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Biomedical subjects

J Gibbs

Publications and source records attributed to J Gibbs.

At least 55 records · Page 3Linked to original sources

The biochemical investigation of epilepsy in childhood.

Metabolic disorders are a relatively uncommon, but important, cause of childhood seizures. Routinely searching for a metabolic disorder in epilepsy is usually unrewarding. Children and adolescents with epilepsy can be selected for appropriate biochemical investigation by considering the seizure type, age of onset, EEG appearance, family history, clinical findings and the results of brain imaging. A limited number of biochemical screening tests can be used to categorize the more common metabolic disorders associated with seizures.

Adolescent↗

An evaluation of nebulized prostacyclin in patients with primary and secondary pulmonary hypertension.

AIMS: To investigate the response to inhaled prostacyclin in patients with primary and secondary pulmonary hypertension and to compare its effects to those of intravenous prostacyclin and inhaled nitric oxide. METHODS AND RESULTS: Twelve patients with pulmonary hypertension (seven primary and five secondary) were studied. All patients had a pulmonary artery balloon flotation catheter inserted into the proximal pulmonary artery and radial arterial line. Prostacyclin was nebulized with 81.min-1 of oxygen and administered in doses increasing from 15 to 50 ng.kg-1.min-1 via a facemask. Eight of these patients also received intravenous prostacyclin in doses of 1 to 5 ng.kg-1.min-1 and nitric oxide in doses of 10 to 100 ppm via a facemask. Haemodynamic measurements were taken during each treatment. In the 12 patients, nebulized prostacyclin produced a significant reduction in mean pulmonary artery pressure from 56 +/- 5 to 45 +/- 4 mmHg (P = 0.0001). The pulmonary vascular resistance decreased by 38% from 964 +/- 169 to 595 +/- 116 dyne.s-1.cm-5 (P = 0.0001). Direct comparison with inhaled nitric oxide and intravenous prostacyclin in eight patients demonstrated that nebulized prostacyclin produced a greater fall in mean pulmonary artery pressure than the other two agents without any significant effect on systemic arterial pressure. CONCLUSION: Nebulized prostacyclin appears to be more effective at reducing pulmonary artery pressure in patients with pulmonary hypertension when compared to intravenous prostacyclin and inhaled nitric oxide. This could have important clinical implications for the management of patients with pulmonary hypertensions.

Administration, Inhalation↗

Predictors of decline in manual performance in older adults.

OBJECTIVE: To determine factors that predict decline in manual performance using a multivariate model of determinants of functional limitation. DESIGN: Longitudinal observational study. SETTINGS: Ambulatory general medicine clinics, residences of homebound individuals, and a continuing care retirement community. PARTICIPANTS: Subjects were 485 persons more than 60 years of age and included continuing care retirement community (CCRC) residents (n = 215), chronically homebound older persons (n = 65), and ambulatory older adults (n = 205). Mean age at baseline was 78 years. MEASUREMENT: Independent variables included demographics, physician measures of upper-extremity joint impairment, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variable was 2-year decline in timed manual performance below a threshold associated with need for long-term care services. RESULTS: The proportion of subjects who exceed a Timed Manual Performance Test threshold of 350 seconds increased slowly from baseline through Year 4 for all age groups but rose rapidly from Year 4 to Year 6 for the oldest group (> 85 years at baseline). Using a discrete survival model, we found that age, education, grip strength, and psychological status predicted crossing the manual performance threshold within a 2-year period. CONCLUSIONS: The findings, coupled with earlier findings that upper extremity joint impairment predicted both grip strength and manual performance, suggest that joint impairment may be an important risk factor for future functional limitation. Since diminished hand function has been shown to predict dependency, development and testing of interventions to maintain or restore upper extremity joint function and reduce pain would appear to be a high research priority.

Age Factors↗

Vena caval bombesin infusion decreases spontaneous meal size in undisturbed rats.

The amphibian tetradecapeptide bombesin (BN) decreases food intake in both humans and animals. Studies have typically examined the effects of BN on scheduled meals in deprived subjects. To investigate the properties of this peptide under more naturalistic conditions, we examined the effects of BN in spontaneously feeding rats. Undisturbed, ad lib-fed male rats (n = 9) with chronic inferior vena caval catheters were infused with saline vehicle and each of 3 doses (2, 4, and 8 micrograms/kg) of BN in counterbalanced order with intervening noninfusion days. Infusions were remotely activated at the onset of the first nocturnal meal and continued for 3 min (34 microliters/min), delivery being completed within the first 2 min of infusion. Feeding was measured via electronic balances linked to a computer. All doses of the peptide significantly decreased the size and duration of the first nocturnal meal. In addition, 4 and 8 micrograms/kg of BN significantly shortened the intermeal interval from the end of the first meal to the beginning of the second meal. Despite this, the satiety ratio (interval/meal size) tended to increase after BN and was significantly increased by the highest dose (8 micrograms/kg), thus indicating a sustained satiety action of the peptide. In summary, these results show that brief, meal-contingent intravenous infusions of BN potently inhibit spontaneous feeding in undisturbed rats.

Animals↗

Simultaneous administration of neuromedin B-10 and gastrin-releasing peptide(1-27) reproduces the satiating and microstructural effects of bombesin.

Bombesin (BN) suppresses food intake more than an equimolar dose of neuromedin B-10 (NMB-10) or gastrin-releasing peptide(1-27) [GRP(1-27)]. Because BN is active at both NMB- and GRP-preferring receptors, it is possible that its greater potency is due to the simultaneous activation of both receptor subtypes. This hypothesis was tested by administering a mixture of NMB-10 and GRP(1-27). The results were consistent with our hypothesis: administration of the mixture of NMB-10 and GRP(1-27) produced an inhibition of intake volume and total licks equivalent to that seen after an equimolar dose of BN and resulted in similar changes in the rate and pattern of licking.

Animals↗

Brief, meal-contingent infusions of gastrin-releasing peptide1-27 and neuromedin B-10 inhibit spontaneous feeding in rats.

We have previously shown that brief, meal-contingent infusions of the amphibian peptide bombesin (BN) reduce meal size in spontaneously feeding rats. These inhibitory effects presumably reflect actions of BN on receptors for its mammalian homologues, which include gastrin-releasing peptide1-27 (GRP) and neuromedin B-10 (NMB). In the present study, we used the spontaneous feeding paradigm to explore the effects of meal-contingent infusions of these mammalian homologues. Undisturbed, ad lib-fed male rats (n = 12) with chronic inferior vena caval catheters were infused with saline, 5 nmol/kg GRP, 5 nmol/kg NMB, and a mixture of 5 nmol/kg GRP and 5 nmol/kg NMB in counterbalanced order, with intervening noninfusion days. Infusions were remotely activated at the onset of the first nocturnal meal and continued for 3 min (34 microliters/min), delivery being completed within the first 2 min of infusion. Feeding was measured via electronic balances linked to a computer. The effects of all peptide conditions were confined to the first nocturnal meal. Significant and comparable decreases in the size and duration of this meal were observed with GRP, NMB, and GRP + NMB, with no significant effects on the intermeal interval or satiety ratio (intermeal interval/meal size). Thus, brief vena caval infusions of GRP and NMB, given alone or together at the onset of the first nocturnal meal, significantly reduced meal size and duration in spontaneously feeding rats.

Animals↗

The management of febrile seizures in the Mersey Region.

The management of children with febrile seizures admitted to hospital within the Mersey region was evaluated by case note review. The patient groups were demographically similar in all the participating hospitals. Most children were admitted for less than 48 hours and nearly all received paracetamol as an antipyretic. There was a marked variation in the number of investigations performed in each hospital, with venepunctures for blood cultures and white blood cell counts ranging from 6 to 56% and from 8 to 70%, respectively. The majority of children had a urinalysis. 23 to 78% of children were prescribed antibiotics. Further studies are required on the value of hospital admission and the appropriate use of investigations and antibiotics in children with febrile seizures.

Acetaminophen↗

Predictors of change in walking velocity in older adults.

OBJECTIVE: To determine factors that predict change in walking velocity in older people using a multivariate model. DESIGN: Longitudinal observational study. SUBJECTS: A total of 588 persons older than age 60, including subjects residing in a continuing care retirement community (CCRC) (n = 248), and homebound (n = 79) and ambulatory (n = 261) subjects. Mean age at baseline = 77. MEASUREMENT: Independent variables included demographics, physician measures of lower-extremity joint impairment and other musculoskeletal and neurological variables, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variables were 2- and 4-year decline in walking velocity below a threshold associated with nursing home placement. MAIN RESULTS: From baseline to Year 4, median walking velocity declined from 61.8 to 53.0 m/min, and the proportion of subjects above a threshold value of 11.5 m/min declined from 95.3% to 80.4%. Age, joint impairment, and weakness of quadriceps, measured at baseline, predicted 2-year and 4-year decline in walking velocity. CONCLUSIONS: The findings indicate that joint impairment and quadriceps strength contribute significantly to crossing a clinically significant threshold in walking velocity among older people over time. Future research is needed to determine whether these risk factors can be modified through preventive interventions such as muscle-strengthening exercises and pain medication.

Activities of Daily Living↗

Cutaneomuscular reflexes recorded from the lower limb in man during different tasks.

1. Cutaneomuscular reflexes have been recorded in ten adult subjects from extensor digitorum brevis (EDB), tibialis anterior (TA), soleus (Sol), quadriceps femoris (Quad) and erector spinae (ES) following electrical stimulation of the digital nerves of the second toe. 2. Recordings were made while subjects were instructed to activate voluntarily the relevant muscles and also when these muscles were active posturally. 3. Reflex responses could comprise three components: an initial increase in EMG (E1), followed by a decrease (I1), followed by a second increase (E2). E1 and I1 were confined to muscles acting at the ankle and in the foot. E2 was most pronounced in EDB but also found in TA, Sol, Quad (1 subject) and ES. No responses were recorded contralateral to the stimulus. 4. E2 was significantly larger when the reflex was recorded during voluntary contraction of the muscle, rather than when the muscle was active posturally. 5. E1 and I1 components are mediated via spinal pathways. E2 requires the integrity of the dorsal columns, sensorimotor cortex and corticospinal tract (Jenner & Stephens, 1982; Rowlandson & Stephens, 1985b). The present study suggests that one or more of these supraspinal pathways is more active during voluntary contraction of lower limb muscles than when these muscles are active posturally.

Adult↗

Organization of inputs to motoneurone pools in man.

1. Surface EMGs were recorded from pairs of muscles involved in movements of the wrist and/or digits in the upper limb and from pairs of intrinsic foot muscles in the lower limb during voluntary isometric contractions. 2. EMGs were also recorded from lower limb and trunk muscles during three different tasks: lying, standing and balancing. 3. To investigate if the co-contraction of muscles was due to the presence of a common drive to each of the two motoneurone pools, cross-correlation analysis of the two multiunit EMG signals was used. 4. Evidence for a common drive was seen between pairs of muscles that share a common joint or joint complex (such as the metacarpophalangeal joints); no evidence was found for a common drive to co-contracting muscles that did not share a common joint. 5. When considering analogous hand and foot muscle pairs, the degree of synchrony was significantly greater for lower limb pairs. 6. Where a common drive was detected with lower limb muscle pairs, the degree of synchrony was significantly larger during balancing than during either lying or standing. 7. The origin of the common drive is discussed. It is concluded that activity in both last-order branched presynaptic fibers and presynaptic synchronization is involved.

Adult↗

The determinants of walking velocity in the elderly. An evaluation using regression trees.

OBJECTIVE: To determine predictors of walking velocity in the elderly. METHODS: Five hundred thirty-two persons from 3 cohorts of elderly persons (retirement community, ambulatory care medical clinic, or chronically homebound population) performed a 10-foot (for the homebound subjects) or 50-foot (for all other subjects) walk time test and underwent a standardized interview, chart review, and clinical examination. The 73 independent variables that were evaluated included demographic, musculoskeletal, neurologic, psychologic, and other comorbidity items. Least-squares and least-absolute-deviation regression tree analyses were performed to determine the strongest predictive factors associated with walking velocity. RESULTS: Sampling cohort (homebound versus non-homebound), quadriceps strength, hip flexion strength, lumbosacral spine impairment, lower joint impairment, and education were found to be associated with walking velocity. Joint pain measures were not associated with walking velocity. CONCLUSION: Muscle strength variables are better predictors of walking velocity than are joint pain variables. Thus, clinical trials and observational studies using walking velocity as an outcome need to take into consideration the influence of muscle strength on this outcome variable.

Aged↗

Odor-induced inhibition of intake after pairing of odor and CCK-8 in neonatal rats.

This study determined whether an odor that was paired with injections of CCK octapeptide would later come to inhibit independent feeding in neonatal rats. An odor so paired in rats that were not food or maternally deprived later reduced feeding during the infants' first independent feeding experience. Devazepide, the CCKA receptor antagonist, blocked the reduced intake when injected prior to the feeding test. These studies demonstrate that CCK is an effective unconditioned stimulus even when the animal is not eating during the conditioning process. Furthermore, the conditioned stimulus (the odor) causes behavioral change either by sensitizing a system that includes the CCKA receptor, by causing the release of endogenous CCK, or by changing some non-CCK system that enhances the processing of CCKA receptor-mediated information.

Animals↗

Prefeeding potentiates anorectic actions of neuromedin B and gastrin releasing peptide.

We report that the anorectic potency of neuromedin B (NMB) and gastrin-releasing peptide (GRP) is potentiated using a prefeed paradigm. During the light phase, adult male Sprague-Dawley rats (groups of n = 6) were given 30-min (pre-feed) access to a liquid diet. Thirty min later rats were injected i.p. with GRP or NMB (0, 8, 16, 32 or 64 micrograms kg-1) and given further access to the liquid diet. In prefed (PF) rats, high doses of NMB (32 and 64 micrograms kg-1) delayed the onset of eating in the test by > 10 min, significantly suppressing 30-min intake. The same doses of NMB in non prefed (NPF) rats were ineffective. Weak effects of GRP in NPF rats to reduce meal size were also enhanced under PF conditions. Exogenous GRP and NMB, in particular, appear to interact with processes stimulated by the postingestive actions of food, supporting a role for peripheral, endogenous GRP and NMB in the development of satiation and the maintenance of postprandial satiety, respectively.

Animals↗

Fourth ventricular injection of the bombesin receptor antagonist [D-Phe6]bombesin(6-13)methyl ester, but not BW2258U89, increases food intake in rats.

To investigate the role of endogenous bombesin-like peptides in the caudal brainstem for the short-term control of food intake, we evaluated the effects of fourth-ventricular injections of two different bombesin (BN) receptor antagonists, [D-Phe6]BN(6-13) methyl ester and BW2258U89, on intake of sweetened, condensed milk in male rats. Although fourth-ventricular administration of BW2258U89 (0.125-20 ng) had no effect on food intake, fourth-ventricular injections of 1.0-20.0 ng of [D-Phe6BN(6-13) methyl ester resulted in an inverted U-shaped, dose-response curve with a maximal effect at 2.5 ng. Microstructural analysis of the licking behavior indicated that the increase in intake was primarily the result of an increased number of licks and an increase in lick efficiency. Behavioral time sampling demonstrated that these changes in intake occurred without the appearance of any competing behavior or significant change in the overall pattern of behavior. Because [D-Phe6BN(6-13) methyl ester appears to be a preferential antagonist at the GRP-preferring receptor, the increased intake that occurred after its administration suggests that an endogenous GRP-mechanism in the caudal brainstem is necessary for the normal, short-term control of sweet milk intake under these conditions.

Animals↗

Meal pattern analysis in rats reveals partial agonist activity of the bombesin receptor antagonist BW2258U89.

The spontaneous feeding behavior of adult male rats was monitored during continuous infusion of the bombesin receptor antagonist BW2258U89 into the coeliac artery (100 micrograms kg-1 h-1) from an osmotic minipump. Nocturnal food intake was suppressed over 5 days of testing. Similar effects followed acute BW2258U89 treatment [100 micrograms kg-1, intraperitoneally (i.p.)]. Moreover, i.p. BW2258U89 mimicked the acute behavioral effects of 2 micrograms kg-1 i.p. bombesin by reducing meal size. Verifying that BW2258U89 can retain its potency throughout the entire period of chronic infusion, we demonstrated that the acute anorectic action of bombesin (4 micrograms kg-1, i.p.) was blocked by pretreatment with a BW2258U89 solution (100 micrograms ml-1 kg-1, i.p.) that was freshly prepared, or incubated for 1 or 6 days at body temperature. These data demonstrate that acute and chronic administration of BW2258U89, at a dose that abolishes the satiety effect of bombesin, significantly suppresses spontaneous feeding. Thus, BW2258U89 appears to attenuate food intake by acting as a partial agonist at peripheral receptors for bombesin-like peptides.

Amino Acid Sequence↗

Cloning of a Schistosoma japonicum gene encoding an antigen with homology to calreticulin.

A recombinant lambda gt11 clone, IVGS3, encoding part of a 55-kDa antigen was isolated from an adult Schistosoma japonicum cDNA library. The protein expressed by this clone was recognised strongly by serum from rats that had been vaccinated with irradiated cercariae (VrS) rendering them highly immune to a challenge infection. Antibodies in VrS which were specific for IVGS3 did not recognise adult worm antigens of S. mansoni, suggesting that the recombinant antigen contains species-specific epitopes, although IVGS3 was weakly recognised by rat serum raised against irradiated S. mansoni cercariae, indicating the presence of a related antigen in this species. A further clone, AM1(p), was obtained which, together with IVGS3 encompasses the entire coding region of the gene which has been called Sj55. Sequence analysis revealed similarities with murine calreticulin, a protein resident in the endoplasmic reticulum. As with murine calreticulin, Sj55 was shown to be a calcium-binding protein. Antigens with homologies to calreticulin have also been described in two other helminths, S. mansoni and Onchocerca volvulus.

Amino Acid Sequence↗

Microstructural analysis of licking behavior following peripheral administration of bombesin or gastrin-releasing peptide.

To determine the effects of bombesin (BN) and gastrin-releasing peptide [GRP(1-27)] on food intake and the microstructure of licking, the rate and pattern of licking were measured by lickometer after intraperitoneal administration of 2, 4, 8, and 16 micrograms/kg of each peptide. Although both peptides inhibited intake significantly, the dose-response functions of the peptides were different. At lower doses (2-4 micrograms/kg) the peptides were equipotent; at higher doses (8-16 micrograms/kg) BN was significantly more potent than GRP(1-27), possibly due to an action of BN on neuromedin B (NMB) receptors. The microstructural results demonstrated that both peptides decreased intake by increasing the rate of decay of licking and decreasing the number of bursts and clusters without changing the initial rate of licking or the size of the bursts and clusters. This combination of microstructural changes is evidence that both peptides increased the postingestive negative feedback effects of the diet without changing the orosensory positive feedback. These results are consistent with, but do not prove, the hypothesis that endogenous GRP(1-27) acts as a postingestive satiety signal in rats.

Animals↗