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Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 37 records · Page 2Linked to original sources

Beta-lactam enhancement of aminoglycoside activity under conditions of reduced pH and oxygen tension that may exist in infected tissues.

Aminoglycoside activity is suppressed under conditions of low pH and oxygen tension that are likely to occur in infected tissues; the suppressive effects of these conditions are additive. Under aerobic conditions, the MIC of amikacin for 10 isolates of Escherichia coli was 4.8 +/- 0.7 micrograms/ml at pH 7.2 and increased to 40.0 +/- 8.2 micrograms/ml at pH 6.0. Under anaerobic conditions, the MIC of amikacin for E. coli was 30.0 +/- 1.5 micrograms/ml at pH 7.2 and greater than 50.0 micrograms/ml at pH 6.0. In vitro and in vivo studies of amikacin activity in an acidic and hypoxic milieu containing beta-lactamase demonstrated substantially enhanced bactericidal activity when amikacin and beta-lactams were used together. Under conditions of reduced pH and oxygen tension, cefotaxime enhanced [3H]-tobramycin uptake by E. coli 14-fold and [3H]amikacin uptake 7-fold and appeared to overcome the suppressive effect of those conditions on uptake of aminoglycosides by bacteria.

Abscess

The pathogenesis of atheroma and the rationale for its treatment.

Several theories have been proposed to explain the mechanism causing atheroma; these include endothelial cell injury, smooth muscle cell proliferation, lipid deposition and an abnormality of the vasa vasorum. Based on these hypotheses, new therapies aimed at causing regression or preventing the development of atheroma include heparin, calcium antagonists, beta-receptor antagonists, lipid lowering agents and drugs that manipulate platelets.

Animals

Analysis of disulphide bridge function in recombinant bovine prolactin using site-specific mutagenesis and renaturation under mild alkaline conditions: a crucial role for the central disulphide bridge in the mitogenic activity of the hormone.

We have previously described a method for isolating Escherichia coli-produced methionyl bovine prolactin (Met-bPRL) and its renaturation using thioredoxin. This report describes an alternative renaturation procedure in which extracted Met-bPRL is incubated in air at pH 10 and 20 degrees C. Within 1 h of such treatment essentially all of the reduced Met-bPRL was converted to the oxidized form; this was accompanied by an increase to full mitogenic activity in the Nb2 cell bioassay. It was also found that, to minimize contamination by high mol. wt Met-bPRL derivatives, it is essential to have a reducing agent (dithiothreitol) present during disruption of the bacteria and to extract the protein at neutral pH. The contribution of each of the three disulphide bridges in bPRL to its bioactivity was studied with Met-bPRL variants, prepared via site-specific mutagenesis, in which cysteines were replaced by serines to prevent disulphide bond formation. Variants lacking the C4-C11 bridge, the C191-C199 bridge or both these terminal bridges were as mitogenic as authentic bPRL. (Variants lacking the C191-C199 bridge had markedly increased solubility in the presence of deoxycholate.) In contrast, variants lacking the C58-C174 bridge had greatly reduced bioactivity, indicating that integrity of the large disulphide loop is crucial to the hormone's mitogenic activity.

Animals

Critical period for monocular deprivation in the cat visual cortex.

1. Cats were monocularly deprived for 3 mo starting at 8-9 mo, 12 mo, 15 mo, and several years of age. Single cells were recorded in both visual cortexes of each cat, and the ocular dominance and layer determined for each cell. Ocular dominance histograms were then constructed for layers II/III, IV, and V/VI for each group of animals. 2. There was a statistically significant shift in the ocular dominance for cells in layers II/III and V/VI for the animals deprived between 8-9 and 11-12 mo of age. There was a small but not statistically significant shift for cells in layer IV from the animals deprived between 8-9 and 11-12 mo of age, and for cells in layers V/VI from the animals deprived between 15 and 18 mo of age. There was no noticeable shift in ocular dominance for any other layers in any other group of animals. 3. We conclude that the critical period for monocular deprivation is finally over at approximately 1 yr of age for extragranular layers (layers II, III, V, and VI) in visual cortex of the cat.

Aging

Flow of excitation within rat barrel cortex on striking a single vibrissa.

1. Extracellular spike recordings were made from single cells in various layers of barrel cortex in adult rats anesthetized with urethan. Response magnitude and latency differences to brief 1.14 degrees deflections of mystacial vibrissae of center (principal) and surround receptive-field vibrissae were measured. Latency differences for pairs of cells in the same penetration to stimulation of the principal vibrissa were also collected. In separate experiments the domains of layer IV cells were mapped for their influence by a single vibrissa and their latencies to this vibrissa were recorded. In all experiments precise locations of layer IV cells in each penetration were identified using dye-lesioning and cytochrome oxidase staining of tangential sections. 2. The results suggest that principal vibrissa data are relayed radially in a column of neurons before parallel relay to adjacent columns. To the principal vibrissa, layers IV and Vb neurons discharged earliest, with layers II and III on average 2 and 3 ms later, respectively. Serial relay from layers IV to III to II was suggested to be the most common event. Although layer Va cells fired next, a single-column organization is not suggested for them because differences in latency or response magnitude to their principal and immediate surround vibrissae were not significant. Layer II, III and IV cells showed no statistical difference in latency to the nearest surround vibrissa but fired significantly later than to their principal input. 3. Because, from our previous studies, surround receptive fields of barrel cells in rat S1 cortex appear to be constructed intracortically, these data suggest a parallel column-column relay for their construction. Horizontal relay between barrels occurred first within the septae between barrels. Mean intracortical transmission velocities were calculated at approximately 0.05 m/s for column-column information transfer.

Animals

The effect of visual experience on development of NMDA receptor synaptic transmission in kitten visual cortex.

We have studied the effect of dark rearing on the development of excitatory amino acid transmission in 6-week-old kittens. In normal kittens, the NMDA component of the visual response decreases between 3 and 6 weeks of age for cells located in layers IV, V, and VI (Fox et al., 1991). Dark rearing to 6 weeks of age prevents this decrease. Subsequent exposure to light allows the decrease to proceed. Ten days in the light after 6 weeks in the dark was sufficient to decrease the NMDA component of the visual response to the same levels seen in light-reared animals of the same age. Comparison of the effect of the non-NMDA antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione with the NMDA antagonist aminophosphonovalerate showed that the changes were due to the relative contributions of NMDA and non-NMDA receptors to the visual response rather than the overall contribution of glutamate receptors. We also studied the receptive field properties of the cells in the various groups of kittens. Cells given 4 d in the light after 6 weeks in the dark showed increased direction selectivity but little change in response firing rate. After 10 d in the light, visual responses did show some recovery toward adult values, but neither average firing rates nor the proportion of direction-selective cells reached the levels found in normal 6-week-old animals, contrary to the suggestion that a short period in the light can reverse the effect of dark rearing completely. These results show that the decrease in the NMDA component of the visual response seen during normal development of the cortex is caused by visual experience. Changes in NMDA receptors and developmental events such as geniculocortical afferent segregation and acquisition of orientation tuning covary as a function of visual experience rather than age, strongly suggesting that NMDA receptors are involved in experience-dependent developmental processes.

2-Amino-5-phosphonovalerate

Analysis of clinical experience with a new twist lock connectology.

The DextroLyte II (Dex II) Peritoneal Dialysis System was designed to improve safety and convenience in dialysis therapy. Connectors introduced with this system have a threaded recessed male connector with a corresponding female counterpart. Products are provided for CAPD, Single Use Y, Long Life Y and CCPD. Safety and convenience features intended to reduce peritonitis rates and improve patient acceptance include the following: 1. Connectors with threaded male and corresponding female counterparts which provide a dual seal 2. Easy-to-break frangible which seals the solution bag until ready for use 3. A flange on the connector ensures proper hand placement by providing a safety shield to prevent contamination during connection 4. A hinged shield containing an impregnated povidone-iodine sponge easily snaps around the bag connector 5. A Quick Disconnect Clamp (QDC) provides external occlusion permitting safe disconnection for bagless techniques without opening the system 6. A standard medication port provides easy access for administration of intraperitoneal medication Results of a multicenter study performed in nine centers are as follows: Total patient participants 121 Total patient months 1207 Overall peritonitis rate 1 episode in 43 patient months We conclude that the Dex II peritoneal dialysis systems provide safe dialysis therapy as evidenced by the exceptional peritonitis rates. Patient acceptance has been excellent due to the inclusion of the safety and convenience features described.

Evaluation Studies as Topic

Clinical experience and comparative analysis of the standard and fast peritoneal equilibration tests (PET).

The fast peritoneal equilibration test (PET) has been proposed as a substitute procedure for the standard PET because it is less expensive and less time consuming since fewer samples must be drawn. This study was undertaken to compare the fast and standard PETs to determine if the fast PET is a viable alternative. Fifteen patients participated in the study. Results from the standard PETs indicate 13 patients had average permeability and 2 patients had high transport. Corresponding fast PETs indicate 10 patients with average permeability, 2 patients with high transport, 1 patient had discrepancies between the D/P ratios and drain volume, and 2 patients were noncompliant and did not complete the fast PET. We conclude that the fast PET is a valid screening tool to evaluate peritoneal membrane permeability in patients who have previously undergone a standard PET. It is cost effective and timesaving. The test is easily invalidated if patients fail to comply with instructions for the test. The fast PET is primarily useful as a screening device to determine whether permeability has changed.

Adult

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