bluuebunny/crossref_metadata_2025 huggingface dataset:
Holoprosencephaly and cleidocranial dysplasia in a patient due to two position‐effect mutations: case report and review of the literature
Authors: Fernandez BA , Siegel‐Bartelt J , Herbrick J‐AS , Teshima I , Scherer SW
Published: September 2005

Holoprosencephaly (HPE) is a genetically heterogeneous developmental field defect in which midline cleavage of the forebrain and craniofacial structures is impaired. Based on the analysis of HPE patients with chromosome rearrangements, at least six loci for the disorder have been assigned. The sonic hedgehog gene (SHH) at 7q36 has been identified as the HPE3 locus. Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by clavicular, pelvic and dental anomalies. It is caused by mutations in the osteoblast‐specific transcription factor CBFA1/RUNX2, which maps to 6p21. We report a 20‐year‐old female with premaxillary agenesis (part of the HPE spectrum), as well as skeletal abnormalities and impacted teeth reminiscent of CCD. She carries a de novo 6;7 reciprocal translocation, with breakpoints at 6p21.1 and 7q36. We have shown previously that the 7q36 breakpoint maps 15 kb telomeric to the 5′ end of SHH, which explains the patient's HPE phenotype. Now, using fluorescence in situ hybridization, we have identified a P1 artificial chromosome clone 800 kb upstream of CBFA1/RUNX2 that spans the 6p breakpoint. We propose that the proband's complex phenotype is due to two position‐effect (PE) mutations, one at each translocation breakpoint, which have altered the expression of the SHH and CBFA1/RUNX2 genes. The role of PE mutations in human disease is also reviewed.
Mapping phenotypes to language: a proposal to organize and standardize the clinical descriptions of malformations
Authors: Biesecker LG
Published: September 2005

Recent developments in molecular biology have markedly speeded the processes involved in determining the molecular etiology of human Mendelian disorders. Nowhere are these changes more evident than in the field that is variously termed molecular dysmorphology, human morphogenesis, or human developmental biology. In contrast to the rapid changes in molecular genetics analysis, the processes and approaches of the clinical component of molecular dysmorphology have not changed substantially, and clinical analysis is therefore becoming relatively slower than molecular discovery. If clinical discovery is to maintain its deserved position at the forefront of human genetics research, new methods must be developed to acquire, archive, and analyze these data. The limitations of current phenotyping, specifically, the limitations of the collection and archiving of clinical data in medical journal case reports and case series manuscripts are demonstrated. Several provocative approaches that have been proposed to advance the field of clinical analysis are reviewed. Lastly, a specific proposal for a system of clinical analysis and archiving of data on human pleiotropic developmental anomaly syndromes is proposed to address these limitations.
Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia
Authors: Evans D , Seedorf U , Beil FU
Published: September 2005

The great majority of patients with type III hyperlipidemia (type III HLP) are homozygous for the ε2 allele of the APOE gene. However, only about 10% of ε2 homozygotes develop type III HLP, and it has been proposed that additional genetic factors are required for the development of the condition. The frequency of two polymorphisms in the APOA5 gene, −1131T>C and S19W, has been determined in 72 hyperlipidemic patients with APOE2/2 genotype attending a lipid clinic. The frequency of both polymorphisms was significantly higher in APOE2/2 patients than in the normal population. Fifty‐three percent of APOE2/2 patients were carriers of one of the polymorphisms compared to 19.7% of controls. Thus, genetic variation in the APOA5 gene is an important cofactor in the development of type III HLP.
Detection of human neutrophil elastase with peptide‐bound cross‐linked ethoxylate acrylate resin analogs
Authors: Edwards J.V. , Caston‐Pierre S. , Bopp A.F. , Goynes W.
Published: September 2005

Abstract:  An assessment of elastase‐substrate kinetics and adsorption at the solid–liquid interface of peptide‐bound resin was made in an approach to the solid‐phase detection of human neutrophil elastase (HNE), which is found in high concentration in chronic wound fluid. N‐succinyl‐alanine‐alanine‐proline‐valine‐p‐nitroanilide (suc‐Ala‐Ala‐Pro‐Val‐pNA), a chromogenic HNE substrate, was attached to glycine‐cross‐linked ethoxylate acrylate resins (Gly‐CLEAR) by a carbodiimide reaction. To assess the enzyme‐substrate reaction in a two‐phase system, the kinetic profile of resin‐bound peptide substrate hydrolysis by HNE was obtained. A glycine and di‐glycine spacer was placed between the resin polymer and substrate to assess the steric and spatial requirements of resin to substrate with enzyme hydrolysis. The enzymatic activities of suc‐Ala‐Ala‐Pro‐Val‐pNA and suc‐Ala‐Ala‐Pro‐Ala‐pNA on the solid‐phase resin were compared with similar analogs in solution. An increase in visible wavelength absorbance was observed with increasing amounts of substrate‐resin and enzyme concentration. Enzyme hydrolysis of the resin‐bound substrate was also demonstrated on a polypropylene surface, which was employed for visible absorbance of released chromophore. A soluble active substrate analog was released from the resin through saponification of the ethoxylate ester linkages in the resin polymer. The resin‐released conjugate of the HNE substrate demonstrated an increased dose response with increasing enzyme concentration. The synthesis and assay of elastase substrates bound to CLEAR resin gives an understanding of substrate‐elastase adsorption and activity at the resin's solid–liquid interface for HNE detection with a solid‐phase peptide.
Porcine dermal collagen graft in pediatric renal transplantation
Authors: Richards S. K. , Lear P. A. , Huskisson L. , Saleem M. A. , Morgan J. D. T.
Published: September 2005

Abstract:  Successful closure of the anterior abdominal wall in infants following renal transplantation of adult organs may present a challenging dilemma to the transplant surgeon. Restricted volume of the recipient abdominal cavity and size discrepancy of donor adult kidney may lead to graft compromise. Pressure on the graft may be exacerbated further in the postoperative period by oedema that may lead to abdominal compartment syndrome. Donor/recipient size disparity remains the major obstacle in infant renal transplantation. We describe the use of a porcine collagen graft to facilitate closure of the abdominal wall following intra‐peritoneal transplantation of an adult cadaveric kidney.
Liver disease in autosomal recessive polycystic kidney disease
Authors: Shneider Benjamin L. , Magid Margret S.
Published: September 2005

Abstract:  Hepatic complications occur in a significant proportion of children with autosomal recessive polycystic kidney disease (ARPKD). PKHD1/fibrocystin, the defective gene in ARPKD, is expressed in the cilia of bile duct epithelium and leads to abnormalities in the rubric of the ductal plate malformation. Portal hypertension and biliary disease are the major liver problems seen in ARPKD. Complete blood counting, physical examination, ultrasonography and magnetic resonance (MR) cholangiography are indicated as screening procedures for hepatic disease in ARPKD. Medical and surgical interventions are potentially indicated for children with portal hypertension and/or biliary disease. A high index of suspicion for the diagnosis of cholangitis needs to be maintained in children with biliary disease. The implications of hepatic disease need to be considered in the decision‐making regarding renal transplantation in ARPKD.
Tissue viral DNA is associated with chronic allograft nephropathy
Authors: Šebeková Katarína , Feber Janusz , Carpenter Blair , Shaw Laura , Karnauchow Tim , Diaz‐Mitoma Francisco , Filler Guido
Published: September 2005

Abstract:  Viral infections post‐renal transplant (Tx) impact on outcome. Increased rejection rates and decreased renal function secondary to acute CMV, EBV and HHV‐6 infections are well described. However, the clinical significance of a mere presence of these viruses on kidney tissue biopsy remains questionable. Thirty‐six kidney biopsies obtained from 17 renal transplants (five females) and two combined liver–kidney recipients (one female) were retrospectively evaluated. Age at Tx ranged from 1.7 to 17.2 yr (median = 7.4). Biopsies were performed as protocol biopsies or when renal function deteriorated, between 6 weeks and 11 yr post‐Tx (median = 1.2 yr). Immunosuppression included steroids and combination of tacrolimus/cyclosporin, mycophenolate mofetil/azathioprin and induction therapy. Fourteen patients received antiviral prophylaxis (ganciclovir/valganciclovir/acyclovir). Renal tissue was classified according to Banff ’97 criteria. Tissue CMV, EBV, HHV‐6 and HHV‐7 was analyzed by PCR. We used an estimation of GFR from average plasma Cystatin C (CysC) and slopes of 1/CysC to assess renal function. The 16/36 biopsies were positive for one virus; 5/36 biopsies were positive for two viruses. In the infected group, Banff ’97 scores for interstitial fibrosis (ci) and tubular degeneration/atrophy (ct) were significantly higher (p < 0.03 vs. the non‐infected group for both). The slope of 1/CysC, or the proportion of patients on antiviral prophylaxis, did not differ significantly between both groups. In conclusion, a significant number of kidney biopsies showed PCR positivity for CMV, EBV, HHV‐6 and HHV‐7. This was associated with a significantly higher Banff score for ci and ct; while renal function was not affected. Further controlled studies are required.
Potential etiologies of biliary atresia
Authors: Bezerra Jorge A.
Published: September 2005

Abstract:  Biliary atresia is the most common cause of neonatal cholestasis and the leading indication for pediatric liver transplantation worldwide. The disease is caused by a progressive inflammatory and fibrosing obliteration of the extrahepatic bile ducts. Although the cause of this obstruction is largely unknown, patient‐based studies have identified environmental and genetic factors that may interact and orchestrate disease pathogenesis. Chief among these factors are infectious and immunologic processes. While infectious agents have varied in different patient populations, studies of liver specimens at different phases of disease point to a pro‐inflammatory commitment of lymphocytes at the time of diagnosis, and to their potential role in regulating bile duct obstruction. A review of these studies is the focus of this article.
Immunization of pediatric solid‐organ transplantation candidates: Immunizations in transplant candidates
Authors: Campbell Andrew L. , Herold Betsy C.
Published: September 2005

Abstract:  Many children who receive solid‐organ transplants have not completed their primary immunizations prior to transplantation. This leaves pediatric transplant recipients susceptible to the vaccine preventable illness of childhood, which if acquired post‐transplantation are associated with increased rates of complications, hospitalization, graft rejection and mortality. The administration of vaccines to transplant candidates earlier and more rapidly than in the healthy child will improve vaccination rates among transplant recipients while not compromising immunogenicity. The recommended vaccines and vaccine schedule are discussed in detail.
Hypertension and ace gene insertion/deletion polymorphism in pediatric renal transplant patients
Authors: Serdaroglu Erkin , Mir Sevgi , Berdeli Afig
Published: September 2005

Abstract:  The objective of the present study was to define the risk factors for hypertension and to analyze the influence of insertion/deletion (I/D) polymorphism of the angiotensin‐converting enzyme (ACE) on hypertension in pediatric renal transplant recipients. Twenty‐six pediatric renal transplant recipients with stable renal function and treated with the same immunosuppression protocol were included in the study. Their mean age was 12.5 ± 3.3 yr and mean time after transplantation was 38.5 ± 39.8 month. Twenty‐four hour ambulatory blood pressure monitoring (ABPM) was performed by SpaceLabs (90207) device. The I/D polymorphism of the ACE was determined by PCR and ACE serum level was analyzed by colorimetric method. Hypertension was present in 15 patients (57.7%) by causal blood pressure measurements and 19 patients (73.1%) by ABPM. Twenty‐two patients (84.6%) were found to be non‐dipper and eight of them had reverse dipping. Only time after transplantation (38 ± 31 vs. 79 ±49 month, p = 0.016) and cyclosporin A trough plasma levels (206 ±78 vs. 119 ± 83 ng/mL, p = 0.020) influenced the presence of hypertension by multiple logistic regression analysis. The distribution of genotypes were II = 2 (7.7%), ID = 8 (30.8%), DD = 16 (61.5%). There was no effect of ACE gene I/D polymorphism or serum ACE levels on hypertension prevalence and circadian variability of blood pressures. Hypertension was related to the time after transplantation and cyclosporin A levels. The ACE gene I/D polymorphism and serum ACE levels did not influence the blood pressure values or circadian variability of blood pressure among pediatric renal transplant patients.
Liver transplantation for hepatoblastoma: Indications and contraindications in the modern era
Authors: Otte Jean‐Bernard , Goyet Jean de Ville de , Reding Raymond
Published: September 2005

Abstract:  In the past 20 yr, a dramatic improvement has been achieved in the outcome of children with hepatoblastoma by combining cisplatin based chemotherapy and surgery. Treatment of patients in the USA is an exception to the rule that all patients should receive neoadjuvant chemotherapy. It is paramount that surgical resection be complete, both macro‐ and microscopically. Complete tumor resection can be achieved after chemotherapy with a partial hepatectomy when the intrahepatic extent is limited to 1–3 sectors. In multifocal (and solitary) hepatoblastomas invading all four liver sectors, and in centrally located tumors with close proximity to the major veins, the SIOPEL‐1 study and an extensive review of the world experience have shown that primary transplantation provides high, long term, disease‐free survival rate in the range of 80%. In contrast, the results of rescue transplants for incomplete tumor resection or disease recurrence after partial hepatectomy are disappointing (in the range of 30%). Hazardous attempts at partial hepatectomy in children with extensive hepatoblastoma should be discouraged. Guidelines are provided for early referral of children with extended hepatoblastoma to a transplant surgeon. There is a trend for a better patient survival after living related liver transplantation. Patients who will become candidates to liver transplantation should be treated with chemotherapy following the same protocols as for children undergoing a partial hepatectomy. There is a concern about cumulative nephrotoxicity of calcineurin inhibitors and chemotherapeutic drugs. Recent data suggest that these patients tolerate lower Tacrolimus trough blood levels than those transplanted for non‐malignant conditions, without increasing the risk of acute rejection. Due to the rarity of the disease, these children should be treated in specialized centers.
Neonatal hemochromatosis: Fetal liver disease leading to liver failure in the fetus and newborn
Authors: Whitington Peter F. , Kelly Susan , Ekong Udeme D.
Published: September 2005

Abstract:  Acute liver failure in the newborn is relatively rare but often fatal. The broadest definition of acute liver failure is failure of the vital functions of the liver occurring within weeks or a few months of the onset of clinical liver disease. Therefore, by definition, any liver failure in the newborn can be construed to be acute liver failure. A second component of the general definition of acute liver failure is the lack of known preexisting liver disease. In the case of neonatal acute liver failure, preexisting disease would by definition be liver disease that affects the fetus. Almost nothing is known about fetal onset liver failure, and there is no literature addressing the subject. This review will address fetal liver disease that leads to liver failure in the fetus or newborn.
Megachemotherapy followed by autologous stem cell transplantation in children with Ewing's sarcoma
Authors: Drabko Katarzyna , Zawitkowska‐Klaczynska Joanna , Wojcik Beata , Choma Marta , Zaucha‐Prazmo Agnieszka , Kowalczyk Jerzy , Gorczynska Ewa , Toporski Jacek , Kałwak Krzysztof , Turkiewicz Dominik , Chybicka Alicja
Published: September 2005

Abstract:  Twenty‐one children with high‐risk Ewing's tumor received high‐dose chemotherapy with a PBSCT. Aim of the study was evaluation of efficiency and safety of this procedure. All but three patients have meta‐static disease at presentation. There were 11 females and the median age at diagnosis was 12 yr (range 4.5–18 yr). Megachemotherapy consisted of melphalan 140 mg/m2/busulfan 16 mg/kg in 12 patients, melphalan 140 mg2/treosulfan 10.0 g/m2 in two patients and melphalan with other drugs in seven patients. Eight of 11 patients transplanted in CR survived with a median follow‐up 24 month (range 14–60) and probability of 2‐year OS is 0.68 and DFS is 0.63. There was no severe regimen‐related toxicity in this group. Children transplanted without remission died: Two of them due to transplant related causes and eight had progression of disease in a median time 7 month after PBSCT. Megachemotherapy with PBSCT is a safe procedure in children with Ewing's sarcoma in remission. Autologos transplantation in children with metastatic Ewing's sarcoma seems to improve their outcome. Patients with Ewing's sarcoma, resistant to conventional therapy and with recurrent disease did not benefit from megachemotherapy. New approaches such as anti‐tumor vaccination or using of imatinib are reasonable to introduce in patients with relapsed or resistant to therapy Ewing's tumor.
Severe poisoning with sotalol and verapamil. Recovery after 4 h of normothermic CPR followed by extra corporeal heart lung assist
Authors: Rygnestad T. , Moen S. , Wahba A. , Lien S. , Ingul C. B. , Schrader H. , Knapstad S. E.
Published: September 2005

In acute poisoning with beta‐blocking drugs and calcium‐channel blockers patients may present with serious symptoms. We present a case of life‐threatening sotalol and verapamil intoxication in a 29‐year‐old female suffering from depression. She was admitted to our hospital a few hours after she had taken 3.6 g verapamil and 4.8 g sotalol. On being found the patient was breathing and had a palpable pulse. On admission the patient experienced a cardiovascular collapse and CPR was started. Echocardiography confirmed cardiac standstill. After 4 h of normothermic CPR, extra corporeal heart lung assist (ECHLA) was established. Vasoactive drugs could be stopped after 2 days with ECHLA, and after 5 days the patient was extubated. The patient experienced several complications (intestinal bleeding, transient nerve paralysis, and renal failure due to rhabdomyolysis) but made a complete recovery and started working 6 months after the poisoning. She was no longer depressed.
N2O‐free low‐flow anesthesia technique for children
Authors: Bozkurt P. , Saygi Emir N. , Tomatir E. , Yeker Y.
Published: September 2005

Background:  The use of N2O during low‐flow anesthesia (LFA) causes difficulty in predicting inspired gas mixtures and oxygen concentration due to accumulation. An alternative technique, which uses a mixture of oxygen and air and a morphine infusion to replace N2O, has been evaluated in children during LFA, and the clinical effects and composition of gases in the system are presented here.

Methods:  Thirty‐five children aged 2–13 years undergoing major urogenital surgery were recruited into the study. Following a standardized induction, anesthesia was maintained with 2% sevoflurane in combination with a morphine infusion. After induction with 4 l min−1, flow rates were reduced to 2 l min−1 and finally to 1 l min−1 at 10 min (0.5 l oxygen + 0.5 l air). The delivered oxygen concentration, oxygen saturation and the inspired and expired O2, sevoflurane and CO2 concentrations were recorded from the start of induction to the end of anesthesia.

Results:  The duration of LFA was 132±89 min. The concentrat‐ion of oxygen delivered by the flow meters during this period was 55–60%. Although the changes in inspired and expired oxygen and sevoflurane and inspired CO2 related to the duration of LFA were statistically significant (P < 0.0001), they were not clinically relevant. All vital parameters were stable. Four patients required supplemental morphine and nine presented emergence agitation.

Conclusion:  We concluded that an N2O‐free LFA technique with 0.5 l min−1 of air and 0.5 l min−1 of O2 supplemented by sevoflurane and a morphine infusion is safe and effective in children. The resulting high‐inspired oxygen concentration prevents occurrence of hypoxic gas mixtures, and the use of supplemental morphine compensates for the absence of N2O and overcomes the possibility of light anesthesia arising from a decrease in the inspired sevoflurane concentration.
Can propofol precipitate pancreatitis in patients with Cushing's syndrome?
Authors: Priya G. , Bhagat H. , Pandia M. P. , Chaturvedi A. , Seth A. , Goswami R.
Published: September 2005

We encountered two cases of acute pancreatitis in patients with Cushing's disease following transnasal transsphenoidal hypophysectomy. In both cases propofol was used in bolus doses, and is thought to be the probable factor for its development. Since elevated cortisol levels in Cushing's disease poses a threat for pancreatitis, there is a possibility that patients with Cushing's disease might be more prone to acute pancreatitis following propofol administration. Anaesthesiologists and physicians dealing with the management of Cushing's disease need to be aware of this possibility.
The pre‐emptive analgesic effect of intra‐articular bupivacaine in arthroscopic knee surgery*
Authors: Tuncer B. , Babacan C. A. , Arslan M.
Published: September 2005

Background:  The purpose of this study was to determine whether intra‐articular injection of bupivacaine prior to surgery provided better pain control after arthroscopic meniscectomy as compared with post‐operative administration of bupivacaine.

Methods:  Forty patients of American Society of Anesthesiologists (ASA) class I or II undergoing arthroscopic meniscectomy were assigned in a randomized, double‐blinded manner into two groups: Group I received 20 ml of 2.5 mg/ml bupivacaine without epinephrine 30 min before skin incision and 20 ml of saline immediately after skin closure. Group II received identical injections in reverse order. All patients received total intravenous anesthesia. Post‐operative pain scores were evaluated at 1, 2, 4, 6, 8, 12 and 24 h at rest and movement of the knee, using a 10‐cm visual analog scale (VAS). The time to first analgesic use and 24‐h analgesic consumption were recorded.

Results:  Pain scores were lower in Group I compared with Group II at 1, 2, 4 and 6 h at rest and on movement (P < 0.05). The time to first analgesic use was longer in Group I, but there was no statistically significant difference in 24‐h analgesic consumption.

Conclusion:  Intra‐articular bupivacaine administered before surgery provided a statistically significant reduction in post‐operative pain scores compared with post‐operative bupivacaine administration.
Is peri‐operative cortisol secretion related to post‐operative cognitive dysfunction?
Authors: Rasmussen L. S. , O'Brien J. T. , Silverstein J. H. , Johnson T. W. , Siersma V. D. , Canet J. , Jolles J. , Hanning C. D. , Kuipers H. M. , Abildstrom H. , Papaioannou A. , Raeder J. , Yli‐Hankala A. , Sneyd J. R. , Munoz L. , Moller J. T. ,   (for the ISPOCD2 Investigators)
Published: September 2005

Background:  The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post‐operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in cortisol level.

Methods:  We studied 187 patients aged over 60 years undergoing major non‐cardiac surgery with general or regional anaesthesia. Saliva cortisol levels were measured pre‐operatively and at 1 day, 7 days and 3 months post‐operatively in the morning (08.00 h) and in the afternoon (16.00 h) using salivettes. Cognitive function was assessed pre‐operatively, on day 7 and at 3 months using four neuropsychological tests. POCD was defined as a combined Z score of greater than 1.96.

Results:  After surgery, salivary cortisol concentrations increased significantly. POCD was detected in 18.8% of subjects at 1 week and in 15.2% after 3 months. The pre‐operative ratios between the morning and afternoon cortisol concentrations (am/pm ratios) were 2.8 and 2.7 in patients with POCD at 1 week vs. those without POCD at 1 week, respectively. The am/pm ratios decreased significantly post‐operatively to 1.9 and 1.6 at 1 week, respectively (P = 0.02 for both). In an analysis considering all am/pm ratios, it was found that the persistent flattening in am/pm ratio was significantly related to POCD at 1 week.

Conclusion:  The pattern of diurnal variation in cortisol level was significantly related to POCD. Thus, circadian rhythm disturbance or metabolic endocrine stress could be an important mechanism in the development of cognitive dysfunction after major surgery.
Inhibitory effects of desflurane and sevoflurane on oxytocin‐induced contractions of isolated pregnant human myometrium
Authors: Yildiz K. , Dogru K. , Dalgic H. , Serin I. S. , Sezer Z. , Madenoglu H. , Boyacı A.
Published: September 2005

Background:  In this study, we investigated the inhibitory effects of desflurane and sevoflurane on oxytocin‐induced contractions of isolated human myometrium.

Methods:  Following delivery of the infant and placenta, a small segment of myometrium was excised from the upper incisional surface of the lower uterine segment and 20 strips, randomly assigned into two groups (n = 10), were obtained from 20 non‐laboring term parturients. The study protocol consisted of a 60‐min period of spontaneous contractions, control recording with oxytocin 2 × 109 m (10‐min period), washout interval of 10 min, volatile administration (three times per 15‐min period) of 0.5, 1 and 2 minimum alveolar concentration (MAC), response to oxytocin (10‐min period), a further washout interval (10‐min period) and subsequent control recording with oxytocin without anesthetics.

Results:  After oxytocin administration, the frequency and amplitude of contractions increased (P < 0.05) and the duration decreased (P < 0.05). The frequency and amplitude of contractions induced with oxytocin decreased significantly at 0.5, 1 and 2 MAC of desflurane and sevoflurane (P < 0.05). The amplitude of contractions was significantly different at 1 MAC between the two groups (P < 0.05). The duration of contractions at 2 MAC decreased in both groups (P < 0.05).

Conclusions:  Desflurane and sevoflurane at 0.5, 1 and 2 MAC inhibit the frequency and amplitude of myometrial contractions induced with oxytocin in a dose‐dependent manner. However, desflurane inhibits the amplitude less than sevoflurane at 1 MAC. We suggest that 0.5 MAC of both agents and 1 MAC of desflurane may be safely used in the presence of oxytocin following delivery of the infant and placenta during Cesarean section without fear of uterine atony and hemorrhage.
Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage
Authors: Haugen O. , Farstad M. , Kvalheim V. , Rynning S. E. , Mongstad A. , Husby P.
Published: September 2005

Background:  Cardiopulmonary bypass (CPB) is associated with increased fluid filtration occasionally leading to post‐operative organ dysfunction. One of the factors determining fluid filtration is the capillary hydrostatic pressure which depends on arterial pressure, venous pressure and pre‐ to post‐capillary resistance ratio. The purpose of this study was to assess whether lowering of the mean arterial pressure and/or the central venous pressure could reduce fluid extravasation during normothermic and hypothermic CPB.

Methods:  Seven piglets were given nitroprusside to a mean arterial pressure of 35–40 mmHg during 60 min of normothermic and 90 min of hypothermic CPB (LP group). They were compared with a control group (C group, n = 7) without blood pressure interventions. Blood chemistry, net fluid balance, plasma volume, colloid osmotic pressure in plasma and interstitial fluid, intravascular protein masses, fluid extravasation rate and total tissue water content were measured or calculated.

Results:  Mean arterial pressure was significantly lower in the LP group than in the C group during CPB. Plasma volume tended to increase in the LP group (P > 0.05), but remained essentially unchanged in the C group. Net fluid balance in the LP group was more positive than in the C group 30 min after CPB start [1.02 (0.15) vs. 0.56 (0.13) ml/kg/min (Mean (SEM) P < 0.05)]. Fluid extravasation rate tended to be higher in the LP group and total tissue water content of the gastrointestinal tract, left myocardium and skin was significantly elevated compared with the C group.

Conclusion:  During CPB, lowering of the mean arterial pressure using nitroprusside did not reduce fluid extravasation. On the contrary, the data may implicate an increase in edema formation during low pressure CPB.
The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery
Authors: Kuitunen A. , Hiippala S. , Vahtera E. , Rasi V. , Salmenperä M.
Published: September 2005

Background:  Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery.

Methods:  Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used.

Results:  Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti‐thrombin III complexes 33.7 ± 3.6, 53.6 ± 7.0 and 44.2 ± 5.3 µg/l 2 h after CPB and F1 + 2 fragment 1.50 ± 0.10, 2.37 ± 0.37 and 2.04 ± 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti‐fibrinolytic drugs (d‐dimers 0.427 ± 0.032, 0.394 ± 0.039 and 2.808 ± 0.037 mg/l 2 h after CPB, respectively). The generation of d‐dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti‐plasmin complexes 0.884 ± 0.095, 2.764 ± 0.254 and 1.574 ± 0.185 mg/l 2 h after CPB, respectively).

Conclusion:  Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery.
Effects of autotransfusion of mediastinal shed blood on biochemical markers of myocardial damage in coronary surgery
Authors: Pleym H. , Tjomsland O. , Åsberg A. , Lydersen S. , Wahba A. , Bjella L. , Dale O. , Stenseth R.
Published: September 2005

Background:  Previous studies have shown conflicting results regarding the effect of autotransfusion of mediastinal shed blood after coronary artery bypass grafting (CABG) on the serum levels of myocardial band (MB) isoenzymes of creatine kinase (CK‐MB) and cardiac troponins. The effect of autotransfusion on serum levels of human heart fatty acid binding protein (H‐FABP), another marker of myocardial necrosis, has not been studied. The aim of the present study was to investigate the effects of autotransfusion of mediastinal shed blood on the serum levels of CK‐MB, cardiac troponin T (cTnT), and H‐FABP after uncomplicated primary CABG.

Methods:  Fifty patients were randomized to post‐operative autotransfusion of mediastinal shed blood or no autotransfusion. Blood samples for the analysis of the biochemical markers of myocardial damage were drawn pre‐operatively and 1, 4, 12, 24, 48, and 72 h after the termination of cardiopulmonary bypass. Samples from the mediastinal shed blood were collected after 1 and 4 h.

Results:  The levels of the biochemical markers of myocardial injury were all markedly elevated in mediastinal shed blood. Autotransfusion did not significantly affect the serum levels of cTnT or H‐FABP. However, during the early post‐operative hours, there was a trend towards a higher level of cTnT and H‐FABP in the autotransfusion group. During the first 24 h after surgery, the autotransfusion group had a significantly higher serum level of CK‐MB.

Conclusion:  Post‐operative autotransfusion of mediastinal shed blood may contribute to elevated serum levels of biochemical markers of myocardial injury.
Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction
Authors: Legeby M. , Sandelin K. , Wickman M. , Olofsson C.
Published: September 2005

Background:  Breast cancer treatment with mastectomy and immediate breast reconstruction (IBR) is associated with intense pain in the primary post‐operative period. The present prospective, placebo‐controlled and double‐blind study aimed to evaluate the analgesic efficacy of diclofenac, a non‐steroid anti‐inflammatory drug (NSAID), in combination with paracetamol and opioids. This was done by 64‐h assessment of post‐operative pain intensity, opioid consumption, blood loss, nausea and tiredness.

Methods:  Fifty women selected for mastectomy and IBR with submuscular implants with or without axillary lymph node dissection (ALND) were randomized to receive diclofenac 50 mg × 3 or placebo rectally in addition to oral paracetamol and intravenous opioids delivered using a patient‐controlled analgesia (PCA) technique.

Results:  During the first 20 h post‐surgery, patients who received diclofenac experienced significantly less pain when resting than those who received placebo. When moving, a non‐significant estimated difference in pain in favour of diclofenac was also noted. Opioid consumption during the first 6 h post‐operatively was 34% less with diclofenac than with placebo. Means (SD) were 16.9 (10.3) mg and 25.6 (10.2) mg, respectively (P = 0.007). After 64 h, the difference was no longer statistically significant. Post‐operative bleeding was significantly higher with diclofenac than with placebo (P < 0.01). Nausea and tiredness did not differ between the groups.

Conclusions:  The addition of NSAID to paracetamol and opioid‐PCA reduced opioid consumption and improved pain relief during the first 20 h at rest but was not convincingly effective during mobilization. Post‐operative blood loss was higher with diclofenac.
Changes in the auditory evoked potentials index by induction doses of four different intravenous anesthetics
Authors: Nishiyama T.
Published: September 2005

Background:  Many studies have investigated the electroencephalographic changes during the induction and maintenance of anesthesia. However, no comparative studies have been performed on the effects of intravenous anesthetics on the auditory evoked potentials index (AAI). The present study was performed to compare the changes in AAI caused by induction doses of thiopental, propofol, midazolam and ketamine.

Methods:  Eighty females, aged 30–70 years, referred for mastectomy, had anesthesia induced with thiopental 4 mg/kg, propofol 2 mg/kg, midazolam 0.1 mg/kg or ketamine 1 mg/kg (each 20 patients). The response to verbal command and the AAI were measured every minute for 5 min.

Results:  The AAI decreased to less than 40 within 1 min with thiopental and propofol. The AAI increased after 3 min with thiopental, but remained low with propofol. The AAI gradually decreased to less than 40 within 4 min with midazolam, but was higher than the AAI with propofol or thiopental. The AAI increased significantly with ketamine. The AAIs at the loss of verbal command were 19 ± 7 with thiopental, 21 ± 8 with propofol, 31 ± 10 with midazolam and 92 ± 2 with ketamine.

Conclusion:  The AAI correlated with changes in hypnotic level, as measured by the response to verbal command, with induction doses of thiopental, propofol and midazolam, but not with ketamine. The AAI decreased to lower levels with propofol and thiopental than with midazolam at the induction of anesthesia.
Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema
Authors: Verheij J. , Van Lingen A. , Raijmakers P. G. H. M. , Spijkstra J.‐J. , Girbes A. R. J. , Jansen E. K. , Van Den Berg F. G. , Groeneveld A. B. J.
Published: September 2005

Background:  Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate.

Methods:  A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal‐dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer.

Results:  The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 × 10−3/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end‐expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without.

Conclusions:  After cardiac surgery, mild pulmonary oedema is relatively common, even in the absence of high filling pressures, and is mainly attributable to a low COP, irrespective of increased permeability in about one‐half of patients. It may prolong mechanical ventilation at EVLW > 10 ml/kg. However, pulmonary radiographic and ventilatory abnormalities may result, at least in part, from atelectasis rather than increased permeability oedema.
Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation
Authors: Hofmann D. , Thuemer O. , Schelenz C. , Van Hout N. , Sakka S. G.
Published: September 2005

Background:  Sufficient cardiac pre‐load for maintaining adequate cardiac output is a major goal in the treatment of critically ill patients. We studied the effects of increasing cardiac output by fluid loading on the indocyanine green plasma disappearance rate (ICG‐PDR) and gastric mucosal regional CO2 tension (PRco2) as an indicator of splanchnic microcirculation.

Methods:  With approval by our ethics committee and written consent, we studied post‐operatively 12 patients (1 female, 11 males; 66 ± 13 years) with elective coronary artery bypass grafting (n = 10) or aortic valve replacement (n = 2). All patients had received pulmonary artery and left atrial catheterization previously for clinical indications. Cardiac output and filling pressures were measured immediately after intensive care unit (ICU) admission and 1 h after the beginning of fluid loading.

Results:  Overall, 630 ± 130 ml of 6% hydroxyethylstarch (130 kDa) was infused with the splanchnic perfusion pressure remaining constant. Norepinephrine and epinephrine dosages were unchanged. The cardiac index increased significantly from 2.8 ± 0.7 to 3.5 ± 0.6 l/min/m2 and the stroke volume index from 30 ± 7 to 38 ± 8 ml/m2. ICG‐PDR showed no significant change, i.e. from 21.2 ± 6.5 to 21.6 ± 6.5%/min. Gastric mucosal PRco2 and the Pco2 gap (difference between regional and end‐tidal CO2 tension) were constant, i.e. changed from 5.1 ± 0.8 to 5.5 ± 1.1 kPa and from 0.9 ± 0.5 to 1.0 ± 0.7 kPa, respectively.

Conclusion:  Increasing cardiac output to supranormal values by fluid loading is not associated with a significant change in ICG‐PDR or gastric mucosal PRco2.
The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting: the impact of a controlled definition
Authors: Keizer A. M. A. , Hijman R. , Kalkman C. J. , Kahn R. S. , Van Dijk D. ,   (on behalf of the Octopus Study Group)
Published: September 2005

Background:  After coronary artery bypass grafting (CABG), 20–30% of patients are reported to suffer from cognitive decline. Studies reporting these high incidences, however, have not included an appropriate control group.

Methods:  We repeatedly administered a series of neuropsychological tests to 112 healthy middle‐aged volunteers not undergoing surgery, and applied two widely used definitions of cognitive decline to their test results. In addition, we re‐analysed the neuropsychological test data of 281 CABG patients with a definition of cognitive decline that takes into account the natural variability of test performance that was found in the volunteers.

Results:  Three months after their first assessment, 14–28% of the volunteers suffered from cognitive decline according to the definitions of cognitive decline after CABG. Using the controlled definition of cognitive decline that takes the natural variability in test performance into account, we found that only 7.7% of the CABG patients suffered from cognitive decline at 3 months after their operation.

Conclusion:  These data suggest that the incidence of cognitive dysfunction after CABG has previously been greatly overestimated.
Stroke volume of the heart and thoracic fluid content during head‐up and head‐down tilt in humans
Authors: Van Lieshout J. J. , Harms M. P. M. , Pott F. , Jenstrup M. , Secher N. H.
Published: September 2005

Background: The stroke volume (SV) of the heart depends on the diastolic volume but, for the intact organism, central pressures are applied widely to express the filling of the heart.

Methods: This study evaluates the interdependence of SV and thoracic electrical admittance of thoracic fluid content (TA) vs. the central venous (CVP), mean pulmonary artery (MPAP) and pulmonary artery wedge (PAWP) pressures during head‐up (HUT) and head‐down (HDT) tilt in nine healthy humans.

Results: From the supine position to 20° HDT, SV [112 ± 18 ml; mean ± standard deviation (SD)], TA (30.8 ± 7.1 mS) and CVP (3.6 ± 0.9 mmHg) did not change significantly, whereas MPAP (from 13.9 ± 2.7 to 16.1 ± 2.5 mmHg) and PAWP (from 8.8 ± 3.4 to 11.3 ± 2.5 mmHg;P < 0.05) increased. Conversely, during 70° HUT, SV (to 65 ± 24 ml) decreased, together with CVP (to 0.9 ± 1.4 mmHg;P < 0.001), MPAP (to 9.3 ± 3.8 mmHg;P < 0.01), PAWP (to 0.7 ± 3.3 mmHg;P < 0.001) and TA (to 26.7 ± 6.8 mS;P < 0.01). However, from 20 to 50 min of HUT, SV decreased further (to 48 ± 21 ml;P < 0.001), whereas the central pressures did not change significantly.

Conclusions: During both HUT and HDT, SV of the heart changed with the thoracic fluid content rather than with the central vascular pressures. These findings confirm that the function of the heart relates to its volume rather than to its so‐called filling pressures.
Influence of hydroxyethyl starch on lipopolysaccharide‐induced tissue nuclear factor kappa B activation and systemic TNF‐α expression
Authors: Tian J. , Lin X. , Li Y. H. , Xu J. G.
Published: September 2005

Background: Several studies have shown beneficial effects of hydroxyethyl starch (HES) on organ damage in the treatment of severe inflammatory situations, but the mechanisms remain unclear. Nuclear factor‐kappa B (NF‐κB) activation is known to contribute to many aspects of inflammatory injury and organ dysfunction in critical illness, and tumor necrosis factor‐alpha (TNF‐α) is considered the most important pro‐inflammatory cytokine. The present study was undertaken to test whether HES (200/0.5) has some effects on tissue NF‐κB activity and systemic TNF‐α expression induced by lipopolysaccharide in order to define a possible mechanism of the beneficial effects of HES.

Methods: Male Wistar rats were randomly divided into seven groups treated with saline, lipopolysaccaride (LPS, 6 mg/kg), LPS plus HES (3.75, 7.5, 15, 30 ml/kg), or HES (30 ml/kg) alone. Two hours after LPS challenge, NF‐κB activation in the lungs, hearts, livers, and kidneys were examined with an electrophoretic mobility shift assay. Four hours after LPS challenge, plasma TNF‐α concentrations were measured using an enzyme‐linked immunosorbance assay.

Results: 3.75 and 7.5 ml/kg HES suppressed LPS‐induced NF‐κB activation in the four tissues and decreased plasma TNF‐α elevation. The effects of 15 ml/kg HES was only significant in inhibiting NF‐κB activity in the lung and liver. No effect of 30 ml/kg HES was revealed in all the cases.

Conclusion: Lower doses of HES may inhibit tissue NF‐κB activation and systemic TNF‐α elevation after LPS challenge, which might be helpful during sepsis.
Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto's thyroiditis
Authors: Kim Kyung‐Hee , Suh Kwang‐Sun , Kang Dong‐Wook , Kang Dae‐Young
Published: September 2005

The purpose of the present study was to investigate the frequency of BRAF mutations in human papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) and to evaluate the association of the BRAF mutation with the clinicopathological features of both of these thyroid disorders. A total of 51 PTC with no HT, 28 PTC with HT and 27 HT with no PTC were evaluated using DNA extracted from paraffin‐embedded specimens. BRAF mutations were analyzed by direct DNA sequencing of the polymerase chain reaction (PCR)‐amplified exon 15. The BRAF missense mutation at codon 599 (T1796A) was present in 46 of 51 PTC (90%) with no HT, 18 of 28 PTC (64%) with HT, four of 28 HT (14%) with PTC, and zero of 27 HT with no PTC. The BRAF mutation at codon 600 (A1798G) was not detected in any case. Clinicopathological examination of 106 patients with either PTC or HT showed that the BRAF mutation was significantly correlated with patient age. These data indicate that the BRAF mutation is associated with a valuable biological property of PTC and may participate in the pathogenesis of PTC arising in HT. These results indicate that the detection of the BRAF mutation in HT can be helpful for prediction of progress to PTC.