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Biomedical subjects

O Lenz

Publications and source records attributed to O Lenz.

At least 19 recordsLinked to original sources

Outcomes in African Americans and Hispanics with lupus nephritis.

Poor outcomes have been reported in African Americans and Hispanics compared to Caucasians with lupus nephritis. The purpose of this retrospective analysis was to identify independent predictors of outcomes in African Americans and Hispanics with lupus nephritis. In total, 93 African Americans, 100 Hispanics, and 20 Caucasians with a mean age of 28 +/- 13 years and an annual household income of 32.9 +/- 17.3 (in 1000 US dollars) were studied. World Health Organization (WHO) lupus nephritis classes II, III, IV, and V were seen in 9, 13, 52, and 26%, respectively. Important baseline differences were higher mean arterial pressure (MAP) in African Americans compared to Hispanics and Caucasians (107 +/- 19, 102 +/- 15, and 99 +/- 13 mmHg, P < 0.05), and higher serum creatinine (1.66 +/- 1.3, 1.25 +/- 1.0, and 1.31 +/- 1.0 mg/dl, P < 0.025). African Americans had lower hematocrit compared to Hispanics and Caucasians (29 +/- 5, and 31 +/- 6, and 32 +/- 7%, P < 0.05), and lower annual household income (30.8 +/- 14.9, 33.1 +/- 15.9, and 42.2 +/- 29.3 in 1000 US dollars; P < 0.05). Lower prevalence of WHO class IV was seen in Caucasians (30%) compared to Hispanics (57%, P = 0.03) and African Americans (51%, P = 0.09). Development of doubling creatinine or end-stage renal disease was higher in African Americans and Hispanics than in Caucasians (31, 18, and 10%; P < 0.05), as was the development of renal events or death (34, 20, and 10%; P < 0.025). Our results suggest that both biological factors indicating an aggressive disease and low household income are common in African Americans and Hispanics with lupus nephritis, and outcomes in these groups are worse than in Caucasians.

Adolescent↗

Percutaneous management of perianastomotic stenosis in arteriovenous fistulae: results of a prospective study.

Surgical creation of new anastomosis has been proposed as the preferred treatment for perianastomotic stenoses of fistulae. However, disadvantages of surgical approach have included (1) frequent conversion of fistula to a graft by using synthetic graft material to create a new anastomosis, (2) shortening the length of the cannulation segment by proximal autologous arteriovenous neoanastomosis, and (3) abandoning the fistula altogether in favor of a synthetic graft. We report the results of a prospective study using percutaneous balloon angioplasty (PTA) to treat fistulae with perianastomotic lesions. Seventy-three consecutive patients undergoing 112 PTA procedures for the treatment of perianastomotic lesions were studied. Primary and secondary patency rates were calculated. Procedure success, procedure-related complications, and conversion of fistulae to grafts were recorded. The initial success rate was 97%. The degree of stenosis before and after PTA was 81 +/- 9 and 11+/-11%, respectively. Primary patency rates at 6, 12, and 18 months were 75, 51, and 41%, respectively. Secondary patency rates at 6, 12, and 18 months were 94, 90, and 90%, respectively. Grade I hematoma occurred in three and vein rupture in two cases. No grafts were inserted. These outcomes are superior to those that have been reported for surgery. The outpatient PTA is safe and effective for the management of perianastomotic stenosis. Because of its advantage of fistula preservation, the percutaneous approach should be considered as the preferred first-line therapy for the management of perianastomotic fistula lesions.

Black or African American↗

New directions in the management of severe lupus nephritis.

Systemic lupus erythematosus, which predominantly affects young women, frequently is complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Based on currently published clinical trials, induction therapy with cyclophosphamide combined with pulse corticosteroids is an efficacious treatment option to preserve renal function, and long-term data are available to support this choice. Mycophenolate mofetil is a promising new agent, and recent data suggest that it is at least as efficacious as cyclophosphamide in the induction and maintenance phase, but with fewer side effects. Cell-depleting agents may be added in patients who fail the traditional regimens, preferentially in the setting of one of the ongoing clinical trials. The number of treatment regimens that the clinician can choose from when confronted with a patient with severe lupus nephritis has increased significantly, and more options are on the horizon. This promises more efficacious and better tolerable therapies, but it also puts an additional obligation on the physician to consider risk-to-benefit ratio, patient preference and adherence, feasibility, and cost; and to engage the patient in an active discussion about the different alternatives.

Cyclophosphamide↗

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment.

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.

Aged↗

Oligonucleotide-based microarray: a new improvement in microarray detection of plant viruses.

Microarrays are one of the new emerging methods in plant virology currently being developed by various laboratories. In this study, a new approach is described on the detection of plant viruses using short synthetic single-stranded oligomers (40 nt) instead of PCR products as capture probes. A microchip detecting potato viruses, PVA, PVS, PVM, PVX, PVY and PLRV, in both single and mixed infections was developed and tested. The chip was also designed to distinguish between the main strains of PVY and PVS. Results of initial tests with PVY(NTN) and PVY(O) strains using several different probes for one virus are presented. Possibilities and advantages of the new oligonucleotide-based microarray approach for plant viral diagnosis are discussed.

Oligonucleotide Array Sequence Analysis↗

A hydrogen-sensing multiprotein complex controls aerobic hydrogen metabolism in Ralstonia eutropha.

H(2) is an attractive energy source for many microorganisms and is mostly consumed before it enters oxic habitats. Thus aerobic H(2)-oxidizing organisms receive H(2) only occasionally and in limited amounts. Metabolic adaptation requires a robust oxygen-tolerant hydrogenase enzyme system and special regulatory devices that enable the organism to respond rapidly to a changing supply of H(2). The proteobacterium Ralstonia eutropha strain H16 that harbours three [NiFe] hydrogenases perfectly meets these demands. The unusual biochemical and structural properties of the hydrogenases are described, including the strategies that confer O(2) tolerance to the NAD-reducing soluble hydrogenase and the H(2)-sensing regulatory hydrogenase. The regulatory hydrogenase that forms a complex with a histidine protein kinase recognizes H(2) in the environment and transmits the signal to a response regulator, which in turn controls transcription of the hydrogenase genes.

Aerobiosis↗

Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.

Adult↗

In vivo study of acetylcholine esterase in basal forebrain, amygdala, and cortex in mild to moderate Alzheimer disease.

It is currently unclear whether impairment of the cholinergic system is present in Alzheimer disease (AD) already at an early stage and to what extent it depends on degeneration of the nucleus basalis of Meynert (nbM). We examined acetylcholine esterase activity in vivo in the nbM, the amygdala, and cerebral neocortex. Measurements were performed in normal controls and in patients with mild to moderate AD with positron emission tomography (PET) and C-11-labeled N-methyl-4-piperidyl-acetate (MP4A) which is a specific substrate of AChE. AChE activity was reduced significantly in amygdala and cerebral cortex. In contrast, AChE activity and glucose metabolism appeared preserved or even increased in the nbM. The results support the concept that neocortical and amygdaloid functional changes of the cholinergic system are an early and leading event in AD, rather than the consequence of neurodegeneration of basal nuclei.

Acetates↗

DNA microarray: parallel detection of potato viruses.

DNA microarray assay has become a useful tool for gene expression studies. Less frequent is its application to detection of viruses or diagnostics of virus diseases. Here we show design of a microscope slide-based microarray assay for simultaneous identification of several potato viruses. Different primer pairs were designed or adopted to obtain specific amplicons from six potato viruses: Potato virus A (PVA), Potato virus S (PVS), Potato virus X (PVX), Potato virus Y (PVY), Potato mop-top virus (PMTV) and Potato leaf-roll virus (PLRV). Purified viral DNA probes were spotted on a microscope slide coated with poly-L-lysine. The same primers were used for preparation of fluorochrome-labeled targets. The latter were denatured and hybridized on the microarray slide (chip). An example of simultaneous assay of two pathogens is given and possibilities of practical application of this type of assay are discussed.

DNA Primers↗

Remarkable variability of apple mosaic virus capsid protein gene after nucleotide position 141.

Eight new sequences of European isolates from almond, apple, hop, prune and pear of the Apple mosaic ilarvirus (ApMV) capsid protein gene are presented. A consensus sequence was established as having 654 nucleotides (nt) and two American and two European isolates were identified to have insertions 6 to 15 nucleotides after nt position 141. The insertion resulted in the American isolate A inframeshift repaired with two point insertions 17 and 68 nt downstream. The RNA around the insertion point can potentially form a stable secondary structure with three hairpins. The insertions could stabilise this structure or could be neutral. The predicted folding of the translated protein is not influenced by the insertions or frameshift, and we speculate that the region after nt position 141 is without reasonable selection pressure and represents a hot spot for the accumulation of insertion mutations in ApMV.

Amino Acid Sequence↗

The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P.

The surface glycoprotein of the Lassa virus, a member of the arenaviridae family, is synthesized as a 76-kDa precursor (GP-C) that is posttranslationally cleaved into an N-terminal 44-kDa subunit and a C-terminal membrane-anchored 36-kDa subunit. Cleavage occurs at the C-terminal end of the unusual recognition motif R-R-L-L. We show here that GP-C is cleaved in the endoplasmic reticulum by the cellular subtilase SKI-1/S1P, an enzyme that has so far been observed to be involved in cholesterol metabolism. Furthermore, we present evidence that only cleaved glycoprotein is incorporated into virions and that this is necessary for the formation of infectious virus. To our knowledge, there have been no previous reports of this type of viral glycoprotein processing, one that may be an interesting target for antiviral therapy.

Animals↗

[Surgical treatment of cicatricial carcinoma--methods and results].

INTRODUCTION: The prognosis of scar carcinoma, also known as Marjolin's ulcer, is poor. Metastases of lymph nodes often appear because of late diagnosis and the underestimation of clinical findings. This has a deep impact on the quality of life of the patients. Scar carcinoma often occurs in burn scars, but also in chronic ulcers of the lower extremities and in chronic pressure sores. METHODS: Between 1994 and 1998 12 patients with scar carcinoma were treated at our hospital. In all cases radical surgery of the entire scar area was undertaken, followed by dissection of the draining lymph nodes. Free flaps, pendicular flaps or splint skin grafts were used to cover the resulting defects. RESULTS: In 16.6% we observed positive lymph nodes. There were two cases of local recurrence. Five patients died during the observation time. In one patient the extremity had to be amputated. CONCLUSION: Early diagnosis and radical excision are requirements, and the quality of life can be improved with plastic surgery. Aftercare and yearly staging measures are mandatory.

Aged↗

PET measurement of cerebral acetylcholine esterase activity without blood sampling.

Measurement of cerebral acetylcholine esterase (AChE) activity is of clinical interest for the differential diagnosis of memory disorders and dementia. We developed and tested a non-invasive method for quantitation of regional cortical AChE activity with carbon-11-labelled N-methyl-4-piperidyl acetate (11C-MP4A) that does not require arterial blood sampling. AChE activity was measured in terms of the rate constant for hydrolysis of 11C-MP4A (k3). The physiological model is based on the very high AChE activity in the basal ganglia, which are used as a reference structure. Non-invasive k3 was compared with k3 determined with a standard technique by fitting kinetic tissue and metabolite-corrected plasma data in nine subjects with and without dementia. Across all regional values, a very high correlation of 0.92 was found, with a tendency towards moderate underestimation of k3 by 5%-14% with the non-invasive technique as compared to the invasive technique. In addition to its advantages with respect to practicability, the new non-invasive technique overcomes problems of the invasive technique that are related to interindividual variation of delay times between cerebral and peripheral tracer arrival and measurement of very small amounts of non-hydrolysed tracer in plasma samples.

Acetates↗

[Electrophysiological methods for diagnosis of entrapment syndromes of peripheral nerves].

Summary. Apart from clinical findings, the diagnosis of compression syndromes of peripheral nerves is based on electrophysiological investigations. This includes the determination of nerve conduction velocities, distal motor latency and electromyography, which gives a qualitative indication of the condition of nerves and their related muscles. In the 1980s, new methods were developed for quantifying the diagnoses of nerve lesions and their recovery. Due to the development of new software, we can now carry out these investigations with commercial equipment. The macro-EMG and the motor-unit-estimation give information about the size and number of activated motor units of muscles. One needs a special needle which derives single-fibre- and macro-potentials for recording of the macro-EMG. The single-fibre-potential is used for triggering. The motor-unit-estimation represents a non-invasive method to determine the approximate number of motor units. Multiple point stimulation of the nerve is used to determine action potentials which are registered by surface electrodes. Afterwards, the medians of amplitudes and areas of motor unit action potential are defined and must be divided by the corresponding value of maximal compound muscle action potential for estimating motor units. In this way, the extent of nerve damage can be determined exactly. Additionally, a post-operative follow-up is possible. Furthermore, these methods give information about regeneration processes after nerve damage and their recovery after reconstruction and transplantation. From our point of view, these methods should be included in investigation routinely.

Decompression, Surgical↗

Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene.

A kindred from South Tyrol (northern Italy) with familial, adult-onset parkinsonism of pseudo-dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and 11C-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson's disease. Similar to findings in the sporadic Parkinson's disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C-raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects.

Adult↗

Matrix accumulation in mesangial cells exposed to cyclosporine A requires a permissive genetic background.

BACKGROUND: Chronic nephrotoxicity is an important adverse effect of cyclosporine A (CsA) therapy. Tubulo-interstitial lesions and arteriolopathy are common histologic findings. Glomerular lesions are also described, but they are of variable severity. The aim of our study is to determine whether CsA has a direct effect on mesangial cells and whether the cellular response depends on the genetic background. METHODS: We studied mesangial cells isolated from mice susceptible (ROP/Le-+Es1(b)+Es1(a), ROP) and resistant to glomerulosclerosis (B6SJLF1, C57). We previously showed that sclerosis-prone and sclerosis-resistant phenotypes are maintained in vitro. We examined whether CsA exposure directly affected extracellular matrix turnover in mesangial cells and whether the response is determined by the genetic background. Extracellular matrix synthesis and degradation were studied by proline incorporation, ELISA, reverse transcription-polymerase chain reaction, zymography, and reverse zymography. We chose a CsA dose that induced neither cytotoxicity nor apoptosis (1 microg/ml). RESULTS: At the dose of 1 microg/ml total collagen accumulation was increased in ROP but not in C57 cells. Matrix metalloproteinase (MMP)-2 activity and mRNA levels were selectively decreased in ROP cells. CsA exposure did not affect tissue inhibitors of MMP (TIMP)-1 and -2 activity or TGF-beta1 mRNA expression and protein synthesis in either cell line. CONCLUSION: CsA increases total collagen accumulation in mesangial cells from sclerosis-prone mice by decreasing MMP-2 activity, but does not affect cells from sclerosis-resistant mice. Thus, CsA directly affects mesangial cells, but only those with a permissive genetic background for glomerulosclerosis.

Animals↗

Isolation and partial characterization of dengue virus type 2 and 4 strains from dengue fever and dengue haemorrhagic fever patients from Mindanao, Republic of the Philippines.

OBJECTIVE: Isolation of dengue virus from dengue fever and dengue haemorrhagic fever cases from Mindanao, Republic of the Philippines. METHODS: 12 patients with clinically suspected dengue fever (DF) or dengue haemorrhagic fever (DHF) presenting in four regional hospitals between August and September 1995 on Minadano were enrolled in the study. Dengue virus was isolated by inoculation of Vero/E6 or C6/36 cells with patient serum. IgM antibodies were measured using a commercial test system. Up to 454 bp of the capsid region and 240 bp of the E/NS1 gene junction of different viral isolates were sequenced and phylogenetically analyzed. RESULTS: Virus could be isolated from seven patients, five isolates were typed as dengue virus type 2 and two as dengue virus type 4 by immunostaining with monoclonal antibodies or by RT/PCR. Phylogenetic analysis confirmed a close relationship of the dengue virus type 2 isolates with viruses isolated in the Philippines in 1983 and 1988. CONCLUSION: As observed in studies from other parts of South East Asia, dengue virus type 2 was readily isolated from dengue haemorrhagic fever cases. Dengue virus type 2 and 4 circulate in Mindanao, Philippines, with dengue type 2 being responsible for most of our severe DF or DHF cases.

Child↗