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Biomedical subjects

M Kessler

Publications and source records attributed to M Kessler.

At least 253 records · Page 14Linked to original sources

Selective effects of aniracetam across receptor types and forms of synaptic facilitation in hippocampus.

Aniracetam reversibly increased synaptic responses mediated by the AMPA but not the NMDA subclass of glutamate receptors in hippocampus and was considerably more potent than structurally similar nootropics. The drug had greater effects on field excitatory postsynaptic potentials (EPSPs) in the dentate gyrus and CA1 region than it did in the CA3 region, suggesting that it differentiates between variants of the AMPA receptor. Ligand binding to glutamate receptors in synaptosomal membrane fractions was minimally changed by aniracetam. Finally, the percent facilitation produced by aniracetam in the CA1 region was not reduced by any of three treatments (4-aminopyridine, changes in extracellular calcium concentrations, paired-pulse stimulation) that affect release but, in accord with a previous report, was substantially decreased by long-term potentiation. These results support the conclusion that aniracetam selectively increases the conductance of a subgroup of synaptic AMPA receptors in hippocampus and suggest that receptor changes underlie the expression of long-term potentiation.

4-Aminopyridine↗

Spectrometric measurements in the anterior eye vasculature of the albino rabbit--a study with the EMPHO I.

Intracapillary haemoglobin oxygenation (oxygen saturation) and haemoglobin concentration (corresponding with blood volume) were measured in different regions of the albino rabbit anterior eye segment using the Erlangen micro-lightguide spectrophotometer (EMPHO I). The tip of the microlightguide (active diameter 210 microns, cover diameter 0.5 mm) was placed in the vitreous by a goniometric mounting and controlled by a micromanipulator. After stepwise elevation of intraocular pressure (IOP) the haemoglobin oxygenation decreased slightly in the iris at an IOP-level of 60 mmHg, whereas in the three regions of the ciliary processes and in the peripheral choroid haemoglobin oxygenation did not decrease until values of 80 mmHg were applied. In contrast, haemoglobin concentration decreases when the IOP increases in all regions except in the pars plana where the haemoglobin concentration increased at 40 and 60 mmHg. The most pronounced reactive hyperaemia was found in the major ciliary processes. Quite passive changes of haemoglobin concentration were seen in the peripheral choroid. Effective regulatory mechanisms must exist which result in IOP-independent (20-60 mmHg) haemoglobin oxygenation, whereas pronounced changes in intracapillary haemoglobin concentration were observed. The decay of both parameters at IOP 80 mmHg is indicative of an exhaustion of their regulatory capacity. Epinephrine topically applied onto the conjunctival sac or injected into the common carotid artery led to a short-term decrease of haemoglobin concentration and, later, a hyperaemic response. A short-term haemoglobin deoxygenation was found especially in the major ciliary processes.

Animals↗

Image correlation of MRI and CT in treatment planning for radiosurgery of intracranial vascular malformations.

Magnetic resonance imaging (MRI) has been incorporated with stereotactic cerebral angiography and computed tomography (CT) in the treatment planning process of heavy ion radiosurgery of intracranial arteriovenous malformations (AVM's). Correlation of the images of the AVM and normal tissue on each of these neuroradiological imaging modalities is achieved by means of fiducial markers. The computerized transfer of angiographic information to the CT images regarding the size, shape, and location of the abnormal vasculature has been described in an earlier report. A separate computer program calculates a fit between individual fiducial markers on the CT and MR images that enables the transfer of contours between the two imaging modalities. The MR images aid in the determination of the 3-dimensional shape of the AVM, adding to the information derived from the two angiographic projections. Currently, MRI cannot replace cerebral angiography in delineating the entire arterial phase of the AVM. Magnetic resonance imaging is invaluable in the treatment planning of angiographically-occult AVM's, determining the location, size, and shape of the volume to be treated. Correlation of the CT and MRI images allows for the transfer of CT-calculated isodose contours to the MRI images to aid in the determination of optimal treatment plans.

Adolescent↗

Reoperation for secondary hyperparathyroidism in chronic renal failure.

From 1972 to 1987, 112 parathyroidectomy (PTX) operations were carried out in 105 haemodialysis or transplant patients by the same surgeon. Twelve had to be reoperated on (19 operations in all) for persistent (9 cases) or recurrent (3 cases) hyperparathyroidism. In six patients morphological tests (echography and technetium-thallium scintigraphy) contributed usefully by detecting parathyroid masses. Repeated surgery was finally effective in nine cases.

Adult↗

Acquired renal cystic disease mimicking adult polycystic kidney disease in a patient undergoing long-term hemodialysis.

Acquired renal cystic disease (ARCD) is defined as the development of multiple cysts in the renal cortex and medulla in patients with chronic renal failure who are free from congenital polycystic kidney disease. ARCD develops generally in contracted kidneys. We report a case of grotesque enlargement of a single kidney in a patient who had been receiving hemodialysis for 18 years. Although the exact causes of ARCD are not known, 3 factors may contribute to the development of nephromegaly; the sex, the duration of hemodialysis and previous unilateral nephrectomy. As in polycystic disease, when the involved kidney reaches considerable size, ARCD may have a favorable effect on anemia caused by chronic renal failure.

Adult↗

Constitutional delay of growth and puberty: do they really reach their target height?

We compared the final adult height (FH) of patients with classic constitutional delay of growth and puberty with their target height (TH) and with the height prediction by the Bayley-Pinneau method (BP). 20 patients and their parents were included in our study: 6 females (mean age 19.1 years) and 14 males (mean age 20.6 years). No significant difference could be detected between TH, FH and BP prognosis. This is in contrast to recent studies using height data partly obtained by self-estimation. We measured our patients and their parents ourselves and were accurately able to calculate their genetically determined TH. This proceeding could explain our results. Our study shows that adolescents with true constitutional delay do not need treatment and that height prediction seems to be accurate.

Adolescent↗

Confirmation of tonsillar anomalies in IgA nephropathy: a multicenter study.

Tonsillar abnormalities have previously been evidenced in IgA nephropathy (IgAN). We report the results of a systematic quantitative analysis of 303 tonsils obtained in 70 IgAN patients and 142 controls. IgG- and IgA-producing plasma cells, stained by immunofluorescence, were enumerated on serial sections of all samples. Both the percentage and number of IgA+ cells were significantly increased in IgAN patients. This anomaly was also observed in age- or sex-matched subgroups of patients. Performed on a large series of individuals this study confirms the dysregulation of IgA production the upper respiratory tract of IgAN patients.

Adolescent↗

Preventing burnout: taking the stress out of the job.

The purpose of this article and of the workshop on this subject presented at the 1989 International Conference on Volunteer Administration is to inform Directors of Volunteers of a new approach to burnout prevention which can directly impact occurrences among themselves and their co-workers. We in volunteer administration are not immune; our burnout rates average 3 1/2 years. This situation, left unchecked, poses a threat to the long term effectiveness of our organizations.

Burnout, Professional↗

Calpain inhibitors improve the recovery of synaptic transmission from hypoxia in hippocampal slices.

Two inhibitors of calcium activated proteases (calpains) were tested for their effects on hypoxia-induced synaptic dysfunction in hippocampal slices. Hypoxic episodes lasting for either one or two minutes beyond the point at which action potentials (fiber volleys) disappeared were used. Leupeptin and calpain inhibitor I had no reliable effects on the rate at which synaptic transmission declined during hypoxia or the time required for loss of action potentials, but both drugs did substantially improve the degree of recovery. Moreover, the percentage of slices meeting an arbitrary criterion for viability after hypoxic treatment was greatly increased by the drug treatment. These results point to the conclusion that proteolysis triggered by calcium influx during hypoxia contributes to pathophysiology.

Animals↗

The effects of adenosine on the development of long-term potentiation.

In previous work we found that a brief period of hypoxia occurring within 1-2 min of high-frequency stimulation disrupts the development of long-term potentiation (LTP) in the CA1 field of rat hippocampal slices. We now report that extracellular application of adenosine if applied within 1 min but not 5 min after high-frequency stimulation similarly prevents LTP. Adenosine was ineffective if DPCPX (1,3-dipropyl-8-cyclopentyl-xanthine), a selective antagonist of adenosine A1 receptors, was present. The post-stimulation application mode excludes the possibility that adenosine interferes with NMDA receptor activation and its role in initiating LTP. It suggests instead that changes in intracellular control systems linked to adenosine receptors can during a brief vulnerable period interrupt the biochemical processes leading to the expression of long-term potentiation.

Adenosine↗

The glycine site modulates NMDA-mediated changes of intracellular free calcium in cultures of hippocampal neurons.

Recent evidence indicates that the N-methyl-D-aspartate (NMDA) receptor-channel complex contains a glycine subunit whose activation may be necessary for channel operation. It has been previously shown that stimulation of the NMDA receptor leads to an increase in intracellular ionic Ca2+ [( Ca2+]i); therefore, we examined the role of the NMDA receptor-associated glycine site in modulating [Ca2+]i using the fluorescent dye Fura II in hippocampal neuron cultures. A 3-s pulse of 200 microM NMDA resulted in a mean [Ca2+]i increase of 363 nM above the average resting concentration of 122 nM. Perfusion of the glycine site antagonist 7-chlorokynurenate (Cl-Kyn) essentially eliminated the NMDA-induced alteration in [Ca2+]i. Either 40 microM glycine or 50 microM D-serine completely reversed the effect of Cl-Kyn, indicating that the drug was acting at the glycine site. The NMDA receptor antagonists 2-amino-5-phosphonovalerate (AP5) and ketamine, which bind to the glutamate recognition site and the ion channel, respectively, also blocked the NMDA-mediated [Ca2+]i response; however, glycine or D-serine did not reverse this effect. These data show that the glycine binding site coupled to the NMDA receptor modulates the NMDA-mediated increase in [Ca2+]i. Antagonists of the glycine site provide a new tool to investigate and possibly control neuroplasticity and neurotoxicity related to the NMDA receptor complex.

2-Amino-5-phosphonovalerate↗

Staphylococcus aureus nasal carriage and infection in patients on continuous ambulatory peritoneal dialysis.

We studied 140 consecutive patients beginning continuous ambulatory peritoneal dialysis (CAPD) at one of seven hospitals to assess the relation of the nasal carriage of Staphylococcus aureus to subsequent catheter-exit-site infection or peritonitis. Shortly before the implantation of the catheters, the patients' anterior nares were cultured for the presence of S. aureus. Antibiotics were not prescribed for the S. aureus carriers, but all the patients were monitored for signs of catheter infection (median follow-up, 10.4 months). At the initiation of CAPD, 63 patients (45 percent) carried S. aureus in the nares. Nasal carriage was more frequent among the 30 patients with diabetes (77 percent) than among the 110 without the disease (36 percent). The carriers of S. aureus had a significantly higher rate of exit-site infection than the noncarriers (0.40 vs. 0.10 episode per year; P = 0.012). Of these episodes, 24 of 34 were caused by S. aureus. The rates of peritonitis of all bacterial types did not differ significantly between the groups, but all 11 episodes of peritonitis caused by S. aureus occurred among the carriers. In 85 percent of the patients with clinical S. aureus infections, the strain from the nares and the strain causing the infection were similar in phage type and antibiotic profile. We conclude that in patients beginning ambulatory peritoneal dialysis, the nasal carriage of S. aureus is associated with an increased risk of catheter-exit-site infection and that the performance of nasal cultures before the implantation of the catheter can identify patients at high risk of subsequent morbidity.

Adult↗

Glycine site associated with the NMDA receptor modulates long-term potentiation.

Recent work has shown that kynurenic acid and several quinoxaline derivatives act as non-competitive NMDA receptor antagonists by binding to the glycine site associated with this receptor. In this study, we have tested the effect of the most potent and selective of these compounds, 7-chlorokynurenic acid (Cl-Kyn), on the induction of long-term potentiation, an event known to involve activation of NMDA receptors. It was found that 30 microM Cl-Kyn reversibly abolished the development of both short-term and long-term potentiation in the CA1 region of hippocampal slices. The effectiveness of Cl-Kyn matched its ability to inhibit 3H-glycine binding and the association of 3H-TCP with the NMDA receptor in binding experiments (Ki 0.7-1 microM). Weak interactions of Cl-Kyn with AMPA receptor sites were observed and may account for a partial, reversible reduction in the epsp. However, blockade of long-term potentiation by Cl-Kyn was completely reversed by simultaneous application of the glycine site agonist D-serine and thus must be attributed to its interaction with the glycine site. These results indicate that the glycine site coupled to the NMDA receptor potently modulates channel function during physiological events related to synaptic activation.

Adaptation, Physiological↗