[How many potential organ donors are there really? : Retrospective analysis of why determination of irreversible loss of brain function was not performed in deceased patients with relevant brain damage]. / Wie viele potenzielle Organspender gibt es wirklich? : Retrospektive Analyse zu nichterfolgter Diagnostik des irreversiblen Hirnfunktionsausfalls bei verstorbenen Patienten mit relevanter Hirnschädigung.

BACKGROUND: No systematic study has previously been undertaken in Germany to ascertain why irreversible brain death determination (BDD) has not been carried out. OBJECTIVE: A comprehensive analysis of reasons for unperformed BDD in deceased patients with acute, severe brain damage could improve the identification of potential organ donors. METHOD: Using the Transplantcheck program of the German Organ Transplantation Foundation (DSO) an analysis of the data from 2016 was undertaken in participating hospitals in Saxony, Saxony-Anhalt and Thuringia (Region East of the DSO), regarding why a BDD was not initiated in deceased patients with primary or secondary brain damage. RESULTS: In 128 of the 144 Region East hospitals, 7889 deceased patients with primary or secondary brain damage were detected. In 7389 patients a BDD was out of the question for a variety of reasons. In 232 patients organ donation was not considered due to an advance directive. In 195 cases treatment was limited based on the patient's infaust neurological prognosis without the possibility of organ donation being discussed with relatives. In 73 cases initiation of BDD was indicated but not performed. CONCLUSION: The number of potential organ donors in Region East of the DSO could be significantly increased by identifying patients where BDD is indicated. By consistent evaluation of patients' wills in terms of organ donation before treatment is withdrawn in patients with poor neurological prognosis, additional potential organ donors could be identified. Furthermore, involving neurointensive care physicians in the care of all patients with brain damage could improve the prognostic assessment.

Cortical correlates of gesture processing: clues to the cerebral mechanisms underlying apraxia during the imitation of meaningless gestures.

The clinical test of imitation of meaningless gestures is highly sensitive in revealing limb apraxia after dominant left brain damage. To relate lesion locations in apraxic patients to functional brain activation and to reveal the neuronal network subserving gesture representation, repeated H2(15O)-PET measurements were made in seven healthy subjects during a gesture discrimination task. Observing paired images of either meaningless hand or meaningless finger gestures, subjects had to indicate whether they were identical or different. As a control condition subjects simply had to indicate whether two portrayed persons were identical or not. Brain activity during the discrimination of hand gestures was strongly lateralized to the left hemisphere, a prominent peak activation being localized within the inferior parietal cortex (BA40). The discrimination of finger gestures induced a more symmetrical activation and rCBF peaks in the right intraparietal sulcus and in medial visual association areas (BA18/19). Two additional foci of prominent rCBF increase were found. One focus was located at the left lateral occipitotemporal junction (BA 19/37) and was related to both tasks; the other in the pre-SMA was particularly related to hand gestures. The pattern of task-dependent activation corresponds closely to the predictions made from the clinical findings, and underlines the left brain dominance for meaningless hand gestures and the critical involvement of the parietal cortex. The lateral visual association areas appear to support first stages of gesture representation, and the parietal cortex is part of the dorsal action stream. Finger gestures may require in addition precise visual analysis and spatial attention enabled by occipital and right intraparietal activity. Pre-SMA activity during the perception of hand gestures may reflect engagement of a network that is intimately related to gesture execution.

The effects of clinical case management on hospital service use among ED frequent users.

This study examined the impact of case management on hospital service use, hospital costs, homelessness, substance abuse, and psychosocial problems in frequent users of a public urban emergency department (ED). Subjects were 53 patients who used the ED five times or more in 12 months. Utilization, cost, and psychosocial variables were compared 12 months before and after the intervention. The median number of ED visits decreased from 15 to 9 (P < .01), median ED costs decreased from $4,124 to $2,195 (P < .01) and median medical inpatient costs decreased from $8,330 to $2,786 (P < .01). Homelessness decreased by -57% (P < .01), alcohol use by -22% (P = .05) and drug use by -26% (P = .05). Linkage to primary care increased 74% (P < .01). Fifty-four percent of medically indigent subjects obtained Medicaid (P < .01). There was a net cost savings, with each dollar invested in the program yielding a $1.44 reduction in hospital costs. Thus, case management appears to be a cost-effective means of decreasing acute hospital service use and psychosocial problems among frequent ED users.

The V3-directed immune response in natural human immunodeficiency virus type 1 infection is predominantly directed against a variable, discontinuous epitope presented by the gp120 V3 domain.

The specific binding of antibodies to the V3 loop in sera from human immunodeficiency type 1 (HIV-1)-infected individuals was investigated. Different V3 structures were analyzed as full-length loops or by pepscan. Our data show that on full-length V3 loops, both variable regions on either side of the tip of the loop (GPGRAF) contribute to a common epitope for type-specific antibodies. Type-specific antibodies bound strongly and at high titers to native V3 loops but negligibly once the loop was denatured. In contrast to the type-specific, discontinuous epitope, the linear, conserved epitopes presented by the full-length V3 loop, the tip, the amino-terminal base, and the carboxy-terminal base were not accessible to serum antibody. When the V3 sequences were analyzed with linear peptides, antibodies bound preferentially to peptides containing the conserved GPGRAF sequence. Thus, two different specificities of V3-directed antibodies were detected in patient sera. Unlike group-specific antibodies directed against GPGRAF peptides, lack of type-specific antibodies directed against the discontinuous epitope was correlated with viral escape from autologous neutralization. Our data suggest that the full-length conformation of the V3 loop is accessible predominantly to highly type-specific antibodies present in sera from HIV-1-infected individuals. These antibodies are directed against discontinuous V3 epitopes, not against conserved linear V3 targets. The implications of these findings for viral escape and blockade of infection with V3-based vaccines are discussed.

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo.

This study was performed to analyse correlates of viral escape in AIDS patients. Peripheral blood mononuclear cells (PBMC) from HIV- donors were inoculated with AIDS patients' serum to detect neutralization-resistant cell-free virus. Infectious virus was detected by polymerase chain reaction (PCR) and analysed by sequencing the V3 region. The escaped virus species was compared with all V3 virus variants found in the patients' PBMC and plasma. In one patient escaped virus was also compared with variants found in CD4+ T cells isolated by FACS from blood, spleen and lymph node. The frequency of the virus variants was determined by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed antibody response against the infectious virus V3 loop was not detectable. In contrast, virus variants unable to infect the donor PBMC in vitro were well recognized by homologous V3-directed antibody. After an interval of 1 year the frequency of these variants clearly decreased, while at the same time the escaped variants grew out and finally represented the predominant viral species both in plasma and PBMC. The infectious variants lacking V3 antibody response were also predominant in CD4+ T cells in spleen and lymph node. Our data indicate that the escape of virus variants is closely related to the lack of V3-directed antibody.

Loss of antibody reactivity directed against the V3 domain of certain human immunodeficiency virus type 1 variants during disease progression.

We have previously shown that in AIDS patients a predominant species of infectious virus can be found which is not neutralized by homologous serum. The presence of the infectious virus was associated with the lack of type-specific antibody directed against the V3 domains of these virions. In contrast to this lack of V3-specific antibody, the other V3 domains of non-infectious virions were well recognized by antibody. To determine whether the lack of a V3-specific antibody response is due to a progressive loss of antibody during human immunodeficiency virus type 1 (HIV-1) infection, we monitored the anti-V3 antibody response in 90 patients over time. Anti-V3 antibodies were monitored by a V3-specific ELISA using 21 different V3 domains as a fusion with glutathione S-transferase (GST-V3) based upon sequences from 11 HIV-1 patient isolates and 10 sequences from an HIV-1 B subtype consensus-like GST-V3 expression library. This strictly heterologous screening showed a loss of V3-specific antibodies in 20 out of the 90 patients tested. To study the in vivo relevance of these findings we analysed V3 antibody loss in two patients. This strictly autologous antibody screening was performed based upon V3 sequences of the patients' cell-free virions. In both patients the loss of a V3-specific antibody could be detected in parallel to a decline of CD4+ T cells. Moreover, the escape of a distinct V3 variant was shown to correlate closely with the loss of the V3-specific antibody.

Antibodies of symptomatic human immunodeficiency virus type 1-infected individuals are directed to the V3 domain of noninfectious and not of infectious virions present in autologous serum.

The present study was designed to determine the antibody specificity for the human immunodeficiency virus type 1 (HIV-1) V3 domains of infectious and noninfectious virions present in the serum of AIDS patients. To accomplish this, HIV-1 was isolated in the presence of autologous antibodies from the serum samples of six AIDS patients in HIV-1-negative donor peripheral blood mononuclear cells by short-term cultivation. The isolated virus, defined as the infectious cell-free virus (iCFV), was characterized by sequence analysis of the proviral DNA coding for the third hypervariable (V3) region of the external glycoprotein gp120. This was carried out by amplifying and cloning the V3 region. In all six cases studied, 20 randomly selected V3 clones derived from the proviral DNA of the iCFV, 20 clones from patient cell-free virus, and 20 clones from cell-integrated virus were sequenced to study the distribution and frequency of the intrapatient virus population. The number of major virus variants in the six patients ranged from three to nine. The various V3 sequences found in the AIDS patients showed the typical amino acid pattern of the syncytium-inducing and non-syncytium-inducing viral phenotypes characteristic for the late stage of infection. However, only one patient-specific iCFV variant was detected within the 20 V3 clones analyzed per virus isolation. For the six patients a total of 34 V3-loop variants, either iCFV or non-iCFV, was observed. All 34 V3-loop sequences were expressed as glutathione-S-transferase fusion proteins (V3-GST). The autologous antibody response to the V3-GST fusion proteins was studied by Western immunoblot analysis. A strong antibody response to almost all non-iCFV V3-GST proteins was found in the sera of the six patients. In contrast, the autologous antibody response to the six iCFV V3 loops was undetectable (in four patients) or very faint (in two patients) compared with that to the non-iCFV V3 loops. Five of the six iCFV loops showed positively charged amino acids at positions strongly associated with the syncytium-inducing phenotype. These findings suggest that our in vitro isolation system selects for virions which are not recognized by V3-specific antibodies and are infectious both in vitro and in vivo.

[Effect of iloprost on aggregation behavior in kidney conditioning and changes in iloprost concentration in kidney preservation]. / Der Einfluss von Iloprost auf das Aggregationsverhalten während der Nierenkonditionierung und Iloprostkonzentrationsveränderungen bei der Nierenkonservierung.

The conditioning of the donor by 1.0 microgram/kg X min Iloprost over 15 minutes leads to a considerable inhibition of the aggregation of thrombocytes in the domestic pig. 160% more ADP had to be added than before the application of Iloprost. When 0.5 microgram/ml Iloprost are added to the perfusion fluid and to the reperfusion fluid 0.22 microgram/ml and 0.27 microgram/ml, respectively, are to be proved in the venous efflux. Whether or not the difference is absorbed or metabolized must remain open. During the 72-hour storage of the kidney in a Euro-Collins-solution with 0.5 microgram/ml Iloprost after 24 hours a decrease of 0.34 microgram/ml, after 48 hours to 0.33 microgram/ml and after 72 hours to 0.20 microgram/ml takes place. Thus Iloprost is present in an effective concentration also after 72 hours. The decrease to one plateau rather speaks for a consumption by active metabolic effect or absorption than for a chemical decomposition.

[Patency of the tympanic tubes]. / Untersuchungen über die Durchgängigkeit von Paukenröhrchen.

A middle ear model was used to examine the patency of different tympanostomy tubes. It is concluded that these tubes provide more of a ventilation than a drainage of the tympanum. The patients need not be overcautious with regard to water with which they may come into contact.