Selective phlebography of the thymus gland with pneumomediastinum in patients with myasthenia gravis

The authors describe the technique of selective phlebography of the thymus under conditions of pneumomediastinum. The investigation of the thymus in 40 patients with myasthenia enabled the authors to conclude that a preliminary administration of gas into the fatty tissue of the anterior mediastinum facilitated catheterization of the thymus veins and favoured a success of selective phlebography, elevated the reliability of differential diagnosis of tumorous and involutional changes of the thymus as well as tumors and portions of a dense fibro-fatty tissue of the anterior mediatinum. The method is characterized by a lower radiation load on the patient and is more economical.     

Expression of CD23 in the germinal center of thymus from myasthenia gravis patients

In order to investigate a pathogenic role of germinal centers which appear in the hyperplastic thymus of myasthenia gravis (MG) patients, we performed an immunohistochemical study using various monoclonal antibodies including CD23. In contrast with tonsilar germinal centers from non-MG individuals, CD23 was strongly and diffusely expressed in the whole area of germinal centers of MG thymi, including the outer zone. In addition, we measured the serum level of soluble CD23 (sCD23) in MG patients at various clinical stages. The high serum sCD23 levels, which were noted in the unthymectomized patients, fell to within normal range over 5 years after thymectomy, and the decline of serum sCD23 correlated well with clinical improvement. CD23 is thought to be responsible for preventing unselected germinal center B cells from entering apoptosis and, in turn, leads to the survival of auto-reactive B cell clones.     

B cell population and its autoimmune activity in the thymus of patients associated with myasthenia gravis

Immunohistochemical studies using antibodies to B lymphocyte and to immunoglobulin G bearing cell were carried out for resected thymus-specimens of 10 patients associated with myasthenia gravis. In each case, abundant B cells (L26 positive cell) resided in the follicles and the medulla of thymus, especially, were congregated in the follicles developing germinal center and around Hassall's corpuscles. Amount of B cell population was various among each case regardless of type of myasthenia gravis or age. B cells were greatly increased in the thymus of patients with values of anti-acetylcholine receptor antibody titers over 100 nmol/l. Although numerous B cells were present in the thymus of these patients, IgG bearing cells were extremely rare. In the most cases, B cells lacked IgG expression. From the results, numerous B cells pre-activating autoimmune antibody production were accumulated in the thymus of patients associated with myasthenia gravis.     

Selective impairment of serum antibody repertoires toward muscle and thymus antigens in patients with seronegative and seropositive myasthenia gravis

We analyzed the antibody (Ab) repertoires of IgM and IgG of patients with seropositive and patients with seronegative myasthenia gravis (MG) toward self antigens by means of a quantitative immunoblotting technique using normal human tissue extracts as sources of self antigens. Repertoires of reactivities of IgG and IgM with liver, kidney and stomach antigens were conserved between myasthenic patients and controls. IgG and IgM Ab repertoires toward muscle antigens differed significantly between patients with seropositive MG and healthy donors, as assessed by multiparametric statistical analysis. Patterns of Ab reactivities to muscle antigens were similar in patients with seronegative MG and healthy controls. Antibody repertoires of IgG and IgM toward thymus antigens of both seropositive and seronegative MG patients, differed significantly from those of healthy individuals. Our results indicate that MG is characterized by a selective impairment of self-reactive Ab repertoires toward muscle and thymus antigens. The observation that self-reactive Ab repertoires toward thymus antigens are similar in patients with seropositive and seronegative MG suggests that both forms of MG share common immunopathological features.     

Evaluation of nursing care in patients with myasthenia gravis

A retrospective study was made of 35 periods of hospital admission between January 1985 and September 1995, of 17 patients diagnosed in the Hospital Josep Trueta, Girona, as having myasthenia gravis. These were all the patients diagnosed as having myasthenia gravis in this ten year period. We studied the characteristics of their stay in hospital and evaluated the planning and practice of nursing care during these 35 periods. Nursing problems or diagnostic difficulties were found on 15 occasions, probably due to lack of knowledge of myasthenia gravis. When a patient had dysphagia, nursing care was increased and any problems identified. 29.4% of the patients were admitted to the intensive care unit. Since this disorder may be very serious, we consider that special training should be given to the nurses attending these patients. An understanding of this disorder and the possible treatments, complications, drugs, etc. would make it possible to give specific, individualized attention which would result in a higher standard of care.     

Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.     

Plasma exchange in myasthenia gravis

OBJECTIVE: To evaluate whether fetal heart rate (FHR) patterns obtained in nonstress testing within 24 hours of delivery in patients with preterm delivery were associated with histologic acute infection, and if so, whether the associations are with maternal as opposed to fetal acute inflammation (acute amnionitis versus acute umbilical vasculitis). METHODS: The data set included 351 consecutive patients delivering from 22 to 32 weeks' gestation (excluding cases of preeclampsia; nonhypertensive abruption; stillbirth; fetal structural and karyotypic anomalies; Rh isoimmunization and hydrops fetalis; and maternal diabetes and hypertension). Severe variable decelerations were defined as FHR < 70 beats per minute lasting > 60 seconds, and decreased fetal heart variability included both reduced beat-to-beat variability and long-term heart rate cyclicity. Amniotic fluid volume was graded sonographically as part of a fetal biophysical profile. Acute inflammation of amnion (indicative of maternal inflammation) and umbilical cord (fetal inflammation) were scored by a single pathologist blinded to clinical data. RESULTS: Severe FHR variable decelerations were directly related to acute amnionitis (P = .012) and acute umbilical vasculitis (P = .0013). In preterm labor, decreased FHR variability was related to acute amnionitis (P = .005). All observations were independent of amniotic fluid volume or use of tocolytic agents. CONCLUSIONS: Severe variable decelerations and decreased FHR variability at < 32 weeks' gestation are related to histologic evidence of acute inflammation.     

Social aspects in myasthenia gravis

The myasthenics in Finland (n = 240) have been registered and treated in one center for more than 10 years. Of this material, an investigation was performed of their medico-social state as of 1 January, 1975. The study comprised 88 per cent (210) of the patients. In the working age (16-64 years) were 181 patients. Compared to the total Finnish population, the myasthenic patients lived more often in urban districts, had had more intermediate-school and university--but less vocational-school education, and belong as a whole to "higher" social classes. The severity and the variability of the disease naturally influenced the disability. A change from severe to slight symptoms occurred in 38 per cent, and 12 per cent of the myasthenics were in complete remission (2/3 of whom had had severe symptoms). One third (72) got a full pension because of myasthenia, and about one tenth (25) because of some other reason. Of these who got a full pension for myasthenia, 7 per cent were in complete remission without any myasthenic symptoms. The influence of thymectomy on the degree of disability was impressive, since more than 50 per cent of disabled myasthenic patients returned to work thereafter. Thus, because of the unpredictable, but on the long term quite favourable course, a full pension should not be prescribed early (during the first 5 years) of the disease. An active treatment may also change the outlook for even the most severely disabled patients.     

Hypophyseal-adreno-gonadal system function in myasthenia patients with tumorous and nontumorous pathology of the thymus

Overall twenty-five patients (all women) who ranged from 16 to 56 years old were examined. They were divided into two groups: group I was formed of subjects with hyperplasia of the thymus gland, group II--thymoma. Blood serum levels of prolactin, progesterone, estriol, estradiol, testosterone hydrocortisone. All patients showed a significant increase in average blood plasma levels of estrogens, testosterone and prolactin. Average levels of progesterone and hydrocortisone in patients with thymus hypertrophy were lower than in controls, while in thymoma patients these were much higher. The data submitted are indicative of substantial differences in the endocrine status of myasthenia patients depending on tumor or nontumor lesion of the thymus gland, which fact may suggest different pathogenetic mechanisms of development of the condition.     

Stapedius reflex decay in myasthenia gravis

Stapedius reflex decay, in response to a one-minute sound stimulus of 500 Hz occurred in six patients with myasthenia gravis. This decay is analagous to the decremental response of muscle action potentials to rapid nerve stimulation. Edrophonium chloride decreases the degree of decay. This represents a useful test in the diagnosis of myasthenia gravis.     

Drug-induced neuromuscular blockade and myasthenia gravis

Myasthenia gravis is an uncommon disorder of the neuromuscular junction resulting in weakness of all striated voluntary muscles. Therapeutic advances have increased patients' age and survival. Older patients with myasthenia gravis may have additional medication needs. Numerous drugs have experimental and clinical evidence of neuromuscular blockade. A MEDLINE search of the English literature from 1966 to the present pertinent to drug-induced myasthenia gravis was performed. Additional literature was obtained from reference citations of relevant articles. Drugs with several reports of neuromuscular blockade were assessed for causality by a recognized probability scale. Prednisone was most commonly implicated as aggravating myasthenia gravis, and D-penicillamine was most commonly associated with myasthenic syndrome. The greatest frequency of drug-induced neuromuscular blockade was seen with aminoglycoside-induced postoperative respiratory depression. However, drugs most likely to impact myasthenic patients negatively are those used in the treatment of the disease. These include overuse of anticholinesterase drugs, high-dose prednisone, and anesthesia and neuromuscular blockers for thymectomy.     

Abnormal T cell receptor V gene usage in myasthenia gravis: prevalence and characterization of expanded T cell populations

The mechanism of the G0/G1 arrest and inhibition of proliferation by quinidine, a potassium channel blocker, was investigated in a tissue culture cell line, MCF-7, derived from a human breast carcinoma. The earliest measurable effect of quinidine on the cell cycle was a decrease in the fraction of cells in S phase at 12 hr, followed by the accumulation of cells in G1/G0 phases at 30 hr. Arrest and release of the cell cycle established quinidine as a cell synchronization agent, with a site of arrest in early G1 preceding the lovastatin G1 arrest site by 5-6 hr. There was a close correspondence among the concentration-dependent arrest by quinidine in G1, depolarization of the membrane potential, and the inhibition of ATP-sensitive potassium currents, supporting a model in which hyperpolarization of the membrane potential and progression through G1 are functionally linked. Furthermore, the G1 arrest by quinidine was overcome by valinomycin, a potassium ionophore that hyperpolarized the membrane potential in the presence of quinidine. With sustained exposure of MCF-7 cells to quinidine, expression of the Ki67 antigen, a marker for cells in cycle, decreased, and apoptotic and necrotic cell death ensued. We conclude that MCF-7 cells that fail to progress through the quinidine-arrest site in G1 die.     

Prognosis of myasthenia gravis: a retrospective study of 380 patients

The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients. A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints. Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission.     

Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis

BACKGROUND: Plasma exchange (PE) is effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except from acetylcholine receptor antibodies (AChRAb) some other inflammatory mediators possibly activated in MG may be also removed during PE. METHODS AND RESULTS: Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients (pts) with MG indicated to the treatment with PE. Pts were subdivided on the basis of the serum levels of AChRAb into 2 groups (8 pts with low AChRAb, 12 pts with high AChRAb). Soluble adhesion molecules and cytokines were measured before the 1st and last PE, at the end of the 1st PE and in the samples of plasma filtrate obtained during the 1st PE. Pts with MG had before the 1st PE higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both the first PE and the course of PE led to the substantial decrease of serum levels of AChRAb, sICAM-1 and sVCAN-1, serum levels of sIL-2R and sTNF-R II were not, however, significantly influenced by both the single and the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrate, too. Pts with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than pts with low AChRAb. CONCLUSIONS: Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in pts with MG indicated to the treatment by PE suggest some systemic activation of immune response which is more pronounced in pts with high circulating AChRAb. PE led to the decrease of serum AChRAb and soluble adhesion molecules due to their effective filtration, but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with synthetic membrane.