Evaluation of a capillary zone electrophoresis system versus a conventional agarose gel system for routine serum protein separation and monoclonal component typing.

Capillary zone electrophoresis of serum proteins is increasingly gaining impact in clinical laboratories. During 2003, we compared the fully automated capillary electrophoresis (CE) system from Beckman (Paragon CZE 2000) with the method agarose gel electrophoresis Sebia (Hydrasis-Hyris, AGE). This new study focused on the evaluation of analytical performance and a comparison including 115 fresh routine samples (group A) and a series of 97 frozen pathologic sera with suspicion of monoclonal protein (group B). Coefficients of variation (CVs %) for the five classical protein fractions have been reported to be consistenly < 9% in within-run and < 10% in between-run imprecision studies with the Paragon 2000 system. The results of the comparison study (group A) demonstrated a good correlation between the CE system and AGE, except for beta-globulin (r = 0.65). Among the 97 pathologic serum samples (group B), there were 90 in which we detected a monoclonal protein by immunofixation (IF) (immunosubtraction (IS) was not used). AGE and Paragon 2000 failed to detect 7 and 12 monoclonal proteins, respectively, leading to a concordance to 92% for AGE and 87% for Paragon 2000 for identifying electrophoretic abnormalities in this group. Beta-globulin abnormalities and M paraprotein were well detected with Paragon 2000. Only 81% (21 vs 26) of the gammopathies were immunotyped with IS by two readers blinded to the IF immunotype. The Paragon 2000 is a reliable alternative to conventional agarose gel electrophoresis combining the advantages of full automation (rapidity, ease of use and cost) with high analytical performance. Qualified interpretation of results requires an adaptation period which could further improve concordance between the methods. Recently, this CE system has been improved by the manufacturer (Beckman) concerning the migration buffer and detection of beta-globulin abnormalities.

Is hyperprolinemia type I actually a benign trait? Report of a case with severe neurologic involvement and vigabatrin intolerance.

Hyperprolinemia type I is a deficiency of proline oxidase (McKusick 23950), leading to hyperprolinemia and iminoglycinuria, usually with renal involvement. Hyperprolinemia type I is considered a benign trait. We reported a case of hyperprolinemia type I with a severe neurologic disorder and without renal involvement. The patient had marked psychomotor delay and right hemiparesis. Epilepsy was characterized by status epilepticus or a cluster of seizures. Laboratory findings revealed elevated levels of proline in the serum, urine, and cerebrospinal fluid without delta1-pyrroline 5-carboxylate dehydrogenase in the plasma or urine. Fluorescence in situ hybridization excluded a chromosome 22q11 deletion. Vigabatrin inhibits ornithine transaminase. Thus, vigabatrin could lead to a depletion of the normal pool of pyrroline 5-carboxylate dehydrogenase and could aggravate the clinical condition of the child. In this study, vigabatrin was discontinued. In the following months, the patient had marked psychomotor improvement, without modification of the epilepsy. We suggest that vigabatrin should be avoided in hyperprolinemia type I.

[Impairment of visual recognition after a traumatic brain injury]. / Evolution des troubles de la reconnaissance visuelle à distance d'un traumatisme cérébral.

Impaired vision and cerebral blindness were observed in a patient who had suffered brain trauma. One year after the trauma, the impairment was characterized by low visual acuity, visual field restricted to central tunnel vision and impaired recognition of objects, line drawings, colors and faces. Vision improved six years after the brain trauma with more rapid recognition of objects and line drawings, increased visual acuity and broadening of the visual field. Reading was possible at this time. However, prosopagnosia remained very severe and was still the primary complaint of the patient. Improvement of visual function continuing for several years after a brain injury is discussed on the basis of cognitive and neurophysiological knowledge. The place of rehabilitation is discussed. Functional improvement is explained by extrastriate cortical afferences and the cortical network of visual pathways.

[Conduction aphasia and phonemic disorder]. / Aphasie de conduction par trouble phonémique.

Conduction aphasia is usually described as a repetition impairment. Semiology or pathophysiology cannot be explained with this definition. We report a single case particularly demonstrative. The patient showed spontaneous speech, denomination, repetition and reading impairments. Main errors were phonemic paraphasia. No arthric disorder nor comprehension impairment was observed. Damage of supramarginalis gyrus and Wernicke's area was found. A cognitive analysis suggested that the phonological buffer and the working memory were impaired. Implication for rehabilitation, which included segmentation and semantisation associated to phonological training, is discussed. The course of the conduction aphasia was good and the patient was able to work again.

[What is a "left"?]. / Qu'est-ce qu'un "gauche"?

OBJECTIVE: Patients with right hemisphere syndrome may be labeled as "gauche" by the rehabilitation staff. This term corresponds to a variety of oddities in behavior or discourse. The aim of this study is to understand the coherence of these oddities with the classical elements of right hemisphere syndrome. MATERIAL: In this article, we present a detailed study of the discourse and the relation with others of a patient with severe left hemineglect, who was followed up for twelve months and did not exhibited any significant change in his symptomatology. METHODS: This study relies on the data from neuropsychological examination, on notes written after rehabilitation session by the therapists and on data from weekly non-directive interviews. RESULTS: This follow-up revealed disturbances of time sense, reduplication for places, misidentification of therapists, pseudo hallucinations, and showed that the transferential relation was "floating". The non-directive interviews permitted the patient to express his own interpretation of his troubles. He described them in terms of gaps in his body "carapace" and disorganization of the oral drive. CONCLUSION: We propose to consider the symptomatology of this patient in relation with the subjective effects of the breaking up of his body image and the concomitant intrusion of the oral object (in the psychoanalytic sense of this term) in his psychic reality.

Rehabilitation of verbal working memory after left hemisphere stroke.

PRIMARY OBJECTIVE: To assess a rehabilitation programme of working memory. RESEARCH DESIGN: Single case multiple-baseline-across-behaviour design in a patient with chronic stroke suffering from a specific impairment of working memory. METHODS: Rehabilitation included training of storage and processing components of verbal working memory. Outcome was assessed with specific working memory tests, non-specific tasks requiring working memory, non-target tasks not requiring working memory and questionnaires addressing daily-life functioning. This assessment was performed twice before the experimental therapy and once after. RESULTS: Cognitive measures were stable before therapy. A statistically significant improvement was found for target measures and for daily-life skills. In contrast, no change was found on non-target tasks. CONCLUSION: Improvement was not apparently related to spontaneous recovery, since performance was stable before therapy. This study suggests that specific cognitive training may improve working memory in patients with brain injury.

Urinary excretion of free cysteine in critically ill neonates.

UNLABELLED: In preliminary observations, significant amounts of free cysteine, a neurotoxic amino acid, were noted in the urine of asphyxiated or septic-shocked neonates. The present study was conducted to determine whether free urinary cysteine was elevated in these critically ill neonates compared with a control group, and to assess the clinical significance of this generation. Free cysteine was measured in the urine of newborn infants with perinatal asphyxia (n = 16) or neonatal sepsis (n = 14) and the urine of a control group (n = 10) by ion-exchange chromatography. Relationships between cysteine levels and the clinical severity, sulfite supply and neurological outcome of the patients were then studied. Urinary cysteine was 27.6 (15-49) mmol mol(-1) creatinine for the patients but was not detectable in the control group. Cysteine levels were correlated with the severity of neonatal septic shock but not with the grade of perinatal asphyxia and did not have a specific influence on the neurological outcome of these patients. The correlation between cysteine level and the severity of neonatal septic shock was indirect and probably linked to higher sulfite administration in this population. CONCLUSION: The mean daily supply of sulfites is high in critically ill neonates, mainly originating from dopamine and generating significant amounts of cysteine. Although a worsening effect attributable to cysteine on the neurological outcome of the patients could not be demonstrated, the appropriateness of cryptic administration of sulfites by way of drug excipients is called into question.

Major hyperpipecolataemia in a normal adult.

We describe the fortuitous discovery of a 44-year-old man with a very high hyperpipecolataemia (250 mumol/L; normal < 2.5). This patient has none of the clinical features seen in peroxisomal diseases, he is a strictly normal intelligent adult. A stereochemical study of this pipecolic acid was performed using D-amino acid oxidase, and identified it as L-pipecolic acid. We suggest that isolated L-hyperpipecolataemia may be a benign trait.

Treatment with vigabatrin may mimic alpha-aminoadipic aciduria.

PURPOSE: We describe a secondary effect of treatment with vigabatrin (VGB). A significant increase in alpha-aminoadipic acid (AAA) occurred in plasma and urine of VGB-treated children, thus mimicking a known rare metabolic disease, alpha-aminoadipic aciduria (AAAuria). METHODS: We studied eight children, aged from 3 months to 5 years, who were receiving VGB for drug-resistant partial epilepsies. Plasma and urine amino acids were assayed with ninhydrin detection on an automated Beckman 6300 analyzer. RESULTS: In eight out of eight children, there was a significant increase of AAA in plasma and in urine. Plasma values ranged from 7 to 8 microM (control values, < 5) and urinary values from 67 to 274 mmol/mol creatinine (control values, < 25). CONCLUSIONS: The concentrations of AAA in these VGB-treated children were as high as the concentrations found in the inherited metabolic disease, AAAuria. This could lead to incorrect diagnosis and to inappropriate genetic counseling. Thus whenever a genetic metabolic disease is suspected, amino acid chromatography testing should be performed before initiation of treatment with VGB.

HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France.

BACKGROUND: Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent increase of cellular iron absorption and storage. OBJECTIVES: To evaluate the incidence and spectrum of HFE mutations and the relative frequency of the two main alleles of transferrin receptor in patients with PCT originating from southern France, and to evaluate the relationship of these genetic data with iron status, and with hepatitis B and C and human immunodeficiency virus (HIV) infections. METHODS: Thirty-six consecutive patients with either sporadic or familial PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined. RESULTS: Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor alleles in PCT patients did not show significant variation compared with the general population. CONCLUSIONS: This study confirms the high frequency of HFE mutations in patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.

[Treatment of urinary tract infections by dibekacin]. / Traitement des infections urinaries par la dibékacine.

In this cooperative trial, 181 patients with various urinary tract infections were treated by dibekacin, a new hemi-synthetic aminoglycoside. Clinical and bacteriological results confirm the efficacy of dibekacin in this indication. Local and systemic tolerance, and thus renal and cochleo-vestibular, were very satisfactory.

[Dibekacin in the treatment of septicemia]. / La dibékacine dans le traitement des septicémies.

During an open multicentric trial (17 centers), we have treated 62 septicemia by dibekacin, alone or associated with other antibacterial drugs. Taking into account the degree of severity of these patients, the results are considered satisfactory in 47 patients. 15 failures were noted (including 9 deaths). General and local tolerance were good, in spite of the duration of treatment.