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Background: Manganese toxicity can occur as a complication of home parenteral nutrition (HPN). Patients can present with Parkinson disease-like symptoms. Preparations of trace elements (TEs) in parenteral nutrition (PN) generally provide amounts in excess of requirements. Our previous review observed 60% of adult HPN patients had high whole-blood manganese levels. Multi-TE (MTE) solutions were subsequently removed from all HPN formulations in January 2015. The aim of this evaluation was to determine whole-blood concentrations of manganese in adult patients receiving HPN to establish whether levels are now maintained within the normal reference range., Methods: A retrospective review of whole-blood manganese levels in all patients receiving HPN between January 2018 and January 2019 from 1 hospital site was carried out., Results: 100 patients were included in the review (59 female and 41 male). Normal whole-blood manganese levels (73-219 nmol/L) were observed in 70% of patients and elevated levels (>219 nmol/L) in 30% of patients. In the patients with elevated levels, 57% had not received manganese supplementation for at least 1 year prior to manganese being measured. Markers of cholestasis were similar between the 2 groups., Conclusions: Incidence of elevated whole-blood manganese concentrations in patients receiving HPN decreased from 60% to 30% upon discontinued use of an MTE solution. Elevated levels remain a concern despite patients being prescribed "manganese-free" PN. Patients receive this TE in amounts adequate to meet requirements through contamination and dietary intake alone, suggesting additional parenteral supplementation of manganese is not required., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Background: Manganese (Mn) is included in current premixed multiple trace element (TE) additives for home parenteral nutrition (HPN). However, there is a risk of oversupplementation of Mn due to contamination from PN additives. Oversupplementation can produce Mn toxicity with neurologic symptoms and abnormalities on brain magnetic resonance imaging (MRI). In 2009, we reported that whole-blood Mn levels were above the upper limit of normal in 16 HPN patients, with 81% having MRI findings. Subsequently, we removed Mn supplementation from all our HPN patients. We present a 5-year follow-up here., Methods: This is a prospective cohort study on 11 of the surviving 16 patients on HPN. All patients had Mn removed from PN and had yearly monitoring of blood Mn levels. Eight patients had a repeat MRI to evaluate for resolution of basal ganglia deposits. Patient demography, clinical history, and bloodwork were recorded., Results: Five of 6 patients who initially had elevated Mn levels had normal levels on follow-up. All patients who had Mn levels measured serially had a decrease in levels; the mean percent decrease of Mn was 38.1% (range, 10.1%-53.8%). Two patients had elevated Mn despite the absence of supplementation. Six of 8 patients who had repeat MRIs had complete resolution abnormalities., Conclusions: Removal of Mn as an additive in HPN solutions resulted in resolution of MRI abnormalities in most patients. Over 5 years, all patients except for 1 maintained normal blood Mn levels. Therefore, Mn levels should be monitored and supplementation be individualized., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Home parenteral nutrition (HPN) has benefited countless patients since its initiation almost 5 decades ago. Over time, HPN has been found to be associated with various complications, including metabolic disorders. Metabolic complications can be grouped into short-term (eg, fluid imbalance, electrolyte disturbances, glucose abnormalities) and long-term (eg, hepatobiliary disorders, metabolic bone disease, iron deficiency anemia, manganese toxicity) categories. There are a number of treatment options for each complication. It is important to evaluate the entire clinical picture prior to initiating an intervention and use evidence-based interventions when available. A dedicated multidisciplinary team is best suited to prevent and manage complications when they are identified.

Background: Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I)., Method: A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN., Results: Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation., Conclusions: Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.

Background and Purpose: There is limited knowledge regarding the long-term outcome of the methcathinone/manganese-induced movement disorder. Our purpose was to define prognosis in intravenous methcathinone abusers affected by this distinctive disorder attributed to manganese (Mn) toxicity. Also, neuropathology from a globus pallidus region biopsy from a former user is reported., Methods: Eighteen methcathinone abusers were categorized as active (five), discontinued (four) or former (nine) users. They were reassessed after a median of 32.5 months (range 3.4-59.6) clinically, on rating scales, and with MRI and blood Mn levels. The biopsy was examined ultrastructurally., Results: Overall the group showed a slight tendency to deterioration at follow-up on clinical assessment of motor functioning, especially the active users. No significant change occurred on parkinsonian rating scale reassessment. Significant reduction in Mn levels occurred in former users, and decreased T1-weighted hyperintensity on basal ganglia MRI occurred in 3 of 4 former and 2 of 3 discontinued users, despite lack of clinical improvement. The biopsy consisted of white matter showing decompacted myelin sheaths and frequent abnormalities of mitochondria., Conclusions: No improvement in this Mn-induced movement disorder occurs after cessation of methcathinone abuse despite improvement of Mn blood levels and/or MRI abnormalities. Ultrastructural abnormalities in a former user confirm structural damage to white matter is associated with the disorder. Methcathinone/Mn toxicity is an important, disabling and permanent medical sequel of intravenous drug abuse in the former Soviet Union., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO2 -RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with MIO@SiO2-RITC nanoparticles exhibited enhancement of the T1 contrast in brain tissue, in particular a time-delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO2-RITC nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, T1-weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, T2*-weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle-based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long-term study of neural function., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Long-term parenteral nutrition (PN) can be associated with micronutrient deficiency or toxicity depending on supplementation. Recently, hypermanganesemia and potential neurological toxicity were reported. The aim of this study was to assess the effect of manganese supplementation in a sample of patients on long-term PN receiving manganese (Mn) as part of a multi-trace element (TE) supplement., Methods: A convenience sample of 16 patients underwent clinical and blood biochemical measurements as well as magnetic resonance imaging (MRI) of the brain. Descriptive statistics were performed., Results: The mean daily Mn supplementation was 7.28 ± 0.97 µmol/d (400 ± 53 µg/d), which was within the American Medical Association Nutrition Advisory Group guidelines of 2.73-14.56 μmol/d (150-800 µg/d) but exceeded the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) 2002 recommendations of 1.09-1.82 µmol/d (60-100 µg/d). The mean whole blood Mn level was 1.38 ± 0.29 times the upper limit of normal (ULN), and 8 of 14 patients with blood measurements had Mn levels above ULN. On MRI, 81% of patients had high signals on T1-weighted images assumed to be Mn deposits in their basal ganglia. Two patients with positive MRI (15%) had a clinical diagnosis of Parkinson disease. Multiple neuropsychiatric complaints were reported, including depression (66%), lack of concentration (42%), memory disturbances (17%), and gait instability (8%)., Conclusion: These results suggest that Mn status is elevated in these patients. Manganese supplementation should be used with caution in patients receiving long-term PN, and attention should be paid to the Mn content of multi-TE supplements.

Background and Purpose: Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users., Methods: During 2006-2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 9-70 (20 ± 15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects., Results: The average total UPDRS score was 43 ± 21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ± 3.8 ppm) than controls (0.82 ± 1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ± 6.2 ppb) in active than in former users (5.6 ± 1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum., Conclusion: Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Manganese ions (Mn(2+) ) enter viable myocardial cells via voltage-gated calcium channels. Because of its shortening of T(1) and its relatively long half-life in cells, Mn(2+) can serve as an intracellular molecular contrast agent to study indirect calcium influx into the myocardium. One major concern in using Mn(2+) is its sensitivity over a limited range of concentrations employing T(1)-weighted images for visualization, which limits its potential in quantitative techniques. Therefore, this study assessed the implementation of a T(1) mapping method for cardiac manganese-enhanced MRI to enable a quantitative estimate of the influx of Mn(2+) over a wide range of concentrations in male Sprague-Dawley rats. This MRI method was used to compare the relationship between T(1) changes in the heart as a function of myocardium and blood Mn(2+) levels. Results showed a biphasic relationship between ΔR(1) and the total Mn(2+) infusion dose. Nonlinear relationships were observed between the total Mn(2+) infusion dose versus blood levels and left ventricular free wall ΔR(1) . At low blood levels of Mn(2+) , there was proportionally less cardiac enhancement seen than at higher levels of blood Mn(2+) . We hypothesize that Mn(2+) blood levels increase as a result of rate-limiting excretion by the liver and kidneys at these higher Mn(2+) doses., (Copyright © 2010 John Wiley & Sons, Ltd.)

We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year-old girl born to consanguineous parents. Blood manganese levels were >3000 nmol/L (normal range <320 nmol/L) and MRI revealed signal abnormalities of the basal ganglia consistent with manganese deposition. An older brother with the same phenotype died at 18 years, suggesting a potentially lethal, autosomal recessive disease. This disorder is probably caused by a defect of manganese metabolism with the accumulation of manganese in the liver and the basal ganglia similar to the copper accumulation in Wilson disease. In order to assess the genetic basis of this syndrome we investigated two candidate genes: ATP2C2 and ATP2A3 encoding the manganese-transporting calcium-ATPases, SPCA2 and SERCA3, respectively. Genotyping of the patient and the family for microsatellite markers surrounding ATP2C2 and ATP2A3 excluded these genes. The patient was found to be heterozygous for both gene loci. Despite the unknown pathophysiology, we were able to develop a successful treatment regime. Chelation therapy with disodium calcium edetate combined with iron supplementation is the treatment of choice, lowering blood manganese levels significantly and improving clinical symptoms.

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing <25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighing > or =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin level > or =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levels > or =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.

The authors report on a 32-year-old man with common variable immunodeficiency and high signal intensity in basal ganglia on T1-weighted images. No signal alteration on T2-weighted and postcontrast images was observed. The patient had elevated levels of manganese in the serum. The authors conclude that the unusual hyperintensity in the basal ganglia area on T1-weighted images resulted from manganese deposition due to liver dysfunction.

Background and Methods: The administration of trace elements is thought to be needed in patients receiving long-term parenteral nutrition. Recently, manganese intoxication or deposition was documented in such patients. We report two cases of manganese intoxication during intermittent parenteral nutrition including manganese. Manganese had been administered for 4 years at a frequency of one or two times per week in one case and for 5 years at a frequency of one or two times per month in the other case. Both cases showed mild symptoms with headache and dizziness. One case had mild hepatic dysfunction and the other did not. The whole-blood manganese level increased in one case, but not in the other case. T1-weighted magnetic resonance images revealed symmetrical high-intensity areas in basal ganglia and thalamus in both cases. After the administration of manganese was stopped, these symptoms all disappeared and the magnetic resonance images abnormalities gradually improved in both patients. Mild long-term manganese intoxication is thus considered to occur regardless of the frequency of using a manganese supplement., Conclusions: Patients should be carefully monitored when receiving long-term parenteral nutrition including manganese, even when the manganese dose is small and the frequency of receiving a manganese supplement is low.

Background: Extrapyramidal syndrome and alterations in brain magnetic resonance images are described in patients undergoing long-term home parenteral nutrition (HPN) and in cholestatic patients. These abnormalities have been correlated to basal ganglia manganese (Mn) accumulation., Methods: A longitudinal 1-year study was conducted on 15 patients undergoing HPN (median duration, 3.8 years; range, 1.7-10; median Mn parenteral supplementation, 0.1 mg/d). Whole-blood, plasma, intra-erythrocytes, and urinary Mn concentrations were measured and brain magnetic resonance was performed at the beginning (time 0) and after 1 year of Mn intravenous supplementation withdrawal (time 1). No patients showed psychosis, extrapyramidal syndrome, or cholestasis., Results: At time zero, 10 of 15 patients (67%) showed paramagnetic accumulation on cerebral magnetic resonance images; at time 1 there was a reduction of cerebral Mn accumulation. In all patients, blood-Mn levels were significantly reduced after 1 year of Mn intravenous supplementation withdrawal., Conclusions: Patients receiving long-term HPN showed an elevated incidence of alterations in brain magnetic resonance images with a median Mn intravenous supplementation of 0.1 mg/d. Mn supplementation withdrawal significantly decreased metal levels in blood and brain storage. We noticed that the intra-erythrocyte Mn level was a good index of Mn status.

Background: Manganese is one of the trace elements that is routinely administered to total parenteral nutrition (TPN) patients. The recommended daily IV dosage ranges from 100 to 800 MICROg. We have used 500 microg daily. Recent reports have suggested neurologic symptoms seen in some patients receiving home parenteral nutrition (HPN) may be due to hypermanganesemia. Therefore, HPN patients and some short-term inpatients receiving TPN were studied to ascertain the relationship between dose and blood levels., Methods: Red blood cell manganese levels were obtained by atomic absorptiometry., Results: The levels in 36 hospitalized, short-term patients obtained within 48 hours of initiating TPN were all normal. The 30 patients receiving TPN from 3 to 30 days had levels that ranged from 4.8 to 28 microg/L (normal, 11 to 23 microg/L). Two patients had abnormal levels, at days 14 and 18. Fifteen of the 21 patients receiving inpatient TPN or HPN for 36 to 5075 days had elevated Mn levels. Only one patient with hypermanganesemia, an inpatient, had abnormal biochemical liver tests (bilirubin and alkaline phosphatase). One of the patients with a high level had some vestibular symptoms attributed to aminoglycoside use and had increased signal density in the globus pallidus on T1-weighted images on magnetic resonance imaging (MRI). A second patient with Mn levels twice normal had no neurologic symptoms, but had similar MRI findings. A third had some basal ganglia symptoms, confirmed by a neurologic evaluation, seizures, and very high Mn levels. The MRI showed no signal enhancement, but motion artifacts limited the study technically., Conclusions: Hypermanganesemia is seen in HPN patients receiving 500 microg manganese daily and may have resulted in some neurologic damage in three patients. Hypermanganesemia is sometimes seen after a short course of TPN in inpatients, as early as 14 days. Patients should be monitored for hypermanganesemia if they receive Mn in their TPN for >30 days. A 500 microg/d dose of Mn is probably excessive, and 100 microg/d should probably never be exceeded. Mn should be eliminated from the solution if the Mn level is elevated and should not be readministered unless the level returns to normal or subnormal. Mn should not be supplemented if the patient has liver disease with an elevated bilirubin.

Background: Hypermanganesemia and cholestatic liver disease are both recognized complications of long-term IV nutrition. Manganese is primarily excreted in bile, and recent studies have indicated that manganese toxicity may play a role in the pathogenesis of IV nutrition-associated cholestasis., Methods: Whole blood and plasma manganese concentrations were measured in patients receiving long-term home IV nutrition (HIN, n = 30). Whole blood manganese concentrations also were measured in patients with chronic liver disease (CLD, n = 10) and control subjects (n = 10)., Results: Whole blood manganese concentrations of all CLD patients were within the reference interval (73 to 210 nmol/L) and were not different from those of the control group (151 +/- 44 nmol/L, CLD vs 155 +/- 35 nmol/L, control; not significant), despite the presence of cholestasis. In contrast, whole blood manganese concentration was increased (>210 nmol/L) in 26 patients, and plasma manganese concentration increased (>23 nmol/L) in 23 of the patients receiving HIN. None of the patients exhibited neurologic signs of manganese toxicity. There was no correlation between whole blood manganese concentrations and markers of cholestasis, IV manganese intake, or duration of HIN. However, plasma manganese concentration correlated both with average weekly IV manganese intake (r = .44, p = .02) and with gamma-glutamyl transferase (r = .43, p = .02) and alkaline phosphatase activities (r = .55, p = .003)., Conclusions: Cholestatic liver disease does not appear to contribute to increased whole blood manganese concentrations in patients not receiving HIN. Plasma manganese concentrations in patients receiving HIN reflect recent manganese exposure and impaired excretion where cholestasis is present. The lack of relationship between plasma and whole blood manganese concentrations suggests that factors other than manganese intake and excretion affect intracellular concentrations.

In this study, hair magnesium (Mg), zinc (Zn), copper (Cu), and manganese (Mn) levels, and serum Zn and Mg levels were measured by atomic absorption spectrophotometer in patients with epilepsy (n = 33) and healthy subjects (n = 21), and results obtained were statistically compared. The mean hair Cu, Mg, and Zn levels of epileptic patients were significantly lower than the levels of control subjects. There was no significant difference between epileptic patients and control subjects in respect to the mean Mn levels. Mean serum Mg levels in epileptic patients showed significant difference, but serum Zn levels were similar among both groups. When the effects of anticonvulsant therapy on Cu, Zn, Mn, and Mg in the hair, and Mg and Zn in the serum were analyzed in epileptics, there was no significant difference between the patients with or without therapy. Likewise, the mean trace element levels in epileptics showed no significant difference according to the type of antiepileptic drug and seizure, and gender. We suggest that the changed element status (Zn, Mg, and Cu) in hair may play an indicator role in the diagnosis of epileptic patients., (Copyright 1999 Lippincott Williams & Wilkins)

Background: Neurologic and radiologic disorders have been reported in patients receiving long-term parenteral nutrition (PN). On the basis of elevated serum manganese levels, some of these abnormalities have been attributed to manganese intoxication. Alterations of the basal ganglia signal intensity on T1-weighted magnetic resonance images (MRIs) have been previously reported, but the precise nature of these alterations remains controversial although the deposition of manganese has been suggested in patients with chronic hepatic encephalopathy due to liver failure., Methods: We report the case of a patient who was receiving PN and exhibited a chronic cholestasis. Neurologic disorders appeared after several months of PN, when a hypersignal in the basal ganglia and white matter was found on T1-weighted MRIs of the brain in association with elevated serum and manganese levels., Results: Elevated autopsic concentrations of manganese were found in the radiologic abnormal cerebral areas., Conclusions: Our observation is the first demonstration of a relationship between high intracerebral manganese levels, radiologic abnormalities, and neurologic disorders during long-term PN. Moreover, serum manganese levels are not a good indicator of cerebral levels. In fact, in our patient, serum manganese levels returned to normal, whereas those of cerebral manganese remained increased.

Background: Manganese deposition was suspected in a pediatric patient who received long-term total parenteral nutrition. T1-weighted magnetic resonance images revealed high intensity areas in the globus pallidus. This study was designed to clarify if these abnormal findings were related to manganese deposition and clinical neurological manifestations., Methods: Whole-blood manganese concentrations were measured during manganese supplementation to total parenteral nutrition and after 5 months without manganese. Magnetic resonance images were also examined on each occasion and compared with the blood level of manganese., Results: The whole-blood manganese level during supplementation was 135 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was 20 micrograms/L after a manganese-free period of 5 months. Accompanied with normalization of manganese level, abnormal high intensity lesions in the globus pallidus on T1-weighted images also disappeared. No neurological manifestation related to the high manganese level was recognized., Conclusions: It is probable that the high manganese level was elicited by manganese supplementation to total parenteral nutrition. This high manganese condition was confirmed by the measurement of whole-blood manganese level, which was associated with the abnormal high intensity lesions on T1-weighted magnetic resonance images.

Manganese is vital in human nutrition. When oral intake is precluded, the recommended parenteral supplementation is 0.15 to 0.8 mg/day. Manganese is excreted primarily in the bile; during cholestasis, serum manganese levels may rise, and manganese toxicity ensue. Neuropsychiatric symptoms are prominent. Phenothiazine-derivative drugs may potentiate manganese toxicity. Serum or whole blood manganese levels should guide manganese therapy in jaundiced patients.

Blood chemistry, nutrition, productivity and fertility were monitored and their interrelationship examined in groups of cows from 15 commercial dairy herds. Plasma urea, albumin, glucose, non-esterified fatty acids (NEFA), acetone, calcium, magnesium, inorganic phosphorus (IP), blood copper, haemoglobin and packed cell volume were examined in relation to the intakes of starch equivalent (SE) digestible crude protein (DCP), calcium, phosphorus, magnesium, sodium, potassium, copper and manganese. The most consistent correlations were found for the regressions of SE intake as a percentage of requirements (I/R per cent) on plasma non-esterified fatty acids, the ratio of SE intake over DCP intake on plasma urea, DCP I/R per cent on plasma urea and phosphorus I/R per cent on plasma IP, but factors other than nutrition accounted for a large part of the variation in all cases. The mean plasma glucose concentration within +/- three days before or after first service of cows which held was higher than that of cows which returned, but the difference was only approaching significance at the 5% level and it is doubtful whether it could be of practical value. No other differences in blood component levels were demonstrated for first or second service. It is concluded that, within the nutritional ranges encountered, the levels of the selected blood components did not show a consistent relationship to nutrient balance or potential fertility. In this context a multiple analytical scheme employing these components would appear to be of limited value, particularly if samples are taken on only one occasion. The technique is more appropriately regarded as an aid to the conventional approach involving the examination of feeding systems and feedstuffs, herd records, management and clinical conditions.

Manganese is excreted primarily via the bile. The objective of this study was to determine if plasma Mn concentrations were elevated in infants and children fed intravenously who developed cholestatic liver disease. An additional aim was to determine the Mn content of intravenous solutions. The study included nine subjects with normal liver function (group A) and five subjects who developed cholestatic liver disease while fed intravenously (group B). Serum total bilirubin in group B had been elevated for 1 wk to 5 months prior to entry into this study. Mean plasma Mn for group A was 0.79 +/- 0.18 ng/ml, which was similar to that for adult controls. The mean for group B was 3.06 +/- 2.07 ng Mn/ml which was significantly higher (p less than 0.005). Plasma Mn was correlated positively with serum total bilirubin (r = 0.874, p less than 0.001). In four group B subjects studied longitudinally, plasma Mn declined. This decline was associated with a decline in serum total bilirubin in one subject and both a decline in serum total bilirubin and a reduction in, or a cessation of, supplemental intravenous Mn in two subjects. In the fourth subject, hepatic dysfunction remained severe, but plasma Mn declined to a near normal value after discontinuing supplemental intravenous Mn. The mean Mn contamination in the final intravenous infusate was 5.1 +/- 2.1 micrograms Mn/1. In conclusion, it is recommended that plasma Mn concentrations be monitored in patients fed intravenously who have evidence of cholestatic liver disease. If monitoring is not feasible, Mn supplements should be withheld.

Some factors affecting the performance of paramagnetic ions as contrast agents for proton NMR imaging have been studied. It is demonstrated that the relaxation rate of an aqueous solution of the ion is not reliably predicted by its magnetic moment, but that significant relaxation enhancement may result when the ion is complexed with large molecules, which increases the dominant correlation time. This enhancement in turn can be altered by factors such as pH and competition for binding. Chelation of the paramagnetic ion, which may be implemented to lower its toxicity, can considerably reduce its efficacy by not only limiting its access to water but also by preventing the enhancement from associations and macromolecules. For manganese the ratio T1/T2 is a useful parameter which is sensitive to the degree of metal binding. These features of paramagnetic relaxation enhancement in tissue are demonstrated in a series of experiments on systems consisting of blood components and manganese.