Osteoinduction of biphasic calcium phosphate scaffolds in a nude mouse model.

Bioceramics combined with isolated stem cells, or with total bone marrow, constitute the main strategies under consideration in the field of bone tissue engineering. In the present preclinical study, two biphasic calcium phosphate scaffolds currently on the market, MBCP® and MBCP+®, with different hydroxyapatite/ß-tricalcium phosphate ratio, were implanted ectopically in a nude mouse model. These scaffolds were supplemented either with human mesenchymal stromal cells, or with human total bone marrow, or rat total bone marrow. Biomaterials alone were found to have potentially low, but non-zero, osteoinductive properties, while biomaterials associated with total bone marrow consistently improved osteoinduction in comparison with high concentrations of isolated human stromal cells.

Sexual morbidity following radical hysterectomy for cervical cancer.

Radical hysterectomy for early stage cervical cancer has satisfactory results in terms of survival, but may impact negatively on a patient's quality of life, which may include sexual dysfunctions. Female sexual dysfunctions (FSD) represent a frequent morbidity but often remain unrecognized and undertreated. Although discussions regarding sexuality are found by many medical doctors to be sensitive and embarrassing, psychosexual counseling is an essential component of comprehensive care for gynecological cancer patients and their partners. The goal of this article is to summarize and discuss available relevant data on FSD in women who have undergone radical hysterectomy for an early stage of cervical cancer.

To move or not to move: imperatives modulate action-related verb processing in the motor system.

It has been suggested that the processing of action-related words involves activation of the motor circuitry. Using fMRI (functional magnetic resonance imaging), the current study further explored the interaction between action and language by investigating whether the linguistic context, in which an action word occurs, modulates motor circuitry activity related to the processing of action words. To this end, we examined whether the presentation of hand action-related verbs as positive or negative imperatives, for example, "Do grasp" or "Don't write," modulates neural activity in the hand area of primary motor cortex (M1) or premotor cortex (Pm). Subjects (n = 19) were asked to read silently the imperative phrases, in which both meaningful action verbs and meaningless pseudo-verbs were presented, and to decide whether they made sense (lexical decision task). At the behavioral level, response times in the lexical decision task were significantly longer for negative, compared to positive, imperatives. At the neural level, activity was differentially decreased by action verbs presented as negative imperatives for the premotor and the primary motor cortex of both hemispheres. The data suggest that context (here: positive vs. negative imperatives), in which an action verb is encountered, modulates the neural activity within key areas of the motor system. The finding implies that motor simulation (or motor planning) rather than semantic processing per se may underlie previously observed motor system activation related to action verb processing. Furthermore, the current data suggest that negative imperatives may inhibit motor simulation or motor planning processes.

Task instructions influence the cognitive strategies involved in line bisection judgements: evidence from modulated neural mechanisms revealed by fMRI.

Manual line bisection and a perceptual variant thereof (the Landmark test) are widely used to assess visuospatial neglect in neurological patients, but little is known about the cognitive strategies involved. In the Landmark test, one could explicitly compare the lengths of the left and right line segments; alternatively, one could compute the centre of mass of the display. We here investigate with functional MRI if these cognitive strategies modulate the neural mechanisms underlying judgements whether pre-transected horizontal lines are correctly bisected (the Landmark test) in normal volunteers. Functional neuroimaging (fMRI) was carried out in 12 healthy volunteers who judged: (a) whether the line segments on either side of the transection mark were of equal length, and (b) whether the transection mark was in the centre of the line. Line centre judgements were made significantly faster than line length comparisons. Increased neural activity common to both strategies was observed in inferior parietal lobes bilaterally and right temporooccipital cortex. Further activations, most likely reflecting general task demands like response selection and motor control, were found in the precentral gyrus bilaterally, supplementary motor area bilaterally, right anterior cingulate, right dorsolateral prefrontal cortex, cerebellar vermis, and right thalamus and right putamen. Explicit length comparisons (relative to line centre judgements) differentially activated left superior posterior parietal cortex, with a tendency toward activation of the equivalent area on the right, while the reverse comparison revealed differential activation in the lingual gyrus bilaterally and anterior cingulate cortex. The activations observed in inferior parietal cortex during task performance using either strategy are consistent with the results of lesion studies. The differential activation of superior posterior parietal cortex following length instructions suggests that explicit comparisons of spatial extent were implicated. The differential activation of bilateral occipital cortex following centre judgements suggests that the centre of a line is extracted at an early stage of visual processing.

Reversible cerebral ischemia in patients with pheochromocytoma.

Cerebral ischemia and symptoms of stroke can occur as a rare manifestation in patients with pheochromocytoma. We describe a 45-year-old woman who was admitted because of a right-sided hemiparesis due to an ischemic lesion in the left hypothalamus. The clinical diagnosis of a pheochromocytoma was proven by highly elevated urinary catecholamines and confirmed histologically after operation. The successful removal of the tumor led to the almost complete recovery of the neurological deficiencies. It is of vital importance to know this atypical presentation of pheochromocytoma. The diagnosis of pheochromocytoma should be suspected in patients with focal cerebral symptoms, particularly in the presence of intermittent hypertension or other paroxysmal symptoms suggestive of pheochromocytoma.

Course of maternal serum magnesium levels in low-risk gestations and in preterm labor and delivery.

OBJECTIVES: To describe the course of total and ionized magnesium and total calcium levels in maternal serum during low-risk pregnancies and to compare women who developed preterm labor and delivery with those who delivered at term. METHODS: 209 women with low-risk pregnancies were enrolled in a prospective trial before the 18th week of gestation. No woman received oral magnesium supplementation. The ionized and total magnesium and total calcium levels in maternal serum were measured every 4-6 weeks. The data were grouped into 3 gestational periods (/=28 weeks of gestation) for overall comparison and analyzed with the general linear model for repeated measurements and ANOVA. p values of < 0.05 were considered statistically significant. RESULTS: 145 gestations were available for analysis. 27 women were hospitalized for preterm labor and in 16 of these preterm delivery occurred. Ionized and total magnesium and calcium levels were significantly lower after the 18th week of gestation than before. The cation levels in women with preterm labor and delivery did not differ from those with term delivery. CONCLUSION: Ionized and total magnesium and calcium levels decrease with increasing gestational age. Preterm labor and delivery do not seem to be related to changes in serum cation levels.

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease.

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1+/-14.8 to 23.9+/-11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n=6), 9 months (n=6), and 12 months (n=4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for "off" symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.

Application of FT-IR microspectroscopy to the study of an injectable composite for bone and dental surgery.

Hydroxypropylmethylcellulose (HPMC) of high-viscosity grade is used as a ligand for a bioactive calcium phosphate ceramic (the filler) in a ready-to-use injectable sterilized biomaterial for bone and dental surgery. Application of physico-chemical methods such as XPS, NMR, or Raman spectroscopy encounters difficulties when used to study such a multiphased material. This paper reports on the application of FT-IR microspectroscopy (FT-IRM) for the investigation of inorganic and organic phases of the rough composite and separated phases obtained by mechanical or chemical extraction methods. A comparison of FT-IRM with the conventional KBr pellet method was made and indicates that the macro and micro FT-IR methods are complementary: the former revealed new chemical groups not visualized with the KBr method whereas the latter detected the major compound of the blend. FT-IR microspectroscopy was revealed to be a powerful method of analysis that is complementary to other existing spectroscopic methods. Moreover, it is expected to be a useful tool in the study of biomaterials in biological samples.

Motor impairment in Wilson's disease. 3: The clinical impact of pyramidal tract involvement.

Magnetic brain stimulation was performed on 24 patients with Wilson's disease (WD). Responses to the right and left first dorsal interosseus muscle (FDI) and to the right and left tibialis anterior muscle (TA) were analysed. In 45% of the patients prolonged central motor conduction times (CCTs) to the FDIs were found, whereas only 12% of the patients presented with prolonged CCTs to the TA muscles. No consistent significant correlations between copper metabolism and pyramidal tract function tested by magnetic brain stimulation were found. An improvement of CCTs and response amplitudes with copper elimination therapy was observed only at early phases of therapy. There was no correlation with duration of therapy or neurological symptoms. Thus magnetic brain stimulation turns out to be sensitive to detect subclinical pyramidal tract impairment in WD but seems to test a too specific aspect of motor impairment in WD to reflect the overall neurological status of the patients. Therefore, it has to be combined with other tests to be used for therapy control.

Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity.

We have examined cytokine regulation of nitric oxide synthase (NOS) in human umbilical vein endothelial cells (HUVEC). 24-h treatment with IFN-gamma (200 U/ml) plus TNF (200 U/ml) or IL-1 beta (5 U/ml) increased NOS activity in HUVEC lysates, measured as conversion of [14C]L-arginine to [14C]L-citrulline. Essentially, all NOS activity in these cells was calcium dependent and membrane associated. Histamine-induced nitric oxide release, measured by chemiluminescence, was greater in cytokine-treated cells than in control cells. Paradoxically, steady-state mRNA levels of endothelial NOS fell by 94 +/- 2.0% after cytokine treatment. Supplementation of HUVEC lysates with exogenous tetrahydrobiopterin (3 microM) greatly increased total NOS activity, and under these assay conditions, cytokine treatment decreased maximal NOS activity. IFN-gamma plus TNF or IL-1 beta increased endogenous tetrahydrobiopterin levels and GTP cyclohydrolase I activity, the rate-limiting enzyme of tetrahydrobiopterin synthesis. Intracellular tetrahydrobiopterin levels were higher in freshly isolated HUVEC than in cultured cells, but were still limiting. We conclude that inflammatory cytokines increase NOS activity in cultured human endothelial cells by increasing tetrahydrobiopterin levels in the face of falling total enzyme; similar regulation appears possible in vivo.

Transition-state structures for enzymatic and alkaline phosphotriester hydrolysis.

The primary and secondary 18O isotope effects for the alkaline (KOH) and enzymatic (phosphotriesterase) hydrolysis of two phosphotriesters, O,O-diethyl p-nitrophenyl phosphate (I) and O,O-diethyl O-(4-carbamoylphenyl) phosphate (II), are consistent with an associative mechanism with significant changes in bond order to both the phosphoryl and phenolic leaving group oxygens in the transition state. The synthesis of [15N, phosphoryl-18O]-, [15N, phenolic-18O]-, and [15N]-O,O-diethyl p-nitrophenyl phosphate and O,O-diethyl O-(4-carbamoylphenyl)phosphate is described. The primary and secondary 18O isotope effects for the alkaline hydrolysis of compound I are 1.0060 and 1.0063 +/- 0.0001, whereas for compound II they are 1.027 +/- 0.002 and 1.025 +/- 0.002, respectively. These isotope effects are consistent with the rate-limiting addition of hydroxide and provide evidence for a SN2-like transition state with the absence of a stable phosphorane intermediate. For the enzymatic hydrolysis of compound I, the primary and secondary 18O isotope effects are very small, 1.0020 and 1.0021 +/- 0.0004, respectively, and indicate that the chemical step in the enzymatic mechanism is not rate-limiting. The 18O isotope effects for the enzymatic hydrolysis of compound II are 1.036 +/- 0.001 and 1.0181 +/- 0.0007, respectively, and are comparable in magnitude to the isotope effects for alkaline hydrolysis, suggesting that the chemical step is rate-limiting. The relative magnitude of the primary 18O isotope effects for the alkaline and enzymatic hydrolysis of compound II reflect a transition state that is more progressed for the enzymatic reaction.

[Programmed autologous transfusion in coronary surgery: experience with 106 patients]. / Transfusion autologue programmée en chirurgie coronarienne: expérience sur 106 patients.

Patients undergoing elective coronary bypass surgery can benefit from Preoperative Autologous Blood Donation (PAB), despite some opinions to the contrary, as a complement of intra-operative blood salvage techniques. We report herein 106 patients eligible for coronary bypass surgery included in our PAB program. We observed a very good tolerance owing to strict exclusion criteria, a close monitoring of vital signs, and as far as we are concerned, to the infusion of a macromolecular solution (Plasmion) in a 1:1 ratio, to maintain intra-vascular volume. We chose a volume replacement because the physiological adaptation to hypovolemia is altered by the beta-blocking and/or vasodilating agents which cannot be discontinued in patients with coronary heart disease. The changes in the hematological parameters are not different from those observed in other patients eligible for PAB. The postoperative hemoglobin level is satisfactory and compatible with a normal myocardial function inasmuch as the cardiopathy has been corrected. The efficiency of PAB is good since overall, 74% of the patients did not require homologous blood, this proportion rises to 84% for patients donating 3 or more units. Preoperative Autologous Blood Donation for patients with coronary heart disease implies a perfect coordination between the Blood Bank physicians and their colleagues from the Cardiology Department. Aside from its well known advantages, PAB allows a stimulation of erythropoiesis, a progressive normovolemic hemodilution perhaps beneficial to patients with coronary heart disease, and finally, a better psychological preparation to surgery.

Interindividual comparability of blood glucose alterations after meals of complex carbohydrates.

Young male and female probands underwent an DGTT (oral glucose tolerance test) using a glucose load of 1 g/kg b.wt. The alterations in blood glucose levels were checked and plotted by a Biostator. A week later groups of those probands were fed an isocaloric meal of complex CH, namely either potatoes, noodles or white bread. The resulting BG curves were also checked by a Biostator. It turned out that: 1. the shapes of the BG curves after glucose load were not interindividually comparable. 2. there was neither a similarity of the shapes of the BG curves within the groups after any of the different CH levels. 3. But if one compares the shape of the BG curves after glucose load and after a meal of any of the complex CH of one and the same person, there is a striking similarity in those curve shapes. The differences between them lie just in the mostly lower BG values of the curves after CH meals compared with those after glucose load. 4. Therefore the resulting graph of both of those curves is in all observed cases a straight line with a probability better than 0.001, called OGTT-calibrating resulting graph.

Decline of proteins C and S and factors II, VII, IX and X during the initiation of warfarin therapy.

Oral anticoagulants achieve an antithrombotic effect only several days after initiation of treatment. A rapid decline of the vitamin-K dependent natural anticoagulants (proteins C and S) during this period might result in a prothrombic phase. We addressed this question by measuring the rates of decline of these proteins, as well as the vitamin K dependent procoagulants, in two groups of patients: A "high dose group" (n = 7), who received a single 40 mg dose of warfarin, and a "low dose group" (n = 20), who received daily individually adjusted doses. In the high dose group an early and marked decline of factor VII:C and protein C antigen was observed, while levels of the other vitamin K dependent factors were still relatively high. In the low dose group, all these proteins declined more gradually. Mean +/- SD of protein C antigen level at 46 hr was 56 +/- 12% in the low dose group, and only 44 +/- 6% (p less than 0.05) in the high dose group. We conclude that during the initiation of warfarin therapy there is a transient prothrombotic phase, which is less marked in patients given daily adjusted doses.

Diazepam and fentanyl as adjuncts to local anesthesia.

A method is presented for supplementing local anesthesia with intravenous diazepam and fentanyl. Ease of administration and high patient acceptance in over 1500 cases is discussed.