Viral emergence in marine mammals in the North Pacific may be linked to Arctic sea ice reduction.

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from 2001-2016, we investigated the timing of PDV introduction, risk factors associated with PDV emergence, and patterns of transmission following introduction. We identified widespread exposure to and infection with PDV across the North Pacific Ocean beginning in 2003 with a second peak of PDV exposure and infection in 2009; viral transmission across sympatric marine mammal species; and association of PDV exposure and infection with reductions in Arctic sea ice extent. Peaks of PDV exposure and infection following 2003 may reflect additional viral introductions among the diverse marine mammals in the North Pacific Ocean linked to change in Arctic sea ice extent.

Struggling with the last breath: breathlessness at the end of life on the AMU.

Breathlessness is one of the most common symptoms experienced at the end of life, affecting all areas of a patient's life. It is frightening and leads to high rates of emergency hospital attendances. Often, there is no easily reversible cause and patients are admitted to the acute medical unit (AMU) in order to manage their symptoms with little overall benefit - frustrating patients and clinicians alike. This review reminds the generalist of the significance of breathlessness as a symptom. It highlights the management strategies available to effect improvement and gives practical tips on how this can be achieved within the busy and time-pressured environment of the AMU.

An atypical presentation of an acute neurological illness: acute motor axonal neuropathy.

Pain is a common symptom amongst patients presenting to the Acute Medical Unit, with an extensive differential diagnosis. We present the case of a patient with back and lower limb pain where the diagnosis of an atypical form of Guillain-Barre Syndrome (GBS) was made. Acute physicians must be vigilant to the less common presentations of GBS and the variations from the "classical" presentation of ascending flaccid paralysis.

Non-Convulsive Status Epilepticus as a cause for prolonged delirium: an under-diagnosed phenomenon?

Delirium is a common cause for acute hospital admissions. There are many potential causes for this presentation, including infection, polypharmacy and metabolic disorders. We present the case of a patient with hyponatraemia and prolonged delirium, in whom the diagnosis of non-convulsive status epilepticus (NCSE) was made following electroencephalography (EEG).

Ventricular dysfunction associated with brain trauma is cause for exclusion of young heart donors.

OBJECTIVE: Ventricular dysfunction (VD) in the context of brain death (BD) is one medical cause that may be reversed to extend the range of donors for cardiac transplant programs. The aim of this study was to identify and quantify the causes for exclusion of potential heart donors and to define risk factors for VD among the BD population. MATERIALS AND METHODS: This study of 100 heart-beating potential donors defined subjects as those younger than 50 years. We defined hemodynamic dysfunction (HD) as failure to achieve hemodynamic objectives despite the use of inotropic agents by protocol or upon diagnosing VD. RESULTS: Among 246 BD subjects were 100 potential heart donors. Of these, 75 were transformed into real donors (RD) including 13 heart RD and 62 noncardiac RD. The conversion rate of BD subjects younger than 50 years to heart RD was 17%. When we analyzed the medical reasons for exclusion of the 62 donors who were not converted to heart RD, we observed that HD was the major cause (34%). When we analyzed the causes for exclusion related to cause of death, cranial trauma predominated (52%; P = .01; relative risk 3.5; 95% confidence interval 1.4-8.5). CONCLUSION: Hemodynamic dysfunction represented the major cause for loss of heart donors; it was associated with younger patients with cranial trauma.

Brain death epidemiology in Uruguay and utilization of the Glasgow coma score in acute brain injured patients as a predictor of brain death.

OBJECTIVE: The knowledge of brain death (BD) epidemiology and the acute brain injury (ABI) progression profile are relevant to improve public health programs, organ procurement strategies, as well as intensive care unit (ICU) protocols aiming to increase the detection of potential donors. The aim of this study was to analyze the BD epidemiology and the ABI progression profile among subjects admitted to ICUs with a Glasgow Coma Score (GCS) < or = 8. MATERIALS AND METHODS: This was a prospective, observational study of BD reported to the National Institute of Donation and Transplantation from 2000-2006. The patients with ABI and GCS < or = 8 who were admitted to 5 ICUs with In-hospital Transplant Coordination were analyzed over the period of 2005-2007. RESULTS: The BD detection increased from 28.7 in 2000 to 58.5 BD pmp in 2006. The real donor global rate increased from 10 to 24.6 pmp from 2000 to 2006. The ABI patients with GCS < or = 8 had a global mortality rate of 56%, including 23.4% who evolved to BD. CONCLUSIONS: This study showed a 200% increment of detected BD and 150% of real donors, although these results are still below the international figures. GCS follow-up appeared to be a good tool to predict the BD outcome. The follow-up of patients with ABI allowed us to improve our BD detection strategy.

Second trimester Doppler ultrasound screening of the uterine arteries differentiates between subsequent normal and poor outcomes of hypertensive pregnancy: two different pathophysiological entities?

The 'classical' concept that pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) primarily originate from defective placentation in early pregnancy has been challenged recently. There is growing evidence that other factors, including maternal predisposing conditions, also play a significant role in the pathophysiology of PIH and PE. The aim of the present study was to test the hypothesis that PIH and PE with an early onset and poor pregnancy outcome is associated with defective placentation, e.g. inadequate spiral artery dilatation and subsequent reduced uteroplacental perfusion, whereas PIH and PE with normal pregnancy outcome is not. Using Doppler ultrasound, we measured the uterine artery pulsatility index (PI) in a population of 531 nulliparous women in the 22nd week of gestation. Uterine artery PI was used as an index of resistance to blood flow in the uteroplacental circulation. Outcome measures were PIH/PE with or without poor pregnancy outcome, preterm birth and intra-uterine growth restriction (IUGR). The results revealed a striking difference between PI values for PIH/PE with and without poor pregnancy outcome. Uterine artery PI in the 22nd week was increased significantly in pregnancies which developed early-onset (before 35 weeks) PIH/PE with a poor pregnancy outcome. In contrast, uterine artery PI values were normal in women who developed PIH/PE, but had a good pregnancy outcome. There was a significant correlation between 22nd week uterine artery PI and subsequent preterm birth or IUGR. Our results indicate that only PIH/PE with poor pregnancy outcome is associated with defective placentation, whereas PIH/PE with good outcome is not. These findings support the concept of heterogeneous causes of hypertensive disorders of pregnancy.

Domoic acid toxicity in Californian sea lions (Zalophus californianus): clinical signs, treatment and survival.

Eighty-one Californian sea lions (Zalophus californianus) with signs of domoic acid toxicity stranded along the coast of California in 1998 when there were blooms of the domoic acid-producing alga Pseudonitzschia australis off-shore. In 2000, a further 184 sea lions stranded with similar clinical signs, but the strandings occurred both during detectable algal blooms and after the blooms had subsided. The clinical signs in these 265 Californian sea lions included seizures, ataxia, head weaving, decreased responsiveness to stimuli and scratching behaviour. Affected animals had high haematocrits, and eosinophil counts, and high activities of serum creatine kinase. They were treated supportively by using fluid therapy, diazepam, lorazepam and phenobarbitone. Fifty-five of the 81 sea lions (68 per cent) affected in 1998 and 81 of the 184 (44 per cent) affected in 2000 died despite the treatment. Three of the 23 sea lions which survived in 1998 were tracked with satellite and radiotransmitters; they travelled as far south as San Miguel Island, California, and survived for at least three months. Eleven of the 129 animals which were released stranded within four months of being released.

Doppler ultrasound screening predicts recurrence of poor pregnancy outcome in subsequent pregnancies, but not the recurrence of PIH or preeclampsia.

OBJECTIVE: To assess the role of Doppler uterine artery screening in the prediction of recurring hypertensive disorders in a high-risk population. METHODS: Ninety-four women with a history of hypertensive disorders in previous pregnancies underwent ultrasound color Doppler to analyze blood flow in the uterine arteries at 21-22 weeks of gestation. We evaluated the performance of the Pulsatility Index (PI) as well as the diastolic notch to predict recurring hypertensive disorders. Outcome measures were the recurrence of hypertensive disorders, and poor pregnancy outcome due to intrauterine death growth retardation, intrauterine death, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, eclampsia, or premature birth. Onset of symptoms was before 35 weeks in all cases of poor pregnancy outcome. RESULTS: Doppler flow recordings were obtained from a well-defined location in both uterine arteries. The predictive value of the uterine artery PI for recurring hypertensive disease was poor and not significant; interestingly, however, the predictive values for poor pregnancy outcome were good (sensitivity 83%, specificity 71%, p < 0.001). The PI also provides a good test for intrauterine growth retardation (sensitivity 80%, specificity 69%, p < 0.01). The "diastolic notch" did not perform as well as the PI. CONCLUSIONS: Uterine artery screening did significantly predict the recurrence of poor pregnancy outcome due to hypertensive complications in this high-risk group. In contrast, gestational hypertension and preeclampsia with normal pregnancy outcome were not significantly predicted by uterine artery screening.

Lymphomas and high-level expression of murine leukemia viruses in CFW mice.

Historically, Swiss Webster mice of the CFW subline, both inbred and random-bred stocks, have been considered to have a low spontaneous occurrence of hematopoietic system tumors, and previous reports of infectious expression of murine leukemia viruses (MuLVs) have been rare and unremarkable. In marked contrast, in the present study of CFW mice from one source observed by two laboratories over a 2-year period, nearly 60% developed tumors, 85% of which were lymphomas, the majority of B-cell origin. All tumors tested expressed ecotropic MuLVs, and most expressed mink cell focus-inducing (MCF) MuLVs. Among normal mice of weanling to advanced age, over one-half were positive for ecotropic virus in tail or lymphoid tissues, and MCF virus was frequently present in lymphoid tissue, less often in tail. Patterns of ecotropic proviral integration indicated that natural infection occurred by both genetic and exogenous routes. Lymphomas were induced in NIH Swiss mice infected as neonates with tissue culture-propagated MuLVs isolated from normal and tumor tissue of CFW mice.

Depression and the dying older patient.

Depression remains a source of considerable suffering among dying older adults. Unfortunately, clinical depression commonly is overlooked in this vulnerable population and often goes untreated. An overview of diagnosing depression in older patients is presented. Various risk factors for depression in the palliative care setting are examined. The somatic therapies that are available for treatment consideration in older, depressed adults nearing death are reviewed.

Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses.

Spontaneous lymphomas occur at high frequency in NFS x V+ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS x V+ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor beta chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS x V+) or absence (NFS x V-) of functional ecotropic MuLV genomes showed that NFS x V-clonal lymphomas developed at about one-half the rate of those occurring in NFS x V+ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS x V+ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis.

Expression of cyclin D1 in mouse B cell lymphomas of different histologic types and differentiation stages.

The G1 cyclin, cyclin D1, has been implicated in the development of human and mouse tumors. Here we describe immunohistochemical analyses of cyclin D1 for a large panel of mouse B cell tumors. In addition, we characterize cyclin D1 expression in a series of cultured cell lines that represent transformed B cells at different stages of development. Immunohistochemical analysis showed that for low-grade lymphomas, cyclin D1 was expressed by 83% of centroblastic centrocytic (CBCC) and 14% of small lymphocytic lymphomas (SLL). For high-grade tumors, 28% of B lymphoblastic and 23% of centroblastic tumors expressed cyclin D1, while all immunoblastic lymphomas were negative. Studies of RNA and protein prepared from cultured B lineage tumors showed that cyclin D1 was expressed by all pre-B and most B cell tumors but not by cell lines representative of late B cell differentiation or by plasma cells. Expression of cyclin D1 in the lymphomas was not associated with alterations in the genomic structure of the Fis-1 (Bcl-1) common proviral integration site or cyclin D1 itself or with cell growth activity as assessed by expression of proliferating cell nuclear antigen (PCNA).

Molecular phylogeny of Fv1.

Alleles at the Fv1 gene of inbred mice confer resistance to infection and spread of vertically or horizontally transmitted murine leukemia viruses (MuLV). The nucleotide sequence of Fv1 bears similarity to the gag of a human endogenous retrovirus, HERV-L, but is more closely related to the gag-coding sequence of a newly described class of HERV-L-related mouse endogenous retroviruses designated MuERV-L. Both observations suggest an origin of Fv1 from endogenous gag sequences. The molecular definition of Fv1 provided an opportunity to determine the phylogeny of the gene among wild mice and its relation to MuERV-L. PCR primers, chosen to include most of the coding region of Fv1 for both the n and b alleles, were used to amplify sequences from animals of the genus Mus, which were then sequenced. Closely related products were obtained from almost all animals examined that evolved after the separation from Rattus, in which the homologous gene was shown to be absent. A phylogenetic tree generated with Fv1 sequence data differs noticeably from that developed with sequence data from other genes. In addition, non-synonymous changes were found to be present twice as frequently as synonymous changes, a fact that departs from the standard behavior of a structural gene. These observations suggest that the Fv1 gene may have been subjected to possible horizontal transfers as well as to positive Darwinian selection.

Care of the terminal head and neck cancer patient in the hospice setting.

The ratio of incidence to mortality is somewhat less than 3:1 for head and neck cancer, and the 5-year relative survival rate is 50%. Despite the high mortality rate, few reports have focused on patients with terminal head and neck cancer. A growing number of these patients end their lives in a hospice facility. A retrospective analysis was undertaken of 67 patients with terminal head and neck cancer who were admitted to the Tel Hashomer Hospice between 1988 and 1992. Patient data were reviewed and analyzed, and the particular characteristics of this population were defined. This study found that terminal head and neck cancer patients seem to receive better support in a hospice than in a general hospital or some family settings.

Urine production rate is related to behavioural states in the near term human fetus.

OBJECTIVE: To investigate the relation between hourly fetal urine production rate (HFUPR) and behavioural states 1F and 2F (corresponding to quiet and active sleep, respectively) in normal near term fetuses. DESIGN: An observational study. SETTING: A clinic for antenatal care at a university hospital. SUBJECTS: Nineteen healthy pregnant women examined at 37 to 40 weeks of gestation. MAIN OUTCOME MEASURES: Fetal behavioural states (1F and 2F) were assessed by means of fetal heart rate patterns (FHR A and FHR B). Using real time ultrasonography, HFUPR (ml/h) was estimated during behavioural states 1F and 2F. RESULTS: During behavioural state 1F, HFUPR was significantly higher than during state 2F (P < 0.01). HFUPR falls by 47% from 50.8 +/- 24.4 ml/h in state 1F to 25.7 +/- 15.0 ml/h in state 2F. CONCLUSIONS: During active sleep (state 2F) hourly fetal urine production rate is considerably reduced as compared to quiet sleep (state 1F).

Behavioural states and Doppler velocimetry of the renal artery in the near term human fetus.

Transition of fetal behavioural state 1F to 2F coincides with cardiovascular changes measured by Doppler velocimetry e.g. a decrease in pulsatility index (PI) in the internal carotid arteries and in the descending aorta, indicating redistribution of blood flow. Recently, we reported a considerable reduction in fetal urine production rate of 47% during fetal behavioural state 2F as compared to 1F. It was suggested that this reduction is caused by an increase in renal vascular resistance during 2F. Using Doppler ultrasound, flow velocity waveforms (FVW) of fetal renal arteries were recorded during behavioural states 1F and 2F. Fetal behavioural states 1F and 2F were assessed by recording fetal heart rate pattern, eye movements and body movements. The PI of the renal artery FVWs were calculated as an index of renal vascular resistance to blood flow. Fifteen healthy pregnant women between 36 and 40 weeks gestational age were studied and the relationship between fetal renal vascular resistance to blood flow and behavioural states was determined. We found that PI values in the renal arteries did not change relative to behavioural state 1F and 2F. These findings suggest that renal vascular resistance to blood flow is not appreciably different in 1F and 2F. This is in contrast with urine production rate which is almost reduced by half during 2F in the near term fetus.

Death of one twin followed by extremely variable flow velocity waveforms in the surviving fetus.

Intrauterine death of one fetus after the second trimester in a twin pregnancy, with continuation of the pregnancy is a rare complication. The risks of morbidity and mortality for the surviving fetus are high. A 32-year-old woman was admitted to the antenatal ward at 27 weeks gestation because of intrauterine death of one twin. During the first 24 h after the death of one twin, Doppler ultrasound assessment showed a remarkable variability in flow velocity waveforms in the umbilical artery of the surviving fetus. Changes from reversed to normal end-diastolic flow velocities were recorded within 6 min. These findings are explained by twin-to-twin transfusion due to intravascular blood pressure changes, or by release of vasoactive substances by the dead fetus.