Intraoperative high flow oxygen therapy for tubeless anaesthesia in thoracoscopic surgery.

Tubeless anaesthesia has become widespread in videothoracoscopic surgery, even in major procedures such as lobectomies. There are several advantages in avoiding general anaesthesia and one-lung mechanical ventilation, such as faster recovery and shorter hospital stays. However, hypoxaemia and hypercapnia are the most reported causes of conversion to general anaesthesia. High Flow Oxygen Therapy (HFOT) generates flow-dependent positive end-expiratory pressure, improves oxygenation and also carbon dioxide washout by flow-dependent dead space flushing. For this reason, intraoperative HFOT may reduce the rate of conversion to general anaesthesia. We report our experience with intraoperative HFOT in a 71-year-old female with lung adenocarcinoma undergoing VATS upper left lobectomy.

Contingency management for smoking cessation among individuals with substance use disorders: In-treatment and post-treatment effects.

INTRODUCTION: Smokers with substance use disorders (SUDs) show elevated tobacco prevalence, and smoking abstinence rates are considerably low. This randomized controlled trial sought to compare the effect of a cognitive behavioral treatment (CBT) that includes an episodic future thinking (EFT) component with the same treatment protocol plus contingency management (CM). This study aims to examine the effect of CM on smoking outcomes and in-treatment behaviors (i.e., retention, session attendance and adherence to nicotine use reduction guidelines), and to analyze whether these in-treatment variables predicted days of continuous abstinence at end-of-treatment. METHOD: A total of 54 treatment-seeking participants (75.9% males, M = 46.19 years old) were allocated to CBT + EFT (n = 30) or CBT + EFT + CM (n = 24). Intervention consisted of eight weeks of group-based sessions. Tobacco abstinence was verified biochemically by testing levels of carbon monoxide (≤4ppm) and urine cotinine (≤80 ng/ml). RESULTS: CM intervention increased 24-hour tobacco abstinence (50% vs. 20%, χ2(1) = 5.4; p = .021) and days of continuous abstinence (M = 5.92 ± 7.67 vs. 5.53 ± 12.42; t(52) = -0.132; p = 0.89) at end-of-treatment in comparison with CBT + EFT intervention. Although not statistically significant, CBT + EFT + CM enhanced in-treatment behaviors, in terms of retention (83.3% vs. 70%; χ2(1) = 0.255; p = .208), sessions attended (12.29 ± 3.22 vs. 10.93 ± 3.26; t(52) = -1.527; p = .133) and adherence to weekly nicotine use reduction targets (41.07% ± 31.96 vs. 35% ±2 6.28; t(52) = -0.766; p = .447). A higher percentage of samples meeting reduction guidelines (ß = 0.609; p<.001) predicted days of continuous abstinence at end-of-treatment. CONCLUSION: Combining CM with CBT + EFT improves short-term quitting rates. Findings suggest the need to incorporate strategies for improving adherence to nicotine reduction guidelines.

In-treatment cigarette demand among treatment-seeking smokers with depressive symptoms.

INTRODUCTION: Despite previous evidence supporting the use of the Cigarette Purchase Task (CPT) as a valid tool for assessing smoking reinforcement, research assessing how environmental changes affect CPT performance is scarce. AIMS: This study addressed for the first time the differential effect of treatment condition [Cognitive Behavioral Treatment (CBT) + Behavioral Activation (BA) versus CBT + BA + Contingency Management (CM)] on cigarette demand among treatment seeking smokers with depressive symptoms. It also sought to assess whether reductions in smoking consumption arranged over the course of an intervention for smoking cessation impact on in-treatment cigarette demand. METHOD: Participants were 92 smokers with depressive symptoms from a randomized clinical trial that received eight weeks of either CBT + BA or CBT + BA + CM. Individuals completed the CPT 8 times; the first during the intake visit and the remaining 7 scheduled once a week in midweek sessions. Cotinine samples were collected in each session. RESULTS: Participants receiving CBT + BA + CM showed higher reduction in cigarette demand across sessions than participants receiving CBT + BA, although this comparison was only significant for the intensity index (p = .004). Cotinine was positively related to cigarette demand (all p values < .001), although this association became less prominent across sessions. In-treatment cotinine decreases were associated with demand reductions (all p values < .001), but this association was not significant for elasticity. CONCLUSIONS: Reductions in nicotine intake arranged over the course of an intervention for smoking cessation impact in-treatment cigarette demand.

[Changes in mitochondrial function induced by dequalinium precede oxidative stress and apoptosis in the human prostate cancer cell line PC-3].

Mitochondria play central roles in diverse physiological and pathological conditions associated with cell survival and death. Delocalized lipophilic cations, such as dequalinium (DQA), are accumulated in cancer cells attracted by the highly negative mitochondrial transmembrane potential of these cells. DQA showed a potent anticancer activity in cells from different malignancies. Here, we report the effect of DQA on PC-3 prostate cancer cells. Incubation with DQA at concentrations between 1.5 and 100 microM from 24 to 48 h decreases cell viability. The decrease in cell viability together with a loss of mitochondrial transmembrane potential induced an increase in reactive oxygen species production and cell death via caspase-3 dependent apoptotic pathway. QA was shown to cause moderate to strong cell death in a time and concentration dependent manner, causing a most advantageous effect at a concentration of 10 microM applied for a long 48 h time period, which might be a consequence of the kinetics of intracellular DQA accumulation in mitochondria, but also of the mechanisms of DQA-induced cell death. This data shows DQA as a promising agent against the human prostate cancer PC-3 cell line, activating the caspase-3 dependent apoptotic pathway. This fact might be beneficial for possible future applications in cancer therapy.

Mapping radon-prone areas using γ-radiation dose rate and geological information.

Identifying radon-prone areas is key to policies on the control of this environmental carcinogen. In the current paper, we present the methodology followed to delineate radon-prone areas in Spain. It combines information from indoor radon measurements with γ-radiation and geological maps. The advantage of the proposed approach is that it lessens the requirement for a high density of measurements by making use of commonly available information. It can be applied for an initial definition of radon-prone areas in countries committed to introducing a national radon policy or to improving existing radon maps in low population regions.

[Growth charts for the Spanish population with neurofibromatosis type 1]. / Gráficos de crecimiento de la población española con neurofibromatosis tipo 1.

OBJECTIVE: To make the charts of stature and head circumference of Spanish pediatric patients affected with neurofibromatosis type 1 (NF1), to compare them with the ones from a healthy population and to review the possible causes of its alterations. PATIENTS AND METHODS: We obtained the data from 251 Spanish patients (122 women and 129 men) with NF1 seen in seven hospitals between the years 2000 and 2002, with ages between 1 month and 18 years old. The calculation of the 50th centile or median was done using the method of mobile variables, and the 3rd and 97th centiles where calculated from this median. RESULTS: Girls with NF1 have a shorter stature than the healthy ones, which becomes evident after 10 years of age. We have not found differences in the stature between boys with the disease and those without it. In regards to head circumference, in boys and girls we have observed that it is bigger throughout life in patients affected with NF1, and that the 50th centile of healthy people correlates with the 3rd centile of those affected, the 97th centile of the healthy ones with the 50th centile of those affected, being the 3rd centile of the healthy people well below the 3rd centile of the affected ones, and the 97th centile of the affected ones well above the 97th of the healthy people. CONCLUSIONS: The short stature in postpuberal girls and the macrocephaly in both sexes at all ages, are primary characteristics in the NF1 and they are not usually related with other alterations, although they are not specific for this illness.

[Precocious puberty and pituitary incidentaloma]. / Pubertad precoz e incidentaloma hipofisario.

The case of an 9-year-old girl with precocious puberty and a non-functioning pituitary adenoma is described. A review of the literature on the incidence, evolution and therapeutic options of pituitary incidentalomas in children and adults is performed.

Molecular and pathogenic characterization of Borrelia burgdorferi sensu lato isolates from Spain.

Fifteen Borrelia burgdorferi sensu lato isolates from questing ticks and skin biopsy specimens from erythema migrans patients in three different areas of Spain were characterized. Four different genospecies were found (nine Borrelia garinii, including the two human isolates, three B. burgdorferi sensu stricto, two B. valaisiana, and one B. lusitaniae), showing a diverse spectrum of B. burgdorferi sensu lato species. B. garinii isolates were highly variable in terms of pulsed-field gel electrophoresis pattern and OspA serotype, with four of the seven serotypes described. One of the human isolates was OspA serotype 5, the same found in four of seven tick isolates. The second human isolate was OspA serotype 3, which was not present in ticks from the same area. Seven B. garinii isolates were able to disseminate through the skin of C3H/HeN mice and to cause severe inflammation of joints. One of the two B. valaisiana isolates also caused disease in mice. Only one B. burgdorferi sensu stricto isolate was recovered from the urinary bladder. One isolate each of B. valaisiana and B. lusitaniae were not able to disseminate through the skin of mice or to infect internal organs. In summary, there is substantial diversity in the species and in the pathogenicity of B. burgdorferi sensu lato in areas in northern Spain where Lyme disease is endemic.

[Pseudotumor cerebri associated with maxillary sinusitis: clinico-pathological study]. / Pseudotumor cerebral asociado a sinusitis maxilar y pleocitosis en líquido cefalorraquídeo.

INTRODUCTION: The pseudotumor cerebri is characterized by increased intracranial pressure in the absence of a space occupying lesions or obstruction to the circulation of cerebrospinal fluid (CSF). Increased pressure but normal composition of the CSF is the diagnostic criterion. Ear infections and other infections such as sinusitis have been cited as possible, but rare, causes. CLINICAL CASE: A 12 year old girl presented with diplopia 10 days after starting treatment for sinusitis. On examination there was paresia of the VI cranial nerve to the left eye and marked bilateral papilledema. She had normal visual acuity with visual field measurements showing increased blind spot field in both eyes. Resonance studies only showed maxillary sinusitis. CSF pressure was 35 cm H2O, with 40 lymphomonocytes and normal biochemical findings. After 15 cm of CSF had been removed treatment was started with acetazolamide, dexamethasone and cefotaxime. A week later the diplopia had disappeared and the CSF pressure was 25, with no cells present. Two months later the visual fields and fundus oculi were normal. After follow-up for one year there was no recurrence. CONCLUSIONS: We describe a case of pseudotumor cerebri associated with maxillary sinusitis. We do not know whether this is a chance association or whether there was a pathophysiological basis. The possibility should be considered so as to treat the cause or predisposing factor. The initial CSF pleocytosis would support the possibility of a relationship of the pseudotumor with an infectious condition (meningeal irritation or para-infectious pleocytosis meningeal irritation or para-infections pleocytosis in the context of an ENT infection), which might have precipitated the problem by interfering with the reabsorption of CSF.

[Non-dystonic torticollis. A report of a case secondary to retropharyngeal abscess]. / Tortícolis no distónico. A propósito de un caso secundario a un absceso retrofaríngeo.

INTRODUCTION: There are many causes of acquired non-dystonic torticollis: cervical bony anomalies, nasopharyngeal infections, tumours of the spinal cord, and posterior fossa, ocular, vestibular and gastrointestinal disorders. In children, non-dystonic is commoner than dystonic torticollis, except for in adverse reactions to drugs. Palatopharyngeal lesions due to a rigid object being impacted in the mouth (pencil-injury) are common in childhood. Many are not dangerous and require no specific treatment, although there is a risk of perforation of the pharyngeal wall and of a retropharyngeal abscess. CLINICAL CASE: We report the case of a 9 year old boy who was seen in the Emergency Department complaining of fever present for four days and progressive cervical rigidity for the past two days which did not improve with myorelaxant drugs. A lateral X-ray of the spine showed prevertebral air and on the oesophagogram a fistula tract was seen. On further questioning the boy admitted that a stick he had had in his mouth had caused damage the day before his fever started. CT showed the extent of the abscess. After a week of treatment with antibiotics and corticosteroids the clinical features disappeared, and on CT after two weeks it was seen that the abscess had resolved. CONCLUSIONS: We suggest that a lateral radiograph of the neck should be done in cases of acquired torticollis, even though there is no suspicious clinical history. Early diagnosis and treatment of retropharyngeal abscesses is essential to prevent extension to adjacent structures, and atlanto-axoid subluxation secondary to the oedema and tension of the ligaments caused by the abscess (Grisel's syndrome).

Distinct regulation of osmoprotective genes in yeast and mammals. Aldose reductase osmotic response element is induced independent of p38 and stress-activated protein kinase/Jun N-terminal kinase in rabbit kidney cells.

In yeast glycerol-3-phosphate dehydrogenase 1 is essential for synthesis of the osmoprotectant glycerol and is osmotically regulated via the high osmolarity glycerol (HOG1) kinase pathway. Homologous protein kinases, p38, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) are hyperosmotically activated in some mammalian cell lines and complement HOG1 in yeast. In the present study we asked whether p38 or SAPK/JNK signal synthesis of the osmoprotectant sorbitol in rabbit renal medullary cells (PAP-HT25), analogous to the glycerol system in yeast. Sorbitol synthesis is catalyzed by aldose reductase (AR). Hyperosmolality increases AR transcription through an osmotic response element (ORE) in the 5'-flanking region of the AR gene, resulting in elevated sorbitol. We tested if AR-ORE is targeted by p38 or SAPK/JNK pathways in PAP-HT25 cells. Hyperosmolality (adding 150 mM NaCl) strongly induces phosphorylation of p38 and of c-Jun, a specific target of SAPK/JNK. Transient lipofection of a dominant negative mutant of SAPK kinase, SEK1-AL, into PAP-HT25 cells specifically inhibits hyperosmotically induced c-Jun phosphorylation. Transient lipofection of a dominant negative p38 kinase mutant, MKK3-AL, into PAP-HT25 cells specifically suppresses hyperosmotic induction of p38 phosphorylation. We cotransfected either one of these mutants or their empty vector with an AR-ORE luciferase reporter construct and compared the hyperosmotically induced increase in luciferase activity with that in cells lipofected with only the AR-ORE luciferase construct. Hyperosmolality increased luciferase activity equally (5-7-fold) under all conditions. We conclude that hyperosmolality induces p38 and SAPK/JNK cascades in mammalian renal cells, analogous to inducing the HOG1 cascade in yeast. However, activation of p38 or SAPK/JNK pathways is not necessary for transcriptional regulation of AR through the ORE. This finding stands in contrast to the requirement for the HOG1 pathway for hyperosmotically induced activation of yeast GPD1.

Oxygenation capacity of hypotonized and crosslinked rat erythrocytes.

Rat erythrocytes subjected to hypotonic-isotonic dialysis, or crosslinking with bifunctional reagents (glutaraldehyde and dimethyl suberimidate hydrochloride) show a high percentage of methemoglobin and decreased oxyhemoglobin content which implies a low oxygen carrying capacity. Such modified cells maintain reversible oxygen binding properties although, they present a high hemoglobin oxygen affinity (low P50) and a diminished cooperativity in binding oxygen to hemoglobin (low n). These results suggest a reduced capacity of liberating oxygen to tissues under low PO2. Changes produced in erythrocytes can not be restored even in the presence of energy (ATP), reduced glutathione and 2,3-bisphosphoglyceric acid during the dialysis process or after crosslinking/permeabilizing treatment.

Betaine transporter cDNA cloning and effect of osmolytes on its mRNA induction.

Cells generally adapt to long-term hyperosmolality by accumulating compatible organic osmolytes, thereby helping to normalize both volume and intracellular inorganic ion concentration. When organic osmolytes are accumulated, as in renal inner medullary cells, it is the sum of their concentrations that is theoretically important. In effect, when one organic osmolyte rises, the others generally fall to maintain their sum approximately constant. The present study addresses the mechanism controlling betaine accumulation. Hypertonicity induces accumulation of betaine, sorbitol, inositol, and other organic osmolytes in PAP-HT25 cells, a line derived from rabbit renal papilla. Hypertonicity increases the betaine transporter expression in these cells. To obtain a specific probe for betaine transporter mRNA, we cloned from PAP-HT25 cells a cDNA that encodes the full protein. We then examined the effect of betaine, sorbitol, and inositol on betaine transporter mRNA abundance. Increased accumulation of any of these three organic osmolytes reduces betaine transporter mRNA. We previously observed similar results for aldose reductase, the enzyme responsible for osmotically regulated sorbitol accumulation. We conclude that the accumulation of organic osmolytes regulates betaine transporter gene expression. Because the aldose reductase gene is controlled in a similar fashion, we surmise that the two genes share a common signal for induction.

Betaine and inositol reduce MDCK cell glycerophosphocholine by stimulating its degradation.

The amount of glycerophosphocholine (GPC) in renal medullary cells in vivo and in cultured renal [Madin-Darby canine kidney (MDCK)] cells varies with extracellular NaCl and urea. We previously showed that this is largely due to modulation of GPC degradation catalyzed by GPC:choline phosphodiesterase (GPC: PDE). GPC also varies inversely with the levels of other compatible osmolytes, the accumulation of which is induced by high tonicity. We tested whether GPC:PDE activity and GPC degradation are affected by accumulation of compatible osmolytes other than GPC. We find that MDCK cell GPC content decreases when the cells take up betaine and/or inositol from the medium. The effect is considerably greater for cells in isosmotic or high-NaCl medium than in high-urea medium. This difference is associated with suppression of betaine and inositol accumulation with high urea. We then measured GPC:PDE activity with a novel chemiluminescent assay. Addition of inositol and/or betaine to the medium greatly increases GPC:PDE activity in cells in isosmotic or high-NaCl media, but the increase is much less in high-urea medium. The increases in GPC:PDE activity, associated with the presence of betaine, are accompanied by commensurate increases in absolute rates of endogenous GPC degradation by cells in isosmotic or high-NaCl medium. We found previously that, in MDCK cells incubated for 2 days in high-NaCl medium, the rate of GPC synthesis from phosphatidylcholine is increased, correlated with an increase in phospholipase activity. However, in the present experiments, betaine accumulation has no effect on phospholipase activity under those conditions and, thus, presumably does not affect GPC synthesis. Collectively, these data support the conclusion that betaine and/or inositol reduces GPC by increasing GPC degradation catalyzed by GPC:PDE. This mechanism enables GPC to be reciprocally regulated relative to other compatible osmolytes, thus maintaining an appropriate total osmolyte content.

CD9 antigen mRNA is induced by hypertonicity in two renal epithelial cell lines.

In diverse organisms, cells adapt to hyperosmotic stress by accumulating organic osmolytes. Mammalian renal medullary cells are routinely under osmotic stress. Two renal cell lines, Madin-Darby canine kidney (MDCK) and PAP-HT25, have been widely used to study mammalian osmotic regulation. In these epithelial cells, extracellular hypertonicity induces gene transcription of proteins directly involved in the metabolism and transport of organic osmolytes. This induction is relatively specific and not part of a generalized stress response. Little is known about the signal transduction pathway between cellular detection of extracellular osmolality and increased specific gene transcription. Here, using differential mRNA display polymerase chain reaction on MDCK cells in isotonic vs. hypertonic medium, we identify a cDNA product corresponding to CD9 antigen mRNA. CD9 antigen is a cell surface glycoprotein originally found in cells of the immune system. Although CD9 antigen has been structurally characterized, its function is unclear. We further demonstrate that CD9 antigen mRNA is present in MDCK and PAP-HT25 cells and that its mRNA abundance is induced by extracellular hypertonicity, but not by heat stress. Also, we show that accumulation of organic osmolytes markedly attenuates the CD9 mRNA induction, as only recently demonstrated with genes involved in the hyperosmotic stress response. This suggests a role for CD9 antigen in this response.

Induction of gene expression by heat shock versus osmotic stress.

Elevated temperature rapidly increases expression of genes for heat shock proteins (HSP), including HSP-70. The response is presumably triggered by denaturation of cell proteins and helps in their renaturation. Hypertonicity may also denature proteins, but the protective response, which is accumulation of compatible organic osmolytes [including betaine and inositol in Madin-Darby canine kidney (MDCK) cells], apparently differs and is slow. Recently, hypertonicity was found also to increase expression of HSP-70 in MDCK cells, a response proposed to provide protection until organic osmolytes can accumulate. Our purpose was to examine whether 1) a gene involved in accumulation of organic osmolytes also responds to heat stress and 2) whether accumulation of organic osmolytes affects expression of HSP-70. We find that 1) the betaine transporter mRNA, which is greatly increased by hypertonicity (515 vs. 315 mosmol), is unaffected by high temperature (42 degrees C vs. 37 degrees C); 2) hypertonicity-induced increases in HSP-70 and betaine transporter mRNA are much greater when the medium (and cell) contain no betaine and no inositol than when high concentrations of these are present; and 3) high betaine greatly inhibits the increase in HSP-70 mRNA at high temperature. We conclude the following. 1) Although heat shock and betaine transporter genes both respond to hypertonicity, the betaine transporter is not a HSP. 2) Accumulation of organic osmolytes attenuates the HSP-70 response to hypertonicity, as it might if the HSP-70 expression were a temporizing response. 3) Betaine inhibits HSP-70 response to elevated temperature, presumably by its known effect of stabilizing proteins.

Neuropsychological evaluation of children with intracranial tumors: impact of treatment modalities.

Antineoplastic treatment has a deleterious effect on intellectual functions, which is mainly attributable to radiotherapy. With the object of determining the neuropsychological disturbances associated with brain irradiation in the child, and to try to differentiate them from the effects caused by the other types of treatment (surgical and chemotherapy) as well as from the effects of the tumor itself, a cross-sectional study was carried out in 25 survivors of medial edge intracranial tumors. In order to monitor the effect of systemic chemotherapy on the cognitive functions, and the effect of prolonged absence from school, two control groups were formed, one made up of subjects treated with chemotherapy for extracranial tumors, and the other of patients with non-malignant chronic disease. Neuropsychological functions were measured using the Spanish version of the Wechsler scale, as well as the following tests: Spreen-Benton, ITPA and TALE scales, Yuste Memory Test, Thurstone Attention Test, and the Rey Complex Figure. In addition to a progressive decline found in the full scale intelligence quotient in children irradiated for intracranial tumors, variance analysis showed that these patients deteriorate mainly in visual attention and memory, but also significantly in verbal fluency and in the Performance Intelligence Quotient and all its subtests, when compared to the control groups. Visual attention and the Wechsler Picture Arrangement and Block Designs, were the tests whose decline correlated with the total radiation administered. The article relates this specific neuropsychological injury with the total brain irradiation dose but also with the structures located in the cone-down fields of irradiation to boost regions in the middle edge intracranial content.