Abnormal innervation of lower limb epineurial arterioles in human diabetes

Summary A quantitative ultrastructural analysis was made of the terminal innervation of epineurial arterioles in the sural nerve of 6 diabetic and 6 nondiabetic patients of comparable age (mean±SD: 68 ±9 non-diabetic, 65±16 diabetic) with end stage peripheral vascular disease. The results demonstrated specific differences, identifiable morphometrically, in the pattern of innervation of epineurial vessels of diabetics compared with non-diabetics. The differences were: 1) in the diabetic group the proportion of perivascular axons found less than 7 m from the nearest smooth muscle cell was significantly less than in the non-diabetic group (p <0.001); 2), the mean distance of the axons from their effector sites, the vascular smooth muscle cells, was nearly twice as far in the diabetic group compared with the nondiabetic group (p <0.05); and 3) the mean absolute number of axons less than 7 from the arteriole in the diabetic group was significantly less than in the non-diabetic group (p <0.01). These results demonstrate that the neuropathy associated with diabetes mellitus also involves the autonomic terminal innervation of some blood vessels. In addition, this neuropathy selectively affects the vasomotor nerves closer than 7 m to the media.     

Comparison of the effects of ascorbyl γ-linolenic acid and γ-linolenic acid in the correction of neurovascular deficits in diabetic rats

Summary Essential fatty acid metabolism is impaired by diabetes mellitus and -linolenic acid rich treatments such as evening primrose oil correct deficits in nerve conduction and endoneurial blood flow in diabetic rats. Other mechanistically unrelated treatments, such as antioxidants and aldose reductase inhibitors have a similar effect and there may be positive interactions with multiple treatments. Our aim was to compare the efficacy of a novel essential fatty acid derivative, ascorbyl -linolenic acid, with that of -linolenic acid in correcting diabetic neurovascular deficits. Eight weeks of diabetes caused 20.4 and 48.2% reductions in sciatic motor conduction velocity and nutritive endoneurial blood flow, respectively. Treatment was given for the last 2 weeks with -linolenic acid (100 mg · kg^–1 · day^–1) either in pure form or as ascorbyl -linolenic acid, an equivalent dose of ascorbate (21 mg · kg^–1 · day^–1) or jointly with ascorbate and -linolenic acid. Conduction velocity was corrected by 39.8, 87.4, 13.2 and 66.8% with -linolenic acid, ascorbyl -linolenic acid, ascorbate and -linolenic acid plus ascorbate, respectively. Corresponding ameliorations of the nutritive blood flow deficit were 44.0, 87.4, 13.2 and 65.7%. For the -linolenic acid plus ascorbate combination, and especially for ascorbyl -linolenic acid, the magnitude of correction for conduction velocity and blood flow was greater than expected for simple addition of ascorbate and -linolenic acid, indicating a synergistic interaction. Thus, with an efficacy 40 times that of evening primrose oil in rats, ascorbyl -linolenic acid may be a suitable candidate for clinical trials of diabetic neuropathy.Abbreviations ARI Aldose reductase inhibitor - GLA -linolenic acid - NCV nerve conduction velocity - NO nitric oxide - ROS reactive oxygen species - PG prostaglandin     

Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis)

Summary Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electro-physiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural new vessels which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a steal effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - IDDM insulin-dependent diabetes mellitus     

Direct measurement of capillary blood flow in the diabetic neuropathic foot

Summary The two major components of the microcirculation in the diabetic neuropathic foot have been examined in detail. Nutritive capillary blood flow was measured directly using the non-invasive technique of television microscopy, applied to the toe nailfold. Arteriovenous shunt flow was assessed using the technique of laser Doppler flowmetry, applied to the toe pulp. Fourteen diabetic patients with peripheral and autonomic neuropathy, 11 with no clinical evidence of neuropathy and 14 normal subjects were studied. Laser Doppler flowmetry (predominantly arteriovenous shunt flow) was increased more than three-fold (p<0.01) in the diabetic patients with neuropathy compared to control subjects, (median 3.57, interquartile range 2.00–5.32 volts vs median 0.93, interquartile range 0.47–2.36 volts respectively). There was no evidence of skin capillary closure. The calculated capillary blood flow (erythrocyte flux) was significantly increased in the diabetic neuropathic patients compared to control subjects (median 76.4, interquartile range 34.4–109.8 picolitres/s vs median 23.2, range 8.0–44.8 picolitres/s, p<0.01). This study demonstrates that foot skin capillary blood flow is increased in diabetic patients with neuropathy. There is, therefore, no evidence to support the supposition that capillary ischaemia, either secondary to a capillary steal phenomenon or advanced microangiopathy, is a feature of diabetic neuropathy under resting conditions.     

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine

Summary N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.Abbreviations TNF Tumour necrosis factor - NAC N-acetylcysteine - GSH glutathione - STZ streptozotocin - MNCV motor nerve conduction velocity - LPS lipopolysaccharide     

Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the ₃-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the ₂-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1–10 mol/kg) and clenbuterol (0.01–1 mol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1–3 mol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10–100 mol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective –adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a ₃-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mol/kg) nor clenbuterol (100 mol/kg) modified the acid secretion induced by histamine. These data suggest that ₃ adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.     

Capsular and ‘O’ serotype determinants of Bacteroides fragilis

Summary Forty-one strains ofBacteroides fragilis, 20 strains of otherBacteroides species and 14 strains of other genera were examined by the indirect immunofluorescent assay (IFA) using anticapsular serum. The sixty-oneBacteroides strains were O serotyped by direct agglutination tests using absorbed antisera raised against 23 strains, each with a different O antigenic determinant. All 41B. fragilis strains tested were positive by IFA with the anticapsular serum, but apart from one strain ofB. distasonis, none of the remaining 19 strains of other bacteroides, i. e.B. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus group andB. ureolyticus, and none of the 14 other bacterial species examined were positive. The majority of strains of saccharolytic bacteroides tested reacted with one of the 23 O antisera and were designated as a specific O serotype; a fewBacteroides strains had multiple agglutination reactions indicating the presence of multiple antigenic determinants. All O serotypes gave positive IFA tests with their homologous O antisera. Common capsular determinants and O antigenic determinants appear to exist on the same strains ofB. fragilis. Serological typing ofB. fragilis and related species would be useful in epidemiological studies.

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Kapsel- und O-Determinanten von Bacteroides fragilis

Zusammenfassung 41 Stämme vonBacteroides fragilis, 20 Stämme andererBacteroides-Spezies und 14 Stämme anderer Genera wurden unter Verwendung von Kapsel-Antiserum mit dem indirekten Immunfluoreszenztest (IFA) untersucht. Die O-Serotypisierung der 61Bacteroides-Stämme erfolgte mit dem indirekten Agglutinationstest; dabei wurden absorbierte Antiseren gegen 23 Stämme verwendet, von denen jeder eine unterschiedliche O-Determinante aufwies. Alle untersuchten 41 Stämme vonB. fragilis waren im IFA mit Kapsel-Antiseren positiv; hingegen war mit Ausnahme eines Stammes vonB. distasonis keiner der übrigen Stämme andererBacteroides-Spezies positiv, das heißt der GruppeB. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus undB. ureolyticus; von den anderen geprüften 14 Bakterienspezies war ebenfalls keine positiv. Die Mehrzahl der Stämme der untersuchten saccharolytischenBacteroides reagierte mit einem der 23 O-Antiseren und wurde einem spezifischen O-Serotyp zugeordnet; einigeBacteroides-Stämme wiesen mehrfache Agglutinations-reaktionen auf, was für das Vorliegen mehrerer Antigendeterminanten spricht. Bei denselben Stämmen vonB. fragilis scheinen gemeinsame Kapsel- und O-Antigendeterminanten vorzukommen. Für epidemiologische Untersuchungen dürfte die Serotypisierung vonB. fragilis und verwandten Spezies von Nutzen sein.

     

The effects of parabiosis on serum and kidney glycosidase activities in spontaneously diabetic mice

Summary Spontaneously diabetic non-obese mice of the ICR strain were newly inbred in Shionogi laboratory, Japan. Animals became diabetic suddenly, more frequently and severely in females. Blood glucose levels were 452±73 mg/100 ml with serum insulin levels of < 1.0 U/ml in the fed state. Parabiosis with normal control ICR mice for 2 weeks decreased the blood glucose level to 260±51 mg/ 100ml (P<0.01) and resulted in serum insulin levels of 46.0±18.0 U/ml (P<0.01). Kidney homogenate -N-acetylglucosaminidase and -galactosidase activities were reduced in diabetic mice (42% and 44% decrease respectively) (P<0.025 and P<0.001), and restored almost to normal after 2 weeks of parabiosis. Renal -mannosidase activity was decreased 43% (P<0.001) in the diabetic mice but unaffected by parabiosis. Serum -N-acetylglucosaminidase, -galactosidase and -glucosidase activities were significantly increased in diabetic mice (179%; 233% and 58% increase respectively) (P<0.005, P<0.001 and P<0.001), and returned to normal with parabiosis.     

Dose/response study of the effects of oestrogens on tumour growth and morphology in the Dunning R3327 prostatic adenocarcinoma

Summary The present study was undertaken to investigate to what extent the oestrogen-induced effects on growth and morphology of the Dunning R3327 rat prostatic adenocarcinoma are dose-dependent. Castrated and testosterone-supplemented rats were used in order to study effects of increasing doses of oestrogens on the tumour. It was found that the lowest dose of oestradiol-17 that reduced the overall growth, the volume density of the epithelium and epithelial cell area in Dunning R3327 prostatic tumours is 10 g given as daily injections. Higher oestrogen doses (50 g, 200 g, and 500 g), in addition to reducing the volume of tumour epithelium, also induced an increase of the volume density of tumour stroma. The area of stroma cell nuclei was increased by 50 g and 200 g oestradiol-17. These observation, may indicate that the lowest effective oestrogen dose is different in the epithelium and stroma of Dunning tumours and that large doses of oestrogen stimulate the stromal compartment. This stimulatory effect did not influence the inhibitory effects seen on the overall growth of the tumour and on the tumor epithelium.     

High plasma leucine concentrations without neurological symptoms in a patient with classical maple syrup urine disease

It has been found that the amino acid analyser used in this study systematically overestimated plasma leucine at high concentrations. The concentration reported as 2249 mol/L had a true value of 1430 mol/L and leucine values reported as >2000 mol/L were approximately 1500 mol/L.     

Twenty-four hour profiles of plasma C-peptide in Type 1 (insulin-dependent) diabetic children

Summary Twenty-four hour profiles of plasma C-peptide an index of endogenous insulin secretion, were performed in 15 Type 1 (insulin-dependent) diabetic children. Plasma C-peptide was detectable in six children, of whom four (C-peptide producers) had peak values above normal fasting levels. In each of the six children with residual B cell function, there was a close correlation between plasma C-peptide and simultaneous blood glucose (r> 0.50, p< 0.05). Post-breakfast peak blood glucose was 10.2 ± 1.7 mmol/l (mean ±SEM) in the C-peptide producers and 18.7 ± 1.7 mmol/l in the 11 children with low or no detectable C-peptide. Mean M-value, an index of deviation from an ideal blood glucose, was lower in the C-peptide producers (p<0.05). It is concluded that residual functioning B cells in diabetic children behave physiologically in that insulin secretion fluctuates in accordance with the prevailing blood glucose; and that the pattern of action of injected insulin is more critical in non-C-peptide producers who lack the post-prandial dampening effect provided by residual endogenous insulin secretion.     

The Role of the MAP-Kinase Superfamily in β-Amyloid Toxicity

The mitogen-activated protein kinase (MAP kinase) pathway participates in a number of reactions of the cell when responding to various external stimuli. These stimuli include growth factor binding to its receptor as well as stressful situations such as hypoxia and oxidative stress. It has been postulated that one of the mechanisms by which -amyloid exerts its toxic effects is to produce oxidative stress. This study therefore investigated whether the MAP-kinase pathway was activated in cells following exposure to -amyloid. Neuroblastoma (N2) cells were used in all experiments. The cells were exposed to 50, 100, and 500 M glutamate, and 10, 30, and 50 M -amyloid, for 24 h. The methyl–thiazolyl tetrazolium salt (MTT) assay was performed to determine the degree of toxicity. The generation of hydrogen peroxide was detected by fluorescence microscopy using the dye dihydrochlorofluorescein diacetate (DCDHF). Extracellular-signal-regulated kinase (ERK) and p38 MAP-kinase phosphorylation, as representatives of the MAP-kinase pathway, was determined. Treating N2 cells with -amyloid resulted in a greater than 50% reduction in cell viability. These cells also showed a significantly higher presence of hydrogen peroxide. Western Blot analysis revealed that the phosphorylation of p38 MAP kinase was dose-dependently increased in cells exposed to glutamate and -amyloid. On the other hand, the phosphorylation of ERK was significantly reduced in these cells. These data therefore suggest that the toxic effects of -amyloid involve the generation of hydrogen peroxide, leading to the activation of p38 and the down-regulation of ERK.     

Bone marrow and peripheral blood globin chain biosynthesis in iron deficiency

Summary Globin chain synthesis was studied in 13 iron-deficient patients. The mean whole-cell globin / ratio in the peripheral blood of 11 patients was 1.05±0.06 which is similar to the value 0.99±0.08 obtained for 10 controls. The ratios odtained for stroma-free globin were not significantly different from those of whole cell preparations. In contrast, the / ratio of bone marrow was 0.73±0.14 in 10 iron deficient patients, which is significantly lower than that of controls. Two other patients had decreased / ratios in the peripheral blood, probably because of the presence of an -thalassemia gene. These results demonstrate a reduced rate of synthesis of chains relative to that of chains in the bone marrow of iron-deficient patients that is not demonstrable in the peripheral blood.This work was partly supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil     

A deletion of 11 bp (CD 131–134) in exon 3 of the β-globin gene produces the phenotype of inclusion body β-thalassemia

Dominant inherited -thalassemias describe those -thalassemia variants that result in a thalassemia intermediate phenotype in individuals who have inherited only a single copy of the abnormal gene. This form of thalassemia is characterized by moderately severe anemia with jaundice and splenomegaly; it is also characterized by the presence of inclusion bodies in the red blood cell precursors and has, therefore, previously been referred to as inclusion body -thalassemia. We describe a case of inclusion body -thalassemia in a 51-year-old Spanish male caused by a deletion of 11 bp (CD 131–134) in exon 3 of the -globin gene. The deletion of 11 bp in exon 3 of the -globin chain is predicted to produce an anomalous chain of 134 amino acids instead of the normal 146 with an extremely altered amino acid sequence from residues 131–134. Although this shortened variant would lead to a missing H helix, which is involved in ₁₁ contact and ₁₂ subunit interactions, the variant chain can still be bound to the heme group and acquire a secondary structure that is not suitable for the formation of stable dimers or tetramers and also less susceptible to proteolytic degradation. This is the first report of such a -thalassemia mutation.     

Islet B-cell dysfunction and the time course of recovery following chronic overinsulinisation of normal rats

Summary Appropriate insulin therapy may preserve or improve islet B-cell function whereas the effects of overinsulinisation are unclear. Pancreatic islet B-cell function was therefore studied after overinsulinisation of normal rats for 4 weeks (fed blood glucose 2.2–4.5 mmol/l, controls 4.1–7.0 mmol/l). Insulin secretion was assessed by a 3-h hyperglycaemic clamp (10.0 mmol/l) performed 1, 48, and 120 h after insulin withdrawal (n=6 in each group). When the clamp was performed 1 h after insulin withdrawal, clamp insulin concentration was 1.6±0.1 g/l, compared to 9.3±1.0 g/l in control rats. The integrated area under the plasma insulin concentration curve was also significantly decreased (4.8±0.4 vs 20.3±2.2 g·l^–1·h^–1, p<0.001), but recovered to 9.4±1.0 g·l^–1·h^–1 after 48 h, and to 17.5±1.4 g·l^–1·h^–1 after 120 h. Pancreatic insulin contents were decreased at 1 h (6±1 g/g wet wt) and 48 h (54±12 g/g wet wt) but not at 120 h (221±30 g/g wet wt) after withdrawal (controls, 303±29 /g wet wt) and there was a strong relationship with pancreatic preproinsulin mRNA and the clamp insulin response. Thus, overinsulinisation with prolonged periods of low blood glucose concentrations impairs islet B-cell function, but is reversible over 5 days.     

Ultrastructural changes in A-cells exposed to diabetic hyperglycaemia. Observations made on pancreas of chinese hamsters

Summary Pancreatic A-cells of chinese hamsters with diabetes of varying severity and duration were examined by electron microscopy. Two predominant changes were observed: 1. Lysosomal digestion of secretory granules (granulolysis, crinophagy) occurred in practically all A-cells of diabetic animals but was rarely observed in those of normoglycemic controls. This is considered a response of A-cells to the cessation of glucagon release secondary to hyperglycemia. 2. In relatively degranulated A-cells of ketotic diabetic animals, dilatation of the cisternae of the RER was seen together with accumulation of pale, flocculent material, possibly reflecting persisting or enhanced glucagon synthesis. In addition, numerous maturing secretory granules were seen in the cisternae of the Golgi complex. Since these apparently contradictory phenomena may be seen in the same cell, it is suggested that granulolysis may not only result from decreased hormone release secondary to hyperglycemia but that different and independent stimulatory signals may exist for glucagon synthesis, for glucagon release, and for the initiation of granulolysis.Supported in part by the Fonds national suisse de la Recherche scientifique (Grants. No. 4848.3 and 3.154.69).     

Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats

Summary Rats injected i. p. with a single dose of nicotinamide (250 mg/kg) 15 min prior to i.v. injection of streptozotocin (65 mg/kg) develop a very mild form of diabetes characterized by slight elevations of plasma glucose, increased levels of HbA₁, and reduced insulin secretion in response to an i.v. glucose tolerance test. These rats gain weight normally and they are not hyperphagic, glycosuric, or polyuric. The effects of this very mild form of diabetes vs overt streptozotocin diabetes of three months duration on regional vascular ¹³¹I-albumin clearance, blood flow (assessed by 15 m ⁸⁵Sr-microspheres), and renal filtration function were examined in male Sprague-Dawley rats. Plasma glucose levels of rats with mild diabetes were 7.4±0.9 (mean±SD) (mmol/l) vs 6.5±0.6 for control rats and 31.3±6.0 for overtly diabetic rats. HbA₁ levels were increased 1.4 fold in mildly diabetic and 2.3 fold in overtly diabetic rats. Vascular clearance of ¹³¹I-albumin was markedly increased in ocular tissues (anterior uvea, retina, and choroid), sciatic nerve, aorta, new (subcutaneous) granulation tissue, and kidney of both diabetic groups, although increases in overtly diabetic rats exceeded those in the mildly diabetic group (2.2–4.6 times control animals vs 1.6–3.3 times, respectively). Likewise, both overt and very mild diabetes markedly increased glomerular filtration rate (1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (9 times and 4 times) and IgG (15 times and 4 times), as well as regional blood flow in the anterior uvea, choroid, and sciatic nerve. Increases in tissue sorbitol levels were much larger in overtly diabetic rats (generally 10–20 times control animals) than in mildly diabetic rats (1.5–3 times controls). myo-Inositol levels were significantly decreased only in lens and sciatic nerve of overtly diabetic rats. These observations indicate that even very mild diabetes is associated with vascular functional changes which develop more slowly than in overtly diabetic rats, but are disproportionately large (in view of the minimal increases in glycaemia and tissue polyol levels) compared to those in overtly diabetic rats.     

Effect of intraduodenal administration of 23-methyl-UDCA diastereoisomers on bile flow in hamsters

3,7-Dihydroxy-23-methyl-5-cholan-24-oic acid (MUDCA) and its two diastereoisomers, - and -MUDCA, were infused intraduodenally in biliary fistula hamsters in order to evaluate the effect on bile flow and their hepatic biotransformation processes compared with the natural analog ursodeoxycholic acid (UDCA). In addition, the corresponding glycine conjugates were compared. The bile acids were administered at different doses (0.7–6 mol/min/kg) over periods of 90 min. The results indicate that the racemic mixture exhibits a potent choleretic effect at both low and high doses, while the two individual diastereoisomers show this effect only at high doses. The presence of a C-23 methyl group in the side chain prevents hepatic amidation and alternative conjugations occur, such as glucuronidation, in order to facilitate their biliary secretion. Biotransformation of the methyl derivatives of UDCA occurred mainly by conversion to more polar glucuronide conjugates. There was little alteration to the molecule and, unlike UDCA, very little amidation occurred. These data indicate that the presence of a C-23 methyl group prevents the usual side-chain amidation common to the most naturally occurring bile acids and that glucuronidation is a requisite for efficient biliary excretion.     

Der Patient als Keimquelle in der Intensivpflegestation

Zusammenfassung 133 Patienten einer Intensivpflegestation, die bei der Aufnahme keine Symptome bakterieller Infektion zeigten und noch keine Antibiotika erhalten hatten, wurden nach dem Zufallsprinzip zwei Gruppen zugeordnet. Eine Gruppe (+Pat.) erhielt eine Antibiotikaprophylaxe mit Penicillinen oder Cephalosporinen, die zweite Gruppe (–Pat.) erhielt keine Antibiotika. Staph. aureus war bei –Pat. im Trachealsekret und in der Umgebung der häufigste potentiell pathogene Keim. Staph. aureus war im Trachealsekret und in der Umgebung der –Pat. signifikant häufiger als bei +Pat.. Klebsiella spp. standen im Trachealsekret und in der Umgebung von +Pat. an erster Stelle. Sie waren im Trachealsekret von +Pat. signifikant häufiger als bei –Pat.. In der ersten Woche des Stationsaufenthaltes traten bei +Pat. starke Veränderungen in der Keimflora der Trachealsekrete auf: die Besiedelung mit gramnegativen Keimen stieg auf fast 100% an, gleichzeitig ging die Frequenz von Staph. aureus zurück. In den Abklatschuntersuchungen aus der Patientenumgebung traten gramnegative Stäbchen bei +Pat. in signifikant höheren Koloniezahlen auf als bei –Pat.. Die paarweisen Vergleiche von Bakterienstämmen aus den Trachealsekreten und aus der Patientenumgebung ergaben, daß +Pat. gramnegative Keime und –Pat. Staph. aureus signifikant häufiger an die Umgebung abgaben. Auf die Kontamination der Patientenumgebung mit Staph. aureus wirkte sich der Faktor der trachealen Intubation nicht aus. Gramnegative Keime waren im Trachealsekret von intubierten Patienten signifikant häufiger als bei nicht intubierten. Derselbe Trend zeigte sich auch in der Patientenumgebung. Die Antibiotikaprophylaxe konnte, wie die klinischen Ergebnisse der Studie zeigten, die Patienten nicht im erwarteten Ausmaß vor Infektionen schützen. Patienten, insbesondere tracheal-intubierte, die Antibiotika erhalten, sind als Streuquellen für hochresistente gramnegative Keime anzusehen.

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The patient as a source of bacteria in intensive care units: Influence of antibiotics and tracheal intubation

Summary 133 patients in an intensive care unit, who prior to admission had not shown any signs of bacterial infection and had not received antibiotic treatment, were assigned to two groups at random. One group received antibiotic prophylaxis with penicillins or cephalosporins (+Pat.), the other group did not receive antibiotics (–Pat.). Staph. aureus was the most frequent facultative pathogen in tracheal secretions and in the environment of –Pat.. This organism was significantly more frequent in –Pat. than in +Pat. in both the tracheal secretions and the enviroment. Klebsiella spp. outnumbered all other species in +Pat.. They were significantly more frequent in tracheal secretions of +Pat. than of –Pat.. In the first week of hospitalisation marked changes were seen in bacterial flora of tracheal secretions of +Pat.. Colonization with gramnegative bacteria rose to nearly 100%, the frequency of Staph. aureus diminishing at the same time. Monitoring by contact cultures revealed that gramnegative rods were significantly more numerous in the environment of +Pat. than of –Pat.. Matching bacterial strains cultured from tracheal secretions and from the environment of the patients proved that +Pat. spread significantly higher numbers of their gramnegative bacteria into the environment. The same is true of –Pat. for Staph. aureus. Intubation had no noticeable effect on the degree of contamination of the surroundings with Staph. aureus. Gramnegative rods were significantly more frequent in tracheal secretions of patients with intubation than in patients without. The same trend was observed for environmental contamination. As the clinical results of this study have shown, antibiotic prophylaxis does not protect patients from infections to the extent expected. Patients, and particularly intubated patients, receiving antibiotic treatment have to be considered as sources of highly resistant gramnegative organisms.

     

Beta-Adrenergic Blockade Decreases Coronary Collateral Blood Flow in Patients with Coronary Artery Disease

The effect of -adrenergic blockade on coronary collateral blood flow has not been clarified. We examined the acute effects of -adrenergic blockade on coronary collateral blood flow. Fifteen patients (Part A) with stable angina were studied while undergoing coronary angioplasty. According to the protocol, all patients underwent a minimum of three balloon inflations. Collateral flow velocity was determined during balloon inflations using the Doppler flow guidewire positioned distally to the lesion. The two tested balloon inflations, the second and third, were maintained for the same length of time. Between the second and third balloon inflations, 1 mg of propranolol was administered IC into the treated artery. Ten controls were studied following saline infusion. In 10 other patients (Part B), the effect of 1 mg IC propranolol on the coronary artery area distal to the lesion was studied, and five patients served as controls. In the treated group, in Part A blood pressure remained stable during the balloon inflations tested. Heart rate decreased from 79 ± 11 to 73 ± 12 beats/min (P < .05), velocity time integral from 9.6 ± 8.2 to 6.6 ± 4.1 cm (P < .05), and ST elevation from 1.3 ± .9 to .9 ± 1.0 mV (P < .05) between the second and third balloon inflations. In the controls the variables examined did not change during the balloon inflations tested. In Part B, neither propranolol nor normal saline had any significant effect on coronary artery lumen area. Thus, IC administration of -adrenergic blockade decreases coronary collateral blood flow, and this potentially worsens the ischemic zone. However, -adrenergic blockade ameliorates myocardial ischemia during coronary angioplasty.