Effects of hyperlipidaemia on glucocorticoid metabolism: results of a randomized controlled trial in healthy young women.

OBJECTIVE: It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is altered in obese individuals. Hyperlipidaemia with elevated levels of free fatty acids (FFAs) is also frequently seen in obesity and in the metabolic syndrome. We hypothesized, therefore, that hyperlipidaemia may alter the activity of the HPA axis. PATIENTS AND METHODS: The effects of hyperlipidaemia, including increased circulating FFAs, on ACTH secretion and cortisol metabolism were analysed in 13 healthy young women during the early follicular phase of two subsequent cycles. We administered a 20% lipid/heparin (LHI) or a saline/heparin infusion (SHI) using a crossover design in random order for 330 min. A detailed characterization of glucocorticoid metabolism was performed by measurement of plasma ACTH, cortisol and urinary excretion rates of adrenal glucocorticoids and the glucocorticoid metabolites. RESULTS: We observed that LHI-induced hyperlipidaemia elevated serum cortisol levels compared to SHI. No changes in plasma ACTH levels, daily urinary excretion rates of adrenal glucocorticoids, glucocorticoid precursors/metabolites and the calculated activities of the 5α-reductase, 3ß-hydroxysteroid dehydrogenase (HSD), 11-, 17-, 21-hydroxylase and 11ß-HSD 1 or 2 were found. CONCLUSION: Our randomized controlled trial suggests that the adrenal sensitivity to ACTH may be enhanced by LHI-induced hyperlipidaemia in normal-weight healthy young women. This effect might contribute to the disturbances of the HPA axis described in women with abdominal obesity and impaired lipid metabolism.

Contact palm burns in toddlers from glass enclosed fireplaces.

We have seen an alarming increase in the incidence of pediatric palm burns associated with gas fireplaces. The increasing popularity of these units places more children at risk. Medical records of patients under the age of 5 years who sustained hand burns from contact with the glass enclosure of gas fireplaces from 1996 through 2002 were reviewed. Thirty-nine patients were identified, with a mean age of 12.8 months. A 15-fold increase in incidence was observed. Thirty-three patients suffered superficial second-degree burns that were treated conservatively. Twenty-one percent of children developed significant wound complications requiring intensive therapy including extension splinting or surgery. Pediatric burns resulting from palmar contact with the glass enclosures of gas fireplaces have emerged as an avoidable new danger within the home. Although most of these injuries heal with conservative treatment alone, many require surgery or other intensive management to regain acceptable function.

Stapled versus hand sewn anastomoses in patients with small bowel injury: a changing perspective.

INTRODUCTION: Recent studies indicate that trauma patients with hollow viscus injuries requiring anastomosis who are managed with stapling have a higher rate of complications than do those in whom a hand-sewn anastomosis is used. We undertook this study to determine whether this finding applied to patients with small bowel trauma at our institution. METHODS: Records of patients with small bowel injuries were retrospectively reviewed. Demographics, severity of injury, injury management, and outcome data were collected. RESULTS: Patients who had their small bowel injuries managed by hand-sewn repair versus resection and stapled anastomosis demonstrated a nonsignificant decrease in overall complication rate (35% vs. 44%) and rate of intra-abdominal complication (10% vs. 18%). Yet the rate of intra-abdominal abscess formation was significantly lower with hand-sewn repair than with resection and stapled anastomosis (4% vs. 13%). However, when hand-sewn primary repairs were excluded from the analysis and injuries that required resection and either stapled or hand-sewn anastomosis were compared, there was a similar overall complication rate (41% vs. 41%) and rate of intra-abdominal complications (17% vs. 21%). CONCLUSION: The rate of intra-abdominal complications did not differ significantly between patients requiring small bowel resection and reanastomosis managed by either a stapled or hand-sewn technique. In our experience, surgical stapling devices appear to be safe for use in repairing traumatic small bowel injury.

Endotoxin tolerance from lipopolysaccharide pretreatment induces nuclear factor-kappaB alterations not present in C3H/HeJ mice.

BACKGROUND: Lipopolysaccharide (LPS) activation of macrophage (MO) cytokine secretion requires activation and translocation of nuclear factor-kappaB (NF-kappaB). Endotoxin tolerance induced in LPS-responsive C3H/HeN MOs by LPS pretreatment results in decreased tumor necrosis factor (TNF) secretion and altered NF-kappaB activation. C3H/HeJ MOs have a genetic defect that renders them tolerant to LPS activation. We hypothesized that the alterations of NF-kappaB activation seen with LPS tolerance in HeN MOs would be present in HeJ mice. METHODS: MOs from C3H/HeJ and C3H/HeN mice were cultured with +/- 10 ng/mL LPS pretreatment for 24 hours and then stimulated with 1 to 1,000 ng/mL LPS. Activation of NF-kappaB was assayed by gel shift using a 32P-labeled specific oligonucleotide 30 minutes after LPS activation. TNF secretion 6 hours after LPS stimulation was measured by bioassay. RESULTS: LPS stimulation activated NF-kappaB in both HeN and HeJ MOs. We observed decreased NF-kappaB activation and a characteristic mobility shift in endotoxin-tolerant MOs from HeN mice that were not present in HeJ MOs. In contrast with the results in HeN mice, LPS pretreatment did not induce any alterations in NF-kappaB activation in HeJ MOs. LPS-stimulated TNF secretion was decreased in HeN MOs after LPS pretreatment. There was no change in TNF secretion in HeJ MOs, but, overall, TNF secretion by these cells was much less than that seen in HeN cells. CONCLUSION: MOs from C3H/HeN mice rendered LPS-tolerant by low-dose LPS pretreatment have alterations in activation of NF-kappaB not present in LPS-hyporesponsive C3H/HeJ mice.

Initial experience with laparoscopic live donor nephrectomy.

BACKGROUND: Advances in laparoscopic instruments and video technology have made laparoscopic donor nephrectomy (LDN) feasible. We report our initial experience with this technique. METHODS: A retrospective review of 30 open donor nephrectomies and our first 30 LDNs was performed to assess donor and recipient outcome and resource usage. RESULTS: LDN was successfully completed in 26 donors (87%). The increased operative time and costs were balanced by less postoperative pain, earlier discharge, earlier return to normal activity and work, fewer incision problems, and less personal financial loss. Recipient outcome was not affected. CONCLUSION: LDN is technically feasible and safe, and recipient graft outcomes are equivalent. Convalescence is shortened, and there is less personal financial loss. LDN offers significant benefit to the donor and may result in increased organ donation.

Civilian rectal trauma: a changing perspective.

BACKGROUND: Recently the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma developed a Rectal Injury Scaling System (RISS). Little data exist regarding its clinical utility. METHODS: We retrospectively reviewed 45 patients with rectal injuries to assess the impact of the RISS on patient management and outcome. We compared RISS grade I patients (group I, partial-thickness injury) with patients with grades 2, 3, and 4 injuries (group II, full-thickness injury). RESULTS: Group II underwent distal rectal washout and repair of the injury twice as often and had a significantly higher rate of diversion of the fecal stream. This was associated with a 3-fold increase in complications. The only complications in group I were in patients managed with diversion of the fecal stream and distal rectal washout. CONCLUSIONS: Our data suggest that aggressive surgical management for RISS grade I injury may not be necessary. Implementation of therapy based on the RISS may improve outcomes of civilian rectal trauma.

Macrophage TNF secretion in endotoxin tolerance: role of SAPK, p38, and MAPK.

PURPOSE: Endotoxin (LPS) activation of macrophages results in phosphorylation of mitogen-activated protein kinases (MAPK), stress-activated protein kinases (SAPK), and p38 kinase. LPS pretreatment inhibits subsequent LPS-stimulated MAPK activation and TNF release and both were reversed if macrophages were treated with phorbol myristate acetate (PMA) before LPS stimulation. In this study we sought to determine if SAPK and p38 tyrosine kinases are required for TNF production and if LPS pretreatment alters their activation. METHODS: TNF production by murine peritoneal exudate macrophages was determined 6 h after stimulation with 100 ng/mL of LPS +/- 24 h pretreatment with 10 ng/mL of LPS. The active, diphosphorylated forms of MAPK (p42, p44), SAPK (p46, p54), and p38 were assayed 30 min after LPS stimulation by Western immunoblot using specific antibodies. In some experiments a p38 kinase inhibitor (SB202190) or the protein kinase C activator (PMA) was added 1 h before LPS stimulation. RESULTS: LPS activated MAPK, SAPK, and p38. LPS pretreatment significantly inhibited MAPK, SAPK, and p38 activation by LPS stimulation. TNF protein secretion and MAPK activation in tolerant macrophages were restored by PMA treatment, but this did not restore SAPK activation. The p38 inhibitor SB202190 blocked LPS-stimulated TNF production. CONCLUSION: LPS pretreatment-induced tolerance decreased LPS-stimulated MAP, SAP, and p38 kinase activation. LPS tolerance in murine macrophages appears to be associated with specific, PMA-reversible defects in MAPK and p38 kinase activation.

In vitro macrophage endotoxin tolerance: defective in vitro macrophage map kinase signal transduction after LPS pretreatment is not present in macrophages from C3H/HeJ endotoxin resistant mice.

Altered endotoxin (LPS) signal transduction in macrophages (Mphi) may mediate development of organ dysfunction in sepsis. C3H/HeJ Mphi have a specific genetic defect that renders them "tolerant" to in vitro LPS activation. LPS tolerance can be induced in normal C3H/HeN Mphi following in vitro LPS pretreatment. In these experiments, in vitro LPS-stimulated activation of Mphi mitogen-activated protein (MAP) kinases were compared in C3H/HeJ and C3H/HeN mice. C3H/HeJ and C3H/HeN Mphi were cultured+/-10 ng/mL LPS pretreatment for 24 h, then stimulated with 0-1,000 ng/mL LPS for 6 h. Western blots were performed on lysates with monoclonal antibody to active ERK1,2 (p42/44), stress-activated protein kinase (SAPK, p54/46), and p38 kinase. Supernatant TNF or IL-1 was determined by bioassay. High dose LPS stimulation activated ERK, SAPK, and p38 kinases in both C3H/HeN and C3H/HeJ Mphi. ERK activation, p46 SAPK, and p38 activation were inhibited in C3H/HeN Mphi after LPS pretreatment, whereas they were unchanged or increased in HeJ Mphi. TNF secretion was significantly decreased in C3H/HeN Mphi following LPS pretreatment, but absent in C3H/HeJ Mphi at all times. Mphi from normal C3H/HeN mice rendered endotoxin tolerant by in vitro, low dose LPS pretreatment have specific signal transduction defects that are not present in genetically LPS hyporesponsive C3H/HeJ mice.

Lipopolysaccharide pretreatment produces macrophage endotoxin tolerance via a serum-independent pathway.

BACKGROUND: Lipopolysaccharide activation (LPSa) of macrophages is thought to occur via a CD14-dependent mechanism with a requirement for the serum factor, lipopolysaccharide binding protein. LPS-stimulated, CD14-dependent signal transduction is associated with phosphorylation of mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-kappaB) translocation, and secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1). Macrophage endotoxin tolerance after low-dose LPS pretreatment (LPSp) is characterized by inhibition of LPSa-stimulated TNF and augmentation of IL-1 secretion. We sought to determine the role of CD14-dependent pathways in the induction of endotoxin tolerance by comparing the effects of LPSp in the presence or absence of serum. METHODS: Murine peritoneal macrophages were exposed to a range of LPSp concentrations in the presence or absence of serum. MAPK activation and NF-kappaB were assayed 30 minutes after LPSp stimulation. TNF production and IL-1 were measured 6 hours after stimulation with 100 ng/mL LPSa, with or without 24-hour 10 ng/mL LPSp. RESULTS: In the presence of serum, 100 ng/mL LPSp activated MAPK and NF-kappaB, whereas no activation of MAPK or NF-kappaB was seen at this LPSp concentration in the absence of serum. The absence of serum during 10 ng/mL LPSp did not prevent LPSp-mediated inhibition of TNF secretion, and it significantly augmented IL-1 secretion after stimulation with 100 ng/mL LPSa in the presence of serum. CONCLUSION: Induction of the alterations in subsequent LPSa-stimulated cytokine secretion characteristic of endotoxin tolerance by LPSp occurs via a serum-independent signal transduction pathway.

In vitro activity of FK-037. A parenteral cephalosporin.

The in vitro activity of FK-037, a new extended spectrum cephalosporin, was determined against 398 recent clinical isolates consisting of ceftazidime-susceptible and -resistant, aerobic Gram-negative rods, penicillin-susceptible and resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus, methicillin-susceptible coagulase-negative staphylococci, and methicillin-resistant coagulase-negative staphylococci. Comparative drugs included ceftazidime, imipenem, and amikacin. Susceptibility testing was performed using a broth microdilution method. FK-037 showed greater activity than ceftazidime against ceftazidime-susceptible, aerobic Gram-negative rods. FK-037 showed enhanced activity compared with ceftazidime against Gram-positive organisms, including penicillin-resistant S. pneumoniae. Mutational frequencies for representative Gram-negative rods were comparable for FK-037 and ceftazidime.

[Beat-by-beat validation of the Oxford Medilog 4500, a 24-hour long-term ECG system with real-time analysis]. / Schlaggenaue Validierung des Oxford Medilog 4500, eines 24-Stunden-Langzeit-EKG-Systems mit Echtzeitanalyse.

We compared the annotation of the AHA and MIT databases beat-to-beat with the classification preformed by the microprocessor of a 24-hour ambulatory electrocardiographic device, based on real-time analysis. Sensitivity and positive predictive accuracy for QRS detection were 99.9% (99.9%) and 99.9% (99.8%) for the AHA database (MIT database respectively). Sensitivity and positive predictive accuracy were 99.1% (96.6%) and 98.3% (94.9%) for ventricular ectopic beats, 98.3% (91.8%) and 96.0% (63.0%) for couplets and 96.4% (74.2%) and 99.2% (41.1%) for salvoes. On 90% of the AHA tapes (MIT tapes) sensitivity and positive predictive accuracy were at least 93.8% (76.6%) and 92.7% (65.5%) for ventricular ectopic beats, at least 98.0% (96.3%) and 54.5% (0%) for couplets and at least 100% (66.6%) and 100% (0%) for salvoes. A sensitivity of 100% was achieved for ventricular ectopic beats on 56% (45%), for couplets on 90% (82%) and for salvoes on 95% (84%) of the AHA tapes (MIT tapes). A positive predictive accuracy of 100% was achieved for ventricular ectopic beats on 49% (52%), for couplets on 76% (61%) and for salvoes on 97% (75%) of the AHA tapes (MIT tapes). Real-time analysis of the Oxford Medilog 4500 proved sufficient for QRS detection and classification of ventricular ectopic beats. The quantification of frequent couplets and salvoes was sufficient, too. Sporadic false-positive detections of complex ventricular ectopic beats produced the false Lown grade IVA/IVB on 10% of the tapes as a consequence. The final computer report must hence be edited by a physician.

[Tachycardias caused by double ventricular responses and unusual atrioventrio-ventricular relations in linear dissociation of the AV node]. / Tachykardien durch doppelte Kammerantworten und ungewöhnliche Vorhof-Kammer-Beziehungen bei Längsdissoziation des AV-Knotens.

Noninvasive recordings in a 69-year-old woman showed phasic shifts between two distinct PR intervals of about 0.21 and 0.58 s suggestive of dual AV nodal conduction in the presence of two intranodal pathways. Episodes of tachycardia exhibited a one to two relationship between P waves and QRS complexes, with the same short and long PR intervals interpreted as simultaneous anterograde fast and slow conduction via the two AV nodal pathways, leading to a double ventricular response to single P waves. Various mechanisms of transition from short to long or long to short conduction times and concealed conduction phenomena could be demonstrated supporting the concept of two functionally separated intranodal pathways.

Unusual mechanism of PR interval variation and nonreentrant supraventricular tachycardia as manifestation of simultaneous anterograde fast and slow conduction through dual atrioventricular nodal pathways.

Noninvasive recordings in a 69-year-old woman showed two distinct PR intervals of about 0.21 and 0.58 s, suggestive of dual AV nodal conduction. Various unusual mechanisms of transition from short to long and from long to short conduction intervals and phenomena of concealed conduction were due to the presence of two functionally separated intranodal pathways. Refractoriness of the slow pathway was associated with bradycardia. Episodes of tachycardia exhibited a one-to-two relationship between P-waves and ventricular activations as a consequence of simultaneous anterograde fast and slow conduction leading to double ventricular responses to single P-waves.

[The influence of different plasma substitutes on blood clotting in isovolaemic haemodilution (author's transl)]. / Gerinnungsveränderungen bei Anwendung verschiedener Dilutionslösungen bei präoperativer isovolämischer Hämodilution

In a clinical study, the influence of 6 per cent Dextran 60 and 6 per cent hydroxyethyl starch (HES) on blood clotting was measured in 2 comparable groups of surgical patients. Haematocrit, platelets, thromboplastin time according to Quick, partial thromboplastin time and fibrinogen level were determined before and after isovolaemic haemodilution, and subsequently during a period of 14 days. There was no significant difference between the diluents with regard to their effect on blood clotting. Changes within each group may be ascribed to the diluting effect of the plasma substitutes.

[The reaction of the cardio-circulatory system during the introduction of the modificated NLA (AUTHOR'S TRANSL)]. / Das Verhalten des kardiozirkulatorischen Systems bei einer modifizierten NLA-Einleitung mit Etomidate. Eine klinisch experimentelle Studie

The hemodynamic effects of Etomidate are examined during the introduction of a modificated NLA. The following parameters are registrated: Heart Rate, Arterial and Mean Arterial Pressure, Pulmonary and Mean Pulmonary Pressure, and Cardiac Output. The Total Periphere Resistance and the Tension-Time-Index are calculated. Apart from a short moment during and immediately after intubation a remarkable constancy of all parameters is found. The alpha-receptor-blocking effect of Etomidate and DHB and the resulting decrease of the Total-Periphere Resistance are compensated by infusion of a colloidsolution. Myoclonias are not observed. Etomidate may be regarded as a drug with few effects on the circulation. It may be thinkable, that by means of Etomidate even in shock a careful introduction is possible.

[Circulatory changes during preoperative isovolaemic haemodilution with a mixed solution of hydroxyethyl starch and 5% human albumine. A clinical study (author's transl)]. / Kreislaufveränderungen bei Präoperativer Isovolämischer Hämodilution mit einer gemischten Lösung aus Hydroxyäthylstärke und Humanalbumin 5%

The influence of preoperative isovolaemic haemodilution on the circulation was examined in a clinical study. Heart rate, mean arterial pressure, mean pulmonary arterial pressure, cardiac output as well as haemoglobin and haematocrit values were determined. Stroke volume, total peripheral resistance, and the modified tension-time-index were calculated. A mixture of human albumin 5% and hydroxy-ethyl-starch was used as a solution for dilution. During the dilution phase the cardiac output increased compensatorily to the decrease of haemoglobin and the haematocrit values. While the heart rate and the mean arterial pressure remained unchanged the total peripheral resistance was reduced. Considering the described conditions and contraindications, preoperative isovolaemic haemodilution is a suitable method to replace an intraoperative blood loss of up to 2000 ml autologously. Thus a posttransfusion hepatitis can be avoided. In addition, preoperative isovolaemic hemodilution improves the microcirculation and may have a prophylactic effect on the thrombosis in the postoperative phase.