Allylmercapturic acid as urinary biomarker of human exposure to allyl chloride

OBJECTIVE: To evaluate the use of urinary mercapturic acids as a biomarker of human exposure to allyl chloride (3-chloropropene) (AC). During three regular shut down periods in a production factory for AC, both types of variables were measured in 136 workers involved in maintenance operations. METHODS: Potential airborne exposure to AC was measured by personal air monitoring in the breathing zone. In total 205 workshifts were evaluated. During 99 workshifts no respiratory protection equipment was used. Mercapturic acid metabolites were measured in urinary extracts by gas chromatography-mass spectrometry (GC-MS). RESULTS: During 86 work shifts when no respiratory protection was used the air concentrations of AC were below the Dutch eight hour time weighted average (8 h-TWA) occupational exposure limit (OEL) of AC (3 mg/m3), whereas in 13 workshifts the potential exposure, as measured by personal air monitoring, exceeded the OEL (3.3 to 17 mg/m3). With the aid of GC-MS, 3-hydroxypropylmercapturic acid (HPMA) was identified as a minor and allylmercapturic acid (ALMA) as a major metabolite of AC in urine samples from the maintenance workers exposed to AC. The concentrations of ALMA excreted were in a range from < 25 micrograms/l (detection limit) to 3550 micrograms/l. The increases in urinary ALMA concentrations during the workshifts correlated well with the 8h-TWA air concentrations of AC (r = 0.816, P = 0.0001, n = 39). Based on this correlation, for AC a biological exposure index (BEI) of 352 micrograms ALMA/g creatinine during an eight hour workshift is proposed. In some urine samples unexpectedly high concentrations of ALMA were found. Some of these could definitely be attributed to dermal exposure to AC. In other cases garlic consumption was identified as a confounding factor. CONCLUSION: The mercapturic acid ALMA was identified in urine of workers occupationally exposed to airborne AC and the increase in ALMA concentrations in urine during a workshift correlated well with the 8 h-TWA exposure to AC. Garlic consumption, but not smoking, is a potential confounding factor for this biomarker of human exposure to AC.     

Chromatographic measurement of urinary steroids in patients with psoriasis

A gas-chromatographic method for urinary steroid measurements by Chrome-5 (Prague) chromatograph with plasma ionization detector is suggested. Glass column 1.5 m long is packed with N-AW chromatone impregnated with 15% SE-30. Detector and evaporator temperature is 260 degrees C. Column temperature is programmed from 200 to 250 degrees C. Quantitative and qualitative analysis of chromatograms in 40 patients and 30 controls permitted assessment of excretion of 17-ketosteroids, hydroxyandrosterone, etiocholanolone, androsterone, dihydroepiandrosterone, beta-cortol compounds, etc., which is important in studies of psoriasis pathogenesis and in assessment of the efficacy of treatment of this and other diseases.     

Inadequate data base.

Suggests that T. I. De Vol's (1974) article comparing British and US graduate enrollment should not have been published since average British enrollment was based on returns from only 38% of the British psychology departments surveyed. Also, no comparison was made between departments that did and did not respond. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inadequate frameworks for understanding bodily homeostasis

Separate nervous systems, somatic and autonomic, were proposed to regulate the portion of the individual's life that is concerned with the external environment and the portion that is concerned with internal homeostasis. Regulation of the autonomic system by the CNS was assigned to the limbic system. Brainstem circuitry, between limbic and autonomic systems, was assigned to the supposedly nonspecific reticular formation. In fact, daily survival depends on integrated control of behavior and internal physiology. In mammals only the brain has the inbuilt programming for patterned co-ordination of these activities. The terms autonomic nervous system, limbic system and reticular formation are at odds with this patterned co-ordination. They should be abandoned and replaced with the term visceral neurons (afferent and efferent) and with reference to relevant specific-neural circuitry in the brain.     

Tissue distribution and urinary excretion of essential elements in rats orally exposed to aluminum chloride

The purpose of this study was to determine disorders in the metabolism of the essential elements (Ca, Fe, Cu, and Zn) in some tissues of rats, as well as to detect the dynamics of urinary excretion of these metals after oral administration of 20 mgAl/kg every day for 8 wk. The elements were determined in brain, kidneys, blood, and urine of the animals in 1st, 2nd, 3rd, 4th, and 8th wk after the exposure to AlCl3. After the 1st wk of aluminium administration, we observed increase of Ca and a decrease of Fe in blood. In brain Ca, Fe, and Cu concentrations were significantly higher in Al-treated rats than in controls after 8-wk exposure. The concentration changes of the essential metals in the tissue were accompanied by increase of the Ca, Fe, and Zn urinary excretion. We assume that the increase in urinary excretion of Ca and the decrease of Fe in the blood may be sensitive indicators of oral aluminium administration.     

In vivo measurement of chloride and water secretion in the jejunum of cystic fibrosis patients

In the present study, we have investigated the possible consequences of the chloride channel defect in the intestine of cystic fibrosis (CF) patients for electrolyte and water transport in the jejunum in vivo, using a multilumen, double occluding balloon catheter, and an Ag/AgCl intraluminal electrode. During a chloride-free perfusion, to optimize the sensitivity of our measurements, the transmural potential difference (PD) (lumen with reference to serosal side) was found to be significantly higher in the jejunum of CF patients (+8.0 +/- 2.1 mV; n = 5) than in healthy control subjects (-2.2 +/- 2.0 mV; n = 9). The chloride concentration measured in chloride-free jejunal perfusates of CF patients was significantly lower than in controls (10.9 +/- 2.3 and 41.4 +/- 8.2 mM, respectively). Possible differences in net chloride and water secretion did not reach statistical significance (chloride secretion controls: -2.1 +/- 0.9 mmol/10 cm/h; CF: -0.8 +/- 0.2 mmol/10 cm/h; water secretion controls: -0.8 +/- 2.5 mL/10 cm/h; CF: -11.7 +/- 8.9 mL/10 cm/h). In control subjects, intraluminally applied theophylline stimulated the secretion of water (delta 23.4 +/- 4.6 mL/10 cm/h) and chloride (delta 4.1 +/- 1.1 mmol/10 cm/h), but not in CF patients (respectively delta 3.6 +/- 3.3 mL/10 cm/h and delta 1.1 +/- 1.1 mmol/10 cm/h). In controls, theophylline caused a significant increase in lumen negativity (PD -10.2 +/- 2.6 mV), but no change could be seen in CF patient transmural PD. These observations provide in vivo evidence for a decreased chloride permeability in the jejunum in CF, resulting in a significant reduction in net electrolyte and water secretion in the presence, but not in the absence, of an intestinal secretagogue.     

Renal water channel expression in newborns: measurement of urinary excretion of aquaporin-2

Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney.     

Inadequate utilization of somato-medical services by psychogenically ill patients

Within the Mannheim Cohort Project on the epidemiology of psychogenic disorders 240 probands of a high risk sample (suffering from medium psychogenic impairment) were randomly selected from the general population and investigated with regard to their realized utilization of the medical and/or psychotherapeutic services of the health care system. On the basis of clinical criteria the probands were classified as case (n = 78) of psychogenic disorder or non-case (n = 162). Increased psychogenic impairment caused by psychoneurotic, character neurotic, or psychosomatic-functional disorders was primarily combined with an intensified utilization of the somatically oriented medical services. Only 2.5% of the cases indicated that the reason for their most recent visit to a physician was psychotherapeutic treatment. In view of the high percentage of psychogenic impaired patients in private practices and general hospitals this seems to be a particularly discrepant finding. In spite of the psychogenic nature of their complaints the cases were confronted with somatically oriented therapy offers like the non-cases. An increased psychogenic impairment did not lead to a qualitative alteration of the utilization of medical and/or psychotherapeutic services. Facing the fact that the utilization of somatically oriented medical services by psychogenic ill patients is still widespread but inadequate this finding is interpreted as indication for an essential demand of further studies on the determinants of psychotherapy acceptance.     

Inadequate cervical mucus--a cause of "idiopathic" infertility

The purpose of this study was to investigate and treat a group of patients referred for "idiopathic" infertility in whom no apparent cause for infertility, apart from inadequate cervical mucus, was found. Hormone investigations revealed that these patients could be divided into two groups: those with low sex steroid profiles despite apparent ovulation, and a second group with normal sex steroid profiles. All patients were treated with ovulation-inducing agents in an attempt to produce "controlled" ovarian hyperstimulation and an improved cervical mucus. Four of six patients conceived. The rationale behind the use of ovulation-inducing agents in this situation is discussed.     

Inadequate management of blood pressure in a hypertensive population

BACKGROUND: Many patients with hypertension have inadequate control of their blood pressure. Improving the treatment of hypertension requires an understanding of the ways in which physicians manage this condition and a means of assessing the efficacy of this care. METHODS: We examined the care of 800 hypertensive men at five Department of Veterans Affairs sites in New England over a two-year period. Their mean (+/-SD) age was 65.5+/-9.1 years, and the average duration of hypertension was 12.6+/-5.3 years. We used recursive partitioning to assess the probability that antihypertensive therapy would be increased at a given clinic visit using several variables. We then used these predictions to define the intensity of treatment for each patient during the study period, and we examined the associations between the intensity of treatment and the degree of control of blood pressure. RESULTS: Approximately 40 percent of the patients had a blood pressure of > or =160/90 mm Hg despite an average of more than six hypertension-related visits per year. Increases in therapy occurred during 6.7 percent of visits. Characteristics associated with an increase in antihypertensive therapy included increased levels of both systolic and diastolic blood pressure at that visit (but not previous visits), a previous change in therapy, the presence of coronary artery disease, and a scheduled visit. Patients who had more intensive therapy had significantly (P<0.01) better control of blood pressure. During the two-year period, systolic blood pressure declined by 6.3 mm Hg among patients with the most intensive treatment, but increased by 4.8 mm Hg among the patients with the least intensive treatment. CONCLUSIONS: In a selected population of older men, blood pressure was poorly controlled in many. Those who received more intensive medical therapy had better control. Many physicians are not aggressive enough in their approach to hypertension.     

Inadequate data in, attractive theory out.

Contends that R. J. Sternberg (see record 1981-06882-001) presented correlations based on independent samples of about 25 cases each, made the usual statistical comparison of each independently with a population parameter of zero, and proceeded to interpret his results as if he had made the appropriate statistical tests. In one set of comparisons, he needed to use a nonzero population parameter representative of previous research findings to define his statistical hypothesis. It is concluded that these errors are endemic in reports of psychological research. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of an automated pyrogallol red-molybdate method for the measurement of urinary protein in rats

Methods for quantitating urinary protein differ in their ranges of linearity, technical ease of performance, and applicability to automated analyzers. The Coomassie Brilliant Blue method is widely used but has limited linearity and its tendency to stain glassware has limited its application to automated analyzers. We evaluated a pyrogallol red-molybdate protein dye-binding method (Biotrol USA, Inc.) on a Hitachi 705 analyzer for the quantitation of urinary protein in rats. This method showed a wide range of linearity (up to 2.6 g/l) and good precision. Within-run CVs of 6.6% and 1.3% and between-day CVs of 10.9% and 1.1% were observed at mean protein concentrations of 0.16 g/l and 1.96 g/l, respectively. In addition, rat urine protein results from this method correlated well (r2 = 0.998, n = 40) with a Coomassie Brilliant Blue method (QuanTtest Blue, Quantimetrix Corporation). No significant or unexpected interferences were encountered with this method. We conclude that the automated pyrogallol red-molybdate method is an acceptable and practical alternative to the Coomassie Brilliant Blue method for the quantitation of urine protein in rats.     

Inadequate cortical feature maps: a neural circuit theory of autism

The autistic syndromes are caused by neurological dysfunctions. The capacity of autistic individuals to form representations of previous sensory impressions, useful for the processing of present information, is impaired. Self-organizing feature maps are mathematical models of cortical feature maps and may be used to simulate cortical processing. Dysfunctional self-organization, resulting in disability to extract features from stimuli, is proposed as a neural circuit theory of autism. The nature and a possible cause of dysfunction self-organization are examined. It is shown that impaired feature detection is valid for explaining the memory function in autism, the lack of drive for central coherence according to Frith's theory of autism, and a number of impairments from the diagnostic criteria. Unequal levels of impairment of different cortical feature maps can account for the typically uneven intelligence profile of autistic individuals. Excessive inhibitory lateral feedback synaptic connection strengths are presented as one factor impairing the development of feature maps. Strong or excessive inhibitory lateral feedback synaptic connection strengths also cause high sensory discrimination and abnormal sensory responses, both documented in autism. A neural circuit theory for autism has been presented. For a proof of this neural circuit theory neurological investigations are required.     

Inadequate literacy is a barrier to asthma knowledge and self-care

STUDY OBJECTIVES: To determine the relationship of literacy to asthma knowledge and ability to use a metered-dose inhaler (MDI) among patients with asthma. DESIGN: Cross-sectional survey. SETTING: Emergency department and asthma clinic at an urban public hospital. PATIENTS: Convenience sample of 273 patients presenting to the emergency department for an asthma exacerbation and 210 patients presenting to a specialized asthma clinic for routine care. INTERVENTIONS: Measurement of literacy with the Rapid Estimate of Adult Literacy in Medicine, asthma knowledge (20 question oral test), and demonstration of MDI technique (six-item assessment). MEASUREMENTS AND RESULTS: Only 27% of patients read at the high-school level, although two thirds reported being high-school graduates; 33% read at the seventh- to eighth-grade level, 27% at the fourth- to sixth-grade level, and 13% at or below the third-grade level. Mean asthma knowledge scores (+/-SD) were directly related to reading levels: 15.1+/-2.5, 13.9+/-2.5, 13.4+/-2.8, 11.9+/-2.5, respectively (p < 0.01). Patient reading level was the strongest predictor of asthma knowledge score in multivariate analysis. Poor MDI technique (< or =3 correct steps) was found in 89% of patients reading at less than the third-grade level compared with 48% of patients reading at the high-school level. In multivariate regression analyses, reading level was the strongest predictor of MDI technique. CONCLUSIONS: Inadequate literacy was common and strongly correlated with poorer knowledge of asthma and improper MDI use.     

Inadequate treatment with HMG-CoA reductase inhibitors by health care providers

PURPOSE: To determine if patients treated with HMG-CoA reductase inhibitors have their LDL cholesterol levels at or below the levels recommended by the National Cholesterol Education Program (NCEP) and if patients on these medications are monitored for potential toxicity. PATIENTS AND METHODS: Ninety patients from the VA Medical Center in San Francisco were randomly selected in this retrospective analysis. All patients were taking a HMG-CoA reductase inhibitor as monotherapy for treatment of high blood cholesterol for a minimum of 1 year. Medical charts and laboratory and pharmacy computer databases were utilized to gather information regarding the patients' medical history, treatment history, relevant laboratory tests, and medication refill profile. RESULTS: The majority of patients, 73%, were secondary prevention patients. Only 33% of the 90 subjects met the LDL cholesterol goal recommended by the NCEP. For the secondary prevention patients, only 24% met goal LDL. Even when the stringency of the NCEP guidelines was reduced by 20% (goal LDL < 120 mg/dL), 50% of the secondary prevention patients were still inadequately treated. Only 2 of the 90 patients were on maximal dosage regimens. Sixty-seven percent of patients had annual lipid panels and 49% had annual liver panels. Forty-five percent of patients followed by nonphysicians met goal LDL while only 29% and 31% of patients followed by attending physicians and residents/fellows met goal LDL, respectively. In addition, patients followed by nonphysicians were monitored more closely for efficacy and toxicity of the medications. CONCLUSIONS: Based on the current NCEP recommendations, patients on monotherapy with HMG-CoA reductase inhibitors are often inadequately treated. Only 33% of the patients evaluated at our institution were at or below the NCEP recommended LDL cholesterol levels and less than half of the patients were adequately monitored for hepatotoxicity.     

Zeta potential measurement and particle size analysis for a better understanding of urinary inhibitors of calcium oxalate crystallization

To better understand urinary inhibitors of calcium oxalate crystallization, both zeta potential measurement and particle size analysis were chosen to illustrate: (1) the potential therapeutic efficacy of G872, a semi-synthetic sulfated polysaccharide, in stone prevention; and (2) the relative contribution of various urinary fractions ?e.g., ultrafiltered urine (UFU), Tamm-Horsfall protein (THP), urinary polyanions precipitated with cetylpyridinium chloride (CPC), urinary macromolecular substances with different concentration ratios (UMS10,50,90 and UMS'10,50,90) and THP-free urine (THPFU)? to total urinary inhibitory activity. The results showed: (1) addition of G872 significantly enhances urinary inhibitory activity and negative zeta potential values; (2) re-addition of the CPC to UFU completely restores urinary inhibitory activity; and (3) artificial urines prepared by mixing UMS'10,50,90 from THPFU with UFU differed in inhibitory activity from that prepared by mixing UMS10,50,90 from a pooled normal urine with UFU. Based on these experimental results, the following speculations can be made: (1) normal human urines are considered to be a protective colloidal system; (2) urinary inhibitory activity originates mainly from CPC and/or UMS; (3) normal THP is a protective material to maintain urinary inhibitory activity; and (4) mutual interaction between urinary inhibitors may change the total urinary inhibitory activity.     

Inadequate control of lipid levels in patients with a previous myocardial infarction

AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid-modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated.