Medical management and positive outcome after prolonged recumbency in a case of equine herpesvirus myeloencephalopathy.

A 17-year-old mare presenting with acute fever, weakness and bladder dysfunction was diagnosed with equine herpesvirus myeloencephalopathy (EHM). The mare become transiently recumbent, underwent parenteral fluid therapy, plasma infusion, steroidal/nonsteroidal anti-inflammatory drugs (SAID/NSAIDs) and bladder catheterization. After 10 days the mare was hospitalized. Neurological evaluation revealed ataxia and proprioceptive deficits mainly in the hind limbs. The mare was able to stand but unable to rise from recumbency or walk. Secondary complications included Escherichia coli cystitis, corneal ulcers and pressure sores. A full-body support sling was used for 21 days. Medical treatment included systemic antimicrobials, NSAIDs, gradual discontinuation of SAIDs, parenteral fluid therapy and bladder lavage. The mare tested positive for Varicellovirus equidalpha 1 (EHV-1) DNA in nasal swab and blood samples on day 13 and in urine samples on days 13 and 25 after the onset of fever. Neurological signs improved over a period of 34 days and the mare was discharged with mild hind limb weakness/ataxia. Secondary complications resolved within 2 weeks. At the eight-month follow-up, marked improvement in locomotory function had been achieved.

Predicting early recurrence after resection of initially unresectable colorectal liver metastases: the role of baseline and pre-surgery clinical, radiological and molecular factors in a real-life multicentre experience.

BACKGROUND: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.

Multidisciplinary lifestyle intervention in the obese: its impact on patients' perception of the disease, food and physical exercise.

BACKGROUND AND AIMS: To be successful, lifestyle intervention in obesity must take into account patients' views. The aim of the present study, conducted using a narrative-autobiographical approach, was to report on the perception of disease, food and physical exercise in a group of 80 obese patients during a structured multidisciplinary lifestyle intervention. METHODS AND RESULTS: Patients underwent lifestyle intervention, of three months' duration, structured in the following steps: 1) an initial medical examination; 2) an interview by a psychologist; 3) an assessment by a dietician, 4) a physical examination by a specialist in sports medicine; 5) an individualized program consisting of 24 sessions (two per week) of structured indoor exercise 6) eight sessions of group therapeutic education; 7) Nordic walking activity combined with walking excursions during weekends. All the narrative autobiographic texts obtained during the lifestyle intervention were submitted for content analysis; data were analysed according to the ''grounded theory'' method. According to patients' descriptions at the end of the intervention, lifestyle intervention resulted in enhanced self-efficacy and a reduction in their dependency on food and people; their fear of change was also diminished because, by undergoing intervention, they had experienced change. CONCLUSION: The findings made in the present qualitative analysis suggest that whenever multidisciplinary lifestyle intervention is planned for patients with obesity, it is of the utmost importance to tailor the approach while taking the following key aspects into account: motivation, barriers and/or facilitators in lifestyle change, patients' perceptions of obesity and relationship with food, diet and exercise.

The combination of immunosuppressive drugs with 8-methoxypsoralen and ultraviolet a light modulates the myeloid-derived dendritic cell function.

The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither immunosuppressive drugs at the lowest concentration nor their combination with PUVA affected myeloid DC generation, but modified DC functions, strengthening the induction of a tolerogenic pattern. As this ID concentration was arbitrarily chosen, further experiments could highlight whether lower concentrations than those used in clinical practice would elicit the same effect on DCs and potentially improve their functional properties. This work describes an original experimental approach exploring the in vitro mechanism of action of the combined procedure of PUVA with immunosuppressive drugs, used in liver transplantation, on DCs generation and function. Our results contribute to the knowledge of the mechanisms of action of this combined procedure on DCs, suggesting useful therapeutic implications for the in vivo therapy.

Transport of protein between cytoplasmic membranes of fused cells: correspondence to processes reconstituted in a cell-free system.

Mixed monolayers containing vesicular stomatitis virus-infected Chinese hamster ovary clone 15B cells (lacking UDP-N-acetylglucosamine transferase I, a Golgi enzyme) and uninfected wild-type Chinese hamster ovary cells were formed. Extensive cell fusion occurs after the monolayer is exposed to a pH of 5.0. The vesicular stomatitis virus encoded membrane glycoprotein (G protein) resident in the rough endoplasmic reticulum (labeled with [35S]methionine) or Golgi complex (labeled with [3H]palmitate) of 15B cells at the time of fusion can reach Golgi complexes from wild-type cells after fusion; G protein present in the plasma membrane cannot. Transfer to wild-type Golgi complexes is monitored by the conversion of G protein to an endoglycosidase H-resistant form upon arrival, and also demonstrated by immunofluorescence microscopy. G protein in the Golgi complex of the 15B cells at the time of fusion exhibits properties vis a vis its transfer to an exogenous Golgi population identical to those found earlier in a cell-free system (Fries, E., and J. E. Rothman. 1981. J. Cell Biol., 90: 697-704). Specifically, pulse-chase experiments using the in vivo fusion and in vitro assays reveal the same two populations of G protein in the Golgi complex. The first population, consisting of G protein molecules that have just received their fatty acid, can transfer to a second Golgi population in vivo and in vitro. The second population, entered by G protein approximately 5 min after its acylation, is unavailable for this transfer, in vivo and in vitro. Presumably, this second population consists of those G-protein molecules that had already been transferred between compartments within the 15B Golgi population, in an equivalent process before cell fusion or homogenization for in vitro assays. Evidently, the same compartment boundary in the Golgi complex is detected by these two measurements. The surprisingly facile process of glycoprotein transit between Golgi stacks that occurs in vivo may therefore be retained in vitro, providing a basis for the cell-free system.

The mammalian gamma-tubulin complex contains homologues of the yeast spindle pole body components spc97p and spc98p.

gamma-Tubulin is a universal component of microtubule organizing centers where it is believed to play an important role in the nucleation of microtubule polymerization. gamma-Tubulin also exists as part of a cytoplasmic complex whose size and complexity varies in different organisms. To investigate the composition of the cytoplasmic gamma-tubulin complex in mammalian cells, cell lines stably expressing epitope-tagged versions of human gamma-tubulin were made. The epitope-tagged gamma-tubulins expressed in these cells localize to the centrosome and are incorporated into the cytoplasmic gamma-tubulin complex. Immunoprecipitation of this complex identifies at least seven proteins, with calculated molecular weights of 48, 71, 76, 100, 101, 128, and 211 kD. We have identified the 100- and 101-kD components of the gamma-tubulin complex as homologues of the yeast spindle pole body proteins Spc97p and Spc98p, and named the corresponding human proteins hGCP2 and hGCP3. Sequence analysis revealed that these proteins are not only related to their respective homologues, but are also related to each other. GCP2 and GCP3 colocalize with gamma-tubulin at the centrosome, cosediment with gamma-tubulin in sucrose gradients, and coimmunoprecipitate with gamma-tubulin, indicating that they are part of the gamma-tubulin complex. The conservation of a complex involving gamma-tubulin, GCP2, and GCP3 from yeast to mammals suggests that structurally diverse microtubule organizing centers such as the yeast spindle pole body and the animal centrosome share a common molecular mechanism for microtubule nucleation.

Intercompartmental transport in the Golgi complex is a dissociative process: facile transfer of membrane protein between two Golgi populations.

The transfer of the vesicular stomatitis virus-encoded glycoprotein (G protein) between Golgi populations in fused cells (Rothman, J. E., L. J. Urbani, and R. Brands. 1984. J. Cell Biol. 99:248-259) is exploited here to study and to help define the compartmental organization of the Golgi stack and to characterize the mechanism of intercompartmental transport. We find that G protein that has just received its peripheral N-acetylglucosamine in the Golgi complex of one cell is efficiently transferred to the Golgi complex of another cell to receive galactose (Gal). Remarkably, this transport occurs at the same rate between these two compartments whether they are present in the same or different Golgi populations. Therefore, a dissociative (presumably vesicular) transport step moves G protein from one part of the Golgi in which N-acetylglucosamine is added to another in which Gal is added. Minutes later, upon receiving Gal, the same G protein molecules are very poorly transferred to an exogenous Golgi population after cell fusion. Therefore, once this intercompartmental transfer has already taken place (before fusion), it cannot take place again (after fusion); i.e., transport across the compartment boundary in the Golgi complex that separates the sites of N-acetylglucosamine and Gal incorporation is a vectorial process. We conclude that transfers between Golgi cisternae occur by a stochastic process in which transport vesicles budding from cisternae dissociate, can diffuse away, and then attach to and fuse with the appropriate target cisterna residing in the same or in a different stack, based on a biochemical pairing after a random encounter. Under these circumstances, a transported protein would almost always randomize among stacks with each intercisternal transfer; it would not progress systematically through a single stack. Altogether, our studies define three sequential compartments in the Golgi stack.

Evaluation of an uncalibrated arterial pulse contour cardiac output monitoring system in cirrhotic patients undergoing liver surgery.

BACKGROUND: The pulmonary artery catheter is invasive and may cause serious complications. A safe method of cardiac output (CO) measurement is needed. We have assessed the accuracy and reliability of a recently marketed self-calibrating arterial pulse contour CO monitoring system (FloTrac/Vigileo) in end-stage liver failure patients undergoing liver transplant. The pattern of alterations known as cirrhotic cardiomyopathy, and the transplant procedure itself, provided an evaluation under varying clinical conditions. METHODS: The cardiac index was measured simultaneously by thermodilution (CI(TD): mean of four readings) using a pulmonary artery catheter and pulse contour analysis (CI(V): mean value computed by the FloTrac/Vigileo over the same time period). Readings were made at 10 time-points during liver transplant surgery (T1-T5) and on the intensive care unit (T6-T10). CI(V) was computed using the latest Vigileo software version 01.10. RESULTS: A total of 290 paired readings from 29 patients were collected. Mean (SD) CI(TD) was 5.2 (1.3) and CI(V) was 3.9 (0.9) litre min(-1) m(-2), with a corrected for repeated measures bias between readings of 1.3 (0.2) litre min(-1) m(-2) and 95% limits of agreement of -1.5 (0.2) to 4.1 (0.3) litre min(-1) m(-2). The percentage error (2SD(Bias)/meanCI(TD)) was 54%, which exceeded a 30% limit of acceptance. Low peripheral resistance and increasing bias were related (r=0.69; P<0.001). The Vigileo system failed to reliably trend CI data, with a concordance compared with thermodilution below an acceptable level (at best 68% of sequential readings). CONCLUSIONS: In cirrhotic patients with hyperdynamic circulation, the Vigileo system showed a degree of error and unreliability higher than that considered acceptable for clinical purposes.

False positive tardus-parvus waveforms after liver transplantation: a case of wide discrepancy between donor and recipient hepatic arteries mimicking anastomotic stenosis.

BACKGROUND: Parvus-tardus waveforms of the hepatic artery after liver transplantation usually indicate an arterial complication and severe impairment of hepatic arterial perfusion with a sensitivity of 91% and a specificity of 99.1%. Thus, it has been emphasized that detection of such waveforms should prompt emergency angiography. MATERIALS AND METHODS: Arterial reconstruction during a liver transplantation was successfully accomplished by an end-to-end anastomosis, performing a "flute-spout" widening of the anastomosis with a 7/0 prolene running suture between a small recipient proper hepatic artery and the donor common hepatic artery. RESULTS: On day 7 posttransplantation color Doppler ultrasonography revealed a parvus-tardus waveform pattern in the hepatic arterial flow. Computed tomographic (CT) angiography showed only a caliber discrepancy between the donor and recipient stumps, excluding an arterial stenosis or thrombosis. Since normal liver function persisted, the patient underwent routine follow-up. After 15 months the patient was alive and well; hepatic artery spectral waveforms were unchanged and liver functions were consistent with a mild hepatitis C virus (HCV) recurrence. CONCLUSIONS: This is a report of false positive tardus-parvus waveforms, due to a discrepancy between the donor and recipient arteries despite a wide anastomosis. Knowledge of technical reconstruction details may be helpful for correct interpretation of color Doppler findings. CT angiography should be considered before more invasive examinations.

Potential applications of extracorporeal photopheresis in liver transplantation.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy performed through a temporary peripheral venous access with documented efficacy in heart and renal transplantation. We originally reported that ECP represented a valuable alternative to treat graft rejection in selected liver transplant (OLT) recipients. We have investigated potential applications of ECP for prophylaxis of allograft rejection. The first field explored was the use of ECP for delayed introduction of calcineurin inhibitors (CNI) among high-risk OLT recipients seeking to avoid CNI toxicity. In 42 consecutive patients that we assigned to prophylaxis with ECP, we were able to delay CNI introduction after postoperative day 8 in one-third of them. The second field was the use of ECP for prophylaxis of acute cellular rejection among ABO-incompatible OLT recipients. In our experience, none of 11 patients treated with ECP developed a cell-mediated rejection. The third field was ECP application in hepatitis C virus-positive patients seeking to reduce the immunosuppressive burden and improve sustainability and efficacy of preemptive antiviral treatment with interferon and ribavirin. Among 78 consecutive patients, we were able to start preemptive antiviral treatment in 69.2% of them at a median time from OLT of 14 days (range = 7 to 130 days). Thirty-six (66.7%) patients completed the treatment course with an end of treatment virological response of 50.0% and a sustained virological response of 38.9%. These preliminary results await validation in larger prospective studies with longer follow-up periods.

Transcranial doppler sonography is useful for the decision-making at the point of care in patients with acute hepatic failure: a single centre's experience.

Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid deterioration of the hepatic function with severe derangements of the mental status in previously healthy subjects due to massive hepatocytes necrosis. Neurological impairment, due to intracranial hypertension and cerebral ischemia, is a key factor because it is a main criterion to decide when to proceed to liver transplantation, which is only treatment for these patients. Therefore, neurological monitoring holds an essential role in the clinical management of ALF patients but it needs to be performed at the point-of-care in the majority of the cases as such critically ill patients cannot be moved away from the ICU because they frequently need continuous hemodynamic, ventilatory and renal support. We herein report and discuss our experience relating to the use of transcranial sonography as a neuro-monitoring tool in ALF patients. In our series this technique allowed a repeatable and reliable non-invasive assessment of cerebral blood flow changes at the bedside thus avoiding the complications associated with the use of an intracranial probe to measure intra-cranial pressure and making it possible to correctly evaluate the timing and feasibility of liver transplantation.

Cost analysis of tumor downsizing for hepatocellular carcinoma liver transplant candidates.

We report the results of a prospective, intent-to-treat (ITT) trial on the costs of selective tumor downsizing (DS) before liver transplantation (LT) for patients affected with hepatocellular carcinoma (HCC). The trial started in January 1997 including adult patients with nodular-type HCC within and beyond the Milan criteria. Patients were downsized with transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and/or radiofrequency ablation (RFA) according to clinical predictors. TACE and RFA were performed as inpatient procedures, while PEI was performed on an outpatient basis. Costs of DS were obtained according to the Tuscany Health Reimbursement Fee Catalog adjusted to yearly inflation rates from 1997 through 2005. Data analysis was performed at 1 year after the last enrollment of 198 patients, including 161 (81.3%) who were transplanted: 34 (17.2%) dropped out and 3 (1.5%) were still on the waiting list. One hundred and fifty-two patients (76.7%) underwent DS for a total of 201 procedures: 159 TACE, 39 PEI, and 3 RFA. Overall costs in Euros (euro) of waitlisting were 861,801.24 euro: 548,460 euro (63.7%) for pretransplantation evaluation; 197,994.84 euro (22.9%) for control visits and hospitalizations; and 115.346.4 euro (13.4%) for DS. Mean costs of DS were 758.58 euro +/- 270 euro per downstaged patient (747.53 euro +/- 257.1 euro Milan; 774.01 euro +/- 287.71 euro non-Milan); 582.85 euro +/- 398.87 euro per waitlisted patient (520.28 euro +/- 406.23 euro Milan; 520.28 +/- 364.48 euro non-Milan); and 716.4 euro per transplanted patient (580.67 euro Milan; 1026.76 euro non-Milan; +76.8%). A selective policy of tumor DS increased the costs of LT waitlisting by 13.4%, but due to higher dropout rates among non-Milan patients, the cost utility of DS was 76.8% higher in the Milan group.

Improvement of diaphragmatic performance through orthotopic application of decellularized extracellular matrix patch.

Muscle tissue engineering can provide support to large congenital skeletal muscle defects using scaffolds able to allow cell migration, proliferation and differentiation. Acellular extracellular matrix (ECM) scaffold can generate a positive inflammatory response through the activation of anti-inflammatory T-cell populations and M2 polarized macrophages that together lead to a local pro-regenerative environment. This immunoregulatory effect is maintained when acellular matrices are transplanted in a xenogeneic setting, but it remains unclear whether it can be therapeutic in a model of muscle diseases. We demonstrated here for the first time that orthotopic transplantation of a decellularized diaphragmatic muscle from wild animals promoted tissue functional recovery in an established atrophic mouse model. In particular, ECM supported a local immunoresponse activating a pro-regenerative environment and stimulating host muscle progenitor cell activation and migration. These results indicate that acellular scaffolds may represent a suitable regenerative medicine option for improving performance of diseased muscles.

Switch to tacrolimus for cyclosporine-induced gynecomastia in liver transplant recipients.

We report herein on two male liver transplant (LT) recipients who presented with cyclosporine (CsA)-related gynecomastia 6 and 10 months after transplantation. The clinical workup showed increased luteinizing hormone (LH), associated with a slight reduction in testosterone blood levels in one patient and increased prolactin levels in the other. After excluding concomitant primary endocrine and/or malignant disease, conversion to tacrolimus (TAC) was performed resulting in clinical improvement of gynecomastia and return of hormone blood levels to normal range within 3 months. Our report confirms a putative role of CsA in post-LT gynecomastia, reversible however upon conversion to TAC.

Predominant role of the Fab fragment in delaying hyperacute rejection in guinea pig-to-rat xenotransplantation.

BACKGROUND: Human intravenous immunoglobulin G delayed xenogeneic hyperacute rejection (HAR) in the guinea pig-to-rat combination. We investigated the respective roles of the Fc and Fab fragments of the IgG molecule in this inhibitory effect. METHODS: By using a guinea pig-to-rat heart transplantation model, the efficiency of IgG, Fab, and Fc in prolonging the grafted heart's survival time (ST) was compared. RESULTS: A dose-dependent increase in the ST was observed with Fab (r=0.74, P < 0.0001), IgG (r=0.57, P < 0.001), and Fc (r=0.51, P < 0.01). The linear regression slopes with Fab and with IgG were, respectively, sevenfold and fourfold steeper than with Fc. The ST was significantly longer than controls (23+/-7 min) after infusion of 2 g/kg IgG (147+/-42 min) or 1 g/kg Fab (176+/-38 min), whereas the highest dose of Fc (1.5 g/kg) did not induce significant prolongation of ST. In terms of equivalent functional doses, 1 g/kg Fab was significantly more potent in prolonging the ST than 1.5 g/kg IgG (87+/-25 min) or 0.5 g/kg Fc (33+/-14 min). Analysis of the rejected hearts evidenced edema, necrosis, and rat C3 deposits characteristic of HAR. CONCLUSION: These results indicated that the delaying action of intravenous immunoglobulin G on HAR in the guinea pig-to-rat combination is mostly mediated through the Fab fragment.

Effects of high altitude exposure on plasma and urinary digoxin-like immunoreactive substance.

Six young healthy subjects underwent a 20 day exposure to altitude, at 4930 m (16,174 ft), to evaluate possible plasma and urine digoxin-like immunoreactive substance (DLIS) changes accompanying the altered water and electrolyte balance induced by hypoxia. We studied DLIS, plasma renin activity (PRA), aldosterone, atrial natriuretic peptide (ANP), and arginine vasopressin (ADH) in serial blood and urine samples. An increase in DLIS in plasma (P less than .005) and urine (P less than .01) was found, while aldosterone was decreased (P less than .02). PRA, ADH, and ANP did not change significantly. A trend to a greater loss of sodium through urinary excretion, correlated with urinary DLIS values (r = 0.47, P less than .01), was observed. Data suggest a possible important role of DLIS in adaptive response of human organism to high altitude.

Oculomotor impairment after 1 night of total sleep deprivation: a dissociation between measures of speed and accuracy.

OBJECTIVES: The present study examined the effects of 40 h of sleep deprivation and of time-of-day on saccadic and smooth pursuit oculomotor performance. METHODS: Nine normal subjects slept for 3 consecutive nights in the laboratory (one adaptation, one baseline, one recovery). Baseline and recovery were separated by a period of 40 h of continuous wakefulness, during which subjects were tested every 2 h. Oculomotor performance assessed at the following hours: 10:00, 12:00, 14:00, 16:00, 18:00, 20:00, 22:00, of both the days preceding and following the sleep deprivation night, as well as at 24:00, 02:00, 04:00, 06:00 and 08:00 h during the deprivation period. RESULTS: Saccade latency increased and peak velocity decreased significantly during the post-deprivation day; saccadic accuracy was unaffected. As regards smooth pursuit performance, phase (a measure of accuracy) was not affected by sleep loss, while velocity gain significantly decreased during the day that followed the sleep deprivation night. Significant time-of-day effects on the considered oculomotor variables except saccadic accuracy were also found, indicating an overall performance impairment during the night. CONCLUSIONS: It is concluded that 40 h of sleep deprivation significantly impaired diurnal performance in pursuit and saccadic tasks. This performance worsening is limited to the measures of speed, while accuracy is not affected by sleep loss. A significant operational relevance of these results is suggested, since saccadic velocity has recently been found to be negatively correlated with simulator vehicle crash rates.

Smooth pursuit and saccadic eye movements as possible indicators of nighttime sleepiness.

Sleepiness is associated with specific variations of spontaneous oculomotor activity. During nocturnal sleep onset periods and also during the Multiple Sleep Latency Test (MSLT) a reduction of both rapid eye movements and blinks are recorded. In many operational contexts it might be even more relevant to assess whether and to what extent voluntary visual ocular control is affected by sleepiness due to sleep deprivation and time-of-day effects. In this study we evaluated, in a laboratory simulation of a sudden inversion of the sleep-wake cycle, the nocturnal modifications of smooth pursuit (SP) and saccadic (SAC) eye movements as possible indicators of sleepiness. Levels of sleepiness were objectively measured by means of MSLT and Maintenance of Wakefulness Test (MWT); subjective ratings of sleepiness were also obtained. After a diurnal sleep, five subjects underwent four nocturnal test sessions, each one comprising an SP and a SAC trial. Both the SP variables considered (velocity gain and phase) showed a trend similar to that one of MWT latencies, being significantly impaired only in the last nocturnal trial, when levels of sleepiness were maximal. Saccadic accuracy showed the same trend, being negatively affected by sleepiness only in the last nocturnal session. In addition, percentage of rejected (inappropriate) saccades showed a linear increase during the night, paralleling the shortening of sleep latency at MSLT and the linear increase of subjective ratings of sleepiness. These results, suggesting that saccadic performance, unlike SP, seems to be more sensitive to increasing levels of sleepiness, encourage further research on this topic.

Effects of hypobaric hypoxia on the human auditory brainstem responses.

Auditory brainstem responses (ABRs) were recorded in six volunteers before, during and after 90-min exposure to hypobaric hypoxia (5,184 m; barometric pressure = 405 mmHg) in an altitude chamber. Waves I, III and V absolute and interpeak latencies were analysed. The main result of the experiment was a significant shortening of the brainstem transmission time (I-V interval) in the recovery from hypoxia compared with the basal condition. This finding could be explained with a slow decay of the compensatory mechanisms acting during hypoxia and/or a transient neuronal hyperexcitability at the end of the hypoxic stress.