Carbamazepine encephalopathy masquerading as Creutzfeldt-Jakob disease.
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Aged↗
Biomedical subjects
J Horvath
Publications and source records attributed to J Horvath.
Possible genotype-phenotype correlations in children with mild clinical course of Canavan disease.
Canavan disease is characterised as a rare, neurodegenerative disease that usually causes death in early childhood. It is an autosomal recessive disorder due to an aspartoacylase (ASPA) deficiency. The causative gene has been mapped to chromosome 17 pter-p13. Here we describe three affected children from two Greek families with an unusually mild course of Canavan disease. All children presented with muscular hypotonia and macrocephaly. Diagnosis was based on elevated N-acetylaspartate in urine, reduced aspartoacylase activity in fibroblasts, and marked white matter changes on cerebral imaging. All three affected individuals exhibited continuous psychomotor development without any regression. Genetic analyses revealed compound heterozygous mutations (Y288 C; F295 S) in two individuals. The Y288 C variant was previously described in a child with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia, partial cortical blindness and retinitis pigmentosa, and slightly elevated N-acetylaspartate in the urine. Demonstration of the same variant in two unusually mildly affected Canavan disease patients and absence of this variant in 154 control chromosomes suggest a possible pathogenic role in mild Canavan disease. In the third individual, two homozygous sequence variants were identified, which comprise the known G274R mutation and a novel K213E variant.
Adolescent↗
Phenotypic heterogeneity of dopa-responsive dystonia in monozygotic twins.
The clinical expression of dopa-responsive dystonia (DRD) was found to be different in a pair of affected monozygotic twins. An earlier onset was associated with a more disabling course of disease. Whereas monozygosity was genetically proven, the search for pathogenic mutations in the GTP-cyclohydrolase-1 gene was negative. The contribution of environmental factors appeared minimal. Intrafamilial variability of DRD phenotype may be related to yet unknown non-Mendelian epigenetic or proteomic factors.
Adult↗
Genotype-phenotype correlations in PCD patients carrying DNAH5 mutations.
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Genotype↗
Sequence analysis of Hungarian LHON patients not carrying the common primary mutations.
We describe sequence analysis of the mitochondrial DNA of five Hungarian patients diagnosed with probable LHON, who do not carry any of the three primary point mutations. We report three novel mutations, one of which might have a pathogenic role.
Amino Acid Substitution↗
Polymer wall coatings for capillary electrophoresis.
This review article describes the preparation of dynamic and static polymeric wall coatings for capillary electrophoresis. Properties of bare fused-silica surfaces and methods for the characterization of capillary coatings are summarized. The preparation and basic properties of neutral and charged wall coatings are considered. Finally, advantages and potential applications of various coatings are discussed.
Acrylic Resins↗
Is (99m)Tc-sestamibi scintimammography complementary to conventional mammography for detecting breast cancer in patients with palpable masses?
UNLABELLED: The aim of this trial was to evaluate in developing countries from different regions the diagnostic performance of (99m)Tc-sestamibi scintimammography (SM) in palpable breast lesions and to verify the clinical usefulness of a joint evaluation with mammography and SM. METHODS: From 10 countries, a total of 238 patients with palpable breast masses (n = 245) were included in this prospective multicenter trial. Prone SM was performed 10 min and 60-90 min (157 patients) after injection using an isotime acquisition of 10 min. Mammography was assessed by the same dedicated imaging radiologist according to breast imaging reporting and data system (BI-RADS) categories for malignancy and breast density. Masked SM findings and mammography findings were checked for a correlation with histopathology findings for excisional biopsy samples. Diagnostic values for breast cancer detection were calculated per lesion. RESULTS: Histopathology revealed 189 cancerous lesions and 56 benign lesions. The sensitivity and specificity of SM were 0.83 and 0.77, respectively. SM diagnostic values did not depend on the incidence of breast cancer in the country of origin or on the timing of imaging (early vs. delayed scans). On mammography, the technique yielded a sensitivity and specificity of 0.85 and 0.66, with 27 mammograms classified as BI-RADS category 1, 33 as category 2, 5 as category 3, 56 as category 4, and 124 as category 5. Thirty-seven lesions were considered to show increased radiologic density. No significant difference was found in SM diagnostic values among different BI-RADS categories or between the groups with low and high breast density. A sensitivity of 96% was calculated when SM and mammography results were combined, with 75% of all false-negative mammography findings classified as true-positive results by SM. CONCLUSION: SM complements mammography in patients with palpable masses and negative mammography findings.
Adult↗
A new absorbed coating for DNA fragment analysis by capillary electrophoresis.
A fully automated coating procedure was devised based on adsorption of a new polymer, poly(dimethylacrylamide-co-allyl glycidyl ether) onto the capillary surface. The whole procedure takes less than 30 min and does not require the use of organic solvents, viscous solutions, or elevated temperature. The coating is stable even under harsh conditions such as alkaline pH, elevated temperature, and denaturant conditions that destroy most other presently available adsorbed coatings. This new adsorbed coating is highly stable and easy to produce in quantity, making it quite unique, and further making it possible to operate with any DNA sieving matrix. Finally, the above-mentioned properties facilitate coating regeneration by a simple wash with a strongly alkaline solution, thus extending the lifetime of the capillary, a highly desirable property for any coating used in biopolymer separations.
Absorption↗
Protein variant separations by cation-exchange chromatography on tentacle-type polymeric stationary phases.
We developed a set of prototype cation-exchange column packings that are based on a hydrophilic coated, pellicular polymeric support with a grafted tentacular surface chemistry that is highly suited to resolving closely related protein variants. These column packings (1) afford minimal band spreading in conjunction with extremely high selectivity, (2) exhibit a very hydrophilic character and (3) have moderate loading capacity. Cytochrome c variants (bovine, horse, rabbit) were baseline-separated, as was native ribonuclease A and its two deamidation products, the Asp67 and isoAsp67 forms. Humanized monoclonal antibody variants differing in the presence of lysine at the C terminus of the heavy chains were baseline-resolved. Finally, the separation of hemoglobin variants found in a sample containing elevated levels of glycated hemoglobin was also demonstrated.
Amides↗
Methodology for the study and projection of surgical and anaesthetic workforce.
The Australian Medical Workforce Advisory Committee has studied the specialties of anaesthesia, general surgery, orthopaedics, ophthalmology and urology in Australia. A methodology is presented for rationalizing various data sources to establish numbers and characteristics of the existing workforce, for applying a variety of information to establish opinion about current adequacy, to project future needs and to advise the mechanisms to ensure delivery of services. This study emphasizes the importance of the cooperative input of governments, health administrations and professional bodies, careful gathering of fundamental data, the studied application of uneven pieces of evidence, recognition of changes in needs and demands, the overlap of sectors of the medical workforce in service delivery, and the requirement for continued study and monitoring. The current size of the workforce in these surgical specialties is found to be satisfactory overall but with some uneven distribution. The anaesthetic workforce is found to be slightly deficient in number overall. The growth of future demand for these specialties was estimated between 1% and 3% per annum and requirements for increases in trainee numbers to meet these projected future demands are defined.
Anesthesia↗
The origin and evolution of viruses (a review).
Viroids and prions might have existed early at the border of inanimate and living worlds. Most extant viruses can be characterized as derivatives of ancestors originating from episomal elements of prokaryotes (DNA phages) and later from eukaryotes. Retroviruses very likely originated from cellular retrotransposons. Retrograde evolution of some large viruses from obligatory intracellular bacteria is possible but the ontogenesis of extant bacteria does not include a viral form of existence (the filterable L forms are not viruses) and well-defined viruses do not regenerate back into vegetative bacterial forms. Biologists experimenting with the evolution of prokaryotic and eukaryotic ancient cells cannot ignore the earliest appearance of viruses within or outside the living matter. Viruses participated in and gave direction to the evolution and natural selection by coexisting with uni- and multicellular organisms for billions of years. The coevolution of viruses and their host cells is characterized by incessant attacks and counterattacks through gene rearrangements and mutations (induced in the virus by an immunological counterattack of the host or by transgression of species barriers by the virus) and recombinations. Recombinations occurred between viral and viral or viral and host genes. Acts of "molecular piracy" as practiced by ancient viruses endowed the virus with the expression of several host genes for the advantage of the virus in its replicative cycle and host-to-host spread. Probably the first immortalized and malignantly transformed cells were induced by viruses as viruses evolved anti-apoptotic measures. While infected cells resort to apoptotic death before the assembly of a new viral progeny, prominent are the anti-apoptotic measures viruses evolved in order to assure the completion of their full replicative cycle. Further, viruses may escape neutralization by host antibodies and may survive a counterattack by the host's T cells directed at virally infected cells of its own. Viruses may induce a form of tolerance and coexist with their host without inducing disease. Persistent and apparently or deceivingly apathogenic or even attenuated viral "quasi-species" populations may contain individual particles that regain virulence due to recombinations and/or gene rearrangements, especially when transgressing species barriers. Xenotropic viruses of animals may replicate in human cells and vice versa confounding experiments with xenotransplants or with use of veterinary viral vaccines for the treatment of human diseases.
Animals↗
Omeprazole-induced interstitial nephritis.
Acute renal impairment secondary to interstitial nephritis is a rare complication of omeprazole. We describe a 50-year-old woman who took 20 mg omeprazole twice daily for endoscopically proved ulcerative esophagitis. At the same time, Duke's C colonic cancer was diagnosed and completely resected. Five fluorouracil/folinic acid adjuvant chemotherapy was tolerated without diarrhea or mouth ulceration. Renal function was normal before her first monthly cycle but markedly deteriorated immediately before the second cycle was due. The patient was symptomatic with lethargy, nausea, and mild vomiting, but she was clinically normotensive and only mildly dehydrated. Her serum creatinine concentration increased despite prolonged intravenous hydration, peaking at 4.4 mg/dl 1 week later. Results of a renal ultrasound were normal, and urinary microscopic findings were unremarkable. Renal biopsy showed interstitial nephritis, and renal function improved on cessation of omeprazole, eventually returning to normal. We describe the 12 cases of omeprazole-induced interstitial nephritis reported previously.
Anti-Ulcer Agents↗
Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent.
Doxorubicin (DOX) and its daunosamine-modified derivative, 2-pyrrolino-DOX, which is 500-1000 times more active than DOX, were incorporated into agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH). The conjugation of DOX with LH-RH analogs was performed by using N-(9-fluorenylmethoxycarbonyl)-DOX-14-O-hemiglutarate, a dicarboxylic acid ester derivative of DOX. Coupling this derivative covalently to the epsilon-amino group of the D-Lys side chain of agonist [D-Lys6]LH-RH or antagonistic analog AC-D-Nal(2)-D-Phe(4Cl)-D-Pal(3)-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-Ala-NH 2 [where Nal(2) = 3-(2-naphthyl)alanine, Pal(3) = 3-(3-pyridyl)alanine, and Phe(4CI) = 4-chlorophenylalanine] was followed by the removal of the 9-fluorenylmethoxycarbonyl protective group to yield cytotoxic derivatives of LH-RH analogs containing DOX. From these DOX containing LH-RH hybrids, intensely potent analogs with daunosamine-modified derivatives of DOX can be readily formed. Thus, cytotoxic LH-RH agonist containing DOX (AN-152) can be converted in a 66% yield by a reaction with a 30-fold excess of 4-iodobutyraldehyde in N,N-dimethylformamide into a derivative having 2-pyrrolino-DOX (AN-207). Hybrid molecules AN-152 and AN-207 fully preserve the cytotoxic activity of their radicals, DOX or 2-pyrrolino-DOX, respectively, in vitro, and also retain the high binding affinity of the peptide hormone portion of the conjugates to rat pituitary receptors for LH-RH. These highly potent cytotoxic analogs of LH-RH were designed as targeted anti-cancer agents for the treatment of various tumors that possess receptors for the carrier peptide. Initial in vivo studies show that the hybrid molecules are much less toxic than the respective cytotoxic radicals incorporated and significantly more active in inhibiting tumor growth.
Amino Acid Sequence↗
Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.
Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.
Animals↗
Severe thrombocytopenia with OKT3 use for steroid-resistant rejection in a cadaveric renal transplant recipient.
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Drug Resistance↗
Rabies virus binding to the nicotinic acetylcholine receptor alpha subunit demonstrated by virus overlay protein binding assay.
A virus overlay protein binding assay was used to study binding of 125I-labelled rabies virus to the acetylcholine receptor (AChR) from Torpedo californica electric organ membranes. After gel electrophoresis of electric organ membranes and transfer of proteins to nitrocellulose, 125I-labelled alpha-bungarotoxin, a curaremimetic neurotoxin, bound to a 40 kDa band and 125I-labelled rabies virus bound to 51 kDa and 40 kDa bands. Binding of rabies virus to the 40 kDa band was inhibited by unlabelled alpha-bungarotoxin. In blots of affinity-purified AChR, labelled virus bound to the 40 kDa alpha subunit and was competed by alpha-bungarotoxin. Based on binding of rabies virus to the alpha subunit and the ability of alpha-bungarotoxin to compete for binding, rabies virus appears to bind to the neurotoxin-binding site of the nicotinic AChR alpha subunit.
Animals↗
Reproductive and neonatal outcomes in captive bred baboons (Papio hamadryas).
Baboons are widely used in biomedical research. Although it is widely held that Papio hamadryas breed well in captivity, each established colony has a different reproductive success often hypothesised to be due to husbandry practices. The National Baboon Colony in Australia is a unique colony that houses Papio hamadryas to mimic that structure seen in the wild. In this article; we have analysed their reproductive parameters and neonatal outcomes. The success of the colony husbandry practices was demonstrated by lack of maternal mortality, low foetal morbidity, and known maternal and paternal linage.
Abortion, Veterinary↗