Klebsiella pneumoniae with extended spectrum beta-lactamase activity associated with a necrotizing enterocolitis outbreak

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in newborn infants, affecting primarily premature neonates. Clustering of cases in epidemics is well-described; many are associated with an identifiable pathogen. PATIENTS AND METHODS: Case reports are presented of six neonates seen with NEC during a 2-month period in 1998. All bacterial isolates were subjected to antibiotic testing, determination of MIC and molecular fingerprinting. RESULTS: Klebsiella pneumoniae with extended spectrum beta-lactamase production was isolated from blood cultures of all six patients. In five patients the isolate appeared to be a single clone. The onset of NEC in the patients was earlier, more rapid and more severe than usual. Four of the six required surgery and five required mechanical ventilation. Two of the six patients died, but only one was directly related to a complication of NEC. All of the patients developed severe thrombocytopenia (platelet count <20 x 10(9)/l), and three developed hepatitis. The K. pneumoniae proved difficult to eradicate. Extended courses of multiple antibiotics were administered and measures were introduced to reduce overcrowding and improve infection control. CONCLUSION: The isolation of a single clone of K. pneumoniae with extended spectrum of beta-lactamase activity during an NEC outbreak highlights the need for strict infection control. This organism caused significant morbidity and was difficult to treat.     

Luminal cross-sectional area and tension–strain relation of the porcine bile duct

The bile duct is a distensible tube serving to transport bile from the liver and gallbladder to the duodenum. The purpose of this study was to characterize the luminal cross-sectional area (CSA) and tension–strain properties during distension of the normal isolated porcine common bile duct in vitro. An impedance planimetric system located inside a balloon was used. Eleven porcine bile ducts were examined in two locations, in the hepatic duct and in the common bile duct. The CSAs obtained in the common bile duct were significantly higher than those in the hepatic duct in the pressure range 0–8 kPa (P < 0.001). The circumferential wall tension (T) – strain (ɛ) relations for both locations fitted to the exponential equation T = a·e ^{b ·ɛ} with determination coefficients of 0.97 ± 0.01. The a and b constants were not statistically different between the two locations indicating that the elastic properties did not differ. In conclusion, the luminal CSAs were larger in the common bile duct when compared to the hepatic duct and the tension–strain relations did not differ between the two segments of the bile duct.     

Morphological abnormalities of the terminal neuromuscular apparatus in recent juvenile diabetes

Summary Muscle biopsies from eight cases of acute juvenile diabetes (a few weeks after the beginning of the disease) revealed well marked degenerative changes combined with vigorous regeneration of the terminal neuromuscular apparatus. This observation is in accordance with previous demonstrations of neurophysiological disturbances at this early stage of diabetes.

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Morphologische Anomalien der neuromuskulären Endplatte bei frisch entdeckten juvenilen Diabetikern

Zusammenfassung Muskelbiopsien von 8 Patienten mit akutem juvenilem Diabetes (einige Wochen nach Krankheitsausbruch) zeigten ausgeprägte degenerative Veränderungen mit kräftigen Regenerationserscheinungen an der neuromuskulären Endplatte. Diese Befunde stimmen mit früher mitgeteilten Beobachtungen neurophysiologischer Störungen dieses Frühstadiums des Diabetes überein.

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Anomalies morphologiques de l'appareil neuro-musculaire terminal dans le diabète juvénile récent

Résumé Dans huit cas de diabete juvénile aigu (quelques semaines après le début de la maladie) des biopsies musculaires ont révélé des modifications dégénératives bien marquées, associées á une puissante régénération de l'appareil neuro-musculaire terminal. Cette observation est en accord avec les démonstrations précédentes de troubles neurophysiologiques à ce stade précoce du diabète.

     

The excretion of C6-C10-dicarboxylic acids in the urine of newborn infants during starvation. Evidence for omega-oxidation of fatty acids in the newborn

The excretion of C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, was measured during the three first days of life in 3 fasting newborns, 2 newborns fed with isocaloric glucose and 2 newborns given mothers'-milk. On the second and third day of life the starved children excreted 27-84 mmol adipic acid/mol creatinine, 6-22 mmol suberic acid/mol creatinine and 4-7 mmol sebacic acid/mol creatinine. The excretion of C6-C10-dicarboxylic acids in the neonates given glucose or mothers'-milk was, for the first three days of life, 0-9 mmol adipic acid/mol creatinine, 0-10 mmol suberic acid/mol creatinine and 0-4 mmol sebacic acid/mol creatinine. The latter amounts are equivalent to the excretion of dicarboxylic acids in older children. It is argued that the detected dicarboxylic acids are formed by omega-oxidation of long-chain monocarboxylic acids followed by beta-oxidation, and that the excreted amounts reflect omega-oxidation activity. It is speculated that the substantial omega-oxidation activity in the starving newborn serve to provide succinyl-CoA-substrate for the citric acid cycle and for gluconeogenesis.     

Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation

Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-alpha (TNF-alpha) concentrations have been implicated in the development of insulin resistance, but direct evidence in humans is lacking. Here, we demonstrate that TNF-alpha infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method. TNF-alpha directly impairs glucose uptake and metabolism by altering insulin signal transduction. TNF-alpha infusion increases phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, and c-Jun NH(2)-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1. These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake. Thus, excessive concentrations of TNF-alpha negatively regulate insulin signaling and whole-body glucose uptake in humans. Our results provide a molecular link between low-grade systemic inflammation and the metabolic syndrome.     

Characterization of transgenic mice with the expression of phenylalanine hydroxylase and GTP cyclohydrolase I in the skin

Phenylketonuria (PKU) is a metabolic disease causing increased levels of phenylalanine in blood and body fluids. Circulating phenylalanine is normally cleared by phenylalanine hydroxylase (PAH) expressed in the liver. The aim of this study is to exploit the skin as a 'metabolic sink' removing phenylalanine from the blood. We have previously showed that the overexpression of PAH and GTP cyclohydrolase I (GTP-CH), the rate-limiting enzyme in the synthesis of the cofactor for PAH, leads to high levels of phenylalanine clearance in primary human keratinocytes. In this study, we have investigated the 'metabolic sink' strategy in an in vivo model by developing three lines of transgenic mice expressing PAH and GTP-CH in various layers of the skin. The promoters used were keratin 14 (K14), involucrin (INV) and a truncated variant of Keratin 1 (K1). The mice were crossbred to a mouse model of human PKU, the PAH(enu2) mouse, in order to obtain mice that do not express PAH in the liver and the kidney. Transgenic mice containing the INV and K14 promoters expressed PAH and GTP-CH in the epidermis. However, the K1 promoter did not lead to detectable gene expression. Analysis of the mice showed that no phenotypic effect was observed in mice expressing PAH and GTP-CH from the INV promoter. However, low level of phenylalanine clearance was observed in mice expressing PAH and GTP-CH from the K14 promoter, suggesting that the skin can be genetically engineered to function as a 'metabolic sink'.     

Torque properties of a rat oesophagus for physiological and diabetic conditions

In this paper the torque of an oesophagus is studied for physiological and diabetic conditions. Since the function of the oesophagus is mainly mechanical, this work is focused on providing quantitative measurement of the passive biomechanical properties of the oesophagus torque. The oesophagus was treated as a membrane when calculating the stress and strain. The torque versus twist-angle relation was approximated to be linear at a specified pressure and longitudinal stretch ratio. Thus, the shear modulus can be computed by the torque, twist angle and polar moment of inertia in this state. The shear modulus varies greatly with the changing inflation pressure and longitudinal stretch ratio. When the longitudinal stretch ratio or transmural pressure is constant, the shear modulus is increased after 28 days of diabetes.     

Social relations as determinant of onset of disability in aging

The purpose of the study was to analyze whether social relations are related to onset of disability among old people at 1.5 year follow-up and whether these relations vary by age and gender. The study is based on baseline and 1.5 year follow-up data on 1396 older non-disabled adults. Social relations were measured by questions about diversity in social relations, social participation, satisfaction with social relations and instrumental social support. Onset of disability was described as developing need of help in at least one of six mobility activities. The results showed that a large diversity in social relations and high social participation were important factors for maintaining functional ability among the 75-year-old men and women, while social support was a risk factor for functional decline among the 80-year-old men. The present study suggests that being "embedded" in a strong network of social relations provides protection against disability by reducing risk of developing disability.     

Biomechanical properties of the anterior urethra of the male rabbit--a study using impedance planimetry

OBJECTIVE: To evaluate the anterior urethra of the male rabbit regarding its luminal cross-sectional area (CSA), CSA distensibility, circumferential tension-strain relation, histology and the collagen content of the tissue. material and methods: Nineteen rabbits were examined with impedance planimetry by distending the urethra at the passage from the spongious to the bulbous part and 1 cm proximally in the bulbous part. Four weeks later, eight rabbits underwent a second examination. After the measurements the urethras were processed for either histology or determination of collagen content. The urethras from six additional rabbits served as controls for histology and collagen content. RESULTS: The CSA and the CSA distensibility were smaller at the distal than the proximal distension site. At both sites the CSA distensibility was high at low luminal pressure loads and decreased with increasing pressure. The circumferential tension-strain plot displayed an exponential relation, with a steeper slope distally than proximally. Repeated biomechanical investigation revealed a significantly increased CSA and a decreased slope of the circumferential tension-strain relation at both distension sites. The biomechanical investigation induced abrasion of the epithelium, extravasation of erythrocytes and separation of the collagen fibres, suggesting oedema of the luminal part of the wall. After 4 weeks the epithelium had changed from transitional to stratified, squamous and often keratinized epithelium and the collagen beneath the epithelium formed a dense network instead of wavy lines as seen in the control urethras. The collagen content was larger at the distal than the proximal distension site. No change in collagen content could be demonstrated between the urethras investigated once or twice with impedance planimetry. CONCLUSIONS: The non-linear pressure-CSA, pressure-CSA distensibility and circumferential tension-strain relations found at both distension sites demonstrate that the urethra yields readily at low pressures, thus facilitating flow. At higher pressure loads, the tissue becomes less distensible, a property that protects it against over-distension and damage. Impedance planimetry cannot be used to study before-and-after phenomena as the biomechanical investigation changed both the histology and the biomechanical properties of the rabbit urethra.