Separation of aceclofenac and diclofenac in human plasma by free zone capillary electrophoresis using N-methyl-D-glucamine as an effective electrolyte additive.

Aceclofenac (A) and diclofenac (D) are effective non-steroidal anti-inflammatory drugs (NSAIDs) derived from the phenylacetic acid with pronounced antirheumatic, anti-inflammatory, analgesic and antipyretic properties. Our work proposes a new, fast-free zone capillary electrophoresis method for the simultaneous determination of aceclofenac and diclofenac in human plasma. The effect of increasing concentrations of N-methyl-D-glucamine organic base on borate run buffer was investigated. A good separation was achieved using a 40 cm x 75 microm uncoated silica capillary, 300 mmol/l sodium borate buffer, 200 mmol/l N-methyl-D-glucamine, pH 8.9, in about 3 min. Moreover, the plasma sample pre-treatment procedure was examined: acidic precipitants such as trichloroacetic acid (TCA), metaphosphoric acid (MPA), perchloric acid (PCA) or 5-sulphosalicylic acid (SSA) cause a total loss of analytes while acetonitrile allows a recovery of 97-98% of both compounds. Its simplicity and rapidity and the low analysis costs demonstrate that our method is a reliable and efficient mean for the comprehensive determination of aceclofenac and diclofenac in human plasma when pharmacokinetics studies are required.     

先天性膈疝修补术后支气管内修补片的移位

先天性膈疝的手术修补包括修补片复位或隔膜的直接缝合。然而，有证据显示有一半的修补片可能重新形成疝。作描述了1例8岁女患儿，她在1岁时接受了先天性膈疝修补术，现在并发了修补片移位及右下段支气管瘘。腹部超声及核磁共振成像提示膈疝复发，然而，胸部CT检查不能证实膈肌的病变。纤维支气管镜发现修补片瘘入支气管，才做出了正确的诊断。     

Exposure to solvents and tardy epilepsy: 2 clinical cases]

Organic solvents (OS) are widely used in industry and craft work. The neurotoxic effects of OS are well known in occupational exposure occurring in poor industrial hygiene conditions. There has been interest recently in a possible epileptogenic effect of OS exposure. Two cases are reported of late onset epilepsy observed in workers heavily exposed to OS. Case 1 was a 27-year-old male painter employed in a car body repair workshop. Solvent exposure was high for a few months because after his regular work, the man continued working as a car body painter in his own private concern. After a period of weakness and headache, probably indicating an excessive solvent absorption, he suffered two generalized paroxysmal seizures during sleep which necessitated hospitalization and continuous treatment with barbiturates. Case 2 was a 44-year-old male painter in a road advertising billboard factory who was continuously exposed to OS. Ten years previously he had been exposed to accidental massive inhalation of solvent vapours while opening a drum of solvents for coloured paint. Acute solvent poisoning followed and seven weeks later he suffered several epileptic episodes associated with typical EEG alterations; for many years, however, treatment was ineffective. In both cases there was neither a history of neurologic disease nor any other neurologic dysfunctions and the results of comprehensive neuroradiological studies were normal. Evidence exists of a chronological connection between high exposure to paint solvents and clinical evidence of late onset epilepsy, but it is not possible to identify a definite causal relationship.(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of T-cell activation by CD4+ CD25+ suppressor T cells

Summary: Depletion of the minor (∼10%) subpopulation of CD4⁺ T cells that co-expresses CD25 (interleukin (IL)-2 receptor α-chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4⁺ T cells with anti-CD25 and complement results in the development of organ-specific autoimmunity. Autoimmune disease can be prevented by reconstitution of the animals with CD4⁺ CD25⁺ cells. CD4⁺ CD25⁺-mediated protection of autoimmune gastritis does not require the suppressor cytokines IL-4, IL-10, or transforming growth factor (TGF)-β. Mice that express a transgenic T-cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/K ATPase all develop severe autoimmune gastritis very early in life. CD4⁺ CD25⁺ T cells are also powerful suppressors of the activation of both CD4⁺ and CD8⁺ T cells in vitro . Suppression is mediated by a cell contact-dependent, cytokine-independent T–T interaction. Activation of CD4⁺ CD25⁺ via their TCR generates suppressor effector cells that are capable of non-specifically suppressing the activation of any CD4⁺ or CD8⁺ T cell. Activation of suppressor effector function is independent of co-stimulation mediated by CD28/CTLA-4 interactions with CD80/CD86. We propose that CD4⁺ CD25⁺ T cells recognize organ-specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4⁺ or CD8⁺ effector cells to suppress the development of autoimmune disease.     

Circadian rhythm of glucose utilization in the pineal body of rats of different ages

Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 mol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging.     

Treatment of myasthenia gravis

Summary In the treatment of myasthenia gravis (MG) considerable progress has recently been achieved. Our experience is based on the observation of 139 patients with an average follow-up of 3 years and 4 months.A treatment plan and results are presented.Indications for thymectomy: all cases of MG in adult life, apart from ocular myasthenia without radiological thymoma and without electrophysiological and pharmacological signs of generalization; before puberty only cases with radiological thymoma and severely incapacitating or life-threatening signs.Median sternotomy is preferable for thymoma, the transcervical approach with a sternal split for non-neoplastic thymus. Mediastinal radiotherapy is indicated after removal of an invasive or adhesive thymoma.Indications for corticosteroids: 1) before thymectomy: respiratory weakness; 2) soon after thymectomy: life-threatening signs; 3) later after thymectomy: incapacitating or life-threatening signs; 4) as an alternative to thymectomy: when surgery cannot be performed or it is not indicated. Oral Prednisone was nearly always preferred: alternate-day high single dose (75 to 115 mg) has given good results in most cases even if in some cases a small dose was required in the off day; inversely a lower alternate-day or daily dose was often sufficient.Long-term results: following this schedule for adult patients good results were scored in 67% of thymomas, in 94% of hyperplasias, and in 62% of unthymectomized patients: in prepuberal life the few cases of severe MG have all shown a favorable evolution.

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Zusammenfassung Bei der Behandlung der Myasthenie wurden in letzter Zeit beachtliche Fortschritte erzielt. Wir teilen hier unsere Erfahrungen anhand von 139 Patienten mit einer durchschnittlichen Katamnese von 3 Jahren und 4 Monaten mit.Wir betrachten als Indikationen für eine Thymektomie: alle Fälle von Myasthenie beim Erwachsenen mit Ausnahme der rein okulären Formen ohne radiologisch nachweisbares Thymom und ohne elektrophysiologische oder pharmakologische Zeichen einer Generalisierung; bei Kindern vor der Pubertät empfehlen wir die Thymektomie nur in Fällen mit radiologisch nachweisbarem Thymom und mit schwerer Beeinträchtigung oder gar Lebensgefährdung durch die Symptome.Die mediane Sternotomie ist beim Thymom vorzuziehen, der transzervikale Zugang mit Spaltung des Sternums für die nicht neoplastischen Thymusvergrößerungen. Mediastinale Strahlentherapie ist nach Exstirpation eines invasiven Thymoms oder eines Thymoms mit Adhäsionen angezeigt.Als Indikation für die Corticosteroidtherapie betrachten wir: 1. wenn vor der Thymektomie Atemstörungen bestehen; 2. wenn bald nach der Thymektomie lebensbedrohliche Symptome auftreten; 3. wenn später nach Thymektomie nennenswert behindernde oder lebensbedrohliche Symptome in Erscheinung treten; 4. als Alternative zur Thymektomie, wenn diese nicht durchgeführt werden kann oder nicht indiziert ist. Die orale Prednisontherapie wurde fast immer vorgezogen: wir gaben an alternierenden Tagen jeweils hohe Einzeldosen (75–115 mg) mit gutem Erfolg in den meisten Fällen. In gewissen Fällen war eine kleine Dosis an den Tagen zwischen der Hauptdose aber genügend, ebenso in Einzelfällen eine allgemein niedrigere Dosierung. Die Langzeiterfolge mit diesem therapeutischen Vorgehen betrugen 67% gute Ergebnisse bei Thymomen und 94% bei Thymushyperplasie. Unter den nicht thymektomierten Patienten wiesen 62% ein gutes Ergebnis auf. Vor der Pubertät zeigten die allerdings wenigen Fälle schwerer Myasthenie alle ein gutes Ansprechen auf die Therapie.

     

Development of an inhalation unit risk factor for hexavalent chromium

A unit risk factor (URF) was developed for hexavalent chromium (CrVI). The URF is based on excess lung cancer mortality in two key epidemiological studies of chromate production workers. The Crump et al. (2003) study concerns the Painesville, OH worker cohort, while Gibb et al. (2000) regards the Baltimore, MD cohort. A supporting assessment was also performed for a cohort from four low-dose chromate plants (Leverkusen and Uerdingen, Germany, Corpus Christi, TX, Castle Hayne, NC). For the Crump et al. (2003) study, grouped observed and expected number of lung cancer mortalities along with cumulative CrVI exposures were used to obtain the maximum likelihood estimate and asymptotic variance of the slope (β) for the linear multiplicative relative risk model using Poisson regression modeling. For the Gibb et al. (2000) study, Cox proportional hazards modeling was performed with optimal exposure lag and adjusting for the effect of covariates (e.g., smoking) to estimate β values. Life-table analyses were used to develop URFs for each of the two key studies, as well as for supporting and related studies. The two key study URFs were combined using weighting factors relevant to confidence to derive the final URF for CrVI of 2.3E-03 per μg CrVI/m³.     

Pulmonary hypertension in systemic lupus erythematosus: prevalence,predictors and diagnostic strategy

ObjectivesTo investigate the prevalence and predictors of pulmonary hypertension (PH) in patients with systemic lupus erythematosus (SLE) and to validate a diagnostic strategy.Methods245 patients with SLE entered a screening program. Possible PH was defined as two consecutive systolic pulmonary arterial pressure (PAP) values ≥ 40 mm Hg by echocardiography. The subsequent diagnostic procedure, including right heart catheterization if needed, confirmed or excluded the diagnosis of PH secondary to cardiopulmonary disease or SLE-related pulmonary arterial hypertension (PAH). Independent predictors of PH were identified by multivariant multiple linear or logistic regression models. The sensitivity (S), specificity (SP), positive (PPV) and negative predictive values (NPV) were calculated for different screening cutoff values.Results88% patients were women. The mean (SD) age at the time of enrolment was 45 (16) years. 12 cases of PH were detected, all secondary, with a resulting prevalence of 5%. Two consecutive echocardiographic PAP measurements ≥ 40 mm Hg performed best as the cutoff point for screening (S 100%, SP 97%, PPV 70, NPV 100), as compared with single PAP measurements ≥ 30 mm Hg or ≥ 40 mm Hg The age at the time of enrolment was the only variable independently associated with PAP values (p = 0.0001), with the SLICC damage index score showing a borderline association (p = 0.08). Only the age at the time of enrolment showed an independent association with PH (OR 1.10, 95% CI 1.06–1.17).ConclusionWe found a low prevalence of PH. Screening echocardiograms in asymptomatic lupus patients are thus not recommended. Two consecutive PAP values ≥ 40 mm Hg by echocardiogram is the best screening cutoff for starting investigations in SLE patients with suspected PH.