Cyanide toxicity of sodium nitroprusside in therapeutic use with and without sodium thiosulphate

Summary Sodium nitroprusside (SNP) as a monoinfusion was administered to 51 patients for periods of a few hours. A further group of 19 patients received SNP for periods of several days as a combination solution of SNP mixed with sodium thiosulphate. The concentrations of cyanide and of thiocyanate in the blood of all patients were measured. In seven of the patients the level of thiosulphate was also measured. Infusion of SNP on its own at levels exceeding 2 µg/kg/min led to the rising of cyanide levels in the blood being proportional to dosage. Infusion of SNP mixed with thiosulphate showed no such accumulation of cyanide in any patient, irrespective of dosage level and duration. The efficacy at lowering blood pressure was fully maintained in the mixed infusion. The elimination half-life for thiosulphate was 16.5 min. Pharmacokinetic calculation of the rise in cyanide level showed that mono-infusions of 5–10 µg SNP/kg/min could within 5–10 h cause a life-threatening cyanide level in the blood. By contrast, mixed influsion of SNP together with thiosulphate, for which light-opaque syringes and tubing must be used, is a procedure free of danger and should become the technique of choice when therapeutically administering SNP in order to lower blood pressure.Supported by the Deutsche Forschungsgemeinschaft     

Diabetic fibrous breast disease

Women with long-standing insulin-dependent diabetes mellitus (IDDM) and radiographically dense mammary glandular tissue can have benign breast masses clinically resembling cancer. The authors have identified 36 patients, aged 20-54 years, with this little-known condition, which the authors call diabetic fibrous breast disease (DFBD). For a diagnosis of DFBD, the patient must fulfill certain stringent requirements: a long-term history of IDDM; radiographically dense glandular tissue; and one or more hard, irregular, easily movable, discrete, painless, palpable breast masses with strong ultrasonographic acoustical shadowing and firm resistance to the back-and-forth motion of the needle used for fine-needle aspiration cytology (FNAC). Patients meeting all criteria can be monitored with serial FNAC procedures to prevent them from undergoing multiple surgical biopsies. During an average of 6 years of monitoring these 36 women, breast cancer did not develop in any mass fulfilling all requirements for DFBD.     

Thoracotomy: Its Role in Diagnosis of Patients With Lung Lesions

Although thoractomy should be avoided where possible, it should not be passed over as a diagnostic tool of great accuracy. Patient discomfort can be lessened by various refinements of technique, and prompt action can often avert major problems at their outset. Bronchoscopy and mediastinoscopy are good diagnostic aids and should usually be booked together, since bronchoscopy alone often does not reveal enough information from which to make a diagnosis.     

Initial experiences with standardized diagnosis and therapy of cerebrovascular insufficiency

In a prospective (uncontrolled) study on 60 patients with cerebro-vascular insufficiency the possibility of a standardized diagnostics and therapy under the conditions of a peripheral medical care hospital are tested. Issuing from national and international publications as well as from own experiences a unique approach in the medical clinic of the County Hospital of Stralsund was tried. For the documentation a data form was developed. In the centre of the diagnostics stood clinical examination, ophthalmological examination, lumbar puncture and cerebral angiography, in the centre of the therapy haemodilution and physiotherapy. The average lethality was 47%, the proportion of the patients younger than 60 years 25%. 82% of the patients suffered from ischaemic insults. Under the conditions mentioned the approach demonstrated is a possible way with satisfying results.     

Poly(ethylene oxide)‐ and Poly(perfluorohexylethyl methacrylate)‐Containing Amphiphilic Block Copolymers: Association Properties in Aqueous Solution

Amphiphilic di‐ and triblock copolymers containing poly(ethylene oxide) (PEO) as the hydrophilic block and poly(perfluorohexylethyl methacrylate) (PFMA) as the hydrophobic block were synthesized by atom‐transfer radical polymerization using hydroxy‐terminated PEO as the macroinitiator. The copolymers were characterized by size exclusion chromatography and ¹H NMR spectroscopy. Self‐association in aqueous solution has been investigated using surface tension measurements, dynamic light scattering (DLS), and transmission electron microscopy (TEM). From surface tension measurements in water, a characteristic concentration (c*) can be detected, which is interpreted as the critical micelle concentration (cmc). The cmc decreases with an increase in fluoro content in the triblock copolymer up to 11 wt.‐% PFMA (solubility limit). DLS studies have been carried out for different samples above the cmc, showing small aggregates (micelles) and single chains for diblock copolymer solutions. In the case of triblock copolymers large clusters were the dominant aggregates in addition to the micelles and single chains. The effect of temperature and concentration on the micelle and cluster formation has been investigated by DLS. Micelle size was found to be resistant to any change by temperature, however, a slight but significant increase in apparent hydrodynamic radius was observed with an increase in concentration, while both temperature and concentration affected the formation of large clusters, especially in concentrated solutions. TEM has been carried out to visualize the morphology of the aggregates after transferring the solution to carbon film. The initial concentration for the preparation of TEM samples was found to have a strong influence on the morphology of the aggregates. By adding colloidal gold particles to the solutions, the typical covering by the polymer was observed by TEM.

Decay‐rate distributions for PEO₁₀F5 (4.0 g · L^?1); obtained from the time correlation functions.     

EDHF: a cytochrome P450 metabolite in coronary arteries

Endothelium-dependent relaxation cannot be fully attributed to the release of nitric oxide or prostacyclin (PGI2). In resistance-sized vessels and coronary arteries a high proportion of endothelium-dependent relaxation, in response to agonist-induced or mechanical stimulation of endothelial cells, can be attributed to the release of 1 or more endothelium-derived hyperpolarizing factor (EDHF). In coronary arteries EDHF has been pharmacologically characterized as a cytochrome P450 (CYP)-derived metabolite of arachidonic acid. We show here that a CYP 2C arachidonic acid epoxygenase, homologous to CYP 2C8/9, is expressed in cultured human endothelial cells and native porcine coronary artery endothelial cells. Down-regulation of CYP 2C protein by transfection of porcine coronary arteries with anti-sense oligonucleotides decreased EDHF-mediated vascular responses while EDHF-mediated hyperpolarisation and relaxation were potentiated by the CYP-inducing compound beta-naphthoflavone. Thus, CYP 2C appears to play a crucial role in the generation of EDHF-mediated responses in porcine coronary arteries.