Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus).

We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms.

Primary Cystic Lymphangioma of the Spleen in an Adult Dog.

Proliferative disorders of lymphatic origin in animals are mostly congenital or occur within the first few months of life. Involvement of internal organs is extremely infrequent. A seven-year-old entire female mixed-breed dog was presented with apathy and poor appetite. Abdominal ultrasonography revealed a focally enlarged spleen with an anechoic round lesion. Splenectomy was performed and pathological examination demonstrated a sponge-like, compressible tumour composed of endothelium-lined vascular cystic spaces filled with eosinophilic proteinaceous material lacking erythrocytes. Immunohistochemical stains showed that cyst-lining cells were strongly positive for CD31 and factor VIII and focally positive for lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Based on these findings, the lesion was identified as splenic cystic lymphangioma. To the best of our knowledge, this is the first description of solitary lymphangioma of the spleen in animals.

Primary Verocay Body-rich Epididymal Leiomyosarcoma in a Dog.

Leiomyosarcomas arising from paratesticular structures are rare. We report a case of epididymal sarcoma in an aged male Rottweiler that had histological features suggestive of neural origin but with muscular histogenesis confirmed by immunohistochemistry. Histologically, the lesion comprised a hypercellular neoplasm that had interlacing bundles of spindloid cells, prominent nuclear palisading and many Verocay bodies. Immunohistochemically, the neoplastic cells were strongly positive for smooth muscle markers but negative for neural markers, leading to the diagnosis of leiomyosarcoma. While the presence of nuclear palisading and Verocay bodies has been regarded as strong evidence for the diagnosis of schwannomas, the present report documents the presence of true Verocay bodies in a non-neuronal tumour. It also indicates that immunophenotyping is required for an accurate diagnosis when Verocay bodies are detected in sarcomatous or spindle cell tumours and provides prognostic information on this case. To the best of our knowledge, this is the first report of the presence of true Verocay bodies in a neoplasm other than a nerve sheath tumour in animals.

Acquired equine polyneuropathy of Nordic horses: A conspicuous inclusion body schwannopathy.

Acquired equine polyneuropathy (AEP), formerly also known as Scandinavian knuckling syndrome, is one of the most prevalent polyneuropathies in equids in Norway and Sweden, with more than 400 cases registered since first observations in 1995. Despite geographical clustering and an association to forage feeding, its aetiology remains unknown. Clinically AEP is characterized by knuckling due to dysfunction of metatarsophalangeal extensor muscles. This neuropathological study aimed to gain further insights in the pathobiology of AEP and its underlying aetiopathogenesis. We thereby confirmed that all affected horses suffered from similar large fibre neuropathy, exhibiting conspicuous Schwann cell inclusions in most samples, suggestive of a primary disruption of Schwann cell metabolism leading to inclusion body schwannopathy with secondary inflammatory changes. The degree of nerve pathology was not predictive of clinical outcome.

Effect of local thermal fluctuations on folding kinetics: a study from the perspective of nonextensive statistical mechanics.

The search through the proteins conformational space is thought as an early independent stage of the folding process, governed mainly by the hydrophobic effect. Because of the nanoscopic size of proteins, we assume that the effects of local thermal fluctuations work like folding assistants, managed by the nonextensive parameter q. Using a 27-mer heteropolymer on a cubic lattice, we obtained--by Monte Carlo simulations--kinetic and thermodynamic amounts (such as the characteristic folding time and the native stability) as a function of temperature T and q for a few distinct native targets. We found that for each native structure, at a specific system temperature T, there exists an optimum q* that minimizes the folding characteristic time τ(min); for T=1, it is found that q* lies in the interval 1.15±0.05, even for native structures presenting significantly different topological complexities. The distribution of τ(min) obtained for specific q>1 (nonextensive approach) and temperature T can be fully reproduced for q=1 (Boltzmann approach), but only at higher temperatures T'>T. However, assuming that the complete set of proteins of each organism is optimized to work in a narrow range of temperature, we conclude that--for the present problem--the two approaches, namely, (T,q>1) and (T>T',q=1), cannot be equivalent; it is not a simple matter of reparametrization. Finally, by associating the nonextensive parameter q with the instantaneous degree of compactness of the globule, q becomes a dynamic variable, self-adjusted along the simulation. The results obtained through the q-variable approach are utterly consistent with those obtained by using a target-tuned parameter q*. However, in the former approach, q is automatically adjusted by the chain conformational evolution, eliminating the need to seek for a specific optimized value of q for each case. Besides, using the q-variable approach, different target structures are promptly characterized by inherent distributions of q, which reflect the overall complexity of their corresponding native topologies and energy landscapes.

Towards open collaborative health informatics - The Role of free/libre open source principles. Contribution of the IMIA Open Source Health Informatics Working Group.

OBJECTIVES: : To analyze the contribution of Free/Libre Open Source Software in health care (FLOSS-HC) and to give perspectives for future developments. METHODS: The paper summarizes FLOSS-related trends in health care as anticipated by members of the IMIA Open Source Working Group. Data were obtained through literature review and personal experience and observations of the authors in the last two decades. A status quo is given by a frequency analysis of the database of Medfloss.org, one of the world's largest platforms dedicated to FLOSS-HC. The authors discuss current problems in the field of health care and finally give a prospective roadmap, a projection of the potential influences of FLOSS in health care. RESULTS: FLOSS-HC already exists for more than 2 decades. Several projects have shown that FLOSS may produce highly competitive alternatives to proprietary solutions that are at least equivalent in usability and have a better total cost of ownership ratio. The Medfloss.org database currently lists 221 projects of diverse application types. CONCLUSIONS: FLOSS principles hold a great potential for addressing several of the most critical problems in health care IT. The authors argue that an ecosystem perspective is relevant and that FLOSS principles are best suited to create health IT systems that are able to evolve over time as medical knowledge, technologies, insights, workflows etc. continuously change. All these factors that inherently influence the development of health IT systems are changing at an ever growing pace. Traditional models of software engineering are not able to follow these changes and provide up-to-date systems for an acceptable cost/value ratio. To allow FLOSS to positively influence Health IT in the future a "FLOSS-friendly" environment has to be provided. Policy makers should resolve uncertainties in the legal framework that disfavor FLOSS. Certification procedures should be specified in a way that they do not raise additional barriers for FLOSS.

Meningeal carcinomatosis in a dog: magnetic resonance imaging features and pathological correlation.

A six-year-old cross breed dog was presented with a four-month history of seizure activity, which was unresponsive to anticonvulsive therapy and an acute deterioration in neurological status, evident as central blindness. Cyst-like structures and nodular enhancement within the subarachnoid space were shown on a magnetic resonance image (MRI) scan. Histopathological examination of brain tissue was consistent with meningeal carcinomatosis.

A non-Gaussian model in polymeric network.

We investigate a finite chain approximation, the non-Gaussian Tsallis distribution, to the polymeric network, which gives an improvement to the Gaussian model. This distribution presents some necessary characteristics, like a cutoff to the maximum chain length and a continuous limit to the Gaussian one for a large number of monomers. It also presents a simple quadratic structure that allows to generalize the Gaussian properties such as exact-moments calculation and Wick theorem. We obtain the free-energy density in its full tensorial structure.

Does antenatal identification of small-for-gestational age fetuses significantly improve their outcome?

OBJECTIVES: Most obstetric clinics have a program for the identification of small-for-gestational age (SGA) fetuses because of the increased risk of fetal complications that they present. We have a structured model for the identification and follow-up of SGA pregnancies. We aimed to determine whether the recognition of SGA antepartum improves fetal outcome. METHODS: All pregnancies at Malmö University Hospital from 1990 to 1998 (n = 26 968) were reviewed. SGA fetuses identified prior to delivery (n = 681) were compared with those not identified (n = 573). Also, all pregnancies with SGA fetuses were compared with those appropriate-for-gestational age (AGA) (n = 24 585). The risk of serious fetal complications (hypoxic encephalopathy grade 2 or 3, intracranial hemorrhage, Apgar score <4 at 5 min, neonatal convulsions, umbilical pH <7.0, cerebral palsy, mental retardation, stillbirth, intrapartum or infant death) was assessed with cross-tabulation and logistic regression analysis, adjusted for gestational age and degree of SGA. RESULTS: When compared with SGA fetuses identified before delivery (54%), SGA fetuses not identified before delivery were characterized by a four-fold increased risk of adverse fetal outcome (odds ratio, 4.1; 95% CI, 2.5-6.8). Similarly, compared with AGA fetuses, SGA fetuses were associated with a four-fold increased risk of serious fetal complications. CONCLUSIONS: A structured antenatal surveillance program for fetuses identified as SGA results in a lower risk of adverse fetal outcome, compared with cases of SGA fetuses not identified antepartum.

Uterine artery score and perinatal outcome.

OBJECTIVE: To evaluate a modified uterine artery score based on the pulsatility index and presence or absence of notching in the Doppler velocity waveform recorded from both uterine arteries in relation to the perinatal outcome. METHODS: A retrospective analysis was performed in 741 third-trimester high-risk pregnancies. The uterine artery score was constructed assigning one point to each abnormal parameter-high pulsatility index and presence of notch-thus ranging from 0 (normal findings in both uterine arteries) to 4 (notch and high pulsatility index in both uterine arteries). In a subgroup with lateral placenta (n = 359), two definitions of abnormal pulsatility index were compared. In the uniform uterine artery score, a pulsatility index > 1.20 in both uterine arteries was considered abnormal, disregarding the placental location; in the subgroup with lateral placenta, the high pulsatility index was defined as > 1.00 on the placental side and > 1.40 on the non-placental side. RESULTS: Receiver-operating characteristic curves did not reveal any difference in the diagnostic capacity between the group with a uniform uterine artery score and the subgroup with lateral placenta (P = 0.54). In the total material, the odds ratios and linear regression analysis showed an increased risk for an adverse perinatal outcome with increasing uterine artery score (P < 0.01). At a uterine artery score > 2, there was a significantly increased risk for operative delivery for fetal distress, neonatal intensive care unit admission, 5-min Apgar score < 7, preterm delivery and delivery of a small-for-gestational age fetus. CONCLUSION: In high-risk third-trimester pregnancies, Doppler velocity waveforms of the uterine arteries can be evaluated using the uterine artery score disregarding the placental location. The uterine artery score possesses a high predictive value regarding adverse perinatal outcome.

Socioeconomic status and perinatal outcome according to residence area in the city of Malmö.

BACKGROUND: Maternal socioeconomic status is known to influence perinatal outcome. Antenatal care is free of charge in Sweden and all pregnant women are followed according to a standardized protocol of surveillance. The city of Malmö in southern Sweden is divided into 124 townships with great differences in socioeconomic standard. The aim of this study was to evaluate perinatal outcome according to the address of residence of the mothers within the city of Malmö. METHODS: Perinatal outcome of 7056 pregnancies was related to three socioeconomic characteristics of the 124 townships in Malmö: percentage of immigrants, percentage of inhabitants on social welfare and the median income. RESULTS: Maternal age was lower, number of abortions and parity were higher in low income areas. Perinatal complications were also more frequent, including low birthweight, small-for-gestational age newborns, maternal anemia, infections, and low 1- and 5-minute Apgar scores. Premature rupture of membranes was associated with low income areas. Symphysiolysis and pre-eclampsia were more frequent in the high income areas. CONCLUSION: Although maternity care is provided free of charge, perinatal complications were more frequent in areas of lower socioeconomic status. In order to improve perinatal outcome, antenatal surveillance should be intensified in low class socioeconomic areas.

A regional perinatal database in southern Sweden--a basis for quality assurance in obstetrics and neonatology.

BACKGROUND: In order to ensure as few avoidable adverse outcomes of pregnancy as possible, it is necessary to continuously evaluate the quality of both obstetric and neonatal care. The eleven southernmost hospitals in Sweden have joined together in a project of developing a regional database, with special emphasis on rapid output of information in order to identify changing trends. METHODS: A regional computerized database has been developed, collecting variables and quality indicators agreed upon by all participants. Specific protocols have been designed for obstetric care, neonatal care and autopsy findings. All participating units transfer information on paper forms or via local computerized information systems. The regional database thus receives data on about 20,000 deliveries annually. RESULTS: Data collection started on September 1, 1994. The first results are due in March 1996, and thereafter on a regular basis every 3 months. Special methods for rapid analysis of raw data have been developed with the help of commercially available data analysis tools. CONCLUSIONS: It is possible to construct an information system with different computer platforms and different database tools at each participating facility, as long as the database systems are locally controllable. That a software is commercially available is no guarantee that data transfer to a central database is possible. Experience from participating sites also indicates that a specialized database is needed for registering obstetric data, as general computerized record-keeping systems are unable to cope with an event concerning more than one subject at a time.

The influence of climate on development of winter depression.

126 patients suffering from winter depression participated in the study. Every second week patients completed the 13 item Beck Depression Inventory (BDI) in the period September to May in the years 1991 to 1994. Local weather data from this period were obtained from the Meteorological Institute, Copenhagen. No significant correlation was found between score on BDI and cloud cover, rainfall or atmospheric pressure. A significant correlation was found between score on BDI and minutes of sunshine, global radiation, length of daylight and temperature. This is in accordance with the theory, that lack of light is a contributing factor for development of winter depression.

No additional metal particle formation using the needle-through-needle combined epidural/spinal technique.

BACKGROUND: Combined epidural/spinal analgesia utilizing a needle-through-needle technique has become very popular in anesthesia. However, findings of concave deformities at the orifice of Tuohy needles after spinal needle passage have raised concerns that metal fragments might be deposited within the epidural space. This study was proposed to investigate whether the needle-through-needle technique does produce metallic flecks. METHODS: Ten unused Tuohy and Hustead epidural needles were inspected microscopically and photomicrographed prior to flushing saline through each into a single tissue culture well. After drying, a single pass was made with a 120 mm 24-gauge Sprotte needle through each epidural needle to maximal extension while the orifice was within another tissue culture well. Each needle was again flushed into a third well before reexamination and photomicroscopy. Each of the wells was inspected for metallic particles by microscopy. Additional freshly unpackaged Tuohy needles were microscopically examined after exposure to a magnetic field. RESULTS: Comparison of micrographs before and after needle experiments revealed concave deformities at the orifice of all the Tuohy and Hustead needles. No particles were observed in either of the two saline-flushed wells or within the well in which the needle-through-needle passes were made. Inspection of unused Tuohy needles exposed to a magnetic field revealed metal filings "standing up" along the bevel of every needle examined. CONCLUSIONS: Metallic particles are not produced by the needle-through-needle technique. However, metal particles are an apparent contaminant of all epidural needles and are probably routinely introduced into patients when the needle is placed.

A randomised trial of compassionate care for the homeless in an emergency department.

Homeless adults often visit emergency departments and often leave dissatisfied. We tested whether compassionate care, by improving patient satisfaction, can alter subsequent use of emergency services. We identified 133 consecutive homeless adults visiting one inner-city emergency department who were not acutely psychotic, extremely intoxicated, unable to speak English, or medically unstable. Half were randomly assigned to receive compassionate contact from trained volunteers. All patients otherwise had usual care and were followed for repeat visits to emergency departments. We found that rates of use were high, with patients making an average of seven visits a year (0.60 per month). More than a third of all patients made two or more visits within two days of each other. The average number of visits per month after intervention was significantly lower for patients who received compassionate care (0.43 vs 0.65, p = 0.018). Analyses adjusting for each patient's previous rate of use confirmed that compassionate care led to a one third reduction in the number of return visits within one month (95% CI 14 to 40%). Compassionate management of selected homeless adults decreases repeat visits to the emergency department. One explanation is that patients tend to return frequently until they are satisfied with their treatment.

Study of the interaction of dextran and enoxaparin on haemostasis in humans.

The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 ml i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-h period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 h and AUC0-24 h in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. Our findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.