PubMed Health⌕ Search

Biomedical subjects

A Blau

Publications and source records attributed to A Blau.

At least 19 recordsLinked to original sources
PubMed2006

Single-chip microelectronic system to interface with living cells.

A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.

Action Potentials↗
PubMed2004

CMOS microelectrode array for the monitoring of electrogenic cells.

Signal degradation and an array size dictated by the number of available interconnects are the two main limitations inherent to standalone microelectrode arrays (MEAs). A new biochip consisting of an array of microelectrodes with fully-integrated analog and digital circuitry realized in an industrial CMOS process addresses these issues. The device is capable of on-chip signal filtering for improved signal-to-noise ratio (SNR), on-chip analog and digital conversion, and multiplexing, thereby facilitating simultaneous stimulation and recording of electrogenic cell activity. The designed electrode pitch of 250 microm significantly limits the space available for circuitry: a repeated unit of circuitry associated with each electrode comprises a stimulation buffer and a bandpass filter for readout. The bandpass filter has corner frequencies of 100 Hz and 50 kHz, and a gain of 1000. Stimulation voltages are generated from an 8-bit digital signal and converted to an analog signal at a frequency of 120 kHz. Functionality of the read-out circuitry is demonstrated by the measurement of cardiomyocyte activity. The microelectrode is realized in a shifted design for flexibility and biocompatibility. Several microelectrode materials (platinum, platinum black and titanium nitride) have been electrically characterized. An equivalent circuit model, where each parameter represents a macroscopic physical quantity contributing to the interface impedance, has been successfully fitted to experimental results.

Action Potentials↗
PubMed2004

A possible favorable effect of colchicine in IgA nephropathy in a carrier of a MEFV mutation.

IgA nephropathy is the most common primary glomerulopathy. Currently, no satisfactory treatment is available and as a result, a significant proportion of affected patients progress to end-stage renal disease. We present a patient with IgA nephropathy in whom continuous colchicine treatment induced remission, which has lasted for 22 years. The patient was a carrier of a mutation in the FMF gene (MEFV). This case raises hopes for a better prognosis in at least one subgroup of IgA nephropathy, consisting of patients who happen to be heterozygous carriers of MEFV mutations.

Adult↗
PubMed2001

Promotion of neural cell adhesion by electrochemically generated and functionalized polymer films.

New strategies for spatially controllable cell adhesion have been developed for brain cells from embryonic chicken. They are based on electrochemically active phenol and pyrrole derivatives, and can be used for the selective coverage of electroconductive substrates. Besides mimicking standard laminin-related adhesion promoting mechanisms by means of an electroactive monomer-linked 18-peptide segment from laminin (SRARKQAASIKVAVSADR), electrochemically generated thin (6-30 nm) polymer films of 3-hydroxybenzyl-hydrazine (3HBH) and 2-(3-hydroxyphenyl)-ethanol (2(3HP)E) with and without mechanically entrapped or covalently linked D-lysine have proved to promote cell adhesion in serum-free medium on indium-doped tin oxide (ITO) substrates during the first 6 culturing days in vitro. The effectiveness of the peptide was strongly density-dependent. Unexpectedly, laminin itself or a combination of laminin and poly-D-lysine (PDL) did not promote cell adhesion and neuron differentiation in serum-free cultures on ITO. However, they worked perfectly well on regular polystyrene substrates in serum-free medium or on ITO when medium with serum was used. This finding might suggest that the adhesion efficiency of laminin does not depend only on the kind of medium supplement but also on the type of substrate. In contrast, the adhesion-promoting properties of "artificial" polymeric films seemed to be based on a more direct cell-film interaction, with the film masking the substrate properties.

Animals↗
PubMed1997

Characterization and optimization of microelectrode arrays for in vivo nerve signal recording and stimulation.

Revealing the complex signal-processing mechanisms and interconnection patterns of the nervous system has long been an intriguing puzzle. As a contribution to its understanding the optimization of the impedance behavior of implantable electrode arrays with via holes is discussed here. Peripheral axons will regenerate through these holes allowing for simultaneous nerve stimulation and signal recording. This approach is part of the ESPRIT project INTER and may eventually lead to devices driving sensory motor prosthesis with closed loop control. In the first set of experiments, micromachined platinum electrode arrays were prepared, characterized and optimized for nerve signal recording. The results of these studies are based on impedance spectroscopy and microscopic techniques. Equivalent circuits were modeled describing formally the electrical response behavior with ohmic resistances between 500 omega and 10 k omega. To attain low impedances for all electrodes on the INTER device, platinum from H2PtCl6 was electrodeposited, and sputter technology as well as electrochemical deposition from H2IrCl6 solution were used to produce thin iridium films. For the former, a lift-off process was established at one of the institutes to generate electrode structures with a line width of 5 microns. As a result in all three cases the electrodes showed almost constant impedances over the entire frequency range (10 Hz-1 kHz), which is relevant for nerve signal recording. In the second set of experiments, electrodes were optimized to allow for nerve stimulation. For this purpose, the charge delivery capacity (CDC) had to be increased and the impedance had to be decreased. Iridium oxide is the material of choice, because its CDC is much higher than the CDC of platinum at 75 microC/cm2 (Ziaie et al., 1991, IEEE Sensors & Actuators Transducers, 6, 124-127). A significant increase of the electrochemically active surface of the electrode structures could be observed by measuring the surface roughness. In first experiments, an activated iridium oxide film was formed with cyclic voltammetry and was evaluated using scanning force microscopy and impedance spectroscopy. The evaluation of the cyclic voltammograms showed a CDC up to 400 mC/cm2 for sputter deposited and oxidatively treated iridium films. Further investigations are directed towards increasing the stability of the iridium oxide electrodes with regard to long-term implants. Parallel experiments aim at the controlled axon adhesion without changing the impedance behavior of the described electrodes.

Electric Impedance↗
PubMed1996

Associations of status and change measures of neuropsychological function with pathologic changes in elderly, originally nondemented subjects.

OBJECTIVE: To describe the association between status and change of neuropsychological function and postmortem neuropathologic findings in subjects with Alzheimer's disease, vascular dementia, normal aging, and pathologic aging. DESIGN: Volunteer cohort study. SETTING: Volunteers were interviewed and tested in outpatient-clinical research offices. PARTICIPANTS: Nondemented, healthy, community-residing subjects, initially between 75 and 85 years of age, who participated in the Bronx Aging Study and had at least 2 years of neuropsychological data and quantitative neuropathologic examinations. MAIN OUTCOME MEASURES: Initial summary neuropsychological score, rate of change score. RESULTS: Summary neuropsychological scores at baseline in subjects who subsequently developed pathologically confirmed Alzheimer's disease or vascular dementia were 0.8 z units lower than those of subjects classified in the normal or pathologic aging subgroups (P < .05). Subjects with Alzheimer's disease showed more neuropsychological change over time than subjects in the normal or pathologic aging groups (P < .001). Normal subjects and subjects with pathologic aging did not differ in baseline scores or rate of change. Level of education was strongly associated with initial neuropsychological scores (P < .004), but not with change scores. CONCLUSIONS: Among elderly, initially nondemented subjects who were followed up until death, subjects with pathologically confirmed Alzheimer's disease or vascular dementia had lower neuropsychological scores at initial evaluation than normal subjects or subjects with pathologic aging. Subjects with Alzheimer's disease had a more rapid rate of decline than normal subjects or subjects with pathologic aging.

Aged↗
PubMed1996

Successful treatment of secondary hyperparathyroidism in hemodialysis patients with oral pulse 1-alpha-hydroxy-cholecalciferol therapy.

We have used high-dose oral pulse therapy with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) to treat 40 hemodialysis patients suffering form secondary hyperparathyroidism. Forty patients with intact parathyroid hormone (PTH) levels of > 150 pg/ml were treated with 4 micrograms oral 1 alpha-OH-D3 twice weekly for 1 year. The mean PTH level was 515 +/- 50 pg/ml prior to treatment, which fell to 191 +/- 42 pg/ml after 6 months of treatment (p < 0.00001), and to 164 +/- 39 pg/ml after 12 months of treatment. Patients with very high PTH levels (> 800 pg/ml) suppressed less well than patients with lower levels (150-300 pg/ml). The therapeutic end point of PTH < 100 pg/ml was achieved in 23 patients (58%). The main side effect of the treatment was hypercalcemia, but this was symptomatic in only 3 patients, all above the age of 70 years. In summary, oral high-dose pulse therapy with 1 alpha-OH-D3 was highly effective in suppressing PTH levels in hyperparathyroid hemodialysis patients, and side effects were relatively few.

Administration, Oral↗
PubMed1995

3,4-diaminopyridine as a treatment for amyotrophic lateral sclerosis.

The slow potassium channel blocker 3,4-diaminopyridine (DAP) enhances acetylcholine release from the nerve terminal and improves conduction in unmyelinated nerve. In this open label pilot study, we examined the effect of DAP combined with inpatient rehabilitation in seven patients with motor weakness due to amyotrophic lateral sclerosis (ALS). A single daily 20 mg oral dose of DAP was gradually increased to the maximum tolerated dose, and serum DAP concentrations were measured. Videotaped motor examination (for subsequent "blinded" review and assignment of a quantitative motor score), Functional Independence Measure (FIM) assessment, nerve conduction studies and neuropsychological evaluations were performed on admission, 1 h after maximum DAP dose, and post-treatment. DAP was tolerated in all patients, though dose was limited by gastrointestinal side effects in five patients. The mean peak serum level was 128 (+/- 50) ng/ml, occurring 1.0 (+/- 0.50) h after dose. A modest but statistically significant (p = 0.045) peak in motor score occurred on DAP. A significant (p = 0.045) improvement from baseline in FIM performance was apparent with DAP. Nerve conduction studies showed small increases in evoked response amplitudes and conduction velocities on DAP, but they did not reach statistical significance. No cognitive or affective changes were apparent. This unblinded pilot study shows that DAP is tolerated in ALS patients, and may be associated with functional and electrophysiologic improvement.

4-Aminopyridine↗
PubMed1994

Eastern European (delta beta) zero-thalassemia: molecular characterization of a novel 9.1-kb deletion resulting in high levels of fetal hemoglobin in the adult.

A novel deletion in the human beta-globin gene cluster associated with increased levels of fetal hemoglobin (HbF) in adult life was molecularly characterized in a member of a family of Eastern European descent. The phenotype of the deletion, documented in five members of the family, shows mild hypochromia and microcytosis (mean corpuscular Hb, 24 to 25.9 pg; mean corpuscular volume, 74 to 78.5 fL) but high production of HbF (13% to 24%) with heterocellular distribution (36% to 86% F cells). Extensive restriction enzyme mapping of the beta-globin cluster and sequencing of the region encompassing the breakpoints showed that the deletion starts 1,612 bp upstream of the cap site of the delta-globin gene, and terminates within the first intron of the beta-globin gene, deleting 9.1 kb of DNA. This length is definitely shorter than the average 12.0 kb of the previously characterized (delta beta) zero-thalassemias. The 5' breakpoint of the new deletion is close to that of the Yugoslavian delta beta-thalassemia deletion, whereas the 3' breakpoint is very close to those of the Turkish and the Greek beta zero-thalassemia deletions. The breakpoints of the deletion occur within a direct repeat containing a tetranucleotide exhibiting homology to a donor-splice site, and is symmetrically flanked by a set of 13- and 14-bp homologous complementary sequences, respectively. It is likely that the deletion may be the result of an "illegitimate" or "nonhomologous" recombination event to which these two short sequences may have contributed. It is of interest that the novel deletion (9.1 kb) is comparable to the Italian HPFH-5 deletion (12.9 kb), regarding both the size and the position of the breakpoints. However, the HPFH-5 deletion includes sequences flanking the breakpoints that are preserved in the new deletion. Considering the resulting two discrete phenotypes (ie, delta beta-thalassemia v HPFH), it can be hypothesized that the deleted sequences in the Italian HPFH-5 mutation may harbor regulatory elements that exert a negative control on the gamma-globin gene expression.

Adult↗
PubMed1994

[Improvement in scleroderma kidney with captopril].

In the past bilateral nephrectomy was often necessary in treating hypertensive scleroderma renal crisis. Since the availability of convertin enzyme inhibitors, many patients who were dialysis-dependent have recovered sufficiently to discontinue dialysis. We describe a 32-year-old woman with scleroderma who developed malignant hypertension and acute renal failure and required dialysis. She was treated aggressively with captopril and other agents. After 15 months, renal function improved and hemodialysis could be discontinued.

Acute Kidney Injury↗
PubMed1994

Cardiovascular effects of nisoldipine in essential hypertension.

The acute hemodynamic effects of nisoldipine (Bay K552) in patients with essential hypertension were studied using nuclear ventriculography. In a cohort of 16 essential hypertension patients, an oral dose of 15 mg nisoldipine significantly lowered blood pressure within 20 min. The effect lasted at least 3 h. Blood pressure that was 160.5 +/- 20.3/108.0 +/- 10.1 mm Hg initially was reduced to 137.0 +/- 14.9/93.8 +/- 9.4 mm Hg at 3 h (P < 0.001). Cardiac output rose, total peripheral resistance fell and ejection fraction rose significantly. End systolic and end diastolic volumes did not change significantly with this dose of nisoldipine. The acute hemodynamic effects of 15 mg nisoldipine administered orally, measured by repeat nuclear ventriculography, were maintained during therapy for the 8 weeks of observation. Thus, nisoldipine is a powerful antihypertensive agent, significantly decreasing BP as well as total peripheral resistance and increasing cardiac index. This effect was prominent after 3 h and wore off about 12 h after each dose. Five of the patients had an initially high heart rate. To these patients propranolol was added in small doses (20-40 mg/day, mean 25 +/- 26 mg/day). This addition did not change the results when the patients were analyzed separately.

Administration, Oral↗
PubMed1993

Hyporeninemic hypoaldosteronism associated with multiple myeloma: 11 years of follow-up.

Hyporeninemic hypoaldosteronism is an important underlying condition, causing hyperkalemia with hyperchloremic metabolic acidosis, disproportionate to the degree of renal insufficiency present. The principal defect in this syndrome is a reduced level of plasma renin activity, which results in secondary hypoaldosteronism. Diabetes mellitus is usually the primary underlying renal disease, though other causes of renal diseases associated with this syndrome have been described. This case report describes for the first time an elderly patient with multiple myeloma, in remission for more than 11 years, associated with the syndrome of hyporeninemic hypoaldosteronism at the time of diagnosis. The complete resolution of the syndrome after vigorous chemotherapy is an intriguing possibility.

Aged↗
PubMed1992

Successful pregnancy in a patient with polycystic kidney disease and advanced renal failure: the use of prophylactic dialysis.

Adult polycystic kidney disease is an inherited disease that is transmitted as an autosomal dominant trait. The clinical manifestations, which develop during the third or fourth decade of life, usually do not affect women during childbearing age and thus do not affect fertility or pregnancy outcome. The patient presented here had polycystic kidney disease and advanced renal failure, and was treated with meticulous fetal surveillance and prophylactic hemodialysis during pregnancy. The successful outcome strengthens the trend to perform prophylactic dialysis in pregnancies with advanced renal failure, despite the lack of controlled studies.

Adult↗
PubMed1992

Effect of low-calorie diets on the sympathetic nervous system, body weight, and plasma insulin in overweight hypertension.

When weight reduction was found to decrease blood pressure in the overweight hypertensive patient, it was hailed as the causative factor. A growing number of recent studies indicate that this association may be secondary to a correlation between diet-associated metabolic change and the sympathetic nervous system. A select group such as overweight hypertensive patients may have a genetic predisposition for such a correlation. In overweight hypertensive patients, low-calorie diet and especially very-low-calorie diet, correlate with improved glucose metabolism, a decrease in plasma insulin concentration, and altered norepinephrine concentrations and thus sympathetic nervous system activity. Several of these studies also show a lack of effect of salt intake on blood pressure. Thus, it seems that metabolic changes caused by the decrease in caloric intake are responsible for the decrease in blood pressure. These must be investigated to understand the effect of the different diets on blood pressure. Very low-calorie diets were found very useful in breaking the vicious circle of severe nonresponsive hypertension to medication.

Blood Pressure↗