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Biomedical subjects

K L Nuttall

Publications and source records attributed to K L Nuttall.

At least 19 recordsLinked to original sources

Abnormal chromatographic patterns of porphyrins in urine.

Urine is the most frequent specimen used in the initial evaluation of adult patients who present with photosensitivity. When urine porphyrins are abnormal, characterization of the chromatogram is facilitated by calculation of uroporphyrin-to-heptacarboxylate porphyrin (uro/hepta) and uroporphyrin-to-isocoproporphyrin (uro/iso) ratios. The most frequent abnormal pattern, and that most consistent with porphyria cutanea tarda (PCT), is an uro/hepta ratio < or =2.0 and an uro/iso ratio < or =18. When the uro/hepta or uro/iso ratios are less consistent with PCT, other less common porphyrin disorders should be considered. These include variegate porphyria, coproporphyria with manifestations of photosensitivity only, adult onset congenital porphyria, mixed porphyrias, and other less frequent porphyrin disorders. After initial evaluation, the diagnosis should ideally be confirmed by additional testing of blood and fecal specimens. Most attacks of the acute porphyrias are associated with a uro/hepta ratio >4, and can be confirmed by an elevated urine porphobilinogen concentration.

Chromatography, High Pressure Liquid↗

Maternal serum alpha-fetoprotein and altitude.

Maternal serum alpha-fetoprotein (MS-alphaFP) testing is widely used to screen for fetal defects. MS-alphaFP concentrations are affected by a number of variables such as gestational age, maternal weight, number of fetuses, race, and insulin-dependent diabetes. Undefined geographic factors may also influence MS-alphaFP. We have examined the effect of altitude in a sample of 1063 MS-alphaFP results selected to span a range of altitudes. The study sample was subjected to linear regression with and without a term for altitude, and multiple-of-the-median (MoM) values were calculated before and after adjusting for altitude. The median MS-alphaFP was found to decrease an average of 1 ng/mL for every 1100 ft increase in altitude, a change approximately equivalent to that seen with an increase in maternal weight of 6 lb. Adjusting for altitude resulted in the reclassification of 36 of 1063 patient results (3.4%), although the clinical utility of this adjustment remains unexamined.

Altitude↗

Carcinoid tumour.

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Carcinoid Tumor↗

Oral dimercaptosuccinic acid and ongoing exposure to lead: effects on heme synthesis and lead distribution in a rat model.

Lead (Pb) exposure and subsequent toxicity continues to be a significant problem in the United States. Treatment with meso-2,3-dimercaptosuccinic acid (DMSA) has been reported to be effective in reducing the body's Pb burden, with fewer adverse side effects than other chelating agents. The oral availability and relative safety of DMSA presents the controversial option of treating patients with Pb poisoning on an outpatient basis. Despite recommendations that children be removed from the Pb contaminated environment, some children will inevitably be exposed to environmental Pb while receiving oral DMSA therapy. The study hypothesized that oral DMSA chelation therapy is beneficial even when faced with continued dietary Pb. Sprague-Dawley rats were exposed to Pb in water for 35 days and then placed in various treatment groups, including groups administered oral DMSA with and without concurrent Pb exposure. The concentration of Pb in blood and critical organs and Pb diuresis were measured. The effect of Pb on heme synthesis was determined by assaying the urinary delta-aminolevulinic acid (delta-ALA), and blood zinc protoporphyrin (ZPP). DMSA reversed the hematological effects of Pb, decreased the blood, brain, bone, kidney, and liver Pb concentration, and produced a marked Pb diuresis, even when challenged with ongoing Pb exposure. In conclusion, even though DMSA treatment without exposure to Pb is optimal, oral DMSA could be beneficial even when challenged with ongoing Pb exposure.

Administration, Oral↗

A model for metal selenide formation under biological conditions.

The essential trace element selenium is known to be capable of reducing the toxicity of heavy metals like cadmium(II), mercury(II) and silver(I). One mechanism by which this occurs is through the formation of an inert metal selenide like silver selenide. It is not clear why selenide should react in the body preferentially with silver(I) over other metals such as zinc(II), an ion which is capable of forming zinc selenide, and which is present at relatively high levels. A reaction is discussed which can account for the ability of mercury(II) and silver(I) to lead to metal selenide formation in preference to zinc(II). Metal ions which have a sufficiently large formation constant for the metal selenide can induce the disproportionation of elemental selenium to produce the metal selenide; both mercury(II) and silver(I) can induce such reactions, whereas zinc(II) cannot. If this model is accurate, it should provide a basis to predict which metal ions can produce metal selenides in the body, and which ions are unlikely to result in metal selenide formation.

Animals↗

Elemental selenium and glutathione reductase.

Selenium is an essential trace element important to several metabolic processes, although selenium in the chemical form of elemental selenium (Se degree) is commonly believed to be biologically inert. Recent data shows that colloidal suspensions of red amorphous elemental selenium are more easily reduced than previously thought, and that such reductions can potentially take place under biological conditions. The enzyme glutathione reductase, already known to be involved in selenium metabolism, is a good candidate to mediate the reduction of colloidal selenium to hydrogen selenide (H2Se), a compound of established biological activity. The implications of this hypothesis include the possibility that elemental selenium may be biologically active at least under some conditions, and that glutathione reductase may function in selenium metabolism primarily by maintaining the glutathione concentration in a reduced state.

Colloids↗

Evaluating serum alpha-tocopherol (vitamin E) in terms of a lipid ratio.

It is well known that accurate assessment of serum alpha-tocopherol requires knowledge of the serum lipids also present. Patient specimens (n = 307) within the standard reference limit of 5-18 mg/L were used to determine the following 95 percent reference interval for a lipid ratio of alpha-tocopherol to the sum of cholesterol and triglycerides [E/(C + T)]: 1.4 (1.20-1.56) - 5.7 (5.51-6.91) mg/g (90 percent confidence interval). In terms of alpha-tocopherol status, patients with low results (< 5 mg/L) were normal on reevaluation with the lipid ratio in 47 percent of those examined (28 of 59), and elevated results (> 18 mg/L) were normal or low in 58 percent (26 of 4.5). Elevated triglycerides developed from non-fasting specimens were one common reason for misleading results when lipids were not considered. When measuring alpha-tocopherol in a patient population, evaluation of the lipid content is needed for accurate assessment in a significant number of cases.

Clinical Laboratory Techniques↗

Identifying delayed separation in plasma homocysteine specimens.

The delayed separation of plasma from the cellular components of blood can lead to falsely elevated homocysteine results. The incidence of delayed separation in patient specimens was examined by using the ratio of arginine to the sum of arginine plus ornithine [arg/(arg + orn)], a ratio <0.50 being consistent with delayed separation. Two groups were examined: 1) low homocysteine (<10 micromol/L, n = 10), and 2) elevated (>18 micromol/L, n = 12). Specimens in the low group showed an average ratio of 0.47, with 6 of 10 <0.50. In contrast, specimens in the elevated group showed an average ratio of 0.31, with 11 of 12 <0.50. Characteristics consistent with delayed separation occurred frequently, but were significantly more frequent (p = 0.009) in the elevated group. This suggests that many homocysteine results may be falsely elevated due to preanalytic collection problems.

Adult↗

Inductively coupled plasma mass spectrometry for trace element analysis in the clinical laboratory.

Inductively coupled plasma mass spectrometry (ICP-MS) is a relatively new technique for trace element analysis. The basic operating principles of ICP-MS are described and our experience with this technique in a clinical setting is discussed for the analysis of serum, whole blood, and urine. Advantages to ICP-MS include the favorable detection limits (0.01 to 0.1 micrograms/L for many elements), simple specimen preparation, high throughput (about 40 specimens per hour), and the ability to measure more than one element simultaneously. A major disadvantage is the high capital cost of the instrumentation. Heavier elements, such as lead, are well-suited for ICP-MS analysis, whereas lighter elements are prone to more interferences. Lighter elements which are not amenable to assay by ICP-MS include chromium and iron. The ability to measure isotopes is a major advantage for mass spectrometry methods and has the potential to expand the usefulness of trace element analysis.

Female↗

Reference intervals for 24-hour and random urine porphyrins.

Urine porphyrin analysis is an important part in evaluation of photosensitivity. Since porphyrin excretion is variable throughout the day, analysis is traditionally based on 24-hour collections. To facilitate the use of random specimens, as well as poorly collected 24-hour specimens, reference limits based on the porphyrin to creatinine ratio have been developed. Based on 1,171 adult specimens, it is estimated that the 95 percent reference limit (90 percent confidence interval) is < or = 3.9 (3.5-5.7) mumol/mol of creatinine for uroporphyrin and < or = 22 (19-34) mumol/mol for coproporphyrin. These values apply to both 24-hour and random specimens, although random specimens show a higher degree of variability. Modest differences exist between males and females, but they are not significant given the degree of uncertainty in the confidence intervals. In terms of more traditional 24-hour units, reference limits correspond to < or = 37 (32-63) nmol/day for uroporphyrin and < or = 221 (195-320) nmol/day for coproporphyrin.

Chromatography, High Pressure Liquid↗

Testing for inborn errors of metabolism in the acutely ill newborn.

The differential diagnosis of the acutely ill newborn should include inborn errors of metabolism along with much more common conditions such as sepsis and hypoxemia. Testing recommendations, which can take place simultaneously with other studies, are presented for the evaluation of inborn errors in acutely ill newborns. Initial hospital-based tests include arterial blood gases, glucose, electrolytes, urinalysis, complete blood count, and cultures. The results from these initial tests are used to categorize the clinical presentation into one of several categories, and each category in turn serves to direct further testing in an efficient manner. Definitive diagnosis often requires referral to a pediatric specialist, as well as testing available only through reference and research laboratories. Transfer to a tertiary care facility may be advisable when evidence for an inborn error is found.

Blood Chemical Analysis↗

Serum succinate by capillary zone electrophoresis: marker candidate for hypoxia.

Serum succinate may offer an alternate analyte to lactate for the evaluation of hypoxia. To evaluate the potential uses of succinate, a relatively rapid capillary zone electrophoresis assay was developed for use in the clinical laboratory setting. Employing a simple indirect ultraviolet detection method with commercially available instrumentation, the limit of detection for serum succinate was determined to be 0.1 mumol/L, the upper limit of linearity 100 mumol/L, and the between-run coefficient of variation about 15 percent. Based on specimens from 202 apparently healthy adults, the non-parametric reference interval was 1.0 to 9.2 mumol/L. Preliminary studies in stored blood show succinate increased 2-fold while lactate increased 11-fold, suggesting that succinate may be a clinically useful marker for hypoxia in patients after blood transfusion. This assay provides a practical tool for the investigation of the clinical applications of succinate.

Adult↗

The adequacy of capillary specimens for determining whole blood lead.

In response to demands for reliable alternatives to collection of venous specimens for determination of whole blood lead levels in children, the Centers for Disease Control has called for increased research into capillary methodologies. In this study, a three tiered approach was developed to assess the adequacy of capillary specimens for determining whole blood lead. Patient blood lead results from capillary and venous specimens were compared for obvious differences. Next, follow-up specimens for patients with elevated lead levels were compared with the initial results. In addition, experiments were conducted to determine whether or not handwashing eliminates gross contamination. Although the differences are not clinically important, the mean, 3.83 micrograms/dL for 5,100 venous specimens, was significantly lower (p < 0.005) then the mean of 4.6 micrograms/dL for 1,100 capillary specimens. Gross contamination was rare. Lead levels in follow-up specimens on patients whose initial screens were elevated were generally low. Handwashing greatly reduced the amount of external lead contamination. It is concluded that capillary specimens are an acceptable alternative to venous specimens for whole blood screening programs provided the patient and collector meticulously follow the prescribed collection protocol. Nevertheless, all elevated whole blood lead screening results, venous or capillary, should be confirmed with a venous collection before follow-up action is taken.

Blood Specimen Collection↗