Metabolism of Schizosaccharomyces pombe under reduced osmotic stress conditions afforded by fed-batch alcoholic fermentation of white grape must.

Strains of Schizosaccharomyces pombe are being increasingly investigated with regards to their grape winemaking potential either in combination with the typical production yeast, Saccharomyces cerevisiae, or in monoseptic fermentations. Their ethanol tolerance and ability to degrade L-malic acid is oenologically convenient but contrasts with the comparatively high acetic acid and acetaldehyde formation potential which is considered undesirable, especially in white winemaking. The purpose of this work was to investigate the performance of a selected S. pombe strain in monoseptic femerntations of white grape must. Traditional batch fermentations were compared with an innovative and automated fed-batch fermentation technique were sugar concentrations are kept low during fermentations to decrease sugar induced osmotic stress. Because of its known effect on growth and ethanol tolerance, the effect of Mg was also tested. While Mg supplementation was not shown to significantly influence residual values of sugars, ethanol, glycerol, organic acids and acetaldehyde, the application of the fed-batch technique led to a fundamental change in yeast physiology. While glycerol values were only slightly reduced, the fed-batch approach allowed obtaining wines devoid of acetic acid whose levels were considerable in wines produced by the traditional batch technique (0.6 g/L). The work demonstrates that the acetic acid metabolism of S. pombe is associated to sugar induced osmotic stress such as for S. cerevisiae, too, and may be controlled by application of suitable fermentation techniques for winemaking.

Empowering patients for radiation therapy safety: Results of the EMPATHY study.

PURPOSE: With the increase of treatment complexity, enhancing safety is a key concern in radiation oncology. Beyond the involvement of the healthcare professional, patient involvement and empowerment could play a major role in that setting. We explored how patients perceived and fulfilled that role during their radiation treatment. MATERIALS AND METHODS: A voluntary and anonymous questionnaire was administered to all patients treated in our department between November 2013 and May 2014. The following data were collected: sociodemographic profile; information received and initiatives to search for additional information; behavior when an unusual treatment event was perceived; active involvement in the safety of the treatment; nature and perception of their own involvement. A statistical analysis was performed to assess behavioral predictors. RESULTS: A total of 155 patients answered the survey. Most of them were treated for prostate (n=58, 37.4%), lung (n=27, 17.4%), head and neck (n=26, 16.8%) and breast (n=25, 16.1%). Only eight patients (5%) had previously received radiation therapy. Ninety-five percent of the patients estimated they had received enough information about their treatment, but 48% would have wanted more. When patients noticed an unusual event during their treatment session, most of them (61%) reported it to the radiation therapist. CONCLUSION: Patient participation to radiation therapy safety should be encouraged to ensure a cooperative risk management. Healthcare professionals need to inform the patients on the basic technical processes involved in their treatment. Patient empowerment should be added to the verifications made by the radiation therapists and physicians but should not replace them.

Evaluation of patients' engagement in radiation therapy safety.

PURPOSE: Treatment safety has become a priority in health policies after several incidents occurred around the world in radiation oncology departments. The aim of this study was to analyse the patients' contribution in that field and to understand which actions empower the patient in that regard. METHODS: Several methods were used in a general hospital and in a comprehensive cancer centre to analyse the activities of the radiation therapists and the patients and the interactions between them: treatment session observations, semidirective interviews with radiation therapists and patients, self and alloconfrontation with radiation therapists and explanatory interviews with patients. RESULTS: Cooperation of the patients in treatment safety acts as an additional step that contributes to safer treatments. Radiation therapy sessions are a creative opportunity for the patient to observe, learn and analyse what is happening. Changes between treatment sessions are a source of anxiety for the patients. This study highlights the factors that favour the patients' participation. A trusting relationship and support from the health professionals can be leveraged in that manner. CONCLUSION: There is a common will shared between the patients and the health professionals towards better treatment safety. The cooperation is still not well-known and underused. This empowerment of the patient cannot be mandatory but should be promoted and developed.

[Can or must the patient participate to risk management in radiotherapy?]. / Le patient peut-il et doit-il participer à la gestion des risques en radiothérapie ?

PURPOSE: The present study aimed at analyzing if patient participation constitutes a promising way of improvement of patient safety, or not. The hypothesis is that patient participation is a means to develop a safety culture based on the cooperation between patients and healthcare providers, to improve patients' satisfaction and to reduce the costs associated to adverse events. PATIENTS AND METHODS: A half-day session was organized on this theme during a training of radiotherapy professionals on risk management. Professionals were first distributed in three subgroups according to their specialty (radiation oncologists, radiation physicists and medical technicians), and had to work on four main questions relating to participation, among which the collection of real situations in which patients effectively contributed (positively or negatively) to patient safety. Results were then collectively discussed. RESULTS: Patient participation allows not only to detect and recover some mistakes or errors made by the professionals (error of identity), but also to decrease patients' risk behaviors (purposely taking the place of another patient in order to be treated faster). However, it must be seen as a possibility offered to patients, and not as an obligation. CONCLUSION: Patient participation to patient safety is a field of study, which requires to be developed in order to define the conditions enhancing such participation and to implement a set of actions to improve healthcare safety by a cooperative management of this one.

[Type 2 diabetes: practical guide for starting ambulatory insulin therapy]. / Diabète de type 2: guide pratique pour débuter une insulinothérapie ambulatoire.

This practical guide describes the most currently used insulins--classified according to their duration of action, the insulin pens and the glucose monitoring devices. Various strategies of insulin treatment for type 2 diabetes are explained, with emphasis on the two most frequently used forms of therapy: combined daily oral agents and nocturnal insulin, and twice daily injections of long-acting insulin. The advantages and disadvantages of premixed insulin are described. Finally, the four main topics of patient education for starting insulin therapy are mentioned.

The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia.

AIMS/HYPOTHESIS: Our hypothesis is that reducing release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with modafinil will enhance symptomatic and hormonal responses to hypoglycaemia. METHODS: Nine healthy men received, in random order, two 100-mg doses of modafinil or placebo, followed by an insulin clamp in which plasma glucose was either reduced stepwise to 2.4 mmol/l or was sustained at euglycaemia (four studies). Catecholamines, symptom scores and cognitive function were measured. RESULTS: Modafinil had no effect on the measured parameters during euglycaemia. During hypoglycaemia, autonomic symptom scores were significantly higher with modafinil (increase at lowest plasma glucose concentration 271.3+/-118.9 vs 211.2+/-80.4/40 min, p=0.019), and the heart rate response was increased (12,928+/-184 vs 6773+/-148 bpm/140 min, p=0.016). Deterioration in performance of two cognitive tasks was reduced: Stroop colour-word test (613+/-204 vs 2375+/-161/65 min, p=0.009) and accuracy of a simple reaction task (11.3+/-1.8 vs 9.4+/-3.7, p=0.039). CONCLUSIONS/INTERPRETATION: We conclude that modafinil improves adrenergic sensitivity and some aspects of cognitive function at hypoglycaemia, possibly by reducing neuronal central GABA concentrations.

The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study.

AIMS: To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in beta-cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic beta-cell and the hypothalamic glucose-sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain. METHODS: Ten healthy males were studied on four occasions and in random order underwent three stepped hypoglycaemic (plasma glucose aims: 3.4, 2.8, 2.4 mmol/l) and one euglycaemic (plasma glucose aim: 5 mmol/l) insulin clamps. Prior to each hypoglycaemic study, volunteers received either 10 mg glibenclamide, or 5 mg/kg diazoxide or placebo orally. Cognitive function, symptom scores and counterregulatory hormone responses were measured at each glycaemic level. RESULTS: There was no statistically significant effect of either drug on the symptoms generated or the counterregulatory hormonal response during hypoglycaemia. However, cognitive function was better preserved during hypoglycaemia in the glibenclamide-treated arm, particularly four-choice reaction time which deteriorated at a plasma glucose 2.5 mmol/l compared with 3.0 mmol/l with diazoxide (P = 0.015) and 2.9 mmol/l with placebo (P = 0.114). CONCLUSIONS: Single doses of pharmacological agents which alter membrane KATP channel activity do not affect the counterregulatory response to hypoglycaemia but may modify cognitive function during cerebral glucopenia. The unexpected effects of glibenclamide on cortical function suggest a novel action of sulphonylureas that warrants further investigation.

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man.

AIMS/HYPOTHESIS: The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers. METHODS: Each subject received an insulin infusion (3 mU.kg(-1).min(-1)) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp. RESULTS: Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02+/-20.84 (means +/- SD) to 15.26+/-13.65 nmol/l per 20 min, p<0.05. Symptom scores (area under curve) decreased from 99.72+/-91.86 to 16.39+/-94.71, p=0.008 (total), 51.8+/-68.61 to 7.78+/-41.61, p=0.03 (autonomic) and 54.17+/-50.61 to 8.6+/-57.99 with oral glucose, p=0.001 (neuroglycopenic). Oral glucose did not influence symptoms during euglycaemia. CONCLUSION/INTERPRETATION: Our data are compatible with the hypothesis that centrally mediated symptomatic and neuroendocrine responses are attenuated by glucose detection in the hepatic portal vein in humans.

The effect of acute hypoglycemia on brain function and activation: a functional magnetic resonance imaging study.

The authors' aim was to examine the regional anatomy of brain activation by cognitive tasks commonly used in hypoglycemia research and to assess the effect of acute hypoglycemia on these in healthy volunteers. Eight right-handed volunteers performed a set of cognitive tasks-finger tapping (FT), simple reaction time (SRT), and four-choice reaction time (4CRT)-twice during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging of the brain on two occasions. In study 1 (n = 6), plasma glucose was maintained at euglycemia (5 mmol/l) throughout. In study 2 (n = 6), plasma glucose was reduced to 2.5 mmol/l for the second set. Performance of the tasks resulted in specific group brain activation maps. During hypoglycemia, FT slowed (P = 0.026), with decreased BOLD activation in right premotor cortex and supplementary motor area and left hippocampus and with increased BOLD activation in left cerebellum and right frontal pole. Although there was no significant change in SRT, BOLD activation was reduced in right cerebellum and visual cortex. The 4CRT deteriorated (P = 0.020), with reduction in BOLD activation in motor and visual systems but increased BOLD signal in a large area of the left parietal association cortex, a region involved in planning. Hypoglycemia impairs simple brain functions and is associated with task-specific localized reductions in brain activation. For a task with greater cognitive load, the increased BOLD signal in planning areas is compatible with recruitment of brain regions in an attempt to limit dysfunction. Further investigation of these mechanisms may help devise rational treatment strategies to limit cortical dysfunction during acute iatrogenic hypoglycemia.

Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery.

OBJECTIVE: To examine the time course for the onset of, and recovery from, acute hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS: Eight healthy male volunteers were studied on 2 occasions in random order using a hyperinsulinemic (1.5 mU x kg(-1) x min(-1)) glucose clamp technique. During control studies, euglycemia (5.01 +/- 0.02 mmol/l) was maintained for 225 +/- 3 min. On the other occasion, after a euglycemic baseline period, arterialized plasma glucose was allowed to fall rapidly to 2.65 +/- 0.02 mmol/l, then maintained at this nadir for 90 min before euglycemia was rapidly restored. RESULTS: Cognitive function assessed by a battery of sensitive tests (4-choice reaction time, Stroop word, and color-word test) became impaired immediately at onset of hypoglycemia (P < 0.05 for all in the hypoglycemic study vs. those in the euglycemic study). Counterregulatory hormone responses (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) and symptomatic awareness of hypoglycemia (assessed by a questionnaire) were relatively delayed, being detected 20 min after the onset of hypoglycemia. There was no diminution (adaptation) of any responses, cognitive, humoral, or symptomatic, during sustained hypoglycemia. During recovery, the 4-choice reaction time continued to be abnormal even after resolution of symptomatic awareness (P = 0.025). CONCLUSIONS: During hypoglycemia, cognitive performance may become impaired before symptomatic awareness. During recovery from hypoglycemia, recovery of cognitive function lags behind the restoration of glucose levels and resolution of symptoms. Our findings have implications for the design of studies examining experimental hypoglycemia and need to be investigated in people with diabetes.

Renal glucose production compensates for the liver during the anhepatic phase of liver transplantation.

The extent of the renal contribution to postabsorptive endogenous glucose production (EGP) in humans is controversial. We measured EGP in the absence of the liver during the anhepatic phase (AH) of liver transplantation in five patients (aged 46.4+/-10.2 years, two women). Stable labeling of plasma glucose (PG) was achieved for a 2-h period before the AH by primed continuous infusion of di-deuterated 6,6[2H2]glucose (1.7 mg/min) and continued throughout the AH. PG was maintained above the fasting level (6.1+/-2.73 mmol/l) with 5% dextrose labeled with 6,6[2H2]glucose throughout the AH (mean level during the AH 0.98+/-0.45 mg x kg(-1) x min(-1)). Isotopic enrichment remained stable at 0.84+/-0.21% atom percent excess throughout. EGP, calculated by use of a modified Steele equation, decreased from 2.6+/-1.24 at baseline to 0.97+/-0.9 mg x kg(-1) x min(-1) (36% baseline, P = 0.045) but recovered at approximately 30 min to reach 1.38+/-0.83 mg x kg(-1) x min(-1) (54% baseline) by 60 min. Epinephrine, lactate, free fatty acid, and glycerol levels increased significantly (0.79+/-0.74 to 3.65+/-2.1 nmol/l, P = 0.005; 1.88+/-0.43 to 3.46+/-0.9 mmol/l, P = 0.024; 543.9+/-215.5 to 705.5+/-219.2 micromol/l, P = 0.012; 75.6+/-30.2 to 139+/-96.3 micromol/l, P = 0.003, respectively). These data show that postabsorptive nonhepatic glucose production in humans may contribute to greater than one-third of overall EGP, increasing when required, and that it is associated with a stress response and increased gluconeogenic substrate availability. We conclude that extrahepatic tissues, most notably those of the kidney, make a significant contribution to EGP in humans.

Genetic mapping of maize streak virus resistance from the Mascarene source. I. Resistance in line D211 and stability against different virus clones.

Maize streak virus (MSV) disease may cause significant grain yield reductions in maize in Africa. Réunion island maize germplasm is a proven source of strong resistance. Its genetic control was investigated using 123 RFLP markers in an F(2) population of D211 (resistant) × B73 (susceptible). This population of 165 F(2:3) families was carefully evaluated in Harare (Zimbabwe) and in Réunion. Artificial infestation was done with viruliferous leafhoppers. Each plant was rated weekly six times after infestation on a 1-9 scale previously adjusted by image analysis. QTL analyses were conducted for each scoring date, and for the areas under the disease, incidence and severity progress curves. The composite interval mapping method used allowed the estimation of the additive and dominance effects and QTL × environment interactions. Heritabilities ranged from 73% to 98%, increasing with time after infestation. Resistance to streak virus in D211 was provided by one region on chromosome 1, with a major effect, and four other regions on chromosomes 2, 3 (two regions) and 10, with moderate or minor effects. Overall, they explained 48-62% of the phenotypic variation for the different variables. On chromosome 3, one of the two regions seemed to be more involved in early resistance, whereas the second was detected at the latest scoring date. Other QTLs were found to be stable over time and across environments. Mild QTL × environment interactions were detected. Global gene action appeared to be partially dominant, in favor of resistance, except at the earliest scoring dates, where it was additive. From this population, 32 families were chosen, representing the whole range of susceptibility to MSV. They were tested in Réunion against three MSV clones, along with a co-inoculation of two of them. Virulence differences between clones were significant. There were genotype × clone interactions, and these were more marked for disease incidence than for severity. Although these interactions were not significant for the mean disease scores, it is suggested that breeders should select for completely resistant genotypes.

Genetic mapping of maize streak virus resistance from the Mascarene source. II. Resistance in line CIRAD390 and stability across germplasm.

The streak disease has a major effect on maize in sub-Saharan Africa. Various genetic factors for resistance to the virus have been identified and mapped in several populations; these factors derive from different sources of resistance. We have focused on the Réunion island source and have recently identified several factors in the D211 line. A second very resistant line, CIRAD390, was crossed to the same susceptible parent, B73. The linkage map comprised 124 RFLP markers, of which 79 were common with the D211×B73 map. A row-column design was used to evaluate the resistance to maize streak virus (MSV) of 191 F(2:3) families under artificial infestation at two locations: Harare (Zimbabwe) and in Réunion island. Weekly ratings of resistance were taken and disease incidence and severity calculated. QTL analyses were conducted for each scoring date and for the integration over time of the disease scores, of incidence, and of severity. Heritability estimates (71-98%) were as high as for the D211×B73 population. Eight QTLs were detected on chromosomes 1, 2, 3, 5 (two QTLs), 6, 8, and 10. The chr1-QTL explained the highest proportion of phenotypic variation, about 45%. The QTLs on chromosomes 1, 2, and 10 were located in the same chromosomal bin as QTLs for MSV resistance in the D211×B73 population. In a simultaneous fit, QTLs explained together 43-67% of the phenotypic variation. The QTLs on chromosomes 3, 5, and 6 appeared to be specific for one or the other component of the resistance. For the chr3-QTL, resistance was contributed by the susceptible parent. There were significant QTL × environment interactions for some of the variables studied, but QTLs were stable in the two environments. They also appeared to be stable over time. Global gene action ranged from partial dominance to overdominance, except for disease severity. Some additional putative QTLs were also detected. The major QTL on chromosome 1 seemed to be common to the other sources of resistance, namely Tzi4, a tolerant line from IITA, and CML202 from CIMMYT. However, the distribution of the other QTLs within the genome revealed differences in Réunion germplasm and across these other resistance sources. This diversity is of great importance when considering the durability of the resistance.

Antenatally diagnosed surgical anomalies: the psychological effect of parental antenatal counseling.

BACKGROUND: Increasing numbers of infants have the diagnosis of a surgical malformation made before birth. This allows (1) fetal intervention, (2) in utero transfer and planned delivery in a surgical center, and (3) antenatal counseling of likely prognosis and outcome. The aim of this study was to assess the effectiveness of antenatal counseling in terms of the parental psychological response. METHODS: Antenatal counseling by a pediatric surgeon and neonatal nurse was given after ultrasound diagnosis of a fetal surgical malformation (eg, gastroschisis, diaphragmatic hernia). Anxiety levels were measured using the Spielberger State-Trait Anxiety Inventory, a tool used by psychologists to assess the inherent level of anxiety, or Trait anxiety (STAI-T), and the current level of anxiety, or State anxiety (STAI-S). RESULTS: Fifty six prospective mothers filled out Spielberger questionnaires (subjects, n = 26; controls, n = 30). Nineteen subjects' partners also completed questionnaires. There was no significant difference in Trait anxiety scores between subjects and controls (41 [interquartile range, 30 to 511 v 38.5 [range, 32 to 47]; P = .58). There was no significant correlation between maternal and paternal Trait anxiety (P = .11). There was a significant reduction in State anxiety scores in both subject mothers (49.5 [interquartile range, 27 to 73) v38 [range, 31 to 49]; P = .01) and fathers (47 [interquartile range, 36 to 55] v 37 [interquartile range, 32 to 49]; P = .006) after pediatric surgical consultation. CONCLUSION: Counseling by specialist staff reduced levels of parental anxiety associated with the diagnosis of fetal surgical malformation.

Reduced counterregulation during hypoglycemia with raised circulating nonglucose lipid substrates: evidence for regional differences in metabolic capacity in the human brain?

We have investigated the potential for the human brain to use lipid fuels during acute hypoglycemia. Nine healthy male subjects underwent hyperinsulinemic (1.5 mU/kg x min) stepped hypoglycemic clamps on two occasions, infusing Intralipid (20%) and heparin (0.1 U/kg x min) on one occasion only (ILH), with an identical study without infusion of ILH acting as a control. Five subjects also underwent euglycemic clamping with Intralipid/heparin infusion. During hypoglycemia, ILH raised circulating levels of nonesterified fatty acids, glycerol, and beta-hydroxybutyrate, although the latter did not rise until after the onset of counterregulation. With ILH, epinephrine responses [area under the curve (AUC), 127.9 +/- 31.7 vs. 175.1 +/- 27.4 nmol/L x 180 min; P = 0.03] and GH responses (AUC, 260 +/- 91 vs. 1009 +/- 150, P < 0.01) were reduced and delayed (glucose thresholds, 2.8 +/- 0.04 vs. 3.0 +/- 0.1 mmol/L; P = 0.04), with a trend toward reduced cortisol responses. Similarly, hypoglycemic symptom scores were diminished during ILH (AUC, 647 +/- 162 vs. 1222 +/- 874; P = 0.03). However, there was no significant effect on the deterioration in four-choice reaction time, one measure of cognitive deterioration [glucose thresholds, 2.6 +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, ILH vs. control (P = 0.75); AUC, 1420 +/- 710 vs. 2250 +/- 1080 ms/min (P = 0.59)]. During euglycemic clamping with Intralipid/heparin infusion studies, there was no rise in hormones, four-choice reaction time, or symptoms other than hunger and tiredness. Both nonesterified fatty acids and glycerol can penetrate the mammalian brain and be metabolized. Raised levels were able to reduce neurohumoral responses to hypoglycemia, but could not protect cognitive function. This suggests that regional differences exist in human brain metabolism between glucose-sensing and cognitive areas of brain, which may be important in the understanding of the mechanisms of glucose sensing and in the genesis of hypoglycemia unawareness in insulin-dependent diabetes.

Effects of glycemic control on protective responses against hypoglycemia in type 2 diabetes.

OBJECTIVE: To determine the effects of glycemic control on the counterregulatory responses to hypoglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Seven poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 +/- 1.1%) were studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/l) before and after improving glycemic control with insulin treatment. Counterregulatory hormones, symptoms, and four-choice reaction time were measured at each glucose plateau. RESULTS: In patients with poorly controlled type 2 diabetes, counterregulatory hormone responses began at higher plasma glucose levels than did those in healthy subjects (epinephrine, 4.4 +/- 0.2 vs. 3.7 +/- 0.2 mmol/l, P = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 +/- 0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses started at much lower plasma glucose levels (e.g., epinephrine, 3.5 +/- 0.3 mmol/l, P = 0.005) and were significantly reduced in magnitude (e.g., area under epinephrine response curve, 306 +/- 93 vs. 690 +/- 107 nmol.min-1.l-1, P = 0.012). This was accompanied by a change in the plasma glucose threshold at which hypoglycemic symptoms first developed from 3.6 +/- 0.2 to 3.0 +/- 0.2 mmol/l (P = 0.019). In contrast, the plasma glucose threshold at which four-choice reaction time deteriorated did not change significantly (3.1 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l, P = 0.125). CONCLUSIONS: Counterregulatory responses begin at normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control with insulin therapy normalizes hormonal responses but lowers the plasma glucose levels at which hypoglycemic symptoms develop to levels associated with impairment of four-choice reaction time, a marker of cognitive function. This process potentially increases the risk of severe hypoglycemia, but to a lesser extent than occurs in type 1 disease.

Europeans outraged over expanded access.

AIDS: The growing chasm between therapeutic options in Europe and America is causing anger and desperation among HIV-infected Europeans and their physicians. Many European doctors and activists accuse Abbott Laboratories and Merck, with the help of Food and Drug Administration (FDA) decisionmaking, of being primarily committed to ensuring that the U.S. market is fully supplied with therapeutic drugs, no matter what the cost is to Europe. Both companies deny any such plans and reveal their manufacturing and supply plans for Norvir (Abbott) and Crixivan (Merck) for the near future in order to meet the needs of the entire AIDS community. The International Association of Physicians in AIDS Care is calling for the replacement of the expanded-access model with a global drug rationing agency which would approve and supervise the distribution of drugs for compassionate use.^ieng

Cognitive functioning and magnetic resonance imaging in chronic fatigue.

BACKGROUND: This study examines whether cognitive dysfunction in chronic fatigue may be accounted for by depression and anxiety or is due to brain pathology evident on magnetic resonance imaging (MRI). METHOD: Twenty-six subjects with chronic fatigue, with and without coexisting depression, and 18 age-matched normal controls were recruited from primary care following a presumed viral illness six months previously. Comparison was made with 13 psychiatric controls with depressive illness on standardised cognitive tests. MRI determined the presence of cerebral white-matter lesions. RESULTS: No substantial differences in performance were shown between subjects with chronic fatigue, most of whom met the criteria for chronic fatigue syndrome, and controls. Subjective cognitive dysfunction increased with psychopathology. White-matter lesions were found in a minority from all groups. Improvement in fatigue and depression coincided with improved performance on cognitive measures. CONCLUSIONS: Subjective complaints of cognitive impairment are a prominent feature of chronic fatigue, but objective cognitive and MRI abnormalities are not. Such complaints probably reflect psychopathology rather than a post-viral process.