[Responsibility due to medication errors in France: a study based on SHAM insurance data]. / Responsabilité liée aux erreurs médicamenteuses : données SHAM.

PURPOSE: The safe medication practices at the hospital constitute a major public health problem. Drug supply chain is a complex process, potentially source of errors and damages for the patient. SHAM insurances are the biggest French provider of medical liability insurances and a relevant source of data on the health care complications. METHODS: The main objective of the study was to analyze the type and cause of medication errors declared to SHAM and having led to a conviction by a court. We did a retrospective study on insurance claims provided by SHAM insurances with a medication error and leading to a condemnation over a 6-year period (between 2005 and 2010). RESULTS: Thirty-one cases were analysed, 21 for scheduled activity and 10 for emergency activity. Consequences of claims were mostly serious (12 deaths, 14 serious complications, 5 simple complications). The types of medication errors were a drug monitoring error (11 cases), an administration error (5 cases), an overdose (6 cases), an allergy (4 cases), a contraindication (3 cases) and an omission (2 cases). Intravenous route of administration was involved in 19 of 31 cases (61%). The causes identified by the court expert were an error related to service organization (11), an error related to medical practice (11) or nursing practice (13). Only one claim was due to the hospital pharmacy. CONCLUSION: The claim related to drug supply chain is infrequent but potentially serious. These data should help strengthen quality approach in risk management.

Vaginal Removal of Very Large Nascent Uterine Myoma - Case Report and Literature Review.

This report shows that even extremely large nascent uterine myomas can be removed vaginally. A 25-year-old nulligravid and nulliparous patient with malaise, hypermenorrhea, and intermittent cramping pain in the lower abdomen was referred to our clinic. Gynecological examination revealed a round cauliflower-like tumor, 7 cm in diameter, originating from the external cervical os with a rough surface and without a palpable stalk or base. Ultrasound scan showed a hyperechogenic mass within the uterine cavity with two distinct subunits: one (55 × 44 mm) well-demarcated from the surrounding structures and the other (43 × 38 mm) in close proximity to the lower part of the anterior uterine wall and in continuity with the myometrium. At surgery, the myoma was completely removed vaginally. Recovery was prompt, complete, and uneventful. Follow-up at one and three months confirmed normal gynecological and sonographic findings. In conclusion, vaginal myomectomy is the treatment of choice for prolapsed pedunculated submucous myoma; even extremely large nascent myomas can be efficiently removed vaginally.

Amount of airflow required for olfactory perception in laryngectomees: a prospective interventional study.

OBJECTIVES: To determine minimum airflow rate required for olfactory stimulation in successfully rehabilitated laryngectomised patients after learning the polite yawning technique (PYT) and to confirm the hypothesis that sense of smell is rehabilitated once the nasal airflow is re-established. DESIGN: Prospective open interventional trial. SETTING: Tertiary academic hospital. PARTICIPANTS: The study population comprised 100 laryngectomised patients. The control group consisted of 100 non-laryngectomised patients of similar age and sex. Rhinomanometry was used to measure air flow in the right and left nostrils, respectively, while the Smell Diskettes Olfaction test (SDOT) was used to test each individual's sense of smell. MAIN OUTCOME MEASURES: The primary endpoint was increasing the airflow, while the secondary endpoint was improvement in the Smell Diskettes Olfaction test score after learning the polite yawning technique. RESULTS: The difference in the Smell Diskettes Olfaction test results before and after introducing the polite yawning technique was statistically significant (F = 53.077; P < 0.001). The number of accurately identified odours increased with each measurement. There was a significant difference among rhinomanometric measurements of airflow through the right (F = 65.002; P < 0.001) and left nostrils (F = 75.465; P < 0.001). Nasal airflow improved with each measurement. The minimum airflow required for olfactory stimulation in successfully rehabilitated patients was approximately 60 cm(3) /s. The control group had considerably better airflow in both nostrils than the laryngectomised group. The difference between the total number of rehabilitated (normosmic) patients (48%) in the laringectomised group and normosmic participants (56%) in the control group (z = 1.132; P = 0.129) was not statistically significant. CONCLUSION: The number of odours identified by laryngectomised patients increased with the volume of nasal airflow. The number of patients with rehabilitated olfactory function approximated the percentage of normosmic individuals in the non-laryngectomised population. These findings confirm the hypothesis that sense of smell is rehabilitated once the nasal airflow is re-established.

Impact of Phytoestrogens on Serum Lipids in Postmenopausal Women.

Objectives: The aim of the study was to assess the impact of soy- and red clover-derived isoflavones on serum lipid levels in postmenopausal women and to compare the effects to the lipid levels of healthy postmenopausal women without phytoestrogen supplementation. Materials and Methods: Blood levels of triglycerides, total cholesterol and cholesterol fractions were assessed. Measurements were performed before treatment and at 6-month intervals over a period of 18 months. The investigation included 74 healthy postmenopausal women randomized into three groups according to treatment. The first group of 23 patients received soy-derived isoflavones, the second group (26 patients) was given red clover-derived phytoestrogens, while the third control group (25 patients) received no supplements. Results: Mean triglyceride, cholesterol and LDL levels of patients in the control group were significantly higher than in both the soy and the red clover groups (p < 0.001) at all three time points, while mean values did not differ significantly between the soy and the red clover groups. The mean HDL levels of patients in the control group was significantly lower than in both the soy and the red clover groups (p < 0.001). Conclusions: Phytoestrogen supplementation had a positive metabolic effect on serum lipid levels in postmenopausal women. The impact on serum lipids levels was similar for soy and red clover.

Laparoscopic management of consecutive ovarian pregnancy in a patient with infertility.

The diagnosis of ovarian pregnancy is based on the improper rise of serum beta-hCG levels, sonographic findings of an empty uterus, highly characteristic ovarian formation with double hyperechogenic ring surrounding small hypoechogenic field, and the laparoscopic verification of Spiegelberg's criteria. We present a case of ovarian pregnancy in spontaneous cycle in 34-year-old woman following two unsuccessful IVF/ET procedures and ovarian pregnancy on contralateral side laparoscopically treated seven months ago, also achieved in non-stimulated, spontaneous cycle. On admission she had a serum hCG level of 596 mIU/mL on cycle day 46 and an empty uterus. Transvaginal sonography showed a 20 mm ring-like thick-walled hyperechogenic structure within the left ovary. The echogenic ring was surrounded by irregular, hypoechogenic structures suggestive of an ovarian pregnancy with periluteal hemorrhage and blood clots. The ruptured cystic ovarian pregnancy and the corpus luteum were removed by laparoscopy. During the procedure we have seen two clips on the right ovary placed laparoscopically to achieve hemostasis after rupture of the ovarian pregnancy seven months ago. Histopathology showed isolated chorionic villi within hemorrhagic areas in the vicinity of the corpus luteum.

Temperature-dependent conformation change in spin-labeled hemoglobin.

Hemoglobin was spin labeled at beta-93(F9)-cysteine with N-oxyl-2,2,6,6-tetramethylpiperidinylmaleimide. The inward shift of the high-field hyperfine line (delta Hx) position in the ESR spectra of the spin label was measured as a function of temperature. One can except that an abrupt change in the microenvironment around the tightly bound spin label will be reflected in the function delta Hx(T) as a discontinuity (break point). This was shown for aquo-, azido-, nitro- and oxyhemoglobin derivatives. The presented results suggest that the microenvironment around the tightly bound spin label in those methemoglobin derivatives that exhibit the mixed-spin state of the heme iron is prone to an abrupt change above a certain ligand-specific temperature. The change in microenvironment of the spin label is probably due to a temperature-dependent change in the teritary structure of the protein.

Comparison of microsomal and solubilized monooxygenases from rat and rabbit by proton magnetic relaxation.

The paper presents results of a comparative study of the haem environment, by proton magnetic relaxation, in P-450 and P-448 monooxygenases from rat and rabbit, induced by phenobarbital and 3-methylcholanthrene, in both species. It was established that the method yields information on the accessibility of the haem iron for solvent molecules (protons), both in microsomes and in solubilized samples of various degrees of purification, i.e. association. The state of micelles in the solutions does not alter the haem iron accessibility. A slight difference was found for the microsomes suspended in a phosphate vs. pyrophosphate buffer, but this is without any consequence with regard to the species and form differences. The correlation time for the highly purified LM2 fraction of rabbit P-450 could not be determined more precisely than before for a sample of lower purity, because the relaxation rates are frequency independent. The correlation time for the rat P-448 monooxygenase was determined by dispersion measurements to be (4.1 +/- 0.4) x 10(-11) s. It was found that the PMRx behaviours of rabbit and rat monooxygenases are more alike in microsomes than in the partially purified solubilized form. The solubilization produces a pronounced alteration of the PMRx temperature dependence only for the rat 3-MC induced monooxygenase P-448. For the P-450 form the haem iron becomes less accessible on solubilization, both for the rabbit and the rat liver monooxygenases, whereas in case of rat liver P-448 the accessibility is considerably enhanced on solubilization. There is a substantial structural specificity of the haem environments from the two animal species, the one from rat being tighter. The reduced, NO-bound rabbit liver monooxygenase was studied also, but the results are not yet conclusive, except the fact that the unpaired spin from NO is thoroughly shielded from the solvent compared with the haem iron from the original sample. The following series of increased haem-iron accessibility emerges from the PMRx studies known so far: rat (P-448) less than rabbit (P-448) less than rat (P-450) less than rabbit (P-450) in microsomes, and rabbit (P-448, with 3-MC bound?) less than Pseudomonas putida (P-450) rat less than (P-448), less than rat (P-450) less than rabbit (P-450) from solubilized samples. For the latter, it appears that increased enzymic specificity goes along with a closing of the haem cleft.

Quaternary structure, hydration, and self-association of hemoglobin. A proton magnetic relaxation study.

The hydration of oxyhemoglobin, carbonylhemoglobin, and deoxyhemoglobin does not depend on the quaternary state of the hemoglobin molecule as revealed through the concentration dependence of proton magnetic relaxation rates. The biphasic relaxation behavior of isotopically diluted solutions of hemoglobin confirms that the self-association of hemoglobin molecules at higher concentration is independent of the quaternary structure. In the case of aquomethemoglobin, a biphasic relaxation and a diminished heme accessibility at higher concentrations are observed, caused by interaction of the associating hemoglobin molecules.

A proton magnetic relaxation study of ferric myoglobin and haemoglobin in water/ethanediol solutions.

Structural alterations of the haem vicinity of the high-spin derivatives of bovine ferric myoglobin (metmyoglobin) and human haemoglobin and the changes of the interaction with inositol hexaphosphate induced by ethanediol were monitored by solvent-proton magnetic relaxation. On addition of ethanediol up to 60% the fluoromet derivatives exhibit a gradual increase in the accessibility of the haem for the molecules from the solvent. In aquomethaemoglobin solutions with more than 25% ethanediol there is no unique explanation of proton magnetic relaxation. Ethanediol enhances the binding of inositol hexaphosphate to methaemoglobin, but the structural consequences of this binding on the haem-pockets seem to be diminished. The mechanisms of the observed structural and functional alterations of myoglobin as well as haemoglobin tetramer are discussed here.

Structural studies by proton magnetic relaxation of stereochemical probes. II. Allosteric effects in human methaemoglobin.

The haem-iron accessibility to solvent molecules in human aquomet- and fluoromethaemoglobin was studied by the magnetic relaxation of protons from a stereochemical probe (methanol in deuterated solutions) in its dependence on allosteric effects induced by inositol hexaphosphate and pH between 5.5 and 8.5. The exchange of methanol with bulk solvent was observed only when inositol hexaphosphate was bound to aquomethaemoglobin, which is consistent with a widening of the haemcrevice compared to the conformation in the absence of inositol hexaphosphate. An increase in alkalinity in the physiological range of the Bohr effect results in a gradual impedence of the solvent dynamics inside the haem-pocket. The fast-relaxation phase of methyl protons indicates that a large number of methanol molecules are under the strong influence of the protein; this effect is considerably smaller with inositol hexaphosphate bound to aquomethaemoglobin. The hypothesis which implies a proton from the coordinated water molecule is responsible for the observed relaxation rates has been critically discussed. The model with a water molecule exchanging between a position next to the sixth-ligand site of the haem-iron and the bulk solvent is further substantiated experimentally. This model has been found to be the simplest and most self consistent in the interpretation of all these proton magnetic relaxation data.

Self-association of oxyhaemoglobin. A nuclear magnetic relaxation study in H2O/D2O solutions.

The proton and deuterium longitudinal relaxation rates were studied at room temperature up to the highest protein concentrations in oxyhaemoglobin solutions of different H2O/D2O composition. The deuterium relaxation rates followed the experimentally well known single linear dependence on protein concentration, the slopes being little influenced by solvent (D2O/H2O) composition. The proton relaxation rates show two different linear dependences on haemoglobin concentration. The entire concentration range is described by two straight lines with the threshold concentration about 11 mM (in haem). The ratio of the slopes is 1.6 (high-to-low HB-conc). Only in the higher concentration range two T1's were observed if the solvent contained more than half of D2O. The slow relaxation phase of protons has T1's similar to those measured in solutions with less than half of D2O. The relaxation of the other phase was ten times faster. The ratio of the proton populations in these two phases was equal to 2 (slow-to-fast) and independent of protein concentration. The fast relaxing protons are attributed to water molecules encaged within two or more haemoglobin molecules which associate for times long enough on the PMR time-scale.

Temperature dependence of ESR spectra of spin-labelled met-hemoglobin.

The maleimide spin-label, firmly fixed to the protein, was used to study conformation changes of various met-hemoglobin derivatives. The temperature dependence of the rotational correlation time shows a distinct conformation change in aquomet-hemoglobin at about 25 degrees C. The other met-hemoglobin derivatives studied (fluoro-, cyano-, aquomet-complexed with inositol hexaphosphate) and carbonmonoxy-hemoglobin exhibit no conformation changes in the temperature range from 0-50 degrees C.

The haem-accessibility in leghaemoglobin of Lupinus luteus as observed by proton magnetic relaxation.

Using the solvent-protons' longitudinal magnetic relaxation rates (p.m.r.) for Lupinus luteus leghaemoglobin derivatives the accessibility of the haem has been evaluated by our "stereo-chemical p.m.r. titration" method with nonexchangeable protons of aliphatic lower alcohols in otherwise deuterated solutions. The haem in leghaemoglobin is more accessible and its protein environment more flexible compared with vertebrate haemoglobins. The correlation time in aquometleghaemglobin aqueous solution has been determined by measuring the frequency dispersion of the p.m.r. rates between 6.1 and 93 MHZ. Taking into account the measured value of tauc = (7.7 +/- 0.5 x 10(-10) s the iron-to-proton inter-spin distances have been calculated. The significance of these distances as well as the electronic g-factor anisotrophy for elucidation of fine structural details of the haem-environment are discussed.