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Biomedical subjects

C Crawford

Publications and source records attributed to C Crawford.

At least 37 records · Page 2Linked to original sources

Sleep abnormalities demonstrated by home polysomnography in teenagers with chronic fatigue syndrome.

To provide objective information about sleep physiology in young people with chronic fatigue syndrome (CFS), home polysomnography (PSG) was performed on 18 teenagers, aged 11-17 years, in whom CFS had been diagnosed according to internationally accepted criteria. The results were compared with those for healthy controls matched individually for gender and age. Compared with controls, CFS subjects showed significantly higher levels of sleep disruption by both brief and longer awakenings. Disruption of sleep in this way could at least contribute to the daytime symptoms of young people with CFS. The underlying cause of the disruption needs to be considered in each individual case. Further research is required to clarify the relative contribution of this neurobiological aspect of CFS in young people.

Adolescent↗

Development of a walking test for the assessment of functional capacity in non-anaemic maintenance dialysis patients.

BACKGROUND: Walk tests may be useful adjuncts or even alternatives to the assessment of peak oxygen uptake (VO2 peak) in patients with low functional capacity. Walk tests are easy to administer, appear to be well tolerated by patients and may represent a more meaningful measure for a patient group as they assess capability as well as fitness. However, the use of walk tests for the assessment of functional capacity in maintenance dialysis patients has received scant attention. The aim of this study was to assess the validity of a walking-stair-climbing test to predict VO2 peak in non-anaemic maintenance dialysis patients. METHODS: In the validation phase of the study, 14 subjects completed a cycle ergometer-graded exercise test (GXT) for the determination of VO2 peak and a walking-stair-climbing task (WALK), each separated by a period of 7 days. Three weeks later, 18 subjects completed two WALK tests, each separated by a period of at least 48 h, to facilitate reliability estimation. Estimates of differentiated and undifferentiated ratings of perceived exertion (RPE) were obtained during and immediately consequent to all exercise tests. RESULTS: VO2 peak (ml kg min) was significantly correlated with total WALK time (s) (r = -0.83; P < 0.001). VO2 peak (ml/kg/min) could be predicted from total WALK time with a standard error of prediction of 11%. Reliability assessment revealed no significant differences for any aspect of the WALK test performance, with intraclass correlation coefficients ranging from r = 0.71 (RPElegs) to 0.96 (total WALK time). CONCLUSION: These results indicate that the WALK test is a valid, reliable and potentially useful method by which to assess the functional capacity of non-anaemic maintenance dialysis patients.

Aged↗

Sleep and psychological disturbance in nocturnal asthma.

Subjective and objective sleep disturbance was studied in children with nocturnal asthma. Relations between such disturbance and daytime psychological function were also explored, including possible changes in learning and behaviour associated with improvements in nocturnal asthma and sleep. Assessments included home polysomnography, parental questionnaires concerning sleep disturbance, behaviour, and mood and cognitive testing. Compared with matched controls, children with asthma had significantly more disturbed sleep, tended to have more psychological problems, and they performed less well on some tests of memory and concentration. In general, improvement of nocturnal asthma symptoms by changes in treatment was followed by improvement in sleep and psychological function in subsequent weeks. The effects of asthma on sleep and the possible psychological consequences are important aspects of overall care.

Adolescent↗

Postnatal development of glutamate receptor-mediated responses in the neostriatum.

Three experimental approaches were used to examine the maturation of N-methyl-D-aspartate (NMDA) receptors in the neostriatum and compare their developmental profile to that of the non-NMDA receptors [alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (KA)]. The first, and least conventional approach utilized infrared videomicroscopy to measure NMDA-induced swelling in single cells in a brain slice. The results demonstrated that NMDA receptors display an incremental pattern of postnatal development with no responses at postnatal day (PND) 3, weak responses at PND 7, the largest responses by PND 14 and slight decreases at PNDs 21 and 28. At PNDs 3 and 7, KA-induced cell swelling was proportionately greater than NMDA-induced cell swelling suggesting earlier maturation of this non-NMDA receptor subtype. The second approach used whole-cell patch clamp analysis to examine NMDA currents and compare their maturation to AMPA/KA-induced currents. Though the data are still preliminary, a very similar developmental pattern emerged. NMDA-induced currents were small and developed slowly after PND 7. In contrast, AMPA/KA-induced currents were larger and appeared to develop earlier. Finally, dizocilpine (MK-801) binding was measured in homogenates of neostriatal tissue. The ontogeny of binding resembled a step function with increases between PNDs 3 and 7 and PNDs 14 and 21. Binding peaked at PND 28 and then declined slightly in the adult (PND 60). The affinity of MK-801 for the receptor did not change during postnatal development. These findings demonstrate the pattern of functional development of glutamate receptors in the neostriatum. The NMDA receptor subtype displays minimal functional development until PND 14. In contrast, neostriatal AMPA/KA receptor function appears to precede NMDA receptor function.

Aging↗

Reaching seriously at-risk populations: health interventions in criminal justice settings.

More than 6 million people are under some form of criminal justice supervision in the United States on any given day. The vast majority are arrested in and return to urban, low-income communities. These are men, women, and adolescents with high rates of infectious diseases such as HIV/AIDS, other sexually transmitted diseases (STDs), and tuberculosis (TB), as well as substance abuse and other health problems. A review of recent literature indicates that an increasing problem for these populations is that they have had little prior access to primary health care or health interventions, and many are returning to their communities without critical preventive health information and skills, appropriate medical services, and other necessary support. Periods of incarceration and other criminal justice supervision offer important opportunities to provide a range of health interventions to this underserved population, and general evaluations show the potential for this strategy. Public health and criminal justice agencies have the expertise and should collaborate to provide interventions needed by incarcerated populations. Moreover, many recently released inmates require primary care for HIV/AIDS, other STDs, and TB. Consequently, timely discharge planning is essential, as are linkages with community-based organizations and agencies that can provide medical care, health education, and necessary supportive services.

Adolescent↗

Home polysomnography norms for children.

Home polysomnography (PSG) by means of ambulatory monitoring systems has distinct advantages over sleep laboratory recordings, especially for children. However, normative data have been lacking. Norms for conventional PSG variables were compiled for 60 children age 5-16 years using the Oxford Medilog ambulatory monitoring system. Recordings were confined to a single night in view of previous demonstrations that the sleep on the first night is not significantly affected by the recording procedure. The results are presented in 5 age subgroups. Broad comparisons with published laboratory PSG norms for children of the same ages suggest that in home recordings sleep duration is longer, and slow wave sleep is much more pronounced with a commensurate reduction in stage 2 NREM sleep. That is, sleep quality and quantity appears better at home even when adaptation to the laboratory situation has been promoted. These new normative data are considered valuable for both clinical and research purposes where physiological sleep studies in children are required.

Adolescent↗

An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD)

The objectives of this study were to compare the efficacy and safety of salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added to existing therapy, in the treatment of patients with chronic obstructive pulmonary disease (COPD). Six hundred and seventy four patients were randomized to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or placebo treatment for a period of 16 weeks. The results showed a significant improvement in daily symptom scores noted for patients taking either 50 microg (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a corresponding decrease in additional daytime salbutamol requirements for both salmeterol groups. The same pattern was reflected for night-time symptoms and additional salbutamol use. During treatment, forced expiratory volume in one second (FEV1) measurements improved significantly in each salmeterol group, with up to a 7% improvement observed at the end of the study. Although no difference was observed between treatment groups for the distance walked in 6 min, patients treated with salmeterol 50 microg b.i.d. were significantly less breathless than those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16 weeks (p=0.004) of therapy. Adverse events were similar in all three groups except for tremor, which was significantly higher in the 100 microg b.i.d. salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and placebo. Salmeterol offered further positive improvement to the effect of therapy in patients with chronic obstructive pulmonary disease when added to their existing regimens. This clinical improvement was similar both with 50 and 100 microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the drug better than those receiving 100 microg b.i.d. salmeterol.

Adult↗

Modulatory actions of dopamine on NMDA receptor-mediated responses are reduced in D1A-deficient mutant mice.

The role of D1 dopamine (DA) receptors in mediating the ability of DA to modulate responses attributable to activation of NMDA receptors was examined in mice lacking D1A dopamine receptors. Specifically, experiments were designed to test the hypothesis that the ability of DA to potentiate responses mediated by activation of NMDA receptors was attributable to activation of D1 receptors. Based on this hypothesis, we would predict that in the D1A mutant mouse, either DA would not induce enhancement of NMDA-mediated responses, or the enhancement would be severely attenuated. The results provided evidence to support the hypothesis. In mutant mice, DA and D1 receptor agonists did not potentiate responses mediated by activation of NMDA receptors. In contrast, in control mice, both DA and D1 receptor agonists markedly potentiated responses mediated by activation of NMDA receptors. The effects of DA in attenuating responses mediated by activation of non-NMDA receptors also were altered in the mutant, suggesting that this action of DA may require coupling or interactions between D1 and D2 receptors. The present studies also provided an opportunity to assess some of the basic electrophysiological and morphological properties of neostriatal neurons in mice lacking D1A DA receptors. Resting membrane potential, action potential parameters, input resistance, excitability, somatic size, dendritic extent, and estimates of spine density in mutants and controls were similar, suggesting that these basic neurophysiological and structural properties have not been changed by the loss of the D1A DA receptor.

Animals↗

Investigation of the interaction of m-calpain with phospholipids: calpain-phospholipid interactions.

Phosphatidyl inositol, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidic acid and sphingomyelin were all found to be effective at reducing the Ca2+ requirement for m-calpain autolysis. In the absence of phospholipid, pig kidney m-calpain required 1.4 mM Ca2+ for 50% autolysis under the assay conditions used. Phospholipids caused a reduction in this Ca2+ requirement to a value between 0.45 mM Ca2+ for phosphatidyl glycerol and 1.1 mM Ca2+ for phosphatidyl ethanolamine. Previous studies (Crawford, C., Brown, N.R. and Willis, A.C. (1990) Biochem. J. 265, 575-579) have shown that the most probable site for phospholipid interaction in calpain is the N-terminal region between residues 39 to 62 of the small subunit of calpain (G17TAMRILGG). In this study we examine the possible role of this G17TAMRILGG region. Three synthetic peptides corresponding to parts of this sequence were used to examine the phospholipid binding sequence. Analysis of the phospholipid vesicle binding properties of these peptides suggested that both the TAMRIL and polyglycine sequences were required for binding to phosphatidyl inositol vesicles.

Amino Acid Sequence↗

Mandibular alveolar ridge augmentation in the dog using distraction osteogenesis.

PURPOSE: This study investigated the use of distraction osteogenesis for alveolar ridge augmentation. MATERIALS AND METHODS: Four dogs each had two superior and two inferior implants placed horizontally into an edentulous mandibular quadrant and, after integration, a distraction device was applied. An osteotomy was made to allow the ridge to be distracted vertically. After 10 mm vertical distraction, the device was stabilized. RESULTS: The vertical augmentation averaged 8.85 +/- 1.05 mm after 10 weeks of healing. Serial sections showed that bone had formed between the distracted segments, creating an augmented ridge. CONCLUSIONS: Distraction osteogenesis has the potential for use in augmentation of the alveolar ridge.

Alveolar Ridge Augmentation↗

Protecting the weakest link: a proposal for universal, unblinded pediatric HIV testing, counselling and treatment.

This paper argues that a system of unblinded, universal testing, counseling and treatment for pediatric HIV should be implemented immediately in New York State. First, it argues that New York's health and social services bureaucracies, in conjunction with special interests that do not represent the interests of children, have resisted efforts to have infants tested and treated for HIV. Second, the paper suggests that the campaign against universal infant screening and treatment reflects our society's continuing, calculated decision to ignore the complexity of the HIV/AIDS epidemic. Third, the paper outlines a plan for a prompt and comprehensive system of HIV testing, counseling and treatment for infants and children, as well as for their parents and families, who are HIV-positive. In the process of articulating the above positions, the paper documents the failure of universal blinded infant HIV screening in New York since 1987. It further explores the inadequacies of the proposed efforts by state and city regulatory authorities to improve the testing and counseling available for pediatric HIV. Although encouraged by New York State's recent move aggressively to test and treat HIV-positive infants and children in foster care, the paper argues that this effort must be expanded to apply to the entire newborn population. Finally, the paper examines in detail the limitations of testing and counseling provided to children in the foster care system.

Child↗

The calpain cleavage sites in the epidermal growth factor receptor kinase domain.

The proteolysis of the human epidermal growth factor receptor cytoplasmic domain by calpain has been studied in vitro using purified recombinant cytoplasmic domain expressed in insect cells. Limited proteolysis produced kinase that was truncated at either N- or C-termini, as well as in the hinge region. We identified seven sites of calpain proteolysis by N-terminal sequencing of purified fragments. Calpain cleaved between the catalytic and autophosphorylation domains at two sites in the sequence Gln996-Asp1059, in the hinge region. Three new sites were also found in the autophosphorylation domain, preceding each of the major autophosphorylation sites. A fourth new site was located in the juxta-membrane domain, C-terminal to the regulatory Thr654. We purified an active 42-kDa fragment generated by calpain proteolysis between Leu659-Gln660 in the juxta-membrane domain, and in the hinge region. A fifth new site of calpain cleavage was found between the nucleotide binding motif Gly-Xaa-Gly-Xaa-Xaa-Gly and the essential Lys721 in the catalytic core of the kinase. Since both of these features are required for catalysis, calpain cleavage at this site may potentially provide a mechanism for down-regulation of kinase activity in vivo, under conditions of calpain activation. Thus the distribution of calpain cleavage sites along the kinase domain is consistent with a role for calpain both as a processing and as a degradative protease in epidermal growth factor receptor signalling.

Amino Acid Sequence↗

Protein kinase C V3 domain mutants with differential sensitivities to m-calpain are not resistant to phorbol-ester-induced down-regulation.

Distinct linker sequences were introduced into the protease-sensitive V3 domain of protein kinase C-alpha and the mutant proteins were expressed in COS-1 cells. Partially purified preparations of these mutants were functionally similar to wild-type protein kinase C-alpha, however their susceptibility to m-calpain was quite distinct, with one mutant being insensitive to cleavage. The three mutants, after expression in COS-1 cells, were found to behave in a manner indistinguishable from wild-type protein kinase C-alpha with respect to subcellular distribution, acute responses to 12-O-tetradecanoyl-phorbol 13-acetate and 12-O-tetradecanoyl-phorbol-13-acetate-induced down-regulation. The data imply that down-regulation of protein kinase C-alpha is likely to involve a general degradative process rather than cleavage by a site-specific protease.

Amino Acid Sequence↗

A comparison of six different plating media used in the isolation of Salmonella.

Seventeen Canadian Federal, Provincial and Public Health Laboratories took part in different phases of a comparative/collaborative study that evaluated rapid methods to the standard Health Protection Branch (HPB) method for the detection of Salmonella. A variety of commercial media were tested, including Brilliant Green Sulpha Agar, Bismuth Sulphite Agar, Hektoen Enteric Agar, Xylose Lysine Deoxycholate Agar, EF-18 Agar and Rambach Agar. Each laboratory compared up to six of these different plating media. Plating of 123 salmonellae cultures and 28 artificially-inoculated foods showed the recovery of Salmonella spp. on the six plating media to be within one log. Therefore, quantitative testing of the media showed them to be comparable in the recovery of salmonellae. Qualitative testing of the six media during the comparative/collaborative study of various methods showed that EF-18 Agar recovered the greatest number of isolates. Hektoen Enteric Agar ranked second, with the other agars being comparable in their recovery of Salmonella spp. Problems with the various media are summarized. Based on our results and those of other researchers, it is recommended that Bismuth Sulphite Agar be compulsory and that at least one other agar be used for newly developed cultural procedures.

Bacteriological Techniques↗

Cerebrospinal fluid rhinorrhoea and Haemophilus influenzae meningitis 37 years after a head injury.

Bacterial meningitis secondary to CSF rhinorrhoea is well recognised. We present a case of meningitis due to Haemophilus influenzae type b associated with a CSF fistula. The patient was 40 years of age at presentation, having sustained a head injury when 3-years-old. He had suffered intermittent rhinorrhoea for 18 months before admission. Delays between head injury and meningitis are well recognised, but our case may represent the longest recorded interval. H. influenzae meningitis in adults is discussed.

Adult↗

The TAPS Project. 22: A five-year follow-up of long-stay psychiatric patients discharged to the community.

A group of 114 long-stay patients in Friern and Claybury Hospitals was assessed while in hospital, and then again one year and five years after discharge to community placements. Neurotic symptoms, verbal and non-verbal behaviour and, most notably, negative symptoms all improved between the two community follow-up interviews. Patients were living under much less restrictive conditions in the community, and their appreciation of this freedom continued to grow over the years. Their social networks were enriched by an increase in the number of friends in the first year after discharge and in the number of confidants in the subsequent four years. There were no adverse outcomes, but these conclusions cannot yet be said to apply to all long-stay residents of mental hospitals.

Activities of Daily Living↗