Four-Way Wada: SEEG-based mapping with electrical stimulation, high frequency activity, and phase amplitude coupling to complement traditional Wada and functional MRI prior to epilepsy surgery.

Presurgical evaluation of refractory epilepsy involves functional investigations to minimize postoperative deficit. Assessing language and memory is conventionally undertaken using Wada and fMRI, and occasionally supplemented by data from invasive intracranial electroencephalography, such as electrical stimulation, corticortical evoked potentials, mapping of high frequency activity and phase amplitude coupling. We describe the comparative and complementary role of these methods to inform surgical decision-making and functional prognostication. We used Wada paradigm to standardize testing across all modalities. Postoperative neuropsychological testing confirmed deficit predicted based on these methods.

Longitudinal neurodevelopmental profile of a pediatric patient with de novo SPTAN1, epilepsy, and left hippocampal sclerosis.

Pathogenic variants in SPTAN1 result in abnormal neurodevelopment but limited information is available on the spectrum of neurodevelopmental profiles associated with variations in this gene. We present novel data collected at two time points over a three-year period in a nine-year-old patient with heterozygous de novo SPTAN1 variant, drug-resistant epilepsy, and left hippocampal sclerosis. Across evaluations, our patient's performance was highly variable, ranging from below age expectation to within age-expected range. The patient exhibited relative cognitive strengths at both time points on verbal-expressive tasks. Weaknesses were seen in her attention, executive function, psychomotor processing speed, fine motor, visual-motor integration, and social skills. Memory findings were consistent those associated with left hippocampal sclerosis. Evaluations resulted in diagnoses including attention deficit hyperactivity disorder and autism spectrum disorder.

Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans.

The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social interactions and enhanced by vasopressin; however, the neural mechanisms mediating this effect in humans are unknown. Using functional magnetic resonance imaging (fMRI) and an implicit social recognition matching task, we employed a double-blinded procedure in which 20 healthy male volunteers self-administered 40 UI of vasopressin or placebo intranasally, 45 min before performing the matching task in the scanner. In a random-effects fMRI analysis, we show that vasopressin induces a regionally specific alteration in a key node of the theory of mind network, the left temporoparietal junction, identifying a neurobiological mechanism for prosocial neuropeptide effects in humans that suggests novel treatment strategies.

Production and characterization of monoclonal antibodies against pigtailed macaque (Macaca nemestrina) cell adhesion molecules.

Our previous in vitro studies indicate a significant role for cell adhesion molecules in the biology of HIV-1 and HTLV-1. Confirmation of the involvement of these molecules in the pathogenesis of retrovirus infection in vivo will require a suitable animal model. The SIV/pigtailed macaque (Macaca nemestrina) model of acquired immunodeficiency syndrome (AIDS) is an ideal system in which to study adhesion molecules and viral pathogenesis. The monoclonal antibodies (MAbs) against human adhesion molecules previously produced in our laboratory either do not react with or fail to block function of pigtailed macaque adhesion molecules. We have used papiovirus-transformed pigtailed macaque B cells as immunogen to generate murine MAbs against macaque adhesion molecules including ICAM-1, VCAM-1, and LFA-1. The specificity of the MAbs was confirmed by immunoprecipitation from lysates of vectorially iodinated cells, flow cytometry analysis of transfected cell lines and primary cells, binding assays on recombinant soluble human VCAM-1 and ICAM-1, and by inhibition of adhesion functions. MAbs against ICAM-1 and VCAM-1 showed positive staining of fixed tissue in immunohistochemistry studies. The same antibodies also blocked the function of these two adhesion molecules. The new MAbs can be used to study the tissue expression of adhesion molecules in SIV-infected animals as well as to test the involvement of these molecules in virus infection. Thus they should prove invaluable as probes of the role of cell adhesion molecules in AIDS pathogenesis in an animal model.

Bifurcations of periodic orbits in axisymmetric scalefree potentials.

We study orbits in potentials with central cusps, emphasizing the spheroidal equidensity (SED) potentials generated by mass distributions with spheroidal equidensity surfaces. The most prominent bifurcations are those related to 1:1 and 4:3 resonances between radial motions and motions perpendicular to the central plane. We find that 1:1 resonances can cause the thin tube orbit, as well as the equatorial plane orbit, to become unstable. We concentrate on period-tripling bifurcations because they appear to be the least understood. We study them via a class of analytic maps. This study suggests that stable period-three orbits generally arise de novo in stable and unstable pairs via a turning-point bifurcation, and not through a bifurcation from the thin tube at a 120 degree rotation angle. The stable period-three orbits typically have only a short span of existence before becoming unstable to a period-doubling instability through a supercritical pitchfork bifurcation.

[Agranulocytosis caused by infectious-toxic bone marrow damage after Borrelia infection]. / Agranulozytose durch infektiös-toxische Knochenmarkschädigung nach Borrelien-Infektion.

A 19-year-old girl developed a fever of up to 40 degrees C and, during an episode of high fever, generalized seizures. Physical examination on admission was unremarkable, except for several small lymph nodes. Differential blood count showed a leukopenia (1700/microliters) with 14% stab and 7% segmented neutrophils. After initial clinical improvement she again became feverish and the differential count now showed agranulocytosis with a total white cell count of 1400/microliters. Because of the time of year and the geographic location borreliosis was now considered in the differential diagnosis. The antibody titre against Borrelia was raised to 1:64 (IgM) and 1:256 (IgG). Her condition and the differential blood count rapidly improved on intravenous antibiotic treatment with cefotiam (2 g two times daily) and gentamicin (120 mg two times daily), as well as filgrastim (granulocyte-colony stimulating factor) subcutaneously. Antibiotic treatment was continued after 6 days with oral ampicillin (1 g three times daily) for 3 weeks. Follow-up examination six weeks later found the patient to be symptom-free.

Early biochemical indicators of the obliterative bronchiolitis syndrome in lung transplantation.

The diagnosis of the obliterative bronchiolitis syndrome in lung transplantation is presently best established by evaluation of postoperative lung function tests. Unfortunately the decline in lung function occurs only when obliteration has progressed significantly and is therefore not an early predictive indicator. To distinguish patients at increased risk for the development of obliterative bronchiolitis, we regularly assessed the chemiluminescence response of polymorphonuclear leukocytes, opsonic capacity, and plasma elastase/beta-N-acetylglucosaminidase in 52 outpatients (25 women and 27 men; mean age 45 +/- 12 years) who underwent transplantation between January 1991 and January 1992. Recent onset bronchiolitis within the described observation period occurred in 16 patients (group obliterative bronchiolitis). A matched cohort of 16 patients was formed according to type of procedure, age and follow-up (control) from the remaining 36 patients. Data obtained from a period 6 months before clinical onset of the syndrome showed a significant drop of the opsonic capacity (group obliterative bronchiolitis = 87% +/- 7%; control = 100% +/- 9%; p < 0.023) and rise of the N-acetyl-D-glucosaminidase (group obliterative bronchiolitis = 7.5 +/- 2 U/L; control = 5.8 +/- 1.8 U/L; p < 0.04). No correlation was found between the number of infectious events or rejection episodes and the incidence of obliterative bronchiolitis. According to these results, it can be concluded that a decrease in the plasma opsonic capacity and a rise in beta-N-acetylglucosaminidase may be early markers before clinical onset of obliterative bronchiolitis. The nonspecific immune system may therefore play an important role in the development of obliterative bronchiolitis.

Surgical treatment of airway complications after lung transplantation.

The treatment of dehiscence or stenosis of the bronchus after lung transplantation has to date consisted of endobronchial stenting or balloon dilation. Operative intervention has been limited to retransplantation with all its limitations. In our series of 121 anastomoses at risk, severe bronchial stenosis occurred in 11 (9%). In five instances the airway complications were treated surgically: two patients underwent retransplantation, one patient had a bilobectomy, and two required sleeve resection of the stenotic segment. All these procedures successfully removed the stenosis. This experience demonstrates that options other than bronchial anastomotic stenting and dilation may be successfully used to overcome posttransplantation anastomotic complications. Conventional resections may result in superior long-term graft function compared with retransplantation, avoiding the immunologically adverse effects of the latter procedure.

Functional results after lung retransplantation.

In selected cases with either acute or chronic graft failure after lung or heart-lung transplantation, retransplantation remains the only therapeutic option. Since December 1987, we have performed a total of 110 single lung, bilateral lung, and combined heart-lung transplantations in 102 patients including five early and four late retransplantations in eight patients. Early retransplantation was indicated for severe reperfusion injury after single lung transplantation (n = 2) or heart-lung transplantation (n = 1), for persistent pulmonary hypertension caused by an unrecognized aortopulmonary window (n = 1), for central airway necrosis, and for contralateral pulmonary artery bleeding after bilateral lung transplantation (n = 1). Two of these patients after single lung transplantation were bridged with extracorporeal membrane oxygenation for 9 and 11 days until single lung retransplantation. Three patients underwent late single lung retransplantation 14, 24, and 26 months after single lung transplantation (n = 2) or heart-lung transplantation (n = 1) for chronic rejection, and an additional patient was treated successfully by bilateral lung retransplantation for obliterative bronchiolitis and central airway stenosis 26 months after bilateral lung transplantation. Two patients died 19 and 140 days, respectively, after acute retransplantation because of early graft failure and progressive rejection, respectively, while the other patients were discharged from the hospital. Mortality was 22.2% in the retransplantation group versus 15.1% (11 of 73 patients) undergoing primary single lung transplantation or bilateral lung transplantation (not significant). Patient survival after retransplantation ranged between 159 and 993 days (median, 453 days). Duration of postoperative ventilation was markedly prolonged in patients who underwent retransplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic rejection following lung transplantation. Incidence, time pattern and consequences.

UNLABELLED: The long-term prognosis following lung transplantation (LTX) depends mainly on the development of chronic rejection which appears clinically as deterioration of the lung function while, histologically, obliterative bronchiolitis (OB) is found. However, it still remains questionable whether heart-lung (HL), double or single lung (DL/SL) transplants behave similarly with regard to incidence and time pattern. Eighty-two patients, transplanted until August 92, were analyzed. Early and late deaths within 180 days postoperatively were excluded. A total of 64 patients at risk could be evaluated. By repeated lung function tests, obstructive airway disease was defined by a drop of 25% or more of the forced expiratory volume in one second (FEV1) in percent of the inspiratory vital capacity. RESULTS: The functional optimum after transplantation was reached after a comparable time-span postoperatively in all groups. Chronic deterioration of the lung function developed earlier following DLTX compared to HLTX and SLTX. Obstructive airway disease was diagnosed in 9/20 (45%) HL, 7/19 (37%) DL, and 7/25 (28%) SL patients. Of these, 4 died and 4 had to be retransplanted for the disease while an additional 15 patients are currently under investigation. It is concluded that the development of obstructive airway disease represents a serious problem in all types of lung transplantation. There is a tendency to earlier development following DLTX--perhaps caused by the greatest immunological potential in this group of patients.

Human immunodeficiency virus infection in microglia: correlation between cells infected in the brain and cells cultured from infectious brain tissue.

In acquired immunodeficiency syndrome, the lesions of the central nervous system in association with the human immunodeficiency virus are thought to be related to an infection of microglia, although no studies are available in which cultured and physiological characteristics of microglia cells infected in vivo have been examined. In this report, we used brain tissue from a child dying of human immunodeficiency virus infection and show that microglia cells were the main cell population being infected. Moreover, isolated macrophage-like cells from fresh brain material revealed a close resemblance to peripheral blood macrophages in their content of surface and intracellular antigens. No virus particles or viral antigens were produced by these cells during the first week of cultivation. Productive infection was readily apparent, however, by day 30. This finding illustrates the slow nature of the virus life cycle in these cells and the minimal cytopathology that accompanied the infection.

[Lung transplantation]. / Lungentransplantation.

In the past 10 years, three different types of lung transplantation were introduced into clinical practice, the combined transplantation of the heart and both lungs (HLTx), unilateral single lung transplantation (SLTx), and bilateral sequential lung transplantation (DLTx). At present, the indications for the various procedures have not been ultimately defined. Through 1991, a total of about 1,100 HLTx, 460 SLTx, and 160 DLTx was performed worldwide. One- und 3-year survival rates amount to 75-60% resp. in HLTx, to 80-70% resp. in SLTx, and to 70-60% resp. in DLTx. In our own experience with 24 HLTx, 32 SLTx, and 18 DLTx patients, global survival rates at one and 3 years are 85 and 80%, resp. The vast majority of surviving patients is able to lead a near normal life both physically and socially.

HAB-1, a new heteromyeloma for continuous production of human monoclonal antibodies.

To obtain suitable cell lines for the immortalisation of human lymphocytes, we constructed a heteromyeloma between the murine myeloma Ag8 and human lymphocytes from a highly malignant polymorphic, centroblastic B-cell lymphoma. The thioguanine-resistant and HAT-sensitive heteromyeloma HAB-1 neither secretes nor contains cytoplasmatic immunoglobulins, the cells being EBV negative but positively stained for HLA-BC and the human proliferation marker Ki-67. The karyotype consists of about 50 murine and 20 human chromosomes. The HAB-1 cells grow in suspension and have a doubling rate of about 25-30 h. In fusion experiments with spleen cells from stomach carcinoma patients HAB-1 cells show a 5-7 times higher fusion efficiency than murine Ag8 cells or another heteromyeloma SPM4-0 and give stable antibody producing products. The cell line will be made available to interested scientists.

ATP dependence of anion uptake by isolated vacuoles: requirement for excess Mg2+.

Vacuoles were isolated from barley mesophyll protoplasts. [14C]Malate or 36Cl- were taken up from the surrounding medium. Uptake was only slightly increased in the presence of equimolar levels of ATP and Mg2+ (as magnesium gluconate). In the presence of excess Mg2+ in the medium, ATP-stimulated uptake of malate and chloride increased several-fold. Stimulation by excess Mg2+ was not observed for ATP-stimulated amino acid uptake by isolated vacuoles. Stimulation of uptake by excess Mg2+ was observed at all malate concentrations upto 10 mmol.l-1. The content of Mg2+ needed for half-maximum stimulation was about 3.5 mmol.l-1 in the presence of 1 mmol.l-1 ATP. The increase in Mg2+ concentration had no effect on the tonoplast ATPase activity.

Pathogenesis of ovine lentivirus-induced arthritis: phenotypic evaluation of T lymphocytes in synovial fluid, synovium, and peripheral circulation.

Sheep and goats develop a chronic, progressive arthritis reminiscent of rheumatoid arthritis, but caused by lentiviruses related to human immunodeficiency virus. The distribution of T lymphocytes in peripheral circulation of two infected sheep with arthritis, one infected sheep with interstitial pneumonia, three asymptomatic sheep, and three uninfected sheep was evaluated. Sheep with clinical disease have depressed ratios of CD4/CD8 lymphocytes in peripheral circulation compared to asymptomatic and uninfected animals. In one sheep, the depressed ratio was due to an absolute increase in CD8-positive lymphocytes. The predominant lymphocyte populations in both synovial fluid and synovium from this animal were also CD8 positive. Macrophages were the other predominant cell population in synovial fluid and were infected with lentivirus. Little cell-free virus was detected in the synovial fluid, although 1 in 400 cells was infected as determined by infectious center assays. Infected cells in the synovial fluid had a reduction in virus gene expression compared to infected cells in peripheral circulation. This reduction in virus gene expression may be due to the presence of interferon-like activity in the synovial fluid.

Childhood poisoning in a paediatric hospital: the Luebeck experience.

1 Case documentations in Poison Control Centres represent today probably the most useful source of information on actual trends. They are generally restricted to toxicologically relevant information, but they do not describe true incidence patterns. Population based analyses of incidence therefore generally consist of retrospective studies of hospital data. The regional and historical limitations of such studies restrict their usefulness in prevention and intervention. A solution could be prospective studies in defined regions. 2 Such a prospective registration of poisoning in children was started in 1982 in the Luebeck Medical School's Paediatric Hospital. This hospital is the only institution treating acute poisoning in the region, so that regional representation of the data can be expected. Based on the experiences of a previous retrospective analysis of 730 poisoning cases treated between 1976 and 1980, a documentation form was developed for the registration of clinically and epidemiologically relevant data. Information on the toxic substance and the poisoned child is complemented by data on the clinical treatment as well as on socio-demographic parameters. 3 The first months' experience with the documentation form, and the results of the registration of 95 cases are presented. Possibilities and limitations of such registration systems are discussed.