Characterization and comparison of commercial oils used for human embryo culture.

STUDY QUESTION: Are there significant differences between the available commercial oil brands used for human IVF? SUMMARY ANSWER: Important differences have been detected among the tested oil brands in their potential to stabilize culture conditions and, more importantly, in their direct effect on embryo development and viability. WHAT IS KNOWN ALREADY: Mineral oil is a critical component of the human culture system due to its protective and stabilizing roles during in vitro embryo development. Many different oils are available on the market, with differences in their viscosity, density and overall quality. STUDY DESIGN, SIZE, DURATION: Thirteen different commercial oil brands were compared. PARTICIPANTS/MATERIALS, SETTING, METHODS: Each oil was firstly analyzed to assess its viscosity, density, peroxide value and potential oxidation. Secondly, the capacity of each oil to reduce pH, osmolality and temperature fluctuations during embryo culture and manipulation was compared. Lastly, a sensitive mouse embryo assay (MEA) protocol, previously optimized to detect toxicity in oils samples, was used to compare the overall quality of the different brands in terms of embryo developmental rates up to the blastocyst stage. At the end of the MEAs, a triple labeling protocol was applied to analyze Oct4+ cells, apoptotic cells and total cell counts in the blastocysts obtained by fluorescence microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: Significant divergences were detected in the rise of osmolality and the equilibration and stability of pH between different oils, which could be correlated to their physico-chemical characteristics. In particular, oil samples with a higher viscosity tended to offer an additional protection against fluctuations in the culture conditions, however, the differences in temperature stability between oils were minor. Two out of the 13 oil samples, which were commercially available, were identified as embryo-toxic by applying the MEA protocol with increased sensitivity for toxicity detection. Additionally, substantial differences in the total number of cells and the number of cells in the inner cell mass of the obtained blastocysts were also detected between oil groups. LIMITATIONS, REASONS FOR CAUTION: A single lot of oil was used for each brand and, thus, lot-to-lot variations in oil quality could not be determined. However, several bottles from the same oil were included to account for potential intra-lot variability. WIDER IMPLICATIONS OF THE FINDINGS: Commercial oils differ in both their physical characteristics and their performance in maintaining the stability of the culture conditions during in vitro embryo culture. Oil selection is important for embryo culture success. Additionally, the detection of embryo-toxic oils which had already been released to the human IVF market showcases the importance of applying sensitive MEA protocols for a better detection of toxicity in this type of samples. STUDY FUNDING/COMPETING INTEREST(S): This study was privately funded. TRIAL REGISTRATION NUMBER: N/A.

Bifidobacterium animalis subsp. lactis BLa80 regulates the intestinal habit in adults with chronic constipation: a multicentre, randomised, double-blind, placebo-controlled study.

Treatment with probiotics can help manage chronic constipation by softening the stools and possibly acting synergistically with front-line treatments. We assessed the efficacy of Bifidobacterium animalis subsp. lactis BLa80 in maltodextrin as a food supplement in regulating the intestinal habit of subjects with chronic constipation with type 1 or 2 stools on the Bristol scale index and/or less than three stools per week. A multicentre, randomised, double-blind, placebo-controlled clinical trial was carried out in subjects aged 18 and over with chronic constipation. The study enrolled forty-six subjects who were randomised one-to-one to receive the potential probiotic in maltodextrin (n = 23) or a placebo (n = 23). Investigators assessed changes in intestinal habits by analysing the mean number of weekly stools and the stool types according to the Bristol Scale. Patients reported constipation symptoms with PAC-SYM (patient assessment of constipation - symptoms), and the impact on quality of life with PAC-QoL (patient assessment of constipation - quality of life) and GI-QLI (gastrointestinal quality of life index). Patients on the intervention group showed a greater tendency to normalise the type of stools than those in the placebo group. This difference towards regular stool types (type 3 and 4) was statistically significant at weeks 8 and 12 relative to week 4 (P-values = 0.006 and 0.027, respectively). The proportion of constipated patients in the experimental group dropped over time, while the rate slightly increased in the placebo group in a statistically significant manner at week 12 relative to week 4 ( P = 0.037). Overall, the present study shows oral intake of B. animalis subsp. lactis BLa80 in maltodextrin for 12 weeks improves intestinal habits in subjects with chronic constipation. Our study provides evidence to the efficacy and safety use of this formulation as an effective tool for improving stool consistency in constipated patients. The trial was registered at ClinicalTrials.gov: NCT05980988.

Does diagnostic testing always decrease antibiotics prescriptions?

BACKGROUND: Empiric prescription to treat infectious diseases in community care settings has caused antibiotics to be overprescribed, increasing antimicrobial resistance (AMR). To reduce antibiotics prescription, the use of point-of-care diagnostic testing (POCT) has been suggested. METHODS: We present a stylized static theoretical economic model to analyse whether the use of POCT always decreases antibiotics prescriptions. We consider the interaction of a group of doctors who differ in their level of concern about AMR when prescribing with a firm selling a POCT, and we characterize the price set by the manufacturer and doctors' decision to employ POCT. RESULTS: We found that the number of antibiotics prescriptions is not always lower. This result depends on the distribution of the doctors' concern about AMR as there is a proportion of doctors who use POCT and then prescribe antibiotics while other doctors change their prescribing behaviour after using POCT and stop giving antibiotics to patients who do not benefit from them. When the proportion of patients who need antibiotic treatment is higher than the proportion of doctors who use POCT and stop prescribing unnecessary antibiotics, the number of antibiotics prescriptions is larger. Our analysis also shows that the use of POCT improves health outcomes. CONCLUSIONS: We should be very careful when we assert that POCT reduces antibiotics prescriptions as there are situations in which the opposite effect occurs.

The "new normal" osmotic threshold: Osmostat reset.

Hyponatremia is the most common electrolyte disorder in hospitalized patients. The syndrome of inappropriate antidiuresis (SIAD) is one of the leading causes of hyponatremia. Although not widely known, SIAD has a vast spectrum of etiologies and differential diagnoses and has been classically divided into four types (A, B, C, D). Frequently, when we use the term SIAD in clinical practice, it refers to subtype A, the so-called classic SIAD. The purpose of reporting this case is to make the clinicians aware of a specific subtype of SIAD, type C, an underdiagnosed entity called osmostat reset (OR). Due to similarities, OR often ends up being misinterpreted as classic SIAD. However, the differentiation between these two entities is crucial due to treatment implications. This manuscript highlights the use of an algorithm, based on the fraction of uric acid excretion, as an approach to the differential diagnosis of hyponatremia.

[Very severe hepatic trauma in childhood. The report of two cases with minimally invasive treatment]. / Traumatismo hepático muy grave en la infancia. A propósito de dos casos con tratamiento mínimamente invasivo.

Liver trauma in children is a pathology that has an increasing incidence mainly due to the implications of growing children in hazardous games and sports adventure, and the frequent car accidents. There has been a shift of management in haemodynamically stable patients towards non-operative management. This allows in most cases a patient's complete recovery without surgical aggression, preventing further damage derived from the handling of the injured liver. Herewith we report two cases of a 6 and 4 year old boys who suffered a very severe traumatic rupture of the liver. They were operated through minimally invasive surgical procedures, achieving complete resolution of the serious damages.

Using point-of-care diagnostic testing for improved antibiotic prescription: an economic model.

BACKGROUND: Antibiotics have been overprescribed to treat infectious diseases and have generated antimicrobial resistances that reduce their effectiveness. Following the rationale behind the new paradigm of personalized medicine, point-of-care diagnostic testing (POCT) has been proposed to improve the quality of antibiotic prescription with the aim of reducing antimicrobial resistances. METHODS: In order to understand whether this recommendation is valid, we create a theoretical economic model to determine under which conditions the expected benefits of using POCT to guide antibiotic prescription are greater than for empiric prescription, where we define the expected benefits as the difference between the economic value of health and the costs of the treatment. We consider the interaction of a group of physicians who express differing levels of uncertainty when prescribing with a firm selling a diagnostic device, and analyse the firm's pricing policy and the physicians' prescribing decisions. We allow the physicians to internalize the external costs of antimicrobial resistances. RESULTS: We find that the use of POCT reduces the number of antibiotic prescriptions. The reduction in antibiotic prescriptions is higher when physicians internalise the costs of antimicrobial resistances. Physicians with relatively high levels of uncertainty use POCT as they are uncertain about the right treatment for a large proportion of patients. Physicians with low levels of uncertainty prefer to prescribe empirically. The segmentation in the population of physicians regarding the uptake of POCT depends on the distribution of levels of uncertainty across physicians. For each test, the firm charges the marginal production costs of the inputs needed to administer the test, and makes its profit from the sales of the testing devices. CONCLUSIONS: From a theoretical perspective, our findings corroborate the fact that POCT improve the quality of antibiotic prescription and reduce the number of prescriptions. Nevertheless, their use is not always recommended as empiric therapy may be preferred when uncertainty is low.

[Palmar hyperhidrosis in childhood: thoracoscopic sympathectomy]. / Hiperhidrosis palmar en la infancia: simpaticolisis toracoscópica y encuesta de satisfacción.

BACKGROUND: Excessive hand sweating, known as palmar hyperhidrosis, is a disabling disorder that starts during the childhood, and can have a strong negative impact on the quality of life of affected children, as they feel rejected by others due to their permanently damp hands, suffering during school activities, contact sports and daily games. MATERIAL AND METHODS: Thoracoscopic sympathicolysis is easy to perform and has proven to be safe, with a short operating time. A review was performed on 48 children who underwent surgical treatment of palmar hyperhidrosis and answered a follow-up questionnaire to evaluate their level of satisfaction. RESULTS: Considering the final surgical results, the 48 patients were completely satisfied with the outcome of the operation. Significant complications or adverse effects were not detected. CONCLUSIONS: The primary palmar hyperhidrosis is a pathology that entails an important reduction in the quality of life of those who suffer it. With the results of this technique in hand, we recommend the endoscopic thoracic sympathicolysis procedure for the treatment of this pathology in paediatrics. The level of patient satisfaction was high.

Cell surface tubulin in leukemic cells: molecular structure, surface binding, turnover, cell cycle expression, and origin.

We report here new characteristics of cell surface tubulin from a human leukemia cell line. These cells (CEM cells) possess tubulin that is readily iodinated on the surface of living cells, turns over at a rate identical to that of other surface proteins, and is present throughout the cell cycle. When removed with trypsin, it rapidly returns to the surface. Peptide mapping of iodinated surface tubulin indicates that it possesses a similar, but not identical, primary structure to total CEM and rat brain tubulin. Living CEM cells are able to bind specifically a subfraction of CEM tubulin from metabolically labeled high speed supernatants of lysed CEM cells. Surface tubulin is more basic than the total tubulin pool. The binding, which is saturable, is inhibited by unlabeled CEM high speed supernatants but not by excess thrice-cycled rat or bovine brain tubulin. Surface tubulin is also shown to bind to living nontransformed normal rat kidney cells but not to normal, circulating, mononuclear white cells. Activated lymphocytes produce a tubulin that binds to CEM cells. Since CEM tubulin was detected in the media of 6-h cultures of CEM cells, we must conclude that at least some of the surface tubulin comes from the media. We further conclude that these leukemic cells produce an unusual tubulin that may bind specifically to any membrane. The presence of iodinatable surface tubulin, however, appears to require both the production of a unique tubulin and the presence of a "receptor-like" surface binding component.

[Our experience with hydro-debridement in varied skin lesions. Technical and innovating advance in pediatric surgery]. / Nuestra experiencia con el hidro-desbridamiento en lesiones cutáneas variadas. Adelanto técnico e innovador en cirugía pediátrica.

We present our experience in the use of Hydrosurgery with debridement of necrotic tissues from skin wounds in children. The Hydrosurgery system uses a high velocity stream of sterile saline solution, which can be controlled according to the state of the lesion. We have used this system in 15 patients suffering from a wide range of pathologies (burns, severe traumatic wounds, skin necrosis etc), achieving its complete resolution in shorter period of time. This method is an innovative technique in the management of patients with acute o r chronic skin lesions that require periodic procedures.

Pre-approval incentives to promote adoption of personalized medicine: a theoretical approach.

BACKGROUND: Currently, personalised medicine is becoming more frequently used and many drug companies are including this strategy to gain market access for very specialized therapies. In this article, in order to understand the relationships between the health authority and the drug company when deciding upon the implementation of personalized medicines, we take a theoretical perspective to model it when the price and reimbursement policy follows a pay-for-performance scheme. During the development of a new drug, the firm must decide whether to generate additional knowledge by investing in additional resources to stratify the target population based on a biomarker or directly apply for marketing authorization for the new treatment without information on the characteristics of patients who could respond to it. In this context, we assume that the pricing policy is set by the health authority, and then we characterize the pricing and investment decisions contingent on the rate of response to the treatment. RESULTS: We find that the price when the firm carries out R&D leading to the personalized treatments is not necessarily higher than the price if the firm does not carry out the R&D investment. When the rate of response to the treatment is too low, then the new drug is not marketed. If the rate of response is too high, personalized medicine is not implemented. For intermediate values of the rate of response, the adoption of personalized medicine may occur if the investment costs are sufficiently low; otherwise, the treatment is given to all patients without additional information on their characteristics. The higher the quality of the genetic test (in terms of its sensitivity and specificity), the wider the interval for the values of the proportional responders for which personalized medicine may be implemented. CONCLUSIONS: Our findings show that pre-approval incentives (prices) to promote the personalized treatments depend on the specific characteristics of the disease and the efficacy of the treatment. The model gives an intuitive idea about what to expect in terms of price incentives when the possibility of personalizing treatments becomes a strategic decision for the stakeholders.

[Prospective study comparing the incidence of wound infection following appendectomy for acute appendicitis in children: conventional treatment versus using reabsorbable antibacterial suture or gentamicin-impregnated collagen fleeces]. / Estudio comparativo de la incidencia de abscesos de pared abdominal en niños intervenidos quirúrgicamente por apendicitis aguda: tratamiento convencional vs con suturas recubiertas de antiséptico o con apósitos impregnados de antibiótico.

Postappendectomy wound infection is frequent in the pediatric age. It causes them important discomfort. We have conducted a prospective clinical study to evaluate this incidence under different surgical management. The subjects were children undergoing appendectomy for acute appendicitis. The patients belonging to the Control Group were operated, by standard surgical technique, along the first 9 months of the study period (n: 58). The Study Group was constituted by 101 children operated during the 9 consecutives months, identical on the basis of demographics and operations undergone, except for the use of, in an alleatory manner, sutures with antiseptic impregnation (Vicryl Plus, Ethicon Johnson & Johnson Medical), to close the incisi6n in children included in Study Sub-Group A, or gentamycin-containing collagen sponge (Collatamp EG, Aculia Fombona, S.A.; Schering-Plough, S.A.), placed within the muscles before wound closure, in the children belonging to the Study Sub-Group B. We have analyzed in the two Groups the incidence of postoperative wound infection and the mean Hospital stay. The use of sutures with antiseptic impregnation and/or gentamycin-containing collagen sponge, significantly reduced the wound infection rates in the children operated on for appendicectomy included in the Study Group, compared with the ones in the Control Group, therefore contributing to decrease the Hospital length of stay.

Endogenous versus exogenous generic reference pricing for pharmaceuticals.

In this paper we carry out a vertical differentiation duopoly model applied to pharmaceutical markets to analyze how endogenous and exogenous generic reference pricing influence competition between generic and branded drugs producers. Unlike the literature, we characterize for the exogenous case the equilibrium prices for all feasible relevant reference prices. Competition is enhanced after the introduction of a reference pricing system. We also compare both reference pricing systems on welfare grounds, assuming two different objective functions for health authorities: (i) standard social welfare and (ii) gross consumer surplus net of total pharmaceutical expenditures. We show that regardless of the objective function, health authorities will never choose endogenous reference pricing. When health authorities are paternalistic, the exogenous reference price that maximizes standard social welfare is such that the price of the generic drug is the reference price while the price of the branded drug is higher than the reference price. When health authorities are not paternalistic, the optimal exogenous reference price is such that the price of the branded drug is the reference price while the price of the generic drug is lower than the reference price.

Hemoglobin Dallas (alpha 97(G4)Asn-->Lys): functional characterization of a high oxygen affinity natural mutant.

Hemoglobin Dallas, an alpha-chain variant with a substitution of lysine for asparagine at position 97(G4), was found to have increased oxygen affinity (p1/2 = 1 mmHg at pH 7.3 and 20 degrees C), diminished cooperativity (n, the Hill coefficient = 1.7) and reduced Bohr effect (about 50%). Addition of allosteric effectors (such as 2,3-diphosphoglycerate, inositol hexakisphosphate and bezafibrate) led to a decrease in oxygen affinity and increase in cooperative energy. Kinetic studies at pH 7.0 and 20 degrees C revealed that (i), the overall rate of oxygen dissociation is 1.4-fold slower than that for HbA and (ii), the carbon monoxide dissociation rate is unaffected. The abnormal properties of this hemoglobin variant can be attributed to a more 'relaxed' T-state.

[Tubulized gastric fundus in the treatment of esophageal atresia]. / Fundus gástrico tubulizado en el tratamiento de las atresias de esófago de segmento largo.

When is impossible to restore the oesophageal continuity in oesophageal atresia (EA), the stomach elevation (whether tubulized or complete) and colon interposition are the most accomplished techniques, usually from the age of six month, in different steps and with the result of a high mortality, prolonged hospitalizations and high familial and economical cost. From a total of 34 EA diagnosed in an eleven years period, we had treated three children, tubulizing the gastric fundus with mechanical sutures in continuity with the distal oesophageal end in neonatal period. The procedure is done with preservation of the distal esophageal end in continuity with the tubuliced gastric fundus with mecanichal staplers. All the patients had needed pneumatic dilatations of the anastomosis After eleven years, eight years and six months follow-up respectively, the clinical behaviour of those patients is suitable, without swallowing problems and with weight and height development in predictable limits. We think that this kind of neoesophagus is useful to treat the long segment EA in newborns as it sets an esophago-gastric tube orthotopically, with homogeneous diameter in a isoperistaltic continuity, in neonatal period and in one step, putting aside the gastrostomy performed at the firsts hours of life and obtaining an important decreasing of mobility and hospitalisation stay.

Some economics on personalized and predictive medicine.

OBJECTIVE: To contribute to the theoretical literature on personalized medicine, analyzing and integrating in an economic model, the decision a health authority faces when it must decide on the implementation of personalized medicine in a context of uncertainty. METHODS: We carry out a stylized model to analyze the decision health authorities face when they do not have perfect information about the best treatment for a population of patients with a given disease. The health authorities decide whether to use a test to match patients with treatments (personalized medicine) to maximize health outcomes. Our model characterizes the situations under which personalized medicine dominates the alternative option of business-as-usual (treatment without previous test). We apply the model to the KRAS test for colorectal cancer, the PCA3 test for prostate cancer and the PCR test for the X-fragile syndrome, to illustrate how the parameters and variables of the model interact. RESULTS: Implementation of personalized medicine requires, as a necessary condition, having some tests with high discriminatory power. This is not a sufficient condition and expected health outcomes must be taken into account to make a decision. When the specificity and the sensitivity of the test are low, the health authority prefers to apply a treatment to all patients without using the test. When both characteristic of the test are high, the health authorities prefer to personalize the treatments when expected health outcomes are better than those under the standard treatment. When we applied the model to the three aforementioned tests, the results illustrate how decisions are adopted in real world. CONCLUSIONS: Although promising, the use of personalized medicine is still under scrutiny as there are important issues demanding a response. Personalized medicine may have an impact in the drug development processes, and contribute to the efficiency and effectiveness of health care delivery. Nevertheless, more accurate statistical and economic information related to tests results and treatment costs as well as additional medical information on the efficacy of the treatments are needed to adopt decisions that incorporate economic rationality.

Prevalence and clinical correlates of microalbuminuria in essential hypertension: the MAGIC Study. Microalbuminuria: A Genoa Investigation on Complications.

The prevalence of microalbuminuria and its relationship with several cardiovascular risk factors and target organ damage were evaluated in a cohort of 787 untreated patients with essential hypertension. Albuminuria was measured as the albumin-to-creatinine ratio in three nonconsecutive, first morning urine samples. The prevalence of microalbuminuria was 6.7%. Albuminuric patients were more likely to be men and to be characterized by higher blood pressure, body mass index, and uric acid levels and lower HDL cholesterol and HDL cholesterol-to-LDL cholesterol ratio. Piecewise linear regression analysis demonstrated that uric acid and diastolic blood pressure significantly influence albuminuria and together account for a large part of its variations. K-means cluster analysis performed on the entire cohort of patients confirmed that microalbuminuria is associated with a worse cardiovascular risk profile. Furthermore, microalbuminuria was associated with the presence of target organ damage (eg, electrocardiographic [ECG] abnormalities and retinal vascular changes). Age and the presence of microalbuminuria act as independent risk factors for the development of ECG abnormalities and retinal vascular changes. Cluster analysis allowed us to identify three subgroups of patients who differed in the presence or absence of microalbuminuria, retinopathy, and ECG abnormalities. We conclude that the prevalence of microalbuminuria in essential hypertension is lower than previously reported. Increased urinary albumin excretion is associated with a worse cardiovascular risk profile and is a concomitant indicator of early target organ damage.

Relevance of the chemical charge of rhodamine dyes to multiple drug resistance.

Previously, we have shown that multiple drug resistant (MDR) Friend leukemia cells (FLC) are cross-resistant to the positively-charged dye, Rhodamine 123 (Rho 123), and that this resistance can be reversed by verapamil (VER). In the present study we used two zwitterionic rhodamine analogs, Rhodamine 116 and Rhodamine 110, and another positively-charged analog, Rhodamine 6G, to determine whether drug accumulation, resistance and modulation were affected by changes in the charge of these compounds. While there was no differential sensitivity between sensitive and resistant FLC to zwitterionic rhodamines, there was marked differential toxicity between these cell types for the positively-charged analogs. The IC50 values were 1000- and 100-fold greater in resistant than in sensitive cells for Rho 123 and Rho 6G respectively. Intracellular drug accumulation was significantly higher in sensitive as compared to resistant cells for both Rho 123 and Rho 6G, but little difference in drug uptake between these two cell types was observed for Rho 110 and Rho 116. It was also found that the intracellular to extracellular ratio of the positively-charged compounds was greater than unity in both sensitive and resistant cells whereas for the zwitterionic analogs this ratio was less than 1. Furthermore, this ratio of drug uptake was found to be significantly higher for Rho 6G than for Rho 123, which correlated with the high oil:water partition coefficient of Rho 6G (115.6). In MDR cells, verapamil increased Rho 123 and Rho 6G accumulation by 9.4- and 8.6-fold respectively. In addition, IC50 values in resistant cells were reduced greater than 100-fold for Rho 6G and greater than 1000-fold for Rho 123 in the presence of 10 micrograms/ml of verapamil. In contrast, less than 2-fold reduction of IC50 values for both of the zwitterionic analogs could be obtained under the same conditions. These results indicate that the chemical charge of rhodamines plays an important role in their differential accumulation, cytotoxicity and sensitivity to modulators such as verapamil, in sensitive and multi-drug resistant cells. The data also suggest that increased lipophilicity of the positively-charged rhodamines may increase their ability to accumulate in, and subsequently kill, MDR cells.

Proline-catalyzed asymmetric aldol reactions between ketones and alpha-unsubstituted aldehydes.

[reaction: see text] With this communication we extend the methodology of proline-catalyzed direct asymmetric aldol reactions to include alpha-unsubstituted aldehydes as acceptors. This important aldehyde class gives the corresponding aldols in 22-77% yield and up to 95% ee when the reactions are performed in pure acetone or in ketone/chloroform mixtures. On the basis of these results we have developed a concise new synthesis of (S)-ipsenol.

Methotrexate, mitoxantrone, 5-fluorouracil and leucovorin in metastatic breast cancer patients.

We have evaluated the efficacy and toxicity of a chemotherapy consisting of methotrexate, mitoxantrone, 5-Fluorouracil and leucovorin in 21 advanced breast cancer patients. Among 20 evaluable patients, objective response was obtained in 6 patients (30%) with two complete responses, stable disease in 4 patients (20%), while 10 patients (50%) progressed. Median progression-free survival and survival were 10 and 15 months, respectively. The most frequently observed side-effects were myelosuppression and emesis; one patient, who had previously received doxorubicin at the maximum dose-limiting cardiac toxicity, died of congestive heart failure after the third cycle. This treatment is moderately effective for advanced breast cancer patients.

[Syringomyelia and pregnancy. Report of a clinical case and review of the literature]. / Siringomielia e gravidanza. Relazione di un caso clinico e revisione della letteratura.

The authors describe a case of pregnancy in a patient previously affected by Arnold-Chiari malformation associated with syringomyelia; from clinical experience and a review of the literature, the possibility is deduced of carrying out the pregnancy physiologically, although by observing close precaution while performing delivery which, by our experience, should be accomplished by partus caesarius in general anaesthesia, taking great care to the evaluation of neurologic parameters.