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Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 181 records · Page 10Linked to original sources

A critical period for experience-dependent synaptic plasticity in rat barrel cortex.

Recordings were made from neurons in layers II, III, and IV of rat barrel cortex. The animals were raised either from the day of birth (P0) or from P2, P4, or P7 with just the D1 vibrissa protruding on one side of the face and the contralateral side intact. Follicles were not ablated, but vibrissae were carefully removed by applying steady tension to the base of each vibrissa. Deprivation was continued until the day of recording (P30-P90), though in most cases vibrissae were allowed to regrow for 4-7 d prior to recording. The area of cortex driven by stimulating the spared D1 vibrissa was found to be enlarged in uni-vibrissae animals, but the characteristic anatomical map of the barrel field, defined by cytochrome oxidase staining, retained its normal form. In animals deprived from P0, layer IV cells outside the D1 barrel responded with short latencies (5-10 msec) to D1 stimulation, a condition never observed in normally reared animals. Short-latency responses to stimulation of regrown, deprived vibrissae were still present in layer IV despite the deprivation. Plasticity decreased rapidly in layer IV between P0 and P4 as judged by two measures: first, the percentage of cells in neighboring barrels that showed short-latency responses to D1 fell from 30% in P0 deprived animals to 18% in P2 and 13% in P4 deprived animals. Second, the percentage of cells in barrels surrounding D1 with larger responses to D1 stimulation than to stimulation of their anatomically related vibrissa also fell from 37% in P0 to 23% in P2 and 12% in P4 deprived animals. The percentage of "shifted cells" showed no further reduction in P7 deprived animals (14%). Plasticity in layers II and III showed little sign of decreasing between P2 and P7 after an initial drop between P0 and P2. Therefore, deprivation started at P4 and P7 had a far greater effect on layers II and III than on layer IV. In animals deprived from P4 onward, not only were responses to D1 stimulation greater in barrels neighboring D1 (in layers II/III), but responses were smaller to principal vibrissa stimulation. This suggests increased lateral transmission from the "experienced" barrel and a failure of vertical transmission within the "deprived" barrels. These results show that changes in the balance of experience acquired through vibrissae can affect development of connectivity in the barrel cortex. The main locus of plasticity is cortical when deprivations are started at P4 and beyond.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Dark-rearing delays the loss of NMDA-receptor function in kitten visual cortex.

Some features of the visual cortex develop postnatally in mammals. For example, geniculocortical axons that initially overlap throughout cortical layer IV segregate postnatally into two sets of interleaved eye-specific bands. NMDA (N-methyl-D-aspartate) receptors are necessary for eye-specific axon-segregation in the frog tectum, and as NMDA receptors play a greater part in synaptic transmission in early life and decrease in function during the period of axon segregation, they may be involved in the segregation of geniculocortical axons: they are well placed to do so as they transduce retinally derived signals essential for segregation. Rearing animals in the dark in early life delays segregation and prolongs the critical period for plasticity. We now report that dark-rearing of kittens also delays the loss of NMDA receptor function in the visual cortex, supporting the view that they play an important part in neuronal development and plasticity.

2-Amino-5-phosphonovalerate↗

An intracellular recording study of stimulus-specific response properties in cat area 17.

Stimulus-specific response properties, such as direction or orientation selectivity, were studied intracellularly in cells recorded from area 17 of the cat. In all 5 direction selective complex cells and one orientation selective simple cell successfully studied, visually evoked excitatory postsynaptic potentials (EPSPs) were tuned to the preferred direction or orientation. Visually evoked inhibitory postsynaptic potentials (IPSPs) were also tuned to the preferred direction/orientation of stimulus. IPSPs evoked by the non-preferred stimulus when present were smaller than those evoked by the preferred stimulus. IPSPs were undetected in two of the 5 cells tested. These results suggest that directionally/orientationally tuned EPSPs make a major contribution to stimulus specificity in visual cortical neurons but IPSPs evoked by a stimulus with null-direction/orientation may sharpen the stimulus specificity.

Animals↗

Urticaria pigmentosa. Systemic evaluation and successful treatment with topical steroids.

Nine patients with adult-onset urticaria pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients.

Administration, Topical↗

Cortisol reduces plasticity in the kitten visual cortex.

We investigated the effect of elevated levels of cortisol on plasticity in the visual cortex of the cat. Animals were given daily injections of cortisol i.m. for 20 days starting around 35 days of age. After 10 days they were monocularly deprived, and after an additional 10 days recordings were made from the visual cortex to construct an ocular dominance histogram. The results were compared with those from normal animals of the same age, and with animals monocularly deprived for the same period but not treated with cortisol. Cortisol reduced the ocular dominance shift in a dose-dependent manner, but did not totally abolish it even at the highest doses used. Two other series of animals were recorded, one slightly later in the critical period and one slightly earlier, with care taken to give cortisol before the animals were exposed to light in the morning. In both cases, cortisol reduced the ocular dominance shift but did not abolish it. To interpret these results, we measured levels of plasma cortisol in normal cats of various ages. Average levels were fairly constant between birth and 12 months of age (0.5-1 microgram/dl), and increased slightly after that, but there was a large variation between animals. Thus elevated levels of cortisol can have a substantial effect on plasticity in the visual cortex of the cat, but the decline of the critical period for plasticity between 6 weeks and 3-5 months of age does not seem to be due to a rise in cortisol levels during this time.

2-Amino-5-phosphonovalerate↗

Loop ileostomy after ileal pouch-anal anastomosis--is it necessary?

Construction of a loop ileostomy is usually advised in patients having an ileal pouch-anal anastomosis to minimize the complication of chronic pelvic sepsis. Formation and closure of a loop ileostomy was associated with a 41 percent and 30 percent complication rate, respectively, in a prospective series of 34 patients. This morbidity must now be assessed in relation to the benefits of avoiding temporary fecal diversion in restorative proctocolectomy.

Adolescent↗

Kinetics of bioaccumulation and clearance of isomeric hexachlorocyclohexanes.

Bioaccumulation experiments were performed on the hexachlorocyclohexane isomers alpha-HCH, beta-HCH, gamma-HCH and delta-HCH, testing them simultaneously. Bioaccumulation factors (BCFs) were calculated from the uptake rate constant (k1) and the clearance rate constant (k2) as: BCF = k1/k2. The BCFs of alpha-HCH (1100 +/- 175) and gamma-HCH (920 +/- 131) were similar. The BCFs of beta-HCH (1520 +/- 276) and delta-HCH (1640 +/- 269), also similar, were significantly higher than those of the alpha- and gamma-isomers.

Animals↗

Clinical validation of four solid state ambulatory monitoring devices in detecting shift of the ST segment.

Continuous monitoring for detection of changes in the ST segment during daily life in patients with stable angina has received increasing attention in recent years. Various reports testify to its role in the detection of silent ischaemia, and its potential usefulness in stratification of risk. Frequency modulated recorders, using magnetic tape for recording with subsequent visual analysis, have been previously validated for the detection of such changes. Analysis, however, is time consuming, and is subject to technical faults due to the presence of moving parts. Several new solid state devices have become available in recent years which provide real-time automated analysis, and have theoretically ideal recording capabilities with frequency response down to 0.05 Hz and linear phase integrity which may be as good, or better than, tape based recorders. We compared each of four solid state devices with a previously validated frequency modulated recording device in patients with angina in order to assess whether such devices correlate well in detecting changes in the ST segment.

Angina Pectoris↗

A proposal for the classification of field placement errors in radiotherapy.

There is an increasing awareness of the high frequency of field placement errors occurring in radiotherapy. If such errors are to be rectified systematically to provide a sustainable improvement in field placement accuracy over a course of treatment, the origins of the errors require unambiguous identification. From an examination of the procedures taking place between the exposure of the prescription and treatment films, we propose resolving field placement errors into four groups: patient motion, entrance field location, field shape or size, and beam direction. We also suggest means by which the components of clinically observed field placement errors may be resolved in practice.

Classification↗

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study.

This study was designed to examine the effects of nisoldipine (relative to placebo), a new dihydropyridine calcium entry blocking agent, in the treatment of silent ischaemia in conventional doses. A total of 409 patients with proven coronary artery disease were screened and of this 64 had at least six episodes or a total duration of 30 min of ST segment depression (1 mm lasting at least 1 min) over 48 h. Fifty-two patients ultimately completed a randomized double-blind cross-over study comparing nisoldipine 5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and number of episodes of ST segment depression when compared to placebo on treatment with nisoldipine 5 mg twice a day and nisoldipine 10 mg daily. However, the confidence limits were wide and crossed the no-treatment effect line. In addition, the nisoldipine doses neither affected the circadian distribution of ischaemic episodes nor caused an alteration of the workload achieved either at peak exercise or at 1 mm ST segment depression measured 24 h after nisoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients with proven coronary artery disease is relatively uncommon; it accounts for approximately 16% of patients with positive exercise. In these patients nisoldipine, given as 5 mg twice a day and 10 mg daily, showed no significant therapeutic effects, either on the frequency or severity of silent ischaemia. New formulations of slow release nisoldipine are consequently being developed so that a fuller 24 h therapeutic profile may be obtained.

Coronary Disease↗

Rapid elimination of a synthetic adjuvant peptide from the circulation after systemic administration and absence of detectable natural muramyl peptides in normal serum at current analytical limits.

Although it is clear that muramyl peptides are involved in sleep associated with bacterial infection, their role in normal physiological sleep is less certain. It has been speculated that "natural" muramyl peptides, derived from degraded gut flora, may pass into the bloodstream, where they play a role in normal sleep (M. Karnovsky, Fed. Proc. 45:2556-2560, 1986). Muramic acid serves as a chemical marker for muramyl peptides, since it is not synthesized by mammals. After injection of synthetic muramyl dipeptide in rabbits, muramic acid was readily detected (after release by acid hydrolysis) in the circulation; however, levels rapidly decreased. This was an important positive control in assessing circulating levels of natural muramyl peptides. Muramic acid was not found in normal serum (detection limit, approximately 500 pmol/ml), demonstrating the absence of appreciable amounts of circulating natural muramyl peptides. At this time we are unable to provide supportive evidence for Karnovsky's hypothesis.

Acetylmuramyl-Alanyl-Isoglutamine↗

Myocardial bridges: morphological and functional aspects.

OBJECTIVE: To assess the arrangement of myocardial bridges. DESIGN: A necropsy study of 90 consecutive hearts (56 male, 34 female). RESULTS: Myocardial bridges, either single or multiple, were seen in 50 (55.6%) of the 90 hearts. The left anterior descending artery was the most commonly affected artery. Thirty five of the 50 hearts which contained in total 41 muscle bridges were dissected further with a magnifying glass. Two different types of muscle bridges could be identified. Thirty one of these 41 myocardial bridges were superficial, crossing the artery transversely towards the apex of the heart at an acute angle or perpendicularly. The remaining 10 myocardial bridges crossed the left anterior descending coronary artery and surrounded it by a muscle bundle that arose from the right ventricular apical trabeculae and crossed the artery transversely, obliquely, or helically before terminating in the interventricular septum. CONCLUSIONS: The superficial type of myocardial bridge does not seem to constrict the artery during systole but the deep muscle bridges, by virtue of their relation with the left anterior descending coronary artery, could twist the vessel and thus compromise its diastolic flow. This may result in ischaemia.

Adolescent↗

Circadian patterns of myocardial ischaemia and the effects of antianginal drugs.

Chronopathology of cardiovascular disease is now well documented. Silent myocardial ischaemia involves the same pathophysiological changes as conventional ischaemia. Early morning peaks in angina and myocardial ischaemia call for adequate timing of medication. beta-blockers abolish the morning peak, and aspirin reduces morning infarctions. The effects of other antianginals on these phenomena are presently unknown.

Angina Pectoris↗

The Medicaidization of certified home health care in New York City.

In New York City, Medicaid has replaced Medicare as the primary payor of certified home health care agencies. This shift has made agencies vulnerable to policy changes and budget cutbacks, changed the client population, and put new demands on service delivery.

Certification↗

Clinical experiences with a single use Y bagless CAPD system applying a quick disconnect clamp for external occlusion.

The Single Use Y set is a disposable CAPD system that incorporates the use of a Quick Disconnect Clamp (QDC) for external occlusion. The system is designed using two types of twist lock connectology. The twist lock bag connector located at the distal end of the set is designed with a flange that provides a safety shelf for proper hand position during bag connection. The proximal patient connector on the Y set is a twist lock design requiring placement of povidone-iodine in the disinfectant chamber of the connector prior to patient connection. The Single Use Y is discarded after use.

Disposable Equipment↗

DNA sequence dependent binding modes of 4',6-diamidino-2-phenylindole (DAPI).

The interactions of DAPI with natural DNA and synthetic polymers have been investigated by hydrodynamic, DNase I footprinting, spectroscopic, binding, and kinetic methods. Footprinting results at low ratios (compound to base pair) are similar for DAPI and distamycin. At high ratios, however, GC regions are blocked from enzyme cleavage by DAPI but not by distamycin. Both poly[d(G-C)]2 and poly[d(A-T)]2 induce hypochromism and shifts of the DAPI absorption band to longer wavelengths, but the effects are larger with the GC polymer. NMR shifts of DAPI protons in the presence of excess AT and GC polymers are significantly different, upfield for GC and mixed small shifts for AT. The dissociation rate constants and effects of salt concentration on the rate constants are also quite different for the AT and the GC polymer complexes. The DAPI dissociation rate constant is larger with the GC polymer but is less sensitive to changes in salt concentration than with the AT complex. Binding of DAPI to the GC polymer and to poly[d(A-C)].poly[d(G-T)] exhibits slight negative cooperativity, characteristic of a neighbor-exclusion binding mode. DAPI binding to the AT polymer is unusually strong and exhibits significant positive cooperativity. DAPI has very different effects on the bleomycin-catalyzed cleavage of the AT and GC polymers, a strong inhibition with the AT polymer but enhanced cleavage with the GC polymer. All of these results are consistent with two totally different DNA binding modes for DAPI in regions containing consecutive AT base pairs versus regions containing GC or mixed GC and AT base pair sequences. The binding mode at AT sites has characteristics which are similar to those of the distamycin-AT complex, and all results are consistent with a cooperative, very strong minor groove binding mode. In GC and mixed-sequence regions the results are very similar to those observed with classical intercalators such as ethidium and indicate that DAPI intercalates in DNA sequences which do not contain at least three consecutive AT base pairs.

Base Sequence↗