Double-peaked Acetaminophen Concentration Secondary to Intestinal Trauma.

BackgroundReduced gastrointestinal motility can alter the toxicokinetics of acetaminophen poisoning. We report a case of altered acetaminophen toxicokinetics due to delayed gastrointestinal absorption, likely secondary to intestinal trauma/surgery.  Case ReportA 37-year-old woman ingested an unknown amount of acetaminophen and ethanol then stabbed herself in the abdomen. The initial acetaminophen was 1,285.9 µmol/L and the time of ingestion was not known. Intravenous acetylcysteine protocol was started. She developed an ileus post-surgery for the stab wounds. At 31 hours post-presentation, the acetaminophen returned undetectable, and the transaminases were normal. After the resolution of the ileus, repeated acetaminophen peaked at 363.3 µmol/L 52 hours post-admission. At 76 hours post-admission, the acetaminophen was undetectable, and transaminases and coagulation parameters were normal. ConclusionsReduction in gastrointestinal motility secondary to trauma and/or surgery must be considered when determining when to initiate or discontinue treatment as well as how long to monitor acetaminophen concentrations.

Sub-inhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is a Gram-negative bacterium and causative agent of porcine pleuropneumonia. This is a highly contagious disease that causes important economic losses to the swine industry worldwide. Penicillins are extensively used in swine production and these antibiotics are associated with high systemic clearance and low oral bioavailability. This may expose A. pleuropneumoniae to sub-inhibitory concentrations of penicillin G when the antibiotic is administered orally. Our goal was to evaluate the effect of sub-minimum inhibitory concentration (MIC) of penicillin G on the biofilm formation of A. pleuropneumoniae. Biofilm production of 13 field isolates from serotypes 1, 5a, 7 and 15 was tested in the presence of sub-MIC of penicillin G using a polystyrene microtiter plate assay. Using microscopy techniques and enzymatic digestion, biofilm architecture and composition were also characterized after exposure to sub-MIC of penicillin G. Sub-MIC of penicillin G significantly induced biofilm formation of nine isolates. The penicillin G-induced biofilms contained more poly-N-acetyl-D-glucosamine (PGA), extracellular DNA and proteins when compared to control biofilms grown without penicillin G. Additionally, penicillin G-induced biofilms were sensitive to DNase which was not observed with the untreated controls. Furthermore, sub-MIC of penicillin G up-regulated the expression of pgaA, which encodes a protein involved in PGA synthesis, and the genes encoding the envelope-stress sensing two-component regulatory system CpxRA. In conclusion, sub-MICs of penicillin G significantly induce biofilm formation and this is likely the result of a cell envelope stress sensed by the CpxRA system resulting in an increased production of PGA and other matrix components.

Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.(AU)

Treatment for calcium channel blocker poisoning: a systematic review.

CONTEXT: Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. OBJECTIVE: To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. METHODS: Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. RESULTS: The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. CONCLUSIONS: The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.

An Internet snapshot study to compare the international availability of the novel psychoactive substance methiopropamine.

CONTEXT: With the increased use of novel psychoactive substances, there is an increasing availability of these substances from Internet-based suppliers. Methiopropamine, first reported in 2011, is a recreational drug available over the Internet. The aim of this study was to investigate availability and cost of methiopropamine in three different countries: the UK, France, and Canada. METHODS: Using the European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, this study, conducted in June 2013, was undertaken in two different languages: in English (the UK and Canada) and in French (France and Canada), using three Internet searching engines: " google.co.uk ", " google.fr " and " google.ca ". RESULTS: A total of 62 sites were found, most of them were found from the English searches. 45% of the suppliers seemed to originate from the UK. The prices of methiopropamine were comparable between suppliers, no matter which search engine or language was used. The cost of a unit of methiopropamine was inversely related to the purchased quantity, going from 19.49 ± 0.15 GBP per gram for a purchase amount of 500 mg to 3.54 ± 0.13 GBP per gram for a purchase amount of 1 kg. DISCUSSION: The results of the present study demonstrate that the sale of methiopropamine has the potential to reach users across the world. It also appears to support that snapshot studies could be used for toxicovigilance across different countries, by studying the Internet market of novel psychoactive substances. CONCLUSION: To date, snapshot studies, used to monitor the Internet novel psychoactive substances market, have only been undertaken in Europe. We have shown that the flexibility of this methodology enables comparison of the online activity of drug sellers between different countries and continents and that, at least for methiopropamine, the UK is the predominant source for Internet supply.

Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup.

BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). METHODS: After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. RESULTS: Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). CONCLUSION: APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.

Four-hour acetaminophen concentration estimation after ingested dose based on pharmacokinetic models.

INTRODUCTION: The United Kingdom has recently changed the indications for N-acetylcysteine treatment for acetaminophen intoxication. Any ingestion over 75 mg/kg is now referred to the hospital. A model based on pharmacokinetic parameters was developed to predict 4-h acetaminophen concentration for this and other ingested doses. METHODOLOGY: EMBASE and Medline were searched to obtain values for volume of distribution, absorption, and elimination constants and bioavailability for acetaminophen. Four-hour concentrations were calculated for ingestion doses currently recommended for hospital referral in different countries. Calculated plasma concentrations at 4 h for several doses were plotted against the Rumack-Matthew and the United Kingdom treatment lines. RESULTS: Six articles were used for the calculations (4 adult and 2 pediatric). In order to achieve a 4-h acetaminophen concentration of 100 mg/L, doses (mg/kg ± 99.9CI) of 180.5 ± 43.2 for adults and 396.1 ± 115.5 for children were calculated. DISCUSSION: A dose of 75 mg/kg would likely yield a 4-h acetaminophen concentrations well below 100 mg/L. Medical toxicologists and poison information specialists are left without evidence-based guidance for which patients or which ingestion history would now warrant referral to hospital for acetaminophen concentration measurement. Larger toxicokinetic studies in acetaminophen overdose are needed to define ingestion dose for referral to hospital.

Treating acetaminophen overdose: thresholds, costs and uncertainties.

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) modified the indications for N-acetylcysteine therapy of acetaminophen (paracetamol) overdose in September 2012. The new treatment threshold line was lowered to 100 mg/L (662 µmol/L) for a 4 hours acetaminophen concentration from the previous 200 mg/L (1325 µmol/L). This decision has the potential to substantially increase overall costs associated with acetaminophen overdose with unclear benefits from a marginal increase in patients protected from hepatotoxicity, fulminant hepatic failure, death, or transplant. Changing the treatment threshold for acetaminophen overdose also implies that ingestion amounts previously thought not to require acetaminophen concentration measurements would need to be revised. As a result, more individuals will be sent to hospitals in order that everyone with a predicted 4 hours concentration above the 100 mg/L line will have concentrations measured and potentially be treated with N-acetylcysteine. Before others consider adopting this new treatment guideline, formal cost-effectiveness analyses need to be performed to define the appropriate thresholds for referral and treatment.

Impact of a specific program focusing on the psychological autonomy and actualization of potential of residents in a long term care unit.

In 1996, the Sherbrooke Geriatric University Institute introduced a specific health and services program focusing on actualization of potential and psychological autonomy designed for long term care clients presenting few or no cognitive deficits. Some 30 residents who met specific criteria were moved to the same unit. To determine the impact of this specific program on the residents, a study was done using a quasi-experimental design with a control group. The residents in the experimental and control groups were evaluated three times: at the beginning of the program (1996), 1 year (1997) and 2 years (1998) later. The main variables measured were: actualization of potential, psychological autonomy, psychological well-being, satisfaction with care and services, social relations, and perception of the freedom allowed by the institution in regard to their choices and decisions. The results indicate that the new program had no effect on the residents' psychological autonomy, actualization of potential and social relations. In addition, the residents in the experimental group indicated less well-being and less satisfaction than those in the control group. Despite these negative elements, the experimental residents like being and want to stay together on the same unit but seem somewhat concerned about the program objectives. These results led the research team to propose that the program objectives and activities be reviewed.

Acceptor hydroxyl group mapping for human milk alpha 1-3 and alpha 1-3/4 fucosyltransferases.

Two different fucosyltransferases (Fuc-Ts) have been isolated from human milk, an alpha 1-3 Fuc-T and an alpha 1-3/4 Fuc-T, for mapping of their acceptor binding sites. Kinetic studies employing a series of monodeoxygenated and modified Gal beta 1-->4Glc-NAc beta OR and Gal beta 1-->3GlcNAc beta OR acceptor substrates showed that modifications are tolerated at every hydroxyl group in these substrates except for 6-OH of galactose and 3- or 4-OH of N-acetylglucosamine. Deoxygenation at these positions rendered these compounds inactive as both substrates and inhibitors. These essential hydroxyl groups, which are required for recognition of the substrates, are identical to the key polar groups that have previously been reported for cloned FucTs III, IV and V.

The myocardial lesions produced by the potassium channel opener aprikalim in monkeys and rats are prevented by blockade of cardiac beta-adrenoceptors.

Aprikalim is a potent, specific, and selective opener of ATP-sensitive K+ (KATP) channels. By virtue of this pharmacological property, aprikalim affords cardioprotection in experimental models of ischemia/reperfusion injury, and, at higher doses, also causes peripheral or coronary vasodilatation. Direct-acting peripheral vasodilators can cause myocardial lesions, particularly in rats and dogs. However, unexpectedly, aprikalim produced this effect also in monkeys. Thus, the primary aim of this investigation was to assess whether in monkeys these myocardial lesions were the direct or indirect consequence of the vascular effects of aprikalim. Cynomologus monkeys were given the beta-adrenoceptor antagonist nadolol (2 mg/kg p.o., twice daily) for 4 consecutive days. On the third and fourth day of the experiment, they received aprikalim (1 mg/kg p.o.). In another series, two monkeys carrying telemetry transmitters for blood pressure and heart rate measurements were also given aprikalim or its vehicle. Finally, aprikalim (1 mg/kg p.o. for 2 days) or its vehicle was administered to rats which were concurrently treated with the beta-adrenoceptor antagonist atenolol (5 mg/kg s.c.) or its vehicle. In cynomologus monkeys, aprikalim produced focal and multifocal myocardial necrosis of minimal to moderate intensity in or near the papillary muscles of the left ventricle. These effects were abrogated by nadolol. Similarly, necrotic lesions were caused by aprikalim only in those rats which had not been pretreated with atenolol. In monkeys, aprikalim produced a marked and long-lasting decrease in aortic blood pressure, accompanied by an even more prolonged tachycardia. These results demonstrate that aprikalim can produce myocardial necrosis not only in rats but also in monkeys. To our knowledge, this is the first time that such adverse effects are reported for a vasodilator in monkeys. More importantly, these effects were prevented by blocking cardiac beta-adrenoceptors. Thus, the myocardial lesions produced by aprikalim may be attributed to its profound and prolonged hemodynamic effects.

Effects found in a one-year oral toxicity study in Sprague-Dawley rats of a novel 5-HT1A receptor partial agonist for the treatment of anxiety in humans.

A potent and selective serotonin (5-HT1A) partial agonist with potential as a human anxiolytic drug was given in oral doses of 0, 5, 15, or 50 mg/kg/day by gavage to Sprague-Dawley rats for 6 or 12 mo. Some animals were allowed 1 mo to recover after each treatment period. The 10-fold increase in dose resulted in a 20-fold increase in drug plasma concentration due to saturable first-pass metabolism. This resulted in disproportionately higher concentrations and greater bioavailability of the 15- and 50-mg/kg/day regimens. Drug exposure was associated with decreased spontaneous activity in the 15- and 50-mg/kg rats. The activity of these rats returned to normal during the recovery period. There were significant (p < 0.05) decreases in mean body weights during the study for 50-mg/kg males, with improvement during the recovery periods. No biologically significant effects were noted in clinical laboratory parameters. Based on organ weight increases and histopathological evaluation, drug-related effects after 6 and 12 mo of treatment were in the pituitary (both sexes) and all treated female reproductive organs. In general, these effects persisted into periods of recovery, except for pituitary hyperplasia, which was not apparent following recovery after treatment for 6 mo. After treatment for 12 mo and the following recovery, there were significant increases in adrenal weights in the 15- and 50-mg/kg/day males with no morphological correlate. There was increased pituitary hyperplasia that persisted through the recovery period in all treated groups in both sexes, but there was no increase in pituitary neoplasms. In treated females, there was also morphologic evidence of persistent diestrus (estrogenic effect) evidenced by endometrial squamous metaplasia, increased corpora lutea, vaginal mucification, and decreased uterine size. The clinical and pathological changes seen with these 2 regimens were considered exaggerated pharmacological effects of the drug on serotonin receptor-rich organs.

HTLV-I/II infection in a high viral endemic area of Zaire, Central Africa: comparative evaluation of serology, PCR, and significance of indeterminate western blot pattern.

The frequency of indeterminate Western blot (WB) seroreactivities against HTLV-I "gag encoded proteins" only, and the use of low specific diagnostic WB criteria led to the overestimation of HTLV-I seroprevalence in initial studies in intertropical Africa and Papua New Guinea. In order to clarify the meaning of such seroreactivity, 98 blood samples of individuals from a high HTLV-I endemic area in Zaire, Central Africa were studied by a WB assay containing HTLV-I disrupted virions enriched with a gp 21 recombinant protein and a synthetic peptide from the gp 46 region (MTA-1), and by the polymerase chain reaction (PCR) with 3 primers pairs and 4 different HTLV-I and or HTLV-II-specific probes. These 98 samples were taken mainly from patients with neurological diseases and from their relatives. Using stringent WB criteria, 28 sera (29%) were considered as HTLV-I-positive, 3 as negative and 67 (68%) as indeterminate. A large proportion of these indeterminate sera would have been considered as HTLV-I-positive samples according to previous low specific WB diagnostic criteria. After PCR, 35 samples (36%) were considered as positive for the presence of HTLV-I proviral DNA. Out of the 67 WB seroindeterminate, 10 (15%) were found HTLV-I-positive by PCR. These 10 individuals exhibited in WB multiple band reactivity with p19 and/or p24 (7 cases of both) associated in 6 cases with rgp 21, but never with MTA-1. No samples were found PCR-positive for HTLV-II despite the findings of 11 sera suggestive of HTLV-II by WB.(ABSTRACT TRUNCATED AT 250 WORDS)

A continuous spectrophotometric assay for glycosyltransferases.

This paper describes a continuous spectrophotometric assay for glycosyltransferases. In this assay, a nucleotide diphosphate is coupled to NADH oxidation via pyruvate kinase and lactate dehydrogenase. The nucleotide diphosphate is produced either directly during the glycosyltransferase mediated reaction, or indirectly by the production of a nucleotide monophosphate during the glycosyltransferase mediated reaction, and subsequent conversion of the nucleotide monophosphate to nucleotide diphosphate using nucleoside monophosphate kinase. Using this assay, kinetic parameters for fucosyl-, sialyl-, and N-acetylglucosaminyltransferases were determined. The assay not only allows continual monitoring of the enzymatic reaction, but is rapid and allows the processing of 96 samples at once since it is performed in 96-well microtiter plates. In addition, the procedure provides a means of monitoring the activity of these enzymes using sugar-nucleotide donor analogs, where radiochemical procedures cannot be used.

Detection of 100 molecules of product formed in a fucosyltransferase reaction.

We present the detection of 100 molecules of enzyme substrate and product. A fucosyltransferase and a fucosidase were used to add and remove, respectively, a monosaccharide from a synthetic oligosaccharide fluorescently labelled with tetramethylrhodamine. The reaction was followed by use of capillary zone electrophoresis, to separate the product and reactant, with laser-induced fluorescence detection. These are the most sensitive enzyme assays reported to date and six orders of magnitude more sensitive than any reported for these two enzymes. This simple technology allows high-sensitivity determination of the activity of any enzyme for which a fluorescent substrate can be synthesized, and brings within reach the ability to assay glycosyltransferase activities in single cells.

Flavobacterium meningosepticum peptide:N-glycosidase: influence of ionic strength on enzymatic activity.

Flavobacterium meningosepticum peptide:N-glycosidase-mediated deglycosylation of N-linked glycan strands of glycoproteins has been found to be strongly influenced by the ionic strength of the assay medium. By use of a modification of a previously published assay procedure for quantitative analysis of glycan release we have been able to improve reproducibility and thus to compare the extent of deglycosylation achieved under a variety of conditions of ionic strength. We have observed that enzyme activity is adversely affected by high ionic strength buffers such as those recommended for deglycosylation of various glycoproteins and recommend the use of low ionic strength buffers for routine use.

Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance.

BACKGROUND: Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain. METHODS: We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial. RESULTS: In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy. CONCLUSIONS: Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.

Neuropathy associated with monoclonal gammopathies of undetermined significance.

Monoclonal proteins (IgM, IgG, and IgA) in the serum or urine of patients with neuropathy may provide a marker for amyloidosis, myeloma, lymphoma, leukemia, Waldenström's macroglobulinemia, or monoclonal gammopathy of undetermined significance (MGUS). The clinical characteristics, course, and electromyographic features among neuropathies associated with monoclonal IgM (IgM-MGUS, 31 patients), monoclonal IgG (IgG-MGUS, 24 patients), and monoclonal IgA (IgA-MGUS, 10 patients) evaluated between 1980 and 1986 were compared. Four statistically significant differences set IgM-MGUS neuropathies apart from IgG-MGUS and IgA-MGUS neuropathies: (1) higher frequency of sensory loss and ataxia, (2) higher frequency of nerve conduction abnormality--10 attributes were significantly worse (none were significantly better), (3) higher frequency of dispersion of the compound muscle action potential, and (4) higher frequency of IgM-MGUS in the MGUS neuropathy cohort than is characteristic of MGUS without neuropathy seen at our institution or than is encountered in epidemiological surveys. These differences were not thought to be due to selection or severity biases. Neither the amount of IgM nor the estimated size of the monoclonal peak was associated with severity of neuropathy. The type and severity of IgM-MGUS neuropathies with anti-myelin-associated glycoprotein antibodies were not significantly different from those without anti-myelin-associated glycoprotein antibodies. A simple relationship between the presence and amount of IgM-MGUS or anti-myelin-associated glycoprotein antibodies and neuropathy cannot be assumed.