bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reference data for cerebrospinal fluid and the utility of amino acid measurement for the diagnosis of inborn errors of metabolism
Authors: Jones CM , Smith M , Henderson MJ 
Published: December 2005

Background: Cerebrospinal fluid (CSF) amino acid analysis is fundamental to the investigation of several inherited metabolic diseases, particularly those presenting with unexplained seizures. CSF glycine measurement is often crucial to the diagnosis of glycine encephalopathy (GE), low CSF serine concentrations are characteristic of 3-phosphoglycerate dehydrogenase deficiency (3-PGDD) and the presence of sulphocysteine is pathognomonic of sulphite oxidase deficiency (SOD), and a vital clue to molybdenum cofactor deficiency (MCD). Limited information is available in the literature on reference values of amino acids in CSF during infancy and CSF samples from healthy individuals are not easily obtained. Methods: In order to establish paediatric CSF amino acid reference ranges, we performed a retrospective analysis of all quantitative CSF amino acid data collected in our laboratory over a five-year period. Amino acid analysis was performed using ion-exchange chromatography on a Biochrom-20 amino acid analyser with ninhydrin detection. CSF samples were collected from infants undergoing investigation for unexplained seizures. Results: About 18 of the 95 samples received were excluded from the reference data-set; one was from a patient in whom a diagnosis of GE was confirmed by enzyme analysis, one was from a patient with CSF sulphocysteine of 19 μmol/L in whom a diagnosis of SOD was confirmed by enzyme analysis; the remaining 16 were clearly bloodstained ( n = 4) or xanthochromic ( n = 12). Frequency of distribution analysis revealed that concentration values for each amino acid demonstrated a right-skewed distribution which was not normalized by log transformation. Data were therefore analysed using non-parametric descriptive statistics and reference ranges were defined by the 2.5th and 97.5th centile limits. Conclusions: Our reference data were derived from 77 CSF samples taken from 77 infants. Median CSF glycine concentration was 9 μmol/L with a reference range of 3-19 μmol/L. For serine, the median CSF concentration was 52 μmol/L with a reference range of 25-105 μmol/L. Sulphocysteine was not normally present in detectable quantities (<1 μmol/L).
Analytical and physiological factors affecting the interpretation of serum testosterone concentration in men
Authors: Diver MJ 
Published: December 2005

Most hospital laboratories estimate the concentration of total circulating testosterone using a non-extraction method on an automated multi-channel immunoassay analyser supplied by a small number of multi-national diagnostic companies. Although these platforms offer advantages of quick turnaround times, small volume sampling and random access analysis, proficiency testing schemes suggest the quality of results produced remains similar to that of the early manual radioimmunoassay. An estimate of the bioavailable, non-sex hormone binding globulin (SHBG) bound fraction of circulating testosterone, be that the free or the free plus albumin-bound, may be a better index of gonadal status than total testosterone alone, especially when a borderline hypogonadal level of total testosterone is found, and may avoid misclassification of hypogonadal or eugonadal men. Free or bioavailable testosterone may be calculated or measured. The free androgen index may not give a true reflection of androgen status in men. In the interpretation of serum testosterone concentrations with results >40 nmol/L, the possibility of exogenous administration or abuse needs to be considered. The marked diurnal rhythm in total testosterone should also be taken into account. There may be a diminution of testosterone secretion with advancing age, but the great majority of older men have a circulating total testosterone concentration well within the accepted reference intervals established for younger men. As testosterone concentration may fluctuate markedly both seasonally and from day to day, it may be judicious to measure levels on more than one occasion. Provided that estimates of serum testosterone are unequivocally eugonadal (12.5-40 nmol/L) or hypogonadal (<7.0 nmol/L), results produced by routine automated immunoassays will in all probability give a satisfactory assessment of androgen status in men. Routine biochemical assessment of gonadal function in men should include measurement of early morning luteininzing hormone, follicle stimulating hormone, prolactin and SHBG together with total testosterone, and if necessary some estimate of bioactive testosterone.
Can lithium-heparin plasma be used for protein electrophoresis and paraprotein identification?
Authors: Davison Andrew S , Darn Simon M , Sodi Ravinder 
Published: December 2005

Introduction: Lithium-heparin plasma is the most commonly used sample type in many hospitals, but it has been suggested that it is not suitable for protein electrophoresis due to the presence of fibrinogen, which can potentially mask a paraprotein band or be misconstrued as one. Here we aimed to demonstrate that lithium-heparin plasma samples could be used for protein electrophoresis and paraprotein typing without or with ethanol treatment to remove the fibrinogen. Method: A lithium-heparin sample from a patient with IgG λ, IgG κ, IgA λ and IgA κ myeloma, a non-specific polyclonal increase and a serum control were treated with ethanol prior to protein electrophoresis. Immunofixation electrophoresis was undertaken to investigate the effect of ethanol treatment on immunoglobulin and light chains. Nephelometry was undertaken to investigate whether ethanol treatment affected the quantification of IgG levels. Densitometric evaluation of proteins after electrophoresis was used to study whether ethanol treatment affected other serum proteins. An audit was also undertaken to ascertain the magnitude of the potential interference from the fibrinogen band in heparinized samples. Results and conclusions: Ethanol treatment significantly but incompletely removed the fibrinogen in lithium-heparin plasma samples and did not affect the integrity of any of the proteins investigated. Even without ethanol treatment, lithium-heparin plasma can be used for protein electrophoresis and paraprotein identification as the instances of interference between fibrinogen and paraproteins was low (2.3%). In rare cases where there is uncertainty or ambiguity, immuno-fixation electrophoresis is recommended. This report has implications in terms of reducing costs and turn-around time as it prevents the need for requesting another serum sample from patients. This may be one step towards a universal sample for all tests.
Macroprolactin(s): composition and reactivity in immunoassays and laboratory interpretation of results of an unusual patient serum
Authors: Ellis AR , Fahie-Wilson M , Axcell M , Sands K , Hill RP 
Published: December 2005

Background: Macroprolactin is a high molecular mass complex of prolactin that may be the cause of elevated serum prolactin as determined by immunoassay. The composition of macroprolactin and its reactivity in immunoassays are variable but the complex has minimal bioactivity in vivo. Hyperprolactinaemia due to unrecognized macroprolactinaemia can lead to misdiagnosis and mistreatment. Methods: Serum from a patient with an unusual pattern of immunoreactivity was distributed to three users of each of the most popular immunoassays represented in the UK National External Quality Assessment Scheme (NEQAS) for prolactin. Clinical details were provided and participating centres were invited to investigate the prolactin content of the specimen according to their local protocol, and to comment on their results. The nature of the macroprolactin in the specimen was investigated in detail by gel filtration chromatography of the native serum and of the serum after adsorption of IgG with protein A, and by affinity chromatography with concanavalin A. Results: Gel filtration studies revealed two peaks of macroprolactin in this serum. These macroprolactins were shown to be different in their IgG content and degree of glycosylation. All eight immunoassays reacted strongly with the macroprolactin present. The majority (78%) of centres that interpreted their results either demonstrated the presence of macroprolactin in the specimen, or suggested it as a likely cause of the hyperprolactinaemia. However, two centres inappropriately excluded macroprolactinaemia as the cause of the elevated prolactin, and a further two did not consider it at all. Data from previous UK NEQAS distributions (between 1996 and 2003) of macroprolactin containing sera are presented which suggest that the frequency of recognition of macroprolactin as a possible cause of hyperprolactinaemia has increased over time. Conclusions: Very high molecular mass forms of prolactin and the presence of multiple molecular mass forms, as detected in the case presented here, are uncommon. Also, the pattern of immunoreactivity reported in this specimen was unusual as most macroprolactins studied previously react less strongly in, for example, the Bayer ADVIA Centaur assay compared to the Roche E170 assay. Both peaks of macroprolactin in this serum reacted in all assays tested. This case highlights the variable nature and immunoreactive behaviour of macroprolactin species.
Second-trimester Down's syndrome serum screening: double, triple or quadruple marker testing?
Authors: Harrison G , Goldie D 
Published: December 2005

Background: The recommendations of the UK National Screening Committee (NSC) are based on the findings of the Serum, Urine and Ultrasound Screening Study (SURUSS). Our study sought to establish if the SURUSS findings, in terms of detection rates (DR) and false-positive rates (FPR) for various second-trimester marker combinations, could be replicated in a local setting. Methods: We investigated the effects of adding inhibin-A and unconjugated oestriol to our existing double test protocol. This retrospective study examined 1000 control pregnancies and 128 affected pregnancies. Results: The inhibin-A method was associated with considerable assay drift and very marked within-batch imprecision (intrabatch percent coefficient of variation [CV] = 17%). At a cut-off of 1 in 250, the quadruple test showed a DR of 72%, the triple test 70% and the double test 63%. There were no significant differences between the FPRs for any of the combinations, which were all between 6.6% and 7.0% for a 1 in 250 cut-off. Conclusions: In our view, the current inhibin-A assay is unacceptable as a screening marker due to poor assay performance. We have reviewed the NSC benchmark programme outcomes, and would suggest that the 2005 target of a DR of at least 60% with an FPR of less than 5% is achievable using triple testing in the second trimester in conjunction with universal scan dating. Our results suggest that the April 2007 target of a DR of 75% with an FPR of less than 3% is unachievable using current second-trimester maternal serum screening.
Serotonin Syndrome Induced by Fluvoxamine and Oxycodone
Authors: Karunatilake Harindra , Buckley Nicholas A 
Published: December 2005

Objective:To report a case of severe serotonergic symptoms following the addition of oxycodone to fluvoxamine.Case Summary:A 70-year-old woman developed severe serotonergic features, including confusion, nausea, fever, clonus, hyperreflexia, hypertonia, shivering, and tachycardia, following the addition of oxycodone 40 mg twice daily to fluvoxamine 200 mg/day, easily fulfilling diagnostic criteria for serotonin syndrome. Discontinuation of the offending drugs resulted in resolution of her symptoms over 48 hours, and no other cause of the syndrome was identified. Use of the Naranjo probability scale indicated a probable relationship between the serotonergic symptoms and the addition of oxycodone to fluvoxamine therapy.Discussion:Serotonin syndrome is a serious adverse reaction usually due to interactions with serotonergic drugs. There have been only 3 previous reports involving oxycodone. Most previous reports of serotonin syndrome involving analgesics have been associated with meperidine, dextromethorphan, and tramadol. Unlike these synthetic opioids, however, oxycodone does not inhibit the reuptake of serotonin. In addition, there are a number of other possible pharmacologic mechanisms for the interaction we observed.Conclusions:Monitoring for serotonergic adverse events should be done when oxycodone is given to patients receiving serotonin-reuptake inhibitors.
Neurotoxicity Related to Valganciclovir in a Child With Impaired Renal Function: Usefulness of Therapeutic Drug Monitoring
Authors: Peyrière Hélène , Jeziorsky Eric , Jalabert Anne , Cociglio Marylène , Benketira Abdelkader , Blayac Jean-Pierre , Hansel Sylvie , Margueritte Geneviève , Hillaire-Buys Dominique 
Published: December 2005

Objective: To report a case of neurotoxicity related to antiviral drugs, discuss the involvement of concomitant medications, and document the pharmacokinetics of ganciclovir (administered as valganciclovir) in a child with impaired renal function. Case Summary: A 13-year-old boy with acute lymphoblastic leukemia was treated for cytomegalovirus retinitis with valganciclovir 450 mg every 2 days in the course of hematopoietic stem cell transplantation. Concomitant medication included omeprazole, furosemide, and acetaminophen. During treatment, when creatinine clearance decreased to 20 mL/min, the child presented with acute neurotoxicity, consisting of mental confusion and hallucinations, which resolved when all medications were stopped. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma (3.85 μg/mL) and cerebrospinal fluid (2.6 μg/mL) 48 hours after the last valganciclovir dose. After recovery of neurologic function, valganciclovir was resumed at a lower dosage (225 mg twice a week) with therapeutic drug monitoring and was well tolerated. However, the cytomegalovirus infection was not resolved. The leukemia relapsed, and the patient had terminal renal failure and died. The Naranjo probability scale indicated a probable relationship between valganciclovir and neurotoxicity. Discussion: Drugs taken by this child (acyclovir, valganciclovir, omeprazole) have been reported to induce neurotoxicity, with the pharmacokinetics of the first 2 being altered by renal failure. At the time when acyclovir was first administered, symptoms of neurotoxicity were already apparent. Moreover, plasma concentrations of ganciclovir were very high during the course of the neurotoxicity. Thus, the adverse effects seemed related to an overdosage of valganciclovir and were worsened by the addition of acyclovir. Conclusions: This case is informative because few clinical and pharmacokinetic data are available concerning the use of valganciclovir in children. A study should be performed to determine the proper pediatric dose of valganciclovir with and without renal impairment to prevent the occurrence of adverse effects.
Can Olanzapine Cause Delirium in the Elderly?
Authors: Lim Christine J , Trevino Christina , Tampi Rajesh R 
Published: December 2005

Objective: To report a case of delirium probably caused by the atypical antipsychotic olanzapine in a 74-year-old man with dementia. Case Summary: A 74-year-old white man with a diagnosis of severe dementia of mixed etiology with behavioral disturbances was admitted to an urban teaching hospital for increasing agitation in the context of worsening dementia. Olanzapine 2.5 mg each evening was started for agitation, and the dose was titrated to 5 mg each evening with additional emergent doses. Memantine, an N-methyl-d-aspartate antagonist, was increased from the admission dose of 10 mg/day to 15 mg/day. The patient developed symptoms of delirium on hospital day 4. Neuroleptic malignant syndrome and other causes of delirium were ruled out. Discontinuation of olanzapine resulted in resolution of the delirium. Discussion: Antipsychotic medications are commonly used to treat symptoms of delirium. Atypical antipsychotics are better tolerated in the elderly because of their fewer adverse reactions compared with other antipsychotics. Olanzapine has been successfully used in the treatment of delirium. However, there have been case reports of delirium associated with olanzapine, probably related to its intrinsic anticholinergic effect. Application of the Naranjo probability scale indicated a probable relationship between the onset of delirium and the use of olanzapine in this patient. As of December 1, 2005, this was the second such report of a case in the elderly. Conclusions: Although olanzapine is useful in the treatment of delirium, elderly patients treated with this drug can develop delirium and hence should be closely monitored.
Effects of Steady-State Lasofoxifene on Cyp2D6- and Cyp2E1-Mediated Metabolism
Authors: Moller Robert A , Fisher Jeannine M , Taylor Ann E , Kolluri Sheela , Gardner Mark J , Obach R Scott , Walsky Robert L 
Published: December 2005

Background: Lasofoxifene, a selective estrogen receptor modulator, may be coadministered with other drugs, raising the issue of drug–drug interactions. Objective: Using a 7-day, open-label, sequential study to determine whether lasofoxifene at steady-state concentration affects cytochrome P450–mediated drug metabolism. Methods: Lasofoxifene was tested in 18 postmenopausal women with probe drugs for CYP2E1 and CYP2D6. Changes in CYP2E1 metabolism were measured by the formation clearance of 6-hydroxychlorzoxazone (6-OHCLZ; Clf,6-OHCLZ) following a 250 mg dose of chlorzoxazone in the absence (day 1) and presence (day 6) of lasofoxifene. Changes in the dextromethorphan/dextrorphan urine metabolic ratio (MRDX) measured the effect on CYP2D6 metabolism following a 30 mg dose of dextromethorphan in the absence and presence of lasofoxifene (days 2 and 7). Results: Steady-state lasofoxifene did not affect the formation clearance of 6-OHCLZ or the urinary MRDX. For 6-OHCLZ, the lower boundary (87.12%) of the 90% confidence interval for the ratio (day 6/day 1) of Clf,6-OHCLZ was well above the clinically acceptable ratio of 60%. Both the individual and group mean Clf,6-OHCLZ values were comparable in the absence and presence of lasofoxifene. For MRDX, the upper boundary (129.37%) of the 90% confidence interval for the ratio (day 7/day 2) of MRDX was well below the stipulated ratio of 200%. The individual and mean MRDX values were comparable in the absence and presence of lasofoxifene. Lasofoxifene was well tolerated; adverse events were mild and transient. Conclusions: Lasofoxifene has no effect on CYP2E1- or CYP2D6-mediated drug metabolism and should not affect drugs metabolized by other cytochrome P450 isoenzymes.
Possible Interaction Between Lopinavir/Ritonavir And Valproic Acid Exacerbates Bipolar Disorder
Authors: Sheehan Nancy L , Brouillette Marie-Josée , Delisle Marie-Soleil , Allan James 
Published: December 2005

Objective:To describe a case of exacerbated mania potentially related to an interaction between lopinavir/ritonavir and valproic acid (VPA) and propose a mechanism of action for this interaction.Case Summary:A 30-year-old man with bipolar disorder and HIV initiated treatment with lopinavir/ritonavir, zidovudine, and lamivudine. Prior to beginning therapy with these antiretrovirals, he was receiving VPA 250 mg 3 times daily, with his most recent VPA concentration measured at 495 μmol/L. Twenty-one days after starting antiretroviral treatment, he became increasingly manic. His VPA concentration at admission was 238 μmol/L, a 48% decrease. The daily VPA dose was increased to 1500 mg, and olanzapine was introduced. The VPA concentration following this dose escalation was 392 μmol/L, and the patient improved clinically.Discussion:Fifty percent of VPA is metabolized by glucuronidation, 40% undergoes mitochondrial β-oxidation, and less than 10% is eliminated by the cytochrome P450 isoenzymes. Ritonavir can induce glucuronidation of several medications including ethinyl estradiol, levothyroxine, and lamotrigine. We believe that ritonavir-mediated induction of VPA glucuronidation resulted in a decrease in VPA concentrations and efficacy. An objective causality assessment suggested that the increased mania was probably related to the decrease in VPA concentration and that a possible interaction exists between lopinavir/ritonavir and VPA.Conclusions:A potential interaction exists between VPA and all ritonavir-boosted antiretroviral regimens. Clinicians should monitor patients closely for a decreased VPA effect when these medications are given concomitantly.
Penetration of Ultraviolet Radiation in the Marine Environment. A Review
Authors: Tedetti Marc , Sempéré Richard 
Published: December 2005

ABSTRACTUV radiation (UVR) is a significant ecological factor in the marine environment that can have important effects on planktonic organisms and dissolved organic matter (DOM). The penetration of UVR into the water column is likely to change in the near future due to interactions between global warming and ozone depletion. In this study we report underwater instruments employed for the measurement of UVR and we review data dealing with the depth of UVR penetration in different oceanic areas including the open ocean, Antarctic waters and coastal waters. We provide the 10% irradiance depth (Z10%) for UV‐A and UV‐B as well as for DNA damage effective dose (DNA), which we calculated from the values of diffuse attenuation coefficients or vertical profiles reported in the literature. We observe a clear distinction between open ocean (high Z10%, no variation in the ratio UV‐B/UV‐A), Antarctic waters (increase in the ratio UV‐B/UV‐A during ozone hole conditions) and coastal waters (low Z10%, no variation in the ratio W‐B/UV‐A). These variations in the penetration of WR could lead to differences in the relative importance of photobiologicaVphotochemical processes. We also compare in this study the penetration of UV‐B (unweighted and weighted by the Setlow action spectrum) and DNA damage effective dose.
Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses
Authors: Sellon Debra C. , Monroe Veronica L. , Roberts Malcolm C. , Papich Mark G. 
Published: December 2005

Abstract

Objective—To determine an infusion rate of butorphanol
tartrate in horses that would maintain therapeutic
plasma drug concentrations while minimizing
development of adverse behavioral and gastrointestinal
tract effects.

Animals—10 healthy adult horses.

Procedure—Plasma butorphanol concentrations
were determined by use of high-performance liquid
chromatography following administration of butorphanol
by single IV injection (0.1 to 0.13 mg/kg of
body weight) or continuous IV infusion (loading dose,
17.8 µg/kg; infusion dosage, 23.7 µg/kg/h for 24
hours). Pharmacokinetic variables were calculated,
and changes in physical examination data, gastrointestinal
tract transit time, and behavior were determined
over time.

Results—A single IV injection of butorphanol was
associated with adverse behavioral and gastrointestinal
tract effects including ataxia, decreased borborygmi,
and decreased defecation. Elimination half-life of
butorphanol was brief (44.37 minutes). Adverse gastrointestinal
tract effects were less apparent during
continuous 24-hour infusion of butorphanol at a
dosage that resulted in a mean plasma concentration
of 29 ng/ml, compared with effects after a single IV
injection. No adverse behavioral effects were
observed during or after continuous infusion.

Conclusions and Clinical Relevance—Continuous
IV infusion of butorphanol for 24 hours maintained
plasma butorphanol concentrations within a range
associated with analgesia. Adverse behavioral and
gastrointestinal tract effects were minimized during
infusion, compared with a single injection of butorphanol.
Continuous infusion of butorphanol may be a
useful treatment to induce analgesia in horses. (Am J
Vet Res 2001;62:183–189)