International round-robin experiment for angle-resolved light scattering measurement.

An international round-robin experiment has been conducted to test procedures and methods for the measurement of angle-resolved light scattering. ASTM E2387-05 has been used as the main guide, while the experience gained should also contribute to the new ISO standard of angle-resolved scattering currently under development (ISO/WD 19986:2016). Seven laboratories from Europe and the United States measured the angle-resolved scattering from Al/SiO2-coated substrates, transparent substrates, volume diffusors, quasi-volume diffusors, white calibration standards, and grating samples at laser wavelengths in the UV, VIS, and NIR spectra. Results were sent to Fraunhofer IOF, which coordinated the experiments and analyzed the data, while ESA-ESTEC, as the project donor, defined conditions and parameters. Depending mainly on the sample type, overall good to reasonable agreements were observed, with largest deviations at scattering angles very close to the specular beam. Volume diffusor characterization unexpectedly turned out to be challenging. Not all participants provided measurement uncertainty ranges according to the Guide to the Expression of Uncertainty in Measurement; often, a single general scatterometer-related measurement uncertainty value was stated. Although relative instrument measurement uncertainties close to 1% are sometimes claimed, the comparison results did not support these claims for specular scattering samples as mirrors, substrates, or gratings.

Forecasting the global demand for HIV monitoring and diagnostic tests: A 2016-2021 analysis.

INTRODUCTION: Despite considerable progress, just over half of the 37 million people eligible to start antiretroviral therapy (ART) have accessed treatment and millions of HIV-positive people still do not know their status. With demand for ART continuing to grow, meeting the ambitious 90-90-90 HIV treatment targets will depend on improved access to high-quality diagnostics to both diagnose infection and monitor treatment adherence in low and middle-income countries (LMICs). Robust projections of future demand for CD4, viral load (VL), HIV early-infant-diagnosis (EID) tests and HIV rapid diagnostic tests (RDTs) are needed as scale-up continues. METHODS: We estimate the current coverage for HIV diagnostics and project future demand to 2021 using a consolidated forecast using data on past coverage and current demand from a number of sources, from 130 predominantly LMIC countries. RESULTS: We forecast that the overall number of CD4 tests is expected to decline between now and 2021 as more countries adopt test-and-treat and shift to VL testing for patient monitoring. Our consolidated forecast projects a gradual decline in demand for CD4 tests to 16.6 million by 2021. We anticipate that demand for VL tests will increase to 28.5 million by 2021, reflecting the increasing number of people who will receive ART and the adoption of VL testing for patient monitoring. We expect that the demand for EID tests will grow more rapidly than in past years, driven by the implementation of testing at birth in programmes globally, in line with WHO guideline recommendations, doubling to 2.1 million tests by 2021. Demand for rapid diagnostic tests is also likely to increase, reaching 509 million tests by 2021. DISCUSSION: In order to achieve the ambitious 90-90-90 targets, it will be essential to maintain and improve access to CD4, VL, EID tests and RDTs. These projections provide insight into the global demand we can expect to see for these HIV monitoring and diagnostic tests, both in relation to historical trends, and the 90-90-90 targets. Our projections will better enable producers to ensure adequate supply, and to support procurement organisations in planning future funding and purchase plans to meet the anticipated demand. The findings highlight the ongoing need for governments and international funding bodies to prioritise improving capacity and access to HIV diagnostic and monitoring technologies in line with demand.

A Diabetes-specific Oral Nutritional Supplement Improves Glycaemic Control in Type 2 Diabetes Patients.

AIMS: Reducing the intake of low molecular weight carbohydrates with artificial nutrition may lower glycaemic response in patients with diabetes. We evaluated effects of a diabetes-specific carbohydrate modified oral nutritional supplement (ONS) during 12 weeks administration in 40 elderly type 2 normal weight patients with diabetes with previous involuntary weight loss. METHODS: Prospective, randomised, double-blind, controlled trial. Patients ingested 2×200 ml/day diabetes-specific or isocaloric standard ONS (control) in addition to their regular diet. Parameters of glucose and lipid metabolism, functional and nutritional status were assessed at baseline, weeks 6 and 12. RESULTS: Postprandial glucose incremental area under the curve (iAUC0-240 min) was comparable between treatment groups on day 1 (467.9±268.4 vs. 505.1±206.1 mmol/l*min, n.s. - arithmetic means±standard deviation) and was significantly lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (355.2±115.8 vs. 634.9±205.9 and 364.9±153.1 vs. 743.4±202.7; both P<0.0001). Postprandial peak glucose was significantly lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (P<0.0001) and the decrease in HbA1c, (baseline to week 12) was markedly pronounced (P=0.028). There were no differences between groups in insulin, HOMA-IR, lipid parameters, nutritional and performance status. Body weight and body mass index (BMI) increased significantly over time in both groups. CONCLUSIONS: Administration of a diabetes-specific ONS for 12 weeks reduced postprandial glycaemia after ingestion of the study treatment and improved long-term glycaemic control in elderly patients with type 2 diabetes and involuntary weight loss, thereby reducing their risk for diabetes-associated long-term complications.

Reversal of PSA progression on abiraterone acetate through the administration with food in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Owing to efficacy and tolerability, abiraterone acetate (AA) is a leading treatment for men with metastatic castration-resistant prostate cancer. Increased serum concentrations of AA, such as by taking AA with food, may lead to the inhibition of additional enzymes in the androgen synthesis pathway implicated in castration-resistant prostate cancer progression. METHODS: Medical records of men with metastatic castration-resistant prostate cancer (mCRPC) who received AA between 1 April 2011 and 31 December 2013 were retrospectively reviewed. The primary outcome was the percent of men with a rising PSA on AA who experienced any PSA decline within 3 months after changing the administration of AA from without food to with food. Secondary outcomes were median time on AA therapy in men who received AA therapy without food versus those that switched administration from without food to with food at PSA progression, and the percent of men who experienced any decline in serum testosterone concentration, and the rate of adverse events observed while taking AA with food. RESULTS: Nineteen men who switched AA administration from without food to with food and 41 patients who administered AA without food only were included in the study. Of those patients who took AA with food at PSA progression, a PSA decline was observed in 3 of the 19 (16%) men, including 3 of the 14 men who had an initial response to AA (21%). Testosterone declined in five out of seven patients from pre-food levels. The median time on AA therapy was increased by nearly 100 days in patients who switched AA administration from without food to with food. No increases in toxicity were observed. CONCLUSION: Some men with mCRPC may benefit from taking AA with food. Further prospective comparative studies are needed to determine if changing AA administration is beneficial.

Resuscitative emergency thoracotomy in a Swiss trauma centre.

BACKGROUND: Resuscitative emergency thoracotomy (ET) is performed as a salvage manoeuvre for selected patients with trauma. However, reports from European trauma centres are scarce. METHODS: A retrospective analysis was undertaken of injured patients who underwent resuscitative ET in the emergency department (ED) or operating room (OR) between January 1996 and September 2008. Survival in the ED and to hospital discharge was analysed using logistic regression. RESULTS: During the study interval 121 patients required a resuscitative thoracotomy, of which 49 (40·5 per cent) were performed in the ED and 72 (59·5 per cent) in the OR. Patients in the OR had higher blood pressure on arrival (median 110 versus 60 mmHg; P < 0·001), were less often in severe haemorrhagic shock (63 versus 94 per cent; P < 0·001), had fewer serious head injuries (Abbreviated Injury Score of 3 or above in 33 versus 53 per cent; P = 0·031) and more often had a penetrating stab wound as the dominating mechanism (25 versus 10 per cent; P = 0·042) compared with those in the ED. Ten patients (20 per cent) survived to hospital discharge after ED thoracotomy, compared with 53 (74 per cent) of those treated in the OR. Penetrating injury and Glasgow Coma Scale score above 8 were independent predictors of hospital survival following ED thoracotomy. No patient with a blunt injury and no detectable signs of life on admission survived. Three of 26 patients with blunt trauma and signs of life on admission survived to hospital discharge. CONCLUSION: Resuscitative ET may be life-saving in selected patients. Location of the procedure is dictated by injury severity and vital parameters. Outcome is best when signs of life are present on admission, even for blunt injuries.

Arterial lactate above 2 mM is associated with increased brain lactate and decreased brain glucose in patients with severe traumatic brain injury.

BACKGROUND: Lactate fuels cerebral energy-consuming processes and it is neuroprotective. The impact of arterial lactate on brain metabolism determined by microdialysis was investigated retrospectively in patients with severe traumatic brain injury (TBI). METHODS: Cerebral microdialysis (glucose, lactate), neuromonitoring (ICP, CPP, ptiO2, SjvO2) and blood gas data collected in 20 patients during pharmacologic coma were grouped within predefined arterial lactate clusters (<1, 1-2, >2 mM). Microdialysis samples were only taken from time points characterized by normoventilation (paCO2 34.5-42 mmHg), sufficient oxygenation (paO2 >75 mmHg) and hematocrit (≥24%) to exclude confounding influences. RESULTS: Elevated arterial lactate ≥2 mM was associated with significantly increased brain lactate which coincided with markedly decreased brain glucose despite significantly increased arterial glucose levels and sufficient cerebral perfusion indirectly determined by normal SjvO2 and ptiO2 values. At elevated arterial lactate levels signs of significantly increased cerebral lactate uptake coincided with markedly decreased cerebral glucose uptake. Infused lactate above 50 mM per 24 hours was associated with significantly decreased cerebral glucose. CONCLUSION: Increased arterial lactate levels were associated with increased cerebral lactate uptake and elevated brain lactate. At the same time brain glucose uptake and brain glucose were significantly reduced. It remains unclear whether arterial lactate is the driving force for the increased cerebral lactate levels or if the reduced glucose uptake also contributed to the increased cerebral lactate levels. Further studies are required to assess the impact of lactate infusion under clinical conditions.

Changes in calculated arterio-jugular venous glutamate difference and SjvO2 in patients with severe traumatic brain injury.

BACKGROUND: Cerebral metabolic impairment is feared to induce secondary brain damage following traumatic brain injury (TBI). The present study was designed to assess the temporal profile of calculated arterio- jugular venous differences in glutamate (AJVDglu) and SjvO(2) in patients subjected to continuous pharmacologic coma. Metabolic impairment was assumed to be reflected by increased jugular venous glutamate levels and decreased jugular venous oxygen saturation (SjvO(2)). METHODS: Arterial and jugular venous blood was drawn once daily for up to 14 days from 14 patients to assess the temporal profile. Plasma glutamate was measured by high performance liquid chromatography. SjvO(2), lactate and paCO(2) were determined in routine blood gas analysis. Calculated AJVD indirectly reflects cerebral uptake (positive values) or cerebral release (negative values). RESULTS: During pharmacologic coma an increase in ICP approaching 20 mmHg was associated with significantly reduced paCO(2) (4.7 ± 0.5 kPa; mean ± standard deviation), markedly decreased SjvO(2) (66.0 ± 4.2%) without reaching ischemic values, and a trend to more negative AJVDglu values (-6.0 ± 14.3 µmol/L), suggesting cerebral glutamate release. Arterio- jugular venous lactate difference (AJVDlac) remained unchanged. CONCLUSION: During pharmacologic coma increased ICP was associated with significantly decreased SjvO(2) which coincided only with a trend to increased cerebral glutamate release. Calculated AJVDglu appears to be inferior in unmasking altered brain metabolism compared to SjvO(2) whenever ICP is increased.

The Spectrum projection package: improvements in estimating incidence by age and sex, mother-to-child transmission, HIV progression in children and double orphans.

BACKGROUND: The Spectrum program is used to estimate key HIV indicators from the trends in incidence and prevalence estimated by the Estimation and Projection Package or the Workbook. These indicators include the number of people living with HIV, new infections, AIDS deaths, AIDS orphans, the number of adults and children needing treatment, the need for prevention of mother-to-child transmission and the impact of antiretroviral treatment on survival. The UNAIDS Reference Group on Estimates, Models and Projections regularly reviews new data and information needs, and recommends updates to the methodology and assumptions used in Spectrum. METHODS: The latest update to Spectrum was used in the 2009 round of global estimates. This update contains new procedures for estimating: the age and sex distribution of adult incidence, new child infections occurring around delivery or through breastfeeding, the survival of children by timing of infection and the number of double orphans.

Insulin differentially influences brain glucose and lactate in traumatic brain injured patients.

BACKGROUND: Hypo- and hyperglycemia must be avoided to prevent additional brain damage following traumatic brain injury (TBI). However, the optimal blood glucose range requiring insulin remains unknown. Cerebral microdialysis is helpful in unmasking signs of metabolic impairment, thereby identifying deleterious blood glucose levels. METHODS: A retrospective analysis of prospectively collected cerebral microdialysis samples obtained from 20 non-diabetic patients with severe TBI treated at the trauma surgical intensive care unit at the University Hospital Zürich, Switzerland. RESULTS: The impact of different arterial blood glucose values and concomitant insulin administration on cerebral interstitial glucose and lactate levels was investigated. In addition, energetic impairment was determined by calculating lactate-to-glucose ratios. Insulin administration was associated with significantly reduced cerebral glucose concentrations and significantly increased lactate-to-glucose ratios with arterial blood glucose levels <5 mM. At arterial blood glucose levels >7 mM, insulin administration was associated with significantly increased interstitial glucose values, significantly decreased lactate concentrations, and markedly diminished lactate-to-glucose ratios. CONCLUSION: Insulin exerts differential effects that depend strongly on the underlying arterial blood glucose concentrations. To avoid energetic impairment, insulin should not be administered at arterial blood glucose levels <5 mM. However, at arterial blood glucose levels >7-8 mM, insulin administration appears to be encouraged to increase extracellular glucose concentrations and decrease energetic impairment reflected by reduced interstitial brain lactate and decreased lactate-to-glucose ratios. Nevertheless, frequent analysis is required to minimize the risk of inducing impaired brain metabolism.

The Spectrum projection package: improvements in estimating mortality, ART needs, PMTCT impact and uncertainty bounds.

BACKGROUND: The approach to national and global estimates of HIV/AIDS used by UNAIDS starts with estimates of adult HIV prevalence prepared from surveillance data using either the Estimation and Projection Package (EPP) or the Workbook. Time trends of prevalence are transferred to Spectrum to estimate the consequences of the HIV/AIDS epidemic, including the number of people living with HIV, new infections, AIDS deaths, AIDS orphans, treatment needs and the impact of treatment on survival. METHODS: The UNAIDS Reference Group on Estimates, Modelling and Projections regularly reviews new data and information needs and recommends updates to the methodology and assumptions used in Spectrum. The latest update to Spectrum was used in the 2007 round of global estimates. RESULTS: Several new features have been added to Spectrum in the past two years. The structure of the population was reorganised to track populations by HIV status and treatment status. Mortality estimates were improved by the adoption of new approaches to estimating non-AIDS mortality by single age, and the use of new information on survival with HIV in non-treated cohorts and on the survival of patients on antiretroviral treatment (ART). A more detailed treatment of mother-to-child transmission of HIV now provides more prophylaxis and infant feeding options. New procedures were implemented to estimate the uncertainty around each of the key outputs. CONCLUSIONS: The latest update to the Spectrum program is intended to incorporate the latest research findings and provide new outputs needed by national and international planners.

Projecting the demographic impact of AIDS and the number of people in need of treatment: updates to the Spectrum projection package.

BACKGROUND: In the Joint United Nations Programme on HIV/AIDS (UNAIDS) approach to HIV and AIDS estimates, estimates of adult prevalence produced by the Estimation and Projection Package (EPP) or the Workbook are transferred to Spectrum to estimate the consequences of the HIV/AIDS epidemic, including the number of people living with HIV by age and sex, new infections, AIDS deaths, AIDS orphans, treatment needs, and the impact of treatment on survival. METHODS: The UNAIDS Reference Group on Estimates, Models and Projections recommends updates to the methodology and assumptions based on the latest research findings and international policy and programme guidelines. The latest update to Spectrum has been used in the 2005 round of global estimates. RESULTS: Several new features have been added to Spectrum in the past two years. New patterns of the age distribution of prevalence over time are based on the latest survey data. A more detailed treatment of mother to child transmission of HIV is now based on information about current breastfeeding practices, treatment options offered to prevent mother to child transmission (PMTCT), infant feeding options, and the percentage or number of pregnant women accessing PMTCT services. A new section on child survival includes the effects of cotrimoxazole and ART on child survival. Projections can now be calibrated with national survey data. A new set of outputs is provided for all adults over the age of 15 in addition to the traditional 15-49 age group. New outputs are now available to show plausibility bounds and regional estimates for key indicators. CONCLUSIONS: The latest update to the Spectrum program is intended to incorporate the latest research findings and provide new outputs needed by national and international planners.

Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples.

OBJECTIVE: Patterns of transmission of HIV are different among different regions of the world and change over time within regions. In order to adapt prevention strategies to changing patterns of risk, we need to understand the behaviours that put people at risk of infection and how new infections are distributed among risk groups. METHODS: A model is described to calculate the expected incidence of HIV infections in the adult population by mode of exposure using the current distribution of prevalent infections and the patterns of risk within different populations. For illustration the model is applied to Thailand and Kenya. RESULTS: New infections in Kenya were mainly transmitted through heterosexual contact (90%), while a small but significant number were related to injecting drug use (4.8%) and men who have sex with men (4.5%). In Thailand, the epidemic has spread over time to the sexual partners of vulnerable groups and in 2005 the majority of new infections occurred among the low risk heterosexual population (43%). Men having sex with men accounted for 21% and sex work (including sex workers, clients, and partners of clients) for 18% of new infections. Medical interventions did not contribute significantly to new infections in either Kenya or Thailand. CONCLUSIONS: The model provides a simple tool to inform the planning of effective, appropriately targeted, country specific intervention programmes. However, better surveillance systems are needed in countries to obtain more reliable biological and behavioural data in order to improve the estimates of incidence by risk group.

Improved plausibility bounds about the 2005 HIV and AIDS estimates.

BACKGROUND: Since 1998 the Joint United Nations Programme on HIV/AIDS and the World Health Organization has provided estimates on the magnitude of the HIV epidemic for individual countries. Starting with the 2003 estimates, plausibility bounds about the estimates were also reported. The bounds are intended to serve as a guide as to what reasonable or plausible ranges are for the uncertainty in HIV incidence, prevalence, and mortality. METHODS: Plausibility bounds were developed for three situations: for countries with generalised epidemics, for countries with low level or concentrated epidemics (LLC), and for regions. The techniques used build on those developed for the previous reporting round. However the current bounds are based on the available surveillance and survey data from each individual country rather than on data from a few prototypical countries. RESULTS: The uncertainty around the HIV estimates depends on the quality of the surveillance system in the country. Countries with population based HIV seroprevalence surveys have the tightest plausibility bounds (average relative range about the adult HIV prevalence (ARR) of -18% to +19%.) Generalised epidemic countries without a survey have the next tightest ranges (average ARR of -46% to +59%). Those LLC countries which have conducted multiple surveys over time for HIV among the populations most at risk have the bounds similar to those in generalised epidemic countries (ARR -40% to +67%). As the number and quality of the studies in LLC countries goes down, the plausibility bounds increase (ARR of -38% to +102% for countries with medium quality data and ARR of -53% to +183% for countries with poor quality data). The plausibility bounds for regions directly reflect the bounds for the countries in those regions. CONCLUSIONS: Although scientific, the plausibility bounds do not represent and should not be interpreted as formal statistical confidence intervals. However in order to make the bounds as meaningful as possible the authors have tried to apply reasonable statistical approaches and assumptions to their derivation. An understanding of the uncertainty in the HIV estimates may help policy makers take better informed decisions to address the epidemic in their respective countries.

Granulocyte colony-stimulating factor does not affect contusion size, brain edema or cerebrospinal fluid glutamate concentrations in rats following controlled cortical impact.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is an established treatment in the neutropenic host. Usage in head-injured patients at risk for infection may aggravate brain damage. In contrast, evidence of G-CSF neuroprotective effects has been reported in rodent models of focal cerebral ischemia. We investigated effects of G-CSF in acute focal traumatic brain injury (TBI) in rats. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with 1.2%) to 2.0% isoflurane and subjected to controlled cortical impact injury (CCII). Thirty minutes following CCII, either vehicle or G-CSF was administered intravenously. Animals were sacrificed 24 hours following CCII. Glutamate concentrations were determined in cisternal cerebrospinal fluid (CSF). Brain edema was assessed gravimetrically. Contusion size was estimated by 2,3,5-triphenyltetrazolium chloride staining and volumetric analysis. RESULTS: Dose-dependent leukocytosis was induced by infusion of G-CSF. Physiological variables were unaffected. Water content of the traumatized hemisphere and CSF glutamate concentrations were unchanged by treatment. Contusion volume was similar in all groups. CONCLUSIONS: A single injection of G-CSF did not influence cortical contusion volume, brain edema, or glutamate concentrations in CSF determined 24 hours following CCII in rats. G-CSF, administered 30 minutes following experimental TBI, failed to exert neuroprotective effects.

Evidence for population level declines in adult HIV prevalence in Kenya.

The HIV/AIDS epidemic in Kenya has been tracked through annual sentinel surveillance in antenatal clinics since 1990. The system started with 13 sites and now has over 35. Behaviours have been measured through national Demographic and Health Surveys in 1993, 1998, and 2003. The surveillance data indicate that prevalence has declined substantially starting in 1998 in five of the original 13 sites and starting in 2000 in another four sites. No decline is evident in the other five original sites although the 2004 estimate is the lowest recorded. Nationally, adult prevalence has declined from 10% in the late 1990s to under 7% today. Surveys indicate that both age at first sex and use of condoms are rising and that the percentage of adults with multiple partners is falling. It is clear that HIV prevalence is now declining in Kenya in a pattern similar to that seen in Uganda but seven or eight years later. Although the coverage of preventive interventions has expanded rapidly since 2000 this expansion was too late to account for the beginnings of the decline in prevalence. More work is needed to understand fully the causes of this decline, but it is encouraging to see Kenya join the small list of countries experiencing significant declines in HIV prevalence.

Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti.

OBJECTIVE: To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour. METHODS: A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. RESULTS: Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d'Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour. CONCLUSIONS: Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.

The use of neuronavigation in transnasal transsphenoidal pituitary surgery.

BACKGROUND: Recurrent pituitary adenomas and localisation of microadenomas potentially cause difficulties during transsphenoidal pituitary surgery. Neuronavigation might improve tumour removal in such cases. METHODS: Between 12/98 and 04/01 transnasal transsphenoidal adenomectomies were performed in 152 patients at our department. In 16 of these patients neuronavigation was chosen as a means of safely approaching the tumour and improving the efficacy of tumour localisation and removal. Mean age of the 7 female and 9 male patients was 51.8 +/- 13.7 years. Patients were subdivided according to the underlying pathology, i. e. microadenomas (n = 8, mean diameter: 5.75 +/- 2.1 mm), and recurrent adenomas (n = 8). The imaging of adenomas was achieved in preoperatively obtained 1 mm transversely reconstructed magnetic resonance sections from a dynamic enhanced 3D-FFE sequence (Gyroscan 1.5 Tesla, Philips). Contour-guided surgery via a transnasal transsphenoidal approach to the sella region was performed using the MKM navigation microscope (Zeiss). RESULTS: Endocrinologic studies revealed secretion of growth hormone (GH), ACTH, and follicle stimulating hormone (FSH) in 5, 4, and 1 patient, respectively. The remaining 7 adenomas did not secrete any hormones. All pituitary tumours were accurately localised by neuronavigation. In all recurrent macroadenomas, the tumours were rapidly and safely approached through the scarred tissue and the tumour volume was significantly reduced. Neither intraoperative nor postoperative complications occurred in these patients. In hormone-secreting pituitary tumours with far lateral localisation, endocrinologic abnormalities were corrected in 5 patients, while hormone secretion was significantly decreased in 3 patients. In 1 patient with histologically verified adenoma, hormone secretion did not significantly change following surgical removal. CONCLUSIONS: Neuronavigation in pituitary surgery is of use in only a small number of cases. Nevertheless, we suggest that contour-guided, transsphenoidal adenomectomy may prove helpful in approaching recurrent adenomas and localising lateral microadenomas.

Anesthesia increases circulating glutamate in neurosurgical patients.

BACKGROUND: The excitotoxic amino acid glutamate is known to aggravate pre-existing neuropathology. Since volatile anesthetics increase plasma amino acid levels, we investigated if the anesthetics isoflurane and propofol increase plasma and cerebrospinal fluid (CSF) glutamate in neurosurgical patients. METHODS: In discectomized patients (n = 15), plasma glutamate was determined at 30 minute intervals before and during isoflurane anesthesia. In craniotomized patients (n = 66), plasma glutamate was assessed during and up to 24 hours after routine isoflurane or propofol anesthesia. CSF samples were withdrawn upon opening of the dura, before surgical manipulations. FINDINGS: During isoflurane anesthesia, plasma glutamate was significantly and reversibly increased in discectomized and craniotomized patients compared to healthy controls (56+/-6 microM; p<0.05), which was mostly sustained in male patients (males: 126+/-12 vs. females: 96+/-6 microM; p<0.05). With propofol, plasma glutamate was increased equally in men and women but to a lesser extent than with isoflurane (mean: 72+/-7 microM). CSF glutamate was significantly increased during isoflurane and propofol anesthesia compared to control lumbar CSF (1.2+/-0.1 microM; p<0.0001), being more prominent in patients with pre-existing brain edema receiving isoflurane (76+/-8 vs. propofol: 40+/-6 microM; p<0.05). CONCLUSIONS: The significant increases in plasma and CSF glutamate which were mostly sustained during isoflurane compared to propofol anesthesia should prompt the identification of anesthetic agents which do not impose a possible burden of glutamate-mediated excitotoxicity in patients with underlying compromised cerebral homeostasis. Detailed neuropsychological investigations following different anesthesia regimen are important to determine if transient elevations in CSF and plasma glutamate levels are of clinical relevance.