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Objective To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction. Methods The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed. Results Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77-0.93 and OR = 1.34, 95% CI = 1.05-1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06-1.25). Significance Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.

Acute encephalopathy in hospitalized patients is common and associated with high mortality. Preservation of physiological sleep has been associated with favorable outcomes in acute brain injury. It is hypothesized that electroencephalographic presence of sleep elements is associated with good outcome in encephalopathic adults.; This observational study was performed at an academic tertiary medical care center. Clinical data, electroencephalogram (EEG) characteristics and outcome of critically ill patients with acute encephalopathy were assessed. EEGs were interpreted regarding the presence of sleep elements (K-complexes, vertex sharp-waves and sleep spindles). Associations between sleep elements and outcome (graded by the Glasgow Outcome Scale, GOS) were analyzed.; One hundred and forty-two consecutive patients with a median age of 64.5 years (range 18-98) and mean Glasgow Coma Scale 10.4 (± 3.8) were included. Leading etiologies were infections (47.2%), intracranial hemorrhages (14.1%) and ischaemic strokes (10.6%). All EEGs demonstrated encephalopathy patterns and 38% had ≥1 sleep element (27.5% K-complexes, 31.7% vertex sharp-waves and 33.8% sleep spindles). Patients without sleep elements were older (P = 0.010) and septic shock was more common (P = 0.014). Amongst sleep elements, K-complexes were significantly associated with good outcome, even after adjusting for possible confounders (odds ratio for GOS 5 = 2.79, 95% confidence interval 1.16-6.69) and without significant effect modification across subgroups.; Whilst EEG sleep elements were detected more frequently in patients with favorable outcome, only K-complexes were significantly and independently associated with good outcome in intensive care unit patients with acute encephalopathy, findings that need to be confirmed in larger prospective studies.

A 41-year-old man, during a neurological consultation, reported “chin twitching” over a period of a week, which was diagnosed as intermittent perioral myoclonia. With only one tonic-clonic seizure seven years before, he had mentioned several episodes of chin twitching over the years. In the clinic, there were intermittent chin movements without apparent confusion, as he was able to provide a complete history and was fully oriented with intact memory. His video-EEG showed paroxysms of polyspike and slow-wave activity, with the longest burst-free interval being 20 seconds. Discharges were maximal over the fronto-central regions, correlating with the chin myoclonus. He was able to tap his hand continuously, and remained alert. The case represents an atypical presentation of idiopathic generalised epilepsy without manifestation of absence or limb myoclonus. Although juvenile myoclonic epilepsy and other idiopathic epilepsies are rarely associated with perioral myoclonia, this sign was the principal clinical feature for this patient. Oral treatment with levetiracetam resolved his seizures. [Published with video sequences]

Background and purpose Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case–control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome. Methods From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed. Results The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98–33.08], alcohol abuse (OR = 3.65, 95% CI 1.25–10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39–5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01–4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16–5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27–25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs). Conclusions Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.

There have been many attempts at defining the electroencephalography (EEG) characteristics of nonconvulsive status epilepticus (NCSE) without a universally accepted definition. This lack of consensus arises because the EEG expression of NCSE does not exist in isolation, but reflects status epilepticus under the variety of pathologic conditions that occur with age, cerebral development, encephalopathy, and epilepsy syndrome. Current NCSE definitions include "boundary conditions," in which electroencephalographic seizure activity occurs without apparent clinical seizures. Furthermore, what appears to one interpreter as status epilepticus, is not to another reader, reflecting the "art" of EEG interpretation. Seizures and epilepsy syndromes have undergone an evolution that has moved beyond a classification of focal or generalized conditions into a syndromic approach. It seems appropriate to make similar changes in the EEG analysis of the syndromes of NCSE. In effect, the literature on epilepsy classification has progressed to incorporate the different NCSE types with clinical descriptions, but the specific EEG evidence for these types is found largely in individual reports, and often by description only. NCSE classification of EEG patterns should derive from the aggregate of published EEG patterns in the respective clinical subtype, supported by an analysis of these EEG studies. The analysis that follows presents clinical descriptions and EEG patterns of NCSE in the neonatal period, infancy, childhood, adulthood, and late adulthood from a syndromic perspective based on age, encephalopathy, cerebral development, etiology, and syndrome. Proceeding from the proposed classification of status epilepticus syndromes in "Status epilepticus: its clinical features and treatment in children and adults" (published in 1994 by Cambridge University Press, New York), we have performed a systematic search for reports presenting EEG patterns of NCSE using the online medical search engine PubMed for 22 different search strategies. EEG patterns were reviewed by two board-certified epileptologists who reached consensus regarding presence of NCSE. From a total of 4,328 search results, 123 cases with corresponding EEG patterns could be allocated to underlying epilepsy syndromes. Typical characteristic, prominent electrographic patterns, and sequential arrangements are elucidated for the different NCSE syndromes. This compendium of patterns by NCSE syndrome classification with illustration of EEGs, and delineation of electroencephalographic features helps define the characteristics and semiologic borderlines among the types of NCSE.

The goal of this study was to survey veterinarians regarding their current initial diagnostic and treatment recommendations for dogs with substage-a high-grade multicentric lymphoma. A written survey was conducted at the 2009 Veterinary Cancer Society conference asking veterinarians to provide demographic information, initial staging diagnostics and treatment recommendations for canine lymphoma. The most commonly recommended staging diagnostics were complete blood count (100%), chemistry panel (100%), urinalysis (85%), lymph node cytology (88%), thoracic radiographs (84%), immunophenotyping (76%) and abdominal ultrasound (75%). The most commonly used first-line B-cell protocols combined the drugs L-asparaginase, cyclophosphamide, doxorubicin, vincristine and prednisone (L-CHOP, 51%). CHOP (30%) and other CHOP-based protocols (12%) were used as well. Thirty-one percent of responders treated B- and T-cell lymphomas differently. Protocol lengths varied from ≤ 16 weeks to >2 years. Current staging and treatment recommendations for canine lymphoma are varied. Efforts to standardize recommendations should be considered.

We retrospectively analysed the clinical characteristics, electroencephalogram (EEG) records, brain magnetic resonance imaging (MRI) scans, antiepileptic therapy and prognosis of a case series with ambulatory non-convulsive status epilepticus (NCSE) which evolved into a malignant form (mNCSE). mNCSE was defined as NCSE that continues or recurs five days or more after the onset of general anaesthesia, including those cases where NCSE recurs upon reduction or withdrawal of anaesthetic therapy. Four women and two men were studied. The mean age was 42.8 years (range: 19-63 years). Two of six patients had a previous diagnosis of epilepsy. Four patients died. Two patients had a good outcome with return to consciousness and activities of daily life, and one of these subjects developed temporal lobe epilepsy. In four patients, the cause of mNCSE was encephalitis. Clinical presentation was complex partial status epilepticus (CPSE) in three patients and generalised NCSE (GNCSE) in the other three. Two of the latter had encephalitis and one was diagnosed with progressive myoclonus epilepsy (PME) of Lafora type. The mean duration of the NCSE episode was 47.5 days (range: 9-139 days; SD: 53.1). In three patients, continuous or rhythmic focal epileptiform discharges were the EEG pattern at onset. In the other three, continuous rhythmic generalised spike-wave, polyspike-wave or sharp slow-wave complexes were observed. Antiepileptic treatment was heterogeneous and patients were treated with an average of 6.0 AEDs (range: 3-10; SD: 3.0). In summary, mNCSE is a severe epileptic condition that occurs often in the context of encephalitis or pre-existing epilepsy. Both CPSE and GNCSE may occur. Although high mortality is associated with mNCSE, some patients may survive with normal or good recovery.

Zusammenfassung Es wird uber Systemmykosen bei Tieren in Osterreich anhand eines Sektionsgutes von 20 Jahren berichtet. Erstmalig werden Mykosen bei einigen Zoo- und Wildtieren sowie Misch- und Mehrfachinfektionen beschrieben. Das Aussehen von Aspergillen, Candida und Zygomyceten im histopathologischen Praparat wird erlautert. Die Probleme der Diagnose opportunistischer Pilze sowie das Zustandekommen von Infektionen mit solchen Pilzen wird diskutiert. Summary Some observations on the occurrence of systemic mycosis of animals in Austria On the basis of autopsies carried out over the last 20 years an account is given of systematic mycosis in animals in Austria. Mycoses in a number of zoological and wild animals, as well as mixed and multiple infections are first described. The features of Aspergillus, Candida and zygomycetes in histological preparations are described. The problem of the diagnosis of opportunist fungi and the occurrence of infections with such fungi are discussed. Resume Quelques observations sur l'apparition de mycoses systemiques chez des animaux en Autriche Des mycoses systemiques animales sont decrites en Autriche sur la base d'autopsies faites durant vingt annees. On decrit en premier des mycoses chez des animaux de parcs zoologiques et sauvages ainsi que des infections mixres et multiples. L'aspect d'Aspergillus, de Candida et des zygomycetes dans une preparation histopathologique est explique. On discute le probleme du diagnostic des champignons opportunistes et de l'apparition d'infections avec de tels champignons. Resumen Algunas observaciones sobre la presentacion de micosis sistemicas en animales en Austria Se informa sobre micosis sistemicas en animales en Austria con arreglo a un caudal de necropsias de 20 anos. Por vez primera se describen micosis en algunos animales de parques zoologicos y en fieras montesas, asi como infecciones mixtas y reiteradas. Se explica el aspecto de los aspergilos, candida y cigomicetos en las preparaciones histopatologicas. Se discuten los problemns relativos al diagnostico de hongos oportunistas, asi como la verificacion de infecciones con hongos semejantes.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.

Objective. Determination of fetal sex is an important part of detailed second-trimester ultrasonography. This task can be hindered by the fetal position, a low amniotic fluid volume, and advanced gestational age. Identification of fetal sex is further important in multiple gestations and prior histories of indeterminate-sex pregnancies. The goal of the study was to compare the effectiveness of 2-dimensional ultrasonography (2DUS) versus 3-dimensional ultrasonography (3DUS) at sex identification and to determine how genitalia measurements taken with 3DUS technology compare with measurements taken with 2DUS. Methods. A total of 111 patients at or beyond 16 weeks’ gestation were recruited. Assignments of fetal sex using 2DUS and 3DUS were compared by the test of proportions. The actual neonatal sex was obtained after delivery. Given such small number of misdiagnoses by either 2DUS or 3DUS, the accuracies of the two modalities were not found to be statistically distinguishable from one another (P = .5585). The penile length, scrotal width, and bilabial diameter according to gestational age were measured and compared with previously published 2DUS data by t tests. Results. Sexes were assigned and interpreted in 65 cases. Ranges of genitalia measurements were plotted against gestational age and were found to be comparable with published data. There was a dramatic difference between the bilabial diameter and scrotal width with advancing gestational age that made sex determination much easier in the third trimester. Conclusions. Although 3DUS did not have better prediction of fetal sex when compared with 2DUS, it may be a useful tool in conjunction with traditional imaging techniques in assigning fetal sex. Key words: ambiguous genitalia; fetus; genitalia; sex; ultrasonography.

The Fulton Section, along the Mississippi River in western Tennessee, USA, is a 1 km continuous exposure (� 20 m vertically) of Quaternary fluvial and lacustrine deposits, inset within Eocene sediments and buried by thick loess. Fossiliferous slackwater lake sediments record maximum aggradation during the last two major glaciations, with deposition between ca. 190-140 ka and Q1 24- 18 14 C ka BP, based on amino acid and radiocarbon chronology, respectively. During the onset of full glacial conditions (ca. 24-22 14 C ka BP), a relatively permanent shallow lake environment is indicated by ostracodes, aquatic molluscs, and both pollen and macrofossils of aquatic plants. By 21.8 14 C ka BP, increasing emergent plants, amphibious gastropods (Pomatiopsis) and heavier d 18 O compositions suggest marsh-like conditions in a periodically drying lake. The surrounding uplands consisted of Picea-Pinus woodlands mixed with cool-temperate hardwoods (e.g.Quercus,Populus,Carya), grasses and herbs. More open conditions ensued ca. 20 14 C ka BP, with loess and slopewash gradually infilling the former lake by 18 14 C ka BP. Modern analogue analyses of ostracodes and palaeontological evidence imply a full glacial climate similar to today's mixed-boreal zone in central Minnesota, USA, about 98C cooler in mean annual temperature than present-day western Tennessee. Copyright # 2009 John Wiley & Sons, Ltd.

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure-free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.

Summary: Both the sexual and asexual fruiting bodies of Aspergillus nidulans were discovered in the lung tissue of a captive rhinoceros, in a biopsy specimen from a human with bronchial stump aspergillosis, and in the guttural pouch of a horse. In addition, a zygomycete with unusual morphology was found in the lungs of the rhinoceros. Zusammenfassung: Es wurden sowohl sexuelle als auch asexuelle Sporen von Aspergillus nidulans im menschlichen Biopsiematerial eines Patienten mit Bronchialstumpfmykose sowie im Luftsack eines Pferdes und im Lungengewebe eines Nashorns gefunden. Beim Nashorn wurde zusatzlich zur Aspergillus-In vasion auch eine Zygomyzeteninvasion mit ungewohnlichen Struk-turen beobachtet.

The linkage of 34 auxotrophic markers in strain HY of Serratia marcescens was studied by means of transductions with phages x and y. The markers could be ordered into 18 loci of different auxotrophies by transduction crosses with phage x (markers in trans-position) 17 of which showed to be linked to at least one of the other loci. A linear map of this section of the genome was constructed. It corresponds well to the map of 8 loci derived from transductive crosses (markers in cis-position) with phage y. Since a virion can transduce about 5 loci at the same time the map represents only a small section of the Serratia genome. No similarity to any part of the maps of Escherichia or Salmonella can be detected. It is discussed why most auxotrophic mutations which were induced by nitrosoguanidine map in this small genomic region.

Lithium therapy can cause a confusional state by direct toxicity, precipitation of nonconvulsive status epilepticus, or by interplay with other neuroleptic medications to produce neuroleptic malignant syndrome or serotonin syndrome. These conditions resemble each other clinically, but EEG may help differentiate among them. We reviewed the EEG patterns with triphasic waves or rhythmic delta activity in lithium toxic patients and discuss clinical and EEG differentiation among syndromes. Lithium toxicity poses significant diagnostic challenges from EEG and clinical perspectives.

A pilot-scale land treatment unit (LTU) was constructed at the former Guadalupe oil production field with the purpose of investigating the effect of co-substrate addition on the bacterial community and the resulting rate and extent of total petroleum hydrocarbon (TPH) degradation. The TPH was a weathered mid-cut distillate (C10-C32) excavated from the subsurface and stockpiled before treatment. A control cell (Cell 1) in the LTU was amended with nitrogen and phosphorus while the experimental cell (Cell 2) was amended with additional complex co-substrate—corn steep liquor. During the pilot LTU operation, measurements were taken of TPH, nutrients, moisture, aerobic heterotrophic bacteria (AHB), and diesel oxidizing bacteria (DOB). The bacterial community was also assayed using community-level physiology profiles (CLPP) and 16S rDNA terminal restriction fragment (TRF) analysis. TPH degradation in both cells was characterized by a rapid phase of degradation that lasted for the first three weeks, followed by a slower degradation phase that continued through the remainder of the project. The initial rate of TPH-degradation in Cell 1 (−0.021 day−1) was slower than in Cell 2 (−0.035 day−1). During the slower phase, degradation rates in both cells were similar (−0.0026 and −0.0024 respectively). AHB and DOB counts were similar in both cells during the fast degradation phase. A second addition of co-substrate to Cell 2 at the beginning of the slow degradation phase resulted in an increased AHB population that lasted for the remainder of the project but did not affect TPH degradation rates. CLPP data showed that co-substrate addition altered the functional capacity of the bacterial community during both phases of the project. However, TRF data indicated that the phylogenetic composition of the community was not different in the two cells during the fast degradation phase. The bacterial phylogenetic structure in Cell 2 differed from Cell 1 after the second application of co-substrate, during the slow degradation phase. Thus, co-substrate addition appeared to enhance the functional capacity of the bacterial community during the fast degradation phase when the majority of TPH was bioavailable, resulting in increased degradation rates, but did not affect rates during the slow degradation phase when the remaining TPH may not have been bioavailable. These data show that co-substrate addition might prove most useful for applications such as land farming where TPH is regularly applied to the same soil and initial degradation rates are more important to the project goals. © 2003 Wiley Periodicals, Inc.

This paper describes a rigorous undergraduate course on environmental dispute resolution. Students get hands-on experience in negotiation cases, developing skills and building theoretical understanding through a series of exercises. With this foundation, the students advance to an extended role-playing case study on oil exploration in the Ecuadorian rain forest. The course provides an integration function both in terms of understanding environmental issues, but also in modeling reality, encouraging action, and building process tools that are essential in addressing environmental and social challenges facing the planet.

Though the reported frequency of infant hydrocele has varied, the frequency of hydrocele in the fetus has not been studied. Our purpose was to determine the frequency of fetal hydrocele in the third trimester and subsequent outcome. Of the 123 fetuses studied, 19 fetuses had hydroceles. Of these, 14 babies were normal at follow-up, one baby had a persistent hydrocele, and four babies were lost to follow-up. Our study suggests that hydrocele is a relatively common finding in the third trimester in utero. Moreover, it suggests that parents can be reassured that, in the absence of other abnormalities, a hydrocele is usually a physiologic finding which resolves spontaneously.

The inactivation of photolyzed rhodopsin requires phosphorylation of the receptor and binding of a 48-kDa regulatory protein, arrestin. By binding to phosphorylated photolyzed rhodopsin, arrestin inhibits G protein (Gt) activation and blocks premature dephosphorylation, thereby preventing the reentry of photolyzed rhodopsin into the phototransduction pathway. In this study, we isolated a 44-kDa form of arrestin, called p44, from fresh bovine rod outer segments and characterized its structure and function. A partial primary structure of p44 was established by a combination of mass spectrometry and automated Edman degradation of proteolytic peptides. The amino acid sequence was found to be identical with arrestin, except that the C-terminal 35 residues (positions 370-404) are replaced by a single alanine. p44 appeared to be generated by alternative mRNA splicing, because intron 15 interrupts within the nucleotide codon for 369Ser in the arrestin gene. Functionally, p44 binds avidly to photolyzed or phosphorylated and photolyzed rhodopsin. As a consequence of its relatively high affinity for bleached rhodopsin, p44 blocks Gt activation. The binding characteristics of p44 set it apart from tryptic forms of arrestin (truncated at the N- and C-termini), which require phosphorylation of rhodopsin for tight binding. We propose that p44 is a novel splice variant of arrestin that could be involved in the regulation of Gt activation.

Adrenoleukodystrophy is an X-linked metabolic disorder with very-long-chain fatty acid (VLCFA) accumulation and multifocal nervous system demyelination, often with early involvement of visual pathways. Dietary therapy with glycerol trioleate and glycerol trierucate (Lorenzo oil) diminishes VLCFA levels. In a study of patients with the adrenomyeloneuropathy phenotype of adrenoleukodystrophy, we used pattern-reversal visual evoked potentials to evaluate visual pathways before and after treatment. Of 108 patients tested, all 26 women and 68 of the 82 men had normal potentials at baseline. Seventy patients were retested at 1 year, at which time VLCFA levels were markedly diminished. Of them, the responses in the 10 men who showed abnormalities at baseline remained abnormal; the latencies in 4 men with initially normal responses became abnormal. No patients improved. There were no correlations between disease duration prior to treatment, baseline P100 latencies, VLCFA levels, or the change in P100 latencies and VLCFA levels after dietary treatment for 1 year. Pattern-reversal visual evoked potentials were abnormal in 17% of the men with adrenoleukodystrophy, and there was no evidence that reduction of VLCFA levels improved or retarded visual pathway demyelination.

We studied the visual system in 59 men with adrenomyeloneuropathy. Pattern-reversal visual evoked potentials, magnetic resonance imaging, and clinical examination revealed that visual pathways are affected in 63% of patients, involving the optic discs, optic nerves, lateral geniculate bodies, optic radiations, and parietooccipital cortex. This indicates both primary demyelination of the optic nerves and discs, and more diffuse involvement of postchiasmal structures.

1. Time resolved birefringence measurements reveal complex structural changes in rod outer segments following a bleaching flash. 2. The detailed character of the observed changes depends upon osmotic integrity of the outer segment envelope membrane. Rod outer segments with intact envelope membranes show a fast initial loss of intrinsic birefringence simultaneous with the formation of metarhodopsin II followed by a slower secondary loss. A subsequent birefringence increase to higher than the dark-adapted level is partially correlated with the formation of retinol. Rod outer segments with ruptured envelope membranes show the initial and secondary losses, but the subsequent recovery only reaches the dark-adapted level. Retinol does not form in such organelles. 3. The slow birefringence changes in intact rod outer segments were qualitatively different when Na+ salts were replaced by equimolar K+ salts in the bathing medium. 4. Glycerol appears to influence both the rate and magnitude of metarhodopsin III formation, and of the spectrally silent secondary birefringence loss.

The relationship between age, education, length and amount of heavy drinking, and performance on five memory tasks was investigated in 54 chronic alcoholics and 18 age-matched controls. Alcoholics with less than 12 yr of heavy drinking differed reliably from long-term (13-22 yr) and extended long-term drinkers (greater than 23 yr) in recognition memory for visual patterns when scores were corrected for age. Compared with controls, both groups of long-term drinkers were deficient on the visual, auditory, and Faces recognition tests. Age and education of alcoholics accounted for part of performance differences; length of alcohol abuse, however, predicted reliably the decline in memory scores on all but the tactual test. The profile of memory performances seemed to decrease linearly with increasing age and length of alcohol abuse.

Cryptococcal infection of the C.N.S. is described in a two-year-old Borzoi dog. The animal showed limb weakness progressing over a period of five months to spastic paraplegia with head tremor, stiffness of the neck and nystagmus. On post-mortem examination there was severe hydrocephalus and granulomatous ependymitis. Cryptococci were found in the lesions and were identified on the basis of morphology and reaction to specific fluorescent antibody. This is believed to be the first case of canine cryptococcosis reported in the United Kingdom.

The paper is concerned with the question of whether Weigle-reactivation (WR) and Weigle-mutagenesis (WM) can be indirectly induced by infection with UV-irradiated phage. Experiments neither with phage λ of Escherichia coli nor with phage χ of Serratia marcescens show such induction-In this respects phage DNA differs from F′-DNA or Hfr-DNA; possible explanations are discussed. In both systems clear plaque mutations can also be induced by UV without irradiation of the host cells; they appear, in unirradiated and irradiated host cells, with an increase in frequency which is greater than proportional to the UV dose. It is concluded that mutation induction of phage in the unirradiated host cells is due to a low level constitutive mutagenic repair; this could either be due to “spontaneous” induction of the mutagenic SOS-function or it could be a mechanism different from this one. Host irradiation would give rise to additional activity by the induced SOS-function leading to WR and WM. It is further concluded that deviation of the induction kinetics from a linear dose-dependence is not due to the necessary induction of SOS-functions.

— In the non-photoreaclivable bacterial strain E. coli B/phr-/MC2 the photoreversion of four groups of u.v.-induced mutations were investigated. They lead to resistance to Chloramphenicol (2 mg/l; “C”), Penicillin (13 or 16 mg/l; “P13” and “P16”) or Streptomycin (3 mg/l; “S”). The u.v.-dose curve is concave for the C-mutations (two to three hits), about linear for P13 and S, and they reach peaks and decrease at high u.v.-doses. Though no photoreactivation of killing (PR) is present there is photoreversion of all four types of mutations (PRM). At u.v.-doses below the peaks in average about 43 per cent mutations are photoreversible. At high u.v.-doses the curves with light-post treatment (L) cross the darkcurves (D). In the photoreactivable strain B/r (by the spontaneous mutation MC2 to Mitomycin-resistance strain B/phr- was made about as u.v.-resistant as B/r is) the photoreversion of the mutation groups C, P13 and P16 (S was not investigated here) was much higher, in average about 77 per cent at low doses. It is assumed that the difference in PRM of about 34 per cent between both strains is due to a PRM-mechanism present in B/r but not in B/phr-/MC2; this mechanism may be the photoreactivating enzyme that opens thymine-dimers. The PRM in B/phr-/MC2 must then be due to a second mechanism which is probably not the dimer opening enzyme. It may be the same mechanism as in the case of mutations of phage kappa which are induced by u.v. and reversed partially by light, both extra cellularly. The premutations giving this second type of PRM may perhaps be cytosine-hydrate in the DNA. Tn average about 23 per cent mutations of B/r are photostable. Since this ratio decreases with low u.v.-doses in the C-mutations and increases in P13 and in P16 probably two types of photostable premutations seem to exist.