bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of bilateral infraorbital nerve block with intravenous fentanyl for analgesia following cleft lip repair in children
Authors: RAJAMANI ARVIND , KAMAT VIJAYLAKSHMI , RAJAVEL VARDARAJA PONNAMBALAM , MURTHY JYOTSNA , HUSSAIN SYED ALTAF
Published: August 2006

Background:  The efficacy of analgesia with bilateral infraorbital nerve block and intravenous (i.v.) fentanyl were compared for cleft lip surgery in children.

Methods:  Eighty‐two children aged 3 months to 10 years undergoing cleft lip repair were prospectively randomized to one of two groups: bilateral infraorbital nerve block (Group B), or i.v. fentanyl (Group F). Group B (n = 41) received bilateral infraorbital injection of 1 ml 0.25% bupivacaine and 2 ml i.v. saline as control. Group F (n = 41) received 2 μg·kg−1 i.v. fentanyl, and bilateral infraorbital injection of 1 ml saline as control. Pain was evaluated by the incidence of tachycardia, hypertension, and/or modified pain score ≥4. The time to awakening, time to first cry and time to feeding were noted.

Results:  Thirty four children (82.9%) in Group B had adequate analgesia compared with 15 (36.6%) in Group F (P < 0.0001, RR of failure 0.27 for Group B). Group B had a mean time to awakening of 5.65 ± 2.52 min (Group F: 9.37 ± 4.50 min; P < 0.0001), time to first cry 32.14 ± 18.22 min (Group F: 28.00 ± 16.27 min; P = 0.3), time to feed 62.05 ± 20.06 min (Group F: 72.44 ± 17.72; P = 0.015), and pain score 2.81 ± 1.38 (Group F: 4.71 ± 1.89; P < 0.0001). There were no major complications.

Conclusions:  Bilateral infraorbital block is superior to fentanyl in terms of analgesia, and time to awakening and feeding.
Comparative evaluation of Bispectral Index and Narcotrend Index in children below 5 years of age
Authors: WALLENBORN JAN , KLUBA KARSTEN , OLTHOFF DERK
Published: August 2006

Background:  The use of electroencephalogram (EEG) monitoring devices for assessing the depth of hypnosis is most difficult in children under 5 years of age.

Methods:  Forty five children aged 0–60 months were included in a prospective observational study. A direct comparison of the processed EEG variables Bispectral IndexTM (BIS, version 3.4) and Narcotrend® Index (NI, version 2.0AF) was to be achieved by simultaneous recording. The ability of these parameters to differentiate between various clinical states was evaluated by using the prediction probability (Pk). Age‐related effects on the BIS and NI were analyzed by dividing the children into three age groups: 0–6, 7–18 and 19–60 months.

Results:  The preanesthesia, conscious children were differentiated from anesthetized patients by the BIS and NI with no overlap (Pk = 1.0). In the awake period the BIS was superior to the NI (Pk to differentiate ‘end of anesthesia’ from ‘awakening’ was 0.97 vs 0.73 respectively; P = 0.002). Patients aged 7–18 months showed higher BIS and NI values in the course of anesthesia than the younger and older children (P = 0.001). On awakening, children aged 0–6 months showed the lowest mean BIS (n.s.) and NI (P = 0.006) values.

Conclusions:  The BIS currently seems to be superior to the NI, but age‐related processing algorithms of the raw EEG must be implemented in both BIS and NI in order to be useful in children younger than 5 years of age.
Recombinant activated factor VII (rFVIIa) treatment in infants with hemorrhage
Authors: BRADY KENNETH M. , BLAINE EASLEY R. , TOBIAS JOSEPH D.
Published: August 2006

Background:  Recombinant activated factor VII (rFVIIa) is approved by the FDA for the treatment of bleeding episodes in patients with hemophilia A or B with inhibitors to factor VIII or factor IX. In addition to the FDA‐approved indications, rFVIIa has been anecdotally reported effective for profound bleeding episodes in adult patients without hemophilia, and proven beneficial for adults with intracranial hemorrhage. In the pediatric literature, case reports have been made with apparent clinical improvement seen after the use of rFVIIa for acute life‐threatening bleeding; however, there are limited data regarding its use in infants <4 months of age. We report our experience with rFVIIa in nine infants with severe hemorrhage of diverse etiologies.

Methods:  This case series of infants under 4 months with coagulopathy and bleeding treated with rFVIIa was collected from two institutions. We report the age, weight and pre‐rFVIIa laboratory values of the patients as well as the clinical scenario and outcomes.

Results:  The nine infants all suffered acute life‐threatening hemorrhage. Two patients were postoperative from cardiac surgery, two with Vitamin K deficiency and intracranial hemorrhage, three with suspected necrotizing enterocolitis and abdominal hemorrhage, and two with pulmonary hemorrhage. The patients ranged in age from 2 days to 4 months, (average age 1 month and average weight 3.3 ± 1.0 kg). Seven of the nine patients had frozen plasma, cryoprecipitate, or platelet administration in failed attempts to correct the coagulation defect prior to receiving rFVIIa. The dose range used in this series was 90–100 μg·kg−1, with 90 μg·kg−1 being the most commonly used dose. The average pre‐rFVIIa INR was 8.7 ± 5.1. Four patients had an immeasurably high INR. All patients had clinical resolution of bleeding after receiving rFVIIa, and seven of nine patients survived.

Conclusions:  rFVIIa is a powerful hemostatic drug whose mechanism of action provides a theoretical specificity to sites of tissue injury. In addition to its FDA‐approved uses in hemophiliac patients, this drug has a potential role in the treatment of life‐threatening hemorrhage from multiple causes.
Tracheal intubating conditions and pharmacodynamics following cisatracurium in infants and children undergoing halothane and thiopental‐fentanyl anesthesia
Authors: MEAKIN GEORGE H. , MERETOJA OLLI  A. , PERKINS RUSSELL J. , WAITE IAN , TAIVAINEN TOMI , WIRTAVUORI KARI , MURPHY ANTHONY K. , RAIHA LEENA
Published: August 2006

Background:  The aims of the present study were to determine the tracheal intubating conditions, onset time, duration of action, and hemodynamic responses following the administration of cisatracurium 0.15 mg·kg−1 to infants and children.

Methods:  One hundred and eighty‐one infants and children aged 1 month to 12 years were randomized to two groups to receive anesthesia with nitrous oxide–oxygen–halothane (group H) or nitrous oxide–oxygen–thiopental‐fentanyl (group TF). Intubation conditions were assessed 120 s after cisatracurium administration using a 4‐part scale. Neuromuscular transmission was monitored by recording the evoked compound electromyogram of the adductor pollicis.

Results:  The proportion of patients with excellent or good intubating conditions was similar in both groups (88 of 90, 98% in group H; 85 of 90, 94% in group TF). However, there was a significantly greater proportion of excellent intubating conditions in group H (79 of 90, 88%) compared with group TF (65 of 90, 72%) (P = 0.01) and recovery time was significantly longer in group H compared with group TF (P < 0.001). There was also a higher proportion of excellent intubating conditions in infants compared with older subjects (P = 0.02) and a shorter onset time (P < 0.001) and longer recovery time (P < 0.001) in younger compared with older patients. Changes in heart rate and arterial pressure were negligible 1 min following the cisatracurium administration.

Conclusions:  Cisatracurium 0.15 mg·kg−1 produces acceptable intubating conditions at 120 s in the great majority of infants and children. Anesthesia background and age have significant effects on intubating conditions and duration of action of cisatracurium.
Anesthesia‐related morbidity and mortality after surgery for muscle biopsy in children with mitochondrial defects
Authors: DRIESSEN JACQUES , WILLEMS SIMONE , DERCKSEN SANDER , GIELE JANNEKE , VAN DER STAAK FRANS , SMEITINK JAN
Published: August 2006

Background:  Children with mitochondrial defects (MD) may have an increased risk for cardiorespiratory and neurological complications from anesthesia. The aim of this study was to determine the incidence of perioperative complications and adverse events in children with MD.

Methods:  We performed a retrospective review of the anesthesia, surgical and medical records of 155 children up to 10 years who underwent a diagnostic surgical muscle biopsy for suspected mitochondrial and muscle disorders between 1999 and 2003. The data of the 122 patients where a definite MD diagnosis was found were analyzed. Anesthesia was conducted according to the discretion of the attending staff. In children with MD the activity of the different complexes of the oxidative phosphorylation system was measured.

Results:  From the preoperative assessment, signs of encephalopathy were most frequent (n = 93), followed by muscle weakness (n = 32), lactic acidosis (n = 15), cardiomyopathy and/or conduction defects (n = 10) and chronic respiratory problems (n = 7). The mean age of the children with MD was 32.4 months (SD = 26.9). The mean duration of anesthesia was 36.0 min (SD = 12.6) and the mean length of stay in the recovery room was 33.0 min (SD = 24.0). There were no major changes in heart rate or blood pressure which required pharmacological intervention during anesthesia or postanesthesia care unit (PACU) stay. A short episode of SpO2 <80% with airway obstruction occurred once in the PACU. Biochemical analysis in the children with a MD showed an isolated deficiency of one of the five protein complexes of oxidative phosphorylation in 42 children, a combination of complex deficiencies in 41 and no definite localization in 39 children.

Conclusion:  With standard preoperative assessment, monitoring and anesthesia management, there were no major peroperative and postoperative anesthesia‐related complications in children undergoing surgical muscle biopsy with a MD diagnosis.
Resolution of pulmonary interstitial emphysema following selective left main stem intubation in a premature newborn: an old procedure revisited
Authors: CHALAK LINA F. , KAISER JEFFREY R. , ARRINGTON ROBERT W.
Published: August 2006

Pulmonary interstitial emphysema (PIE) contributes to worsening respiratory status in already compromised premature infants. Various treatments for PIE include high‐frequency ventilation, postural therapy, pneumonectomy or lobectomy and selective bronchial intubation. While right main stem bronchus intubation is easy to perform at the bedside for treatment of PIE in the left lung, left main stem bronchus intubation for the treatment of right‐sided PIE remains challenging and the technique was rarely reported and poorly described.

In this case report, we revisit this procedure and describe successful treatment of right lung PIE with hyperinflation by selective left main stem intubation at 2 weeks of life in a 24‐week‐old premature infant who had respiratory distress syndrome and pulmonary hemorrhage. A detailed description is given to allow clinical bedside replication following specific anatomic landmarks.
Atelectasis in children undergoing either propofol infusion or positive pressure ventilation anesthesia for magnetic resonance imaging
Authors: LUTTERBEY GOETZ , WATTJES MIKE P. , DOERR DOROTHEA , FISCHER NICOLAS J. , GIESEKE JUERGEN , SCHILD HANS H.
Published: August 2006

Background: Atelectasis because of anesthesia is a recognized problem but may be affected by the anesthetic technique. We compared magnetic resonance images of atelectasis in children undergoing two types of anesthesia.

Methods: Children requiring anesthesia for magnetic resonance imaging (MRI) had additional lung imaging sequences at the beginning and the end of anesthesia. Children had either i.v. propofol infusion (PI) without an artificial airway (n = 26) or positive pressure ventilation (PPV) via a tracheal tube (n = 20); the technique was chosen for clinical reasons. The extent of atelectasis was scored by two independent radiologists.

Results: The median ages (range) for PI and PPV groups were 45 months (1–77 months) and 18 months (2–74 months), respectively. The proportion of children with atelectasis was different in the first lung scan (42% vs 80%), but in the second scan atelectasis was seen frequently in both groups (82% vs 94%) with a greater extent in the PPV group. The atelectasis score was higher in young children, but all children had normal oxygen requirements and saturations.

Conclusions: Many factors may influence the development of atelectasis but this study found less extensive atelectasis with PI than PPV. PI allows for sufficient motionlessness, required for high diagnostic image quality in pediatric MRI.
Minor increase of endtidal CO2 during sevoflurane‐induced malignant hyperthermia
Authors: BONCIU MONALISA , DE LA CHAPELLE ARNAUD , DELPECH HENRY , DEPRET THIERY , KRIVOSIC‐HORBER RENEÉ , AIMÉ MARC RAUCOULES
Published: August 2006

Malignant hyperthermia (MH) in a pediatric patient during sevoflurane anesthesia with only a minor rise of endtidal CO2 is described. MH was considered because of increased rectal temperature. The outcome was favorable after the initiation of a few simple measures (increased minute ventilation, cessation of sevoflurane). As recommended by the regional MH Reference Center, dantrolene was not used. In vitro contracture tests were performed on muscle biopsies from both parents. A strong contracture in response to halothane confirmed the father's MH susceptibility, thereby according a high probability of an MH episode in his son.
Host propagation permits extreme local adaptation in a social parasite of ants
Authors: Schönrogge K. , Gardner M. G. , Elmes G. W. , Napper E. K. V. , Simcox D. J. , Wardlaw J. C. , Breen J. , Barr B. , Knapp J. J. , Pickett J. A. , Thomas J. A.
Published: August 2006

The Red Data Book hoverfly species Microdon mutabilis is an extreme specialist that parasitises ant societies. The flies are locally adapted to a single host, Formica lemani, more intimately than was thought possible in host–parasite systems. Microdon egg survival plummeted in F. lemani colonies > 3 km away from the natal nest, from c. 96% to 0% to < 50%, depending on the hoverfly population. This is reflected in the life‐time dispersal of females, measured at < 2 m, resulting in oviposition back into the same ant nests for generation after generation. To counter destabilizing effects on the host, Microdon manipulates the social dynamics of F. lemani by feeding selectively on ant eggs and small larvae, which causes surviving larvae to switch development into queens. Infested colonies rear double the number of new queens, thus propagating the vulnerable local genotype and compensating for damage to the host colonies. The consequences of such extreme host specificity for insect conservation are discussed.
Decoupling the direct and indirect effects of nitrogen deposition on ecosystem function
Authors: Manning Pete , Newington John E. , Robson Helen R. , Saunders Mark , Eggers Till , Bradford Mark A. , Bardgett Richard D. , Bonkowski Michael , Ellis Richard J. , Gange Alan C. , Grayston Susan J. , Kandeler Ellen , Marhan Sven , Reid Eileen , Tscherko Dagmar , Godfray H. Charles J. , Rees Mark
Published: August 2006

Elevated nitrogen (N) inputs into terrestrial ecosystems are causing major changes to the composition and functioning of ecosystems. Understanding these changes is challenging because there are complex interactions between ‘direct’ effects of N on plant physiology and soil biogeochemistry, and ‘indirect’ effects caused by changes in plant species composition. By planting high N and low N plant community compositions into high and low N deposition model terrestrial ecosystems we experimentally decoupled direct and indirect effects and quantified their contribution to changes in carbon, N and water cycling. Our results show that direct effects on plant growth dominate ecosystem response to N deposition, although long‐term carbon storage is reduced under high N plant‐species composition. These findings suggest that direct effects of N deposition on ecosystem function could be relatively strong in comparison with the indirect effects of plant community change.
Harvest reserves reduce extinction risk in an experimental microcosm
Authors: Fryxell John M. , Lynn Denis H. , Chris Philip J.
Published: August 2006

Overharvesting by humans threatens a substantial fraction of endangered species. Reserves have recently received enormous attention as a means of better conserving harvested resources, despite limited empirical evidence of their efficacy. We used manipulated microcosms to test whether reserves reduce extinction risk in mobile populations of harvested Tetrahymena thermophila, a ciliate. Here we show that patterns of population distribution inside and outside reserves can be accurately predicted on the basis of simple models of diffusion coupled with logistic controls on local population growth. No extinctions occurred in eight experimental trials with reserves, whereas extinction occurred in seven of eight trials without reserves, as predicted by population viability models based on stochastic population processes. These results suggest that marine reserves may be an effective means of improving long‐term viability in heavily harvested fish species.
Land cover associated with hantavirus presence in Paraguay
Authors: Goodin Douglas G. , Koch David E. , Owen Robert D. , Chu Yong‐Kyu , Hutchinson J. M. Shawn , Jonsson Colleen B.
Published: August 2006

Aims Hantaviruses are zoonotic, aetiological agents maintained by rodents of the family Muridae. The occurrence of hantavirus in rodent hosts has been correlated to a number of climatic and environmental factors, including landscape structure. To date, most of these correlative studies have been conducted at moderate to fine spatial resolution. Our aim is to determine whether land cover classes defined at a mapping resolution of 1 km2are associated with rodents with antibodies to hantavirus in Paraguay.

Location The Republic of Paraguay.

Methods A total of 362 rodents from 10 species known to host hantaviruses were tested for the presence of hantavirus antibodies, resulting in 27 seropositive individuals. This data base was then combined with a map of six land cover types derived from coarse resolution remote sensing data to create a series of contingency tables, which were used to relate serostatus to land cover type using nonparametric tests of proportions and qualitative comparison of observed and expected values.

Results There was a significant difference in habitat association between seropositive and seronegative rodents when species were pooled. Seropositive rodents were found with disproportionately high frequency in areas where human disturbance in the form of intensive and mosaic agricultural landscapes was present.

Main conclusions Human‐disturbed land cover classes have a detectable relationship to the hantavirus serostatus of host population rodents when observed at coarse spatial resolutions. Although coarse‐grained analysis does not lead to any conclusions as to why agricultural land cover is more likely to harbour seropositive rodents, the relationship between them could form the basis for a monitoring system designed to relate land cover change to potential viral outbreaks in rodents and humans.
The Balassa–Samuelson Effect in a Developing Country
Authors: Gente Karine
Published: August 2006

Some Asian countries experience small real exchange rate appreciations or even a real depreciation despite a fast growth in tradable productivity. A key‐characteristic of these countries is that they are constrained on capital inflows. Is the Balassa–Samuelson theory still valid in those countries? Are there other factors likely to explain real exchange rate (RER) changes? To address these questions, we develop a two‐sector model in which a small open economy faces a constraint on capital inflows. In this setting, the RER does not only depend on productivity, but also on other factors like the rate of time preference, the age dependency ratio or the level of the external constraint. A calibration of the constrained economy model seems to match at least qualitatively empirical evidence for China, Hong Kong, Indonesia, Malaysia, Thailand, and Singapore, between 1970 and 1992.
One-Year Prevalence and Socio-Cultural Aspects of Chronic Headache in Turkish Immigrants and German Natives
Authors: Kavuk I , Weimar C , Kim BT , Gueneyli G , Araz M , Klieser E , Limmroth V , Diener HC , Katsarava Z
Published: August 2006

The aim of this research was to study the prevalence of chronic headache (CH) and associated socio-cultural factors in Turkish immigrants and native Germans. Five hundred and twenty-three Turkish and German company employees were screened using a standard questionnaire. Those who suffered from headaches were also examined by a neurologist. Complete data were available for 471 (90%) subjects. Thirty-four participants (7.2%) had CH. Two independent factors for association with CH could be identified: overuse of acute headache medication (OR = 72.5; 95% CI 25.9-202.9), and being a first-generation Turkish immigrant compared with native Germans (OR = 4.4; 95% CI 1.4-13.7). In contrast, the factor associated with chronic headache was not increased in second-generation Turkish immigrants. Medication overuse was significantly more frequent in first-generation Turkish immigrants (21.6%) compared with second-generation Turkish immigrants (3.3%) and native Germans (3.6%; X2 = 38.0, P < 0.001). First-generation Turkish immigrants did not contact headache specialists at all, compared with 2.8% of second-generation Turkish immigrants and 8.8% of native Germans ( X2 = 118.4, P < 0.001). Likewise no first-generation Turkish immigrant suffering from CH received headache preventive treatment, compared with 6.6% of native Germans ( X2 = 19.1, P = 0.014). The data from this cross-sectional study reveal a high prevalence of chronic headache as well as a very low utilization of adequate medical care in first-generation Turkish immigrants in Germany.
Blink Reflex R2 Amplitudes in Cervicogenic Headache, Chronic Tension-Type Headache and Migraine
Authors: Sand T , Møll-Nilsen B , Zwart A J
Published: August 2006

Blink reflex R2 amplitude was investigated in seven patients with cervicogenic headache (CEH), 12 patients with chronic tension-type headache, 23 patients with migraine (10 with aura) and 17 headache-free controls. Standard electrical stimulation of the supraorbital nerve was applied and the response was recorded from the ipsilateral and the contralateral orbicularis oculi muscles. Low R2 amplitude was found in CEH patients compared with control subjects. Headache is unilateral in CEH and the ipsilateral and contralateral responses after stimulation on the painful side were most depressed. R2 amplitude was not significantly affected in migraine and tension headache patients. The results suggest that lower brainstem excitability is reduced in CEH. A state of hypoactivity may be present in caudal trigeminal nucleus neurons on the symptomatic side.
Discontinuation of Medication Overuse in Headache Patients: Recovery of Therapeutic Responsiveness
Authors: Zeeberg P , Olesen J , Jensen R
Published: August 2006

It is generally accepted that ongoing medication overuse nullifies the effect of prophylactic treatment, although few data support this contention. We set out to describe the treatment outcome in patients withdrawn from medication overuse and relate any improvement to a renewed effect of prophylaxis. For patients with probable medication-overuse headache (pMOH), treated and dismissed from the Danish Headache Centre in 2002 and 2003, we assed, from prospective headache diaries, the headache frequency before and after withdrawal of offending drugs and compared these frequencies with the headache frequency at dismissal. Among 1326 patients, 337 had pMOH. Eligible were 175, mean age 49 years, male/female ratio 1: 2.7. Overall, there was a 46% decrease in headache frequency from the first visit to dismissal ( P < 0.0001). Patients with no improvement 2 months after complete drug withdrawal ( N = 88) subsequently responded to pharmacological and/or non-pharmacological prophylaxis with a 26% decrease in headache frequency as measured from the end of withdrawal to dismissal ( P < 0.0001). At dismissal, 47% were on prophylaxis. Former non-responders to medical prophylaxis had a 49% decrease in headache frequency from first visit to dismissal ( P < 0.0001), whereas those who had never received prophylaxis had a 56% reduction ( P < 0.0001). This difference was not statistically significant ( P = 0.22). Almost all MOH patients benefit from drug withdrawal, either just from the withdrawal or by transformation from therapeutic non-responsiveness to responsiveness. According to the International Classification of Headache Disorders, 2nd edn, the MOH diagnosis requires improvement after drug withdrawal. Our data suggest that these diagnostic criteria are too strict.
Use of a ROSA26:GFP transgenic line for long‐term Xenopus fate‐mapping studies
Authors: Gross Joshua B. , Hanken James , Oglesby Ericka , Marsh‐Armstrong Nicholas
Published: August 2006

Widespread and persistent marker expression is a prerequisite for many transgenic applications, including chimeric transplantation studies. Although existing transgenic tools for the clawed frog, Xenopus laevis, offer a number of promoters that drive widespread expression during embryonic stages, obtaining transgene expression through metamorphosis and into differentiated adult tissues has been difficult to achieve with this species. Here we report the application of the murine ROSA26 promoter in Xenopus. GFP is expressed in every transgenic tissue and cell type examined at post‐metamorphic stages. Furthermore, transgenic ROSA26:GFP frogs develop normally, with no apparent differences in growth or morphology relative to wild‐type frogs. ROSA26 transgenes may be used as a reliable marker for embryonic fate‐mapping of adult structures in Xenopus laevis. Utility of this transgenic line is illustrated by its use in a chimeric grafting study that demonstrates the derivation of the adult bony jaw from embryonic cranial neural crest.
Regional variations in the density and arrangement of elastic fibres in the anulus fibrosus of the human lumbar disc
Authors: Smith Lachlan J. , Fazzalari Nicola L.
Published: August 2006

Elastic fibres are critical components of the extracellular matrix in dynamic biological structures that undergo extension and recoil. Their presence has been demonstrated in the anulus fibrosus of the human lumbar intervertebral disc; however, a detailed regional analysis of their density and arrangement has not been undertaken, limiting our understanding of their structural and functional roles. In this investigation we have quantitatively described regional variations in elastic fibre density in the anulus fibrosus of the human L3–L4 intervertebral disc using histochemistry and light microscopy. Additionally, a multiplanar comparison of patterns of elastic fibre distribution in the intralamellar and interlamellar zones was undertaken. Novel imaging techniques were developed to facilitate the visualization of elastic fibres otherwise masked by dense surrounding matrix. Elastic fibre density was found to be significantly higher in the lamellae of the posterolateral region of the anulus than the anterolateral, and significantly higher in the outer regions than the inner, suggesting that elastic fibre density in each region of the anulus is commensurate with the magnitude of the tensile deformations experienced in bending and torsion. Elastic fibre arrangments in intralamellar and interlamellar zones were shown to be architecturally distinct, suggesting that they perform multiple functional roles within the anulus matrix structural hierarchy.
The postnatal development of cerebellar Purkinje cells in the Göttingen minipig estimated with a new stereological sampling technique – the vertical bar fractionator
Authors: Jelsing Jacob , Gundersen Hans Jørgen G. , Nielsen Rune , Hemmingsen Ralf , Pakkenberg Bente
Published: August 2006

The postnatal development of total number and perikaryon volume of cerebellar Purkinje cells was estimated in the Göttingen minipig cerebellar cortex using a new stereological approach, the vertical bar fractionator. Data were obtained from the brains of five neonate and five adult female Göttingen minipigs. The total number of Purkinje cells ranged from 1.83 × 106 in the neonate to 2.82 × 106 in the adult Göttingen minipig. The number‐weighted mean perikaryon volume of Purkinje cells increased concurrently from around 6800 µm3 in the neonate to 17 600 µm3 in the adult. The study demonstrates that a pronounced postnatal neurogenesis in Purkinje cell number and perikaryon volume is part of the growth and development of the cerebellum in the Göttingen minipig. The Purkinje cells of the Göttingen minipig were found to be substantially large compared with human and represents the largest cells described hitherto from mammalian cerebella. The vertical fractionator is a new sampling technique, which allows the combination of a fractionator design on vertical bar sections excluding exhaustive sampling and bias from artificial edges. By design, the sections are perfect stereological vertical sections and provide the basis for unbiased estimates of total number of structural entities in the brain, including surface area, fibre length and particle volume.
Prediction of volumetric strain in the human temporomandibular joint cartilage during jaw movement
Authors: Koolstra J. H. , Van Eijden T. M. G. J.
Published: August 2006

Human temporomandibular joint loading causes pressurization and flow of interstitial fluid in its cartilaginous structures. This largely determines its load‐bearing and maintenance capacity. It was hypothesized that during cyclical jaw movements normal pressure distribution dynamics would enable fluid to reach all necessary cartilage regions. This was tested qualitatively by analysis of local volumetric strain dynamics during jaw open–close movements predicted by a dynamic model of the human masticatory system. Finite‐element analysis was performed in separate regions of the articular cartilage layers and articular disc. Heterogeneous patterns of dilatation and compression were predicted. Compression was found to be more dominant during jaw closing than opening. The pressure gradient in the superior layer of the articular disc was more mediolaterally orientated than in its inferior layer. The findings suggest that, where necessary, regionally the cartilage can imbibe fluid to protect the subchondral bone from impact loads effectively. In the disc itself presumably all areas receive regular refreshment of interstitial fluid.
The zona pellucida of the koala (Phascolarctos cinereus): its morphogenesis and thickness
Authors: Chapman Jamie A. , Leigh Christopher M. , Breed William G.
Published: August 2006

In this study the ultrastructural organization of the koala oocyte and the thickness of the surrounding extracellular coat, the zona pellucida, has been determined to ascertain whether there is coevolution of the morphology of the female gamete with that of the highly divergent male gamete that is found in this marsupial species. Ovaries from several adult koalas were obtained and prepared for transmission electron microscopy. Oocytes in large tertiary follicles were somewhat smaller than those of most other marsupials, although their ultrastructural organization appeared similar and included many yolk vesicles. The zona pellucida surrounding the oocytes in tertiary follicles was approximately 8 µm thick and thus is of similar thickness to that of some eutherian mammals but at least twice as thick as that of most marsupial species so far studied. The results indicate that the koala oocyte is unusually small for a marsupial species whereas the zona pellucida is, by contrast, much thicker. How this relates to sperm–egg interaction at the time of fertilization has yet to be determined.
Differential availability/processing of decorin precursor in arterial and venous smooth muscle cells
Authors: Franch Rafaella , Chiavegato Angela , Maraschin Maddalena , Candeo Serena , Ausoni Simonetta , Villa Antonello , Gerosa Gino , Gasparotto Lisa , Parnigotto Pierpaolo , Sartore Saverio
Published: August 2006

The existence of specific differentiation markers for arterial smooth muscle (SM) cells is still a matter of debate. A clone named MM1 was isolated from a library of monoclonal antibodies to adult porcine aorta, which in vivo binds to arterial but not venous SM cells, except for the pulmonary vein. MM1 immunoreactivity in Western blotting involved bands in the range of Mr 33–226 kDa, in both arterial and venous SM tissues. However, immunoprecipitation experiments revealed that MM1 bound to a 100‐kDa polypeptide that was present only in the arterial SM extract. By mass spectrometry analysis of tryptic digests from MM1‐positive 130‐ and 120‐kDa polypeptides of aorta SM extract, the antigen recognized by the antibody was identified as a decorin precursor. Using a crude decorin preparation from this tissue MM1 reacted strongly with the 33‐kDa polypeptide and this pattern did not change after chondroitinase ABC treatment. In vitro, decorin immunoreactivity was found in secreted grainy material produced by confluent arterial SM cells, although lesser amounts were also seen in venous SM cells. Western blotting of extracts from these cultures showed the presence of the 33‐kDa band but not of the high‐molecular‐weight components, except for the 100‐kDa monomer. The 100/33‐kDa combination was more abundant in arterial SM cells than in the venous counterpart. In the early phase of neointima formation, induced by endothelial injury of the carotid artery or vein‐to‐artery transposition, the decorin precursor was not expressed, but it was up‐regulated in the SM cells of the media underlying the neointima in both models. Collectively, these data suggest a different processing/utilization of the 100‐kDa monomer of proteoglycan decorin in arterial and venous SM cells, which is abolished after vein injury.
Functional anatomy of interhemispheric cortical connections in the human brain
Authors: Zarei Mojtaba , Johansen‐Berg Heidi , Smith Steve , Ciccarelli Olga , Thompson Alan J. , Matthews Paul M.
Published: August 2006

Interhemsipheric interaction between the human cerebral hemispheres is served by abundant white‐matter fibres in the human corpus callosum (CC). Damage to these fibres has notable behavioural and cognitive sequelae that depend on the exact location of the fibre loss. Until now, correlations between fibre loss and neurological disorders have been limited to post‐mortem studies. Here we used probabilistic diffusion magnetic resonance imaging tractography to produce a two‐dimensional map of the CC in the mid‐sagittal plane. We observed an antero‐posterior topography of interhemispheric tracts within the CC, consistent with our current neuroanatomical understanding of post‐mortem studies in human. Callosal tract to the left and right hemispheres had comparable volume. Gender, a factor that is often reported to affect CC shape and geometry, also had no effect on the volume of the tracts. Our map showed high consistency across individuals. We propose that this map might be useful in the study of the effects of damage to human CC in neurodegenerative and cognitive disorders.
Evidence of solitary chemosensory cells in a large mammal: the diffuse chemosensory system in Bos taurus airways
Authors: Tizzano Marco , Merigo Flavia , Sbarbati Andrea
Published: August 2006

The diffuse chemosensory system (DCS) of the respiratory apparatus is composed of solitary chemosensory cells (SCCs) that resemble taste cells but are not organized in end organs. The discovery of the DCS may open up new approaches to respiratory diseases. However, available data on mammalian SCCs have so far been collected from rodents, the airways of which display some differences from those of large mammals. Here we investigated the presence of the DCS and of SCCs in cows and bulls (Bos taurus), in which the airway cytology is similar to that in humans, focusing our attention on detection in the airways of molecules involved in the transduction cascade of taste [i.e. α‐gustducin and phospholipase C of the β2 subtype (PLCβ2)]. The aim of the research was to extend our understanding of airway chemoreceptors and to compare the organization of the DCS in a large mammal with that in rodents. Using immunocytochemistry for α‐gustducin, the taste buds of the tongue and arytenoid were visualized. In the trachea and bronchi, α‐gustducin‐immunoreactive SCCs were frequently found. Using immunocytochemistry for PLCβ2, the staining pattern was generally similar to those seen for α‐gustducin. Immunoblotting confirmed the expression of α‐gustducin in the tongue and in all the airway regions tested. The study demonstrated the presence of SCCs in cows and bulls, suggesting that DCSs are present in many mammalian species. The description of areas with a high density of SCCs in bovine bronchi seems to indicate that the view of the DCS as made up of isolated cells totally devoid of ancillary elements is probably an oversimplification.
Intra‐ and intermuscular variation in human quadriceps femoris architecture assessed in vivo
Authors: Blazevich Anthony J. , Gill Nicholas D. , Zhou Shi
Published: August 2006

Despite the functional importance of the human quadriceps femoris in movements such as running, jumping, lifting and climbing, and the known effects of muscle architecture on muscle function, no research has fully described the complex architecture of this muscle group. We used ultrasound imaging techniques to measure muscle thickness, fascicle angle and fascicle length at multiple regions of the four quadriceps muscles in vivo in 31 recreationally active, but non‐strength‐trained adult men and women. Our analyses revealed a reasonable similarity in the superficial quadriceps muscles, which is suggestive of functional similarity (at least during the uni‐joint knee extension task) given that they act via a common tendon. The deep vastus intermedius (VI) is architecturally dissimilar and therefore probably serves a different function(s). Architecture varies significantly along the length of the superficial muscles, which has implications for the accuracy of models that assume a constant intramuscular architecture. It might also have consequences for the efficiency of intra‐ and intermuscular force transmission. Our results provide some evidence that subjects with a given architecture of one superficial muscle, relative to the rest of the subject sample, also have a similar architecture in other superficial muscles. However, this is not necessarily true for vastus lateralis (VL), and was not the case for VI. Therefore, the relative architecture of one muscle cannot confidently be used to estimate the relative architecture of another. To confirm this, we calculated a value of whole quadriceps architecture by four different methods. Regardless of the method used, we found that the absolute or relative architecture of one muscle could not be used as an indicator of whole quadriceps architecture, although vastus medialis, possibly in concert with VL and the anterior portion of VI, could be used to provide a useful snapshot. Importantly, our estimates of whole quadriceps architecture show a gender difference in whole quadriceps muscle thickness, and that muscle thickness is positively correlated with fascicle angle whereas fascicle length is negatively, although weakly, correlated with fascicle angle. These results are supportive of the validity of estimates of whole quadriceps architecture. These data are interpreted with respect to their implications for neural control strategies, region‐specific adaptations in muscle size in response to training, and gender‐dependent differences in the response to exercise training.
Morphological changes of isolated rat pancreatic islets: a structural, ultrastructural and morphometric study
Authors: Morini Sergio , Braun Mark , Onori Paolo , Cicalese Luca , Elias George , Gaudio Eugenio , Rastellini Cristiana
Published: August 2006

Improved techniques for pancreatic islet extraction can yield a reasonable number of transplantable cells. However, the isolation and purification process may damage the islets and impair their physiological functions. The aim of this study was to determine the effect of the isolation procedure on the structure of isolated islets and to correlate this with their functionality. Islets were isolated from rat pancreata and purified by Eurocollins‐Ficoll discontinuous density gradient processing, and then processed for light microscopy, and scanning and transmission electron microscopy. Morphometric analysis was also performed. Islet functionality was determined by reversal of streptozotocin‐induced diabetes and the intraperitoneal glucose tolerance test in a syngeneic rat model of pancreatic islet transplantation. Fragments of variable size and shape comprised a relatively large proportion (26%) of the isolated endocrine tissue. Isolated islets showed slight alterations of cell ultrastructure. Major damage (including breakage of the plasma membrane) and loss of cells were observed in the peripheral cells of the isolated islets. An equal mass of islet equivalent (IEq, islets with an average diameter of 150 µm), but with a different islet equivalent/islet number ratio, was transplanted in diabetic animals. When larger and more complete islets were transplanted (higher ratio), better function of the graft was observed by reversal of hyperglycaemia and response to the glucose tolerance test as compared with the functionality and response of smaller (fragmented) islets transplanted (lower ratio). Digestion, trauma and hypoxia during isolation are responsible for qualitative and quantitative changes of isolated islets. Alterations in normal secretory function after the transplant were related to lower islet equivalent/islet number ratio. The incomplete integrity of the islets may explain the failure of the fine glycaemic metabolic regulation.
Biological tooth replacement
Authors: Sartaj Rachel , Sharpe Paul
Published: August 2006

Teeth develop from a series of reciprocal interactions that take place between epithelium and mesenchyme during development of the mouth that begin early in mammalian embryogenesis. The molecular control of key processes in tooth development such as initiation, morphogenesis and cytodifferentiation are being increasingly better understood, to the point where this information can be used as the basis for approaches to produce biological replacement teeth (BioTeeth). This review outlines the current approaches, ideas and progress towards the production of BioTeeth that could form an alternative method for replacing lost or damaged teeth.
Bioengineered nerve regeneration and muscle reinnervation
Authors: Kingham Paul J. , Terenghi Giorgio
Published: August 2006

The peripheral nervous system has the intrinsic capacity to regenerate but the reinnervation of muscles is often suboptimal and results in limited recovery of function. Injuries to nerves that innervate complex organs such as the larynx are particularly difficult to treat. The many functions of the larynx have evolved through the intricate neural regulation of highly specialized laryngeal muscles. In this review, we examine the responses of nerves and muscles to injury, focusing on changes in the expression of neurotrophic factors, and highlight differences between the skeletal limb and laryngeal muscle systems. We also describe how artificial nerve conduits have become a useful tool for delivery of neurotrophic factors as therapeutic agents to promote peripheral nerve repair and might eventually be useful in the treatment of laryngeal nerve injury.
Gene‐linked shift in ganglioside distribution influences growth and vascularity in a mouse astrocytoma
Authors: Abate Laura E. , Mukherjee Purna , Seyfried Thomas N.
Published: August 2006

Brain tumor growth and progression is dependent upon vascularity, and is associated with altered ganglioside composition and distribution. In this study, we examined the influence of gangliosides on growth and vascularity in a malignant mouse astrocytoma, CT‐2A. Ganglioside distribution was altered in CT‐2A tumor cells using an antisense construct to β‐1,4‐N‐acetylgalactosaminyltransferase (GalNAc‐T), a key enzyme that uses the simple ganglioside GM3 as a substrate for the synthesis of the more complex gangliosides, GM2, GM1 and GD1a. GalNAc‐T gene expression was significantly lower in CT‐2A cells stably transfected with the antisense GalNAc‐T plasmid, pcDNA3.1/TNG (CT‐2A/TNG) than in either non‐transfected CT‐2A or mock‐transfected (CT‐2A/V) control tumor cells. GM3 was elevated from 16% to 58% of the total ganglioside distribution, whereas GM1 and GD1a were reduced from 17% and 49% to 10% and 17%, respectively, in CT‐2A/TNG tumor cells. Growth, vascularity (blood vessel density and Matrigel assay) and vascular endothelial growth factor (VEGF) expression was significantly less in CT‐2A/TNG tumors than in control CT‐2A brain tumors. In addition, the expression of VEGF, hypoxia‐inducible factor 1α (HIF‐1α) and neuropilin‐1 (NP‐1) was significantly lower in CT‐2A/TNG tumor cells than in control CT‐2A tumor cells. These data suggest that gene‐linked changes in ganglioside composition influence the growth and angiogenic properties of the CT‐2A astrocytoma.
Cyclin‐dependent kinase 5 influences Rohon‐Beard neuron survival in zebrafish
Authors: Kanungo Jyotshnabala , Li Bing‐Sheng , Zheng Yali , Pant Harish C.
Published: August 2006

Cyclin‐dependent kinase 5 (cdk5), a member of the cyclin‐dependent kinase family, is expressed predominantly in post‐mitotic cell populations. Unlike the other cdks, cdk5 is abundant and most active in differentiated neurons. Here, we describe the function of a cdk5 ortholog in zebrafish. Cdk5 catalytic activity is meager but present in early stages of development. However, at 24 h post‐fertilization (hpf), the activity is remarkably higher and continues to be high through 48 and 72 hpf. Knocking down cdk5 by micro‐injection of a specific siRNA resulted in decreased cdk5 protein level accompanied by reduced kinase activity. In the cdk5 siRNA‐injected embryos, the number of primary sensory Rohon‐Beard (RB) neurons was significantly reduced and there were more apoptotic cells in the brain. These phenotypes were rescued by co‐injection of cdk5 mRNA. Within the first two days of development, RB neurons undergo apoptosis in zebrafish. To examine whether cdk5 has a role in RB neuron survival, cdk5 mRNA was injected into the one‐ to two‐cell embryos. In these embryos, RB neuron apoptosis was inhibited compared with the uninjected control embryos. These results suggest that in zebrafish, cdk5 influences RB neuron survival and potentially regulates early neuronal development.
The activation loop phosphorylation of protein kinase D is an early marker of neuronal DNA damage
Authors: Besirli Cagri G. , Johnson Eugene M.
Published: August 2006

In neurons, DNA damage induces protein synthesis‐dependent apoptosis mediated by the mitochondrial intrinsic cell‐death pathway. Signal transduction cascades activated by genotoxic stress upstream of the mitochondria are largely unknown. We identified protein kinase D (PKD) as one of the earliest markers of neuronal DNA damage. Phosphorylation of the PKD‐activation domain could be detected within 15 min of genotoxic stress and was concurrent with ataxia telangiectasia‐mutated (ATM) activation. PKD stimulation was selective to DNA damage and did not occur with other stress stimuli examined. In vivo, both young and adult rats showed increased levels of phosphorylated PKD in neuronal tissues after injection of DNA‐toxin etoposide. These results indicate that PKD activation is an early neuronal response to DNA damage, suggesting that signaling downstream of PKD may be critical for neuronal survival after genotoxic stress.