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Biomedical subjects

J V Cook

Publications and source records attributed to J V Cook.

At least 19 recordsLinked to original sources

Magnesium supplementation for the management of essential hypertension in adults.

BACKGROUND: Epidemiological evidence on the effects of magnesium on blood pressure is inconsistent. Metabolic and experimental studies suggest that magnesium may have a role in the regulation of blood pressure. OBJECTIVES: To evaluate the effects of magnesium supplementation as treatment for primary hypertension in adults. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. SELECTION CRITERIA: Inclusion criteria were: 1) RCTs of a parallel or crossover design comparing oral magnesium supplementation with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or magnesium supplementation was combined with other interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: Twelve RCTs (n=545) with eight to 26 weeks follow-up met our inclusion criteria. The results of the individual trials were heterogeneous. Combining all trials, participants receiving magnesium supplements as compared to control did not significantly reduce SBP (mean difference: -1.3 mmHg, 95% CI: -4.0 to 1.5, I(2)=67%), but did statistically significantly reduce DBP (mean difference: -2.2 mmHg, 95% CI: -3.4 to -0.9, I(2)=47%). Sensitivity analyses excluding poor quality trials yielded similar results. Sub-group analyses and meta-regression indicated that heterogeneity between trials could not be explained by dose of magnesium, baseline blood pressure or the proportion of males among the participants. AUTHORS' CONCLUSIONS: In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of a causal association between magnesium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of magnesium supplementation on blood pressure and cardiovascular outcomes.

Adult↗

Calcium supplementation for the management of primary hypertension in adults.

BACKGROUND: Metabolic studies suggest calcium may have a role in the regulation of blood pressure. Some epidemiological studies have reported that people with a higher intake of calcium tend to have lower blood pressure. Previous systematic reviews and meta-analyses have reached conflicting conclusions about whether oral calcium supplementation can reduce blood pressure. OBJECTIVES: To evaluate the effects of oral calcium supplementation as a treatment for primary hypertension in adults. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. SELECTION CRITERIA: Inclusion criteria were: 1) RCTs comparing oral calcium supplementation with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or calcium supplementation was combined with other interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: We included 13 RCTs (n=485), with between eight and 15 weeks follow-up. The results of the individual trials were heterogeneous. Combining all trials, participants receiving calcium supplementation as compared to control had a statistically significant reduction in SBP (mean difference: -2.5 mmHg, 95% CI: -4.5 to -0.6, I(2 )= 42%), but not DBP (mean difference: -0.8 mmHg, 95% CI: -2.1 to 0.4, I(2) = 48%). Sub-group analyses indicated that heterogeneity between trials could not be explained by dose of calcium or baseline blood pressure. Heterogeneity was reduced when poor quality trials were excluded. The one trial reporting adequate concealment of allocation and the one trial reporting adequate blinding yielded results consistent with the primary meta-analysis. AUTHORS' CONCLUSIONS: In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of calcium supplementation on blood pressure and cardiovascular outcomes.

Adult↗

Antenatal hydronephrosis: negative predictive value of normal postnatal ultrasound--a 5-year study.

AIM: To determine whether normal postnatal ultrasound, as part of a strict screening protocol for the detection and follow-up of antenatal hydronephrosis, effectively excludes the majority of babies with congenital urinary tract abnormalities that would otherwise present with a urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed all babies who had postnatal follow-up of antenatally detected hydronephrosis over a 5-year period at our institution, a district general Trust with a specialist paediatric unit. We then studied all babies presenting with urinary tract infection before their first birthday to our institution over the same period. By cross-referencing these two study groups we were able to determine which babies developed a urinary tract infection having been previously discharged after normal postnatal ultrasound. RESULTS: Four hundred and twenty-five babies had postnatal follow-up of antenatal hydronephrosis. Of these, 284 were investigated with ultrasound alone. In the same 5-year period, 230 babies presented with urinary tract infection before their first birthday. Only three of these babies had been previously discharged after normal postnatal ultrasound. The negative predictive value of a normal postnatal ultrasound was therefore 98.9% (281/284) for babies who subsequently presented with a urinary tract infection before their first birthday. CONCLUSION: Careful antenatal and postnatal ultrasound with strict protocols is effective in detecting congenital renal tract abnormalities. Infants discharged after normal postnatal ultrasound are highly unlikely to still have an undetected urinary tract abnormality. We suggest that all babies with antenatal hydronephrosis are started on prophylactic antibiotics at birth, pending further investigation. All babies without features of severe obstruction antenatally should have their postnatal ultrasound delayed for a month. We recommend selective use of micturating cystourethrogram (MCUG), and delaying this investigation until the baby is 3 to 4 months old to allow for spontaneous resolution of vesicoureteric reflux. We do not believe that all babies with antenatal hydronephrosis require MCUG, providing a clear protocol is followed.

Algorithms↗

Key factors in the optimization of paediatric X-ray practice.

Justification of radiological requests, standardization of procedures and optimization of protection measures are key principles in the protection of individuals exposed to ionizing radiation for diagnostic purposes. Nowhere is this more pertinent than in the imaging of children and, following the recent introduction of the Ionising Radiation (Medical Exposure) Regulations, there is now a regulatory requirement for diagnostic radiology departments to demonstrate compliance with these principles. A study was undertaken to compare all aspects of paediatric radiological practice at two specialist and two non-specialist centres. An initial study involved analysis of nearly 3000 patient doses. The second phase of the project involved assessment of referral criteria, radiographic technique and approximately 100 radiographs at each centre by two consultant paediatric radiologists. While all radiographs were found to be diagnostically acceptable, major differences in technique were evident, reflecting the disparity in experience between staff at the specialist and non-specialist centres. The large number of sub-optimum films encountered at the latter suggests that there is a need for specific training of less experienced radiographic and clinical staff.

Child↗

Client-centred care means that I am a valued human being.

Canadian occupational therapists have increasingly adopted a client-centred approach to practice. Interpretation of what "client-centred" means has been diverse and varied. Professionals have written about the characteristics of this approach to care but no reported studies could be found that examined the client's perspective. The omission of the client perspective is puzzling when partnership, client involvement in decision making, and client empowerment are thought to be fundamental elements of this approach to practice. A qualitative research approach, using focus groups was employed to explore the opinions and perspectives of individuals with experience of mental illness and the mental health service delivery system. Seventeen individuals participated in three focus groups to discuss the meaning of a client-centred approach to practice. Participants assessed the inadequacies of past and present practices and recommended needed changes. Their central message was the need for individuals with mental illness to be viewed as valuable human beings by service providers and by society.

Adolescent↗

Opportunity, not prescription: an exploratory study of the experience of occupational engagement.

Occupational therapy practice is based upon the belief that the use of occupation-as-means can promote the health and sense of well-being of individuals with disability. Despite a firm commitment to the construct of occupation by the profession, little empirical evidence has been generated which supports the basic tenets of practice. In the psychosocial literature, no studies could be located which directly investigated the use of occupation-as-means to mental health. An exploratory study was conducted with eight participants of an occupation-based, women's mental health group. In-depth interviews and participant observation were utilized to explore the meaning of occupational engagement for these women. The experience of occupational engagement is presented in the form of a conceptual model named occupational spin-off. Occupational spin-off represents conceptually the experience of occupational engagement for the participants in the research study and describes a process of occupation-as-means to mental health. The processes of affirmation, confirmation, actualization, and anticipation collectively contribute to and maintain occupational spin-off. The process of occupational spin-off contributes to an understanding of why these participants have remained out of hospital, and why they are feeling better. Implications of this process model for clinical practice and future research are suggested.

Data Collection↗

An intramolecular disulfide bond between conserved extracellular cysteines in the gonadotropin-releasing hormone receptor is essential for binding and activation.

In this study, site-directed mutagenesis and biochemical strategies have been used to establish whether disulfide bonding between extracellular Cys residues contributes to the structural integrity of the GnRH receptor (GnRH-R) and, if so, to delineate the nature of the bonding patterns involved. The majority of G protein-coupled receptors (GPCRs) contain a pair of conserved Cys residues in the first and second extracellular domains, and these residues have been shown to form a receptor stabilizing disulfide bridge structure. However, many GPCRs contain other nonconserved Cys residues, and in some GPCRs these have also been shown to contribute to receptor integrity and stability. The rat GnRH-R contains four extracellular Cys residues. Two are conserved throughout the GPCR superfamily and lie at positions Cys114 and Cys195 in the first and second extracellular loops, respectively. The other two Cys residues occupy nonconserved positions at Cys14 in the amino terminus and Cys199 in the second extracellular loop. To assess the role of extracellular Cys residues in disulfide bonding interactions, each of these residues were mutated to Ala, expressed in COS-1 cells, and ligand binding and second messenger properties ascertained. To monitor levels of wild-type (WT) and mutant receptor cell surface expression, a hemagglutinin (HA) epitope tag was incorporated into the receptor constructs (GnRH-R WT, Cys14Ala, Cys114Ala, Cys195Ala, and Cys199Ala). Cys199Ala mutant maintained levels of receptor binding and second messenger production comparable with the WT GnRH-R, whereas mutant Cys14Ala exhibited some ligand binding and functional receptor activity, albeit at a reduced level. Mutations Cys114Ala and Cys195Ala showed no functional responses despite displaying levels of cell surface expression similar to the WT receptor. Specific binding of the WT and mutant receptors Cys14Ala and Cys199Ala was inhibited in the presence of the disulfide bond reducing agent, DTT, implying that disulfide bonds are formed and can be reduced in these mutant receptors. This study demonstrates that GnRH-R residues Cys114 and Cys195 have a disulfide bonding interaction role essential for the maintenance of receptor function. In contrast, Cys14 and Cys199 are not involved in disulfide bonding that is required for ligand binding or second messenger production.

Amino Acid Sequence↗

Understanding the transition to community living after discharge from an acute care hospital: an exploratory study.

OBJECTIVES: This study was conducted to obtain patients' experiences in making the transition from an acute care hospital to their homes in the community. METHOD: Data were gathered through group and telephone interviews with a volunteer sample of 27 discharged patients. Analysis involved two stages: categorization of shared themes and interpretation of individual occupational experiences. RESULTS: Informants described their experiences of transition in terms that were analytically categorized as Perceived Self-Efficacy, Resources, Dimensions of Occupation, and Environmental Constraints and Opportunities. Analysis of individual patient transcripts suggests the presence of an hierarchical ordering of desired occupations. CONCLUSION: Understanding patients' perceptions of enabling and disabling experiences has implications for predischarge and postdischarge practice in occupational therapy.

Activities of Daily Living↗

Understanding the potential of occupation: a qualitative exploration of seniors' perspectives on activity.

This article presents the results of a qualitative study that explored the characteristics and potential of occupation. Semistructured interviews with 12 seniors who live in the community followed by member-checking groups were used to explore informants' perspectives on the importance and role of occupation in their lives by asking them about their activities. Themes pertinent to the characterization of activity, the contributions of activity, and a condition allowing for the potential of activity emerged from the inductive analysis. These themes provide information about how occupation naturally functions in the lives of seniors and suggest a tentative conceptualization of the characteristics and potential of occupation. The findings have implications for research regarding occupation and for clinical practice aimed at enabling occupation.

Activities of Daily Living↗

"Doing" in mental health practice: therapists' beliefs about why it works.

OBJECTIVE: The purpose of this study was to explore the beliefs of occupational therapists working in mental health regarding the therapeutic value of "doing" as a treatment modality. Doing was defined as any activity or action-oriented approach that was identified and used by the participating therapists. METHOD: Eleven occupational therapists working in a variety of mental health areas were observed as they conducted 3 to 6 regularly scheduled therapy sessions. They were then interviewed about their activity-related beliefs. Audiotapes of the 44 treatment sessions and 11 interviews were transcribed and then coded to identify emergent themes and categories of beliefs about activity. RESULTS: Participants used a variety of activities in both task-based and verbally based treatment sessions. Multiple reasons for activity use were cited, particularly in relation to the task-based sessions. Two main themes related to the value of activity were (a) benefits of activity for the client and (b) benefits in facilitating the process of therapy. Categories of client-related benefits included skill development; impairment reduction; self-awareness; positive self-concept; interaction or connection with others; healthy, balanced routines; pleasure; and enhancement of occupational role performance. Perceived effects on the therapeutic process included creating a therapeutic context, enhancing client readiness, facilitating communication, and providing an organizing framework. CONCLUSION: Occupational therapists working in mental health hold diverse beliefs about the value of doing in treatment. Basing practice on clearly identified and evidence-based beliefs will assist in ensuring a viable and valued future for the profession in this important domain of health services.

Adult↗

A disulfide bonding interaction role for cysteines in the extracellular domain of the thyrotropin-releasing hormone receptor.

The roles of disulfide and sulfhydryl groups in the specific binding of TRH to its receptor have been examined. In all TRH receptors (TRH-Rs) isolated from different species so far, there are only two extracellular cysteine residues (Cys98 in the extracellular loop between transmembrane helices 2 and 3 and Cys179 in the extracellular loop between transmembrane helices 4 and 5) that are in positions homologous to cysteine residues in other G protein-coupled receptors. Another Cys (Cys100) is located in close proximity to Cys98 at the interface between the first extracellular loop and third transmembrane domain. To assess the role of these TRH-R Cys residues in disulfide bonding interactions, they were mutated to either Ser or Ala. Six mutant receptors (Cys98Ser, Cys98Ala, Cys179Ser, Cys179Ala, Cys100Ser, and Cys100Ala) were expressed in COS-1 cells and tested for their ability to bind TRH and to activate total inositol phosphate (IP) formation. TRH-R mutants Cys100Ser and Cys100Ala showed TRH binding affinities and IP activation similar to the wild-type (WT). In contrast, mutants Cys98Ser, Cys98Ala, Cys179Ser, and Cys179Ala showed no high affinity TRH binding. The potencies of Cys98Ala and Cysl79Ala as measured by IP stimulation were decreased by four orders of magnitude when compared with WT. Cys98Ser potency decreased by five orders of magnitude, whereas Cys179Ser showed no IP production. Northern blotting confirmed expression of all the mutant TRH-Rs at the messenger RNA (mRNA) level. An epitope tag derived from the Haemophilus influenza hemagglutinin protein was incorporated at the NH2 termini of the TRH-R WT and TRH-R Cys mutants to allow the independent assessment of cell surface expression of receptor protein. TRH-R mutants that failed to show receptor binding (Cys98Ser, Cys98Ala, Cys179Ala) showed WT levels of cell surface receptor expression, indicating that loss of receptor binding in these mutants is not attributable to loss of receptor expression. In contrast, cell surface expression of Cysl79Ser, which showed no ligand induced IP stimulation, could not be detected. Dithiothreitol, a disulfide bond reducing agent, and p-chloromercuribenzoic acid (p-CMB), a sulfhydryl blocking compound, reduced specific TRH binding in a dose-dependent manner. The inhibition of binding by dithiothreitol implies that the integrity of a disulfide bond is important for TRH binding to its receptor. The dramatic inhibition of TRH binding by p-CMB indicates that free sulfhydryl groups are also associated with the binding of the ligand to its receptor. This study presents evidence that a disulfide bond exists between Cys98 and Cys179 which is essential for maintaining the receptor in the correct conformation for ligand binding. Cys100 is not thought to have a disulfide bonding interaction role. Results obtained after chemical modification have shown that free sulfhydryl groups within the TRH-R may also have a role in ligand interactions.

Amino Acid Sequence↗

A comparison of doses and techniques between specialist and non-specialist centres in the diagnostic X-ray imaging of children.

A dosimetric survey of 14 routine X-ray examinations in children was carried out between 1993 and 1995. Two children's hospitals and four general hospitals took part in the survey which involved the calculation and measurement of nearly 3000 doses. Entrance surface doses (ESD) were calculated from exposure factors for radiographic procedures, and dose-area products (DAP) were recorded for both radiographic and fluoroscopic procedures. Doses were in good agreement with earlier studies, but for some procedures were significantly lower than those reported from other European countries. The main dose influencing factors for radiographic procedures were found to be the speed of the film-screen system and the use of an antiscatter grid. For the main head/trunk examinations, specialist centres often delivered higher doses to the younger children as a result of widespread use of a grid. In fluoroscopy, where the main dose influencing factors were the use of a grid and the dose rate dependence of the image intensifier, the children's hospitals consistently delivered significantly lower doses. Both ESDs and DAPs were found to increase with patient age for the main head/trunk examinations, although in some cases (AP/PA chest) this relationship was weak. The dependence of dose on age necessitates the subdivision of the paediatric sample into a number of age categories. It is suggested that all authors use the same age groupings.

Adolescent↗

Rapid desensitization of GnRH-stimulated intracellular signalling events in alpha T3-1 and HEK-293 cells expressing the GnRH receptor.

The gonadotropin-releasing hormone receptor (GnRH-R) desensitizes following chronic exposure to GnRH or its agonists. However, it is not certain whether the GnRH-R undergoes rapid homologous desensitization analogous to other members of the G-protein coupled receptor (GPCR) superfamily. This study investigated rapid desensitization events in two cell lines expressing the GnRH-R; (the pituitary gonadotrope alpha T3-1 cell line and the stably transfected human embryonal kidney cells, HEK-293). In both cell types, total inositol phosphate (IP) production did not desensitize, increasing linearly over 10 min. Short-term GnRH pretreatment also did not desensitize the rapid phase ( < or = sec) of the early Ins1,4,5P3 response despite a partial desensitization of the plateau phase ( > 1 min). It is likely that Ins1,4,5P3 metabolism rather than desensitization is responsible for this partial effect. In contrast, GnRH-stimulated calcium responses did desensitize in a dose-dependent fashion in both alpha T3-1 and HEK 293 cells expressing the GnRH-R. These results suggest that rapid GnRH-R desensitization occurs at a level beyond both the receptor and phospholipase C (PLC) activation. These events were receptor specific and not related to cell type, since similar rapid desensitization profiles were observed in both GnRH-R expressing pituitary and nonpituitary cell types. In contrast, profiles of GnRH-stimulated calcium responses were cell type specific.

Animals↗

Case report: thrombosis of the inferior vena cava--an unusual presentation of protein C deficiency.

In children, venous thrombosis is uncommon and this is true particularly for one of the inferior vena cava. Recurrent superficial venous thrombosis is a well-recognized presenting symptom of Protein C deficiency but thrombosis of the inferior vena cava as the initial manifestation of this condition has only rarely been reported. We present a case of a 13-year-old boy in whom the first indication of Protein C deficiency was an isolated thrombosis in the intra-hepatic inferior vena cava noted on a routine ultrasound examination.

Adolescent↗