[Should you operate on a uterine septum ?] / Faut-il opérer un septum utérin ?

Uterine septum is the most common congenital uterine malformation and may cause obstetric problems such as repeated miscarriages, premature deliveries or dystocial presentations. It also appears to be associated with infertility. The uterine septum can be demonstrated by ultrasound, MRI and hysteroscopy. The benefit of hysteroscopic septoplasty remains controversial although most studies agree on the benefits of this treatment. It improves the fertility and obstetrical future of women by increasing the rate of pregnancies and live births and reducing the rate of miscarriages. Resection of the uterine septum is therefore encouraged in symptomatic patients but also in prophylaxis, in asymptomatic patients in order to increase the chances of carrying their pregnancy to term.

Le septum utérin est la malformation utérine congénitale la plus fréquente et peut être à l'origine de problèmes obstétricaux tels que des fausses couches à répétition, des accouchements prématurés ou des présentations dystociques. Par ailleurs, il semble également associé à une infertilité. Le septum utérin peut être mis en évidence à l'aide de l'échographie, de l'IRM et de l'hystéroscopie. Le bénéfice d'une septoplastie hystéroscopique reste controversé bien que la plupart des études s'accordent sur les bienfaits de ce traitement. En effet, il permet d'améliorer la fertilité et l'avenir obstétrical des patientes en augmentant le taux de grossesses et de naissances d'enfants vivants et en réduisant le taux de fausses couches. La résection du septum utérin est donc encouragée chez les patientes symptomatiques, mais également, en prophylaxie, chez des patientes asymptomatiques afin d'augmenter les chances de mener leur grossesse à terme.

Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

Occurrence of Taeniidae in a Middle Pleistocene speleothem of the Bàsura cave (Toirano, Liguria, Italy).

OBJECTIVE: This study aims to (i) analyse whether speleothems may contain fossil parasitic worm eggs and, if so, (ii) identify the pathogens involved, and (iii) place them in geological, palaeontological, and chronological contexts to know the zoonoses that could affect human and animal populations during the Middle Pleistocene. MATERIALS: A sample of calcite dated to the beginning of MIS 9 and MIS 8 from the Bàsura cave (Liguria, Italy) was analysed. METHODS: The chemical protocol applied is characterised using hydrochloric acid, the reduction of hydrofluoric acid application time, and by the absence of the use of base, dense liquor or acetolysis. RESULTS: An embryophore of a taeniid was recovered. CONCLUSIONS: Endoparasitic worm eggs can be found in speleothems. A taeniid embryophore was found in a calcite level dated to MIS 9. Zoonoses related to the Taeniidae family existed 300,000 years ago in the northern Mediterranean region and may have affected Middle Pleistocene predators, carnivores, or humans. Speleothems are good tools for paleoparasitological studies. SIGNIFICANCE: This is the oldest taeniid recovered and identified. LIMITATIONS: A more precise determination of the genus of this taeniid is not possible in the absence of more precise palaeontological data. SUGGESTIONS FOR FURTHER RESEARCH: An application of this approach to other Pleistocene speleothems could broaden the spectrum of parasites and their zoonoses over remote Pleistocene periods.

Daily practice management of septate uterus: reproductive outcome after septoplasty.

Background: Septate uterus is the most common uterine malformation found in women presenting poor reproductive history. Hysteroscopic septoplasty (HS) restores the uterine anatomy in a safe procedure. Objectives: The goal of our study is to determine the reproductive outcomes after HS of symptomatic septate uterus. Materials and Methods: In a retrospective observational single centre study the reproductive outcomes and complications after HS were evaluated in 31 women with symptomatic septate uterus. The patients were separated into two groups according to the symptoms - infertility or recurrent pregnancy loss (RPL). Main outcome measures: were the pregnancy and live birth rate and secondarily the complication rate. Furthermore, the results were analysed depending on the need of assisted reproductive techniques (ART). Results: The treatment has resulted in an overall pregnancy rate of 71% for both groups. The spontaneous pregnancy rate is 45% and 8 pregnancies resulted from ART (26%). The overall first live birth rate is 51.6%. A decrease has been noticed in the miscarriage rate from 95.24% to 24% (p<0.001) in the overall population. Conclusions: In patients with a symptomatic septate uterus hysteroscopic septoplasty is a safe and effective procedure. The favourable results pointing out the benefits of surgery on the reproductive outcomes as well as the relatively simple and safe technique of HS make the intervention attractive.

New research directions in medulloblastoma.

INTRODUCTION: Medulloblastoma is the most common type of pediatric malignant brain tumor where the most important amount of clinical and radiological data has been accumulated in recent years. This has led to its sophistication in the management of these patients with a clear benefit for the patients. Long-term outcome and sequelae have been described and their causes well understood such as preventive measures which can now be implemented. MATERIAL AND METHODS: This review paper does not attempt to make a systematic review of the literature in the field of research regarding medulloblastoma. It rather reflects more the opinion of a pediatric oncological team involved for a long time in this type of research. Therefore, a relevant literature review was carried out and selected by the senior author. RESULTS: Medulloblastoma is no longer a single entity but a group of at least 4 different diseases with a specific oncogenesis. In addition, biomarkers for prognosis have emerged to complement the known clinico-radiological risk factors. If this biological classification has allowed to modulate the therapeutic strategies, it has not yet brought many new drugs (except for the Sonic Hedgehog inhibitors) in the armamentarium against medulloblastomas. Consequently, some high-risk tumors remain difficult to cure. Combining data on oncogenesis and prognostic biomarkers will allow to define risk groups more specifically. New targeted therapies that are more effective and less toxic are desperately needed. Alternatively, it is also justified to study preventive measures to decrease the sequelae of the tumor and its treatments. From the therapeutic point of view, we scarcely know the biological determinants of chemosensitivity and radiosensitivity, as well as those associated with metastases which are indeed invaluable for tailored therapeutic strategies. CONCLUSION: If some genetic causes of medulloblastoma are known, the occurrence of the disease is largely unexplained for the others, justifying more research in this area. If genomics (and to a lesser extent epigenomics) of these neoplasms has been well studied, little is known on their proteomics and on the regulatory networks involved in the biological behavior of these tumor cells. New models are developed to test these aspects.

Current recommendations for cancer surveillance in Gorlin syndrome: a report from the SIOPE host genome working group (SIOPE HGWG).

Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum of benign and malignant tumors. Basal cell carcinomas (BCC), odontogenic keratocysts and medulloblastomas are the main tumor types encountered, but meningiomas, ovarian or cardiac fibromas and sarcomas have also been described. The clinical features and tumor risks are different depending on the causative gene. Due to the rarity of this condition, there is little data on phenotype-genotype correlations. This report summarizes genotype-based recommendations for screening patients with PTCH1 and SUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 in PTCH1, and at age 20 in SUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 for PTCH1 PV carriers only. For medulloblastomas, repeated brain MRI from birth to 5 years should be proposed for SUFU PV carriers only. Brain MRI for meningiomas and pelvic ultrasound for ovarian fibromas should be offered to both PTCH1 and SUFU PV carriers. Follow-up of patients treated with radiotherapy should be prolonged and thorough because of the risk of secondary malignancies. Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required.

A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings. BACKGROUND: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear. METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized. RESULTS: Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent. CONCLUSIONS: In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.

Influence of Ca2+ concentration on the clearance and circulating levels of intact and carboxy-terminal iPTH in pentobarbital-anesthetized dogs.

The role of hormone secretion and hormone clearance in the differential control of circulating levels of intact (I-) and carboxy-terminal (C-) immunoreactive parathyroid hormone (iPTH) was evaluated in 18 pentobarbital-anesthetized dogs. Catheters were installed in the aorta, left renal, and hepatic veins for sampling. Hepatic and renal blood flows were calculated from sulfobromophtalein (BSP) and p-aminohippuric acid (PAH) extraction and clearance. I- and C-iPTH were measured during a 1 h of infusion of CaCl2 or Na2EDTA. High-performance liquid chromatography (HPLC) profiles of I- and C-iPTH in and out of the liver and kidney were also obtained. Data on two dogs (one CaCl2 and one Na2EDTA infusion) were pooled for the analysis of one parathyroid function using a four-parameter mathematical model. Results obtained in the basal state and during analysis of the parathyroid function were also compared with those of 24 awakened dogs. Results are means +/- SD. Anesthetized dogs had lower levels of Ca2+ (1.29 +/- 0.03 vs. 1.34 +/- 0.04 mmol/l; p < 0.001) and higher levels of I- (11.5 +/- 5.7 vs. 3.0 +/- 1.9 pmol/l, p < 0.001) and C-iPTH (52 +/- 20.9 vs. 22.8 +/- 10.5 pmol/l; p < 0.001) than awakened dogs. Their stimulated (S) and nonsuppressible (NS) I-iPTH levels were increased 2- and 4-fold, respectively, while similar C-iPTH levels rose only 1.35- and 1.75-fold; this caused their S (4.4 +/- 0.7 vs. 6.8 +/- 1.9; p < 0.001) and NS (24.6 +/- 11.8 vs. 49.8 +/- 27.5; p < 0.05) C-iPTH/I-iPTH ratios to decrease. This was not explained by different renal clearance rates of I- and C-iPTH since both were similar at approximately 10 ml/kg/minute and unaffected by Ca2+ concentration. Clearance of all I- and C-iPTH HPLC molecular forms by the kidney appeared equal. A 50% decrease in the hepatic clearance of I-iPTH to approximately 12 ml/kg/minute in pentobarbital-anesthetized dogs, related to a lower hepatic blood flow, explained the higher levels of S and NS I-iPTH in these animals. I-iPTH hepatic clearance was unaffected by Ca2+ concentration. C-iPTH hepatic clearance was much lower at approximately 5 ml/kg/minute, abolished by hypercalcemia, and reduced by the influence of anesthesia on hepatic blood flow. This also explained the higher S C-iPTH levels in anesthetized animals. I-PTH(1-84) detected by the C-iPTH assay explained only 37.6% of the hepatic C-iPTH clearance in hypocalcemia and 73.3% in hypercalcemia. Overall, our results indicate that total C-iPTH clearance is about 40.2% that of I-iPTH in hypocalcemia and 41.3% in hypercalcemia. This would only explain a 2.4- to 2.5-fold difference in circulating levels of I- and C-iPTH if secretion rates were equal; the larger difference observed in S and NS C-iPTH/I-iPTH ratio values is thus mainly explained by different production rates.

Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH/PTH-related peptide receptor.

Even if the carboxyl-terminal (C-) fragments/intact (I-) PTH ratio is tightly regulated by the ionized calcium (Ca(2+)) concentration in humans and animals, in health and in disease, the physiological roles of C-PTH fragments and of the C-PTH receptor remain elusive. To explore these issues, we studied the influence of synthetic C-PTH peptides of various lengths on Ca(2+) concentration and on the calcemic response to human (h) PTH-(1-34) and hPTH-(1-84) in anesthetized thyroparathyroidectomized (TPTX) rats. We also looked at the capacity of these PTH preparations to react with the PTH/PTHrP receptor and with a receptor for the carboxyl (C)-terminal portion of PTH (C-PTH receptor) in rat osteosarcoma cells, ROS 17/2.8. The Ca(2+) concentration was reduced by 0.19 +/- 0.03 mmol/liter over 2 h in all TPTX groups. Infusion of solvent over 2 more h had no further effect on the Ca(2+) concentration (-0.01 +/- 0.01 mmol/liter), whereas infusion of hPTH-(7-84) or a fragment mixture [10% hPTH-(7-84) and 45% each of hPTH-(39-84) and hPTH-(53-84)] 10 nmol/h further decreased the Ca(2+) concentration by 0.18 +/- 0.02 (P<0.001) and 0.07+/-0.04 mmol/liter (P< 0.001), respectively. Infusion of hPTH-(1-84) or hPTH-(1-34) (1 nmol/h) increased the Ca(2+) concentration by 0.16 +/- 0.03 (P < 0.001) and 0.19 +/- 0.03 mmol/liter (P < 0.001), respectively. Adding hPTH-(7-84) (10 nmol/h) to these preparations prevented the calcemic response and maintained Ca(2+) concentrations equal to or below levels observed in TPTX animals infused with solvent alone. Adding the fragment mixture (10 nmol/h) to hPTH-(1-84) did not prevent a normal calcemic response, but partially blocked the response to hPTH-(1-34), and more than 3 nmol/h hPTH-(7-84) prevented it. Both hPTH-(1-84) and hPTH-(1-34) stimulated cAMP production in ROS 17/2.8 clonal cells, whereas hPTH-(7-84) was ineffective in this respect. Both hPTH-(1-84) and hPTH-(1-34) displaced (125)I-[Nle(8,18),Tyr(34)]hPTH-(1-34) amide from the PTH/PTHrP receptor, whereas hPTH-(7-84) had no such influence. Both hPTH-(1-84) and hPTH-(7-84) displaced (125)I-[Tyr(34)]hPTH-(19-84) from the C-PTH receptor, the former preparation being more potent on a molar basis, whereas hPTH-(1-34) had no effect. These results suggest that C-PTH fragments, particularly hPTH-(7-84), can influence the Ca(2+) concentration negatively in vivo and limit in such a way the calcemic responses to hPTH-(1-84) and hPTH-(1-34) by interacting with a receptor different from the PTH/PTHrP receptor, possibly a C-PTH receptor.

The set point of parathyroid hormone stimulation by calcium is normal in progressive renal failure.

An increased set point of PTH stimulation by ionized calcium (Ca++) has been observed in renal failure patients with severe secondary hyperparathyroidism. The extension of this concept to all renal failure patients has remained problematic, even if it could explain elevated PTH levels in the absence of other biochemical abnormalities. We were particularly interested in seeing whether the concept could fit patients with progressive renal failure (PRF). To achieve this, we studied 26 normals (N), 9 patients with PRF, and 12 hemodialyzed patients (HD) in the basal state and during parathyroid function tests. The latter two groups were studied at the end of winter and end of summer, respectively. Patients with PRF had normal levels of Ca++, PO4, and 1,25(OH)2D, and they had low-normal concentrations of 25(OH)D; their basal I- and C-PTH levels were 3- and 4-fold higher than N, as were their creatinine levels. HD had significantly lower levels of Ca++ and 1,25(OH)2D, and they had higher levels of phosphate, creatinine, I-PTH, and C-PTH than N or PRF. Stimulated levels of I-PTH were similar in N (13.6 +/- 4.3 pmol/L) and PFR (18 +/- 3.3 pmol/L) and elevated in HD (37.1 +/- 28.7 pmol/L; P < 0.001 vs. N, and P < 0.05 vs. PRF). Nonsuppressible I-PTH was increased 2-fold in PRF (N = 0.64 +/- 0.19 vs. PRF = 1.28 +/- 0.46 pmol/L; P < 0.01) and 6-fold in HD (3.95 +/- 2.85 pmol/L; P < 0.001 vs. others). But the set point of I-PTH stimulation by Ca++ was normal in PRF (N = 1.18 +/- 0.03 vs. PRF = 1.20 +/- 0.04 mmol/L; not significant) and decreased in HD (1.09 +/- 0.04 mmol/L; P < 0.001 vs. others). Similar results were obtained with the set point of C-PTH and of the C-PTH/I-PTH ratio. A positive correlation was observed between serum Ca++ concentration and the set point value when all three populations were analyzed together (r = 0.759, n = 47, P < 0.0001). These results indicate that the set point of PTH stimulation is normal in PRF and decreased in hypocalcemic HD. The set point seems to adjust to the ambient Ca++ concentration of the patients, by mechanisms yet to be elucidated. This does not suggest participation of this factor to the genesis of the secondary hyperparathyroidism of PRF.

A developmental study of the affective value of tempo and mode in music.

Do children use the same properties as adults in determining whether music sounds happy or sad? We addressed this question with a set of 32 excerpts (16 happy and 16 sad) taken from pre-existing music. The tempo (i.e. the number of beats per minute) and the mode (i.e. the specific subset of pitches used to write a given musical excerpt) of these excerpts were modified independently and jointly in order to measure their effects on happy-sad judgments. Adults and children from 3 to 8 years old were required to judge whether the excerpts were happy or sad. The results show that as adults, 6--8-year-old children are affected by mode and tempo manipulations. In contrast, 5-year-olds' responses are only affected by a change of tempo. The youngest children (3--4-year-olds) failed to distinguish the happy from the sad tone of the music above chance. The results indicate that tempo is mastered earlier than mode to infer the emotional tone conveyed by music.

Origin of parathyroid hormone (PTH) fragments detected by intact-PTH assays.

BACKGROUND: Intact parathyroid hormone (I-PTH) assays react with non-(1-84)PTH, large carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. They account for up to 50% of I-PTH in renal failure and may be implicated in PTH resistance. We wanted to know if they were secreted by the parathyroid glands and generated by peripheral metabolism of PTH(1-84). METHODS: Anesthetized normal and nephrectomized (NPX) rats were injected i.v. with 1.5 microg human (h) PTH(1-84). Blood was obtained from 8 rats at 2, 4, 6, 8, 12, 24, 48 and 96 min. I-PTH (Allegro I-PTH) was measured in all samples. Pools of serum were fractionated by HPLC at each time point and the fractions assayed to quantitate hPTH(1-84) and non-(1-84)PTH. Secretion studies were performed with dispersed cells from 5 parathyroid adenomas. The serum of 10 patients with primary hyperparathyroidism and cell supernatants were fractionated by HPLC and were analyzed as described. RESULTS: hPTH(1-84) disappeared from serum biexponentially. The half-life of the first exponential was similar in normal (2.08 min) and NPX (1.94 min) rats, while that of the second was longer in NPX rats (32.4 vs 20.9 min). The residual quantity of hPTH(1-84) under the curve was greater in NPX (6964+/-2392 pmol) than in normal rats (3229+/-561 pmol; P<0.001). Non-(1-84)PTH concentration was maximal at 8 min in both groups and was higher in NPX (92.8+/-13.8 pmol/l) than in normal rats (38.8+/-7.2 pmol/l; P<0.01). The area under the curve of non-(1-84)PTH was also greater in NPX (1904+/-405 pmol) than in normal rats (664+/-168 pmol; P<0.001). All parathyroid adenomas secreted non-(1-84)PTH. It represented 21.1+/-3.9% of secreted and 32.5+/-1.3% of circulating I-PTH in primary hyperparathyroidism. CONCLUSIONS: Non-(1-84)PTH, like other C-PTH fragments, originates from both the peripheral metabolism of hPTH(1-84) and from parathyroid gland secretion. Renal failure influences its concentration by increasing the amount of substrate available and by reducing non-(1-84)PTH clearance. Its higher proportion in serum relative to cell supernatants in primary hyperparathyroidism reflects the added role of peripheral metabolism and the longer half-life of fragments.

Breathing frequency and use of expiratory muscles do influence the dynamic positive end-expiratory pressure.

End-expiratory air trapping due to obstructive airway disease can be estimated through the measurement of intrinsic positive end-expiratory pressure PEEPi. The influence of breathing-frequency and use of expiratory muscles on PEEPi were measured in 10 normal and 10 chronic bronchitic patients (COPD). Insignificant control values of PEEPi increased to measurable values at high breathing rate in normal subjects. Control values were higher in COPD patients and increased at fast breathing rate. When corrected for the use of expiratory muscles according to simultaneous gastric pressure drop, PEEPi decreased in COPD, but still increased at high rate. We conclude that modifying the respiratory rate can increase PEEPi values independently of the severity of airway obstruction and the use of expiratory muscles. Before estimating the pathological value of a PEEPi measurement or evaluating the effects of a treatment, we always need to know the simultaneous breathing frequency.

Does inspiratory behaviour affect the efficiency of non-invasive ventilation in COPD patients?

Non-invasive ventilation (NIV) is more and more used. Some failures of the technique have been reported, and efforts are needed to understand them. Collaboration (inspiratory behaviour) of the patient during NIV could play a role in the success of this technique. We have studied the influence of this one on the efficiency of NIV. While ventilating 10 stable chronic obstructive pulmonary disease patients with a nasal pressure support ventilation (PSV), we measured their flow and volume with a pneumotachograph and oesophageal and gastric pressures during three different respiratory voluntary behaviours: relaxed inspiration, active inspiratory effort and resisted inspiration. We showed that when compared with the relaxed inspiration: (a) Active inspiratory effort increases slightly minute ventilation from 14.8 +/- 4.7 to 15.41 +/- 4.19 during PSV 10/0 without change of breathing frequency but with an important increase of inspiratory work (W(OB)) from 14.47 +/- 9.43 to 28.55 +/- 25.35 J/min (P=0.008). PEEPi increases with active behaviour during PSV but not during BiPAP. (b) A resisted inspiration decreases inspiratory work (to 7.53 +/- 8.6 J/min) at the price of a decrease of the minute ventilation to 11.47 +/- 4.20 l/min (P=0.06). Results of ventilation, PEEPi and work parameters were identical during the bilevel pressure support (15/5 cm H2O). The aims of NIV being to increase ventilation and unload the inspiratory muscles, our results suggest that during NIV, a relaxed spontaneous breathing is preferable. These differences between the inspiratory behaviours could affect the expected benefits of PSV in acutely ill patients.

Normal parathyroid function with decreased bone mineral density in treated celiac disease.

Decreased bone mineral density (BMD) has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH) remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7+/-3.7 years (range 1.1 to 15.9). In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH) (3.77+/-0.88 pmol/L versus 2.28+/-0.63 pmol/L, P<0.001), which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score), patients had significantly lower BMDs of the hip (-0.60+/-0.96 SDs, P<0.05) and lumbar spine (-0.76+/-1.15 SDs, P<0.05). T scores were also decreased for the hip (-1.3+/-0.9 SDs, P<0.0001) and lumbar spine (-1.4+/-1.35 SDs, P<0.0001), with two to three patients being osteoporotic (T score less than -2.5 SDs) and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs) in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not, an important determinant of the actual bone mass of patients. Normal parathyroid function in treated patients suggests a lack of previous severe secondary hyperparathyroidism and/or complete adaptation to prior changes in parathyroid function.

Unusual atrial pro-arrhythmic effect of flecainide: a contemporary review.

The authors report the case of a patient with drug-resistant atrial fibrillation, who developed, for more than 2 hours, a well-tolerated attack of palpitations, after taking 500 mg of flecainide acetate. The Holter monitoring demonstrated atrial flutter with 1:1 AV conduction and a ventricular rate at 220 bpm. This atrial pro-arrhythmic effect is rare and the mechanism is discussed.

Randomized trial of paroxetine in end-stage COPD.

BACKGROUND: Although the underlying pathology is initially confined to the lungs, the associated emotional responses to chronic obstructive pulmonary disease (COPD) contribute greatly to the resulting morbidity. The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms. METHODS: We conducted a 12-week, randomized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Questionnaire (CRQ), an evaluative COPD-specific quality-of-life questionnaire, was the primary outcome. RESULTS: 23 patients were randomized and 15 completed the trial (8 on Paroxetine; 7 on placebo). In the per-protocol analysis, we observed statistically and clinically significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ: emotional function (adjusted mean difference: 1.1; 95% confidence interval [CI]: 0.0 - 2.2) and mastery (difference: 1.1; CI: 0.4 - 1.8). Dyspnea and fatigue improved, but to an extent that did not reach statistical significance. In the intention-to-treat analysis, none of the differences in CRQ scores was significant. Paroxetine was not associated to any worsening of respiratory symptoms. CONCLUSIONS: The results of this small randomized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present. This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD.

Grafting odorant binding proteins on diamond bio-MEMS.

Odorant binding proteins (OBPs) are small soluble proteins found in olfactory systems that are capable of binding several types of odorant molecules. Cantilevers based on polycrystalline diamond surfaces are very promising as chemical transducers. Here two methods were investigated for chemically grafting porcine OBPs on polycrystalline diamond surfaces for biosensor development. The first approach resulted in random orientation of the immobilized proteins over the surface. The second approach based on complexing a histidine-tag located on the protein with nickel allowed control of the proteins' orientation. Evidence confirming protein grafting was obtained using electrochemical impedance spectroscopy, fluorescence imaging and X-ray photoelectron spectroscopy. The chemical sensing performances of these OBP modified transducers were assessed. The second grafting method led to typically 20% more sensitive sensors, as a result of better access of ligands to the proteins active sites and also perhaps a better yield of protein immobilization. This new grafting method appears to be highly promising for further investigation of the ligand binding properties of OBPs in general and for the development of arrays of non-specific biosensors for artificial olfaction applications.