Unknown Origin (unknown + origin)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Fatal Graft-Versus-Host Disease Presenting as Fever of Unknown Origin in a Pancreas-After-Kidney Transplant Recipient

F. L. Weng
Acute graft-versus-host disease (GVHD) is a rare complication of pancreas transplantation. We describe a 54-year-old male with type 1 diabetes who received a zero-antigen mismatched pancreas-after-kidney transplant from a pancreas donor who was homozygous at the HLA-B, -Cw, -DR, and -DQ alleles. Starting on postoperative day (POD) #22, the patient developed persistent fevers. Workup was notable only for low-grade cytomegalovirus viremia, which was treated. The fevers eventually disappeared. On POD #106, the patient was noted to have a diffuse erythematous rash. A skin biopsy was consistent with GVHD. Short tandem repeat DNA analysis of both peripheral blood lymphocytes and skin demonstrated mixed chimerism, confirming the diagnosis of GHVD. Soon after diagnosis, the patient developed pancytopenia and fevers and died of multiorgan failure on POD #145. Transplant clinicians should consider GVHD as a possible, although admittedly rare, cause of fevers of unknown origin in recipients of pancreas transplants. [source]

Correlation of Noninvasive Electrocardiography with Invasive Electrophysiology in Syncope of Unknown Origin: Implications from a Large Syncope Database

Konstantinos A. Gatzoulis
Background: The evaluation of syncope can be expensive, unfocussed, and unrevealing yet, failure to diagnose an arrhythmic cause of syncope is a major problem. We investigate the utility of noninvasive electrocardiographic evaluation (12-lead ECG and 24-hour ambulatory electrocardiographic recordings) to predict electrophysiology study results in patients with undiagnosed syncope. Methods: We evaluated 421 patients with undiagnosed syncope who had an electrocardiogram (ECG), an electrophysiology study, and 24-hour ambulatory monitoring. Noninvasive testing was used to predict electrophysiology testing outcomes. Multivariable logistic regression analysis adjusting for age, sex, presence of heart disease, and left ventricular ejection fraction (LVEF) was used to assess independent predictors for sinus node disease, atrioventricular node disease, and induction of ventricular tachyarrhythmias. Results: Patients were divided into four groups: group 1, abnormal ECG and ambulatory monitor; group 2, abnormal ECG only; group 3, abnormal ambulatory monitor; and group 4, normal ECG and ambulatory monitor. The likelihood of finding at least one abnormality during electrophysiologic testing among the four groups was highest in group 1 (82.2%) and lower in groups 2 and 3 (68.1% and 33.7%, respectively). In group 4, any electrophysiology study abnormality was low (9.1%). Odds ratios (OR) were 35.9 (P < 0.001), 17.8 (P < 0.001), and 3.5 (P = 0.064) for abnormal findings on electrophysiology study, respectively (first three groups vs the fourth one). ECG and ambulatory monitor results predicted results of electrophysiology testing. Conclusion: Abnormal ECG findings on noninvasive testing are well correlated with potential brady- or/and tachyarrhythmic causes of syncope, in electrophysiology study of patients with undiagnosed syncope. [source]

Risk Factors for Speech Delay of Unknown Origin in 3-Year-Old Children

Thomas F. Campbell
One hundred 3-year-olds with speech delay of unknown origin and 539 same-age peers were compared with respect to 6 variables linked to speech disorders: male sex, family history of developmental communication disorder, low maternal education, low socioeconomic status (indexed by Medicaid health insurance), African American race, and prolonged otitis media. Abnormal hearing was also examined in a subset of 279 children who had at least 2 hearing evaluations between 6 and 18 months of age. Significant odds ratios were found only for low maternal education, male sex, and positive family history; a child with all 3 factors was 7.71 times as likely to have a speech delay as a child without any of these factors. [source]

Reticulated platelet counts correlate with treatment response in patients with idiopathic thrombocytopenic purpura and help identify the complex causes of thrombocytopenia in patients after allogeneic hematopoietic stem cell transplantation

CYTOMETRY, Issue 4 2007
Anna-Katharina Thomas-Kaskel
Abstract Background: In thrombocytopenic conditions of unknown origin, quantification of reticulated platelets (RP) in the peripheral blood by flow cytometry has been shown to differentiate increased platelet (Plt) turnover from insufficient Plt production. Methods: We used a whole blood flow cytometry method combining thiazole orange and anti-CD41a-staining to assess RP in 71 healthy subjects, six with thrombocytopenic myelodysplastic syndrome (MDS), nine with liver cirrhosis, 14 patients with idiopathic thrombocytopenic purpura (ITP), and 12 patients who had undergone hematopoietic stem cell transplantation (HSCT). Results: Patients with MDS had normal, patients with liver cirrhosis had slightly elevated RP counts compared to healthy subjects. ITP patients had elevated RP counts, and RP >15% were associated with treatment response (P = 0.015). In 7/10 patients after HSCT, an increase of RP preceded Plt recovery, whereas in patients with secondary thrombocytopenia after normal regeneration, the assessment of RP allowed the differentiation between conditions with high Plt turnover, such as GvHD and microangiopathy, indicated by high RP counts, and graft failure, indicated by low RP counts. Conclusions: Our data provide the rationale for prospective studies on the diagnostic and prognostic value of RP counts in larger patient populations with ITP and after HSCT. © 2007 Clinical Cytometry Society [source]

Ultrastructural analysis of the smooth-to-striated transition zone in the developing mouse esophagus: Emphasis on apoptosis of smooth and origin and differentiation of striated muscle cells

Jürgen Wörl
Abstract The exact mechanism of smooth-to-striated muscle conversion in the mouse esophagus is controversial. Smooth-to-striated muscle cell transdifferentiation vs. distinct differentiation pathways for both muscle types were proposed. Main arguments for transdifferentiation were the failure to detect apoptotic smooth and the unknown origin of striated muscle cells during esophageal myogenesis. To reinvestigate this issue, we analyzed esophagi of 4-day-old mice by electron microscopy and a fine-grained sampling strategy considering that, in perinatal esophagus, the replacement of smooth by striated muscle progresses craniocaudally, while striated myogenesis advances caudocranially. We found numerous (1) apoptotic smooth muscle cells located mainly in a transition zone, where smooth intermingled with developing striated muscle cells, and (2) mesenchymal cells in the smooth muscle portion below the transition zone, which appeared to give rise to striated muscle fibers. Taken together, these results provide further evidence for distinct differentiation pathways of both muscle types during esophagus development. Developmental Dynamics 233:964,982, 2005. © 2005 Wiley-Liss, Inc. [source]

Worst case scenario: Carcinoma of unknown origin

Michael L. Cibull M.D.
No abstract is available for this article. [source]

Role of Transesophageal Echocardiography in Detecting Implantable Cardioverter Defibrillator Lead Infection

Sanjeev Wasson
Implantable cardioverter defibrillator (ICD) lead infection is a rare condition with reported incidence of 0.2% to 16%. It usually presents with persistent bacteremia or fever of unknown origin and requires high clinical suspicion for diagnosis. Whenever ICD lead infection is suspected, transesophageal echocardiography is the diagnostic technique of choice for detection and characterization of the lesions. Lead infections are extremely difficult to manage conservatively and surgical removal of the entire defibrillator system is recommended along with antimicrobial therapy. We describe a case of recurrent staphylococci bacteremia due to an ICD lead infection in a patient with arrhythmogenic right ventricular dysplasia. (ECHOCARDIOGRAPHY, Volume 20, April 2003) [source]

De novo epileptic confusion in the elderly: A 1-year prospective study

EPILEPSIA, Issue 6 2010
Olivier Veran
Summary Purpose:, Nonconvulsive status epilepticus (NCSE) is clinically difficult to diagnose, especially in old patients without epilepsy, and requires electroencephalography (EEG) for diagnosis. Its incidence among elderly patients with confusion of unknown origin (CUO) remains undetermined. Methods:, A 1-year prospective study was conducted in patients aged 60 years or older, for whom EEG was requested because of confusion considered to be of unknown origin after initial clinical, biologic, and imaging investigations. Diagnosis criteria included a validated clinical assessment scale to confirm confusion. Results:, Of 44 patients with confirmed CUO, 7 presented with de novo NCSE. NCSE population had a mean age of 76 years (range, 60,97 years). No statistically significant differences were found between NCSE patients and others for age, drugs, presence of myoclonia, eyelid myoclonia, tachycardia, or agitation. In contrast, an acute onset (<24 h), gender (100% female among NCSE patients), and lack of clinical response to simple commands were significantly associated with NCSE. No differences between the two groups were evidenced for mortality and morbidity (length of hospitalization, social outcome, and so on). Discussion:, Almost 16% of patients aged 60 or older with confusion of unknown origin had NCSE, according to this first prospective study. Female patients with rapid onset (<24 h) of symptoms and lack of response to simple commands were at a higher risk of presenting with NCSE. [source]

The clinical utility of MRI in patients with neurodevelopmental disorders of unknown origin

H. M. Engbers
Introduction:, Neuroimaging of the brain in the diagnostic work-up of patients with neurodevelopmental disorders is a matter of continuing debate. Recommendations range from performing brain imaging in all patients with neurodevelopmental disorders to performing an MRI only in those with indication on clinical examinations. Important indications for neuroimaging are head size abnormalities and focal neurological findings. Methods:, Patients with neurodevelopmental disorders of unknown origin (n = 410), referred to a specialized tertiary diagnostic center for neurodevelopmental disorders were included in a retrospective analysis. A 1-day work-up, including an MRI of the brain was performed. Studied were the: (i) yield of MRI scans of the brain and (ii) associations of specific clinical symptoms/signs with abnormal and diagnostic MRI scans. Results:, (i) In 30.7% of the 410 patients with neurodevelopmental disorders (n = 126), abnormal MRI scans were observed, leading to an etiological diagnosis in 5.4% of the patients (n = 22). (ii) Pyramidal disorders (P = 0.001), epilepsy (P = 0.04) and an abnormal head circumference (P = 0.02) were associated with an abnormal MRI scan. The presence of one of the following neurological symptoms/signs: movement disorders, pyramidal disorders, epilepsy, or an abnormal head circumference was associated with a diagnostic MRI scan (P < 0.001) (diagnostic MRI % in neurological versus no neurological symptoms/signs, 13.0% versus 1.9%). Conclusion:, Neuroimaging of the brain in a tertiary care center for patients with neurodevelopmental disorders of unknown origin is useful, especially in case of neurological symptoms/signs. [source]

Progressive dementia caused by Hashimoto's encephalopathy , report of two cases

J. Spiegel
Dementia induced by Hashimoto's encephalopathy (HE) seems to be a rare condition. We report on two patients, who revealed a syndrome consisting of a rapid progressive dementia with myocloni. In both patients, the detection of antithyroid antibodies enabled the diagnosis of HE. The symptoms receded completely during a high-dose glucocorticoid therapy. In patients with rapidly progressive dementia or with dementia of unknown origin, HE should be considered. [source]

Upper limb movement interruptions are correlated to freezing of gait in Parkinson's disease

Alice Nieuwboer
Abstract Freezing of gait (FOG) in patients with Parkinson's disease (PD) is a common problem of unknown origin, which possibly reflects a general motor control deficit. We investigated the relationship between the frequency of freezing episodes during gait and during a bimanual task in control and subjects with PD with and without FOG. Group differences in spatiotemporal characteristics were also examined as well as the effects of visual cueing. Twenty patients with PD in the off-phase of the medication cycle and five age-matched controls performed a repetitive drawing task in an anti-phase pattern on a digitizer tablet. The task was offered at two different speeds (comfortable and maximal) and two different amplitudes (small and large) with and without visual cueing. The results showed that freezing episodes in the upper limbs occurred in only 10.4% of patient trials and that their occurrence was correlated with FOG scores (Spearman's rho = 0.64). Overall, few spatiotemporal differences were found between freezers, non-freezers and controls, except for an overshooting of the target amplitude in controls. Effects of visual cueing were largely similar in all groups, except for the variability of relative phase, which decreased in non-freezers and controls, and was unaffected in freezers. Despite the fact that general motor differences between subgroups were small, freezing episodes were manifest during a bimanual repetitive upper limb task and were correlated to FOG. Further study into upper limb movement breakdown is warranted to understand the parallel deficits that lead up to FOG. [source]

Salivary gland parameters and clinical data related to the underlying disorder in patients with persisting xerostomia

Ianthe Van Den Berg
This study assessed salivary gland parameters and clinical data in patients referred to our clinic because of persisting xerostomia of unknown origin, in order to facilitate early diagnosis and recognition of the underlying disorder. Most patients were referred for diagnostic analysis of a possible Sjögren's syndrome (SS). A complete diagnostic work-up was available in all patients (n = 176), including data on salivary gland function, saliva composition, sialography, salivary gland swelling, pattern of complaints, general health, and medication. Patients were diagnosed with SS (n = 62), sialosis (n = 45), sodium retention syndrome (n = 30), or medication-induced xerostomia (n = 9). In 30 patients no disease related to salivary gland pathology was found. Unstimulated whole salivary flow was decreased in all patients, except in patients with sodium retention syndrome and in patients without salivary gland pathology. Submandibular/sublingual salivary flow was lowest in SS patients. SS and sialosis patients had increased salivary potassium concentrations, whereas only SS patients had increased sodium concentrations. About half of the sialosis patients mainly complained of persistent parotid gland swelling. Xerostomia-inducing medication was used by most patients. It was concluded that gland-specific sialometry and sialochemistry is useful in discriminating between the various disorders causing persisting xerostomia. [source]

What causes hidradenitis suppurativa?

Lübeck Ralf Paus
Fortunately, the recently founded Hidradenitis Suppurativa Foundation (HSF; http://www.hs-foundation.org), to which EXP DERMATOL serves as home journal, has broken with this unproductive tradition and has encouraged publication of the current CONTROVERSIES feature. This is exclusively devoted to discussing the pathobiology of this chronic neutrophilic folliculitis of unknown origin. Although traces of terminological bickering remain visible, it does the HS experts in our virtual debate room credit that they engage in a constructive and comprehensive dissection of potential pathogenesis pathways that may culminate in the clinical picture we know under the competing terms HS or acne inversa. These experts sketch more often complementary than mutually exclusive pathogenesis scenarios, and the outlines of a conceivable consensus on the many open pathobiology questions begin to emerge in these CONTROVERSIES. Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy. [source]

When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico

Rodofo Acuna-Soto
Abstract During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60,70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease. [source]

Stereoselective biosynthesis of chloroarylpropane diols by the basidiomycete Bjerkandera adusta: exploring the roles of amino acids, pyruvate, glycerol and phenyl acetyl carbinol

Peter James Silk
Abstract Bjerkandera adusta produces many chlorometabolites including chlorinated anisyl metabolites (CAMs) and 1-arylpropane-1,2-diols (1, 2, 3, 4) as idiophasic metabolic products of l -phenylalanine. These diols are stereoselectively biosynthesized from a C7 -unit (benzylic, from l -phenylalanine) and a C2 -unit, of unknown origin, as predominantly erythro (1R,2S) enantiomers. Of the labeled amino acids tested as possible C2 -units, at the 4,10 mM level, none were found to efficiently label the 2,3-propane carbons of the diols. However, glycine (2- 13C), l -serine (2,3,3-d3) and l -methionine (methyl-d3) entered the biomethylation pathway. Neither pyruvate (2,3- 13C2), acetate (1,2- 13C2), acetaldehyde (d4) nor ethanol (ethyl-d5) labeled the 2,3-propane carbons of the diols at the 4,10 mM level. Pyruvate (2,3- 13C2) and l -serine (2,3,3-d3) (which also entered the biomethylation pathway) did, however, effectively label the 2,3-propane carbons of the ,-ketols and diols at the 40 mM level as evidenced by mass spectrometry. Glycerol (1,1,2,3,3-d5) also appeared to label one of the 2,3-propane carbons (ca. 5% as 2H2 in the C3 side chain) as suggested by mass spectrometric data and also entered the biomethylation pathway, likely via amino acid synthesis. Glycerol (through pyruvate), therefore, likely supplies C2 and C3 of the propane side chain with arylpropane diol biosynthesis. Incubation of B. adusta with synthetic [2- 2H1,2- 18O]-glycerol showed that neither 2H nor 18O were incorporated in the ,-ketols or diols. The oxygen atom on the C2 of the ketols/diols, therefore, does not appear to come from the oxygen atom on the C2 of glycerol. Glycerol, however, can readily form l -serine (which can then form pyruvate via PLP/serine dehydratase and involve transamination washing out the 18O label and providing the oxygen from water), and can then go on to label the C2 -unit. Labeled ,-ketol, phenyl acetyl carbinol (5) (PAC; ring-d5, 2,3- 13C2 propane) cultured with B. adusta leads to stereospecific reduction to the (1R,2S)-diol (6) (ring-d5 and 2,3- 13C2); in all other metabolites produced, the 2,3- 13C2 label is washed out. Incubation of the fungus with 4-fluorobenzaldehyde (13) produces a pooling of predominantly erythro (1R,2S) 1-(4,-fluorophenyl)-1,2-propane diol (18 as diacetate) (through the corresponding ,-ketols 16, 17). Blocking the para-position with fluorine thus appears to prevent ring oxygenation and also chlorination, forcing the conclusion that para-ring oxygenation precedes meta-chlorination. [source]

MLL/GRAF fusion in an infant acute monocytic leukemia (AML M5b) with a cytogenetically cryptic ins(5;11)(q31;q23q23)

Ioannis Panagopoulos
More than 30 fusions involving the MLL gene at 11q23 have been reported in acute myeloid leukemia (AML). Some of these chimeras are rather common, such as MLL/MLLT3(AF9), but many are quite rare, with some, for example, MLL/GRAF, described only in a single case. The MLL/GRAF fusion, in which the reciprocal hybrid was not expressed, suggesting that the former transcript was the leukemogenic one, was detected in a juvenile myelomonocytic leukemia with a t(5;11)(q31;q23). Here, we report a second case,an infant acute monocytic leukemia (AML M5b),with an MLL/GRAF fusion. By conventional G-banding, the karyotype was normal. However, Southern blot and fluorescence in situ hybridization analyses revealed that MLL was rearranged and that the 5, part of the MLL gene was inserted into 5q in the vicinity of 5q31, which harbors GRAF. Reverse-transcriptase polymerase chain reaction (PCR) showed that exon 9 of MLL was fused in-frame with exon 19 of GRAF. Extralong genomic PCR with subsequent sequence analysis demonstrated that the breakpoints occurred in intron 9 of MLL, nine base pairs (bp) downstream from exon 9, and in intron 18 of GRAF, 117 bp downstream from exon 18. A 6-bp insertion (ACACTC) of unknown origin was present at the junction. The putative MLL/GRAF fusion protein would retain the AT-hook DNA-binding domain, the DNA methyl transferase motif, the transcription repression domain of MLL, and the SH3 domain of GRAF. As expected, the reciprocal GRAF/MLL was neither expressed nor generated at the genomic level as a consequence of the ins(5;11)(q31;q23q23). On the basis of the now-reported two cases with MLL/GRAF, we conclude that this transcript,but not the reciprocal one,characterizes a rare genetic subgroup of infant AML. © 2004 Wiley-Liss, Inc. [source]

Detection of unidentified chromosome abnormalities in human neuroblastoma by spectral karyotyping (SKY)

Ninette Cohen
Spectral karyotyping (SKY) is a novel technique based on the simultaneous hybridization of 24 fluorescently labeled chromosome painting probes. It provides a valuable addition to the investigation of many tumors that can be difficult to define by conventional banding techniques. One such tumor is neuroblastoma, which is often characterized by poor chromosome morphology and complex karyotypes. Ten primary neuroblastoma tumor samples initially analyzed by G-banding were analyzed by SKY. In 8/10 tumors, we were able to obtain additional cytogenetic information. This included the identification of complex rearrangements and material of previously unknown origin. Structurally rearranged chromosomes can be identified even in highly condensed metaphase chromosomes. Following the SKY results, the G-banding findings were reevaluated, and the combination of the two techniques resulted in a more accurate karyotype. This combination allows identification not only of material gained and lost, but also of breakpoints and chromosomal associations. The use of SKY is therefore a powerful tool in the genetic characterization of neuroblastoma and can contribute to a better understanding of the molecular events associated with this tumor. © 2001 Wiley-Liss, Inc. [source]

Acquired von Willebrand's syndrome resulting from untreated hypothyroidism in two prepubertal girls

HAEMOPHILIA, Issue 6 2006
Summary., Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder associated with a number of different diseases, including hypothyroidism. We describe two prepubertal girls with AvWS and undiagnosed hypothyroidism due to thyroiditis Hashimoto. The patients had neither family history nor symptoms of bleeding disorders. Substitution therapy with levothyroxine led to normalization of the coagulation parameters. We report these cases in order to raise awareness among paediatricians so that the AvWS should be suspected and searched for with the appropriate laboratary tests in all cases of hypothyroidism. Moreover, patients with bleeding diathesis of unknown origin should also be investigated for hypothyroidism. [source]

Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy,

HEPATOLOGY, Issue 2 2009
Patrick Ingiliz
Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m2, HIV RNA: 200 copies/mL, CD4 count: 365/mm3, duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content. Conclusions: HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance. (HEPATOLOGY 2008.) [source]

Defective regulation of cholangiocyte Cl,/HCO,3 and Na+/H+ exchanger activities in primary biliary cirrhosis

HEPATOLOGY, Issue 6 2002
Saida Melero
Primary biliary cirrhosis (PBC) is a disorder of unknown origin with autoimmune features. Recently, impaired biliary secretion of bicarbonate has been shown in patients with PBC. Here we have investigated whether bile duct epithelial cells isolated from PBC patients exhibit defects in transepithelial bicarbonate transport by analyzing the activities of 2 ion exchangers, Cl,/HCO,3 anion exchanger 2 (AE2) and Na+/H+ exchanger (NHE) in isolated cholangiocytes. AE2 and NHE activities were studied in basal conditions and after stimulation with cyclic adenosine monophosphate (cAMP) and extracellular adenosine triphosphate (ATP), respectively. Cholangiocytes were grown from needle liver biopsies from 12 PBC patients, 8 normal controls, and 9 patients with other liver diseases. Also, intrahepatic cholangiocytes were cultured after immunomagnetic isolation from normal liver tissue (n = 6), and from recipients undergoing liver transplantation for end-stage PBC (n = 9) and other forms of liver disease (n = 8). In needle-biopsy cholangiocytes, basal AE2 activity was significantly decreased in PBC as compared with normal livers and disease controls. In addition, we observed that though cAMP increased AE2 activity in cholangiocytes from both normal and non-PBC livers, this effect was absent in PBC cholangiocytes. Similarly, though in cholangiocytes from normal and disease control livers extracellular ATP induced a marked enhancement of NHE activity, cholangiocytes from PBC patients failed to respond to purinergic stimulation. In conclusion, our findings provide functional evidence that PBC cholangiocytes exhibit a widespread failure in the regulation of carriers involved in transepithelial H+/HCO,3 transport, thus, providing a molecular basis for the impaired bicarbonate secretion in this cholestatic syndrome. [source]

Low-grade fever: how to distinguish organic from non-organic forms

M. Affronti
Summary Background and aim:, Low-grade fever (LGF) is defined as a body temperature between 37.5 and 38.3 °C, which is below the classical value reported for fever of unknown origin (FUO). We attempted to characterise its epidemiology, aetiology and clinical aspects to improve the methodological approach to diagnosis. Design and Methods:, We reviewed and evaluated a survey of patients with LGF, followed as outpatients of our Department, a tertiary referral centre from 1997 to 2008. The same classifications were applied for classical FUO, and in the patients diagnosed with LGF, we also investigated for habitual hyperthermia (HH). Results:, Seventy-three patients were selected and divided into two groups: group A included 32 patients classified with organic fever and group B included 41 patients with HH. Aetiology of organic LGF was: infectious disease 59%; neoplasm 3.1%; inflammatory non-infectious disease 6.2%; miscellaneous 18.7%; undiagnosed 12.5%. Mean age was significantly higher in the organic fever than in the HH group (p < 0.02). Splenomegaly and loss of weight were significantly associated with organic fever (p < 0.05), while dizziness and general malaise were associated with HH. Lack of any pathological signs at physical examination was significantly more frequent in HH (p < 0.0001). Among the biochemical tests, white blood cells and C-reactive protein were more frequently above normal limits in group A than in group B (p < 0.05). Conclusions:, In our experience, LGF requires the same methodological diagnostic approach as FUO, because there is no relationship between body temperature values and the severity of the underlying diseases, and the aetiological spectrum is also the same. [source]

Value of 18F-FDG-PET/CT in patients with fever of unknown origin and unexplained prolonged inflammatory syndrome: a single centre analysis experience

L. Federici
Summary Objective:, The aim of our study was to evaluate the diagnostic contribution of 18F-fluoro-deoxyglucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life. Patients and methods:, We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. 18F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis. Results:,18F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal 18F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal 18F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering 18F-FDG-PET/CT. We considered that 18F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection. Conclusions:, Our study supports the potential interest of 18F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, 18F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions. [source]

Hashimoto's thyroiditis associated with idiopathic retroperitoneal fibrosis: case report and review of the literature

A. M. Pizzini
Summary Idiopathic retroperitoneal fibrosis (IRF) is a rare disease of unknown origin, characterised by an inflammatory proliferative fibrosing process occurring in the retroperitoneum. Hashimoto's thyroiditis (HT) is a form of chronic thyroiditis that in some cases shows an extensive replacement of thyroid parenchyma by fibrous tissue. We report the rare association of IRF with HT in a 68-year-old woman presenting with pulmonary oedema, acute renal failure due to bilateral hydronephrosis and a firm diffuse goitre with hypothyroidism. The so far reported cases of IRF associated with chronic thyroiditis are reviewed, and the possible aetiopathogenetic link between these two entities is discussed. [source]

Use of electron spin resonance measurements on irradiated sperma lentil seeds to indicate accidental irradiation

Mustafa Korkmaz
Summary The results of electron spin resonance studies on ,-irradiated micro- and macrosperma lentil seeds are reported. Spectra of non-irradiated intact sperma were composed of an equally spaced sextet originating from the presence of Mn2+ ions and a single weak resonance line. Irradiation produced a linear increase in the radical signal intensity in the radiation dose range (0.5,5 kGy) studied, without affecting the Mn2+ signal. Signal intensities of both sperma followed compound exponential decay curves originating from the presence of three different radical species. Heating the sperma cause irreversible decreases in both radical and Mn2+ signal intensities. Two radical species, described in the present work, and a radical of unknown origin were used to explain the experimental results. [source]

Examining criteria for identifying and differentiating fossil faunal assemblages accumulated by hyenas and hominins using extant hyenid accumulations

B. F. Kuhn
Abstract Numerous authors have put forth criteria for distinguishing between assemblages collected by hyenas and hominins. Of the seven most recognised criteria used to distinguish hyenid from hominin assemblages, it has recently been suggested that four be rejected and three retained. The four rejected criteria are: an excessive proportion of horns and horn cores in hyena accumulated assemblages; the absence of small, hard, compact bones; mortality profiles; and the ratio of cranial bones to postcranial bones. The three criteria previous researchers suggested be retained are: a carnivore MNI ratio of ,20%; an abundance of cylinder fragments; and hyena-inflicted damage upon the bones. In this examination of over 27,000 faunal remains associated with all three species of extant bone-collecting hyenids from four countries and two continents, six of the seven previously established criteria and reconsiderations of criteria have been evaluated. The results of the present study indicate that of the six criteria examined, none, as written, are indicative of hyenid activity on bone assemblages of unknown origin. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Hypomineralized molars and incisors of unknown origin: treatment outcome at age 18 years

Summary. Objective., To assess the outcome of treatment of hypomineralized molars and incisors of unknown aetiology (MIH) in 18-year-olds. Design., A follow-up study including clinical examination, panoramic radiography and intraoral photos. Sample and method., Seventy-six individuals treated at the Eastman Dental Institute in Stockholm during 1978,2001 with the diagnosis MIH. Severity of enamel defects in molars and incisors, prevalence and distribution of extracted molars, type, quality and median duration of restorations, periradicular condition of affected molars, dental occlusion and space closure in cases of extraction, as well as the individual's satisfaction with the treatment, were assessed. Results., Severe defects with enamel surface breakdown in all four molars occurred in 42% of the individuals and 29% had at least one incisor with yellow/brown opacity in the enamel. At follow up, 42% of the individuals had at least one molar extracted; 18% had all four molars extracted. The median duration of the molar restorations (n = 153) was 5 years. Of the individuals with restored molars, 48% had at least one unacceptable restoration. Periradicular pathology was observed in three molars. The sagittal relations did not differ between individuals with and without extraction of molars. Space closure was acceptable in 87% of the individuals with extracted molars. Eighty percent were satisfied with the treatment. Conclusions., Extraction of molars with severe enamel defects gave good or acceptable results in a majority of the patients while conservative restorative treatment resulted in a need for additional treatment in approximately half of the patients. [source]

Effect of an Educational Intervention on Optimizing Antibiotic Prescribing in Long-Term Care Facilities

(See Editorial Comments by Dr. Lona Mody on pp 130, 1302)
OBJECTIVE: To assess the effect of an educational intervention aimed at optimizing antibiotic prescribing in long-term care (LTC) facilities. DESIGN: Cluster randomized, controlled trial. SETTING: Eight public LTC facilities in the Montreal area. PARTICIPANTS: Thirty-six physicians. INTERVENTION: The educational intervention consisted of mailing an antibiotic guide to physicians along with their antibiotic prescribing profile covering the previous 3 months. Targeted infections were urinary tract, lower respiratory tract, skin and soft tissues, and septicemia of unknown origin. In the prescribing profile, each antibiotic was classified as adherent or nonadherent to the guide. Physicians in the experimental group received the intervention twice, 4 months apart, whereas physicians in the control group provided usual care. MEASUREMENTS: Data on antibiotic prescriptions were collected over four 3-month periods: preintervention, postintervention I, postintervention II, and follow-up. A generalized estimating equation (GEE) model was used to compare the proportion of nonadherent antibiotic prescriptions of the experimental and control groups. RESULTS: By the end of the study, nonadherent antibiotic prescriptions decreased by 20.5% in the experimental group, compared with 5.1% in the control group. Based on the GEE model, during postintervention II, physicians in the experimental group were 64% less likely to prescribe nonadherent antibiotics than those in the control group (odds ratio=0.36, 95% confidence interval=0.18,0.73). CONCLUSION: An educational intervention combining an antibiotic guide and a prescribing profile was effective in decreasing nonadherent antibiotic prescriptions. Repetition of the intervention at regular intervals may be necessary to maintain its effectiveness. [source]

The renin,angiotensin system as a primary cause of polyarteritis nodosa in rats

Barbara S. Peters
Abstract Polyarteritis nodosa is a necrotizing vasculitis of medium-sized arteries of unknown origin. Hypertension is present in 30% of patients with polyarteritis nodosa. In those cases, high renin levels are thought to be secondary to renal involvement. The present study was performed to identify causal factors of polyarteritis nodosa. In cyp1a1ren-2 transgenic rats, vasculitis of medium-sized arteries resembling classical polyarteritis nodosa can be induced. In this model, oral administration of indole-3-carbinol (I3C) activates the liver-specific cyp1a1 promoter, leading to prorenin expression in a dose-dependent manner. After the first 6 weeks of chronic induction with 0.125% I3C, the mean arterial pressure reached a plateau of about 170 mmHg. Ten out of 11 I3C-treated rats, which were chronically instrumented with a telemetric device to measure blood pressure, developed polyarteritis nodosa within 10 weeks of I3C treatment. I3C alone or instrumentation alone did not cause polyarteritis nodosa. The angiotensin-converting enzyme inhibitor captopril completely prevented the development of polyarteritis nodosa, indicating that local angiotensin II generation is a pathogenetic factor in this model. The renin,angiotensin system can play a primary role in the development of polyarteritis nodosa in rats. [source]

Clear cell sarcoma of soft tissue: diagnostic utility of fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction

Choladda V. Curry
A 7-year-old girl presented with pain and progressive swelling on the left plantar surface. Biopsy of a 2.5 cm mass showed nests of large round to oval neoplastic cells with abundant amphophilic to clear cytoplasm, prominent nucleoli and high mitotic activity. Occasional cells showed spindled morphology. Infrequent melanin pigment was present. Melanocytic markers (HMB45, S-100) were diffusely positive. A diagnosis of clear cell sarcoma of soft tissue (CCSS) was made, and the mass was re-excised with negative margins. 28 months later, a 1.0 cm pulmonary nodule was identified and wedge excision showed metastatic CCSS. Cytogenetics showed a complex karyotype (unbalanced translocation der(12;14)(q10;q10), additional chromosome 22 material of unknown origin). Although the CCSS translocation t(12;22)(q13;q12) was not identified, EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH). Reverse transcription polymerase chain reaction (RT-PCR) showed an EWS-ATF1 fusion transcript, confirmed by direct sequencing. CCSS requires differentiation from malignant melanoma, because of overlapping clinical presentations, sites of involvement, histomorphology, immunocytochemical profiles and ultrastructure. In many circumstances, definitive diagnosis is only possible with confirmation of the CCSS-defining translocation. [source]

Clear Cell Sarcoma of Soft Tissue with Cytogenetic and Molecular Analyses

C. Vejabhuti
A 7-year-old girl presented with pain and progressive swelling on the left plantar surface. Biopsy of a 2.5 cm mass demonstrated nests of large oval tumor cells with high nuclear-to-cytoplasm ratio, amphophilic to clear cytoplasm, prominent nucleoli, and brisk mitotic activity. Occasional cells showed spindled morphology. Infrequent melanin pigment was present. Melanocytic markers (HMB45, S-100) were diffusely positive. A diagnosis of clear cell sarcoma of soft tissue (CCSS) was made, and the tumor was re-excision with negative margins. 28 months later, a 1.0 cm pulmonary nodule was identified and showed CCSS. Cytogenetics demonstrated a complex karyotype (unbalanced translocation der(12;14)(p10;q10), additional chromosome 22 material of unknown origin). Although the CCSS translocation t(12;22)(q13;q12) was not identified, EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH). RT-PCR demonstrated an EWS-ATF1 fusion transcript, confirmed by direct sequencing. CCSS requires differentiation from malignant melanoma, due to overlapping clinical presentations, sites of involvement, histomorphology, immunocytochemical profiles, and ultrastructure. In many circumstances, definitive diagnosis is only possible with confirmation of the CCSS tumor-defining translocation. [source]