A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres. RESULTS: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.

[Filter attachment]. / Ein Filter-Vorsatzgerät.

The filter attachment enables rapid and continuous transfusion of stored erythrocytes and of stored whole blood. This attachment is used both with a microfilter and a largepore transfusion device. The filter attachment enables bloodless preparation of the transfusion. The blood volume previously remaining in the microfilter, can now be transfused completely.

["Old new" problem of the lues risk in transfusion medicine: the effect of the serum and ACD stabilizer at different temperatures on the infectiosity of Treponema pallidium (Nichols strain)]. / Zum "alten neuen" Problem des Luesrisikos in der Transfusionsmedizin: Einfluss von Serum und ACD-Stabilisator bei verschiedenen Temperaturen auf die Infektiosität von Treponema pallidum (Stamm Nichols).

The portion of warm and fresh blood transfusions had increased obviously. This is accompanied by a decrease of the restrictive period of the former 72 and the presently 48 hours for blood units to be transfused. Therefore, the danger of a symphilis transmitted by transfusion is impending again. This is realized insufficiently and the syphilis may occur, if blood is drawn in the seronegative phase of the primary stage of syphilis and transfused within the restrictive period. Model trials on the infectivity of Treponema pallidum revealed that the syphilis cannot be transmitted by blood and its derivates drawn in the seronegative phase after storage at 4 degrees C for 24 hours. Therefore, the reduction of the restrictive period to 48 hours is justified.

[The amino acid picture--studies on stored blood]. / Aminosäurespiegel-Untersuchungen an Blutkonserven.

In 6 blood units with increased duration of storage alterations of amino acid levels were measured. Total amino acid concentration rises to 27%, while the amount of essential amino acids increases to 11% The E/T-quotient decreases slightly; so does the quotient of essential to non essential amino acids. The changes of concentrations of amino acids in stored whole blood can deteriorate the metabolic situation of patients with disorders of liver or kidney function. These patients as well as intensive care patients, in whom insufficiency of liver and kidney often is seen, should get transfusions of packed cells instead of whole blood.

[Preventive-medicine screening methods in the examination of blood donors]. / Die präventivmedizinische Bedeutung von Blutspenderuntersuchungen.

From a blood transfusion service with ca. 7000 donors a year, there was a loss of donors whose blood, having undergone medical tests, was found to be unsuitable. Details of all such donors were carefully documented. The results were ascertained by attentive control of the health of the donors which, in part, exceeded the minimum requirements laid down by the existing regulations. The relatively high loss of donors and the kind of disease underline the importance of these control checks, as an aspect of preventive medicine. This is of particular importance with regard to the results of so-called "new donors", who register for the first time. They had to undergo examination, and were only allowed to give blood when all the results of the tests had been submitted. The question then arises as to whether the regulations for the differing minimum requirements for the examination of "occasional donors" and "regular donors" can be maintained. A reduction of the expenditure on the present regulation examination of donors is not advocated because of both responsibility towards the blood donors, and in view of the increasing significance, to the medical care of patients, of the proximity of a clinic to an expedient transfusion service.

[Comparison of erythrocyte concentrations of ATP, ADP, AMP and 2,3-BPG in storage of five different additive solutions and in serum]. / Vergleich der erythrozytären Konzentrationen von ATP, ADP, AMP und 2,3-BPG bei Lagerung in fünf verschiedenen additiven Lösungen und in Serum.

In this study, we compared the ability of serum and of 5 additive solutions for the liquid storage of red blood cells to preserve the cellular contents of 2,3-BPG and the adenylate nucleotides ATP, ADP and AMP. As to the adenylates, PAGGS-M showed the best results. However, the difference to SAG-M was significant only after 7 weeks. On the other hand, serum appears to be the best medium for the conservation of 2,3-BPG. Between the 1st and 3rd week of storage, the decrease of 2,3-BPG was somewhat slower in PAGGS-M and SAG-M compared with the other 3 additive solutions.

Characterization of amphotericin B aerosols for inhalation treatment of pulmonary aspergillosis.

In recent years, the incidence of invasive pulmonary aspergillosis has increased in patients receiving immunosuppressive therapy and/or organ transplantation. For prophylaxis against Aspergillus infections, amphotericin B may be a useful drug when inhaled as aerosol. In this study, the aerosolization of amphotericin B was investigated using eight different medical nebulizers under various operating conditions and with different amphotericin B concentrations in the solution. The output of each nebulizer was characterized by the mass flow of spray (drug) leaving the mouthpiece and by the size distribution of the droplets. An effective prevention of pulmonary aspergillosis via amphotericin B inhalation requires a high pulmonary deposition of the drug within an acceptable time of administration associated with a low deposition in the oropharyngeal region. To evaluate the dosages of drug delivered by various types of nebulizers to different regions of the respiratory tract, a semi-empirical deposition model was applied which is based on experimental aerosol deposition data from over 20 normal adults. The main results of the study are: Solutions with amphotericin B concentrations up to 10 mg/ml can be converted into sprays by means of medical nebulizers without any problems. For most nebulizers, the slight foaming of the amphotericin B solution has no effect on the production of the aerosol. To optimize amphotericin B treatment of the lungs via inhalation, sprays with mass flows above 100 mg/min and with mass median aerodynamic diameters (MMAD) below 3 microns should be slowly inhaled by the subject. Applying these criteria to the nebulizers investigated, three out of eight devices have proved suitable for amphotericin B treatment via inhalation.

[Analysis of irregular antibodies at the department of transfusion medicine of the Hamburg-Eppendorf University Hospital 1984-1988]. / Analyse irregulärer Antikörper in der Abteilung für Transfusionsmedizin am Universitäts-Krankenhaus Hamburg-Eppendorf von 1984-1988.

In the University Hospital of Hamburg-Eppendorf (UKE) we performed approximately 80,000 screening tests for irregular RBC antibodies in the years 1984-1988. Among 1,815 (2.27%) positive tests, Rhesus and concomitant antibodies occurred in 0.77% (615/80,000), other clinically important antibodies in 0.37% (293 cases). We found significantly less Rh antibodies than in the previous period of the mid seventies (Rh prophylaxis, completely Rh-compatible transfusions).

[Rapid and sensitive determination of the adenylate energy charge in stored erythrocytes using high pressure liquid chromatography]. / Schnelle und sensitive Bestimmung des Adenylat-Energy-Charge in gelagerten Erythrozyten mittels Hochdruck-Flüssigkeits-Chromatographie (HPLC).

Using reversed-phase high-performance liquid chromatography (HPLC), we developed a fast method for the determination of the adenine-nucleotides ATP, ADP, and AMP in human red blood cells (RBC). The method is sensitive (10(-9)-10(-10) M), specific (greater than 95% peak-homogeneity), and the results are well reproducible. The three substances are assayed in a single step, which is essential for the exact determination of the adenylate-energy-charge (AEC). We applied the technique to fresh and stored RBC's. After six weeks' storage in PAGGS-sorbitol we found only a slight decrease in ATP content, but marked increases in ADP and AMP contents. Accordingly, there was a decrease in the AEC, whereas the total nucleotide pool (TNP) did not change significantly. As AEC and TNP reflect the state of the cellular energy metabolism, they are related to the viability of stored RBC. Thus, we consider the described method to be helpful for the quality control of RBC stored in new or modified media.

Treatment of patients with severe head injury by triamcinolone: a prospective, controlled multicenter clinical trial of 396 cases.

The present studies were conducted to test whether the outcome of severe head injury is improved by early administration of the synthetic corticosteroid triamcinolone. In a prospective, double-blind, multicenter clinical trial, 396 patients with severe head injury were randomized to a steroid group (n = 187) receiving 200 mg triamcinolone acetonide (Volon A soluble) i.v. within 4 h after trauma, followed by 3 x 40 mg/day i.v. for 4 days, and 3 x 20 mg/day i.v. for a further 4 days, and a placebo group (n = 209) receiving injections which did not contain any active drug. The placebo group was subjected to the same standard treatment procedures. Clinical features were not different between the groups upon admission to hospital. Subdural hematoma, epidural hematoma, and focal supratentorial contusion were among the most frequent diagnoses. The result of treatment with triamcinolone was assessed at discharge from the hospital and at 1 year after trauma, using the Glasgow Outcome Scale. Differences in favor of steroid treatment could be detected with regard to the patients' condition at discharge (P = 0.0634). More patients with steroids had a good recovery (49.2% vs 40.7%), and fewer died (16.0% vs 21.5%). Differences in outcome were even more pronounced (P < 0.0145) in patients with a focal lesion and a Glasgow Coma Score on admission of < 8 (n = 93). In this group, 34.8% of the patients made a good recovery, as against 21.3% of the placebo group; mortality was also lower in the verum group (19.6% vs 38.3%). The results indicate that a major subgroup of patients with severe head injury benefits from early administration of triamcinolone. Efficacy of the treatment can be expected, in particular, in patients with a focal cerebral lesion and a Glasgow Coma Score of < 8 on admission. Administration of steroids beginning at the scene of an accident would therefore be beneficial in these cases.

[Oxygen affinity and regeneration capacity of SAG-M and PAGGS-M stored erythrocytes]. / Sauerstoffaffinität und Regenerationsfähigkeit in SAG-M und PAGGS-M gelagerter Erythrozyten.

In order to estimate the leftward shift of the oxygen dissociation curve of hemoglobin following storage of red blood cells (rbc) in the additive solutions SAG-M and PAGGS-M, respectively, we performed blood gas analyses after equilibrating the cells with a gas mixture containing 4% of O2 and 5% of CO2 at pH 7.4 and 37 degrees C. Additionally, we took advantage of these nearly physiological conditions to measure the recovery of the hemoglobin function in vitro. We observed a good correlation between 2,3-BPG and p50 (i.e. the oxygen tension, at which hemoglobin is half-saturated with oxygen). Within the first 3 weeks of storage, the 2,3-BPG content fell to one fifth of its original value, whereas the p50 declined from 26.6 to about 20 mm Hg. Compared to fresh cells, rbc stored for longer than 3 weeks will thus deliver 30% less oxygen to the myocardium. The rbc's ability to restore these parameters remained unchanged throughout 7 weeks of storage.