Nature as nurture: Rural older women's perspectives on the natural environment.

Rural older women are surrounded by nature, a dynamic context for human development. Informed by place attachment and attention restoration theory, and guided by a life course perspective, this qualitative study focused on the perceived influence of nature in the lives of 34 rural older women. Using grounded theory techniques to analyze in-depth interviews, two primary findings emerged: (a) nature was integral to the women's identity; and (b) interactions with nature were motivated by prior positive spiritual and psychological outcomes. Findings revealed the power of the natural environment as a resource for coping with the challenges associated with aging.

Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5-hydroxyindoleacetic acid: three case examples.

The results for plasma 5-hydroxyindoleacetic acid (5-HIAA), whole blood serotonin and the chromogranins on three patients following their treatment for carcinoid disease with somatostatin analogues are presented. Two of the patients (a 56-year-old woman and a 55-year-old man) demonstrated a good clinical response following treatment, with initial high blood serotonin and plasma 5-HIAA concentrations showing a significant decline. However, blood serotonin concentrations remained above the reference range during the course of treatment, whereas plasma 5-HIAA remained borderline high or marginally elevated with respect to the clinical cut-off concentration. The third patient, a 79-year-old man, demonstrated saturation of platelets with serotonin and increasing elevation of plasma 5-HIAA, which later fell with the introduction of interferon into this patient's treatment regimen. Results for the plasma chromogranin fragments, pancreastatin (Chromogranin A) and GAWK (Chromogranin B), showed a much greater degree of variability in all three cases. This study shows promise for plasma 5-HIAA as a useful marker for monitoring carcinoid disease. The limitations of blood serotonin expressed to the platelet count are highlighted.

Acetylcodeine as a marker of illicit heroin abuse in oral fluid samples.

A method was developed using liquid chromatography linked to atmospheric pressure ionization-tandem mass spectrometry (LC-MS-MS) for the measurement of the opiates, morphine, codeine, 6-monoacetylmorphine (6-MAM), acetylcodeine (AC), and heroin in oral fluid collected from patients attending a substance abuse clinic. Of the 513 oral fluid samples tested, 297 showed detectable concentrations of 1 or more of the opiates and their respective percentage incidence being morphine (97%), codeine (82%), 6-MAM (77%), acetylcodeine (55%), and heroin (45%). A high percentage of these opiate-positive samples (40%) had detectable concentrations of all opiates tested. Significant correlations (p < 0.0001) were found between AC and 6-MAM (r = 0.95), heroin and 6-MAM (r = 0.81), and heroin and AC (r = 0.84). Although none of the subjects in this study were being treated with prescription heroin, nine showed detectable concentrations of heroin with no detectable AC. The mean concentration of heroin in these latter samples was very low compared with samples showing detectable AC (24 vs. 2571 microg/L). Several studies have reported the usefulness of measuring AC in urine for detection of illicit heroin abuse. This study demonstrates that the same marker can also be applied to oral fluid. The additional measurement of heroin in oral fluid is of limited use in monitoring subjects attending a substance abuse clinic.

Quantitative analysis of buprenorphine and norbuprenorphine in urine using liquid chromatography tandem mass spectrometry.

Buprenorphine is an opioid analgesic drug that is used as an alternative to methadone to treat heroin addiction. Established methods for the analysis of buprenorphine and its metabolites in urine such as gas chromatography-mass spectrometry (GC-MS) involve complicated sample extraction procedures. The aim of the present study was to develop a sensitive yet straightforward method for the simultaneous analysis of buprenorphine and norbuprenorphine in urine using liquid chromatography-MS-MS. The method comprised an enzymatic hydrolysis using Patella vulgata b-glucuronidase, followed by centrifugation and direct analysis of the supernatant. The limits of detection and quantitation were < 1 microg/L for buprenorphine and < 1 and 4 microg/L, respectively, for norbuprenorphine. Assay coefficients of variation (CVs) were < 15%, with the exception of concentrations close to the limit of quantitation, where CVs were below 20%. In direct comparison with an established GC-MS protocol, the method showed minimal negative bias (8.7% for buprenorphine and 1.8% for norbuprenorphine) and was less susceptible to sample carryover. The extent of conjugation in unhydrolyzed urine was investigated and found to be highly variable, with proportions of unconjugated buprenorphine and norbuprenorphine of 6.4% [range 0% to 67%; standard deviation (SD) 9.7%] and 34% (range 0% to 100%; SD 23.8%), respectively.

Interference by venlafaxine ingestion in the detection of tramadol by liquid chromatography linked to tandem mass spectrometry for the screening of illicit drugs in human urine.

Confirmation of the presence of illicit drugs in human fluids by liquid chromatography linked to atmospheric pressure ionisation tandem mass spectrometry (LC/MS/MS) is becoming increasingly popular. A rapid LC/MS/MS method is described using reversed phase gradient elution chromatography on a 50 x 3 mm base deactivated C8 column with identification of drugs based on their Multiple Reaction monitoring (MRM) transitions, retention time, and co-elution of stable isotopic analogues where available. The method is used for drug confirmation following initial screening by immunoassay, and identification of drugs such as tramadol, for which no immunoassay is available. False positive results for tramadol were observed in cases where subjects were being treated with the commonly prescribed antidepressant drug venlafaxine. This was a result of the presence of the metabolite O-desmethylvenlafaxine, which has a similar transition to tramadol. This study highlights the need to consider drug metabolites, as well as parent drugs in interferences in LC/MS/MS methods.

Hereditary coproporphyria: comparison of molecular and biochemical investigations in a large family.

Hereditary coproporphyria (HCP) is the least common of the three autosomal dominant acute porphyrias. To compare the sensitivity of metabolite measurements for the identification of asymptomatic HCP, we carried out a molecular and biochemical investigation of a large family in which HCP is caused by a previously unreported frameshift mutation (c.119delA). Thirteen of 19 asymptomatic family members, aged 10-72 years, were shown by mutational analysis to have HCP. The faecal coproporphyrin isomer III:I ratio was increased in all of these 13 family members; faecal total porphyrin concentration and urinary porphyrin excretion were increased in 11 and 8 of them, respectively. Plasma porphyrin concentrations were marginally increased in three individuals and plasma fluorescence emission scanning showed a porphyrin peak at 618 nm in two of these. Our results add to the evidence that an increased faecal porphyrin coproporphyrin III:I ratio is a highly sensitive test for the detection of clinically latent HCP in individuals over the age of 10 years; its sensitivity below this age remains uncertain. They also show that plasma fluorescence emission scanning is not useful for the investigation of families with HCP.

Replacement of immunoassay by LC tandem mass spectrometry for the routine measurement of drugs of abuse in oral fluid.

BACKGROUND: There is increasing interest in the use of oral fluid as the matrix for the detection of drugs of abuse which requires the use of sensitive immunoassays to achieve the low detection limits required. The use of liquid chromatography linked to tandem mass spectrometry (LC/MS/MS) is explored as a possible replacement for immunoassay in screening for drugs of abuse in oral fluid samples. METHODS: Oral fluid samples collected from 72 subjects attending an addiction clinic were screened for opiates, cocaine, methadone and benzodiazepines using both enzyme-linked immunosorbent assays (ELISA) and LC/MS/MS. The latter analysis used a short gradient elution with individual drugs detected by multiple reaction monitoring using tandem mass spectrometry. Results between the two methods were compared qualitatively using the cut-off concentrations defined by the ELISA assays. RESULTS: With regard to the ELISA assays which show group specificity, LC/MS/ MS detected the presence of 6-monoacetylmorphine, morphine or dihydrocodeine in all but two of 49 samples positive for opiates. Of 55 samples positive for benzodiazepines by ELISA, all but two were confirmed by LC/MS/MS. Overall, LC/MS/MS compared favourably with ELISA for detection of specific drugs or their metabolites in the case of morphine, methadone and the cocaine metabolite benzoylecgonine. Many of the discrepant results between the two assays were a result of samples with drug concentrations near to the cut-off concentrations and the imprecision of these assays at very low concentrations. CONCLUSION: LC/MS/MS offers a more flexible, specific and sensitive alternative to the screening of oral fluid samples for drugs of abuse than ELISA. A wide range of drugs and metabolites can be detected from a single sample injection.

Plasma aluminium: a redundant test for patients on dialysis?

BACKGROUND: Aluminium toxicity as a cause of dementia, osteodystrophy and anaemia in patients receiving renal dialysis was first described in the 1970s and led to the regular monitoring of aluminium in plasma and dialysate water. However, aluminium phosphate binders have now been replaced by calcium-based binders or sevelamer and reverse osmosis (RO) water is used in the preparation of dialysate fluid. This has reduced the exposure of dialysis patients to aluminium and it is therefore opportune to review aluminium monitoring in patients undergoing regular renal dialysis. METHODS: Plasma and water aluminium results were audited over the period January 2000-January 2004, with results obtained from nine renal dialysis units in the UK. Patients with a plasma aluminium concentration in the toxic range (>3.7 micromol/L) were followed up by contacting the relevant consultant. RESULTS: Plasma aluminium results were collected on 1626 patients over the four-year period (mean=0.47 micromol/L, median=0.3 micromol/L, range 0.07-30.26 micromol/L, n=5918). Forty-six patients had an aluminium concentration >3.7 micromol/L and nine were not retested. Only three patients had a repeat aluminium concentration >2.2 micromol/L, one being a result of desferrioxamine treatment, with no further clinical information available on the other two. All renal units are using RO water to prepare dialysate and aluminium-based phosphate binders are no longer prescribed. Only one of 212 RO water aluminium concentrations measured was >10 microg/L. Patients with clinical symptoms of overt aluminium toxicity were not identified in this population. CONCLUSION: The role of aluminium monitoring in long-term renal dialysis patients needs re-evaluation. Regular monitoring of plasma aluminium may not be required, but should be considered in any patient showing signs or symptoms of aluminium toxicity or exposed to a contaminated water supply. It is more important that RO water supplies are maintained and monitored. Environmental aluminium as a source of sample contamination should be considered and eliminated during blood collection and sample processing.

Trace element concentrations in patients on home enteral feeding: two cases of severe copper deficiency.

BACKGROUND: Enteral feeding is the fastest growing area of artificial nutrition, with the annual rate of growth being estimated at 20-25% a year. Previous studies have demonstrated trace element deficiencies in patients on long-term home enteral nutrition (HEN). METHODS: The trace elements zinc, selenium, copper and manganese were measured in blood samples from 37 patients on HEN using atomic absorption spectroscopy. RESULTS: Plasma zinc concentrations (range 7.4-14.4 micromol/L) were below the reference range (12.6-22.0 micromol/L) in 30 patients, plasma selenium concentrations (range 0.73-1.76 micromol/L) were below the reference range (0.8-2.0 micromol/L) in only one patient. Whole blood manganese (range 74-309 nmol/L) and plasma manganese (range 13-51 nmol/L) were above both respective reference ranges (73-210 nmol/L and 9-24 nmol/L) in four patients. Two patients showed severely low plasma copper concentrations of 2.4 micromol/L and 2.5 micromol/L, and responded to treatment with extra copper supplementation. CONCLUSION: Although enteral feeds contain adequate concentrations of trace elements, problems with bioavailability may occur and patients receiving long-term enteral feeding should be monitored with regard to plasma trace element concentrations.

Micronutrient concentrations in patients with malignant disease: effect of the inflammatory response.

BACKGROUND: Micronutrient deficiencies may occur in patients with malignancy due to a variety of possible causes, including unbalanced dietary intake and adverse effects of treatment. In addition, many patients show signs of a chronic inflammatory response, which can affect circulating concentrations of certain vitamins and trace elements. Our aim was to examine the effect of the inflammatory response, as determined by plasma C-reactive protein (CRP) concentrations, on a range of micronutrients in patients with malignancy. METHODS: Blood samples were collected from 50 patients with various malignancies for the measurement of vitamins A, E, C and B(1), the trace elements copper, zinc, selenium and manganese and the inflammatory marker CRP. Vitamin A was measured as retinol and vitamin E as alpha-tocopherol. Vitamin C measurement included both ascorbic acid and dehydroascorbic acid. The vitamins were assayed by high-performance liquid chromatography and the trace elements by atomic-absorption spectroscopy. RESULTS: Concentrations of zinc and selenium below their respective reference ranges and copper and manganese above their respective reference ranges were commonly found in the cancer group. However, none of these elements showed any significant correlation with CRP (P >0.01). Reduced levels of vitamin A, C and B(1) were commonly found in the cancer group. Vitamins A and C showed a significant negative correlation with CRP (r(s)=-0.66, P <0.0001 and r(s)=-0.53, P = 0.0005, respectively). Vitamin E showed no correlation with CRP. CONCLUSION: The inflammatory response is a major consideration in the interpretation of vitamin A and C concentrations in patients with malignancy.

An audit of biological monitoring of industrial lead workers by a UK laboratory over a 2-year period.

BACKGROUND: Medical surveillance of workers in the lead industry is under the statutory control of the Control of Lead at Work Act (CLAW). Over the years the CLAW regulations have been updated with a reduction in the suspension concentration for blood lead and the introduction of an action limit. As a result of these changes, an audit of blood lead measurement together with an evaluation of haemoglobin and zinc protoporphyrin (ZPP) measurements, also requested as part of surveillance, is required. METHODS: Results of measurements for blood lead, ZPP and haemoglobin in lead-exposed workers in 58 industries within the UK were collected over a 2-year period. RESULTS: For male workers, 8.8% of blood lead results [range 1-88 microg/dL (0.05-4.25 micromol/L), median 29 microg/dL (1.4 micromol/L), n = 3010] were above the action limit and 5.6% above the suspension limit set by CLAW. For female workers, 1.9% of blood lead results [range 1-74 micro g/dL (0.05-3.58 micromol/L), median 7 microg/dL (0.34 micromol/L), n = 161] were above the action limit. No significant correlation was found between blood lead and haemoglobin in the male workers (rs =-0.04, P = 0.024) and only a slight negative correlation for the female workers (rs =-0.25, P = 0.0016). ZPP showed an exponential relationship with blood lead in the male workers with a wide scatter of results. CONCLUSION: Haemoglobin and ZPP offer little towards the assessment of lead exposure in industrial workers. Blood lead in accordance with the CLAW regulations still offers the most appropriate means of industrial monitoring.

Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease.

BACKGROUND: Carcinoid disease is an uncommon disorder resulting from tumours of the enterochromaffin cells. Current biochemical investigation usually involves the measurement of 5-hydroxyindole-3-acetic acid (5-HIAA) in 24-h urine collections. Because of the problems associated with urine collections (i.e. inconvenience, accuracy of collection and requirement for preservatives) two alternative markers, fasting plasma 5-HIAA and whole blood serotonin (5-hydroxytryptamine), have been studied. METHODS AND RESULTS: Whole blood serotonin concentration and plasma and urine 5-HIAA concentrations were measured by high-performance liquid chromatography in 31 patients suspected of having carcinoid and 26 known carcinoid patients. Receiver operator characteristic curve analysis of the data showed no statistical difference between the three markers (P>0.01) with regard to their discriminating function. However, fasting plasma 5-HIAA assay showed greater stability than whole blood serotonin assay and is more convenient for the patient than a 24-h urine collection. At a cut-off value of 118 nmol/L plasma 5-HIAA assay showed a sensitivity of 89%, a specificity of 97% and a test efficiency of 93%. Whole blood serotonin assay was further limited by its saturation in platelets at 40 nmol/10(9) platelets which made it less suitable for monitoring the treatment of carcinoid disease. CONCLUSION: Fasting plasma 5-HIAA concentration provides a more convenient screening test for carcinoid and overcomes the problems associated with 24-h urine collections, without any loss of diagnostic precision.

Effects of a multicomponent intervention on functional outcomes and process of care in hospitalized older patients: a randomized controlled trial of Acute Care for Elders (ACE) in a community hospital.

BACKGROUND: Older persons frequently experience a decline in function following an acute medical illness and hospitalization. OBJECTIVE: To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients. DESIGN: Randomized controlled trial. SETTING: Community teaching hospital. PATIENTS: A total of 1,531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997. INTERVENTION: ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness. MEASUREMENTS: The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction. RESULTS: Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P = .027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; P = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P < .05). CONCLUSIONS: ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes.

Older women, their children, and grandchildren: a feminist perspective on family relationships.

Using gerontological and feminist frameworks, we explored the relationships older women have with their children and grandchildren. In-depth, qualitative interviews were conducted with 34 women, ranging in age from 55 to 88. From our analyses of the women's perceptions of their family relationships, two themes were prevalent: the centrality of children and the peripherality of grandchildren in their everyday lives. The women had varying degrees of involvement with their children and grandchildren, and these relationships contributed to their sense of self and family. Their relationships were not stagnant, but were continually reshaped as both the women and their family members proceeded through the life course.

Measurement of phenylalanine and tyrosine in plasma by high-performance liquid chromatography using the inherent fluorescence of aromatic amino acids.

An isocratic high-performance liquid chromatography (HPLC) method is described using the natural fluorescence of phenylalanine and tyrosine compared with that of an internal standard N-methyl phenylalanine. Plasma precipitated with 6% perchloric acid was separated isocratically using a base-deactivated C18 column with 5% acetonitrile in water as the mobile phase. Fluorescent measurements at an excitation wavelength of 215 nm and emission 283 nm showed only three peaks for tyrosine, phenylalanine and the internal standard eluting within 9 min. Inter-batch coefficients of variation for phenylalanine were 2.9% and 1.8% at levels of 70 and 567 mumol/L, respectively, and 2.9% at a level of 63 mumol/L for tyrosine. The results for phenylalanine for this method showed a small mean positive bias (11 mumol/L) when compared with the target all-method means for UK National External Quality Assessment Scheme samples (n = 31). The results for tyrosine showed a small positive mean bias (10 mumol/L) when compared with an ion-exchange chromatographic method (n = 40). This method provides a quick and simple alternative to those using HPLC with pre- or post-column derivatization for monitoring patients with phenylketonuria. It is also less subject to interferences than HPLC methods using ultraviolet detection, particularly for the early eluting tyrosine peak.

The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and its significance in the mechanism of lead toxicity on haem synthesis.

Protoporphyrin and zinc-protoporphyrin were measured in the erythrocytes of normal subjects, workers exposed to lead and patients with iron deficiency and erythropoietic protoporphyria (EPP). Results showed significantly higher levels of zinc-protoporphyrin in the lead-exposed workers (P < 0.0001), patients with iron deficiency (P < 0.0001) and EPP patients (P < 0.001) compared with normal subjects. The lead-exposed workers showed the highest levels of zinc-protoporphyrin, which were significantly greater than both the iron-deficient and EPP patients (P < 0.0001). They also showed a higher ratio of zinc-protoporphyrin to free protoporphyrin compared with normal subjects (P < 0.0001) but no significant difference in this ratio was found when compared with iron-deficient patients (P = 0.1). These results are discussed in light of the controversy concerning the mechanism of formation of zinc-protoporphyrin in lead exposure.