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P Wallace

Publications and source records attributed to P Wallace.

At least 73 records · Page 4Linked to original sources
PubMed1995

Neurological examination of the preterm and full-term infant at risk for developmental disabilities using the Dubowitz Neurological Assessment.

The Dubowitz Neurological Assessment of the Preterm and Full-term Infant was used to evaluate infants at risk for developmental disabilities. Criteria for categorising the results of the Dubowitz Neurological Assessment were developed by documenting the findings on a group of relatively low risk infants managed in a NICU. The criteria, expressed as a number of deviant responses on items in the assessment, were used to test the concurrent and predictive validity. The Dubowitz Neurological Assessment was found to correlate with a perinatal risk rating and the findings on brain ultrasonography, indicating concurrent validity. Predictive validity was demonstrated by correlation with neurodevelopmental outcome and neurological status at 1 year corrected age. The sensitivity and specificity of the assessment were also used to develop a management protocol for graduates of the NICU.

Apgar Score↗
PubMed1995

Development of an animal model of fluoxetine akathisia.

1. Akathisia describes the pattern of intense inner restlessness often associated with neuroleptic and antidepressant treatment. 2. The authors postulated that drug-induced akathisia would be characterized by more position changes and less time spent immobile, in the absence of significant increase in ambulation. In contrast, a psychomotor stimulant would produce both activation and ambulation. 3. Procedures and instruments were developed to test this hypothesis. Adult rats were habituated for 72 hours to the testing environment, and their precise pattern of movements was tracked and recorded (10 reading per second; resolution 0.04 mm) by an infrared motion analysis system. Activity was recorded for a 90 min period after a single injection of sub-stereotypic doses of d-amphetamine (0, 0.3, 1.0 mg/kg) or racemic fluoxetine (0, 3.0, 10.0, 20.0, or 30.0 mg/kg, s.c.). 4. Amphetamine produced both activation and ambulation. Activation was indicated by a decrease in time spent immobile, and an increase in the temporal scaling exponent, which reflects the degree the animal is "acting' in its environment, and the number of position changes. Enhanced locomotion was inferred from marked increases in both the total distance traversed and the ratio of forward movements-to-reversals and a decrease in the spatial scaling exponent, indicative of a less complex and more linear movement pattern. 5. Fluoxetine caused animals to spend more time active, but exerted little effect on locomotion. Activation was indicated by a decrease in time spent immobile and an increase in the temporal scaling exponent and number of position changes. Fluoxetine failed to significantly effect either the ratio of forward movements-to-reversals or the spatial scaling exponent. 6. These findings provide an operational definition and methodology that can be used to differentiate between psychostimulant effects and akathisic effects. This approach may have utility for screening drugs for akathisic potential, for exploring underlying mechanisms, and for developing novel treatments.

Akathisia, Drug-Induced↗
PubMed1995

The treatment of intractable rejection with tacrolimus (FK506) in pediatric liver transplant recipients.

We report our experience in 17 pediatric orthotopic liver transplant (OLT) patients converted from cyclosporine (CsA) to FK506 for intractable acute and chronic rejection. FK506 was initiated orally at a dose of 0.3 mg/kg/day in most patients; the dose was then adjusted to achieve serum levels of 0.5-1.5 ng/ml. Azathioprine was discontinued and low-dose prednisone maintained. The median time between liver transplantation and FK506 conversion was 41 months. Patients have been treated for an average of 14.8 +/- 9.6 months. Six patients were converted for acute rejection and 11 for chronic rejection, i.e., vanishing bile duct syndrome (VBDS). After FK506 conversion, the actual patient and graft survival was 88% and 82%, respectively, in the group as a whole. Two patients died, one of chronic active hepatitis C and the other of lymphoma. Three patients, all with VBDS, did not respond to FK506 and therefore required retransplantation. The serum bilirubin is currently normal in 14 patients and the serum transaminases < 100 IU/ml in 12. The mean bilirubin pre-FK506 of patients successfully converted to FK506 was 4.2 mg/dl compared to 11.8 mg/dl in patients who failed conversion. Major complications included nephrotoxicity, neurotoxicity, and lymphoma. The mean glomerular filtration rate (GFR) of 97 +/- 29 mls/min/1.73m2 prior to FK506 conversion dropped to 51 +/- 20 mls/min/1.73m2 (p = 0.0001) after a mean of 13.6 months of FK506 therapy. Three patients have developed B-cell lymphomas; two of them responded to decreased immunosuppression and one died. We conclude that intractable liver graft rejection in children is most successfully reversed if FK506 is instituted before cholestasis becomes pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

The antinociceptive effect of 1-(2-trifluoromethylphenyl) imidazole (TRIM), a potent inhibitor of neuronal nitric oxide synthase in vitro, in the mouse.

1-(2-trifluoromethylphenyl)imidazole (TRIM) is a potent inhibitor of neuronal (mouse cerebellar) and inducible (lung from endotoxin-pretreated rats) isoforms of nitric oxide synthase (NOS) with IC50 values of 28.2 microM and 27.0 microM, respectively. In contrast, TRIM is a poor inhibitor of bovine aortic endothelial NOS with an IC50 of 1057.5 microM. TRIM (10-50 mg kg-1) administered i.p. exhibits dose-related antinociceptive activity in the mouse (assessed as inhibition of late phase formalin-induced hindpaw licking behaviour) with an ED50 of 85.8 mumol kg-1. In contrast, TRIM (50 mg kg-1, i.p.) failed to influence mean arterial blood pressure in the urethane-anaesthetized mouse. Thus, TRIM may be of use as an experimental tool with which to investigate the biological roles of nitric oxide (NO) within the central nervous system.

Analgesics↗
PubMed1995

Evaluation of the feasibility, reliability and diagnostic value of shortened versions of the geriatric depression scale.

BACKGROUND: Many scales have been developed to assess depression, but they are often too lengthy to be of practical use in general practice consultations. AIM: A study was undertaken to investigate the feasibility, reliability and diagnostic value of the geriatric depression scale and its shorter versions for screening in general practice. METHOD: A total of 586 consecutive consulting patients aged 65 years and over were studied in nine general practices in the west of the Netherlands (13 doctors). The 30-item version of the geriatric depression value was compared with the diagnostic interview schedule as a reference test. RESULTS: The reference test indicated a major depression in six patients while 27 patients had a dysthymic disorder (that is, a chronic mild depression). Five per cent of patients required help for 50% of the questions on the geriatric depression scale. The diagnostic value of the 30-item, 15-item, 10-item and four-item versions did not differ significantly, but the one-item version performed no better than chance. Two items discriminated best between patients who were and who were not depressed (P < 0.05), only one of which was included in a previously proposed four-item version of the scale. The reliability of the proposed four-item version was 0.64, the reliability of the other versions ranging from 0.70 to 0.87. CONCLUSION: The results for the different versions of the geriatric depression scale suggest the use of a 10-item or a four-item version. For practical purposes, the smallest subset would be the most desirable: the four-item version. These scales may be better suited for exclusion rather than inclusion purposes. The feasibility of screening for depression in elderly people in a general practice setting is discussed in the light of the results of the study.

Aged↗
PubMed1994

Augmented antinociception following 7-nitro indazole and flurbiprofen in the conscious mouse.

Co-administration of the nitric oxide synthase inhibitor, 7-nitro indazole (1 mg/kg i.p.), with the cyclooxygenase inhibitor, flurbiprofen (5-75 mg/kg i.p.), resulted in significantly enhanced antinociceptive activity in mice (formalin-induced hindpaw licking assay) without affecting hindpaw inflammation. No antinociception was observed in animals pretreated with 7-nitro indazole (1 mg/kg i.p.) and flurbiprofen (100 micrograms subplantar). Flurbiprofen (50 mg/kg i.p.) pretreatment did not influence the inhibition of cerebellar or spinal cord nitric oxide synthase activity observed after 7-nitro indazole (1 or 25 mg/kg i.p.) administration and did not alter blood pressure in anaesthetised animals. Thus, flurbiprofen acts by a mechanism unrelated to a local anti-inflammatory effect in the hindpaw. Since nitric oxide synthase inhibitors are antinociceptive by an effect in the spinal cord (dorsal horn) this would appear to be a likely location for the nitric oxide synthase and cyclooxygenase enzymes targetted by 7-nitro indazole and flurbiprofen respectively.

Amino Acid Oxidoreductases↗
PubMed1994

Population based study of fatigue and psychological distress.

OBJECTIVES: To determine the prevalence of fatigue in the general population and the factors associated with fatigue. DESIGN: Postal survey. SETTING: Six general practices in southern England. SUBJECTS: 31,651 men and women aged 18-45 years registered with the practices. MAIN OUTCOME MEASURES: Responses to the 12 item general health questionnaire and a fatigue questionnaire which included self reported measures of duration, severity, and causes of fatigue. RESULTS: 15,283 valid questionnaires were returned, giving a response rate of 48.3%, (64% after adjustment for inaccuracies in the practice registers). 2798 (18.3%) of respondents reported substantial fatigue lasting six months or longer. Fatigue and psychological morbidity were moderately correlated (r = 0.62). Women were more likely to complain of fatigue than men, even after adjustment for psychological distress. The commonest cited reasons for fatigue were psychosocial (40% of patients). Of 2798 patients with excessive tiredness, only 38 (1.4%) attributed this to the chronic fatigue syndrome. CONCLUSION: Fatigue is distributed as a continuous variable in the community and is closely associated with psychological morbidity.

Adolescent↗
PubMed1994

beta ig-h3: a transforming growth factor-beta-responsive gene encoding a secreted protein that inhibits cell attachment in vitro and suppresses the growth of CHO cells in nude mice.

beta ig-h3 is a novel gene first discovered by differential screening of a cDNA library made from A549 human lung adenocarcinoma cells treated with transforming growth factor-beta 1 (TGF-beta 1). It encodes a 683-amino-acid protein containing a secretory signal sequence and four homologous internal domains. Here we show that treatment of several types of cells, including human melanoma cells, human mammary epithelial cells, human keratinocytes, and human fibroblasts, with TGF-beta resulted in a significant increase in beta ig-h3 RNA. A portion of the beta ig-h3 coding sequence was expressed in bacteria, and antisera against the bacterially produced protein was raised in rabbits. This antisera was used to demonstrate that several cell lines secreted a 68-kD beta IG-H3 protein after treatment with TGF-beta. Transfection of beta IG-H3 expression plasmids into Chinese hamster ovary (CHO) cells led to a marked decrease in the ability of these cells to form tumors in nude mice. The beta IG-H3 protein was purified from media conditioned by recombinant CHO cells, characterized by immunoblotting and protein sequencing and shown to function in an anti-adhesion assay in that it inhibited the attachment of A549, HeLa, and WI-38 cells to plastic in serum-free media. Sequencing of cDNA clones encoding murine beta ig-H3 indicated 90.6% conservation at the amino acid level between the murine and human proteins. Finally, the beta ig-h3 gene was localized to human chromosome 5q31, a region frequently deleted in preleukemic myelodysplasia and leukemia. The corresponding mouse beta ig-h3 gene was mapped to mouse chromosome 13 region B to C1, which confirms a region of conservation on human chromosome 5 and mouse chromosome 13. We suggest that this protein be named p68 beta ig-h3.

Amino Acid Sequence↗
PubMed1994

Effect of 7-nitro indazole on neurotransmission in the rat vas deferens: mechanisms unrelated to inhibition of nitric oxide synthase.

1. The effect of the nitric oxide synthase (NOS) inhibitor, 7-nitro indazole (7-NI), on sympathetic and purinergic neurotransmission in the rat isolated vas deferens preparation has been studied. 2. 7-NI (50-200 microM) caused a dose- and frequency-dependent inhibition of the phasic (predominantly purinergic) contractile response of the rat vas deferens to electrical (field) stimulation (100 V, 0.5 ms). Greatest inhibition occurred at lower frequencies of stimulation (0.1-10 Hz). The sustained tonic contractile response (predominantly noradrenergic) was inhibited only at a high frequency of stimulation (60 Hz) and only at the highest concentration of 7-NI studies (200 microM). 3. 7-NI (100 microM) significantly reduced the contractile response of the vas deferens to exogenous ATP (20 microM-5 mM) and the stable P2X purinoceptor agonist, alpha, beta-methylene ATP (2.5 and 25.0 microM) but was without effect on contractions due to noradrenaline (0.1-50 microM) indicating a lack of antagonist effect on post-junctional alpha 1 adrenoceptors. 4. The effect of 7-NI (100 microM) on the phasic contractile response to field stimulation (0.1 and 2.0 Hz) was unaffected by preincubation of preparations with yohimbine (1.0 microM) or propranolol (0.01-10.0 microM) indicating the absence of involvement of alpha 2- or beta-adrenoceptors in this response. 5. 7-NI (50-600 microM) caused dose-related inhibition of contractions elicited by addition of a depolarizing concentration of KCl (64 mM). 6. The effect of 7-NI (100 microM) on the phasic contractile response to field stimulation (0.1 and 2.0 Hz) was unaffected by preincubation of preparations with L-arginine (1 mM). Neither L-arginine (1 mM) nor NC nitro L-arginine methyl ester (L-NAME, 100 LM) affected the response of the vas deferens to field stimulation at 0.1 or 2.0 Hz. Nitric oxide synthase (NOS) enzyme activity, measured as the conversion of[3H]-L-arginine to [3H]-citrulline, was not detectable in rat vas deferens homogenates.7. 7-Nr preferentially inhibits the purinergic component of the response of the rat vas deferens to field stimulation. The mechanism of action of 7-NI is not known but is not related to NOS inhibition. It seems likely that 7-NI combines an antagonist action at smooth muscle cell P2X-purinoceptors with the ability to inhibit the cellular influx of calcium ions. Although these hitherto unrecorded effects of 7-NI occur at relatively high concentrations, the effects described may contribute to the pharmacological effects of this NOS inhibitor.

Adenosine Triphosphate↗
PubMed1993

Whose responsibility is it anyway? Hospital admission and discharge of older people in an inner-London District Health Authority.

The division of responsibilities that exists between primary and secondary health care services and health and social care services may create problems in the provision of care to patients whose needs mean that a number of different agencies are involved in their care. The objective of all the agencies involved is the smooth transfer of clients between different sectors of care provision. One client group thought to be particularly vulnerable to dislocations in the continuous pattern of care provision is older people. Problems over the division of responsibility between professional groups are particularly evident on admission to and discharge from hospital. It is the latter rather than the former aspect that has been the focus of research. An extensive multi-methods study of the admission and discharge of older people from hospital in an inter-city District Health Authority was undertaken. This paper examines the transfer of older people between different elements of the health and social care systems. Our study illustrates that on neither admission nor on discharge was there a clearly defined mechanism for affecting liaison between hospital and community. Clearly, the responsibility for this task must be delegated to a specific group. However, such responsibility must be given within a properly resourced and managed system, otherwise the current position of blurred responsibilities will remain. It is unclear as to how the reform of the National Health Service and the introduction of the internal market and the purchaser/provider division will aid the improved co-ordination which this study has identified as being required.

Aged↗
PubMed1993

Spinal and metabolic loading during simulations of golf play.

Changes in stature during physical activity reflect alterations in spinal column length that occur as a result of loading the spine. The shrinkage is associated with loss of intervertebral disc height. This study aimed to measure both the load on the spine during simulations of a round of golf and the physiological responses to carrying golf clubs. Fine measurement of stature was achieved using a computer-linked stadiometer inclined to 13 degrees. Shrinkage was measured (n = 6) after performance regimens which mimicked (1) the ambulatory activity during golf play, (2) ambulation and skills employed in par performance and (3) ambulation and carriage of clubs. Our observations indicate significant shrinkage associated with golf skills, mean shrinkage after nine holes being 2.53 mm compared to 1.78 mm in the walking condition. The highest shrinkage was observed when the player carried his clubs, the amount of stature loss being 4.76 mm over nine holes. The highest rates of shrinkage occurred over the first three holes. In a second experiment to further examine the effects of carrying the golf clubs, five of the subjects walked on a motor-driven treadmill at 5 km h-1 for 5 min. Carrying the clubs caused a 15% increase in VO2 and a 25% rise in VE compared to normal walking. Increases were found also in perceived exertion. The physical and physiological loadings associated with recreational golf were deemed to be light to moderate and do not denote undue strain in occasional practices.

Adult↗
PubMed1993

L-NG-nitro arginine p-nitroanilide (L-NAPNA) is anti-nociceptive in the mouse.

L-NG-nitro arginine p-nitroanilide (L-NAPNA), L-NG nitro arginine methyl ester (L-NAME) and L-NG-monomethyl arginine (L-NMMA) inhibit rat cerebellar nitric oxide synthase (NOS) with IC50s of 1.4 +/- 0.1 microM, 0.81 +/- 0.16 microM and 5.1 +/- 0.07 microM respectively. L-NAPNA inhibits the late phase of formalin-induced hindpaw licking (ED50, 57.2 mg kg-1) and acetic acid induced abdominal constrictions (ED50, 25 mg kg-1) in the mouse. L-NAPNA is approximately 65 times less active than L-NAME as an inhibitor of endothelium-dependent relaxation in the rabbit aorta and about 10 fold less potent as a vasopressor in the anaesthetized mouse. LNAPNA shows some degree of selectivity for the central NOS isoform and may be of clinical interest for the treatment of pain.

Amino Acid Oxidoreductases↗
PubMed1993

The risk of alcohol.

We have reviewed 156 papers which provided sufficient information to relate individual alcohol consumption to risk for a variety of physical damage. Overall, there was evidence for a dose-response relationship between level of alcohol consumption and risk of harm for liver cirrhosis, cancers of the oropharynx, larynx, oesophagus, rectum (beer only), liver and breast, and blood pressure and stroke. An increased risk of cardiac arrhythmias, cardiomyopathy and sudden coronary death was associated with heavy drinking. There was evidence for a protective effect of alcohol consumption against risk of coronary heart disease, which could be achieved at consumption levels of less than 10 g alcohol a day. The mortality of non-drinkers was higher than that of moderate drinkers in some studies. Level of alcohol consumption and total mortality were dose-related when non-drinkers were excluded. The finding of a dose-relationship between alcohol and harm suggested causality. It was not possible to define individual risk for all harms at a given level of alcohol consumption because of variations in methodology, but some idea of the order of magnitude of the increased risk can be obtained from calculating trends of pooled log-odds ratios. At levels of alcohol consumption of more than 20-30 g a day, all individuals are likely to accumulate risk of harm. Current guidelines on upper limits of lower risk drinking in different countries (168-280 g of alcohol a week for men and 84-140 g a week for women) reflect levels at which the risk of total mortality is not greatly increased above one.

Alcohol Drinking↗
PubMed1993

7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure.

7-Nitro indazole (7-NI) inhibits mouse cerebellar nitric oxide synthase (NOS) in vitro with an IC50 of 0.47 microM. Following i.p. administration in mice, 7-NI (10-50 mg kg-1) produces dose-related anti-nociception as evidenced by an inhibition of late phase (15-30 min) but not early phase (0-5 min) hindpaw licking time following subplantar injection of formalin (10 microliters, 5% v/v). The ED50 for this effect was 26 mg kg-1 (equivalent to 159.5 mumol kg-1). Similar i.p. administration of 7-NI (20 and 80 mg kg-1) in urethane-anaesthetized mice failed to increase MAP. Thus, 7-NI is a novel inhibitor of NOS which exhibits selectivity for the brain enzyme. Accordingly, 7-NI may be a useful starting point for the development of selective, centrally acting NOS inhibitors devoid of cardiovascular side effects and as a tool to study the central pharmacological effects of nitric oxide (NO).

Amino Acid Oxidoreductases↗
PubMed1993

Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects.

1. 7-Nitro indazole (7-NI, 10-50 mg kg-1), 6-nitro indazole and indazole (25-100 mg kg-1) administered i.p. in the mouse produce dose-related antinociception in the late phase of the formalin-induced hindpaw licking and acetic acid-induced abdominal constriction assays. The ED50 values (mg kg-1) were as follows: 7-NI (27.5 and 22.5), 6-nitro indazole (62.5 and 44.0) and indazole (41.0 and 48.5) in the two assays respectively. 3-Indazolinone, 6 amino indazole and 6-sulphanilimido indazole (all 50 mg kg-1) were without effect. With the exception of 5-nitro indazole (50 mg kg-1) which produced sedation, none of the other indazole derivates examined caused overt behavioural changes. 2. The antinociceptive effect of 7-NI (25 mg kg-1, i.p.) in the late phase of the formalin-induced hindpaw licking assay was partially (46.7 +/- 16.2%, n = 18) reversed by pretreatment with L- but not D-arginine (both 50 mg kg-1, i.p.). 3. The time course of 7-NI induced antinociception in the mouse was correlated with inhibition of brain (cerebellum) nitric oxide synthase (NOS) activity. Maximum antinociceptive activity and NOS inhibition was detected 18-30 min following i.p. administration. In contrast, no antinociceptive effect or inhibition of cerebellar NOS was detected 75 min post-injection. 4. 7-NI, 6-nitro indazole, indazole, 3-indazolinone and 6-amino indazole (all 50 mg kg-1) failed to influence mean arterial pressure (MAP) over the 45 min after i.p. administration in the anaesthetized mouse. Similarly, 7-NI (25 mg kg-1) administered i.v. in the anaesthetized rat did not increase MAP or influence the vasodepressor effect of i.v. injected acetylcholine (ACh) over the same period.5. 7-NI (100 microM) did not influence the vasorelaxant effect of ACh (IC50, 0.2 +/- 0.04 microM, cf. 0.16+/-0.06 microM, n = 6) in phenylephrine-precontracted rabbit aortic rings.6. These data provide further evidence that antinociception following administration of 7-NI in the mouse results from inhibition of central NOS activity and is not associated with inhibition of in vivo vascular endothelial cells NOS. Accordingly, 7-NI (or a derivative thereof) may provide an alternative approach to the development of novel antinociceptive drugs.

Amino Acid Oxidoreductases↗
PubMed1993

Intensive conventional insulin therapy for type II diabetes. Metabolic effects during a 6-mo outpatient trial.

OBJECTIVE: To determine whether tight glycemic control can be obtained using intensive conventional split-dose insulin therapy in the outpatient management of type II diabetes without development of unacceptable side effects. RESEARCH DESIGN AND METHODS: Fourteen type II diabetic subjects were treated with an intensive program of conventional insulin (subcutaneous NPH and regular insulin before breakfast and supper) for 6 mo. Insulin dose adjustments were based on an algorithm built on frequent CPG measurements (4-6 times/day). Patients were monitored biweekly as outpatients and admitted 1 day/mo for metabolic evaluation. RESULTS: Glycemic control was achieved by 1 mo (mean plasma glucose fell from 17.5 +/- 0.9 to 7.7 +/- 0.7 mM, P < 0.001) and remained in this range thereafter. Hypoglycemic events at 1 mo were infrequent (mean +/- SE events per patient per month: 4.1 +/- 0.3) and mild in nature, and progressively decreased to 1.3 +/- 0.5 events/mo by 6 mo. After treatment, basal HGO fell 44% from 628 +/- 44 to 350 +/- 17 mumol.m-2.min-1 (P < 0.001), and maximal rates of glucose disposal measured by hyperinsulinemic euglycemic clamp (1800 pmol.m-2.min-1) improved from 1418 +2- 156 to 1657 +/- 128 mumol.m-2.min-1 (P < 0.05). The total dose of exogenous insulin required was 86 +/- 13 U at 1 mo and 100 +/- 24 U at 6 mo. During treatment, mean serum insulin levels increased from 308 +/- 80 to 510 +/- 102 pM (P < 0.05), while body weight increased from 93.5 +/- 5.8 to 102.2 +/- 6.8 kg (P < 0.001). Both pre- and posttreatment glucose disposal rates correlated with the total exogenous insulin dose required to achieve glycemic control (r = -0.75 and -0.78, both P < 0.005). Weight gain was inversely related to the pretreatment glucose disposal rate (r = -0.53, P < 0.05) and directly correlated with both mean day-long serum insulin level (r = 0.67, P < 0.01) and total exogenous insulin dose (r = 0.62, P < 0.02). CONCLUSIONS: Intensive CIT, when combined with CBG measurements, can be used to rapidly improve glycemic control in type II diabetes without development of unacceptable hypoglycemia. This degree of metabolic improvement, however, requires large doses of exogenous insulin to overcome peripheral insulin resistance and results in greater hyperinsulinemia with progressive weight gain.

Algorithms↗