Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma.

Purpose: To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA).Methods and Materials: Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 +/- 4.6 cm(3). Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 +/- 37.2 months.Results: Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively.Conclusions: SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual.

Increased flow of fatty acids toward beta-oxidation in developing seeds of Arabidopsis deficient in diacylglycerol acyltransferase activity or synthesizing medium-chain-length fatty acids.

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid beta-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0. 06 mg g(-1) dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward beta-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via beta-oxidation and that a considerable flow toward beta-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids.

Linezolid alone or combined with rifampin against methicillin-resistant Staphylococcus aureus in experimental foreign-body infection.

We investigated the activity of linezolid, alone and in combination with rifampin (rifampicin), against a methicillin-resistant Staphylococcus aureus (MRSA) strain in vitro and in a guinea pig model of foreign-body infection. The MIC, minimal bactericidal concentration (MBC) in logarithmic phase, and MBC in stationary growth phase were 2.5, >20, and >20 microg/ml, respectively, for linezolid; 0.01, 0.08, and 2.5 microg/ml, respectively, for rifampin; and 0.16, 0.63, >20 microg/ml, respectively, for levofloxacin. In time-kill studies, bacterial regrowth and the development of rifampin resistance were observed after 24 h with rifampin alone at 1x or 4x the MIC and were prevented by the addition of linezolid. After the administration of single intraperitoneal doses of 25, 50, and 75 mg/kg of body weight, linezolid peak concentrations of 6.8, 12.7, and 18.1 microg/ml, respectively, were achieved in sterile cage fluid at approximately 3 h. The linezolid concentration remained above the MIC of the test organism for 12 h with all doses. Antimicrobial treatments of animals with cage implant infections were given twice daily for 4 days. Linezolid alone at 25, 50, and 75 mg/kg reduced the planktonic bacteria in cage fluid during treatment by 1.2 to 1.7 log(10) CFU/ml; only linezolid at 75 mg/kg prevented bacterial regrowth 5 days after the end of treatment. Linezolid used in combination with rifampin (12.5 mg/kg) was more effective than linezolid used as monotherapy, reducing the planktonic bacteria by >or=3 log(10) CFU (P < 0.05). Efficacy in the eradication of cage-associated infection was achieved only when linezolid was combined with rifampin, with cure rates being between 50% and 60%, whereas the levofloxacin-rifampin combination demonstrated the highest cure rate (91%) against the strain tested. The linezolid-rifampin combination is a treatment option for implant-associated infections caused by quinolone-resistant MRSA.

Blood pressure response to central and/or peripheral inhibition of phenylethanolamine N-methyltransferase in normotensive and hypertensive rats

We studied the effects on blood pressure and heart rate of two different phenylethanolamine N-methyltransferase (PNMT) inhibitors in normotensive, in two-kidney renal hypertensive, and in deoxycorticosterone-salt (DOC-salt) hypertensive rats. One compound (SK&F 64139) blocks the conversion of norepinephrine to epinephrine in both the central and the peripheral nervous system, whereas the other (SK&F 29661) does not cross the blood-brain barrier and therefore is active mostly in the adrenal glands. In the rats given SK&F 29661, practically no acute blood pressure changes were in the adrenal glands. In the rats given SK&F 64139 induced only a minor blood pressure and heart rate response in normotensive and two-kidney renal hypertensive rats. However, in DOC-salt hypertensive rats, it reduced arterial pressure to approximately normal levels and concomitantly slowed pulse rate. There was a close correlation between the magnitude of the blood pressure response observed in all SK&F 64139-treated animals and the control plasma norepinephrine (4 = -0.795, P less than 0.001) and epinephrine (r = -0.789, P less than 0.001) levels. These results suggest an important role for central epinephrine in regulating the peripheral sympathoadrenomedullary and the baroreceptor reflex activity, particularly when the maintenance of the high blood pressure is not renin-dependent.

Strokes and TIAs during and after Carotid Artery Doppler: Cause or Coincidence?

The aim of the present study was to explore the prevalence of acute cerebrovascular symptoms temporally related to carotid Doppler examination (DEx), in order to increase the awareness and recording of such events and to discuss possible mechanisms. All adult patients who complained of acute onset neurologic symptoms during or shortly after a carotid DEx, between 01/2003 and 12/2011 in the University Hospital of Lausanne were prospectively collected. We identified four consecutive patients with acute onset neurologic symptoms during or shortly after a carotid DEx among approximately 13,500 patients who underwent carotid DEx in our facility during the nine-year period (0.015% of all examined carotids). Clinical data, imaging reports and CTA (CT angiography) or/and ultrasound images are presented for each patient. Ischemic cerebrovascular events during or immediately after cervical Doppler could be due to chance or to several physical factors. They should be promptly recognized by Doppler personnel and properly treated, but do not put into question the overwhelming benefits of Doppler in cerebrovascular patients.

Le vélo électrique: un outil pour la santé ou un gadget "écolo" [Electrically assisted bicycles: health enhancement or "green" gadget?].

Electrically assisted bicycles (EAB) are flourishing in cities throughout the world and capitalize on ecological and practical advantages, helping in the fight against pollution, CO2 emissions and traffic jam. Human power is necessary to activate the electrical support, so that it equals to a moderate intensity physical activity (> 3 MET), or a vigorous one on hilly courses (>6 MET). The ecological benefits are obvious and transportation departments tend to support citizens who purchase one. EAB offer increased mobility at speeds of 15 to 25 km/h depending on hills and fitness of the rider, but could cause more accidents. EAB is linked to a real physical activity beneficial for health, but potentially more dangerous than a traditional bicycle.

Giving or Receiving Something for Sex: A Cross-Sectional Study of Transactional Sex among Ugandan University Students.

OBJECTIVE: This study sought to determine the prevalence of transactional sex among university students in Uganda and to assess the possible relationship between transactional sex and sexual coercion, physical violence, mental health, and alcohol use. METHODS: In 2010, 1954 undergraduate students at a Ugandan university responded to a self-administered questionnaire that assessed mental health, substance use, physical violence and sexual behaviors including sexual coercion and transactional sex. The prevalence of transactional sex was assessed and logistic regression analysis was performed to measure the associations between various risk factors and reporting transactional sex. RESULTS: Approximately 25% of the study sample reported having taken part in transactional sex, with more women reporting having accepted money, gifts or some compensation for sex, while more men reporting having paid, given a gift or otherwise compensated for sex. Sexual coercion in men and women was significantly associated with having accepted money, gifts or some compensation for sex. Men who were victims of physical violence in the last 12 months had higher probability of having accepted money, gifts or some compensation for sex than other men. Women who were victims of sexual coercion reported greater likelihood of having paid, given a gift or otherwise compensated for sex. Respondents who had been victims of physical violence in last 12 months, engaged in heavy episodic drinking and had poor mental health status were more likely to have paid, given a gift or otherwise compensated for sex. CONCLUSIONS: University students in Uganda are at high risk of transactional sex. Young men and women may be equally vulnerable to the risks and consequences of transactional sex and should be included in program initiatives to prevent transactional sex. The role of sexual coercion, physical violence, mental health, and alcohol use should be considered when designing interventions for countering transactional sex.

16-OR: Investigation of Sharp Trauma and Gunshot Cases Using Post-mortem CT-Angiography

Investigation of violent death, especially cases of sharp trauma and gunshot, is an important part of medico-legal investigations. Beside the execution of a conventional autopsy, the performance of a post-mortem Multi-Detector Computed Tomography (MDCT)-scan has become a highly appreciated tool. In order to investigate also the vascular system, post-mortem CT-angiography has been introduced. The most studied and widespread technique is the Multi-phase post-mortem CT-angiography (MPMCTA). Its sensitivity to detect vascular lesions is even superior to conventional autopsy. The application of MPMCTA for cases of gunshot and sharp-trauma is therefore an obvious choice, as vascular lesions are common in such victims. In most cases of sharp trauma and in several cases of gunshots, death can be attributed to exsanguinations. MPMCTA is able to detect the exact source of bleeding and also to visualize trajectories, which are of most importance in these cases. The reconstructed images allow to clearly visualizing the trajectory in a way that is easily comprehensible for not medically trained legal professionals. The sensitivity of MPMCTA for soft tissue and organ lesions approximately matches the sensitivity of conventional autopsy. However, special care, experience and effective use of the imaging software is necessary for performing the reconstructions of the trajectory. Large volume consuming haemorrhages and shift of inner organs are sources of errors and misinterpretations. This presentation shall give an overview about the advantages and limitations of the use of MPMCTA for investigating cases of gunshot and sharp-trauma.

Perforation colique néonatale focale spontanée en dehors de la grande prématurité : rare et potentiellement insidieuse [Focal spontaneous colic perforation in term or near-term neonates: rare and potentially insidious].

Two cases of neonatal focal spontaneous colic perforations are reported. The 1st infant, born at 36 3/7 weeks gestational age, presented on day 3 with crying, abdominal distension, and liquid stools. Clinical examination showed a slightly irritable hypothermic (35.7 °C) infant with a distended abdomen and few bowel sounds. Blood tests were normal apart from an elevated C-reactive protein level (59 mg/l). The abdomen x-ray was erroneously considered normal. The infant's condition remained stable for nearly 3 days. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was started on antibiotics and operated. Macroscopically, the entire gut was normal apart from a focal sigmoid perforation, which was stitched. A transmural colic biopsy revealed focal vascular dilation but was negative for necrotising enterocolitis or Hirschsprung disease. The infant recovered quickly. She is now a healthy, normal 3-year-old. The 2nd infant, born at 38 5/7 weeks gestational age, presented between day 1 and 2 with clinical signs of infection associated with slowly progressive ileus. The chest and abdomen x-ray was mistakenly considered normal. Frank septicemia developed. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was operated. Macroscopically, the small intestine was normal, the ascending and transverse colons were dilated, and the descending and sigmoid colons were narrow. Three cecal perforations were discovered and stitched. An ileostomy and multiple colic biopsies were also performed. The postoperative course was complicated by persistent septic ileus due to descending and sigmoid colon leaks, which led to colic resections with end-to-end anastomosis. Rectal aspiration biopsies were also performed. At 1 month of age, the infant was discharged from the hospital. The ileostomy was closed in two steps at 2 and 5 months of age. A normal sweat test excluded cystic fibrosis. All colic and rectal biopsies revealed nonspecific inflammatory signs and excluded necrotizing enterocolitis and Hirschsprung disease. Nonspecific irregular thinning of muscularis mucosae and muscularis propria were observed in the two resected colic segments. The boy is now a healthy 7-year-old. The incidence of neonatal focal spontaneous colic perforations at term or close to term is unknown but probably very rare. Our department is the neonatal referral center for approximately 14,000 annual births. In the last 10 years (2000-2009), out of 5115 neonatal admissions in our unit, only ten cases have presented a neonatal spontaneous intestinal perforation, seven of ten in very-low-birth-weight infants and three of ten in term or near-term neonates (one with Hirschsprung disease and the two cases reported herein). In the same period, 108 infants suffered from necrotizing enterocolitis, seven of 108 were term infants and 6 out of 7 had a congenital heart disease. The medical literature is poor on the subject of focal spontaneous colic perforations at term; no risk factor is described. The most specific clinical sign seems to be the abdominal distension. The presence of pneumoperitoneum on an abdominal x-ray is the most sensitive paraclinical sign. In case of an intestinal perforation, surgery must be performed quickly. The vital prognosis seems to be good. The objective of this study was to draw pediatricians' attention to focal spontaneous colic perforations in term or close to term newborns. In the cases reported, the diagnostic delays could have been prevented if the entity - with its radiological manifestation - had been well known.

Computed tomography of the cervical spine: comparison of image quality between a standard-dose and a low-dose protocol using filtered back-projection and iterative reconstruction.

OBJECTIVE: To compare image quality of a standard-dose (SD) and a low-dose (LD) cervical spine CT protocol using filtered back-projection (FBP) and iterative reconstruction (IR). MATERIALS AND METHODS: Forty patients investigated by cervical spine CT were prospectively randomised into two groups: SD (120 kVp, 275 mAs) and LD (120 kVp, 150 mAs), both applying automatic tube current modulation. Data were reconstructed using both FBP and sinogram-affirmed IR. Image noise, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were measured. Two radiologists independently and blindly assessed the following anatomical structures at C3-C4 and C6-C7 levels, using a four-point scale: intervertebral disc, content of neural foramina and dural sac, ligaments, soft tissues and vertebrae. They subsequently rated overall image quality using a ten-point scale. RESULTS: For both protocols and at each disc level, IR significantly decreased image noise and increased SNR and CNR, compared with FBP. SNR and CNR were statistically equivalent in LD-IR and SD-FBP protocols. Regardless of the dose and disc level, the qualitative scores with IR compared with FBP, and with LD-IR compared with SD-FBP, were significantly higher or not statistically different for intervertebral discs, neural foramina and ligaments, while significantly lower or not statistically different for soft tissues and vertebrae. The overall image quality scores were significantly higher with IR compared with FBP, and with LD-IR compared with SD-FBP. CONCLUSION: LD-IR cervical spine CT provides better image quality for intervertebral discs, neural foramina and ligaments, and worse image quality for soft tissues and vertebrae, compared with SD-FBP, while reducing radiation dose by approximately 40 %.

Intermittierende oder Persistierende Rhinitis bei Kindern und Jugendlichen mit Asthma: «The Swiss LARA paediatrics survey [Intermittent or persistent rhinitis in children and adolescents with Asthma: «the Swiss LARA paediatrics survey»].

Asthma and allergic rhinitis are chronic inflammatory airway diseases which often occur concomitantly. The objective of the LARA program was to identify the comorbidities and characteristics of asthma (A), intermittent or persistent rhinitis (IPR) and physician defined atopic dermatitis (AD) in 6- to 16-year old asthmatic Swiss children and adolescents. Overall, 126 general practitioners and paediatricians collected the data of 670 asthmatics. Approximately one third of the asthmatic children in Switzerland had well-controlled asthma. Almost two thirds of these asthmatics suffered from concomitant IPR. The latter presented with significantly less symptoms while the treatment rates with inhaled corticosteroids (approximately 90%) and leukotriene-receptorantagonists (approximately 50%) were comparable. However, there were almost twice as many passive smokers in the less well-controlled group. The prevalence of AD was similar in both groups. IPR and AD may play an important role as risk factors in the future development of asthma.

Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL).

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.

Does a mandatory telemedicine call prior to visiting a physician reduce costs or simply attract good risks?

This paper aims to estimate empirically the efficiency of a Swiss telemedicine service introduced in 2003. We used claims' data gathered by a major Swiss health insurer, over a period of 6 years and involving 160 000 insured adults. In Switzerland, health insurance is mandatory, but everyone has the option of choosing between a managed care plan and a fee-for-service plan. This paper focuses on a conventional fee-for-service plan including a mandatory access to a telemedicine service; the insured are obliged to phone this medical call centre before visiting a physician. This type of plan generates much lower average health expenditures than a conventional insurance plan. Reasons for this may include selection, incentive effects or efficiency. In our sample, about 90% of the difference in health expenditure can be explained by selection and incentive effects. The remaining 10% of savings due to the efficiency of the telemedicine service amount to about SFr 150 per year per insured, of which approximately 60% is saved by the insurer and 40% by the insured. Although the efficiency effect is greater than the cost of the plan, the big winners are the insured who not only save monetary and non-monetary costs but also benefit from reduced premiums. Copyright © 2010 John Wiley & Sons, Ltd.

Radiotherapy for GIST progressing during or after tyrosine kinase inhibitor therapy: A prospective study.

PURPOSE: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant, and radiotherapy is recommended only for palliation of bone metastases in current treatment guidelines. No registered prospective trial has evaluated GIST responsiveness to radiotherapy. PATIENTS AND METHODS: Patients with GIST progressing at intra-abdominal sites or the liver were entered to this prospective Phase II multicenter study (identifier NCT00515931). Metastases were treated with external beam radiotherapy using either conformal 3D planning or intensity modulated radiotherapy and conventional fractionation to a cumulative planning target volume dose of approximately 40Gy. Systemic therapy was maintained unaltered during the study. RESULTS: Of the 25 patients entered, 19 were on concomitant tyrosine kinase inhibitor therapy, most often imatinib. Two (8%) patients achieved partial remission, 20 (80%) had stable target lesion size for ⩾3months after radiotherapy with a median duration of stabilization of 16months, and 3 (12%) progressed. The median time to radiotherapy target lesion progression was 4-fold longer than the median time to GIST progression at any site (16 versus 4months). Radiotherapy was generally well tolerated. CONCLUSIONS: Responses to radiotherapy were infrequent, but most patients had durable stabilization of the target lesions. GIST patients with soft tissue metastases benefit frequently from radiotherapy.