < 0.001). A strong correlation was noted between serum Mg and urinary Mg levels. All patients had low urinary Mg values even though 9 of 16 (56%) had normal serum Mg values. Two patients with normal serum Mg concentrations had urinary Mg values of 20 mg/24 h (25% of normal). Serum, but not urinary, Mg correlated significantly with the length of remaining small bowel (P = 0.03). CONCLUSIONS: Urinary Mg declines before serum Mg and is an earlier and more reliable indicator of evolving Mg deficiency. On the basis of these observations and those showing beneficial effects of parenterally administered Mg supplements on urinary citrate excretion (and, presumably, formation of calcium oxalate stones), replacement of Mg in patients with gut failure should be targeted at normalizing urinary Mg.

Adult↗
PubMed1995

Effects of insulin on plasma magnesium in noninsulin-dependent diabetes mellitus: evidence for insulin resistance.

Insulin influences both glucose metabolism and magnesium homeostasis in humans. The present studies sought to determine whether insulin-induced stimulation of magnesium uptake is impaired in noninsulin-dependent diabetes mellitus (NIDDM) and enhanced by acute hyperglycemia. To do so, we measured plasma magnesium concentrations in diabetic and nondiabetic subjects on two occasions: once when glucose concentrations were maintained constant and once when glucose concentrations were varied to mimic a postprandial pattern. The same amount of insulin was infused on both occasions in a manner that reproduced the systemic insulin concentrations normally observed after glucose ingestion. During the prandial insulin infusion, the decrement in the plasma magnesium concentration was lower (P < 0.05) in the diabetic patients than that in the nondiabetic subjects during both the euglycemic (4.1 +/- 0.9 vs. 7.8 +/- 1.3 mmol/L.4 h) and hyperglycemic (1.7 +/- 1.1 vs. 6.6 +/- 1.4 mmol/L.4 h) studies. Glucose disappearance also was lower (P < 0.05) in the diabetic patients than that in the nondiabetic subjects, and the insulin-induced decrement in plasma magnesium was correlated (P < 0.01) with glucose disappearance. On the other hand, despite higher (P < 0.05) rates of disappearance in the hyperglycemic than euglycemic experiments, the decrement in plasma magnesium did not differ in either group on either occasion. We conclude that insulin resistance in subjects with NIDDM impairs the ability of insulin to stimulate magnesium as well as glucose uptake.

Blood Glucose↗
PubMed1995

Guamanian neurodegenerative disease: investigation of the calcium metabolism/heavy metal hypothesis.

OBJECTIVE: There is a high prevalence of neurodegenerative disease (parkinsonism, dementia, and motor neuron disease) on the western Pacific island of Guam. We sought evidence in support of the hypothesis that these conditions are triggered by nutritional deficiencies of calcium and magnesium leading to secondary hyperparathyroidism that then facilitates the entry of calcium and toxic heavy metals into the brain. METHODS: We analyzed indices of calcium metabolism plus blood-serum, urine, nail, and hair heavy metal concentrations in 12 patients with Guamanian neurodegenerative disease and 12 Chamorro control subjects. RESULTS: All 12 patients with Guamanian neurodegenerative disease had normal values for serum total and ionized calcium, 25-hydroxyvitamin D, and 24-hour urine collections for calcium. Eleven of 12 patients had normal serum parathyroid hormone values and alkaline phosphatase levels. No patient had reduced serum phosphorus or magnesium values although a minority of patients and controls had low urinary magnesium concentrations. Median blood-serum and 24-hour urine collections for heavy metals (aluminum, arsenic, cadmium, copper, iron, lead, manganese, mercury, and zinc) were statistically similar in the patient and control groups except for a slight elevation of blood, but not urine, lead in the patient group. Concentrations of heavy metals in hair and nails were similar in the two groups. CONCLUSIONS: We could find no evidence in support of abnormalities of calcium metabolism or heavy metal absorption as a major causative factor in the development of neurodegenerative disease on the island of Guam.

Aged↗
PubMed1995

Essential and toxic element concentrations in fresh and formalin-fixed human autopsy tissues.

The concentrations of five essential elements and six potentially toxic elements were determined in seven organs collected at autopsy from 30 human subjects. Elemental analyses were carried out by graphite furnace atomic absorption spectroscopy, and inductively coupled plasma emission spectroscopy, and inductively coupled plasma mass spectroscopy, and concentrations in fresh and formalin-fixed tissues were compared. Formalin-fixation long-term storage has little effect on most element concentrations in tissue, except for Al and Mn, which changed with prolonged storage in formalin. The kidney and liver contained the greatest concentrations of toxic elements compared with other organs, whereas the essential elements were uniformly distributed among all organs. There was no more than a 10-fold difference in the tissue concentration of the elements studied among the organs, except for the concentration of Fe in liver, and Ca and Mg in bone. We also demonstrate that these elements are homogeneously distributed in tissues.

Aluminum↗
PubMed1994

The liver biopsy diagnosis of Wilson's disease. Methods in pathology.

The authors present a simple liver biopsy protocol that is a reliable and cost-effective method of diagnosing hepatic Wilson's disease. Biopsy specimens are obtained in routine fashion, without the need for copper-free solutions or instruments. The samples are then embedded in paraffin, stained for copper and copper-associated protein, and studied by light microscopy. Subsequently, a sample of hepatic parenchyma is excised from the paraffin block for chemical quantitation of tissue copper. This combination of methods generally yields reliable results and allows confirmation of the diagnosis in cases of Wilson's disease in which special stains for copper are negative. In most instances, electron-microscopic studies are not necessary.

Adult↗
PubMed1993

Urinary oxalate and glycolate excretion patterns in the first year of life: a longitudinal study.

To determine the range of normal values, we studied urinary excretion of oxalate and glycolate prospectively and longitudinally in a cohort of 30 healthy term infants. Random urine samples were obtained at 2 days, 2 weeks, and 2, 4, 6, and 9 months of age. The results had a log-normal distribution. The mean oxalate/creatinine ratio, as determined by the oxalate oxidase method, was 0.08 (in milligrams of oxalate to milligrams of creatinine) with a normalized range of 0.02 to 0.31. The mean ratio when oxalates were measured by using the Olthuis assay was 0.13 (range 0.03 to 0.53). The mean glycolate/creatinine ratio was 0.07 (range 0.02 to 0.26). These values did not correlate with increasing age. The oxalate/creatinine ratios were higher in formula-fed infants than in those who were fed human milk (0.14 +/- 0.16 vs 0.08 +/- 0.04; p < 0.01).

Creatinine↗
PubMed1993

Liver biopsy diagnosis of homozygous hemochromatosis: a diagnostic algorithm.

The diagnosis of homozygous hemochromatosis (HH) should be based on appropriate findings on liver biopsy specimens. In cases with equivocal morphologic features, quantitative tissue iron determination and calculation of the hepatic iron index generally enable one to distinguish HH from other types of hepatic iron overload. In this article, we describe a diagnostic algorithm that is designed to avoid diagnostic errors because of histologic misinterpretation or erroneous, usually false-negative, chemical iron studies. The algorithm also delineates a cost-effective method of using quantitative tissue iron analysis. Diagnostic biopsy features of uncomplicated HH include (1) hemosiderosis that involves primarily hepatocytes, with or without inactive cirrhosis, and (2) a tissue iron index of 1.9 or higher. Findings such as prominent fatty changes or lymphocytic piecemeal necrosis indicate the presence of HH in conjunction with another complicating condition or secondary iron overload in the absence of HH.

Algorithms↗
PubMed1992

Arsenic analysis II: rapid separation and quantification of inorganic arsenic plus metabolites and arsenobetaine from urine.

We describe the rapid separation of inorganic arsenic plus metabolites from arsenobetaine or seafood arsenic in urine. Traditional, high-pressure liquid chromatography is replaced by disposable silica-based cation-exchange cartridges for this separation. Both fractions are quickly separated and collected for analysis by atomic absorption spectrophotometry. Analytical recovery of both fractions is > or = 95%, with an overall precision (CV) ranging from 1.6% to 6.4%. Using this method, we correctly identified the sources of arsenic exposure, whether of inorganic or seafood origin, in 11 urine specimens supplied by the Centre de Toxicologie du Quebec.

Animals↗