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Biomedical subjects

P Keen

Publications and source records attributed to P Keen.

At least 19 recordsLinked to original sources
PubMed1999

Use of the Iowa Self-Assessment Inventory with older hospitalized patients.

This study examined the utility of the Iowa Self-Assessment Inventory (ISAI) as a multidimensional screening tool for older adults in the acute care hospital setting. A sample of 98 patients age 60 and older were administered the ISAI, the Short Geriatric Depression Scale, and the Mini-Mental State Examination. The findings suggest the ISAI is useful for screening for depression but does not detect differences in cognition. However, qualitative data and literature review support the continued search for a holistic, humanistic screening tool to increase the quality and effectiveness of patient care.

Acute Disease↗
PubMed1995

Leucocyte and erythrocyte counts during a multi-stage cycling race ('the Milk Race').

Venous blood samples were taken from eight competitors in mid-evening after a racing day, and in the early morning before the next day's race, three times during the course of the Milk Race, 1992. These were used to gather information about the changes in circulating leucocyte levels in response to the exceptionally high sustained daily workload required during a major multi-stage race. The primary objective was to provide knowledge of 'normal' values against which future clinical judgements of abnormality might be made in these unusual circumstances. During the race, estimated energy output was about 25 MJ (6000 kCal)/day. The mean total circulating leucocyte numbers (per litre of blood), and those of individual leucocyte classes (neutrophil, lymphocyte, monocyte, eosinophil and basophil) were all inside the normal range both in the morning and in the evening. Evening counts were, however, 30-50% higher than morning counts, for all classes except eosinophils. We conclude that individual clinical decisions about leucocyte levels can best be made using normal (sedentary man) values if a morning sample is taken.

Adult↗
PubMed1994

Effect of exercise on simple reaction times of recreational athletes.

To examine the effect of moderate and fatiguing exercise on the simple reaction times of recreational athletes, 12 subjects took a simple reaction-time test while at rest and while cycling on a Monark cycle ergometer at 70% and 100% of maximum workload. To estimate 70% and 100% of maximum workload the subjects underwent a standard incremental test until exhaustion, defined as subjects being unable to maintain the required pedal rate of 70 rpm. Simple reaction time during maximal exercise was significantly slower than in the other two conditions which did not differ significantly from one another. Heart rate and rate of perceived exertion differed significantly for all three conditions.

Adolescent↗
PubMed1991

Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro.

1. Opioids have been shown to inhibit substance P (SP) release from primary afferent neurones (PAN). In addition, opioid receptors have been identified on PAN of the vagus nerves. Sodium cromoglycate (SCG) decreases the excitability of C-fibres in the lung of the dog in vivo. We have utilised a multi-superfusion system to investigate the effect of opioids and SCG on the release of SP from the rat trachea in vitro. 2. Pretreatment of newborn rats with capsaicin (50 mg kg-1 s.c. at day 1 and 2 of life) resulted in a 93.2 +/- 6.3% reduction in tracheal substance P-like immunoreactivity (SP-LI) content when determined by radioimmunoassay in the adult. 3. Exposure to isotonically elevated potassium concentrations (37-90 mM), capsaicin (100 nM-10 microM), and bradykinin (BK; 10nm-1 microM) but not des-Arg9-BK (1 microM) stimulated SP-LI release by a calcium-dependent mechanism. 4. SCG (1 microM and 100 microM) did not affect spontaneous, potassium (60 mM)- or BK (1 microM)-stimulated SP-LI release. 5. Morphine (0.1-100 microM) caused dose-related inhibition of potassium (60 mM)-stimulated SP-LI release with the greatest inhibition of 60.4 +/- 13.7% at 100 microM. The effect of morphine was not mimicked by the kappa-opioid receptor agonist, U50,488H (10 microM) or the delta-opioid receptor agonist, Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE). 6. The effect of morphine was totally abolished by prior and concomitant exposure to naloxone (100 nM) which had no effect on control release values. 7. We conclude that opioid receptors, predominantly of the MM-opioid receptor subtype, inhibit SP-LI release from PAN in the rat trachea and suggest that centrally inactive MM-opioid receptor agonists may have therapeutic potential in the treatment of asthma.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

GABAB receptor modulation of the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro.

1. The role of gamma-aminobutyric acid (GABA) as an inhibitory transmitter in the central nervous system is well documented. Recently, GABAA and GABAB receptors have been identified in the peripheral nervous system, notably on primary afferent neurones (PAN). We have utilised a multi-superfusion system to investigate the effect of selective GABA receptor agonists and antagonists on the release of substance P (SP) from the rat trachea in vitro. 2. GABA (1-100 microM) did not affect spontaneous release of SP-like immunoreactivity (LI) but caused dose-related inhibition of calcium-dependent potassium (60 mM)-stimulated SP-LI release. The greatest inhibition of 77.7 +/- 18.8% was observed at 100 microM. 3. The inhibitory effect of GABA was mimicked by the GABAB receptor agonist, (+/-)-baclofen (1-100 microM), but not the GABAA receptor agonist, 3-amino-1-propane-sulphonic acid (3-APS, 1-100 microM). Baclofen (100 microM) had no effect on SP-LI release stimulated by capsaicin (1 microM). 4. The inhibitory effect of baclofen (30 microM) was significantly reduced by prior and concomitant exposure to the GABAB receptor antagonist, phacolofen (100 microM) but not the GABAA receptor antagonist, bicuculline (10 microM). Neither antagonist, alone, affected spontaneous or potassium-stimulated SP-LI release. 5. We conclude that activation of pre-synaptic GABAB receptors on the peripheral termini of PANs in the rat trachea inhibits SP-LI release and suggest that GABAB receptor agonists may be of value in the therapeutic treatment of asthma.

Animals↗
PubMed1990

Axonal transport of substance P-like immunoreactivity in ganglioside-treated diabetic rats.

This study examined the effect of treatment of control and streptozotocin-diabetic rats with a mixture of gangliosides, derived from bovine brain, on parameters of axonal transport of substance P-like immunoreactivity (SPLI) and its levels in sciatic nerve and lumbar spinal ganglia. Rats were treated daily (10 mg/kg i.p.) for 28 days and compared with untreated control and diabetic groups. The duration of diabetes was 28 days in both cases. Untreated diabetic rats showed deficits in accumulation of axonally transported SPLI proximal (59% of controls) and distal (34% of controls) to sciatic nerve ligations (left in place for 12 h). Rates of accumulation were unaltered by diabetes. There were small numerical reductions in the SPLI content of unconstricted sciatic nerve and of L4 and L5 dorsal root ganglia in diabetic rats. None of these diabetes-associated changes was altered by ganglioside treatment, nor was there any indication of an effect of gangliosides on substance P in non-diabetic rats. The implications are discussed in relation to the possible pathogenesis of diabetic neuropathy.

Animals↗
PubMed1989

Reciprocal regulation of tachykinin- and vasoactive intestinal peptide-gene expression in rat sensory neurones following cut and crush injury.

The relative abundance of preprotachykinin- (PPT), actin- and vasoactive intestinal peptide- (VIP) mRNA's was measured in L5 dorsal root ganglia of rats after resecting or crushing the sciatic nerve. PPT-mRNA levels fell to 40% of control values 3, 6 and 9 days following nerve resection. Crushing produced a lesser fall at 3 and 6 days with a partial recovery at 9 days. Following resection actin-mRNA levels transiently rose to twice control values and had returned to normal by day 9. VIP-mRNA was not detectable in control ganglia but increasing amounts of VIP-mRNA were present 3, 6 and 9 days after nerve injury. The results are discussed in terms of the control mechanisms operating.

Actins↗
PubMed1989

Essential fatty acid treatment--effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats.

This study was designed to examine the effect of dietary supplementation with essential fatty acids (evening primrose oil--5% weight:weight added to the diet) on acute neurophysiological and neurochemical defects in streptozotocin-diabetic rats. Diabetic rats, which were not given evening primrose oil, showed highly significant elevations of nerve sorbitol and fructose combined with a depletion of nerve myo-inositol. In those animals there was also a 40% reduction (p less than 0.02) in the accumulation of axonally transported substance P-like immunoreactivity proximal to a 12 h sciatic nerve ligature together with reduced motor nerve conduction velocity (13% [p less than 0.001] and 20% [p less than 0.001] in two separate experiments). Treatment of other diabetic rats with evening primrose oil prevented completely the development of the motor nerve conduction velocity deficit without affecting sorbitol, fructose or myo-inositol levels or the deficit in axonal transport of substance P. In a second experiment, treatment of diabetic rats with evening primrose oil was associated with significant attenuation of the conduction velocity deficit, but not complete prevention.

Animals↗
PubMed1989

Substance P levels in peripheral nerve, skin, atrial myocardium and gastrointestinal tract of rats with long-term diabetes mellitus. Effects of aldose reductase inhibition.

This study measured the content of substance P-like immunoreactivity (SPLI) in peripheral nervous tissue (lumbar dorsal root ganglia, sciatic nerve), skin (snout, foot), gastrointestinal tract (stomach, terminal ileum) and in the atria of the heart. Animals studied were long-term (11 months) streptozotocin-diabetic rats compared with age-matched control rats. All diabetic rats were given a very long acting insulin preparation twice weekly to reduce morbidity. Half of the diabetic rats were given the aldose reductase inhibitor, sorbinil (mean dose 30 mg/kg/day body weight by dietary admixture) over the entire protocol. Diabetic rats (given insulin only) showed marked accumulation of sorbitol and fructose together with myo-inositol depletion in their sciatic nerves. The sciatic nerves of the sorbinil-treated diabetic rats contained amounts of sorbitol, fructose and myo-inositol which were similar to those of non-diabetic rats, in spite of large amounts of nerve glucose in the sorbinil-treated animals. Thus, the inhibition of aldose reductase was successful. The L4 and L5 dorsal root ganglia of the diabetic rats showed reduced SPLI (63% and 72% respectively of control ganglia; P less than 0.05). There was also numerical reduction in sciatic nerve SPLI (84% of control nerve). There were no effects of sorbinil treatment on the reduced SPLI levels in ganglia or sciatic nerve. In the gastrointestinal tract the levels of SPLI were reduced in diabetic rats even when data were adjusted to take account of tissue hypertrophy (diabetic SPLI/whole stomach was 60% controls, P less than 0.01 and SPLI/cm ileum was 78%, though the latter did not attain statistical significance). In skin SPLI/unit area was raised in the diabetic rats to 145% of controls for foot skin and 151% for snout skin. Changes in SPLI content of gastrointestinal tract were unaffected by sorbinil treatment; in the skin the elevations were enhanced to 188% and 270% of respective control values for foot and snout skin. The SPLI content of the atria was unaffected by diabetes or sorbinil. These data are not consistent with a generalised impairment of delivery of substance P by axonal transport in experimental diabetes; special factors appear to influence the levels in neurones innervating different tissues. Exaggerated flux through the polyol pathway appears to be uninvolved.

Aldehyde Reductase↗
PubMed1989

Penetration of antibiotics into bovine neutrophils and their activity against intracellular Staphylococcus aureus.

The penetration of three antibiotics, penicillin, chloramphenicol and erythromycin into bovine neutrophils, either alone or containing previously ingested Staphylococcus aureus, was determined, and their intracellular activity against these bacteria was measured. Uptake of radiolabelled antibiotics was assessed by rapidly separating neutrophils from extracellular antibiotic by centrifugation through silicone oil. Intracellular activity was estimated by comparing the numbers of bacteria surviving intracellularly in neutrophils exposed to antibiotic for 3 h at ten times the MBC, with those surviving intracellularly in untreated neutrophils. Penicillin was slightly concentrated within the neutrophils, reaching a maximum intracellular concentration 1.75 times that of the extracellular concentration; this is the C/E ratio. Chloramphenicol entered to a greater extent with a maximum C/E ratio of 7.08. Erythromycin became highly concentrated within the neutrophils with a C/E ratio of 11.46 after 90 min incubation. The presence of ingested staphylococci significantly reduced the uptake of chloramphenicol, but had no significant effect on the penetration of the other antibiotics. Intracellular activity studies indicated that, at ten times MBC, only penicillin had any significant activity against intracellular staphylococci, reducing survival by 28%. This work demonstrates that penetration of certain antibiotics can be altered by the presence of ingested staphylococci and that high intracellular levels of antibiotics do not necessarily ensure good intracellular activity against pathogenic micro-organisms.

Animals↗
PubMed1989

Effects of sorbinil treatment in rats with chronic streptozotocin-diabetes; changes in lens and in substance P and catecholamines in the iris.

This study was performed on male Wistar rats with streptozotocin-induced diabetes mellitus of 11 months duration. There were two diabetic groups; both were given a long-acting insulin twice weekly to reduce morbidity. One group received no additional treatment whilst the other was given the aldose reductase inhibitor, sorbinil, by dietary admixture (approximate dose was 30 mg/day/kg body weight). At the end of the protocol the lenses of the diabetic rats given insulin alone showed markedly reduced dry weight (70% of controls; p less than 0.01) with increased water content (152% of controls; p less than 0.01). Both of these changes were absent from the lenses of the sorbinil-treated diabetic rats. Lenses from both groups of diabetic rats had elevated glucose contents, with greater levels in the group which received insulin alone. Polyol pathway metabolites were also raised in the diabetic lenses, though sorbinil treatment had markedly attenuated sorbitol accumulation without affecting fructose levels. Lens myo-inositol was almost absent from the diabetic rats which received only insulin (6% of control levels relative to lens dry weight; p less than 0.01). This depletion was substantially attenuated, but not prevented in the sorbinil-treated group (58% of control levels). In the iris the noradrenaline and adrenaline contents were unaltered in either diabetic group. In startling contrast, the iris content of substance P-like immunoreactivity was almost trebled in the insulin alone-treated diabetic rats (282% of controls; p less than 0.01), an effect which was prevented completely by sorbinil (127% of controls; not significantly different).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Deficient axonal transport of substance P in streptozocin-induced diabetic rats. Effects of sorbinil and insulin.

This study measured the accumulation of substance P-like immunoreactivity (SPLI) proximal and distal to 12-h constricting ligatures applied to rat sciatic nerves. There were three separate experiments, and the baseline for each consisted of control and age-matched rats with 3 wk of untreated streptozocin-induced diabetes. We compared the effects of twice-daily insulin treatment, daily sorbinil (25 mg.kg-1.day-1 p.o.), and a combination of both treatments. In untreated diabetic rats the anterograde accumulation of SPLI was reduced by 30-40%. This deficit was unaffected by sorbinil alone but was attenuated by insulin and prevented completely by insulin and sorbinil combined. There were also indications that diabetes caused reductions in retrograde accumulation of SPLI and its content in unconstricted nerve and the L4 dorsal root ganglion. The fraction of SPLI undergoing net anterograde or retrograde movement and the velocities of accumulation were unaffected by diabetes or the treatment regimens. These findings indicate a reduction in the amount of substance P moved by axonal transport in diabetic rats that is related partly to aldose reductase activity and partly to some other insulin-correctable consequence of experimental diabetes.

Animals↗
PubMed1987

Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor 'statil'.

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor 'Statil' throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia. Axonal transport of SPLI was studied by measurement of accumulation at 12 h ligatures on the left sciatic nerve. There were no differences between the 3 groups either in the calculated anterograde and retrograde mean rates of accumulation (ranges 6.0 to 7.6 and 0.38 to 0.72 mm/h respectively) or mobile fractions of SPLI (means from 0.54 to 0.58). There were, however, marked reductions in anterograde and retrograde accumulations of SPLI in the constricted nerves of the 'untreated' diabetics (respectively 57 and 33% of controls; P less than 0.01 for both). In the 'Statil'-treated rats these deficits were attenuated (80 and 75% of controls). Diabetes also reduced the SPLI content of unligated sciatic nerve and trigeminal ganglion (65 and 75% of controls). 'Statil' prevented the deficit in the ganglion, but not in the nerve. 'Statil' treatment prevented the myo-inositol depletion and attenuated the sorbitol and fructose accumulation seen in the sciatic nerves of the untreated diabetic animals suggesting effective inhibition of aldose reductase in this tissue. The total SPLI content of the stomach and 1-cm segments of ileum were unaltered in the diabetic animals but due to the increased weights of these tissues the SPLI content per unit weight was reduced. These changes were unaffected by 'Statil'.

Aldehyde Reductase↗
PubMed1987

Effects of neonatal 6-hydroxydopamine administration on different substance P-containing sensory neurones.

Rats were treated neonatally with 6-hydroxydopamine. This resulted in a greater than 93% depletion of noradrenaline content of all tissues examined in adult animals. There was a significant increase in the substance P content of semilunar ganglion, L5 dorsal root ganglion and of sciatic nerve. There was a corresponding increase in substance P synthesis as measured by axonal transport in the sciatic nerve. The noradrenaline content and ratio of noradrenaline: substance P in the iris of control animals were 2102 pg/mg and 24 respectively and, confirming the results of other workers, 6-hydroxydopamine treatment caused a doubling of this substance P content. Terminal fields in skin of face and paw had noradrenaline contents of 75 and 41 pg/mg respectively and noradrenaline: substance P ratios of 4.0 and 2.2 respectively and in these areas 6-hydroxydopamine treatment caused a much lesser increase in substance P content. We conclude that the response of sensory neurones to 6-hydroxydopamine is governed by the relative density of the sympathetic and sensory innervations in their terminal areas, possibly reflecting intensity of competition for nerve growth factor.

Animals↗
PubMed1986

Regeneration of primary afferent neurons containing substance P-like immunoreactivity.

We compared changes in levels of substance P-like immunoreactivity (SPLI) in L4-6 dorsal root ganglia (DRG), L4-6 dorsal roots, sciatic nerve, tibial nerve and hind foot skin in rats following resection or crush injury of the sciatic nerve. The initial depletion of SPLI, which occurred in all areas sampled, was similar after either type of lesion. In DRG and dorsal roots, recovery to control values occurred in SPLI levels 35-45 days after sciatic crush, but not after resection. In sciatic nerve proximal to the injury, a partial recovery in SPLI content to about 60% of control occurred following crush injury, but not following resection. Distal to the injury, tibial nerve levels recovered rapidly following crush injury, consistent with the previously observed rapid regeneration of SPLI-containing axons. After resection, no recovery was observed until after 35 days, when it appeared that some axons succeeded in crossing the resection zone and regaining the distal nerve stump. Delayed and poor recovery of SPLI levels was observed in foot skin, even after crush injury. This correlated with the poor recovery of the plasma extravasation reaction, a functional index of SP-innervation of skin. In contrast, reinnervation by high-threshold mechanoreceptors was more rapid and complete, in agreement with a previous study. We conclude that although SPLI-containing axons regenerate rapidly, they appear to reinnervate skin less successfully than other afferents. Axon regeneration is associated with a recovery of SPLI levels which fell after axotomy: no recovery occurs if regeneration is prevented. Recovery was almost complete in DRG and roots, but incomplete in sciatic nerve. This peptide transmitter in afferent neurons thus behaves in a similar fashion to previously studied low-molecular weight transmitters and related materials in efferent neurons. Since recovery of SPLI levels begins before there is evidence for target reinnervation, it seems that axon regeneration is a sufficient condition for reversal of some axotomy-induced changes in these neurons. Further studies on substance P synthesis and on the response of individual DRG neurons to axotomy and regeneration will be required to explain fully the discrepancy between partial recovery of SPLI levels in sciatic nerve and full recovery in DRG and dorsal roots.

Animals↗