bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel locus for autosomal dominant hereditary gingival fibromatosis, GINGF3, maps to chromosome 2p22.3‐p23.3
Authors: Ye X , Shi L , Cheng Y , Peng Q , Huang S , Liu J , Huang M , Peng B , Bian Z
Published: August 2005

Hereditary gingival fibromatosis (HGF) is a rare, benign disorder characterized by slowly progressive fibrous overgrowth of the gingiva. To date, two loci have been mapped in familial cases with autosomal dominant non‐syndromic HGF: GINGF (MIM 135300) on chromosome 2p21‐p22 and GINGF2 (MIM 605544) on chromosome 5q13‐q22. Of the two loci, only SOS1 (son of sevenless one, MIM 182530) gene underlying GINGF locus has been identified. Ascertainment of a large Chinese family has allowed the mapping of a novel locus to 2p22.3‐p23.3, GINGF3. Haplotype construction and analysis localized the new locus to an 11.4‐cM interval between markers D2S2221 (telomeric) and D2S1788 (centromeric). The maximum two‐point limit of detection (LOD) score of 3.45 (θ = 0) and multipoint LOD score of 5.00 for marker D2S390 strongly supported linkage to this region. Thus, this genetic interval is distal to and does not overlap with the previously described locus, GINGF, on 2p21‐p22.
Localization of a novel autosomal recessive non‐syndromic hearing impairment locus DFNB55 to chromosome 4q12‐q13.2
Authors: Irshad S , Santos RLP , Muhammad D , Lee K , McArthur N , Haque S , Ahmad W , Leal SM
Published: August 2005

Hereditary hearing impairment (HI) is the most genetically heterogeneous trait known in humans. So far, 54 autosomal recessive non‐syndromic hearing impairment (ARNSHI) loci have been mapped, and 21 ARNSHI genes have been identified. Here is reported the mapping of a novel ARNSHI locus, DFNB55, to chromosome 4q12‐q13.2 in a consanguineous Pakistani family. A maximum multipoint LOD score of 3.5 was obtained at marker D4S2638. The region of homozygosity and the 3‐unit support interval are flanked by markers D4S2978 and D4S2367. The region spans 8.2 cm on the Rutgers combined linkage‐physical map and contains 11.5 Mb. DFNB55 represents the third ARNSHI locus mapped to chromosome 4.
Copper‐replacement treatment for symptomatic Menkes disease: ethical considerations
Authors: Sheela SR , Latha M , Liu P , Lem K , Kaler SG
Published: August 2005

We describe a child with classical Menkes disease with a novel ATP7A mutation, intractable seizures, severe hypotonia and developmental delay, hypopigmentation of the skin and hair, and failure to thrive, who was treated with daily subcutaneous copper histidine injections for 2½ years, beginning at 15 months of age. He became seizure‐free and pigmentation of his skin and hair darkened, but he continued to have severe developmental delays. His condition remains stable 8 months after stopping treatment. We review the ethical aspects of offering copper treatment for Menkes disease infants diagnosed after neurological symptoms become manifest. These include (1) the prospect for any benefits, (2) the potential risks and discomforts, (3) the parents' wishes with respect to treatment, (4) the family's understanding of the treatment's potential futility, (5) the family's understanding of the investigational nature of this treatment, (6) the potential for treatment to have an adverse impact on unaffected family members, (7) whether the ultimate decision regarding treatment should rest with health care providers or with the patient's parents, and (8) the duration of treatment. The ethical issues encountered in providing possibly futile treatment in this difficult disorder seem relevant to other pediatric medical conditions as well.
Parental smoking and allergic sensitization in offspring defined by skin prick testing
Authors: Larsson Matz L , Magnuson Anders , Montgomery Scott M
Published: August 2005

Investigations of parental smoking during childhood and allergic sensitization have produced contradictory results, but this may be because of variations in the definition of allergy and other influences. We investigated associations of parental smoking with an objective measure of allergy, skin prick testing (SPT), and considered associations with maternal and paternal smoking, independently of each other. A stratified random sample, aged 22–74 yr, of 720 Swedish FinEsS‐study members were skin prick tested for 15 allergens. Subjects with at least one positive SPT were defined as atopic. Data on childhood exposures, including parental smoking, were collected by structured interview. Logistic regression used atopy as the dependent variable. After adjustment, paternal smoking was statistically significantly associated with an increased risk and maternal smoking a non‐statistically significant decreased risk in offspring, with odds ratios (and 95% confidence intervals) of 1.48 (1.04–2.10) and 0.73 (0.48–1.12), respectively. Analysis of families with a non‐smoking mother produced an odds ratio for paternal smoking of 1.61 (1.09–2.37). The negative association between maternal smoking and atopy may not operate through passive smoke exposure and could conceal a significant increased risk associated with passive exposure to tobacco smoke in childhood.
Anaphylactic reaction and unrelated, subsequent, known side effects during therapy with thiethylperazine
Authors: Rossetti Giovanni , Livio Françoise , Roulet Eliane , Hofer Michael F.
Published: August 2005

We report the first case presenting with successive anaphylactic reaction and extra‐pyramidal syndrome after treatment with thiethylperazine maleate (thiethylperazine). Both reactions were caused due to this anti‐emetic drug, but an additive effect of clemastine fumarate, prescribed to treat the anaphylactic reaction, is suggested by the sequence of events. We discuss the importance of knowing the pharmacological similitudes of common prescribed drugs in order to avoid the occurrence of side effects.
Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: A longitudinal birth cohort study
Authors: Henderson John , Hilliard Tom N. , Sherriff Andrea , Stalker Deborah , Shammari Nufoud Al , Thomas Huw M. ,   the ALSPAC Study Team
Published: August 2005

Several epidemiological studies have reported recurrent wheezing and asthma in children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The relationship with allergic sensitization is less clear and recent evidence suggests an interaction between atopy and RSV infection in the development of asthma. Data from a large, population‐based, birth‐cohort (Avon Longitudinal Study of Parents and Children) were used to compare outcomes of children according to whether or not they had been admitted to hospital in the first 12 months with RSV‐proven bronchiolitis. Outcomes considered were 12‐month prevalence of wheeze at two ages (between 30–42 and 69–81 months), cumulative prevalence of doctor‐diagnosed asthma at 91 months and skin prick test defined atopy at 7 yr. Multivariable logistic regression models were used to calculate odds ratios for outcomes adjusted for potential confounders. A total of 150 infants (1.1% of the cohort) were admitted to hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30–42 months and 22.6% vs. 9.6% at 69–81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30–42 (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69–81 months (OR 3.5 [1.8, 6.6]) and with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not with atopy (OR 0.7 [0.2, 1.7]). In a population‐based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by age 7 yr.
A prospective study of wheezing in young children: The independent effects of cockroach exposure, breast‐feeding and allergic sensitization
Authors: Silva Jorgete M. , Camara Ataide A. , Tobias Kátia R. C. , Macedo Izolete S. , Cardoso M. Regina A. , Arruda Eurico , Chapman Martin D. , Platts‐Mills Thomas A. E. , Karla Arruda L. , Ferriani Virgínia P. L.
Published: August 2005

The objective of this study was to evaluate risk factors for persistent wheezing in a group of 2–4‐year‐old children after an index‐wheezing episode in infancy. Eighty infants who had been seen at the Emergency Department for an episode of acute wheezing were followed for 2 yr in this prospective study. Caregivers completed a questionnaire, and children underwent clinical evaluation and skin prick testing 2 yr following the index‐wheezing episode. Detection of respiratory viruses and analysis of exposure to major indoor allergens were carried out at enrollment. Immunoglobin E antibodies were measured at the beginning of the study and at the end of follow‐up, using the CAP system. Logistic regression analysis was performed to identify factors associated with persistent wheezing. Seventy‐three children (44 boys) completed the study. After 2 yr, 38 (52%) reported three or more wheezing episodes in the past 12 months (persistent wheezers). Independent risk factors for persistence of wheezing were allergic sensitization and exposure to cockroach allergen in the kitchen. Breast‐feeding for at least 1 month was a protective factor. A strong association between allergic sensitization and persistence of wheezing was found in a group of very young children living in a subtropical area.
Postoperative extradural analgesia with morphine and ropivacaine. A double‐blind comparison between placebo and ropivacaine 10 mg/h or 16 mg/h
Authors: Axelsson K. , Johanzon E. , Essving P. , Weckström J. , Ekbäck G.
Published: August 2005

Background:  Some controversy exists in the literature on the benefit of epidurals compared to patient‐controlled intravenous analgesia (PCA). Also, the dose of ropivacaine for epidural analgesia when combined with morphine remains uncertain. The aim of this study was to compare the epidural vs. PCA technique and high‐dose vs. low‐dose ropivacaine combined with morphine during knee replacement surgery.

Methods:  In this prospective, randomized, double‐blind study, postoperative pain relief with a combination of epidural ropivacaine (Group L: 10 mg h−1, Group H: 16 mg h−1) and morphine (0.16 mg h−1) was evaluated in 30 patients. A placebo group (Group PL) of 15 patients having PCA morphine served as the control. Visual analog pain (VAS), morphine consumption, sensory and motor block and side‐effects were recorded during 48 h.

Results:  VAS scores at rest were significantly lower in Groups L and H compared to Group PL. On movement, Group H had lower VAS scores than Group PL during 3–27 h (P < 0.05) and Group L during 4–9 h (P < 0.05), while Group L had lower a VAS than Group PL during 9–18 h (P < 0.05). Morphine consumption after 48 h was greater in Group PL (64.6 ± 36.3 mg) vs. Group L (23.3 ± 33.9 mg) (P < 0.001) and Group H (4.3 ± 9.6 mg) (P < 0.0001). Mild motor block was seen in Group H in 20% and 14% patients at 24 h and 48 h, respectively, but time to mobilization was similar between the groups. Pruritus was more common in the ropivacaine groups (P < 0.05).

Conclusion:  Lumbar epidural analgesia using a combination of ropivacaine (16 mg h−1) and morphine (0.16 mg h−1) provides superior analgesia compared to the PCA technique or ropivacaine (10 mg h−1) and morphine (0.16 mg h−1). Although this resulted in a mild motor block during the first 12 h, patient mobilization was similar in all groups.
Combined general‐epidural anesthesia decreases the desflurane requirement for equivalent A‐line ARX index in colorectal surgery
Authors: Lu C.‐H. , Borel C. O. , Wu C. ‐T. , Yeh C.‐C. , Jao S.‐W. , Chao P.‐C. , Wong C.‐S.
Published: August 2005

Background:  The present study used the A‐line ARX index, derived from auditory evoked potential measurements, to examine the effect of epidural lidocaine on the end‐tidal concentration of desflurane during general anesthesia.

Methods:  Thirty ASA I–II patients scheduled for elective colorectal surgery were included and randomized, in a double‐blinded fashion, to receive general anesthesia, and 15 ml of either 2% lidocaine (group GE, n = 15) or normal saline (group GS, n = 15) was administered epidurally with a maintenance infusion rate of 6 ml h−1. After a 10‐min high‐flow oxygen wash‐in period, desflurane was titrated to a target A‐line ARX index (AAI) of 20 ± 5.

Results:  Epidural lidocaine reduced the end‐tidal concentration of desflurane required to maintain an adequate clinical effect by 42% compared to general anesthesia alone (2.6% vs. 4.5%, respectively; P < 0.001). The initial mean value of AAI was 87.8 (range 78–99) in group GE and 88.13 (79–99) in group GS before general anesthesia induction, the AAI values were approximately 19.7 (15–25) in group GE and 20.2 (16–25) in group GS during anesthesia maintenance, and returned to 84.53 (77–98) in group GE and 86.87 (79–98) in group GS when the patients regained consciousness in the recovery room. No statistical difference in the AAI values was observed either before, during, or after emergence of anesthesia. No patient reported intraoperative awareness.

Conclusions:  Lower‐than‐expected concentrations of volatile anesthetics are sufficient to maintain appropriate a clinical anesthesia effect during combined general‐epidural anesthesia under auditory‐evoked potential monitoring.
Colloid vs. crystalloid preloading to prevent maternal hypotension during spinal anesthesia for elective cesarean section
Authors: Dahlgren G. , Granath F. , Pregner K. , Rösblad P. G. , Wessel H. , Irestedt L.
Published: August 2005

Background:  Hypotension associated with spinal anesthesia for cesarean section is still a clinical problem. Colloid solutions seem preferable to crystalloid solutions for preloading. In most studies the overall rate of hypotension is reported. Few studies have, however, investigated the maternal and neonatal consequences of different levels of maternal hypotension.

Methods:  In this randomized, double‐blinded study 110 patients presenting for elective cesarean section received either 1000 ml acetated Ringer's solution or 1000 ml 3% dextran 60 solution immediately before spinal anesthesia. The effect on overall hypotension, clinically significant hypotension (hypotension associated with maternal discomfort defined as nausea, retching/vomiting, dizziness or chest symptoms) and severe hypotension (systolic arterial pressure <80 mmHg) was studied.

Results:  Dextran reduced the incidence of overall hypotension from 85 to 66% (P = 0.03), reduced the incidence of clinically significant hypotension from 60 to 30% (P = 0.002) and reduced the incidence of severe hypotension from 23 to 3.6% (P = 0.004) compared to Ringer's solution. There were neither differences in neonatal outcome between treatment groups nor between neonates grouped after severity of maternal hypotension.

Conclusion:  Clinically significant hypotension seems to be a more suitable outcome variable than overall hypotension. The protective effect of the colloid solution increased with increased severity of hypotension.
Colloids decrease clot propagation and strength: role of factor XIII‐fibrin polymer and thrombin–fibrinogen interactions
Authors: Nielsen V. G.
Published: August 2005

Colloid‐mediated hypocoagulability is clinically important, but the mechanisms responsible for coagulopathy have been incompletely defined. Thus, my goal was to elucidate how colloids decrease plasma coagulation function. Plasma was diluted 0% or 40% with 0.9% NaCl, three different hydroxyethyl starches (HES, mean molecular weight 450, 220 or 130 kDa), or 5% human albumin. Samples (n = 6 per condition) were activated with celite, and diluted samples had either no additions or addition of fibrinogen (FI), thrombin (FIIa) or activated Factor XIII (FXIIIa) to restore protein function to prediluted values. Thrombelastographic variables measured included clot propagation (angle, α), and clot strength (amplitude, A; or shear elastic modulus, G). Dilution with 0.9% NaCl significantly decreased α, A and G‐values compared to undiluted samples. Supplementation with FI, but not FIIa or FXIIIa, resulted in 0.9% NaCl‐diluted thrombelastographic variable values not different from those of undiluted samples. FI supplementation of HES 450, HES 220, HES 130 and albumin‐diluted samples only partially restored α, A and G‐values compared to undiluted samples. FIIa addition only improved clot propagation and strength in albumin‐diluted samples. FXIIIa supplementation improved propagation in samples diluted with HES 450, HES 220 and albumin, and clot strength improved in HES 450 and albumin‐diluted plasma. Considered as a whole, these data support compromise of FIIa‐FI and FXIIIa – fibrin polymer interactions as the mechanisms by which colloids compromise plasma coagulation. Investigation to determine if clinical enhancement of FXIII activity and/or FI concentration (e.g. fresh‐frozen plasma, cryoprecipitate) can attenuate colloid‐mediated decreases in hemostasis is warranted.
Continuous peripheral nerve blockade in lower extremity surgery
Authors: Navas Á. M. , Gutiérrez T. V. , Moreno M. E.
Published: August 2005

Peripheral nerve blocks afford numerous benefits for lower extremity surgery. There is growing interest in continuous peripheral nerve blocks, mainly for treatment of postoperative pain, a field that represents a challenge to the anaesthesiologist. This paper seeks to review the efficacy of continuous lower limb blocks for postoperative pain relief. Not only do continuous peripheral nerve blocks afford specificity of analgesic area but current research has shown that they enhance postoperative analgesia and patient satisfaction. New techniques and devices are increasingly appearing, and catheters are constantly being developed and improved; an example being the stimulating catheter, which represents one of the newest advances in this area.

The above techniques show that continuous postoperative analgesia with catheters in the lower extremities is not only possible, but indeed provides sustained effective postoperative analgesia, reduces use of opioids, and improves rehabilitation and patient well‐being with minimal side‐effects. These techniques could prove an alternative to postoperative pain treatment following ambulatory surgery.
Effective systolic orifice area of the aortic valve: implications for Doppler echocardiographic cardiac output determinations
Authors: Schmidt C. , Theilmeier G. , Van Aken H. , Flottmann C. , Wirtz S. P. , Kehl H‐G. , Hoffmeier A. , Berendes E.
Published: August 2005

Background:  Substantial research using echocardiography has established that stroke volume (SV) or cardiac output (CO) can be measured non‐invasively at the level of the aortic valve (AV) with high accuracy. Stroke volume is the product of the velocity time integral occurring at the sampling site and the effective systolic AV orifice area (AVOAeff). Nevertheless, a generally accepted method for the determination of AVOAeff is still lacking.

Methods:  Aortic valve OAeff was measured in 228 consecutive patients scheduled for coronary artery surgery. Two widely adopted methods were applied to approximate the constantly changing orifice area of the AV: (1) the circular orifice model (AVOA–CM), and (2) the triangular orifice model (AVOA–TM). Aortic valve OA–CM assumes the shape of a circle as an appropriately time averaged geometrical model, and AVOA–TM takes the shape of an equilateral triangle for granted.

Results:  The AV was easily imaged by echocardiography in both short‐ and long‐axis views in all patients. Relying on AVOA–CM, AVOAeff was 3.49 ± 0.77 cm2. AVOA–TM estimates were 2.80 ± 0.55 cm2 (mean ± SD). The results did not agree (bias analysis).

Conclusions:  The echocardiographic measurement of SV or CO at the level of the AV has to be reconsidered.
Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study*
Authors: Duru S. , Koca U. , Öztekin S. , Olguner Ç. , Kar A. , Çoker C. , Ulukuş Ç. , Taşc C. , Elar Z.
Published: August 2005

Background:  Anti‐inflammatory action of Antithrombin III (AT III) is still not well understood in ischemia/reperfusion (I/R) injury. In the present study, we aimed to investigate the anti‐inflammatory action of AT III on remote lung and local skeletal muscle tissue injury in a rat model of bilateral lower limb I/R model.

Methods:  Bilateral lower limb ischemia and reperfusion were produced by means of tourniquets occlusions and releases, respectively. Three groups of rats were used in this controlled study: sham group (sham, n=3) underwent 5 h of anesthesia only; control group (I/R, n=7) underwent 3 h of bilateral lower limb ischemia followed by 2 h of reperfusion; and AT III pretreated group (I/R‐AT III, n=6) underwent the same procedure as the control group, but also received i.v. 250 U kg−1 AT III 30 min before ischemia induction under midazolam and fentanyl anesthesia.

Measurements and results:  Lung and muscle tissue accumulation of polymorphonuclear leukocytes (PMN) were assessed by measuring tissue myeloperoxidase (MPO) activity. Histopathological changes in tissues were assessed by PMN counts in the lung, and muscle tissues and by histological lung injury score. Plasma 6‐keto prostaglandin F1α and tumor necrosis factor alpha levels were measured by an enzyme immunoassay technique. Myeloperoxidase activity could not be detected in the muscle tissues of all groups. The lung and muscle tissue PMN counts in the I/R group were significantly higher compared with the I/R‐AT III group (P < 0.05).

Conclusions:  Data from the present study provides some evidence that AT III pretreatment attenuates remote lung and local skeletal muscle tissue injury caused by lower limb I/R.
Impact of postoperative shed blood transfusion, with or without leucocyte reduction, on acute‐phase response to surgery for total knee replacement
Authors: Muñoz M. , Cobos A. , Campos A. , Ariza D. , Muñoz E. , Gómez A.
Published: August 2005

Background:  In patients undergoing total knee replacement (TKR) most blood loss occurs postoperatively and return of unwashed filtered shed blood (USB) from postoperative drainage may represent an alternative to allogeneic blood transfusion (ABT). We evaluated the impact of USB return, with or without leucocytes, on the acute‐phase response (APR) after TKR.

Patients and methods:  Forty‐eight TKR patients, intended to receive postoperative USB, entered the study. Blood samples were obtained before and 6, 24, 72 h and 7 days after surgery, and from the USB before and after it passed through a 40‐µm filter (Group F40) or a leucocyte‐reduction filter (Group LRF). Haematimetric parameters, APR proteins (albumin, prealbumin, ceruloplasmin, haptoglobin, C‐reactive protein), complement C3 and C4, and cytokines (IL‐1β, IL‐6, IL‐8, IL‐10, and TNF‐α) were measured in all samples.

Results:  Twenty‐eight patients (Group F40 = 14, Group LRF = 14) received a mean of 1.2 USB units, without any clinically relevant incident, and did not need additional ABT. Sixteen out of the 20 remaining patients who received neither USB nor ABT served as a control group for the postoperative APR study. All patients showed the typical postoperative APR profile and there were no significant differences between groups for APR parameters, postoperative complications, or hospital stay.

Conclusions:  Postoperative blood salvage and return, with or without a LRF, after TKR does not present any clinically relevant side‐effects and does not modify APR induced by surgery. These findings seem to confirm the clinical experience that postoperative USB return is safe and questions the beneficial effect of using LRF.
Effects of remifentanil and alfentanil on seizure duration, stimulus amplitudes and recovery parameters during ECT
Authors: Akcaboy Z N. , Akcaboy E Y. , Yigitbas B. , Bayam G. , Dikmen B. , Gogus N. , Dilbaz N.
Published: August 2005

Background and objective:  Propofol may decrease seizure duration in electroconvulsive therapy. Although not proven, prolonged seizures may be more efficacious. The goal of this study was to evaluate and compare effects of alfentanil and remifentanil on seizure duration, recovery parameters and degree of stimulus amplitude in patients undergoing electroconvulsive therapy.

Methods:  Twenty‐four ASA I–II patients enrolled in this prospective, randomized trial, each receiving a total of seven electroconvulsive therapies. Patients were randomized to receive only Propofol, group P (0.75 mg kg−1, n = 8), Propofol with alfentanil, group A (10 µg kg−1 alfentanil + 0.5 mg kg−1 Propofol, n = 8) and Propofol with remifentanil, group R (1 µg kg−1 remifentanil +0.5 mg kg−1 propofol, n = 8) via an iv route. Supplemental doses of propofol were given as required to achieve loss of consciousness. Succinylcholine 0.5 mg kg−1 iv was given to all groups for muscular paralysis. We recorded hemodynamic parameters, cortical and motor seizure durations, and recovery parameters.

Results:  Mean motor seizure duration was found to be significantly longer in patients receiving propofol‐remifentanil anesthesia (53.3 ± 13.6 s) and propofol‐alfentanil anesthesia (52.2 ± 0.4 s) compared with propofol anesthesia (37.6 ± 9.2 s) (P = 0.001). Recovery parameters and stimulus amplitudes were similar in groups A and R; significantly different from group P (P = 0.001).

Conclusions:  Adding 10 µg kg−1 alfentanil or 1 µg kg−1 remifentanil to reduced doses of propofol provided unconsciousness and increased seizure durations. For patients who need higher stimulus amplitudes for longer seizure durations, combining low‐dose propofol with alfentanil or remifentanil may be good alternative regimens for ECT.
Bradycardia and hypertension in anticipation of, and exacerbated by, peribulbar block: a prospective audit
Authors: Van Den Berg A. A.
Published: August 2005

Background:  Changes in heart rate (HR), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) occur in anticipation of, and following, injection of a peribulbar local analgesic agent. We examined these changes in two groups of awake patients given a pre‐medication of either hydroxyzine 1.0 mg/kg alone (control) or hydroxyzine 1.0 mg/kg with morphine 0.05 mg/kg.

Methods:  HR, SAP and DAP of 100 patients per group were monitored the day before surgery (baseline), every 5 min in the anesthesia holding room before peribulbar injection, every minute for the first 5 min after peribulbar injection and then every 5 min until transfer to the operating room. Within and between pre‐medication group values of HR, SAP and DAP before and after peribulbar injection were compared with baseline.

Results:  The two groups of patients were similar. Before peribulbar injection, HR was unchanged in the hydroxyzine group, but 6% slower in those given morphine (P < 0.01). After injection, HR slowed in both groups, by 5% and 7% (P < 0.01, both comparisons), respectively. In anticipation of injection, SAP increased in both groups to 20% and 16% above baseline, respectively, and increased further after injection to 26% and 24% above baseline, respectively (P < 0.001, all comparisons). In both groups, maximum SAP following injection exceeded maximum SAP before injection (P < 0.02, both comparisons). DAP increased by 4% (P < 0.05) in the hydroxyzine group before injection, and by 5% and 4%, respectively (P < 0.005 and P < 0.05, respectively) after peribulbar injection.

Conclusion:  The audit reveals pronounced increases in SAP accompanied by lesser increases in DAP and a tendency to slowing of HR in awake patients in anticipation of peribulbar injections. Peribulbar injections cause further increases in blood pressure and mild bradycardia. These changes occur similarly in patients pre‐medicated with hydroxyzine or hydroxyzine plus morphine. A mix of neuro‐humoral influences (anxiety/catecholamine/baroreceptor/trigemino‐vagal) are postulated as etiological.
Inter‐observer agreement of tests used for prediction of difficult laryngoscopy/tracheal intubation
Authors: Rosenstock C. , Gillesberg I. , Gätke M. R. , Levin D. , Kristensen M. S. , Rasmussen L. S.
Published: August 2005

Background:  Guidelines recommend pre‐operative airway evaluation for the prediction of airway management difficulties. Combining tests for evaluation increases the accuracy of the assessment. One model including seven parameters transformed into a simplified airway risk index (SARI) has been proven to be valid. We determined the inter‐observer agreement of the specific test combinations included in SARI as well as of the total score.

Methods:  Four observers assessed 136 patients, 120 without and 16 with a difficult airway history. Two residents and two specialists in anaesthesia performed the airway assessment consisting of the measurement of the mouth opening, the thyromental distance (TMD), the ability to protrude the mandible and an evaluation of the Mallampati class and head and neck mobility. Body weight was also recorded. Inter‐observer agreement between specialists and residents, separately, was analysed using kappa statistics and Spearman's correlation analysis and the limits of agreement were evaluated using the 95% confidence interval. The agreement between pairs of assessors was also evaluated.

Results:  The inter‐observer agreement was good to excellent for both specialists and residents when measuring mouth opening (Spearman's correlation coefficient R = 0.88–0.97) and the horizontal distance between the upper and lower incisors during jaw protrusion (R = 0.56–0.97). The Mallampati classification assessment demonstrated satisfactory to complete inter‐observer agreement (κ = 0.41–1). The assessment of TMD and neck mobility showed considerable discrepancies between observers.

Conclusions:  We demonstrated good inter‐observer agreement using three tests from SARI and recommend the Mallampati classification, mouth opening and ability of jaw protrusion for pre‐operative airway evaluation. A simplification of the assessment of TMD and neck mobility is warranted.
Ethical issues in intensive care – a survey among Scandinavian intensivists
Authors: Tallgren M. , Klepstad P. , Petersson J. , Skram U. , Hynninen M.
Published: August 2005

Background:  The general principles of medical ethics are universally accepted. In practice, however, there is variation on how these principles are interpreted by people with different cultural backgrounds. The aim of this study was to document the views of Scandinavian intensive care physicians on intensive care unit (ICU) admission, triage, withholding and withdrawal of intensive care, and communication between the patient, the family and the ICU team.

Methods:  A questionnaire was developed and sent to 84 intensive care physicians working in Denmark, Finland, Sweden and Norway.

Results:  The response rate was 61%. In general, the responses were in agreement with published guidelines. Nevertheless, there was considerable variation on what factors are taken into account when priority decisions are made. In addition, the views on the content of information provided to the family varied. A majority of 80% reported priority decisions being made on a regular basis. Less than one‐half of the respondents had correct knowledge regarding the existence or lack of national guidelines on intensive care ethics. Only 8% of the respondents were aware of guidelines published by the Society of Critical Care Medicine.

Conclusion:  Variation in priority determinants between individual physicians may compromise justice in health care. An effort should be made to discuss and adopt mutual principles. In addition, the quality of information available to the patients' representatives deserves our attention. The results of this study could be used as a basis for discussion when guidelines on the ethical aspects of intensive care are developed and reviewed.
Nitrous oxide diffusion into tracheal tube cuffs – efficacy of a new prototype cuff pressure release valve
Authors: Dullenkopf A. , Gerber A. C. , Weiss M.
Published: August 2005

Background:  The aim of this study was to evaluate the performance of a new cuff pressure release valve (CPRV), in which the release pressure can be adjusted from 10 to 25 cmH2O, particularly intended to control pressure in paediatric cuffed tracheal tubes and to avoid cuff hyperinflation caused by N2O diffusion.

Methods:  In vitro: the PRV was set to 10, 15, 20 or 25 cmH2O release pressure and connected to a cuffed tube placed into a box flushed with 66% N2O in O2. The cuff pressure was monitored with and without CPRV for 60 min. Experiments were performed four times using two different CPRVs. In vivo: with Institutional Review Board approval, CPRV was studied in 50 children undergoing general anaesthesia with tracheal intubation and standardized anaesthesia technique (including 66% N2O in O2) and ventilator settings. Patients were randomized into two groups (with and without CPRV). The cuff pressure baseline was 20 cmH2O and CPRV was set to 25 cmH2O. If the cuff pressure exceeded 25 cmH2O, it was manually released to 20 cmH2O. The numbers of deflations in both groups were noted and compared by Mann–Whitney U‐test (P < 0.05).

Results:  In vitro: the cuff pressure exceeded 50 cmH2O after 60 min without CPRV, but did not exceed the settings with CPRV. In vivo: there was no need to manually deflate the cuff in the CPRV group but, in every patient in the control group, three (two to seven) deflating manoeuvres were required within the first hour of anaesthesia (P < 0.0001).

Conclusion:  The CPRV allows reliable cuff pressure release at various pressure levels and reliably prevents cuff pressure increases caused by N2O.
In vivo characterization of the angiotensin‐(1–7)‐induced dopamine and γ‐aminobutyric acid release in the striatum of the rat
Authors: Stragier Bart , Hristova Ilina , Sarre Sophie , Ebinger Guy , Michotte Yvette
Published: August 2005

The effect of angiotensin (Ang)‐1–7 on dopamine, γ‐aminobutyric acid (GABA) and glutamate release in the striatum of the rat was examined using in vivo microdialysis. Ang‐(1–7) was administered locally in the striatum through the microdialysis probe. At a concentration of 100 µm, Ang‐(1–7) caused a significant increase in extracellular dopamine and GABA but had no effect on glutamate release. The Ang‐(1–7)‐induced dopamine release was blocked by EC33, an inhibitor of aminopeptidase A, an enzyme which converts Ang‐(1–7) into Ang‐(3–7), suggesting that this effect occurs after metabolism into Ang‐(3–7). Indeed, administration of Ang‐(3–7) (10–100 µm) into the striatum caused a more potent increase in the striatal dopamine release than Ang‐(1–7). Because Ang‐(3–7) is an inhibitor of insulin‐regulated aminopeptidase (IRAP) and because Ang IV, another IRAP inhibitor, also causes a concentration‐dependent increase in dopamine in the rat striatum, IRAP may be involved in this effect. In contrast, EC33 had no effect on the Ang‐(1–7)‐induced GABA increase but the GABA release was blocked by the putative AT1‐7 receptor antagonist A779 (0.1 µm) and by the nitric oxide synthase inhibitor L‐NAME (1 mm). These drugs could not block the effect of Ang‐(1–7) on the striatal dopamine release suggesting that only the observed effects on GABA release are mediated by the AT1‐7 receptor and/or are associated with a release of nitric oxide.
Spatio‐temporal Ca2+ dynamics of moth olfactory projection neurones
Authors: Carlsson Mikael A. , Knüsel Philipp , Verschure Paul F. M. J. , Hansson Bill S.
Published: August 2005

We studied the Ca2+ dynamics of odour‐evoked glomerular patterns in the antennal lobe of the moth Spodoptera littoralis using optical imaging. Here we selectively stained a large population of antennal lobe output neurones, projection neurones, by retrograde filling with FURA‐dextran from the inner antennocerebral tract in the protocerebrum. Different plant‐associated odorants evoked distributed patterns of activated glomeruli that were odour dependent and repeatable. These patterns were, however, dynamic during the period of odour exposure. Temporal responses differed across glomeruli and were stimulus dependent. Next we examined how the correlations between patterns evoked by different odorants changed with time. Initially, responses to structurally similar compounds were highly correlated, whereas responses to structurally different compounds differed. Within the period of odour exposure (1 s) we found a significant reduction in similarity of responses evoked by different odours, irrespective of initial similarity, whereas trial‐to‐trial correlations remained high. Our results suggested an ability for coarse classification at the initial encounter with an odour source. With time, however, the discrimination ability increases and structurally similar odours can be distinguished.
Up‐regulation of VGLUT2 expression in hypothalamic‐neurohypophysial neurons of the rat following osmotic challenge
Authors: Kawasaki Akiko , Hoshi Koichi , Kawano Michihiro , Nogami Haruo , Yoshikawa Hiroyuki , Hisano Setsuji
Published: August 2005

A second vesicular glutamate transporter (VGLUT2) has been reported to be expressed in neurosecretory neurons of the hypothalamic‐neurohypophysial system. To study its role in the neurosecretory neurons, we evaluated the expression of the VGLUT2 gene in the paraventricular (PVN) and supraoptic (SON) nuclei as well as the immunoreactivity in the neurohypophysis under euhydrated and chronic hyperosmotic conditions with in situ hybridization and immunohistochemistry. The intensity of hybridization signals in the PVN, SON and thalamus of rats subjected to water deprivation for 7 days, or drinking 2% NaCl for 4 or 7 days, was compared with that of euhydrated rats (control). The overall intensity in the entire PVN or SON, but not the thalamus, was higher in osmotically stimulated rats than in controls. Within the PVN, a significantly higher intensity of signals than that of controls was found only in the dorsolateral posterior magnocellular region in 4‐day salt‐loaded rats and in all subregions in water‐deprived or 7‐day salt‐loaded rats. The intensity in the SON was higher in the stimulated rats than in controls, regardless of subregions. In the neurohypophysis, VGLUT2 staining was frequently localized in vasopressin terminals of control rats and was apparently reduced in stimulated rats. These results indicate that VGLUT2 is principally expressed in magnocellular vasopressin neurons, suggesting some local effect of intrinsic glutamate on neurohypophysial hormone secretion.
Purkinje cell spinogenesis during architectural rewiring in the mature cerebellum
Authors: Cesa Roberta , Morando Laura , Strata Piergiorgio
Published: August 2005

Spines can grow and retract within hours of activity perturbation. We investigated the time course of spine formation in a model of plasticity involving changes in brain architecture where spines of a dendritic domain become innervated by a different neuronal population. Following a lesion of rat olivocerebellar axons, by severing the inferior cerebellar peduncle, new spines grow on the deafferented proximal dendrite of the Purkinje cells (PCs) and these new spines become innervated by parallel fibres (PFs) that normally contact only the distal dendrites. The varicosities of climbing fibre (CF) terminal arbors disappear within 3 days of the lesion. Spine density in the proximal dendritic domain begins to rise within 3 days and continues to increase towards a plateau at 6–8 days. In ‘slow Wallerian degeneration’ mice, in which axonal degeneration is delayed, climbing fibre varicosities virtually disappear at 14 rather than 3 days. Spine density in the proximal dendritic domain is similar to control Purkinje cells up to 14 days and increases significantly 18 days postlesion. The delayed spinogenesis in the latter mutant is the result of a persistence of the climbing fibre presynaptic structure in the absence of activity. Therefore, climbing fibre activity itself is not directly responsible for the suppression of spine formation, but suppression mechanisms tend to become weaker as long as the structural dismantling of the presynaptic varicosities proceeds. Thus, spinogenesis is guided by two different mechanisms; a rapid one related to changes in homotypic remodeling and a slower one, which requires the removal of a competitive afferent.
Nerve growth factor‐induced circadian phase shifts and MAP kinase activation in the hamster suprachiasmatic nuclei
Authors: Pizzio Gastón A. , Hainich Ernesto C. , Plano Santiago A. , Ralph Martin R. , Golombek Diego A.
Published: August 2005

Circadian rhythms are entrained by light and by several neurochemical stimuli. In hamsters housed in constant darkness, i.c.v. administration of nerve growth factor (NGF) at various times in their circadian cycle produced phase shifts of locomotor activity rhythms that were similar in direction and circadian timing to those produced by brief pulses of light. Moreover, the effect of NGF and light were not additive, indicating signalling points in common. These points include the immediate‐early gene c‐fos and ERK1/2, a component of the mitogen‐activated protein kinases (MAPK) family. NGF activates c‐FOS and ERK1/2‐MAPK in the suprachiasmatic nuclei, the site of a circadian clock in mammals, when administered during the subjective night but not during the day. The effect of NGF on ERK1/2 activation was not inhibited by the administration of MK‐801, a glutamate/NMDA receptor antagonist. These results suggest that NGF, acting through MAPK activation, plays a role in photic entrainment of the mammalian circadian clock.
Membrane‐associated guidance cues direct the innervation of forebrain and midbrain by dorsal raphe‐derived serotonergic axons
Authors: Petit Audrey , Kennedy Timothy E. , Bagnard Dominique , Doucet Guy
Published: August 2005

Unlike many neurons that extend an axon precisely to a single target, individual dorsal raphe 5‐HT neurons project to multiple brain regions and their axon terminals often lack classical synaptic specializations. It is not known how 5‐HT axon collaterals select between multiple target fields, or even if 5‐HT axons require specific guidance cues to innervate their targets. Nor is it known how these axon collaterals are restrained within specific innervation target regions. To investigate this, we challenged explants of dorsal raphe with co‐explants, or cell membrane preparations of ventral midbrain, striatum or cerebral cortex. We provide evidence for membrane‐associated cues that promote 5‐HT axon growth into each of these three target regions. The axon growth‐promoting activity was heat‐, protease‐ and phosphatidylinositol‐phospholipase‐C (PI‐PLC)‐sensitive. Interestingly, 5‐HT axons specifically lost the ability to grow in heterotypic explants, or membrane carpets, following contact with ventral midbrain or striatal, but not cortical, explants or membranes. This inductive activity associated with striatal and ventral midbrain membranes was sensitive to both high salt extraction and PI‐PLC treatment. By contrast, the activity that inhibited 5‐HT axon growth onto heterotypic membranes was sensitive only to high salt extraction. These results provide evidence that a glycosylphosphatidylinositol (GPI)‐linked membrane protein promotes 5‐HT axon growth, and that short‐range membrane‐bound, as well as GPI‐linked, molecules contribute to the guidance of 5‐HT axon collaterals. These findings suggest that 5‐HT axon collaterals acquire a target‐induced growth‐inhibitory response to alternative targets, increasing their selectivity for the newly innervated field.
Spatial learning with unilateral and bilateral hippocampal networks
Authors: De Hoz Livia , Moser Edvard I. , Morris Richard G. M.
Published: August 2005

This study investigated the ability of animals to learn both reference memory and delayed matching‐to‐place variants of the watermaze after large lesions of the hippocampus that deliberately spared only small remnants of the structure. Groups were created that had differing blocks of residual tissue in the septal pole of the hippocampus (15% or 30% of total volume), located either unilaterally (30 or 50% on one side, 0% on the other) or bilaterally (30 + 30%). These groups were capable of learning the reference memory task, as indexed by normal spatially focused searching in a probe trial, but their rate of learning was slower than that of sham‐lesioned rats. An impairment in the rate of learning was also seen in the delayed match–to‐place task, where one‐trial memory was observed only at the shortest (5 s) intertrial interval in the lesioned groups with the largest sparing. In both tasks performance was proportional to the volume of hippocampus spared and independent of whether this was unilaterally or bilaterally located. The findings are compatible with distributed processing accounts of hippocampal memory storage.
Clinical utility of human glandular kallikrein 2 within a neural network for prostate cancer detection
Authors: Stephan Carsten , Jung Klaus , Soosaipillai Antoninus , Yousef George M. , Cammann Henning , Meyer Hellmuth , Xu Chuanliang , Diamandis Eleftherios P.
Published: August 2005

OBJECTIVE

To assess, using artificial neural networks (ANNs), human glandular kallikrein 2 (hK2), prostate‐specific antigen (PSA), and percentage free/total PSA (f/tPSA), for discriminating between prostate cancer and benign prostatic hyperplasia (BPH).

MATERIAL AND METHODS

Serum samples from 475 patients with prostate cancer (n = 347) or BPH (n = 128) within the PSA range of 1–20 ng/mL were analysed for tPSA, fPSA and hK2 (research assay, Toronto, Canada). Data were analysed in the ranges of 1–4, 2–4, 4–10, and 2–20 ng/mL tPSA. Back‐propagation ANN models with the variables PSA, f/tPSA, and hK2, hK2/fPSA and hK2/(f/tPSA) were constructed. The diagnostic validity was evaluated by receiver‐operating characteristic (ROC) curve analysis.

RESULTS

Whereas the median concentration of hK2 was not significantly different between patients with BPH or prostate cancer in any of the tPSA ranges, the f/tPSA, hK2/fPSA and hK2/(f/tPSA), and the hK2‐based ANN outputs were always significantly different between patients with prostate cancer or BPH. Using ROC curve comparison, all variables were significantly better than hK2 in all ranges. The hK2‐based ANN performed better than f/tPSA except in the 4–10 ng/mL tPSA range. At 90% and 95% sensitivity, the hK2‐based ANN was also significantly better than f/tPSA in the 1–4 ng/mL tPSA range. hK2/(f/tPSA) achieved equal results to the hK2‐based ANN except in the range 2–20 ng/mL tPSA.

CONCLUSIONS

The hK2‐based ANN improves the outcome of f/tPSA but not hK2/(f/tPSA) in almost all analysed subgroups. When comparing the results at 90% and 95% sensitivity the hK2‐based ANN only performed significantly better than f/tPSA in the lowest tPSA range. Only in lower tPSA ranges do hK2‐based ANNs show an advantage for further improving prostate cancer detection.