Catastrophic Antiphospholipid Syndrome after Orthotopic Liver Transplant.

Background: Catastrophic antiphospholipid syndrome (CAPS) is an autoimmune thrombogenic disorder of small and large vessels caused by autoantibodies against phospholipids and phospholipid-binding proteins. This severe form of antiphospholipid syndrome (APS) presents clinically with simultaneous life-threatening multiorgan thrombosis and the presence of two or more persistent antiphospholipid antibodies (APL) confirmed on testing 12 weeks apart. Case Presentation. We describe a case report of a 66-year-old woman with detected antinuclear antibodies (ANA) pretransplant diagnosed with CAPS following orthotopic liver transplant. The patient had acute respiratory failure; Doppler ultrasound and CT angiogram confirmed thrombosis in the hepatic artery, subsequent occlusion of the jump graft, and a splenic infarct. Hypercoagulability workup showed elevated levels of anticardiolipin IgG and beta-2-glycoprotein IgG/IgM and positive lupus anticoagulant, treated with steroids and anticoagulation. The patient was discharged after one month and was transitioned from heparin to life-long warfarin. Conclusion: Our patient provided a standard presentation of CAPS with abnormal pretransplant levels of antinuclear antibodies (ANA). Although there have been studies investigating the relationship between anticardiolipin antibodies and lupus anticoagulants and APS, the relationship between pretransplant positive ANA or antimitochondrial antibodies (AMA) and CAPS has yet to be explored. Further studies will be needed to determine the significance of these antibodies. We recommend preoperative APL testing for patients with positive ANA and AMA at preliver transplant presentation.

Seasonal and social influences on fecal androgen and glucocorticoid excretion in wild male long-tailed macaques (Macaca fascicularis).

Whereas it is well known that in strictly seasonal breeding primates (income breeders), alike other vertebrates, males show pronounced changes in testicular and adrenal hormone levels concurrent with reproductive activity, hormonal patterns in males of non-strictly seasonal breeding primate species (capital breeders) and their relation to seasonal and social correlates remain largely unknown. In the present study, we examined the annual pattern of fecal androgen and glucocorticoid excretion and their relationship to environmental (rainfall, temperature) and social factors (number of cycling females, male aggression and copulation rates, male dominance rank) in a group of wild long-tailed macaques (Macaca fascicularis), a species with a moderate degree of reproductive seasonality and classified as capital breeder. The study was carried out in the Gunung Leuser National Park, North Sumatra, Indonesia over a period of ten months encompassing the conception and the birth season. Our results show that male long-tailed macaques exhibit a distinct annual variation in both androgen and glucocorticoid levels. Androgen (but not glucocorticoid) levels were significantly elevated during the conception period in association with elevated rates of male-male aggression and copulatory activity, both strongly related to the number of cycling females in the group. Neither glucocorticoid nor androgen levels were related to male dominance rank or to the environmental parameters investigated. Interestingly, levels of both hormones started to increase in the late birth season and thus 1-2 months prior to the mating season, suggesting that male long-tailed macaques go through pre-breeding hormonal changes in preparation for prospective challenges. Our data thus provide the first evidence that males of a non-strictly seasonal breeding species/capital breeder show endocrine patterns generally similar to those found in strictly seasonal/income breeders.

Virological monitoring of white storks (Ciconia ciconia) for avian influenza.

Between 2003 and 2008, more than 600 white stork (Ciconia ciconia) nestlings in the German federal state of Brandenburg were ringed and examined for influenza A viruses. With the spread of highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 among wild birds in Germany in spring 2006, dead wild birds, including 88 white storks, were tested for infection with HPAIV. Furthermore, fresh fecal samples were examined by RT-PCR to monitor the occurrence of HPAIV in adult storks. While the monitoring of nestlings and adult white storks failed to yield evidence of influenza A virus infections in these birds, two storks found dead in April 2006 in the same location tested positive for HPAIV H5N1. Sequence analysis revealed that the virus isolated from one of the storks belonged to clade 2.2, which was commonly found in wild birds in the north of Germany and other European countries during the epidemic in 2006. Despite these two cases, white storks seemed to serve as neither a vector nor as a reservoir for HPAIV in Germany. The risk of white storks transmitting HPAIV to domestic poultry and humans is low.

Evaluation of a new meropenem-EDTA double-ended Etest strip for the detection of the cfiA metallo-beta-lactamase gene in clinical isolates of Bacteroides fragilis.

Thirty-five Bacteroides fragilis clinical isolates with varying susceptibility to meropenem were analysed with a prototype of a double-ended Etest strip containing meropenem +/- EDTA, designed for the detection of the CfiA metallo-beta-lactamase. Phenotypic results obtained with this new Etest strip were related to the genotype and compared to the results of the Etest containing imipenem +/- EDTA. Whereas the Etest with imipenem +/- EDTA only allowed detection of isolates with high-level resistance (both MICs of imipenem and meropenem >32 mg/L), reflecting the possible underestimation of CfiA prevalence in B. fragilis, the Etest with meropenem +/- EDTA proved to be more accurate, particularly for isolates with low-level carbapenem resistance, suggesting its potential for broader detection of CfiA production.

Evaluation of canine heat-shock transcription factor 4 as a candidate for primary cataracts in English Cocker Spaniels and wire-haired Kromfohrlanders.

Canine heat-shock transcription factor 4 (HSF4) was evaluated as a candidate for primary cataracts in English Cocker Spaniels (ECS) and wire-haired Kromfohrlanders (KFL). We sequenced exon 9 and its flanking regions of the HSF4 gene in ECS and KFL but were not able to detect a previously reported insertion mutation associated with primary cataracts in Staffordshire Bull Terriers and Boston Terriers. Another single nucleotide polymorphism (LOC489766:g.3243A>G) in intron 9 was identified and included in linkage and association tests together with two flanking microsatellites. Linkage and association tests with primary cataracts in ECS and KFL were not significant. Therefore, we could not verify that the mutation in exon 9 of canine HSF4 gene is causative for primary cataracts in ECS and wire-haired KFL.

Generalized fatal Cowpox virus infection in a cat with transmission to a human contact case.

A 4-month-old female domestic shorthair cat was infected by a virus of the Poxvirus family. The animal developed a severe pneumonia and generalized ulcerating lesions of the skin. Histologically, typical eosinophilic intracytoplasmic inclusion bodies indicative of an Orthopoxvirus (OPV) infection were present. The lung showed grey-white to haemorrhagic nodular lesions with a central zone of complete necrosis of alveolar and bronchial tissue. Electron microscopy from skin and lung nodules revealed typical square-shaped OPV particles. Cultivation of the virus on chorio-allantoic membranes of embryonated chicken eggs resulted in haemorrhagic plaques. Restriction enzyme analysis, PCR and sequencing of the D8L gene identified the OPV isolate as a typical Cowpox virus. It was transmitted by the cat to a human contact person who developed a local nodular dermatitis at the inoculation site in association with signs of general infection and had an increase of OPV-specific neutralizing antibodies in paired serum samples.

A virological survey in migrating waders and other waterfowl in one of the most important resting sites of Germany.

Wild birds are considered a potential reservoir or a carrier of viral diseases and may therefore play a role in the epidemiology of economically important or zoonotic diseases. In 2001 and 2002, a survey with special emphasis on virus isolation in migrating waders and some other birds were conducted. In one of the most important inland resting sites for migratory waterfowl, tracheal and cloacal swabs were collected from 465 waders representing 19 different species, and 165 other birds that were not captured on purpose. A total of 42 avian viruses were isolated, 34 of these were identified as paramyxoviruses (PMVs). The majority of isolates came from waders and wild ducks, and were characterized as PMV-1. In contrast, PMV-4 was found in wild ducks only, PMV-6 was mainly detected in wader species. Four avian influenza viruses (AIVs), belonging to H4 and H3 haemagglutinin subtype, were isolated from wild duck species. Furthermore, four reo-like viruses were isolated from one particular wader species for the first time. The majority of virus positive birds were <1 year old and did not show any clinical symptoms. There was no evidence for the presence of West Nile virus in these birds. These results confirm that the restricted resting sites in Western Europe must be considered as important locations for the intra- and interspecies transmission of avian viruses.

[Case report: Porcine circovirus type 2 infection in an European wild boar (Sus scrofa) in the state of Brandenburg, Germany]. / Porzine Circovirus Typ 2-Infektion bei einem Wildschwein (Sus scrofa) im Land Brandenburg.

This case represents the first case of Porcine Circovirus Type 2 (PCV-2)--infection in a free living European wild boar associated with morphological lesions, which are regarded as characteristic for Postweaning Multisystemic Wasting Syndrome (PMWS) in domestic pigs. The animal, an approximately 10 month old male, was found dead in a rural area within the state of Brandenburg, Germany. The closest commercial pig farm is located in 3 km distance from the spot where the carcass was found. At necropsy, the animal was found to be in a runted condition. Morphological investigation revealed two lesion complexes. Firstly, lymphatic depletion was present in different organs. Mainly the white pulp of the spleen was affected, where lymph follicles and periarteriolar lymphatic sheaths were nearly completely depleted of lymphoid cells. The former lymphatic areas could only be identified by the presence of histiocytic cells. Secondly, there were widely distributed lesions indicative of a bacterial septicemia i.e. purulent-necrotizing lymphadenitis, pulpous hyperplasia of the spleen, miliary lytic liver necroses and foci of fibrinous pneumonia. Within the lesions, bacterial colonies were found (short Gram-negative rods). Bacteriology revealed a septicemic Salmonella choleraesuis var. Kunzendorf--infection. Virologically, the animal was tested with negative results for Classical Swine Fever Virus and PRRSV. The unusual depletion of the lymphatic tissue mainly in the spleen led to the suspicion of a PCV-2 infection. Typical circoviral particles were found by negative-contrast electron microscopy in samples from spleen and lymph nodes. Using a commercial antiserum against Porcine Circovirus, positive staining was found by fluorescence microscopy in tonsils, spleen and lymph nodes. Finally, the virus was identified to be PCV-2 by species-specific PCR. The presented case rises the questions if PCV-2 is endemic in the European wild boar population at least in certain areas, if it is of pathogenetic importance for wild boars and if the virus present in wild boars is identical to that present in domestic pigs with PMWS.

Proton dynamics in letovicite, (NH4)3H(SO4)2: a 1H and 14N NMR spectroscopic study.

The improper ferroelastic phase letovicite (NH4)3H(SO4)2 has been studied by 1H MAS NMR as well as by static 14N NMR experiments in the temperature range of 296-425 K. The 1H MAS NMR resonance from ammonium protons can be well distinguished from that of acidic protons. A third resonance appears just below the phase transition temperature which is due to the acidic protons in the paraelastic phase. The lowering of the second moment M2 for the ammonium protons takes place in the same temperature range as the formation of domain boundaries, while the signals of the acidic protons suffer a line narrowing in the area of Tc. The static 14N NMR spectra confirm the temperature of the motional changes of the ammonium tetrahedra. Two-dimensional 1H NOESY spectra indicate a chemical exchange between ammonium protons and the acidic protons of the paraphase.

Neuropeptide content of peripheral nerve in relation to nerve function in neuropathy.

OBJECTIVE: In this study an APAAP (alcalic-phophatase-anti-alcalic-phosphatase) technique was used to distinguish afferent (calcitonin-gene-related-peptide (CGRP) or substance-P-(SP) positive) and autonomic (tyrosin-hydroxylase (TH), neuropeptide Y (NPY) or vasoactive-intestinal-polypeptide- (VIP) positive) nerve fibers in sural nerve biopsy material from patients with moderate sensory neuropathy. A panneuronal marker against protein-gene-product 9.5 (PGP 9.5) was used for detection of the total amount of nerve fibers. Second aim was to analyze possible correlations between the impairment in tests for the function of unmyelinated fibers (i.e. thermal threshold testings, sensitivity to painful mechanical stimulation, axon reflex-mediated flare reaction and sudomotor activity) and nerve pathology. RESULTS: A high correlation between CGRP and SP (p < 0.00003) and between TH and NPY, respectively, (p < 0.004) was found, but not between afferent and autonomic markers or between specific markers and PGP 9.5. While no correlations between sensory neuropeptides (CGRP and SP) and specific testings of afferent fiber function or between neuropeptide content and clinical data could be demonstrated, there was a significant correlation between the TH content of the sural nerve and the sweat output, stimulated by acetylcholine iontophoresis at the level of the foot (p = 0.019) and upper leg (p = 0.011). CONCLUSION: This study demonstrates the possibility of visualizing subgroups of unmyelinated nerve fibers in sural nerve biopsies selectively with this technique. The density of TH-positive sympathetic nerve fibers, but not the density of afferent c-fibers, is correlated with corresponding results in specific tests of c-fiber function.

[Observer variability in the radiologic interpretation of interstitial lung disease]. / Variabilidad de observadores en la interpretación radiológica de la afección pulmonar intersticial.

OBJECTIVES: To study intra and interobserver variability of two pediatric neumologists in X-ray readings of interstitial lung disease (ILD), to determine the effect of clinical data on the readings, and to evaluate their interpretation in terms of the histopathology diagnosis. DESIGN: Prospective, cross sectional, comparative, blinded. SETTING: The Instituto Nacional de Pediatria of Mexico City. MATERIAL AND METHODS: Chest X-rays of 45 ILD pediatric patients with diagnosis confirmed by open lung biopsy were read by the two observers three times at two weeks intervals and in a randomized fashion. The observers were blinded to previous readings of both observers as well as to the diagnosis. The first two readings were done with no clinical information given to the observers, but some was given for the third reading (age of inception, length of evolution, and main symptoms at time of the X-rays). A classification in one of 5 patterns (lineal, reticular, reticulonodular, grounded glass, honeycomb) was established by the observers. Associations of patterns with anatomopathological diagnosis was explored. Weighted kappa was used in the statistical analysis. RESULTS: With one exception, good agreement (Kw 0.57-0.88) was found intra and interobservers. CONCLUSION: We believe the low variability is the result of the 15 years of shared experience of the two observers participating in this study.

[Hepatitis C-associated vasculitic mononeuritis multiplex]. / Hepatitis-C-assoziierte vaskulitische Mononeuritis multiplex.

HISTORY AND CLINICAL FINDINGS: A 56-year-old woman with hepatitis C had symptoms of a polyneuropathy with asymmetrical distal pareses and painful sensory disturbances in the limbs. INVESTIGATION: In addition to positive serology for hepatitis C cryoglobulins were demonstrated and complement C4 was reduced. Biopsy of the sural nerve showed a vasculitic neuropathy. TREATMENT AND COURSE: The multiple neuropathy (cryoglobulinaemia neuropathy), associated with hepatitis C, was treated with corticosteroids (starting with 60 mg/d prednisolone) and the neurological abnormalities regressed well. CONCLUSION: Vasculitis associated with hepatitis C should be included in the differential diagnosis of peripheral neuropathy.

[Urine test strips for cerebrospinal fluid diagnosis of bacterial meningitis]. / Urinteststreifen zur Liquordiagnostik der bakteriellen Meningitis.

BACKGROUND: Diagnosis of bacterial meningitis is due to granulocytic pleocytosis of CSF. In developing countries and in hospitals without continuous availability of a clinical laboratory a bedside-method of diagnosing meningitis is desired. METHODS: 75 CSF samples were tested for granulocytes and protein with reagent strips and the results were compared with those obtained from the clinical laboratory. RESULTS: All 48 samples with normal cell count were correctly diagnosed negative using reagent strips. Twenty-five samples of 27 samples with granulocytic pleocytosis were correctly recognised as right positive (sensitivity 92.6%; specificity 100%). All 48 samples with normal protein were correctly tested normal. Twenty-one samples of 27 samples with elevated protein were correctly diagnosed right positive (sensitivity 77.8%; specificity 100%). CONCLUSION: Testing CSF for granulocytes and protein with urine reagent strips is a bedside-method which allows a rapid and reliable decision whether CSF is normal or granulocytically pleocytotic.

[Myositis--a rare complication of Crohn disease]. / Myositis--eine seltene Komplikation des M. Crohn.

Crohn's disease is a chronic relapsing inflammatory disorder primarily affecting the gastrointestinal system. Extraintestinal manifestations such as erythema nodosum, iridocyclitis, arthritis and sclerosing cholangitis are frequent. We report on a 57-year old male patient with the symptoms of Crohn's disease. Clinically he showed signs of a muscle disorder and muscle biopsy demonstrated a perimysial inflammation with lymphocytes and histiocytes. Complete remission was achieved by immunosuppressive treatment. Six cases presented in the literature are reviewed and the autoimmunological aspects of the pathogenesis discussed.

[Follow-up studies and disorders of endocrinologic function in MELAS syndrome]. / Verlaufsbeobachtungen und endokrinologische Funktionsstörungen beim MELAS-Syndrom.

The clinical course of MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is described in five cases. The age of onset was 9.2 years on average. Cerebral symptoms occurred at an age of 24.6 years on average. The diagnosis was only made later. Three patients died during the follow-up period. The mean age at death was 33.3 years, the average duration of the disease, 19.6 years. All patients suffered from progressive hearing loss, multiple strokes, and complex-partial and generalized seizures. They all had short stature, normal early development and 'ragged red fibers' in the muscle biopsy. Imaging studies (CT and MRI) showed bilateral calcification of basal ganglia and multiple strokes. One patient, admitted with epileptic status as initial symptom, showed lymphocytic pleocytosis in the cerebrospinal fluid; thus, in her case the differential diagnosis included encephalitis. Four patients were studied by dynamic endocrinological testing. Endocrinological disturbances were detected in three patients. Two of them suffered from hypothalamic-pituitary failure and one patient exhibited hyperprolactinemia. Endocrinological disturbances were considered an expression of the underlying cytopathy. Cerebral symptoms occurred rather late in the course of the disease and indicated poor prognosis.

99m-Tc-HMPAO-SPECT in diagnosis of early cerebral vasculitis.

The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's syndrome. Of these, 18 patients showed overt neuropsychiatric symptoms, so-called major symptoms (e.g. motoric or sensible defects); 6 had mild symptoms like headache or cognitive disorders, so-called minor symptoms: 16 patients did not present with any of these symptoms. SPECT abnormalities were detected in 16 of the 18 patients with overt neuropsychiatric symptoms (89%). Five of the 6 patients with minor symptoms (83%) and 5 of the 16 patients without neurological symptoms (31%) also had SPECT abnormalities. There was no relation to disease activity or duration. We concluded that the high sensitivity of SPECT (87.5%) in detecting perfusion abnormalities among the evaluated group of patients indicates its suitability for early diagnosis of vasculitic CNS involvement.