bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity
Authors: Fu Amy K. Y. , Fu Wing-Yu , Ng Alberto K. Y. , Chien Winnie W. Y. , Ng Yu-Pong , Wang Jerry H. , Ip Nancy Y.
Published: April 2004

The activity of cyclin-dependent kinase 5 (Cdk5) depends on the association with one of its activators, p35 and p39, which are prominently expressed in the nervous system. Studies on the repertoire of protein substrates for Cdk5 have implicated the involvement of Cdk5 in neuronal migration and synaptic plasticity. Our recent analysis of the sequence of signal transducer and activator of transcription (STAT)3, a key transcription factor, reveals the presence of potential Cdk5 phosphorylation site. We report here that the Cdk5/p35 complex associates with STAT3 and phosphorylates STAT3 on the Ser-727 residue
in vitro
and
in vivo
. Intriguingly, whereas the Ser phosphorylation of STAT3 can be detected in embryonic and postnatal brain and muscle of wild-type mice, it is essentially absent from those of Cdk5-deficient embryos. In addition, treatment of cultured myotubes with neuregulin enhances the Ser phosphorylation of STAT3 and transcription of STAT3 target genes, such as c-fos and junB, in a Cdk5-dependent manner. Both the DNA-binding activity of STAT3 and the transcription of specific target genes, such as fibronectin, are reduced in Cdk5-deficient muscle. Taken together, these results reveal a physiological role of Cdk5 in regulating STAT3 phosphorylation and modulating its transcriptional activity.
Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans
Authors: Fontana Luigi , Meyer Timothy E. , Klein Samuel , Holloszy John O.
Published: April 2004

Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 ± 1.9 vs. 25.9 ± 3.2 kg/m
2
; percent body fat, 8.7 ± 7% vs. 24 ± 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was ≈40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT.
Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin's lymphoma cells from autonomous Fas-mediated death
Authors: Dutton A. , O'Neil J. D. , Milner A. E. , Reynolds G. M. , Starczynski J. , Crocker J. , Young L. S. , Murray P. G.
Published: April 2004

Hodgkin's lymphoma (HL) is characterized by the presence of malignant so-called Hodgkin's/Reed-Sternberg (HRS) cells, which display resistance to certain apoptotic stimuli, including a lack of sensitivity to Fas-mediated cell death. However, the mechanisms responsible for their resistance to apoptosis inducers have not been elucidated. Here we confirm that both HL-derived cell lines and the HRS cells of primary HL tissues express Fas ligand (FasL) along with the inhibitory c-FLIP protein. Down-regulation of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) through the use
of
specific small inhibitory RNAs (siRNAs) leads to reduced viability of the L428 and L591 HL-derived cell lines. To determine whether endogenous FasL was responsible for the reduction in cell viability observed after down-regulation of c-FLIP, L428 and L591 cells were treated with c-FLIP-specific siRNAs with and without siRNAs directed to FasL. Treatment of these cells with both c-FLIP- and FasL-specific siRNAs in combination restored cell viability to near control levels. Our results provide a mechanism whereby HRS cells are protected from autonomous FasL-mediated cell death while preserving their ability to evade immunosurveillance. Targeting c-FLIP could provide a novel approach to the treatment of HL.
Comparison of a Lower-lipid Propofol Emulsion with the Standard Emulsion for Sedation during Monitored Anesthesia Care
Authors: Song Dajun , Hamza Mohamed A. , White Paul F. , Byerly Stephanie I. , Jones Stephanie B. , Macaluso Amy D.
Published: April 2004

Background

The currently used emulsion formulations of 1% propofol contain 10% soybean oil. However, a new emulsion of 1% propofol (Ampofol) containing 50% less lipid has recently become available for clinical investigation. This study was designed to compare the pharmacodynamic properties of Ampofol with those of a standard formulation (Diprivan) when administered for intraoperative sedation.

Methods

Sixty healthy outpatients undergoing minor operations with local anesthesia were randomly assigned to receive either Ampofol (n = 31) or Diprivan (n = 29) for intravenous sedation. The sedation was initiated with an intravenous loading dose of propofol, 0.75 mg/kg, followed by an initial infusion rate of 50 microg x kg(-1) x min(-1) to achieve an Observer's Assessment of Alertness/Sedation score of 3. The targeted level of sedation was maintained with a variable-rate propofol infusion during the operation. The onset times to achieving a sedation score of 3, the severity of pain on injection of the loading dose, intraoperative hemodynamic variables, and electroencephalographic Bispectral Index values were recorded. In addition, recovery times, postoperative pain and nausea, and patient satisfaction with the sedative medication were assessed.

Results

There were no significant differences between Ampofol and Diprivan with respect to onset times, dosage requirements, Bispectral Index values, hemodynamic variables, recovery times, or patient satisfaction scores. The incidence of moderate pain on injection was higher in the Ampofol group (26%vs. 7% with Diprivan; P < 0.05).

Conclusions

Ampofol was equipotent to Diprivan with respect to its sedative properties during monitored anesthesia care. Although both groups received pretreatment with intravenous lidocaine, Ampofol was associated with more pain on injection.
Can Acceleromyography Detect Low Levels of Residual Paralysis?
Authors: Capron Florent , Alla Francois , Hottier Claire , Meistelman Claude , Fuchs-Buder Thomas
Published: April 2004

Background

The incidence of residual paralysis, i.e., a mechanomyographic train-of-four (TOF) ratio (T4/T1) less than 0.9, remains frequent. Routine acceleromyography has been proposed to detect residual paralysis in clinical practice. Although acceleromyographic data are easy to obtain, they differ from mechanomyographic data, with which they are not interchangeable. The current study aimed to determine (1) the acceleromyographic TOF ratio that detects residual paralysis with a 95% probability, and (2) the impact of calibration and normalization on this predictive acceleromyographic value.

Methods

In 60 patients, recovery from neuromuscular block was assessed simultaneously with mechanomyography and acceleromyography. To obtain calibrated acceleromyographic TOF ratios in group A, the implemented calibration modus 2 was activated in the TOF-Watch S; to obtain uncalibrated acceleromyographic TOF ratios in group B, the current was manually set at 50 mA (n = 30 for each). In addition, data in group B were normalized (i.e., dividing the final TOF ratio by the baseline value). The agreement between mechanomyography and acceleromyography was assessed by calculating the intraclass correlation coefficient. Negative predictive values were calculated for detecting residual paralysis from acceleromyographic TOFs of 0.9, 0.95, and 1.0.

Results

Group A

: For a mechanomyographic TOF of 0.9 or greater, the corresponding acceleromyographic TOF was 0.95 (range, 0.86-1.0), and the negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 37% (95% CI, 20-56%), 70% (95% CI, 51-85%), and 97% (95% CI, 83-100%), respectively. Group B: Without normalization, an acceleromyographic TOF of 0.97 (range, 0.68-1.18) corresponded to a mechanomyographic TOF of 0.9 or greater, with negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 being 40% (95% CI, 23-59%), 60% (95% CI, 41-77%), and 77% (95% CI, 58-90%), respectively. After normalization, an acceleromyographic TOF of 0.89 (range, 0.63-1.06) corresponded to a mechanomyographic TOF of 0.9 or greater, and the negative predictive values of acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 89% (95% CI, 70-98%), 92% (95% CI, 75-99%), and 96% (95% CI, 80-100%), respectively.

Conclusion

To exclude residual paralysis reliably when using acceleromyography, TOF recovery to 1.0 is mandatory.
Propofol Modulates γ-Aminobutyric Acid–mediated Inhibitory Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus
Authors: Wang Xin , Huang Zheng-Gui , Gold Allison , Bouairi Evguenia , Evans Cory , Andresen Michael C. , Mendelowitz David
Published: April 2004

Background

Although it is well recognized that anesthetics modulate the central control of cardiorespiratory homeostasis, the cellular mechanisms by which anesthetics alter cardiac parasympathetic activity are poorly understood. One common site of action of anesthetics is inhibitory neurotransmission. This study investigates the effect of propofol on gamma-aminobutyric acid-mediated (GABAergic) and glycinergic neurotransmission to cardiac parasympathetic neurons.

Methods

Cardiac parasympathetic neurons were identified in vitro by the presence of a retrograde fluorescent tracer, and spontaneous GABAergic and glycinergic synaptic currents were examined using whole cell patch clamp techniques.

Results

Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) increased the duration and decay time of spontaneous GABAergic inhibitory postsynaptic currents. To determine whether the action of propofol was at presynaptic or postsynaptic sites, tetrodotoxin was applied to isolate miniature inhibitory postsynaptic currents. Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) prolonged the decay time and duration of miniature inhibitory postsynaptic currents, indicating that propofol directly alters GABAergic neurotransmission at a postsynaptic site. Propofol at high concentrations (> or =50 microm) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 microm had no effect on glycinergic neurotransmission.

Conclusions

Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations (> or =1.0 microm), propofol facilitated GABAergic responses in cardiac vagal neurons by increasing decay time, which would increase inhibition of cardioinhibitory cardiac vagal neurons and evoke an increase in heart rate. At higher supraclinical concentrations (> or =50 microm), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.
Lidocaine Inhibits Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor and Suppresses Proliferation of Corneal Epithelial Cells
Authors: Hirata Masashi , Sakaguchi Masahiro , Mochida Chikako , Sotozono Chie , Kageyama Kyoko , Kuroda Yoshihiro , Hirose Munetaka
Published: April 2004

Background

Although lidocaine is recognized as an excellent topical corneal analgesic, its toxic effect on corneal epithelial cells limits its use during corneal epithelial wound healing. Mechanism of the impairment of corneal reepithelialization with lidocaine, however, has not been evaluated. The authors' previous study revealed that lidocaine inhibits the activity of tyrosine kinase receptors through the interaction with specific amino acid sequences around autophosphorylation sites, including acidic, basic, and aromatic amino acids. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with an important role in epithelial cell proliferation after corneal wounding, also possesses these amino acids sequences around autophosphorylation sites. The authors hypothesized that lidocaine would suppress tyrosine kinase activity of EGFR and would impair corneal epithelial cell proliferation.

Methods

To investigate the effect of lidocaine (4 microM-40 mM) on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR, the authors studied purified EGFR in microtubes. They cultured human corneal epithelial cells (HCECs) with EGF and lidocaine to investigate the effect of lidocaine on cell proliferation and on autophosphorylation of EGFR in HCECs.

Results

Lidocaine (> or =400 microM) significantly suppressed EGF-stimulated autophosphorylation of the purified EGFR. In the HCEC study, EGF alone stimulated cell proliferation and increased autophosphorylation of EGFR in HCECs. Lidocaine (> or = 400 microM) significantly suppressed both the proliferation of HCECs promoted by EGF and EGF-stimulated autophosphorylation of EGFR.

Conclusion

Lidocaine directly inhibits tyrosine kinase activity of EGFR and suppresses the corneal epithelial cell proliferation.
Isoflurane Differentially Modulates Medullary ON and OFF Neurons While Suppressing Hind-limb Motor Withdrawals
Authors: Jinks Steven L. , Carstens Earl , Antognini Joseph F.
Published: April 2004

Background

Isoflurane acts primarily in the spinal cord to block movement; however, it is unclear how supraspinal sites might contribute to anesthetic effects on quantified parameters of movement such as force.

Methods

The authors investigated the effects of isoflurane on spontaneous and noxious heat-evoked activity of nociceptive reflex-modulating ON and OFF cells in the rostral ventromedial medulla of rats. Single ON or OFF neurons were recorded simultaneously with hind-limb withdrawal force elicited by graded noxious thermal hind paw stimulation. Isoflurane concentrations were administered in reference to each animal's minimum alveolar concentration (MAC) of isoflurane.

Results

From 0.65 to 1.15 MAC, isoflurane dose-dependently reduced spontaneous activity of ON cells by 70% (P < 0.001). OFF-cell spontaneous activity was dose-dependently increased 138% (P < 0.001). ON-cell heat-evoked activity was depressed 95% by isoflurane from 0.65 to 1.15 MAC (P < 0.001). Isoflurane-induced changes in ON- and OFF-cell activity paralleled similar reductions in withdrawal force, with the largest change in both neuronal activity and withdrawal force occurring between 0.85 and 1.15 MAC. For the lowest stimulus temperature, excitatory responses of ON cells and inhibitory responses of OFF cells were significantly greater for trials in which withdrawals occurred than for trials in which no withdrawal occurred, suggesting that responses in both classes of neurons were related to movement rather than the stimulus alone.

Conclusions

The results show that isoflurane modulation of ON- and OFF-cell activity corresponds to anesthetic-induced reductions in hind-limb withdrawal force, and therefore, the effects of isoflurane on these classes of neurons in rostral ventromedial medulla might contribute to motor depression.
Ultrasound-guided Lumbar Facet Nerve Block
Authors: Greher Manfred , Scharbert Gisela , Kamolz Lars P. , Beck Harald , Gustorff Burkhard , Kirchmair Lukas , Kapral Stephan
Published: April 2004

Background

Lumbar facet nerve (medial branch) block for pain relief in facet syndrome is currently performed under fluoroscopic or computed tomography scan guidance. In this three-part study, the authors developed a new ultrasound-guided methodology, described the necessary landmarks and views, assessed ultrasound-derived distances, and tested the clinical feasibility.

Methods

(1) A paravertebral cross-axis view and long-axis view were defined under high-resolution ultrasound (15 MHz). Three needles were guided to the target point at L3-L5 in a fresh, nonembalmed cadaver under ultrasound (2-6 MHz) and were subsequently traced by means of dissection. (2) The lumbar regions of 20 volunteers (9 women, 11 men; median age, 36 yr [23-67 yr]; median body mass index, 23 kg/m2 [19-36 kg/m2]) were studied with ultrasound (3.5 MHz) to assess visibility of landmarks and relevant distances at L3-L5 in a total of 240 views. (3) Twenty-eight ultrasound-guided blocks were performed in five patients (two women, three men; median age, 51 yr [31-68 yr]) and controlled under fluoroscopy.

Results

In the cadaver, needle positions were correct as revealed by dissection at all three levels. In the volunteers, ultrasound landmarks were delineated as good in 19 and of sufficient quality in one (body mass index, 36 kg/m2). Skin-target distances increased from L3 to L5, reaching statistical significance (*, **P < 0.05) between these levels on both sides: L3r, 45+/-6 mm*; L4r, 48+/-7 mm; L5r, 50+/-6 mm*; L3l, 44+/-5 mm**; L4l, 47+/-6 mm; L5l, 50+/-6 mm**. In patients, 25 of 28 ultrasound-guided needles were placed accurately, with the remaining three closer than 5 mm to the radiologically defined target point.

Conclusion

Ultrasound guidance seems to be a promising new technique with clinical relevance and the potential to increase practicability while avoiding radiation in lumbar facet nerve block.
Effect of Methylprednisolone on Neuropathic Pain and Spinal Glial Activation in Rats
Authors: Takeda Kenji , Sawamura Shigehito , Sekiyama Hiroshi , Tamai Hisayoshi , Hanaoka Kazuo
Published: April 2004

Background

Basic data are lacking regarding the efficacy and mechanisms of action of corticosteroids in neuropathic pain. Because recent studies indicate that spinal glial activation mediates the pathologic pain states, the authors sought to determine the effects of systemic and intrathecal methylprednisolone on the development and maintenance of neuropathic pain and spinal glial activation in a rat model.

Methods

Rats were anesthetized, and L5 and L6 spinal nerves were tightly ligated. Then, continuous infusion of systemic (4 mg x kg(-1) x day(-1)) or intrathecal (80 microg x kg(-1) x day(-1)) methylprednisolone or saline was started. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively with von Frey and Hargreaves tests, respectively. Spinal astrocytic activation was evaluated with glial fibrillary acidic protein immunoreactivity on day 7. In other groups of rats, continuous 3-day treatment with intrathecal methylprednisolone or saline was started 7 days after spinal nerve ligation, when neuropathic pain had already developed. Behavioral tests and immunostaining were performed up to 3 weeks after the treatment.

Results

Spinal nerve ligation induced mechanical allodynia and thermal hyperalgesia on days 4 and 7 postoperatively. Glial fibrillary acidic protein immunoreactivity was remarkably enhanced on day 7. Both systemic and intrathecal methylprednisolone inhibited the development of neuropathic pain states and glial activation. Three-day treatment with intrathecal methylprednisolone reversed existing neuropathic pain state and glial activation up to 3 weeks after the treatment.

Conclusion

: Systemic and intrathecal methylprednisolone inhibited spinal glial activation and the development and maintenance of a neuropathic pain state in a rat model of spinal nerve ligation.
Spinal Adenosine Receptor Activation Reduces Hypersensitivity after Surgery by a Different Mechanism Than after Nerve Injury
Authors: Obata Hideaki , Li Xinhui , Eisenach James C.
Published: April 2004

Background

Intrathecal adenosine has antinociceptive effects under conditions of hypersensitivity. T62 (2-amino-3-(4-chlorobenzoyl)-5,6,7,8-tetrahydrobenzothiophen) is an allosteric adenosine receptor modulator that enhances adenosine binding to the A1 receptor. Intrathecal T62 reduces hypersensitivity to mechanical stimuli in a rat model of neuropathic pain by a circuit that totally relies on activation of alpha2 adrenoceptors. Here, the authors tested whether this same dependence was present in the acute setting of hypersensitivity after surgery.

Methods

Intrathecal catheters were inserted in male Sprague-Dawley rats. An incision of the plantar aspect of the hind paw resulted 24 h later in hypersensitivity, as measured by applying von Frey filaments to the paw. At this time, rats received intrathecal T62, clonidine, or the combination in a blinded, isobolographic design. The effect of the alpha2-adrenoceptor antagonist idazoxan on T62 was also tested.

Results

Intrathecal T62 produced a dose-dependent antihypersensitivity effect, with no effect on ambulation or activity level. Clonidine also produced a dose-dependent antihypersensitivity effect. The ED40 (95% confidence interval) for T62 was 0.77 (0.63-0.91) microg, and that for clonidine was 1.23 (0.56-1.9) microg. Isobolographic analysis indicated synergism between T62 and clonidine. Intrathecal pretreatment with idazoxan only partially inhibited the antihypersensitivity effect of T62.

Conclusions

Intrathecal T62 is effective for postoperative hypersensitivity. The synergy of T62 with clonidine and its only partial antagonism by idazoxan suggest that T62 does not rely entirely on activation of alpha2 adrenoceptors. These results indicate that, after surgery, T62 acts via a mechanism different from that of spinal nerve ligation, a model of chronic neuropathic pain.
Queuing Theory Accurately Models the Need for Critical Care Resources
Authors: McManus Michael L. , Long Michael C. , Cooper Abbot , Litvak Eugene
Published: April 2004

Background

Allocation of scarce resources presents an increasing challenge to hospital administrators and health policy makers. Intensive care units can present bottlenecks within busy hospitals, but their expansion is costly and difficult to gauge. Although mathematical tools have been suggested for determining the proper number of intensive care beds necessary to serve a given demand, the performance of such models has not been prospectively evaluated over significant periods.

Methods

The authors prospectively collected 2 years' admission, discharge, and turn-away data in a busy, urban intensive care unit. Using queuing theory, they then constructed a mathematical model of patient flow, compared predictions from the model to observed performance of the unit, and explored the sensitivity of the model to changes in unit size.

Results

The queuing model proved to be very accurate, with predicted admission turn-away rates correlating highly with those actually observed (correlation coefficient = 0.89). The model was useful in predicting both monthly responsiveness to changing demand (mean monthly difference between observed and predicted values, 0.4+/-2.3%; range, 0-13%) and the overall 2-yr turn-away rate for the unit (21%vs. 22%). Both in practice and in simulation, turn-away rates increased exponentially when utilization exceeded 80-85%. Sensitivity analysis using the model revealed rapid and severe degradation of system performance with even the small changes in bed availability that might result from sudden staffing shortages or admission of patients with very long stays.

Conclusions

The stochastic nature of patient flow may falsely lead health planners to underestimate resource needs in busy intensive care units. Although the nature of arrivals for intensive care deserves further study, when demand is random, queuing theory provides an accurate means of determining the appropriate supply of beds.
Hemoglobin Einstein: Semisynthetic deletion in the B‐helix of the α‐chain
Authors: Srinivasulu Sonati , Manjula Belur N. , Nagel Ronald L. , Tsai Ching‐Hsuan , Ho Chien , Prabhakaran Muthuchidambaran , Acharya Seetharama A.
Published: April 2004

The influence of the deletion of the tetra peptide segment α23–26 of the B‐helix of the α‐chain of hemoglobin‐A on its assembly, structure, and functional properties has been investigated. The hemoglobin with the deletion, ss‐Hemoglobin‐Einstein, is readily assembled from semisynthetic α1–141 des23–26 globin and human βA‐chain. The deletion of α23–26 modulates the O2 affinity of hemoglobin in a buffer/allosteric effector specific fashion, but has little influence on the Bohr effect. The deletion has no influence on the thermodynamic stability of the α1β1 and the α1β2 interface. The semisynthetic hemoglobin exhibits normal intersubunit interactions at the α1β1 and α1β2 interfaces as reflected by 1H‐NMR spectroscopy. Molecular modeling studies of ss‐Hemoglobin‐Einstein suggest that the segment α28–35 is in a helical conformation, while the segment α19–22 is the nonhelical AB region. The shortened B‐helix conserves the interactions of α1β1 interface. The results demonstrate a high degree of plasticity in the hemoglobin structure that accommodates the deletion of α23–26 without perturbing its overall global conformation.
Urinary fluoride excretion by preschool children in six European countries
Authors: Ketley Clare E. , Cochran Judith A. , Holbrook W. Peter , Sanches Leonor , Van Loveren Cor , Oila Anna‐Maria , O'Mullane Denis M.
Published: April 2004

Abstract ‐ Objective:To measure and compare 24‐h urinary fluoride excretion in children aged 1.5‐3.5 years from European study sites and to use these data to estimate the 24‐h fluoride intake.Method:Twenty‐four‐hour urine samples were collected from 3‐year‐old children (n = 86) who were already participating in a European multicentre study. Samples were collected from Cork, Ireland (n = 19) where the water is fluoridated to a concentration between 0.8 and 1.0 ppm and from five sites with a water fluoride concentration <0.15 ppm: Knowsley, England (n = 18); Oulu, Finland (n = 18); Reykjavik, Iceland (n = 4); Haarlem, the Netherlands (n = 6); Almada/Setubal, Portugal (n = 21). The volume of the samples was measured; they were analysed for fluoride concentration and the 24‐h urinary fluoride excretion was calculated. From this an estimate of the daily fluoride intake was made.Results:It was found that the mean fluoride excretion in response to the usual conditions of fluoride intake in the children in the nonfluoridated areas ranged from 0.16 mg (±0.08) in Oulu to 0.33 mg (±0.27) in Almada/Setubal with an overall mean of 0.23 mg (±0.19). The mean 24‐h fluoride excretion in fluoridated Cork was 0.37 mg (±0.11). There was a significant difference between the fluoride excretion in the nonfluoridated areas and that in the fluoridated areas, and the data were broadly in agreement with WHO standards.Conclusions:The daily urinary fluoride excretion and estimated fluoride intake in these children appeared to be within acceptable limits.
The Hidden Strengths in Family Business: Functional Conflict
Authors: Cosier Richard A. , Harvey Michael
Published: April 2004

Conflict is likely in family businesses. Although some types of conflict are negative and should be minimized, other types are helpful and should be understood and encouraged to improve decisions. Using Jehn's (1997) framework, three types of conflict are identified and related to family business issues. A framework for conflict resolution is presented. Finally, recommendations for introducing and managing positive conflict in family businesses are offered.
Decline of Subpolar North Atlantic Circulation During the 1990s
Authors: Häkkinen Sirpa , Rhines Peter B.
Published: April 2004

Observations of sea surface height reveal that substantial changes have occurred over the past decade in the mid- to high-latitude North Atlantic Ocean. TOPEX/Poseidon altimeter data show that subpolar sea surface height increased during the 1990s, and the geostrophic velocity derived from altimeter data exhibits declining subpolar gyre circulation. Combining the data from earlier satellites, we find that subpolar circulation may have been weaker in the late 1990s than in the late 1970s and 1980s. Direct current-meter observations in the boundary current of the Labrador Sea support the weakening circulation trend of the 1990s and, together with hydrographic data, show that the mid- to late 1990s decline extends deep in the water column. Analysis of the local surface forcing suggests that the 1990s buoyancy forcing has a dynamic effect consistent with altimetric and hydrographic observations: A weak thermohaline forcing allows the decay of the domed structure of subpolar isopycnals and weakening of circulation.
Lipoprotein-Associated Phosphatidylethanol Increases the Plasma Concentration of Vascular Endothelial Growth Factor
Authors: Liisanantti Marja K. , Hannuksela Minna L. , Rämet Maria E. , Savolainen Markku J.
Published: April 2004

Objective—To study whether qualitative changes in high-density lipoprotein (HDL) phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis, we investigated whether phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) from endothelial cells.

Methods and Results—PEth increased the secretion of VEGF into the culture medium of EA.hy 926 endothelial cells. The mitogen-activated protein kinase (MAPK) phosphorylation increased by 3.3-fold and protein kinase C (PKC) by 2.2-fold by PEth-containing HDL. Moreover, we showed that intravenous injection of PEth incorporated into HDL particles increased plasma concentration of VEGF by 2.4-fold in rats in vivo. Similar effect was observed when the rats were injected with HDL particles isolated from alcohol drinkers.

Conclusions—HDL particles containing PEth affect endothelial cells by MAPK and PKC signaling. This may mediate the effects of ethanol on the arterial wall by increasing VEGF secretion from endothelial vascular cells. That may explain, at least in part, the beneficial effect of moderate alcohol consumption on atherosclerosis.
Temperature along the Axillary Nerve during Radiofrequency-Induced Thermal Capsular Shrinkage
Authors: McCarty Eric C. , Warren Russell F. , Deng Xiang-Hu , Craig Edward V. , Potter Hollis
Published: April 2004

Background

There have been reports of axillary nerve palsy after thermal capsular shrinkage with radiofrequency energy-generating devices. The exact cause of this is unknown.

Hypothesis

The temperature of the axillary nerve increases during shoulder capsular shrinkage at various degrees of shoulder abduction.

Study Design

Laboratory study.

Methods

Fifteen cadaveric shoulders had fiberoptic thermometer probes placed at various points along the axillary nerve and major branches under the capsule. The shoulders underwent thermal capsular shrinkage with a radiofrequency energy-inducing device at various positions of abduction.

Results

With the arm at the side, temperatures above 50°C (56°-61°C) were evident along the teres minor branch of the axillary nerve in 4 of 6 specimens. The increase in temperature was noted in the middle to posterior aspect of the inferior capsule. At 45° of abduction, 4 of 5 shoulders demonstrated increases in temperature greater or equal to 50°. Three of 4 shoulders tested at 90° of abduction revealed similar temperature increases.

Conclusions

The arthroscopic technique of thermal capsular shrinkage causes an increase in the temperature of the axillary nerve and its branches in 11 of 15 cadaveric specimens tested at various arm positions—particularly affected is the teres minor branch.

Clinical Relevance

Orthopaedic surgeons using the radiofrequency device for thermal capsular shrinkage need to be aware of the possible increase in temperature along the axillary nerve and its branches during this procedure. The clinical effect of this type of increase on the nerve is unknown.
“All-Inside” Meniscal Repair Devices
Authors: Miller Mark D. , Kline Alex J. , Jepsen Kerry G.
Published: April 2004

Background

Although the use of “all-inside” absorbable meniscal repair devices has become popular, numerous complications have been reported. The authors applied their well-established goat model to evaluate three “all-inside” meniscal repair devices.

Methods

A “tear” was created in the medial meniscus of both knees in 26 goats. The animals were randomized into four groups, and the meniscus was treated as follows: (A) meniscal repair with Mitek Fastner, (B) meniscal repair with BioStinger, (C) meniscal repair with Mitek Clearfix Screw, and (D) no repair. All animals were sacrificed at 6 months postoperatively, and all specimens were carefully evaluated and results recorded and compared with historical results of meniscal repair with suture in this same animal model.

Results

Meniscal repair results with all three all-inside devices studied were inferior to suture repair. Chondral injury was present in 75% to 100% of repairs with all-inside devices and none of the control specimens.

Discussion/Conclusion

Although new all-inside meniscal repair devices are relatively quick and easy, results may not be as good as with traditional suture techniques. The high rate of chondral injury associated with these devices in the goat model is worrisome for chondral damage in humans, especially in patients with smaller or tighter knees.
Initial Fixation Strength of Flexible All-Inside Meniscus Suture Anchors in Comparison to Conventional Suture Technique and Rigid Anchors
Authors: Zantop Thore , Eggers Ann Katleen , Weimann Andre , Hassenpflug Joachim , Petersen Wolf
Published: April 2004

Background

The newest generation of meniscus repair devices is designed to combine the benefits of the all-inside technique with the biomechanical properties of sutures.

Hypothesis

New flexible all-inside suture anchors have better fixation strength than rigid anchors, but there is no difference when compared to conventional horizontal and vertical mattress sutures.

Study Design

Controlled laboratory study.

Methods

In fresh-frozen bovine menisci, initial fixation strength, stiffness, and failure mode of different meniscus fixation techniques (FastT-Fix, RapidLoc, Meniscus Arrow, horizontal and vertical 2.0 Ethibond sutures) were evaluated in a computer-based materials testing machine at a rate of 12.5 mm/sec.

Results

The vertical and horizontal FastT-Fix suture anchors were the strongest devices with regard to pullout strength, with no significant difference compared to the vertical 2-0 Ethibond sutures. Horizontal sutures, Meniscus Arrow, and RapidLoc had significantly lower pullout strength. Vertical and horizontal FastT-Fix suture anchors showed significantly higher stiffness than the other devices.

Conclusions

Biomechanical properties of flexible all-inside meniscus anchors (FastT-Fix) are comparable to conventional vertical suture techniques. Characteristics of the flexible RapidLoc are comparable to rigid anchors (Meniscus Arrow).

Clinical Relevance

From the biomechanical point of view, flexible all-inside meniscus refixation devices are an alternative to conventional suture techniques and rigid meniscus anchors.
The Effect of Growth Factors on Biomechanical Properties of the Bone-Patellar Tendon-Bone Graft after Anterior Cruciate Ligament Reconstruction
Authors: Yasuda Kazunori , Tomita Fumihisa , Yamazaki Shuji , Minami Akio , Tohyama Harukazu
Published: April 2004

Background

No studies have dealt with the effect of growth factors on the free tendon autograft in anterior cruciate ligament reconstruction.

Hypothesis

Application of exogenous transforming growth factor-β and epidermal growth factor may affect the structural properties and histology of the bone-patellar tendon-bone autograft after anterior cruciate ligament reconstruction.

Study Design

Controlled laboratory study.

Methods

Twenty dogs underwent anterior cruciate ligament reconstruction with the autogenous bone-patellar tendon-bone graft in bilateral knees. In 10 animals, 12 ng transforming growth factor-β and 300 ng epidermal growth factor mixed with fibrin sealant of 0.6 mL were applied to the left knee. In the remaining 10 dogs, fibrin sealant alone was applied to the left knee. No additional treatments were applied to the right knee.

Results

The growth factor application increased the stiffness and maximum failure load of the femur-graft-tibia complex at 12 weeks (P = .016 and P = .012, respectively); the sham treatment did not significantly affect them. Histologically, most of the cells in the grafts treated with growth factors had spindle-shaped nuclei; cells in the other grafts had round-shaped nuclei.

Conclusions

Application of transforming growth factor-β and epidermal growth factor improves the structural properties of the autograft after anterior cruciate ligament reconstruction in the canine model.

Clinical Relevance

Application of growth factors is a possible strategy to prevent graft deterioration in anterior cruciate ligament reconstruction.
Contact Pressure at Osteochondral Donor Sites in the Patellofemoral Joint
Authors: Garretson Ralph B. , Katolik Leonid I. , Verma Nikhil , Beck Paul R. , Bach Bernard R. , Cole Brian J.
Published: April 2004

Background

The lowest contact pressure point is presumed to be the best site to harvest an osteochondral plug and minimize morbidity.

Hypothesis

Patellofemoral contact pressures are not uniform and are lowest along the medial patellofemoral articulation.

Study Design

Controlled laboratory study.

Methods

Seven cadaveric knees were tested with an electroresistive, dynamic pressure sensor placed onto the femoral side of the patellofemoral joint. The extensor mechanism was loaded with 89.1 N and 178.2 N, and the knee was manually cycled 3 times (0°-105°) per load. Mean trochlear pressures were calculated.

Results

Mean contact pressures were greatest in the central trochlea (5.80 kgf/cm2), followed by the lateral (2.56 kgf/cm2) and medial trochlea (1.60 kgf/cm2) at 89.1 N (P < .05). At 178.2 N, pressures increased to 9.47, 5.81, and 2.75 kgf/cm2, respectively (P < .05). Lateral trochlear pressures decreased moving distally from 1.25 to 0.50 kgf/cm2 at 89.1 N and 4.57 to 1.29 kgf/cm2 at 178.2 N.

Conclusions

Contact pressures are lowest along the medial trochlea and decrease distally along the lateral trochlea.

Clinical Relevance

Osteochondral plugs from the medial femoral trochlea may be desirable if trochlear size permits. If harvesting from the lateral femoral trochlea, consider harvesting distally near the sulcus terminalis.
Abnormal Rotational Knee Motion during Running after Anterior Cruciate Ligament Reconstruction
Authors: Tashman Scott , Collon David , Anderson Kyle , Kolowich Patricia , Anderst William
Published: April 2004

Background

The effectiveness of anterior cruciate ligament reconstruction for restoring normal knee kinematics is largely unknown, particularly during sports movements generating large, rapidly applied forces.

Hypothesis

Under dynamic in vivo loading, significant differences in 3-dimensional kinematics exist between anterior cruciate ligament-reconstructed knees and the contralateral, uninjured knees.

Study Design

Prospective, in vivo laboratory study.

Methods

Kinematics of anterior cruciate ligament-reconstructed and contralateral (uninjured) knees were evaluated for 6 subjects during downhill running 4 to 12 months after anterior cruciate ligament reconstruction, using a 250 frame/s stereoradiographic system. Anatomical reference axes were determined from computed tomography scans. Kinematic differences between the uninjured and reconstructed limbs were evaluated with a repeated-measures analysis of variance.

Results

Anterior tibial translation was similar for the reconstructed and uninjured limbs. However, reconstructed knees were more externally rotated on average by 3.8 ± 2.3° across all subjects and time points (P = .0011). Reconstructed knees were also more adducted, by an average of 2.8 ± 1.6° (P = .0091). Although differences were small, they were consistent in all subjects.

Conclusions

Anterior cruciate ligament reconstruction failed to restore normal rotational knee kinematics during dynamic loading.

Clinical Relevance

Although further study is required, these abnormal motions may contribute to long-term joint degeneration associated with anterior cruciate ligament injury/reconstruction.
The Influence of Locally Applied Platelet-Derived Growth Factor-BB on Free Tendon Graft Remodeling after Anterior Cruciate Ligament Reconstruction
Authors: Weiler Andreas , Förster Cornelius , Hunt Patrick , Falk Roman , Jung Tobias , Unterhauser Frank N. , Bergmann Volker , Schmidmaier Gerhard , Haas Norbert P.
Published: April 2004

Background

Ligaments and tendons do not gain mechanical properties of the native tissue after injury or grafting.

Purpose

To determine the influence of platelet-derived growth factor on tendon graft remodeling.

Study Design

Laboratory animal study.

Methods

Forty-eight sheep underwent anterior cruciate ligament reconstruction and were sacrificed after 3, 6, 12, and 24 weeks. In 6 animals at each time point, platelet-derived growth factor was locally delivered via coated sutures. After mechanical testing, tissue samples were taken for histologic, immunohistochemical, and electron microscopy evaluations.

Results

With platelet-derived growth factor treatment, cross-sectional area was significantly lower at 3 and 12 weeks. Load to failure was significantly higher at 6 weeks. Tensile stress was significantly higher at 3 and 12 weeks. Crimp length was significantly higher at 3 and 6 weeks. Vascular density was significantly higher at 6 weeks. Electron microscopy showed a significantly higher collagen fibril amount at 12 weeks. Differences in these parameters at other time points were not significant.

Conclusions

There were alterations in several but not all time points. The local application of platelet-derived growth factor alters the tissue's mechanical properties during free tendon graft remodeling after anterior cruciate ligament reconstruction. Growth factors present a promising tool toward the complete mechanical restitution of a healing ligament substitute.
Injury Mechanisms for Anterior Cruciate Ligament Injuries in Team Handball
Authors: Olsen Odd-Egil , Myklebust Grethe , Engebretsen Lars , Bahr Roald
Published: April 2004

Objective

To describe the mechanisms for anterior cruciate ligament injuries in female team handball.

Study Design

Descriptive video analysis.

Methods

Twenty videotapes of anterior cruciate ligament injuries from Norwegian or international competition were collected from 12 seasons (1988-2000). Three medical doctors and 3 national team coaches systematically analyzed these videos to describe the injury mechanisms and playing situations. In addition, 32 anterior cruciate ligament-injured players in the 3 upper divisions in Norwegian team handball were interviewed during the 1998-1999 season to compare the injury characteristics between player recall and the video analysis.

Results

Two main injury mechanisms for anterior cruciate ligament injuries in team handball were identified. The most common (12 of 20 injuries), a plant-and-cut movement, occurred in every case with a forceful valgus and external or internal rotation with the knee close to full extension. The other main injury mechanism (4 of 20 injuries), a 1-legged jump shot landing, occurred with a forceful valgus and external rotation with the knee close to full extension. The results from the video analysis and questionnaire data were similar.

Conclusions

The injury mechanism for anterior cruciate ligament injuries in female team handball appeared to be a forceful valgus collapse with the knee close to full extension combined with external or internal rotation of the tibia.
The Effect of Length on the Structural Properties of an Achilles Tendon Graft as Used in Posterior Cruciate Ligament Reconstruction
Authors: DeFrate Louis E. , van der Ven Alexander , Gill Thomas J. , Li Guoan
Published: April 2004

Background

The clinical outcomes of posterior cruciate ligament reconstruction are varied. No previous studies have investigated the effect of graft length on the structural properties of the graft.

Hypothesis

Graft length significantly affects the structural properties of posterior cruciate ligament grafts.

Study Design

Controlled laboratory study.

Methods

Eight Achilles tendon grafts were tested under tensile loads up to 400 N at 3 different lengths: long (75 mm), medium (48 mm), and short (34 mm). These 3 lengths represent midtunnel fixation, inlay fixation, and fixation near the ligament insertions.

Results

Shortening the graft from both long to medium and from medium to short increased the stiffness by approximately 25%. Long and medium grafts displaced significantly more than medium and short grafts, respectively.

Conclusion

The effective length of a graft, which is determined by where it is fixed, should be considered an important variable in posterior cruciate ligament reconstruction.
Reflexive Muscle Activation Alterations in Shoulders with Anterior Glenohumeral Instability
Authors: Myers Joseph B. , Ju Yan-Ying , Hwang Ji-Hye , McMahon Patrick J. , Rodosky Mark W. , Lephart Scott M.
Published: April 2004

Background

Patients with glenohumeral instability have proprioceptive deficits that are suggested to contribute to muscle activation alterations.

Hypothesis

Muscle activation alterations will be present in shoulders with anterior glenohumeral instability.

Study Design

Posttest-only control group design.

Methods

Eleven patients diagnosed with anterior glenohumeral instability were matched with 11 control subjects. Each subject received an external humeral rotation apprehension perturbation while reflexive muscle activation characteristics were measured with indwelling electromyography and surface electromyography.

Results

Patients with instability demonstrated suppressed pectoralis major and biceps brachii mean activation; increased peak activation of the subscapularis, supraspinatus, and infraspinatus; and a significantly slower biceps brachii reflex latency. Supraspinatus-subscapularis coactivation was significantly suppressed in the patients with instability as well.

Conclusions and Clinical Relevance

In addition to the capsuloligamentous deficiency and proprioceptive deficits present in anterior glenohumeral instability, muscle activation alterations are also present. The suppressed rotator cuff coactivation, slower biceps brachii activation, and decreased pectoralis major and biceps brachii mean activation may contribute to the recurrent instability episodes seen in this patient group. Clinicians can implement therapeutic exercises that address the suppressed muscles in patients opting for conservative management or rehabilitation before and after capsulorraphy procedures.