A microbiological study of Papillon-LeFevre syndrome in two patients

Aim-To analyse the microflora of subgingival plaque from patients with Papillon-Lefevre syndrome (PLS), which is a very rare disease characterised by palmar-plantar hyperkeratosis with precocious periodontal destruction. Methods-Bacterial isolates were identified using a combination of commercial identification kits, traditional laboratory tests, and gas liquid chromatography. Some isolates were also subjected to partial 16S rDNA sequencing. Plaque samples were also assayed for the presence of Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in a quantitative enzyme linked immunosorbent assay (ELISA) using monoclonal antibodies. Results-The culture results showed that most isolates were capnophilic and facultatively anaerobic species-mainly Capnocytophaga spp and Streptococcus spp. The latter included S constellatus, S oralis, and S sanguis. Other facultative bacteria belonged to the genera gemella, kingella, leuconostoc, and stomatococcus. The aerobic bacteria isolated were species of neisseria and bacillus. Anaerobic species included Prevotella intermedia, P melaninogenica, and P nigrescens, as well as Peptostreptococcus spp. ELISA detected P gingivalis in one patient in all sites sampled, whereas A actinomycetemcomitans was detected in only one site from the other patient. Prevotella intermedia was present in low numbers. Conclusions-Patients with PLS have a very complex subgingival flora including recognised periodontal pathogens. However, no particular periodontopathogen is invariably associated with PLS.

Finding gold in our shadow: psychotherapy and the shadow syndrome

Drawing on the work of Carl Jung and Robert Bly, Yaro Starak explores how 'shadow work' can be used within a Gestalt group therapy environment to uncover the 'gold in our shadow bags' - hidden inner strengths and resources that we were previously unaware of that may lead to healing and transformation. (editor abstract)

Orally administered Giardia duodenalis extracts enhance an antigen-specific antibody response

We have identified novel adjuvant activity in specific cytosol fractions from trophozoites of Giardia isolate BRIS/95/HEPU/2041 (J. A. Upcroft, P. A. McDonnell, and P. Upcroft, Parasitol. Today, 14:281-284, 1998). Adjuvant activity was demonstrated in the systemic and mucosal compartments when Giardia extract was coadministered orally with antigen to mice. Enhanced antigen-specific serum antibody responses were demonstrated by enzyme-linked immunosorbent. assay to be comparable to those generated by the gold standard, mucosal adjuvant cholera toxin. A source of adjuvant activity was localized to the cytosolic component of the parasite. Fractionation of the cytosol produced fraction pools, some of which, when coadministered with antigen, stimulated an enhanced antigen-specific serum response. The toxic component of conventional mucosal adjuvants is associated with adjuvant activity; therefore, in a similar way, the toxin-like attributes of BRIS/95/HEPU/2041 may be responsible for its adjuvanticity. Complete characterization of the adjuvant is under way.

Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Premature calvarial synostosis and epidermal hyperplasia (Beare-Stevenson syndrome-like anomalies) resulting from a P250R missense mutation in the gene encoding fibroblast growth factor receptor 3

We report on a patient with a severe premature calvarial synostosis and epidermal hyperplasia. The phenotype was consistent with that of a mild presentation of Beare-Stevenson syndrome but molecular analysis of the IgIII-transmembrane linker region and the transmembrane domain of the gene encoding the FGFR2 receptor, revealed wild-type sequence only. Subsequently, molecular analysis of the FGFR3 receptor gene identified a heterozygous P250R missense mutation in both the proposita and her mildly affected father. This communication extends the clinical spectrum of the FGFR3 P250R mutation to encompass epidermal hyperplasia and documents the phenomenon of activated FGFR receptors stimulating common downstream developmental pathways, resulting in overlapping clinical outcomes. (C) 2001 Wiley-Liss, Inc.

Clinical trials with glycoprotein IIB/IIIA antagonists - No benefit without bleeding?

As the glycoprotein GPIIb/IIIa receptor is the final common pathway in platelet aggregation, antagonists of this receptor cause a profound inhibition of aggregation induced by any agonist. The short-term efficacy and safety of GPIIb/IIIa antagonists in patients undergoing coronary angioplasty was demonstrated with murine 7E3 Fab, but this antibody was immunogenic. Abciximab is a chimeric human-mouse monoclonal antibody that is less immunogenic. The first major trial with a GPIIb/IIIa antagonist was the EPIC trial with abciximab, which showed that abciximab reduced the ischemic complications of coronary balloon angioplasty and atherectomy in high-risk patients, but increased the risk of bleeding. Subsequent studies showed that using less concurrent heparin reduced bleeding. Abciximab also reduced the rate of revascularization. Further studies have shown that the benefits of abciximab extended to all patients undergoing angioplasty (EPILOG), including patients with unstable angina (CAPTURE) and acute myocardial infarction (RAPPORT). Clinical trials with eptifibatide and tirofiban have failed to demonstrate benefit, at the doses used, in angioplasty. Abciximab and eptifibatide, but not oral xemilofiban, improve the safety of the coronary stenting procedure. Shortterm intravenous treatment with lamifiban, eptifibatide or tirofiban is beneficial in acute coronary syndromes (unstable angina, non-Q wave myocardial infarction). Orally active GPIIb/IIIa antagonists are being developed for use in acute coronary syndromes and myocardial infarction. However, no benefit has been shown with lefradafiban in acute coronary syndromes and sibrafiban and orbofiban are harmful. Eptifibatide, lamifiban and abciximab improve coronary patency in myocardial infarction, and long-term trials of GPIIb/IIIa antagonists are being conducted in acute myocardial infarction. Abciximab can cause thrombocytopenia, and all the GPIIb/IIIa antagonists increase the incidence of bleeding, but there is no excess of intracranial hemorrhage. (C) 2001 Prous Science. All rights reserved.

Clinical assessment of HIV-associated lipodystrophy syndrome: bioelectrical impedance analysis, anthropometry and clinical scores

Background Diagnosis of the HIV-associated lipodystrophy syndrome is based on clinical assessment, in lack of a consensus about case definition and reference methods. Three bedside methods were compared in their diagnostic value for lipodystrophy. Patients and Methods. Consecutive HIV-infected outpatients (n = 278) were investigated, 128 of which also had data from 1997 available. Segmental bioelectrical impedance analysis (BIA) and waist, hip and thigh circumferences were performed. Changes in seven body regions were rated by physicians and patients using linear analogue scale assessment (LASA). Diagnostic cut-off values were searched by receiver operator characteristics. Results. Lipodystrophy was diagnosed in 85 patients (31%). BIA demonstrated higher fat-free mass in patients with lipodystrophy but not after controlling for body mass index and sex. Segmental BIA was not superior to whole body BIA in detecting lipodystrophy. Fat-free mass increased from 1997 to 1999 independent from lipodystrophy. Waist-hip and waist-thigh ratios were higher in patients with lipodystrophy. BIA, anthropometry and LASA did not provide sufficient diagnostic cut-off values for lipodystrophy. Agreement between methods, and between patient and physician rating, was poor. Conclusion: These methods do not fulfil the urgent need for quantitative diagnostic tools for lipodystrophy. BIA estimates of fat free mass may be biased by lipodystrophy, indicating a need for re-calibration in HIV infected populations. (C) 2001 Harcourt Publishers Ltd.

Detection of West Nile virus antigen in mosquitoes and avian tissues by a monoclonal antibody-based capture enzyme immunoassay

An antigen capture immunoassay to detect West Nile (WN) virus antigen in infected mosquitoes and avian tissues has been developed. With this assay purified WN virus was detected at a concentration of 32 pg/0.1 ml, and antigen in infected suckling mouse brain and laboratory-infected mosquito pools could be detected when the WN virus titer was 10(2.1) to 10(3.7) PFU/0.1 ml. In a blindly coded set of field-collected mosquito pools (n = 100), this assay detected WN virus antigen in 12 of 18 (66.7%) TaqMan-positive pools, whereas traditional reverse transcriptase PCR detected 10 of 18 (55.5%) positive pools. A sample set of 73 organ homogenates from naturally infected American crows was also examined by WN virus antigen capture immunoassay and TaqMan for the presence of WN virus. The antigen capture assay detected antigen in 30 of 34 (88.2%) TaqMan-positive tissues. Based upon a TaqMan-generated standard curve of infectious WN virus, the limit of detection in the antigen capture assay for avian tissue homogenates was approximately 10(3) PFU/0.1 ml. The recommended WN virus antigen capture protocol, which includes a capture assay followed by a confirmatory inhibition assay used to retest presumptive positive samples, could distinguish between the closely related WN and St. Louis encephalitis viruses in virus-infected mosquito pools and avian tissues. Therefore, this immunoassay demonstrates adequate sensitivity and specificity for surveillance of WN virus activity in mosquito vectors and avian hosts, and, in addition, it is easy to perform and relatively inexpensive compared with the TaqMan assay.

Long QT syndrome in dogs with tick toxicity (Ixodes holocyclus)

Objective To evaluate cardiac electrical function in dogs with tick toxicity. Design A prospective clinical investigation of 39 client-owned dogs treated for naturally occurring tick toxicity. Procedure An ECG was performed on each dog on several occasions; at admission to hospital with tick toxicity, 24 h later, at discharge from hospital when clinically normal and approximately 12 months later. Results The mean QT interval corrected for heart rate (QTc) was prolonged at admission, 24 h and at discharge compared to the QTc measured 12 months later. T wave morphology was altered in dogs at admission. All other parameters were within normal limits. Conclusions The prolonged QTc interval and altered T wave morphology of dogs with tick toxicity reflects delayed cardiac repolarisation and is comparable with long QT syndrome (LQTS) in people who are predisposed to polymorphic ventricular tachycardia and sudden death. Resolution of ECG changes lagged behind clinical recovery.

Jules Cotard (1840-1889) - His life and the unique syndrome which bears his name

Dr. Jules Cotard (1840-1889) was a Parisian neurologist who first described the delire des negations. Cotard's syndrome or Cotard's delusion comprises any one of a series of delusions ranging from the fixed and unshakable belief that one has lost organs, blood, or body parts to believing that one has lost one's soul or is dead. In its most profound form, the delusion takes the form of a professed belief that one does not exist. Encountered primarily in psychoses such as schizophrenia and bipolar disorder, Cotard's syndrome has also been described in organic lesions of the nondominant temporoparietal cortex as well as in migraine. Cotard's delusion is the only self-certifiable syndrome of delusional psychosis. Jules Cotard, a Parisian neurologist and psychiatrist and former military surgeon, was one of the first to induce cerebral atrophy by the experimental embolization of cerebral arteries in animals and a pioneer in studies of the clinicopathologic correlates of cerebral atrophy secondary to perinatal and postnatal pathologic changes. He was the first to record that unilateral cerebral atrophy in infancy does not necessarily lead to aphasia and was also the pioneer of studies of altered conscious states in diabetic hyperglycemia.