Adenosine triphosphate for cardioversion of supraventricular tachycardia in two hydropic fetuses.

OBJECTIVE: We performed a retrospective study to check the effectiveness of adenosine triphosphate (Striadyne) for cardioversion of fetal supraventricular tachycardia (SVT) and to evaluate neonatal outcome after prenatal treatment of severe SVT with fetal hydrops. METHODS: Two hydropic fetuses with SVT were treated with Striadyne injection into the umbilical vein, as an additional treatment to the digoxin given intravenously to the mother. Both fetuses were in severe condition, with ultrasound, Doppler and laboratory signs of fetal distress and congestive heart failure. RESULTS: Sinus rhythm was obtained in both cases for different periods of time, without side effects of Striadyne. The children survived. There were severe cardiac and neurologic problems after delivery. CONCLUSIONS: Striadyne was an effective drug in converting SVT to the sinus rhythm in hydropic fetuses. Digoxin was useless in these fetuses in spite of the therapeutic level which was obtained in both mothers. We suppose that fetal SVT causing fetal hydrops could be the reason of brain damage, and intensive antiarrhythmic treatment seemed to be necessary.

Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population.

T-cell co-stimulation delivered by the molecules B7-1 or B7-2 through CD28 has a positive effect on T-cell activation, whereas engagement of cytotoxic T-lymphocyte antigen 4 (CTLA-4) by these molecules inhibits activation. In vivo administration to mice of blocking monoclonal antibodies or Fab fragments against CTLA-4 can augment antigen-specific T-cell responses and, thus, therapy with monoclonal antibody against CTLA-4 has potential applications for tumor therapy and enhancement of vaccine immunization. The effects of B7-1 and B7-2 co-stimulation through CD28 depend on the strength of the signal delivered through the T-cell receptor (TCR) and the activation state of T cells during activation. Thus, we sought to determine whether these factors similarly influence the effect of B7-mediated signals delivered through CTLA-4 during T-cell activation. Using freshly isolated human T cells and Fab fragments of a monoclonal antibody against CTLA-4, we demonstrate here that CTLA-4 blockade can enhance or inhibit the clonal expansion of different T cells that respond to the same antigen, depending on both the T-cell activation state and the strength of the T-cell receptor signal delivered during T-cell stimulation. Thus, for whole T-cell populations, blocking a negative signal may paradoxically inhibit immune responses. These results provide a theoretical framework for clinical trials in which co-stimulatory signals are manipulated in an attempt to modulate the immune response in human disease.

Cross-reactivity of T-cell clones specific for altered peptide ligands of myelin basic protein.

We have determined that certain altered peptide ligands (APLs) can induce T-cells specific for the native peptide myelin basic protein (MBP) p85-99 to secrete Th2-type cytokines such as IL-4 and IL-5 in the absence of significant Th1-type cytokines. However, it is not known whether stimulation with APLs will activate autoreactive T cells or a distinct population of cells. In the present study, 18 T-cell clones that reacted with either MBP p85-99 or one of three APLs of the peptide substituted at TCR contact residues were generated. T-cells were tested functionally for their reactivity to the original stimulating peptide as well as to the MBP APLs. In addition, the T-cell receptor (TCR) alpha and beta chains of each of these clones were sequenced. In a series of T-cell clones isolated from a multiple sclerosis patient, stimulation of T-cells with the APL 93A, which has an alanine for lysine substitution at the TCR contact residue 93, did not induce substantial proliferation of MBPp85-99-specific T-cell clones, indicating that a distinct set of T-cell clones was induced. However, this was not the case for another set of T-cell clones from a different individual in which the 93A peptide induced clonal expansion of T-cells highly reactive with the native MBPp85-99 antigen. Thus, the potential beneficial effect of using APLs to induce downregulatory cytokines appears to depend on the specific T-cell repertoire of the individual patient.

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.

Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.

Direct ex vivo analysis of activated, Fas-sensitive autoreactive T cells in human autoimmune disease.

The frequency of clonally expanded and persistent T cells recognizing the immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in subjects with typical relapsing remitting multiple sclerosis (MS). T cells expressing mRNA transcripts encoding T cell receptor (TCR)-alpha and -beta chains found in T cell clones previously isolated from these subjects recognizing the MBPp85-99 epitope were examined. In contrast to frequencies of 1 in 10(5)-10(6) as measured by limiting dilution analysis, estimates of the T cell frequencies expressing MBPp85-99-associated TCR chain transcripts were as high as 1 in 300. These high frequencies were confirmed by performing PCR on single T cells isolated by flow cytometry. MBPp85-99 TCR transcripts were present in IL-2 receptor alpha-positive T cells which were induced to undergo Fas-mediated cell death upon antigen stimulation. These data demonstrate that at least a subpopulation of patients with MS can have a very high frequency of activated autoreactive T cells.

[Class II HLA antigens in patients with multiple sclerosis from Warsaw and Gdansk regions]. / Antygeny HLA II klasy u chorych na stwardnienie rozsiane z regionu Warszawy i Gdanska.

An investigation of class II histocompatibility antigens was carried out in patients with definite diagnosis of multiple sclerosis (MS) according to Poser's criteria. There were 42 patients from Warsaw and 98 patients from Gdansk. Histocompatibility antigens were assayed with microlymphocytotoxicity test. 6 antigens on locus DR and 1 antigen on locus DQ were evaluated. The antigen frequencies were compared in the two groups using the chi-square test. The antigen HLA-DQw1 occurred significantly more frequently in MS patients compared to healthy control group. Antigens HLA-DR2 and DR3 occurred more frequently in patients from Gdansk than Warsaw region.

Pargyline pretreatment prevents immunological changes induced by MPTP in mice.

The relationship between the central dopaminergic and the immune system is poorly understood. Experimental work suggest that damage of the nigrostriatal system may influence immunity. Immunological abnormalities have been described in Parkinson's disease and in a mouse model of this disorder induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this report, we present evidence that reduced numbers of L3T4 T cells in blood, and diminished primary antibody response to sheep erythrocytes in MPTP treated mice can be restored by pargyline pretreatment. Since pargyline prevents dopamine depletion in the striatum in MPTP treated animals, our data extend previous experimental observations and support a possible role for dopamine in immune regulation.

Oligoclonal expansion of gamma delta T cells in cerebrospinal fluid of multiple sclerosis patients.

We have used a PCR based method to analyse TCR gamma chain repertoire and clonality of gamma delta T cells in the CSF and blood of II MS patients. Samples collected from nine patients with other neurological diseases were used as a control. Five controls had central nervous system inflammation and four had non-inflammatory processes. We have observed a decreased percentage of gamma delta T cells expressing TCR gamma with V gamma 9 and J gamma P fragments in the CSF samples in comparison with the blood. We did not final clonal expansion of the gamma delta T cells in any control case. Clonal expansion of gamma delta T cells occurred in five of II MS cases in the CSF but not in the blood. Two of these clones expressed TCR gamma rearranged with V gamma 9 and J gamma 1 fragments, two others used V gamma 10 and J gamma P1, and one used V gamma 9 and J gamma P fragments. We found no correlation between clonality and clinical state of patients, duration of the disease or number of cells in CSF. Our study provides additional evidence for the possible role of the gamma delta T cells in the MS pathogenesis.

[The alpha-fetoprotein level analysis in open neural tube defects and chromosomal aberrations in the fetus]. / Analiza poziomu alfa-fetoprotein w przypadkach otwartych wad cewy nerwowej i aberracji chromosomowych u plodu.

During the last 12 years 4258 amniocenteses were performed between the 12th and 20th week of gestation (including 323 early amniocenteses carried out before 15th week). In every case, cytogenetical examination was performed and concentration of AFP was determined. In cases with elevated AFP level electrophoresis of AchE izoenzymes was performed. The results of the tests enabled us to calculate laboratory standard values of AFP in the amniotic fluid for 12th to 20th weeks of gestation. In 22 of 44 pregnancies with Down's syndrome the value of AFP concentration was below the 25th percentile of the laboratory normal value. In 5 of 10 pregnancies with Edward's syndrome AFP level exceeded significantly the 75th percentile of the laboratory norm. In two cases it was due to coexisting spina bifida and in one case due to omphalocele. In 28 amniotic fluid samples AFP concentration exceeded normal level and electrophoresis of AchE revealed additional band. In 26 cases increased values of AFP were due to open neural tube defect in the fetus: 13 cases of anencephaly and 13 cases of spina bifida; in the remaining two other cases omphalocele was found.

[Risk factors of late ventricular arrhythmias after total correction of tetralogy of Fallot in children]. / Czynniki ryzyka wystepowania komorowych zaburzen rytmu serca w póznym okresie po korekcji calkowitej zespolu Fallota u dzieci.

The authors present an analysis of pre-, intra- and postoperative risk factors of late ventricular arrhythmias in 100 children in 5-12 years after total correction of the tetralogy of Fallot. Complex arrhythmias (III-V class according to Lown classification) were found in 19% of patients. Risk factors were: in the pre- and intraoperative period--marked endocardial fibrosis of the right ventricular outflow tract, long bypass time (> 180 min) and aortic cross-clamp (> 90 min), in the post-operative period-left ventricular dysfunction in echocardiographic examination and age > 10 years at time of the study. Complex ventricular arrhythmias were more frequent in patients with associated supraventricular arrhythmias and with progressive bundle branch block.

[Diagnosis of Wilson disease by methods of molecular genetics]. / Diagnostyka choroby Wilsona z zastosowaniem metod genetyki molekularnej.

Wilson's disease is an inborn error of cooper metabolism, inherited as an autosomal recessive gene. According to the variety of clinical features (most frequency hepatic, neurological, psychiatric and haematological) the clinical diagnostics often meets a number of difficulties. It is important to establish the diagnosis in the pre-symptomatic period, because treatment can prevent developing of the disease. The diagnosis is usually established after biochemical blood tests, that is the serum cooper and ceruloplasmin, 24-hour urinary cooper excretion and the functional test with radioactive cooper. However, all the methods quite frequently do not make it possible to confirm or exclude the diagnosis in sporadic cases. Sometimes, it is also impossible to distinguish between preclinical homozygotes and heterozygotes. Localizing of the pathogenic gene on the long arm of chromosome 13 opens new diagnostic prospects. Still, it is essential to find genetic markers situated next to the gene for applying the linkage analysis. It will also help to isolate the gene and to establish the primary biochemical defect of the disease.

Immunological changes in the MPTP-induced Parkinson's disease mouse model.

The role of the central dopaminergic system in modulating immune response is not completely established. We examined the influence of central dopamine depletion on selected parameters of immune functions in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated and untreated mice. IgM antibody production of splenocytes to sheep red blood cells was reduced in MPTP-treated mice (P < 0.001). Proliferation of splenocytes in response to a wide range of mitogen concentrations (Concanavalin A, phytohaemagglutinin, lipopolysaccharide) was also significantly diminished in MPTP-treated mice. Production of migration inhibition factor (MIF) was diminished only in low mitogen concentration. Our results obtained in the experimental model of Parkinson's disease provide evidence that the damage of the central dopaminergic pathways induces alterations of some immune functions in mice.

[Emergency epicardial dissection of the accessory pathway in a patient with atrioventricular nodal reentrant tachycardia]. / Przeciecie dodatkowego szlaku przewodzenia w trybie pilnym u chorego z uporczywym czestoskurczem przedsionkowo-komorowym.

Diagnostic and therapeutic problems in 14 year old patient with concealed WPW syndrome were presented. Paroxysms of atrio-ventricular reentrant tachycardia 180-220/min were frequently recurring, usually with normal QRS pattern. Tachycardias often had to be terminated by intravenous administration of antiarrhythmic drugs. Long term treatment with various antiarrhythmic agents did not prevent recurrence of tachycardias but they became sustained and were recurring more often. Their other side effects manifested with sinus node disfunction and depression of the heart muscle. The electrophysiologic study revealed right anterior septal accessory pathway. Epicardial dissection of the accessory pathway was urgently performed. The control electrophysiologic study revealed no evidence of conduction through the accessory pathway. The patient did not require antiarrhythmic treatment. During the 12 months follow up no tachycardia occurred.

[Indications for emergency surgical treatment of ectopic atrial tachycardia]. / Chirurgiczne leczenie ektopowego czestoskurczu przedsionkowego--ze wskazan pilnych.

Recurrent automatic atrial tachycardia can induce dilated cardiomyopathy. We present clinical and therapeutic problems of 16 years old male with ectopic left atrial tachycardia refractory to pharmacological therapy. In this patient long periods of atrial tachycardia 200-240/min due to lack of effective medication caused cardiac failure. Uncontrolled taking of various antiarrhythmic drugs and persistent tachycardia led to cardiogenic shock. The electrophysiologic study revealed focus of the tachycardia localized in the area of left cardiac auricle. The rate of the tachycardia was changing from 84 to 240/min, with periods of Mobitz I block in the AV node. In periods of 1:1 AV conduction the tachycardia had sometimes LBBB QRS morphology. The atrial tachycardia provoked unsustained ventricular one. The patient was operated. Resection of left auricle and mitral valvuloplasty were performed. After the operation the patient regained undisturbed sinus rhythm and symptoms of heart failure disappeared.

[Transesophageal stimulation of the left atrium in children with arrhythmia (preliminary report)]. / Stymulacja przezprzelykowa przedsionka lewego w zaburzeniach rytmu serca u dzieci (doniesienie wstepne).

The conduction system of the heart was studied in 41 patients with cardiac arrhythmias by oesophageal stimulation of the left atrium. 31 children had a history of paroxysmal supraventricular tachycardia, 5 supraventricular or/and ventricular premature beats and 5 were studied because of suspected bradycardia-tachycardia syndrome. In all patients stimulation of the left atrium was well tolerated. There were no side effects or complications. The results showed that oesophageal stimulation of the left atrium was a faithful noninvasive method in diagnostic studies of the conduction system of the heart. This method was effective in studying the mechanism of supraventricular arrhythmias.