Impedance-based in vitro eye irritation testing enables the categorization of diluted chemicals.

Products containing chemicals with eye irritation potential need to be labeled with the respective hazard symbol. To avoid the testing of numerous dilutions of chemicals on animals, their labeling is directed by a theoretical approach. In this report, a previously described in vitro tissue model of the cornea based on human epithelial cells was used for eye irritation testing of dilutions. As a sensitive and non-destructive method to analyze the barrier function of the epithelium, impedance spectroscopy was applied. Moreover, the morphology and viability of the epithelial models were assessed. We tested four chemicals that, neatly, cause severe damage to the eye: tetrahydrofuran, acetic acid, diethylethanolamine, and benzalkonium chloride. With our test method, we were able to determine the concentrations of the chemicals which are critical for the integrity of the cornea. The threshold was < 0.1% for the most and > 5% for the least toxic substance. The described test system is not only an alternative for animal models but also for the theoretical examination of the hazard potential of diluted chemicals. By using the advantages of tissue engineering and non-destructive analysis tools, we can achieve more precise and safer labeling of the eye irritation potential of products.

In-situ tear fluid dissolving nanofibers enable prolonged viscosity-enhanced dual drug delivery to the eye.

Liquid and semi-solid formulations are the most commonly used drug delivery systems for ophthalmic diseases. Upon application into the conjunctival sac, these systems introduce a variable and unphysiologically high liquid volume to the eye, resulting in overflow and extensive nasolacrimal drainage, accounting for dosing inaccuracy and short ocular residence time. In this study, we present nanofibrous electrospun scaffolds composed of biocompatible polymers, overcoming these challenges by immediate drug release. The fibers incorporate gentamicin and dexamethasone, intended for the treatment of bacterial conjunctivitis. Upon contact with the ocular surface, the nanofibers immediately dissolve in the tear fluid, quantitatively releasing the two actives, yielding over92% drug recovery, determined with fluorimetric and chromatographic quantifications methods. Simultaneously, the viscosity of the tear fluid increases, shown by complex viscometry measurements. A newly developed ex vivo microfluidic porcine cornea model was used to evaluated ocular residence time. In contrast to fluid eye drops, the contact time was significantly prolonged and 20 min after application, an increase in drug availability on the ocular surface of 342% was observed. Biocompatibility of the polymer system was demonstrated in an OECD approved in vitro cornea model. The antibacterial activity after processing was evaluated according to EUCAST guidelines, and storage stability of the system was confirmed over a 12-week period. This innovative drug delivery system poses a highly promising platform technology, overcoming challenges associated with conventional dosage forms for drug delivery to the anterior eye and thus significantly advancing therapeutic approaches.

[Preclinical management of cardiac arrest-extracorporeal cardiopulmonary resuscitation]. / Präklinisches Management bei Herz-Kreislauf-Stillstand ­ extrakorporale kardiopulmonale Reanimation.

BACKGROUND: The chances of surviving out-of-hospital cardiac arrest (OHCA) are still very low. Despite intensive efforts the outcome has remained relatively poor over many years. In specific situations, new technologies, such as extracorporeal cardiopulmonary resuscitation (eCPR) could significantly improve survival with a good neurological outcome. OBJECTIVE: Does the immediate restoration of circulation and reoxygenation via eCPR influence the survival rate after OHCA? Is eCPR the new link in the chain of survival? MATERIAL AND METHODS: Discussion of current study results and guideline recommendations. RESULTS: The overall survival rates after OHCA have remained at 10-30% over many years. Despite low case numbers more recent retrospective studies showed that an improved outcome can be achieved with eCPR. In selected patient collectives survival with a favorable neurological outcome is possible in 38% of the cases. CONCLUSION: Survival after cardiac arrest and the subsequent quality of life dependent on many different factors. The time factor, i.e. the avoidance of a no-flow phase and reduction of the low-flow phase is of fundamental importance. The immediate restoration of the circulation and oxygen supply by eCPR can significantly improve survival; however, large randomized, controlled trials are currently not available.

[Anesthesia and intensive care ventilators: differences and usability in COVID-19 patients]. / Anästhesie- und Intensivbeatmungsgeräte: Unterschiede und Nutzbarkeit bei COVID-19-Patienten.

The current coronavirus disease 2019 (Covid-19) pandemia is a highly dynamic situation characterized by therapeutic and logistic uncertainties. Depending on the effectiveness of social distancing, a shortage of intensive care respirators must be expected. Concomitantly, many physicians and nursing staff are unaware of the capabilities of alternative types of ventilators, hence being unsure if they can be used in intensive care patients. Intensive care respirators were specifically developed for the use in patients with pathological lung mechanics. Nevertheless, modern anesthesia machines offer similar technical capabilities including a number of different modes. However, conceptual differences must be accounted for, requiring close monitoring and the presence of trained personnel. Modern transport ventilators are mainly for bridging purposes as they can only be used with 100% oxygen in contaminated surroundings. Unconventional methods, such as "ventilator-splitting", which have recently received increasing attention on social media, cannot be recommended. This review intends to provide an overview of the conceptual and technical differences of different types of mechanical ventilators.

[Update: acute hypercapnic respiratory failure]. / Update: akute hyperkapnische respiratorische Insuffizienz.

BACKGROUND: Hypercapnic respiratory failure is a frequent problem in critical care and mainly affects patients with acute exacerbation of COPD (AECOPD) and acute respiratory distress syndrome (ARDS). In recent years, the usage of extracorporeal CO2 removal (ECCO2R) has been increasing. OBJECTIVE: Summarizing the state of the art in the management of hypercapnic respiratory failure with special regard to the role of ECCO2R. METHODS: Review based on a selective literature search and the clinical and scientific experience of the authors. RESULTS: Noninvasive ventilation (NIV) is the therapy of choice in hypercapnic respiratory failure due to AECOPD, enabling stabilization in the majority of cases and generally improving prognosis. Patients in whom NIV fails have an increased mortality. In these patients, ECCO2R may be sufficient to avoid intubation or to shorten time on invasive ventilation; however, corresponding evidence is sparse or even missing when it comes to hard endpoints. Lung-protective ventilation according to the ARDS network is the standard therapy of ARDS. In severe ARDS, low tidal volume ventilation may result in critical hypercapnia. ECCO2R facilitates compensation of respiratory acidosis even under "ultra-protective" ventilator settings. Yet, no positive prognostic effects could be demonstrated so far. CONCLUSION: Optimized use of NIV and lung-protective ventilation remains standard of care in the management of hypercapnic respiratory failure. Currently, ECCO2R has to be considered an experimental approach, which should only be provided by experienced centers or in the context of clinical trials.

Replacing the Draize eye test: Impedance spectroscopy as a 3R method to discriminate between all GHS categories for eye irritation.

Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78% with a reproducibility of 88.9% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.

Wohlfahrtiimonas chitiniclastica: current insights into an emerging human pathogen.

Since the first description of Wohlfahrtiimonas chitiniclastica in 2008, a number of well described case reports demonstrating its pathogenic role in humans have been published. Infections may be closely linked to flies, such as Wohlfahrtia magnifica, Lucilia sericata, Chrysomya megacephala or Musca domestica. These insects are potent vectors for the distribution of W. chitiniclastica causing local or systemic infections originating from wounds infested with fly larvae. However, other potential sources of transmission of W. chitiniclastica have been described such as soil or chicken meat. Infections in humans reported to date comprise wound infections, cellulitis, osteomyelitis and sepsis. This review summarizes all the literature available up to now and gives the current knowledge about this emerging human pathogen. Additionally, four patients with proven W. chitiniclastica infections treated at Dresden University Hospital between 2013 and 2015, are included. Special focus was placed on microbiological identification and antibiotic susceptibility testing of the pathogen.

The second window of desflurane-induced preconditioning is mediated by STAT3: role of Pim-1 kinase.

BACKGROUND: Late ischemic preconditioning is mediated via nuclear transcription factor signal transducer and activator of transcription 3 (STAT3). Pim-1 kinase reduces infarct size in cardiomyocytes and is regulated by STAT3. We tested the hypothesis that late desflurane-induced preconditioning (DES-SWOP) is mediated via STAT3 and Pim-1. METHODS: After institutional approval, pentobarbital-anesthetized male C57BL/6 mice were subjected to 45 min coronary artery occlusion (CAO) and 3 h reperfusion. Control animals received no additional intervention. Desflurane was administered 48 h before CAO either alone or in combination with the janus kinase/STAT3 inhibitor AG-490 (40 µg/g i.p., 20 min before desflurane administration) or the Pim-1 kinase inhibitor II (PIM-Inh.II, 10 µg/g i.p., 15 min before CAO). Infarct size (IS) and area at risk were determined with triphenyltetrazolium chloride and Evans blue, respectively. Additionally, cytosolic and nuclear fractions were separated at two different time points and expression of STAT3, phospho-STAT3(Ser727) , phospho-STAT3(Tyr705) , Pim-1, Bad and phospho-Bad(Ser112) were determined by Western Blot analysis. Data were analyzed with one-way or two-way ANOVA and post hoc Duncan test and are presented as mean ± SEM. RESULTS: IS was 47 ± 2% (n = 7-8 per group) in control animals (CON). DES-SWOP reduced myocardial infarct size to 23 ± 4%* (*P < 0.05 vs. CON). AG-490 alone did not affect myocardial infarct size (44 ± 7%), but abolished DES-SWOP (44 ± 4%). Blockade of Pim-1 did not affect the protection by DES-SWOP (34 ± 4%*). Desflurane reduced cytosolic content and enhanced nuclear content of phospho-STAT(S) (er727) . After 48 h, desflurane enhanced Pim-1 activity, whereas Pim-1 expression remained unchanged. CONCLUSION: These data suggest that DES-SWOP is mediated by activation and nuclear translocation of STAT3. The impact of Pim-1 in DES-SWOP signaling remains unclear.

[Venoarterial extracorporeal membrane oxygenation for out-of-hospital cardiac arrest. Case series of prehospital and in-hospital therapies]. / Venoarterielle extrakorporale Membranoxygenierung beim präklinischen Herz-Kreislauf-Stillstand. Fallserie prä- und innerklinischer Behandlungen.

Despite new concepts and strategies of basic and advanced life support, the outcome of patients with out-of-hospital cardiac arrest (OHCA) remains poor. The main reason accounting for these poor results is a low-flow phase during conventional cardiopulmonary resuscitation (CPR) with insufficient end organ perfusion. The early use of venoarterial extracorporeal membrane oxygenation (vaECMO) during CPR, i.e. extracorporeal resuscitation (ECPR) might improve OHCA survival rates as well as the neurological outcome in resuscitated patients. This article on a case series discusses the management of ECPR in three patients with OHCA. All patients suffered from a witnessed OHCA and received effective bystander CPR. After subsequent advanced cardiac life support could not achieve a return of spontaneous circulation (ROSC), vaECMO support was established as a bridge to therapy on site or after transportation to a primary or tertiary hospital. During the course of therapy two patients died and one patient was discharged after a full recovery. Early ECPR might improve the outcome in patients with prolonged cardiac arrest without ROSC. The use of ECPR should be based on the individual decision of an experienced ECPR team considering defined inclusion and exclusion criteria. As the outcome mainly depends on the duration and quality of conventional CPR, ECPR support should be requested immediately after establishing advanced life support (approximately 10-15 min).

[Venoarterial extracorporeal membrane oxygenation in an awake patient : Use of the mobile ECMO team for fulminant pulmonary embolism]. / Venoarterielle extrakorporale Membranoxygenierung am wachen Patienten : Einsatz des mobilen ECMO-Teams bei fulminanter Lungenarterienembolie.

The current report highlights the use of venoarterial extracorporeal membrane oxygenation (va-ECMO) in a case of pulmonary embolism complicated by right ventricular failure. A 38-year-old woman was admitted to a secondary care hospital with dyspnea and systemic hypotension. Diagnostic testing revealed a massive pulmonary embolism. Thrombolytic therapy was unsuccessful necessitating thromboendarterectomy in the presence of cardiogenic shock. To allow the necessary transport of the highly unstable patient to a tertiary care center a mobile ECMO team was called in. The team immediately initiated awake va-ECMO as a bridge to therapy. Extracorporeal support subsequently allowed a safe transportation and successful completion of the surgical procedure with complete recovery.

[Therapy of acute respiratory distress syndrome : Survey of German ARDS centers and scientific evidence]. / Therapie des akuten Lungenversagens : Umfrage an deutschen ARDS-Zentren und wissenschaftliche Evidenz.

BACKGROUND: In addition to specific treatment of the underlying cause, the therapy of acute respiratory distress syndrome (ARDS) consists of lung protective ventilation and a range of adjuvant and supportive measures. AIM: A survey was conducted to determine the current treatment strategies for ARDS in German ARDS centers. MATERIAL AND METHODS: The 39 centers listed in the German ARDS network in 2011 were asked to complete a questionnaire collecting data on the clinic, epidemiology as well as diagnostic and therapeutic measures regarding ARDS treatment. RESULTS: Of the centers 25 completed the questionnaire. In 2010 each of these centers treated an median of 31 (25-75 percentile range 20-59) patients. Diagnostic measures at admission were computed tomography of the thorax (60 % of the centers), whole body computed tomography (56 %), chest x-ray (52 %), abdominal computed tomography (32 %) and cranial computed tomography (24 %). Transesophageal echocardiography was performed in 64 %, pulmonary artery pressure was measured in 56 % and cerebral oximetry in 12 %. Sedation was regularly interrupted in 92 % of the centers and in 68 % this was attempted at least once a day. A median minimum tidal volume of 4 ml/kg (range 2-6) and a maximum tidal volume of 6 ml/kg (4-8) were used. Methods to determine the optimal positive end-expiratory pressure (PEEP) were the best PEEP method (60 %), ARDS network table (48 %), empirical (28 %), pressure volume curve (16 %), computed tomography (8 %), electrical impedance tomography (8 %) and others (8 %). Median minimum and maximum PEEPs were 10 cmH2O (range 5-15) and 21 cmH2O (15-25), respectively. Median plateau pressure was limited to 30 cmH2O (range 26-45). The respiratory rate was set below 20/min in 20 % and below 30/min in 44 %. Controlled ventilator modes were generally preferred with 80 % using biphasic positive airway pressure (BIPAP/BiLevel), 20 % pressure controlled ventilation (PCV) and 4 % airway pressure release ventilation (APRV). Assisted modes were only utilized by 8 % of the centers. Recruitment maneuvers were used by 28 %, particularly during the early phase of the ARDS. Muscle relaxants were administered by 32 % during the early phase of the ARDS. Complete prone positioning was used by 60 % of the centers, whereas 88 % utilized incomplete (135°) prone positioning. Continuous axial rotation was utilized by 16 %. Spontaneous breathing tests were used in 88 % of the centers with 60 % performing these at least once a day. Supportive therapies were frequently applied and mainly consisted of nitrous oxide (44 %), prostacycline (48 %) and corticosteroids (52 %). A restrictive fluid therapy was used in 48 % and a special nutrition regimen in 28 % of the centers. Of the participating centers 22 were able to offer extracorporeal membrane oxygenation (ECMO). In this case, respiratory therapy was modified by further reducing tidal volumes (91 %), inspiratory pressures (96 %) as well as using lower respiratory rates (≤ 8/min in 31 %). Only 9 % reduced PEEP during ECMO. Regular recruitment maneuvers were used by 14 %. Positioning maneuvers during ECMO were used by 82 %. CONCLUSIONS: Lung protective ventilation with reduced tidal volumes as well as inspiratory pressures represents the current standard of care and was utilized in all network centers. Prone positioning was widely used. Promising adjuvant therapies such as the muscle relaxation during the early phase of the ARDS, fluid restriction and corticosteroids were used less frequently. During ECMO respirator therapy was generally continued with ultraprotective ventilator settings.

Desflurane-induced post-conditioning against myocardial infarction is mediated by calcium-activated potassium channels: role of the mitochondrial permeability transition pore.

BACKGROUND: Desflurane (DES)-induced preconditioning is mediated by large-conductance calcium-activated potassium channels (BK(Ca)). Whether BK(Ca) are involved in anaesthetic-induced post-conditioning is unknown. We tested the hypothesis that DES-induced post-conditioning is mediated by BK(Ca) upstream of the mitochondrial permeability transition pore (mPTP). METHODS: Pentobarbital-anaesthetized male C57Black/6 mice were subjected to 45 min coronary artery occlusion (CAO) and 3 h reperfusion. Animals received either no intervention or dimethylsulphoxide (DMSO, 10 µl g(-1)). DES (1.0 MAC, 7.5 vol%) was administered for 18 min, starting 3 min before the end of CAO. The following agents were given either alone or in combination with DES: the BK(Ca) activator NS1619 (1 µg g(-1)), the BK(Ca) inhibitor iberiotoxin (IbTx, 0.05 µg g(-1)), the mPTP opener atractyloside (ATRA, 25 µg g(-1)), and the mPTP inhibitor cyclosporine A (CYC A, 10 µg g(-1)). Infarct size (IS) was determined with triphenyltetrazolium chloride and the area at risk with Evans Blue, respectively. RESULTS: IS in control animals was 48(6)%. Neither DMSO, IbTx nor ATRA affected myocardial IS. DES alone or NS1619 alone or the combination reduced IS (P<0.05), CYC A alone or in combination with IbTx or DES also reduced IS (P<0.05). DES-induced reduction of myocardial IS was completely abolished by IbTx and was partially blocked by ATRA and ATRA partially blocked IS reduction by NS1619. CONCLUSIONS: These data suggest that DES-induced post-conditioning against myocardial infarction is mediated by BK(Ca) and mPTP. Cardioprotection by BK(Ca) activator NS1619 might occur, at least in part, independently of mPTP.

Hummingbirds pay a high cost for a warm drink.

Endotherms must warm ingested food to body temperature. Food warming costs may be especially high for nectar-feeding birds, which can ingest prodigious volumes. We formulated a mathematical model to predict the cost of warming nectar as a function of nectar temperature and sugar concentration. This model predicts that the cost of warming nectar should: (1) decrease as a power function of nectar concentration, and (2) increase linearly with the difference between body temperature and nectar temperature. We tested our model on rufous hummingbirds (Selasphorus rufus). A typical experiment consisted of feeding birds nectar of a given concentration at 39 degrees C (equivalent to body temperature) and then at 4 degrees C, and vice versa. We used the percentage change in metabolic rate between the two food temperatures to estimate the cost of warming nectar. The model's predictions were accurately met. When birds had to hover rather than perch during feeding bouts, estimated food-warming costs were only slightly lower. The cost of warming nectar to body temperature appears to be an important yet overlooked aspect of the energy budgets of nectar-feeding birds. Hummingbirds feeding on 5% sucrose solutions at 4 degrees C have to increase their metabolic rate by an amount equivalent to that elicited by a 15 degrees C drop in ambient temperature.

Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer.

We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of malignant, as opposed to nontransformed cells, were killed by high-avidity transgenic mouse and allogeneic human CTLs specific for the A2.1-presented MDM2 epitope. Whereas the self-A2.1-restricted human T cell repertoire gave rise only to low-avidity CTLs unable to recognize the natural MDM2 peptide, human A2.1+ T lymphocytes were turned into efficient MDM2-specific CTLs upon expression of wild-type and partially humanized high-affinity T cell antigen receptor (TCR) genes derived from the transgenic mice. These results demonstrate that TCR gene transfer can be used to circumvent self-tolerance of autologous T lymphocytes to universal tumor antigens and thus provide the basis for a TCR gene transfer-based broad-spectrum immunotherapy of malignant disease.

Targeting p53, hdm2, and CD19: vaccination and immunologic strategies.

Peptides presented by class I major histocompatibility complex (MHC) molecules and derived from normal self-proteins that are expressed at elevated levels by cells from a variety of human (Hu) malignancies provide, in theory, potential target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based immunotherapy of cancer and hematologic malignancies. However, as such tumor- and leukemia-associated self-proteins are also expressed at low levels in some types of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self-MHC-self-peptide complexes may also represent thymic and/or peripheral tolerogens, thereby preventing immune responses. This is particularly true for class I MHC-peptide complexes expressed by bone marrow-derived cells in the thymus, as such expression would cause negative selection of immature thymic T cells with high avidity for self-MHC-self-peptide complexes. This intrathymic deletion of potentially self-reactive T cells could result in a peripheral T cell repertoire purged of CTL precursors with sufficient avidity to recognize natural tumor associated self-epitopes presented by class I MHC molecules on tumor cells. HLA-transgenic (Tg) mice provide the basis of an experimental strategy that exploits species differences between Hu and murine (Mu) protein sequences in order to circumvent self-tolerance and obtain HLA-restricted CTL specific for epitopes derived from tumor- and leukemia-associated Hu self proteins, such as p53, Her-2/neu, hdm2 and CD19.

On-line haemodiafiltration versus low-flux haemodialysis. A prospective randomized study.

BACKGROUND: Current methods of renal replacement therapy lead only to an insignificant removal of larger, potentially toxic, substances, which are excreted by healthy kidneys. On-line preparation of substituate from dialysate and the use of high-flux membranes allow substantial convective removal of such substances. A modified on-line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances, such as low-molecular-mass proteins, has a clinical impact. METHODS: In a prospective, controlled study over 24 months, 44 unselected chronic dialysis patients were randomized to undergo either low-flux haemodialysis (HD; n = 21) or haemodiafiltration (HDF; n = 23). To eliminate confounding factors, low-molecular efficacy was matched (Kt/V 1.8), and the same membrane material (polysulfone), ultrapure dialysate and the same treatment duration (4.5 h) were applied to each group. RESULTS: Morbidity, mortality, blood pressure, dialysis-associated hypotensive episodes, haematocrit and erythropoietin dose did not differ between the groups. The same was true for body weight and, accordingly, bioimpedance values, clinical hydration score, skinfold thickness, plasma albumin, prealbumin and transferrin. beta2-Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years. In HDF, beta2 microglobulin decreased from similar values to 18 mg/l predialysis (P<0.01) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months. CONCLUSION: In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time-span of 2 years during HDF had no clinical implication compared with extremely (and for routine practice unrealistically) well-dialysed patients with low-flux HD. In the absence of any side-effects of on-line HDF and supposing that plasma beta2-microglobulin is a marker of morbidity, on-line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae.

Combined therapy in human immunodeficiency virus-infected children--a 4-year experience.

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of > 400 cells/microliters per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of < 400 cells/microliters per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulin (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)