[Mandatory reporting of antimicrobial-resistant pathogens. What should, what can be achieved? : assessment related to the particular facility seems crucial]. / Meldepflicht für Antibiotika-resistente Erreger. Was soll, was kann sie leisten? : Die Bewertung in Bezug auf die jeweilige Einrichtung erscheint wichtig.

Antimicrobial-resistant organisms are regarded as a particular threat to the public health of the European population. In Germany the requirement for a national rollout reporting of positive laboratory test results for methicillin-resistant Staphylococcus aureus (MRSA) in blood cultures was implemented in 2009. This was followed in 2011 by the introduction of a laboratory-based, rollout reporting system for the detection of gram-negative bacteria with acquired carbapenem-resistance (carbapenem-resistant organisms, CRO) in the federal state of Hessen. This article will present the experience gained in Frankfurt am Main with the existing reporting system. Blood or cerebrospinal fluid cultures positive for MRSA were reported from all Frankfurt clinics between 2010 and 2013. The objective of preventing nosocomial infections by introducing a mandatory reporting for MRSA in blood cultures was only partially achieved by the reporting procedure on a population scale. Instead, reporting on a clinic-based scale, i.e., incidence per 1,000 patient days should be used. Moreover, mandatory reporting of clusters of nosocomial colonizations with MRSA could be an appropriate measure for the timely prevention of nosocomial infections with these organisms. CROs were reported from nearly all clinics as well as the ambulatory setting. Different reporting criteria have resulted not only in a greatly varying workload for the institutions and the health authorities but also in vastly different numbers of reported events. Regarding the importance of CRO, mandatory reporting seems reasonable. Criteria of reporting should be simple and easily comprehensible, i.e., all 4MRGN (gram-negative bacteria with resistance against four antibiotic groups such as acylureidopenicillins, third- and fourth-generation cephalosporins, fluorchinolones, and carbapenems) according to the German Commission on Hospital Hygiene and Infection Prevention (KRINKO) should be considered. Reporting and evaluation of multidrug-resistant organisms (MDRO) in a population-based system does not seem to be sufficient regarding these organisms with high importance for hospital hygiene; mandatory reporting on an anonymous clinic-based scale should be used.

Tuberculosis among drug users and homeless persons: impact of voluntary X-ray investigation on active case finding.

BACKGROUND: Illicit drug use and homelessness are major contributors to the incidence of tuberculosis (TB) among inhabitants of major cities. OBJECTIVE: The primary objective of this study was to establish a sustainable low-threshold chest X-ray screening programme for pulmonary TB among illicit drug users and homeless persons and to integrate this into the existing public health programme for active case finding. A secondary objective was to estimate the coverage of the programme, assess other risk factors and determine TB rates and treatment outcome in these two groups. METHODS: Illicit drug users and homeless persons were asked to voluntarily participate in an X-ray screening programme. The coverage of the intervention, total number and characteristics of cases and the follow-up of treatment were assessed. RESULTS: A total of 4,529 chest radiographs were made from 3,477 persons, of whom 66% were homeless and 34% were illicit drug users, between May 2002 and April 2007. Coverage for screening once every 2 years ranged between 18 and 26%. Thirty-nine TB cases (14 drug users, 25 homeless persons) were identified, representing 8.7% of the total case load of 448 notified cases of pulmonary TB in Frankfurt during this period. Among the drug users, human immunodeficiency virus coinfection (10/14) seemed to play a key role in the development of TB. The case-finding rate of 861/100,000 radiographs (1,122/100,000 persons) is as high as that in routine contact investigations (1,078/100,000). Among all individuals with TB, 76% completed treatment. CONCLUSION: A novel targeted TB screening approach with voluntary radiographic examination of illicit drug users and homeless persons can be integrated into the existing public TB prevention programme and provides a high case-finding rate.

Transcriptomic fingerprints in human peripheral blood mononuclear cells indicative of genotoxic and non-genotoxic carcinogenic exposure.

For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effect markers provide limited mechanistic insight, and do not allow detection of exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure in human peripheral blood cells (PBMC). Whole genome gene expression changes were investigated following 20 h of in vitro exposure to a high and low concentration of eight genotoxic and three non-genotoxic carcinogenic compounds using whole genome microarrays. Per condition, PBMC of five independent donors were exposed, all in the presence of human liver S9. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic gene sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomarkers of carcinogen exposure.

[Influenza vaccination rates in Hessian hospitals]. / Influenzaimpfquoten in hessischen Krankenhäusern.

Influenza infections have been shown to spread in hospitals rapidly; nosocomial transmissions occur frequently. Influenza vaccination of health care personnel (HCP) is an effective strategy for preventing influenza infections among personnel and patients. In summer 2011 we conducted an anonymous questionnaire among Hessian hospitals assessing influenza vaccination rates, kind and concept of vaccination programmes. Overall, 95.8% (68/71) of hospitals surveyed offered influenza vaccinations for HCP free of charge. Influenza vaccination rates have been recorded only by 70.4% (50/71). Over 80% (season 2009/2010: 41/50- season 2010/2011: 44/50) of hospitals questioned, mentioned influenza vaccination rates under 20%. Our findings confirm that the influenza vaccination rates might be less than the generally assumed and communicated influenza vaccination rates of 20-25%. Thirty years since the German Standing Committee on Vaccination (STIKO) recommended that all HCP get vaccinated against influenza, vaccination rates still remain below 30%. Measures to improve influenza vaccination rates among HCP are required. Monitoring of vaccination rates is a precondition to assess the acceptance of a vaccination programme.

[Prevention of nosocomial transmission of human immunodeficiency virus (HIV) from HIV-positive healthcare workers. Recommendations of the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V]. / Prävention der nosokomialen Übertragung von humanem Immunschwächevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen. Empfehlungen der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. und der Gesellschaft für Virologie (GfV) e.V.

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.

The impact of the 2009 influenza A(H1N1) pandemic on attitudes of healthcare workers toward seasonal influenza vaccination 2010/11.

The emergence of the influenza A(H1N1)2009 virus provided a major challenge to health services around the world. However, vaccination rates for the public and for healthcare workers (HCWs) have remained low. We performed a study to review the reasons put forward by HCWs to refuse immunisation with the pandemic vaccine in 2009/10 and characterise attitudes in the influenza season 2010/11 due to the emergence of influenza A(H1N1)2009. A survey among HCWs and medical students in the clinical phase of their studies was conducted, using an anonymous questionnaire, at a German university hospital during an influenza vaccination campaign. 1,366 of 3,900 HCWs (35.0%) were vaccinated in the 2010/11 influenza season. Of the vaccinated HCWs, 1,323 (96.9%) completed the questionnaire in addition to 322 vaccinated medical students. Of the 1,645 vaccinees who completed the questionnaire, 712 had not been vaccinated against the influenza A(H1N1)2009 virus in the 2009/10 season. The main reason put forward was the objection to the AS03 adjuvants (239/712, 33.6%). Of the HCWs and students surveyed, 270 of 1,645 (16.4%) stated that the pandemic had influenced their attitude towards vaccination in general. Many German HCWs remained unconvinced of the safety of the pandemic (adjuvanted) influenza vaccine. For this reason, effective risk communication should focus on educating the public and HCWs about influenza vaccine safety and the benefits of vaccination.

[Web-based evidence of treatment capacity. An instrument for optimizing the interface between prehospital and hospital management]. / Web-basierter Versorgungskapazitätsnachweis. Ein Instrument zur Schnittstellenoptimierung zwischen Präklinik und Klinik.

BACKGROUND: The outcome of injured patients depends on intrastractural circumstances as well as on the time until clinical treatment begins. A rapid patient allocation can only be achieved occur if informations about the care capacity status of the medical centers are available. Considering this an improvement at the interface prehospital/clinical care seems possible. MATERIAL AND METHOD: In 2010 in Frankfurt am Main the announcement of free capacity (positive proof) was converted to a web-based negative proof of interdisciplinary care capacities. So-called closings are indicated in a web portal, recorded centrally and registered at the local health authority and the management of participating hospitals. RESULTS: Analyses of the allocations to hospitals of all professional disciplines from the years 2009 and 2010 showed an optimized use of the resources. A decline of the allocations by the order from 261 to 0 could be reached by the introduction of the clear care capacity proof system. The health authorities as the regulating body rarely had to intervene (decline from 400 to 7 cases). Surgical care in Frankfurt was guaranteed at any time by one of the large medical centers. CONCLUSION: The web-based care capacity proof system introduced in 2010 does justice to the demand for optimum resource use on-line. Integration of this allocation system into the developing trauma networks can optimize the process for a quick and high quality care of severely injured patients. It opens new approaches to improve allocation of high numbers of casualties in disaster medicine.

[MRSA bloodstream infections in hospitals in Frankfurt/Main, Germany, 2010 : Results of the mandatory notification and suggestions for improvement]. / MRSA in Blutkulturen in Frankfurter Krankenhäusern 2010 : Ergebnisse der Meldepflicht nach Infektionsschutzgesetz und Vorschläge zu ihrer Verbesserung.

Since 1 July 2009 in accordance with the statuary order based on the German law for infectious diseases (Infektionsschutzgesetz), MRSA in blood and liquor must be notified to the public health authorities. The aim of extension of the notification to report is to improve the surveillance of nosocomial infections and the prevention of nosocomial MRSA infections. In addition to MRSA detection, data on symptoms and risk factors, e.g., medical devices, must also be reported. In this report, data of bloodstream MRSA infections in hospitals in Frankfurt/Main, Germany, for the first complete year (2010)were evaluated. In 2010, 58 MRSA-positive bloodstream infections were reported by the 17 hospitals in Frankfurt to the health protection authorities, i.e., 0.0360 MRSA/1,000 patient-days (range: 0- 0.109/1,000 patient-days). However, 10 of these infections initially had not been reported to the public health department in charge for the hospitals, but to the health departments according to the patient's addresses. Although most of the infections were reported from large hospitals (>100,000 patient-days/year), the highest incidences (0.0416/1,000 patient-days) were reported from small hospitals (<50,000 patient-days/year). Of the blood specimen, 13 (22.4%) were drawn on the first day of hospital stay, thus, indicating an imported infection. While 90% of the patients with MRSA in the bloodstream suffered from fever, 80% had sepsis and 34.5% suffered from pneumonia. Medical devices, such as central venous catheters and PEG, were reported from 60% of the patients. In the MRE network Rhine-Main region, the public health authorities asked for some more detailed information, such as risk factors for MRSA colonization (history for MRSA, recent hospital stay or antibiotic therapy, skin disorders, dialysis, residence in a retirements home), and for screening results as well as for the MRSA management, i.e., isolation of the patient and, if necessary, the contact patient. In 55% of the cases, the patients were identified by the clinics themselves as being patients with MRSA risk factors, mainly because of a history of MRSA (29%), recent hospital stay (71%), and antibiotic therapy during the last 6 months (52%). Screening was performed in 31 (53%) of the patients, most of them (71%) with positive MRSA nose swab. If the patients were screened, significantly fewer contact patients had to be screened and isolated later. Thus, to improve surveillance data on MRSA bloodstream infections, the notification route to the public health authorities responsible for the clinic hosting the patient must be strictly obeyed in order to avoid underreporting und underassessment of nosocomial infection. Although asking for clinical symptoms may be useful to validate the result in some cases, focus should be placed on risk factors and risk management, including screening and isolation. Only then can the aim of improving surveillance and reduction of nosocomial MRSA infection be achieved.

[Measles in 2010. Knowledge and vaccination status of medical students]. / Masern im Jahr 2010. Wissensstand und Impfstatus von Medizinstudenten.

OBJECTIVES: In 2002, the WHO Regional Office for Europe developed a strategic plan for measles in the WHO European Region. WHO recommends that at least 95% of children receive two doses of measles vaccine. This plan targeted the elimination of measles for the year 2010 and is supported by the Federal Republic of Germany. METHODS: Questionnaire survey, serological tests and check-up of the certificates of vaccination were offered to second year medical students of Goethe University Frankfurt/Main, Germany. RESULTS: Only 62.3% of medical students had received two doses of measles vaccine. Serological data showed that 23.1% were not immune against measles. Important gaps of knowledge were identified in the knowledge test of the survey; less than one third of the students (n=95/324) were able to answer more than 50% of the questions correctly. DISCUSSION: The suboptimum measles-vaccination coverage shows that the goal of eliminating measles will not be met across Europe by the target year 2010. Both occupational and public health measures need to make sure that vaccination programs should achieve a minimum of 95% coverage with two doses. In addition, the obligation to notify the authorities even of suspected cases serve the same purpose and measures to improve the knowledge of medical students are required. Consequent surveillance systems are necessary to investigate chains of measles infections. Healthcare workers play a decisive role in this issue.

[Costs of the influenza pandemic for the public health services - calculations based on the model of the metropolitan region Frankfurt am Main]. / Inkrementelle Kosten der A/H1N1-Pandemie für den Öffentlichen Gesundheitsdienst - Berechnungen am Beispiel der Metropole Frankfurt am Main.

The influenza pandemic of 2009 has been the biggest challenge to the public health services in post-war Germany. This study investigates the impact on the overall costs for the public health authorities of the metropolitan region Frankfurt am Main which arose in the context of the pandemic as well as the specific costs of the implementation and realisation of the vaccination campaign during the pandemic. In 2009 the incremental costs for the Health Protection Authority of the City of Frankfurt am Main for the prevention and logistics caused by this pandemic amounted to € 223,537.91, whereas costs which could be directly attributed to the vaccination campaign (vaccine not included amounted to only a fraction thereof (€â€Š45,401.48). The per-capita costs for vaccinated citizens were €â€Š10.66.  These results clearly demonstrate the importance of adequate financial resources for the public health authorities to cope with infectious disease outbreaks and future pandemics.

[Management of the influenza pandemic on a local health authority level]. / Management der Influenzapandemie auf kommunaler Ebene.

In most cities and districts, the influenza pandemic of 2009 could be handled without any restrictions in providing medical care or any disturbance in public life. Despite its relatively mild course, the local public health services reached their limits of capacity. Based on nationwide regulations, the local management determines the success of the measures. Evaluating the experience on the community level offers the chance of facing future pandemics more efficiently. Press conferences, press releases, and the internet are the most reliable tools to inform the public even in terms of personnel expenses. Telephone conferences and internet platforms help to reduce time-consuming meetings. An electronic database and logbook provide up-to-date information for all parties involved and allow quick, rational, coordinated, and transparent decision-making. Local evaluation of registration data, reports on cases of illness, and the availability of hospital beds on a daily basis allow intervention at an early stage to cope with the pandemic efficiently and helps save resources. Recruitment of external personnel, e.g., for the call center and the vaccination campaign, relieves the public health employees in charge with respect to their main tasks of directing and management functions.

[Low influenza vaccination rates among healthcare workers. Time to take a different approach]. / Niedrige Influenzaimpfquoten bei Mitarbeitern im Gesundheitswesen. Zeit für einen neuen Ansatz.

Despite decades of effort to encourage healthcare workers (HCWs) to be immunized against influenza, vaccination levels remain insufficient in Germany, with only one in five HCWs receiving the annual influenza vaccination. To prevent nosocomial influenza outbreaks and to ensure the protection of patients and HCWs, new approaches to increase vaccination rates are needed. The experience in the USA has shown that declination forms have increased vaccination coverage. One possible approach for Germany would be a combination of declination forms with the exclusive use of vaccinated staff in defined areas. This approach would respect a HCWs decision to refuse medical treatment, while at the same time protecting vulnerable patients. In addition, the influenza vaccination rates of HCWs should be collected in order to evaluate the implementation of vaccination policies. Similar to the setting of desired vaccination coverage for the chronically ill, a clearly defined vaccination goal should be established for HCWs.

[Influenza pandemic: Would healthcare workers come to work? An analysis of the ability and willingness to report to duty]. / Influenzapandemie: Würde das Krankenhauspersonal zur Arbeit kommen? Eine Analyse der Bereitschaft und Möglichkeit der Weiterarbeit.

In the event of an influenza pandemic, the workload of healthcare workers (HCWs) would raise dramatically. Moreover, due to the nature of this occupation, one's own risk of infection is also increased. Given this background, the question arises as to whether HCWs would actually report to work during an influenza pandemic. To answer this question an anonymous and voluntary questionnaire was distributed to HCWs of a German university hospital during the seasonal influenza vaccination. In total, 36.2% of respondents declared that, in the event of a potential influenza pandemic, they would not go to work. The provision of adequate personal protective equipment, such as masks (88.2%), was highlighted as an important precautionary measure. The confidence of employees in public policy, the public health system, and in employers was, altogether, judged to be insufficient; public policy received the worst results in this respect. Pandemic preparedness plans should consider both the proportion of ill employees, as well as the proportion of employees who may be absent due to personal fears or private responsibilities. Appropriate protective measures should be clarified and communicated in the prepandemic phase. Initiatives to strengthen workers' confidence in the fact that everything would be done to protect them against becoming ill in the event of a pandemic also need to be implemented.

Transportation capacity for patients with highly infectious diseases in Europe: a survey in 16 nations.

Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. In most European Union member states specialized isolation facilities are responsible for the management of such cases. Ground ambulances are often affiliated with those facilities because rapid relocation of patients is most desirable. To date, no pooled data on the accessibility, technical specifications and operational procedures for such transport capacities are available. During 2009, the 'European Network for HIDs' conducted a cross-sectional analysis of hospitals responsible for HID patients in Europe including an assessment of (a) legal aspects; (b) technical and infrastructure aspects; and (c) operational procedures for ground ambulances used for HID transport. Overall, 48 isolation facilities in 16 European countries were evaluated and feedback rates ranged from 78% to 100% (n = 37 to n = 48 centres). Only 46.8% (22/47) of all centres have both national and local guidelines regulating HID patient transport. If recommended, specific equipment is found in 90% of centres (9/10), but standard ambulances in only 6/13 centres (46%). Exclusive entrances (32/45; 71%) and pathways (30/44; 68.2%) for patient admission, as well as protocols for disinfection of ambulances (34/47; 72.3%) and equipment (30/43; 69.8%) exist in most centres. In conclusion, the availability and technical specifications of ambulances broadly differ, reflecting different preparedness levels within the European Union. Hence, regulations for technical specifications and operational procedures should be harmonized to promote patient and healthcare worker safety.

A pro-inflammatory genotype predisposes to Barrett's esophagus.

INTRODUCTION: Severity of mucosal inflammation is shown to be associated with Barrett's esophagus (BE) development in animals. It has therefore been postulated that a strong pro-inflammatory host response predisposes to BE. AIM: To determine the impact of cytokine gene polymorphisms on the development of BE. METHODS: The multiplex SNaPshot method was used to determine interleukin (IL)-12B (A+1188C), IL-10 (C-592A, C-819T, A-1082G), IL-8 (A-251T), IL-6 (G-174C) and IL-2 (G-330T) gene polymorphisms in 255 patients with BE and 247 patients with reflux esophagitis (RE). RESULTS: The presence of the IL-12B C-allele, which is associated with increased IL-12p70 expression, was more frequently observed in BE than in RE patients [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.2-2.7; P = 0.007). The risk of BE was increased in patients in whom the IL-12B C-allele coincided with a hiatal hernia (OR 2.9; 95% CI 1.32-6.58; P = 0.008). The IL-10(-1082) GG genotype, which is associated with higher IL-10 levels, was also associated with a decreased risk of BE when it was associated with the IL-12B C-allele, indicating IL-10-dependent down-regulation of IL-12p70 expression. A combination of the IL-12B AA genotype and the IL-10 AA or AG genotypes was associated with RE (OR 1.4; 95% CI 1.05-1.85; P = 0.011). CONCLUSION: A genetic profile predisposing to a strong pro-inflammatory host response, mediated by IL-12p70 and partially dependent on IL-10, is associated with BE. This risk further increases when this genotype coincides with a hiatal hernia, suggesting that exposure to gastroesophageal reflux in the presence of a pro-inflammatory genetic background is a driving force in the development of BE.

A curriculum for training healthcare workers in the management of highly infectious diseases.

The SARS epidemic, the threat of bioterrorism, and recent examples of imported highly infectious diseases (HID) in Europe have all highlighted the importance of competent clinical and public health management of infectious disease emergencies. Although the European Union of Medical Specialists in Europe and the Infectious Diseases Society of America have developed curricula for training in infectious disease medicine, neither of those mentions training in the management of HIDs. The European Network for Infectious Diseases (EUNID, http://www.eunid.com) is a European Commission co-funded network of experts in HID management, created to help improve the preparedness for HID emergencies within Europe. One of EUNID's agreed tasks is the development of a curriculum for such a training. Between April 2005 and September 2006, EUNID developed a curriculum and accompanying training course on the basis of a questionnaire that was sent to all country representatives and discussion, followed by amendment of drafts shared through the project website, and a final consensus meeting. The resulting curriculum consists of a two-module course covering the core knowledge and skills that healthcare workers need to safely treat a patient who has, or who may have, an HID. The first module introduces theoretical aspects of HID management, including disease-specific knowledge, infection control, and the public health response, through didactic teaching and class-based discussion. The second module involves a "skill station" and a clinical scenario, and equips trainees with relevant practical skills, including the use of specialised equipment and teamwork practice in patient management. Together, the curriculum and course contribute to the creation of a common framework for training healthcare professionals in Europe, and although they are designed primarily for clinicians that are directly involved in patient care, they are relevant also to public health professionals and others who may be involved in HID management and emergency response.

Effect of blood transfusion on IL-2 production.

Spleen cells from B10.A mice transfused with B10.D2 blood suppress the immune responses of normal B10.A to B10.D2 in coculture as early as 2 days posttransfusion. In addition, the ability of B10.A mice to respond in cell-mediated lymphocytotoxicity (CML) is significantly impaired as early as 2 days after B10.D2 transfusion. Experiments were performed to characterize the cells mediating the suppressive effect and to determine whether the inability of transfused mice to generate a cytotoxic response is due to an inhibition of IL-2 production. To characterize the suppressor cells, spleen cells from B10.A mice were assayed 2 or 16 days after B10.D2 transfusion for the ability to suppress mixed lymphocyte culture (MLC) and CML responses of normal B10.A mice in coculture. The putative suppressor cells were either passed over a Sephadex G-10 or nylon wool column, treated with anti-Thy antibody or left untreated before addition to the coculture. Untreated cells from transfused mice suppressed the CML response of normal B10.A both 2 and 16 days posttransfusion, while the effect on the MLC response was inconsistent. Passage of the cells over Sephadex G-10 or nylon wool before assaying abrogated the suppressive effect, while treatment with anti-Thy antibody had no effect. These results suggest that the suppressor cells appearing shortly after blood transfusion have the characteristics of macrophages and not T lymphocytes. To determine the effect of transfusion on IL-2 production, cells from transfused mice were assayed for their ability to produce IL-1 and IL-2 and for the formation of IL-2 receptors. In addition, the effect of exogenous IL-1 and IL-2 on restoring the CML response of transfused mice to normal was assayed. The production of IL-1 by transfused mice was normal, while the production of IL-2 was significantly suppressed both 2 and 16 days posttransfusion. Activated cells from normal and transfused mice showed equal ability to absorb IL-2, indicating that IL-2 receptor formation is normal after transfusion. The addition of exogenous IL-2, but not IL-1, to CML cultures containing cells from transfused mice as responders restored the response to normal. These results indicate that the inability of transfused mice to respond in CML is due, at least in part, to an inability to produce IL-2. This could be mediated by prostaglandins released by activated macrophages.

The effect of timing of multiple donor-specific or nonspecific blood transfusions on skin allograft survival in ALS-treated mice.

The effect of timing of multiple transfusions on skin allograft survival in antilymphocyte serum (ALS)-treated mice was studied using donor-specific or nonspecific transfusions. Transfusions were given every 4, 7, 14, or 21 days and skin grafting was done 10 days after the last transfusion. To study the effect of donor-specific transfusion, four DBA/2 transfusions were given to ALS-treated B6AF1 recipients followed by grafting with DBA/2 skin. To study the effect of nonspecific transfusions, five CF1 transfusions were given to ALS-treated B6AF1 mice, followed by grafting with C3H/He skin. Transfusions of both donor-specific and nonspecific blood every 4 days had no effect on prolonging graft survival, compared with ALS-treated controls. Transfusions of both types of blood every 7, 14, or 21 days significantly prolonged graft survival, with maximum survival observed in the group receiving transfusions every 14 days. The effect of varying the interval between the last transfusion and skin grafting was studied using multiple transfusions of nonspecific blood. Five weekly CF1 blood transfusions were given to ALS-treated B6AF1 mice. Skin grafting with C3H/He skin was done 2, 5, 10, 30, or 60 days after the last (5th) transfusion. Maximum graft prolongation was achieved when grafting was done 2 days after the last transfusion. Significant graft prolongation was also achieved when grafting was done 5, 10, or 30 days after the last transfusion. Of the mice grafted 60 days after the last transfusion, 60% showed no graft prolongation compared with controls, and survival of 40% of the grafts in this group was prolonged.

Suppressor cells in specific unresponsiveness to skin allografts in thymectomized, ALS-treated, marrow-injected mice.

Spleen cells from thymectomized antilymphocyte serum (ALS)-treated B6AF1 mice bearing enhanced C3H/He grafts after the infection of C3H/He marrow were assayed for their ability to suppress the response to C3H/He grafts after transfer to syngeneic B6AF1 recipients. Cells were transferred from thymectomized ALS-treated B6AF1 mice that had received either a C3H/He graft alone, C3H/He marrow alone, or both a graft and marrow. Cells were removed from donors and transferred at either day +13, +42, +62, +100, or +150. Spleen cells from thymectomized mice were unable to transfer unresponsiveness regardless of donor treatment or time of transfer.

Effect of splenectomy on specific unresponsiveness to skin allografts induced in ALS-treated, marrow-injected mice.

The role of the spleen in the induction and maintenance of unresponsiveness to skin allografts and in the generation of suppressor cells has been studied in ALS-treated B6AF1 mice grafted with C3H/He skin and injected with C3H/He marrow. B6AF1 mice were splenectomized either before the induction of unresponsiveness or on day +13, +28, or +42 after unresponsiveness was induced. Graft survival in the splenectomized mice was compared to that observed in nonsplenectomized ALS-treated, marrow-injected controls. Graft survival was prolonged equally in all splenectomized groups and the nonsplenectomized controls. To study the effect of the spleen on the generation of suppressor cells, lymph node cells were removed at day +42 from splenectomized ALS-treated, marrow-injected B6AF1 mice bearing C3H/He skin grafts and transferred to ALS-treated B6AF1 recipientso ALS-treated BTAF1 recipients grafted with C3H/He skin. Graft survival in the secondary recipients receiving lymph node cells from splenectomized donors was compared to that observed in ALS-treated B6AF1 mice that received lymph node cells transferred from nonsplenectomized enhanced donors. Suppressor cell activity could be detected in the nodes of splenectomized mice, but a higher dose of lymph node cells was required to transfer unresponsiveness from splenectomized donors compared to nonsplenectomized donors. These results indicate that the spleen is not necessary for the induction or maintenance of unresponsiveness to skin allografts in ALS-treated, marrow-injected mice. In addition, suppressor cells can be generated in the lymph nodes of unresponsive mice in the absence of the spleen, although the production of suppressor cells appears to be less effective in splenectomized mice than in mice with intact spleens.