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The combination of pulmonary emphysema and liver cirrhosis in early childhood is documented for the first time in a 31/2 year old girl with homozygous (ZZ) deficiency of a1-antitrypsin. Examination of relatives in the generation of parents and grand parents revealed 7 heterozygous (MS) and five normal members (MM). Lung function tests showed altered respiratory function in 4 out of these 7 heterozygous subjects. Measurement of trypsin inhibitory capacity in plasma gave a good correlation to the genotype, however determinations of a1-antitrypsin coincided with it to a lesser degree. A high trypsin inhibitory capacity was detected in the tears of the propositi, which was shown to be immunologically distinguishable from serum a1-antitrypsin. Similarly, antiprotease activity was demonstrated in nasal secretions. This too did not reflect the serum profile.

Conventional thrombolytic therapy with streptokinase (SK) at the standard dose (loading dose, 250,000 IU; maintenance dose, 100,000 IU/h) after recent surgery may provoke a tendency towards severe bleeding secondary to plasminaemia associated with clotting disorders. In contrast, ultrahigh-dose SK therapy regimen (loading dose, 4 million IU; maintenance dose, 1-2 million IU/h) can minimize the risk of bleeding. Since the circulating plasminogen (Plg) can immediately bind to SK to form the so-called SK-Plg activator complex, free plasminogen is no longer available for conversion to systemic plasmin. In a pilot study, greater than 30 patients presenting with acute respiratory distress syndrome (ARDS) received ultrahigh-dose SK therapy following recent surgery. Although the period between surgery and thrombolysis was 2.5 days on average, no major haemorrhages occurred. In addition, a surprisingly high survival of 50% was reported. Although the efficacy of the ultrahigh-dose SK regimen in ARDS has not been definitively confirmed, this regimen is well accepted for the treatment of severe pulmonary embolism after surgery. Another promising indication for the use of this therapy is catheter-induced thrombosis of the major central veins. Additional, albeit rare, situations in which this treatment can be used include intrabronchial administration of thrombolytic agents after blood aspiration or their selective intravenous use following severe venous thrombosis in high-risk patients. This paper demonstrates the feasibility of thrombolytic therapy in these indications and discusses the benefit/risk ratio of the different agents tested.

The goal of analgesia and sedation in intensive care units is most often achieved using numerous drug combinations, mostly justified by physicians' and nurses' habits instead of rational pharmacological criteria for the choice of drugs and dosages. The present paper aims at defining the analgesic situation of ventilated intensive care patients and concludes from analogy with other, better understood states of pain that the importance of analgesic drugs is frequently overrated. To achieve effective analgesia and sedation in individual patients, the dosage must be titrated to individual needs. The author suggests that standardized baseline analgesia should be used, which enables sedation to be titrated, whereas the opposite is not practicable in clinical routine.

A brief survey on the ultrastructure, the chemical composition and the immunological properties of bacterial cell wall peptidoglycan (mucopeptide) is presented. This paper deals with the various recently discovered biological activities of peptidoglycan. These could be divided into three different groups, namely: 1. Endotoxin-like properties: pyrogenicity, induction of the local Shwartzman reaction, increase in non-specific resistance to bacterial infection, release of 5-hydroxytryptamine from rabbit platelets, complement activation,gelation of amebocyte lysate. 2. Inflammatory reactions of skin and internal organs, aggressin activity (virulence factor), inhibition of phagocytosis of bacteria by granulocytes and macrophages, inhibition of growth of cell cultures, cytotoxity to granulocytes and macrophages. 3. Potentiation of humoral and cellular immune responses (adjuvant), enhancement of tumor defense in experimental animals. The potential mechanisms of action of peptidoglycan are discussed and attention is focused on the implications of the various peptidoglycan activities for medicine.

This paper discusses the problem if the plasma protein binding of benzodiazepine derivatives can influence distribution and pharmacological activity of the drugs. The distribution of the benzodiazepines in the organism is influenced not only by the plasma protein binding of the drugs, but also by several other factors, especially since the drugs are mostly lipophilic. Thus, an effect of the plasma protein binding on the distribution can only be expected if the benzodiazepine derivative is highly bound to the plasma proteins. Thus results have been shown only for diazepam and chlordiazepoxid, which indicate an effect of the plasma protein binding on distribution and pharmacological activity, for example the existence of a direct correlation between unwanted CNS depressions and low plasma albumin concentrations and a direct correlation between the plasma protein binding and the biological half-life. There are no observations available on a displacement of other drugs from their binding to plasma proteins by benzodiazepines. The observed displacement of thyroid hormones from their binding to plasma proteins seems to have only a significance for thyroid function tests in vitro. It was shown that benzodiazepines decrease the amount of L-tryptophan bound to serum albumin in vitro and in vivo and increased therewith the L-tryptophan concentration in the brain. At present it can not be confirmed if these observations bear any significance on the pharmacological activity of the drugs. But these experiments demonstrate the significance of the use of albumin as a model for the interaction of drugs with tissue or receptorproteins.

This paper reports on a method which allows the separation of proteins of non concentrated CSF by means of the microzone technic. Pherograms of high quality were possible when the CSF contained more than 10 mg/dl total protein. Protein separation is completed in 16 min when one cellulose acetate strip with 150 V and 2 mA or when 150 V and 4 mA with two strips are used. Proteins were stained with nigrosine. The theoretical basis, technical details and error range of this method of protein separation are discussed.