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[Microbiological diagnosis of septicemia (author's transl)].

To detect microorganisms in the blood it is necessary not only that the microbiologist uses reliable methods, but also that the clinician takes a sufficient number of blood samples at the right point in time using a correct method for drawing the blood. The best results are obtained if the blood sample is transferred to the culture media at the bedside. The media should contain anticoagulants, osmosis stabilizers and preparations to neutralize the microbial action of the blood (caused by intrinsic and extrinsic factors). Up until now sodium polyanetholsulfonate ("Liquoid") has proved to be the most suitable additive. The procedure used for blood culturing must enable growth of aerobes, anaerobes and microbes with cell-wall damage. Today, modern methods such as radiometry, impedance measurement and microcalorimetry are used or are in the process of being developed which facilitate screening for positive cultures. Antigens, cell-wall constituents and metabolites of bacteria and fungi present in the blood stream can be detected by means of counter-immunoelectrophoresis, the Limulus test and gas chromatography, without culturing being necessary. Concentration techniques such as filtration and centrifugation are also being refined to enable a more reliable and earlier detection of septicemia.

Adult↗

Effects of ethanol on vestibular nucleus neurons responding to sinusoidal rotation.

Effects of ethanol applied by electro-osmosis were examined on the rat vestibular nucleus neurons responding to vestibular nerve stimulation and horizontal sinusoidal rotation. Ethanol (50-150 nA) inhibited the neurons monosynaptically activated by vestibular nerve stimulation and also suppressed the activity of the type I neuron, which responded with an increase in firing on ipsilateral rotation and a decrease on contralateral rotation. However, the drug did not affect the type II neuron, which showed the opposite response to the ipsi- and contralateral rotation compared with the type I neuron. Iontophoretic application of atropine (25-50 nA) inhibited spontaneous and rotation-induced firing in both type I and II neurons. These results suggest that ethanol inhibits the type I neuron projecting to the abducens nucleus, thereby impairing the vestibulo-ocular reflex.

Action Potentials↗

[Sialic acid containing compounds in the hemofiltrate of patients with chronic renal insufficiency. II. Isolation and structure determination of sialoglycopeptides].

Four sialyl glycopeptides have been isolated from the hemofiltrate of a patient with end stage renal disease using reverse osmosis, gel filtration and ion-exchange chromatography. Structural studies including one- and two-dimensional 1H-NMR spectroscopy, FAB mass spectrometry and enzymatic degradation indicated the following structures: (Formula: see text). While the disialyl glycopeptide has been previously characterized from normal and pregnancy urine, the three other sialyl glycopeptides could be isolated for the first time from biological material. The origin of these compounds and their possible clinical relevance is subject to further investigations.

Female↗

Chronic peritoneal dialysis.

Since the introduction of the permanent peritoneal catheter, interest in chronic peritoneal dialysis is increasing. The automatic peritoneal dialysis cycler and the reverse osmosis peritoneal dialysis machine have been other development that made chronic peritoneal possible. Chronic peritoneal dialysis is indicated for the children, the elderly, those without hemodialysis access sites, those living along (for home dialysis) and the diabetics, whose retinopathy seems to progress less on peritoneal dialysis than on hemodialysis. Patients awaiting a kidney transplant can be maintained equally satisfactorily on peritoneal dialysis as on hemodialysis. Because of its simplicity almost any patient can be trained for home peritoneal dialysis, and a high incidence of rehabilitation can be achieved. A flow rate of 4 1/hr with 21 exchanges, 40 hours a week, seem to the ideal dialysis requirements. Complications of chronic peritoneal dialysis include those related to the permanent catheter such as one or two way obstruction and those related the dialysis itself. The latter can be either acute (i.e. peritonitis etc.) or chornic such as neuropathy, renal osteodystrophy, anemia etc. Integrated with hemodialysis and transplantation, peritoneal provides the nephrologists with the ability to treat his patients with the most appropriate treatment.

Ascitic Fluid↗

[Isolation and NMR spectroscopic characterization of sialic acid compounds and hemofiltrate of chronic uremia patients].

Eight sialyloligosaccharides have been isolated from the hemofiltrate of a patient with end stage renal disease using reverse osmosis, gel filtration, ion-exchange and high-performance liquid chromatography. The structures were predominantly elucidated by one- and two-dimensional 1H- and 13C-NMR spectroscopy: 1 NeuAc alpha 2-3Gal beta 1-4Glc; 2 NeuAc alpha 2-6Gal beta 1-4Glc; 3 NeuAc alpha 2-3Gal beta 1-4GlcNAc; 4 NeuAc-alpha 2-6Gal beta 1-4GlcNAc; 5 NeuAc alpha 2-3Gal beta 1-4-GlcNAc alpha 1-P; 6 NeuAc alpha 2-6Gal beta 1-4GlcNAc alpha 1-P; 7 NeuAc alpha 2-3Gal beta 1-3GalNAc alpha 1-P; 8 NeuAc alpha 2-8NeuAc. While compounds 1-7 are also components of normal human urine, di-N-acetyl-D-neuraminic acid (8) could be isolated for the first time from biological material. The origin and possible clinical relevance of these compounds have to be proved in further investigations.

Blood↗

[Treatment of aluminum-induced osteopathy with desferrioxamine in dialysis-dependent renal failure].

Presenting two patients on long-term dialysis with marked osteopathy due to aluminium intoxication we described the symptoms, pathogenesis and therapy of the disease. Two patients were treated with the chelating agent desferrioxamine which lead to a striking improvement in clinical symptoms and removal of aluminium from bone. Osteopathy due to aluminium intoxication is refractory to Vitamin D and its metabolites. Using reversed osmosis in dialysis the high aluminium levels in bone result mainly from the long-term use of phosphate binders. Therapy of choice is the treatment with desferrioxamine.

Adult↗

[Studies of the possibility of repeated use of capillary dialyzers. I. Renovation method and the evaluation of biological reactivity].

A method devised by the authors of renovation of capillary dialyzers, after rinsing the blood and the liquid systems of the dialyzers is discussed. After rising the blood and the liquid systems of the dialyzers by water at 2 atm.--water being conditioned by the apparatus for reverse osmosis--in the liquid system overpressure of 2 atm was produced by water, the by 0.5% solution of sodium hypochlorite. After 2-3 minutes sodium hypochlorite was rinsed out and both systems were filled in by 1-2% formaldehyde solution. Immediately before using the dialyzer in the same patient the fluid system was rinsed with conditioned water, and the blood system with 21 of sterile distilled water and with 41 of 0.9% NaCl solution. In order to facilitate the renovation process a semi-automatic apparatus was designed, which makes it possible to renovate two dialyzers at once. This method makes it possible to use 80% capillary dialyzers four times with lateral input of the blood system, and four times 100% ones with central input. Experiments on animals and clinical observations and bacteriological studies shoved that the renovation process was atoxic, apyrogenic and sterile. No damage of capillaries and no reactions in subsequent use in patients under dialysis were observed.

Animals↗

Desalinated water hygiene and scientific bases for its investigation.

In view of the increasing scarcity of fresh water reserves in many countries of the world, a thorough hygienic evaluation of the different methods of desalinating highly mineralized underground and sea waters for economic and drinking purpose becomes indispensable. In addition to generally accepted hygienic criteria (favourable organoleptic properties, innocuous chemical composition and epidemiological safety), introduction of supplementary criteria for the assessment of the characteristic of the quality of freshened drinking water is necessary, i.e., its full value in the physiological sense and stability of drinking properties. The necessity of hygienic tests concerned with the study and regulation of the mineral and microelement composition of desalinated drinking water as well as of its microbial composition, structural peculiarities, the so-called "deuterium number" and the presence of various organic substances in desalinated water was pointed out. A certain degree of priority should be given to the study of the mentioned indices in hygienic assessment of the different methods of water desalination (distillation, freezing out, ion exchange, electrodialysis, inverse osmosis and others).

Hygiene↗

Dialysis dementia in Europe. Report from the Registration Committee of the European Dialysis and Transplant Association.

The diagnosis of dialysis dementia was confirmed in 150 patients treated in sixty-five dialysis centres in Europe in 1976 and 1977. The prevalence was approximately 600 per 100,000 European dialysis patients. The illness was confined to certain geographical areas, 90 of the patients being treated in only fifteen centres. It occurred more frequently in patients dialysed with unprocessed and softened water than in those treated with water processed by deionisation or reverse osmosis. Two-thirds of the patients had osteodystrophy, often painful and fracturing. Morbidity was severe and progressive and only 23 patients were still alive in 1978. The condition seems to be due to aluminium toxicity and should be preventable by water processing in centres where water aluminium content is raised.

Aluminum↗

Dysbaric osteonecrosis. Etiological and pathogenetic concepts.

Dysbaric osteonecrosis appears to be independent of decompression sickness. The 2 conditions, however, may share etiologic and pathogenetic factors. The incidence of osteonecrosis is influenced by the number of hyperbaric exposures, extent of pressure, decompression profile and possibly by the rate of compression and degree of obesity. Though etiology and pathogenesis are unclear, osteonecrosis is probably due to ischemia, with gas bubbles causing direct or indirect circulatory impairment. In vitro experiments, as well as human and animal studies, suggest multiple pathogenetic mechanisms: intraosseous vessel compression by extravascular bubbles; vessel obstruction by bubbles, fibrin thrombi, platelet aggregates, clumped erythrocytes or coalesced lipids; and narrowing of arterial lumina by bubble-induced myointimal thickening. Obstructing materials, whether autochthonous or embolic, may result from blood-bubble interface reactions. Rheologic changes and blood flow redistribution could play contributing roles. It seems likely that multiple pathogenetic factors act in concert or sequentially. Proposed nonischemic changes, such as hyperoxic injury gas-induced osmosis, or autoimmunity, lack sufficient supporting evidence. The peculiar vulnerability of bone may be related to gas supersaturation of the fatty marrow; sensitivity to extravascular gas pressure because of tissue rigidity; poor vascularization; and the presence of uranium 238 which promotes nucleation and subsequent gas bubble formation.

Animals↗

Serum aluminium in haemodialysis patients: relation to osteodystrophy, encephalopathy and aluminium hydroxide consumption.

The serum aluminium concentration of 82 patients undergoing regular dialysis treatment in a large dialysis department was measured. Duration of known uraemia, total cumulative aluminium hydroxide consumption, present level of aluminium hydroxide consumption and chronic interstitial nephropathy as primary kidney pathology were all positively correlated to serum aluminium concentration. Serum aluminium concentration was positively correlated to the incidence of clinical osteodystrophy and negatively correlated to bone mineral content. There was, however, no correlation to parathyroid hormone concentration or parathyroidectomy. The highest serum aluminium concentration was accompanied by clinical dialysis encephalopathy. The centre uses reverse osmosis for water purification, and there has never been measurable aluminium contamination. On the basis of these findings it is concluded that: the source of aluminium in our patients is aluminium hydroxide consumption and not the dialysis water; aluminium plays no role in the development of osteitis fibrosa; the findings are consistent with the theory that hyperaluminaemia plays a role in the development of osteomalacia, and serum aluminium measurement may be useful in the diagnosis of dialysis encephalopathy.

Adolescent↗

Membrane filters and membrane-filtration processes for health care.

The development of membrane-filtration processes is reviewed, and current types and uses of membrane filtration in health care is discussed. Development of adequate support structures for filters and of disposable filtration devices has facilitated development of filtration processes for pharmaceutical industry, manufacturing in hospital pharmacies, and direct patient care. Hydrophobic filters have also been developed; aqueous solutions cannot wet the pore structures of these filters and therefore cannot pass. Sterility-testing systems have also been developed. There are two types of filters: depth (constructed of compacted fibers) and membrane (which have a homogeneous internal structure). Depth filters retain only a portion of particles in a particular size range and are generally not acceptable for use in health care. Membrane filters retain all particles of a given size. Types of membrane filters are selected for specific uses based on needed flow rates, particulate load, and retention capability. Membrane filters may be validated using bacterial-passage, bubble-point, and diffusion tests. Most membrane filters used in health care are microporous filters that retain particles in the 0.1-10-micron size range. Applications are currently being developed for ultrafilters, which retain both particles and substances with large molecular structures such as proteins, and reverse-osmosis filter membranes, which allow only water or water-miscible solvents of very low molecular weights to pass. Experience in engineering designs, quality assurance, and test procedures has led to the development of many safe, reliable, and effective membrane products for health care.

Micropore Filters↗

[Determination of the plasma aluminum concentration of hemodialysis patients].

Plasma aluminium concentration was followed up in 28 patients with chronic renal insufficiency, treated with hemodialysis in the course of four years. Increased value of plasma aluminium was established as compared with a control group of healthy subjects, not observing any clinical signs of dialysis dementia. Slight increase of plasma aluminium at the end of the dialysis, was observed when the dialysis solution was prepared with non-purified potable water. When purified water, by reverse osmosis, was used the plasma aluminium concentration of the patients was not changed during the dialysis (the differences observed were not statistically significant). That fact provided grounds the authors to admit that the reason for the plasma aluminium increase during dialysis was the aluminium found in the dialysis solution, which necessitates water meeting the standard requirements for the allowable aluminium content, to be used for the needs of hemodialysis.

Aluminum↗

[History and importance of electrically excitable artificial membranes].

Solubility of narcotics in lipids has promoted the quest for non-aqueous and lipidic models of cell membranes. Artificial phosphatidic bilayers have been proposed. They display ionic conductance and excitability only if they are in contact with cyclic ion-carrier or specific substances, such as the protein fraction EIM. However many lipidic substances form non-bilayer membranes ion-conducting and excitable, without any specific additive. Only a small amount of free fatty acid is necessary. This is the condition for penetration through cation exchange. Coloured cations and cationic drugs undergo large exchange. Cu++, Hg++, emetine ++ cations have very high exchange coefficients which can be experimentally measured and which explain their respective antifungal, antibacterial and antiamoebian actions. The possible processes of membrane excitation are discussed. First the classical pores, specific of K+ and Na+ transfers and their "gating" mechanisms, because cell membranes are bi-ionic systems. Artificial membranes, are mono-ionic systems. But recent work shows that the axon membrane can be transformed into a monoionic system with Co++ as the only cations inside and outside the axon. Suggestions for the excitation processes are proposed. a) The assumption of a single energy barrier corresponding to minor conformational changes of structure. b) The membrane may be thixotropic. An outside cation penetrating the membrane would leave behind itself a wake of fluidity into which the next cations could penetrate if they follow each other closely. If they progress widely apart (under a small field), the ionic current would soon stop as the structure solidifies. c) The most promising suggestion is that anionic fixed charges in the membranes and cations form electrostatically bound ion-pairs. Dissociation of such pairs, that is conductance, augments markedly when dielectric constant increases. This process could be produced by water carried by incoming cations, that is by electro osmosis. This is exactly what occurs in Teorell's membrane oscillator in which a model membrane of fritted glass displays, under a weak current, oscillations of water flux and of potentials. The calculations pertaining to this model can be generalised if the electroosmotic water flux is assumed in increase the dielectric constant of the lipidic membrane. Thus the notion of an electroosmotic increase upon the dielectric constant of the membrane offers an alternative to the pore theory. Besides other phenomena show the role of low dielectric constants. The conductance of lipids containing coloured cations increase when subjected to illumination. The radiant energy absorbed then surpasses the association energy of ion pairs.

Animals↗

Healing of fracturing-bone disease occurring in patients on dialysis. A prospective study.

Ten patients developed fracturing-bone disease (osteomalacia) while on dialysis against water with high levels of aluminium. Eight patients remained on dialysis, using de-ionized or reverse-osmosis water, and 2 received a renal transplant. Clinical improvement as regards bone pain and proximal muscle weakness occurred in 6 months and radiographic evidence of healing of the pseudofractures was seen at approximately 12 months. Associated osteopenia and hyperparathyroidism were found in most patients, but no significant change in either was noted during the study period. The serum parathyroid hormone levels rose significantly in the patients who remained on dialysis. The chest and pelvic deformities typical of healed osteomalacia were seen. This dramatic improvement can only be attributed to the removal of some water-borne element, either by changing the water used in the dialysis or by successful renal transplantation. Aluminium-containing phosphate binders were used throughout the study in the patients on dialysis, and hypophosphataemia was never a feature.

Adult↗

Large-scale isolation of middle and higher molecular weight uremic toxins.

Reverse osmosis (40 bar) using membranes with a nominal cut-off of 500 Dalton is a useful method for the desalting and concentration of hemofiltrates (20-30 L) or even dialysates (120-240 L) from patients with end-stage renal failure. The removal of electrolytes and lower molecular weight solutes from the middle and higher molecular weight fractions can be carried out in one step. The freeze-dried residues show characteristic differences in their molecular weight distributions which are dependent upon their origin (Cuprophane dialysates or RP-6-hemofiltrates). Subfractionation is performed using Sephadex G-15 macrocolumns (2 m x 5 cm), the LKB-Ultrogel AcA 54 and Sephacryl S-200 as well as ion exchange chromatography. The fractions are characterized by their ability to suppress the incorporation of 3H-thymidine into rat bone-marrow as well as HeLa cell cultures. The greatest inhibitory activity originates from those fractions which are not dialysable using Visking tubes in vitro. The results indicate that the middle and higher molecular weight spectra do in fact overlap, suggesting that also higher molecular weight substances are involved in uremic intoxication.

Animals↗

Osmotic concentration of polypeptides from hemofiltrate of uremic patients.

Hemofiltrate from uremic patients was concentrated 15- to 40-fold by osmotic removal of water across a reverse osmosis membrane which retains salts and proteins. Salts and low molecular weight components were removed from the concentrate by partial dialysis using a highly impermeable cellulose membrane. Following this desalting step, 100- to 500-fold concentration could be achieved by evaporation at low pressure. The concentrate was fractionated on Sephadex G15 columns. Fractions were tested for their toxicity to human cells in culture. Fractions containing components with molecular weights greater than 700 daltons inhibited 3H-thymidine incorporation into the DNA of HeLa and skin fibroblast cells more than did low molecular weight peptides and an iso-osmolar control. Components eluting in the molecular weight range of angiotensin I and vitamin B-12 were most inhibitory. These studies show that hemofiltrate from uremic patients is a readily available source of toxic polypeptides. The osmotic concentration and gel chromatographic procedures described should make available large amounts of these molecules for further studies.

Animals↗

Modelling cortical cataractogenesis: 1. In vitro effects of glucose, sorbitol and fructose on intact rat lenses in medium 199.

After 2 days, lenses with intact capsules from adults rats remained clear when incubated in medium 199 with a normal glucose concentration but showed opacities when the level of glucose was increased up to 10 times normal. Scanning electron microscopy of the fixed lenses demonstrate globular degeneration in the visibly opaque lenses. The depth of degeneration increased as a function of the glucose concentration in the medium, as did the opacity. Thus, in glucose-induced cataracts, as in other types of cortical cataracts, opacity and globular degeneration of the lens appear to be associated. Sorbitol (but not fructose) also induced globular degeneration and lens opacities, indicating that there may be a mechanism of cataractogenesis other than osmosis. The high risk of cataracts in persons with controlled diabetes may be related to the observation that, in vitro, a lower concentration of glucose in medium 199, 8.9 mM (1.6 times the normal level), with 96 hours of incubation was as effective as the minimum concentration capable of causing cataracts, 11.1 mM (2 times the normal level), with 24 hours of incubation.

Animals↗