The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.

Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to crossreactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants.

Necrotizing pulmonary aspergillosis and ventricular assist device infection: case report and review of literature.

Necrotizing pulmonary aspergillosis and Aspergillus device infection are rare and have potentially fatal complications after left ventricular assist device (LVAD) implantation. To date, few cases of patients surviving Aspergillus device infection have been published, with survival reported only after device removal. We present a patient implanted with an LVAD in whom necrotizing pulmonary aspergillosis with device involvement was successfully treated by segmentectomy and prolonged antifungal treatment without device exchange or removal. Similar cases in the literature were searched for and are discussed in view of the severity of this complication.

Ainsliaolide D: a new sesquiterpene lactone from Ainsliaea pertyoides.

Ainsliaolide D, a new guaiane-type sesquiterpene lactone, was isolated from the roots of Ainsliaea pertyoides Fr. var. albotomentosa Beauverd. Its structure was determined based on spectral data.

[Acquired Gitelman syndrome associated with Sjögren's syndrome and scleroderma]. / Syndrome de Gitelman acquis au cours d'un syndrome de Gougerot-Sjögren associé à une sclérodermie.

Tubulopathy can complicate autoimmune diseases. It is usually a distal tubular acidosis, but Fanconi syndrome or Bartter syndrome has been exceptionally reported. We report a case of acquired Gitelman syndrome in a 32-year-old male who also presented diffuse scleroderma autoimmune thyroiditis, and Sjögren's syndrome. Only three cases of Sjögren syndrome associated with Gitelman syndrome have been previously reported in literature. The absence of other cases in the family and absence of mutation SLC12A3 emphasise the relation between autoimmune disease and this tubulopathy.

Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study.

INTRODUCTION: The efficacy of midodrine for the management of patients with neurocardiogenic syncope was assessed prospectively in a randomized control study. METHODS AND RESULTS: Patients who had at least monthly occurrences of syncope and a positive tilt-table test were included in the study. A total of 61 patients were randomly allocated to treatment either with midodrine or with fluid, salt tablets, and counseling. Midodrine was given at a starting dose of 5 mg three times a day and increased up to a dose of 15 mg three times a day when required. Midodrine was given during the daytime every 6 hours. Thirty-one patients were assigned to treatment with midodrine; the other 30 patients were advised to increase their fluid intake and were instructed to recognize their prodromes and abort the progression to syncope. Patients were followed-up for at least 6 months. A quality-of-life questionnaire was administered at the time of randomization and 6 months after. At the 6-month follow-up, 25 (81%) of 31 midodrine-treated patients and 4 (13%) of the 30 fluid-therapy patients had remained asymptomatic (P < 0.001). One patient had to discontinue taking midodrine due to severe side effects and another six patients experienced minor side effects that did not require drug discontinuation. CONCLUSION: Midodrine appeared to provide a significant benefit in patients with neurocardiogenic syncope. To prevent recurrence of symptoms, dose adjustments were required in about one third of patients.

Validation of a diagnosis model for differentiating bacterial from viral meningitis in infants and children under 3.5 years of age.

The aim of this study was to validate, in a population of infants and children under 3.5 years of age, a diagnosis model that provides a figure for the probability of bacterial meningitis (pABM), based on four parameters collected at the time of the first lumbar tap: the cerebrospinal fluid (CSF) protein level, CSF polymorphonuclear cell count, blood glucose level, and leucocyte count. The best cut-off value for distinguishing between bacterial and viral meningitis was previously found to be 0.1, since 99% of meningitides associated with pABM<0.1 were viral. The charts of 103 consecutive children aged 0.1-3.5 years who had been hospitalised for acute meningitis were reviewed. Each case was sorted into the following three categories for aetiology: bacterial (positive CSF culture, n=48); viral (negative CSF culture and no other aetiology, and no antibiotic treatment after diagnosis, n=36); and undetermined (fitting neither of the first two definitions, n=19). After computation of pABM values in each case, the predictive values of the model were calculated for different pABM cut-off values. The results confirmed that the best cut-off pABM value was 0.1, for which the positive and negative predictive values in this model were 96% and 97%, respectively. Only one case of bacterial meningitis (lumbar tap performed early in an infant with meningococcal purpura fulminans with negative CSF culture) was associated with a pABM value of <0.1. This model is quite reliable for differentiating between bacterial and viral meningitis in children under 3.5 years of age, and it may enable physicians to withhold antibiotics in cases of meningitis of uncertain aetiology.

Prospective validation of a diagnosis model as an aid to therapeutic decision-making in acute meningitis.

The aim of this study was to validate a diagnosis model that provides pABM, the probability of bacterial versus viral meningitis, based on four parameters collected at the time of first lumbar tap: cerebrospinal fluid protein level, cerebrospinal fluid polymorphonuclear cell count, blood glucose level, and leucocyte count. The model was evaluated prospectively as an aid to therapeutic decision-making in 109 consecutive patients with acute meningitis and negative cerebrospinal fluid Gram stain. In each case pABM was computed before a therapeutic decision and three diagnoses were established successively: (i) clinical evaluation, i.e. before pABM computation (bacterial meningitis, viral meningitis, or meningitis of undetermined origin); (ii) computation of pABM (viral meningitis if pABM< 0.1, bacterial meningitis otherwise); and (iii) determination of definitive diagnosis (bacterial meningitis: positive cerebrospinal fluid culture; viral meningitis: negative cerebrospinal fluid culture, no other aetiology and no treatment; meningitis of undetermined origin: cases fitting neither of the first two diagnoses). The computed diagnosis was viral meningitis in 78 of the 80 cases diagnosed definitively as viral meningitis, and bacterial meningitis in four of the five cases diagnosed definitively as bacterial meningitis. Negative and positive predictive values and accuracy of the model were 98.7%, 66.7%, and 96.5%, respectively. The clinical diagnosis was undetermined in 22 cases, 15 of which were diagnosed definitively as viral cases; in all of these 15 cases, the computed diagnosis was viral meningitis, leading the physician to refrain from starting antibiotics in all of them. The results confirm that the model evaluated is reliable and aids in the identification of patients in whom antibiotics can be safely avoided.

Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required? Yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications.

OBJECTIVES: We sought to determine the yield of in-hospital monitoring for detection of significant arrhythmia complications in patients starting sotalol therapy for atrial arrhythmias and to identify factors that might predict safe outpatient initiation. BACKGROUND: The need for hospital admission during initiation of antiarrhythmic therapy has been questioned, particularly for sotalol, with which proarrhythmia may be dose related. METHODS: The records of 120 patients admitted to the hospital for initiation of sotalol therapy were retrospectively reviewed to determine the incidence of significant arrhythmia complications, defined as new or increased ventricular arrhythmias, significant bradycardia or excessive corrected QT (QTc) interval prolongation. RESULTS: Twenty-five patients (20.8%) experienced 35 complications, triggering therapy changes during the hospital period in 21 (17.5%). New or increased ventricular arrhythmias developed in 7 patients (5.8%) (torsade de pointes in 2), significant bradycardia in 20 (16.7%) (rate <40 beats/min in 13, pause >3.0 s in 4, third-degree atrioventricular block in 1, permanent pacemaker implantation in 3) and excessively prolonged QTc intervals in 8 (6.7%) (dosage reduced or discontinued in 6). Time to the earliest detection of complications was 2.1 +/- 2.5 (mean +/- SD) days after initiation of sotalol, with 22 of 25 patients meeting criteria for complications within 3 days of monitoring. Baseline electrocardiographic intervals or absence of heart disease failed to distinguish a low risk group. Multivariate analysis identified absence of a pacemaker as the only significant predictor of arrhythmia complications (p = 0.022). CONCLUSIONS: Because clinically significant complications can be detected with in-hospital monitoring in one of five patients starting sotalol therapy, hospital admission is warranted for initiation of sotalol. Patients without pacemakers are at higher risk for these complications.

[Autoimmunity: a concept to be revisited?]. / L'auto-immunité: un concept à réviser?

Autoimmunity is thought to be a defect in immunologic tolerance, resulting in the activation and expansion of self antigen-specific T and B lymphocyte clones and the production of circulating antibodies, and a myriad of cytokines and other inflammatory mediators. This hypothesis, which speculates on an aberrant response of the immune system to normal self antigens has exerced a powerful influence on clinical investigations and therapeutic researches. Although much information has accumulated, the mechanism of autoimmune disease remains poorly understood and little attention has been paid to the hypothesis that autoimmune diseases might be caused by a conventional immunological response against self antigens for which tolerance has never been established. Clinical practice would undoubtedly get a lot out of it, as well as new therapeutic measures.

Paradoxical failure of QT prolongation during cardioinhibitory neurocardiogenic syncope.

QT modulation was explored in 31 patients with cardioinhibitory neurocardiogenic syncope. Despite a marked in increase in RR intervals, the QT interval remained stable.

Changes in left ventricular volume during head-up tilt in patients with vasovagal syncope: an echocardiographic study.

We tested the hypothesis that patients who have vasovagal syncope during head-up tilt have a greater decrease in their left ventricular volume in response to tilt than do normal subjects. Measurements were done in the supine position and during graded tilt by using two-dimensional echocardiography. We compared seven patients with vasovagal syncope with nine normal volunteers. The rate of reduction of end-diastolic volume index during tilt was faster in the vasovagal group than in normal subjects. A more significant reduction of stroke index and ejection fraction during tilt was found in the vasovagal group than in normal subjects, possibly because of more peripheral translocation of blood volume in the venous system during tilt and an early vagal effect on ventricular contraction.

[Way, aim, state and perspective of the Aujeszky's disease (AD) eradication program in North Rhine Westphalia]. / Weg, Ziel, Stand und Perspektive der AK-Bekämpfung in Nordrhein-Westfalen.

In August 1991 a program to eliminate Aujeszky's disease from the whole pig herds in North Rhine Westphalia within six years was initiated. The wide area vaccination program combined with the eradicating program was so successful that most farms in North Rhine Westphalia were free of infection till February 1995, only 1% of the farms have not taken part in this program. As a consequence of the different situation of the control of the Aujeszky's disease in other states changes of the decree which has the objectives of eradicating Aujeszky's disease are planned. The changes should allow to transport pigs from herds which are not free of infection after April 1, 1995 too under certain circumstances. To keep the present eradicating success in North Rhine Westphalia special protection measures are necessary. This includes especially the decree of the state protection decree which came into effect on April 1, 1995.

Head-up tilt and hemodynamic changes during orthostatic hypotension in patients with supine hypertension.

OBJECTIVES: This study assessed the mechanism(s) of the decrease in upright blood pressure in patients with supine hypertension by using the tilt test and a hemodynamic approach. BACKGROUND: Orthostatic hypotension in patients with supine hypertension creates a pathophysiologic and therapeutic dilemma. METHODS: We studied 28 consecutive patients with history of orthostatic intolerance amounting to recurrent syncope in 13 of them (15 men, 13 women; mean [SD] age 65 +/- 11 years). They all had supine hypertension (systolic blood pressure > 160 mm Hg) and orthostatic hypotension (found to be a decrease in systolic blood pressure > 30 mm Hg during tilt test). Cardiac output, cardiopulmonary volume and systemic resistance were assessed by radionuclide first-pass technique (technetium-99m red blood cell tagging). Total blood volume was determined by radioiodinated serum albumin, and the ratio of cardiopulmonary to total blood volume was used as an index of venous capacitance. RESULTS: Twenty-one patients had accentuated venous pooling defined as a tilt-induced decrease in cardiopulmonary volume/total blood volume ratio > 15% from baseline or a supine ratio < 14% (normal 16% to 18%), or both. Seven of the 28 patients had autonomic insufficiency; 6 of the 7 also had venous pooling; 1 patient had autonomic insufficiency only. Neither clinical history nor changes during tilt differentiated the subgroups. Plasma catecholamine levels increased during head-up tilt in all subgroups, and differences in their increase were not significant between patients with venous pooling and those with autonomic insufficiency. However, radionuclide hemodynamic variables revealed that patients with venous pooling compensated for the decrease in stroke volume by increasing peripheral resistance, whereas patients with autonomic dysfunction did not. CONCLUSIONS: Orthostatic hypotension in patients with supine hypertension may have multiple etiologies. Hemodynamic assessment with determination of cardiopulmonary volume and systemic vascular resistance differentiated between venous pooling and autonomic insufficiency in these patients; head-up tilt and plasma catecholamine levels did not. These findings may have important therapeutic implications.

The role of pacing for the management of neurally mediated syncope: carotid sinus syndrome and vasovagal syncope.

The role of permanent cardiac pacing for the management of neurocardiogenic syncope is controversial; however, it does have a secondary role in appropriately selected individuals. Neurocardiogenic syncope includes vaso-vagal and enhanced antagonism of sympathetic-parasympathetic mechanisms. Differentiation of the so-called cardiac inhibitory, vasodepressor, and mixed forms of these disorders is frequently misleading when establishment of effective treatment strategies is attempted. Cardiac pacing can artificially restore near-normal heart rate and atrioventricular synchrony during a neurocardiogenic syncopal episode; however, cardiac pacing does not alter the peripheral vasodilatation, nor does it prevent the occurrence of the reflux response. Syncopal patients with carotid sinus hypersensitivity or vasovagal responses that include marked bradycardia and loss of atrioventricular synchrony can be supported by dual-chamber cardiac pacing in combination with other therapeutic interventions that diminish the severity of the reflex response. The conditions of patients with carotid sinus syndrome and carotid sinus hypersensitivity are frequently improved with cardiac pacing, and the conditions of elderly patients with vasovagal syncope are commonly improved with artificial pacing. The classic younger patient with malignant vasovagal syncope derives less benefit from artificial pacing; however, in carefully selected persons dual-chamber pacing combined with drug therapy and education decreases syncopal episodes and permits a return to normal activities.

Is absolute hypovolemia a risk factor for vasovagal response to head-up tilt?

To test the hypothesis that hypovolemia is associated with an increased incidence of vasovagal syncope during head-up tilt (HUT) 45 patients with history of syncope or presyncope were studied. Blood volume (radio-iodinated serum albumin) was determined, then subjects underwent a graded HUT (from 15 degrees-60 degrees HUT) with cuff blood pressure and ECG monitoring. All patients were kept on their own medications during evaluation. Thirty patients (12 male, 18 female, mean age 50 +/- 19 [SD] years) had hypovolemia, defined as blood volume < 90% of lab normal for corresponding sex, while 15 patients (7 male, 8 female, mean age 52 +/- 21 years) were normovolemic with blood volume ranging from 91%-110% of sex-matched normal subjects. The normovolemic patients served as controls. During HUT, a vasovagal response was elicited in 5 of the 30 hypovolemics and in 4 of the 15 normovolemic (16.7% and 26.7%, respectively, P = NS). In those who developed vasovagal response, the changes of heart rate and blood pressure during HUT were not significantly different between hypovolemics and normovolemics, neither at the endpoint (vasovagal response) nor immediately before the development of the vasovagal response. In patients with nonvasovagal events, four types of hemodynamic responses to tilt were observed: normal blood pressure response associated with normal heart rate increase, normal blood pressure response in association with accentuated increase in heart rate, orthostatic hypotension with normal acceleration of heart rate, and orthostatic hypotension with accelerated increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity and specificity of the tilt table test in young patients with unexplained syncope.

UNLABELLED: The usefulness of the head-up tilt testing (HUT) has been previously addressed in diagnosing vasovagal neuroregulatory syncope in the teenage population. However, data concerning sensitivity and specificity is deficient due to the lack of control groups. We compared the response to HUT in young patients referred because of syncope or near syncope (n = 44, mean age 16 +/- 3 years SD) to healthy young volunteers with a normal physical examination and no previous history of syncope (n = 18, mean age 16 +/- 2 years) and to determine the sensitivity and specificity of HUT. The graded tilt protocol was performed at 15 degrees, 30 degrees, and 45 degrees (each for 2 min), and then 60 degrees for 20 minutes. Cuff blood pressure was measured every minute and lead II ECG was continuously monitored. RESULTS: 25 of the 44 patients (57%) developed a vasovagal response or became symptomatic after 13.8 +/- 5.7 minutes of HUT. Three of the 18 volunteers (17%) had a vasovagal response and became symptomatic after 9 +/- 3 minutes of HUT. There was no statistical difference among the four groups (with and without tilt induced vasovagal response) in terms of age and baseline hemodynamic data. The sensitivity of 20 minutes HUT was 57% and its specificity was 83%. The presyncopal hemodynamic response in patients with history of syncope that was characterized by a significant decrease in systolic blood pressure and lack of increase of diastolic blood pressure as compared with baseline and with other groups.(ABSTRACT TRUNCATED AT 250 WORDS)