Pathogen-reduced Ebola virus convalescent plasma: first steps towards standardization of manufacturing and quality control including assessment of Ebola-specific neutralizing antibodies.

BACKGROUND: Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti-infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen-reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework. MATERIALS AND METHODS: Ebola virus convalescent plasma manufacture and distribution was managed by a collection centre, two medical centres and an expert group from the European Blood Alliance. Ebola virus convalescent plasma was collected twice with an interval of 61 days from a donor recovering from Ebola virus disease in Germany. After pathogen reduction, the plasma was analysed for Ebola virus-specific immunoglobulin G (IgG) antibodies and its Ebola virus neutralizing activity. RESULTS: Convalescent plasma could be collected without adverse events. Anti-Ebola virus IgG titres and Ebola-specific neutralizing antibodies in convalescent plasma were only slightly reduced after pathogen reduction treatment with S59 amotosalen/UVA. A patient in Italy with Ebola virus disease was treated with convalescent plasma without apparent adverse effects. DISCUSSION: As proof of principle, we describe a concept and practical implementation of pathogen-reduced Ebola virus convalescent plasma manufacture, quality control and its clinical application to an Ebola virus disease patient.

The effect of increased centrifugation temperature on the quality of red-blood-cell concentrates of automated whole blood processing.

BACKGROUND AND OBJECTIVES: There are manual and automated methods to separate whole blood (WB) available. The Atreus whole blood processing system is an automated method, which combines centrifugation and expression of components into a single device. A major difference to conventional methods is that centrifugation temperature is not controlled at 22°C. The aim of this study was to examine the influence of increased centrifugation temperatures on the quality of red-blood-cell concentrates (RCC) after active cooling of WB prior to processing. MATERIALS AND METHODS: A total of 28 WB were processed: 16 at centrifugation temperatures of up to 28°C (1st protocol) and 12 at 34°C (2nd protocol). RCC quality parameters were tested weekly for 42 days. RESULTS: Red-blood-cell concentrates (RCC) quality complied with the European and German guidelines. Haemolysis was not significantly different throughout storage. Significant statistical differences were detected between both protocols in potassium concentration at the end of storage and in ATP levels at the day of processing. CONCLUSION: Centrifugation temperatures of up to 34°C are well tolerated by the red blood cells with minimal interference with the RCC quality parameters.

Detection of antibodies in eluates of immunoadsorption causing humoural rejection in patients after solid organ transplantation.

The influence of antibodies (AB) against human leukocyte antigen (HLA) on antibody mediated rejection (AMR) is still discussed controversially. Here we demonstrate to what extent post transplant detected HLA-AB and non-HLA-AB against Angiotensin II type 1 receptor (AT1 R-AB), endothelin-1 type A receptor (ETA R-AB) and glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX affect the graft outcome. A total of 13 transplant recipients (9 kidneys and 4 hearts) suffering from AMR were analysed. Before immunoadsorption (IA) treatment HLA-AB (CDC) in sera were detected in 27% versus 39% in eluates and 46% versus 87% by using ELISA. We could not find any AB against GP in sera. In eluates, however, we could detect AB against GP: GP IIb/IIIa in 86% of all samples with titres from 1:1 to 1:32, GP Ib/IX (up to 1:32) in 76% and GP Ia/IIa with titres from 1:1 to 1:16 in 82%. Further we detected anti-endothelial cell antibodies (AECA) against receptors AT1 and ETA in sera before IA in 22%, after IA in 10% and in eluates in 42% of all samples. The antibody titres vary from 1:1 to 1:256. Our investigation pointed out, that AMR is still possible without detectable AB in serum and consolidates the hypothesis that clinical relevant non-HLA-AB and HLA-AB are partly fixed on the graft. IA is qualified to detach these fixed AB.

[Selective immunoadsorption in neurologic complications of systemic lupus erythematosus]. / Selektive Immunadsorption bei neurologischen Komplikationen eines systemischen Lupus erythematodes.

Vasculitis of the nervous system is a rare cause of multifocal neurologic symptoms and may involve both the central and peripheral nervous systems. Typical symptoms include headache, encephalopathy with cognitive impairment and psychotic symptoms, epileptic seizures, and peripheral neuropathies. Here we report the case of a 71-year-old female presenting with Raynaud's syndrome and paresthesia of the feet. Several weeks later she was admitted to our hospital with a status epilepticus and complex partial seizures. On admission she had mild aphasia, distal paresis of the arms without sensory deficits, and disorientation with hallucinations. Cerebral MRI revealed small, multifocal infarctions in several arterial territories. Multiple cerebral artery stenoses were detected by ultrasound. Examination of the CSF was unremarkable. Serologic tests for autoimmune disorders detected Ro antibodies compatible with systemic lupus erythematosus or Sjögren's syndrome. A sural nerve biopsy revealed ischemic axonal neuropathy. During administration of i.v. methylprednisolone, the symptom progression stopped but dosages could not be tapered due to severe CNS symptoms (mental decline, disorientation, aphasia, hallucinations). Slow but sustained clinical improvement was achieved by immunoadsorption over 3 weeks followed by a combined high-dose immunosuppressive treatment with cyclophosphamide and prednisolone that paralleled a reduction in anti-Ro titers and normalization of cerebral blood flow velocities as detected by repeated transcranial Doppler sonography. Systemic vasculitis may present with multiple neurologic and psychiatric symptoms due to involvement of the central and peripheral nervous systems. After excluding systemic infection, immunosuppressive therapy should be started early. In our case a combination of high-dose methylprednisolone, immunoadsorption with elimination of Ro antibodies, and cyclophosphamide led to the patient's recovery.

[Incidence of postoperative complications in geriatric gynecology]. / Zur Häufigkeit post-operativer Komplikationen in der geriatrischen Gynäkologie.

The results of a retrospective-study concerning postoperative complications after gynecologic geriatric surgery (506 patients, aged 60 years and over) at the Departement of Gynecology and Obstetrics of the District Hospital Stralsund/GDR are presented. In 106 patients (10,94 per cent) we have registered post-operative complications, in particular anaemia, fever and wound-period (1967 to 1971 = 8,22%, 1977 to 1981 = 13,29%). Gynecologic surgery in the aged requires a carefully clinical management in preoperative diagnostic and an intensive postoperative care.

[Desire for children and family planning in Algeria (Approach to reproduction in Arab countries) (author's transl)]. / Kinderwunsch und Familienplanung in Algerien. Ein Beitrag zum Reproduktionsverhalten in arabischen Ländern.

Arab patients in the Gynaecological Hospital of the University of Oran, Algeria, were observed. Aspects relating to desire for children, family planning, and parity are discussed in conjunction with the outcome of the latest Algerian census. Three of four children in one family are considered an optimum solution. Early marriage and early gravidity still are widespread. Family planning continues to play a minor role, and only 25.3 per cent of all patients reviewed took to oral contraceptives for shorter or longer periods of time. - The percentages of primiparae and secundiparae in all births as well as the high percentage of multigravidity are parameters by which the approach to reproduction differs substantively from behaviour patterns in Europe. Traditional thinking of couples and resulting behaviours as well as religious and social motivations and insufficient use of family planning facilities are the major reasons.

[Differential diagnosis of uterus myomatosus in young patients]. / Zur Differentialdiagnose des Uterus myomatosus bei jungen Patientinnen.

Fibromyoma uteri in teenagers are rare findings. The case of a nineteen-years-old woman with fibromyoma uteri is presented. The diagnostic management and the operative treatment are discussed.

[The giant-child in the obstetrical material of district hospital of Stralsund (author's transl)]. / Das Riesenkind im geburtshilflichen Krankengut der Frauenklinik Stralsund. (Eine Studie zum Auftreten von Riesenkindsgeburten aus dem Zeitraum von 1945 bis 1975).

A clinical report is given about the giant-children (so-called big-babies) observed in the years 1945 to 1975 at the departement of obstetrics and gynecology of the district hospital of Stralsund. We have found 103 children within a birth-weight greater than or equal to 5000 g among 422229 newborns (= 0.24%) in this period. The obstetrical importance of the giant-children is shown by the advanced frequency of operations and the higher perinatal mortality. The maternal adipositas seems to be related to the intrauterine overgrowth of the fetus.

[Friedrich Wilhelm von Halem and his contributions to the inauguration of the thalasso-therapy in Prussia in the 18th century. A medico-historical survey]. / Friedrich Wilhelm von Halem - der Promotor der Thalassotherapie in Brandenburg-Preussen -- ein Absolvent der Frankfurter Viadrina. Ein medizinhistorischer Beitrag.

This article is dedicated in remembrance of Friedrich Wilhelm von Halem, a former student of the University Frankfurt-on-Oder (Viadrina) in later eighteenth-century Germany. Friedrich Wilhelm von Halem from Aurich, was the first physician in the period of the German Enlightenment, who had introduced the thalasso-therapy as a part of a new health-conception. His pioneering achievement led to the foundation of the first health resort on the german coast of the North-Sea in Norderney (East Frisian Islands), May 1797.

[Obstetric-perinatal status 1990 in the Oder region (a contribution to the obstetric-perinatal care in East Brandenburg)]. / Zur geburtshilflich-perinatologischen Situation des Jahres 1990 in der Oder-Region (Ein Beitrag zum Stand der geburtshilflich-perinatologischen Betreuung in Ost-Brandenburg).

On the background of the first All-German-Perinatal-Study in 1992 the results in obstetrics and perinatology in the Oder-Region (east part of the State of Brandenbourg) in 1990 are described. In comparison to the results in a previous study (1985) we found a drastical decline in the number of births (newborns 1985: 10244; 1990: 7723); in addition to the changing in the reproduction- and health-care behaviour, too, we have noted a decreasing perinatal mortality from 7.5% in 1985 to 4.9% in 1990. The ameliorated monitoring-rate (cardiotocography-rate) of the fetus (1985: 71%, 1990: 88.4%) and the decreasing still-birth-rate may be the main cause of this phenomenon. Clinic-births were the most common deliveries, the house-birth was the great exception; only 0.2% of all deliveries occurred at home or otherwhere. Our data support that there is no difference, except the birth-rate, in relation to the situation in the "old" Federal Republic of Germany.

[Collection of obstetric-perinatologic outcome data in the Frankfurt (Oder) district]. / Zur Erfassung geburtshilflich-perinatologischer Leistungskennziffern im Bezirk Frankfurt (Oder).

To assess health-care and quality in perinatal care a questionnaire was sent to all of the gynaecologic departments in the district of Frankfurt (Oder), GDR, asking details about prenatal care examination, fetal monitoring and perinatal mortality. The results of this pilot study indicate a high level in quality of health care in that region (perinatal mortality in 1985: 7.5%). Our findings suggest that quality-control and quality-comparisons are measures to ameliorate health, care organization, too. The reasons for the change in perinatal mortality will be analyzed in further investigations.

[Postnatal development of children of obese mothers]. / Zur postnatalen Entwicklung von Kindern adipöser Mütter.

In a five-years-period (1981-1985) we have investigated maternal obesity in 68 women with a prepregnant weight greater than or equal to 90 kg. The course of pregnancy, delivery and fetal outcome were analyzed in 54 (1.09%) non-diabetic females with a single-term-gravidity (age range 20 to 34 years). Fetal birth body-mass and -length did not show any significant differences in comparison to data collected in a control-group (infants of non-obese females). The fetal outcome was without differences in both groups (no perinatal deaths). In a prospective study covering the first three years of life we have registered the postnatal gain of body-mass and -length which increased in both sex. Up the 6th month of life we have registered a significantly higher weight gain (in male infants) in the study-group as in the control-group. There were no differences in early motor-, behavioral- and mental-development (walking alone, talking words), only the frequency in non-specific diseases of the respiratory system was a little bit higher in children of the study-group. Nevertheless, it seems to be necessary--to avoid adverse effects on the health and well-being in overweight children--to create an intensive prepregnant care and a diligently pediatric surveillance during the childhood period for counselling the involved parents, too.

[The geriatric patient in surgical gynecology. Results of the treatment of geriatric patients--a postoperative quality control]. / Die geriatrische Patientin in der operativen Gynäkologie. Behandlungsergebnisse geriatrischer Patientinnen--eine postoperative Qualitätskontrolle.

This paper presents results of a retrospective study covering 506 older women (age range: 60 years and older), who were treated by major gynecologic operations in a twenty-years-period between 1962 and 1981 at the Department of Gynecology and Obstetrics at the District Hospital of Stralsund. The total number of patients operated on during these twenty years was 6,246, the frequency of the operated older women 10.11 per cent. In two control periods (1967-1971 and 1977-1981) there was a slight increased of these patients in the last period from 8.22 per cent to 13.29 per cent. Comparing postoperative outcome and complication rate of the geriatric patients group there is no statistically significant difference to another group of patients (age range: 30-40 years) undergoing gynecologic surgery in 1981. Indications for gynecologic surgery showed age-dependent differences in the two groups. Our conclusions are that retrospective studies concerning clinical assuring of professional quality of medical care are not sufficient enough. As a result of this study we present our concept for medical data processing (documentation) regarding quality-assessment of gynecologic surgical care.

[Laparoscopic tubal coagulation--technic and follow-up results]. / Laparoskopische Tubenkoagulation--Technik und Nachuntersuchungsergebnisse.

This report presents 155 cases of laparoscopic electrocoagulation of the fallopian tubes. 53 coagulations were performed with unipolar devices, 102 ones with bipolar technique.--The patency of tubal obliteration was tested 12 weeks after the operation hysterosalpingographically.--In 4 cases the contrast medium was forced through the obliterated part of the fallopian tube, but controlled a half year later the tubes are completely closed. Hysterosalpingographic studies are not suited to criticize the reliability of laparoscopic sterilization. Severe operative and early postoperative complications were not to be seen.--The laparoscopic bipolar coagulation of the fallopian tubes is a method without the high of electric accidents. There is a great efficacy in producing sterility.

PIP: This report presents 155 cases of laparoscopic electrocoagulation of the fallopian tubes. 53 coagulations were performed with unipolar devices, and 102 with the bipolar technique. The patency of tubal obliteration was tested 12 weeks after the operation hysterosalpingographically. In 4 cases, the contrast medium was forced through the obliterated part of the fallopian tube, but controlled 1/2 year later, the tubes are still completely closed. Hysterosalpingographic studies are not appropriate for criticism of the reliability of laparoscopic sterilization. Severe operative and postoperative complications were not demonstrated. The laparoscopic bipolar coagulation of fallopian tubes is a method without a high number of electrical accidents. This is an effective method for achieving sterility. (author's modified)