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Biomedical subjects

J Cox

Publications and source records attributed to J Cox.

At least 145 records · Page 8Linked to original sources

Antigen processing: where tumor-specific T-cell responses begin.

It is well established that tumor-specific CD8+ T cells have the capacity to prevent and cure malignancies in animals under experimental conditions. This has raised expectations that it will prove possible to achieve similar successes with human cancers. CD8+ T cells recognize peptides of 8-10 residues derived from cytosolic proteins that are bound to the class I molecules of the major histocompatibility complex. To most effectively manipulate the T-cell response to tumor cells, it is essential to understand the means by which the peptide-class I complex is created in cells. An overview of this process is provided with an emphasis toward the recent findings made by our laboratory.

Animals↗

Relationship between blood pressure measured in the clinic and by ambulatory monitoring and left ventricular size as measured by electrocardiogram in elderly patients with isolated systolic hypertension.

OBJECTIVE: To assess the additional diagnostic precision conferred by ambulatory blood pressure monitoring on clinic blood pressure measurement in evaluating the severity of isolated systolic hypertension. METHODS: The association between left ventricular size as determined by ECG voltages [R-wave voltages in lead V5 (RV5) and S-wave voltages in lead V1 (SV1)] and blood pressure as assessed by clinic measurements and ambulatory blood pressure monitoring was studied in 97 elderly patients included in the placebo run-in phase of the Syst-Eur trial. The additional diagnostic precision conferred by ambulatory monitoring on clinic blood pressure measurements was assessed by relating the residual ambulatory blood pressure level to the ECG-left ventricular size. The residual ambulatory blood pressure level was calculated by subtracting the predicted ambulatory blood pressure level for each patient (using the linear regression equation relating both techniques for the group) from the observed ambulatory blood pressure. RESULTS: Clinic systolic blood pressure was on average 20 mmHg higher (P < 0.001) than daytime ambulatory blood pressure while diastolic blood pressure was similar with both techniques. The sum of SV1 + RV5 was significantly related to clinic systolic pressure (r = 0.25), and 24-h (systolic, r = 0.37; diastolic, r = 0.29), daytime (systolic, r = 0.30; diastolic, r = 0.19) and night-time (systolic, r = 0.33; diastolic, r = 0.28) ambulatory blood pressure levels. These findings were not affected by adjustment for gender, age and the body mass index. The sum of SV1 + RV5 was significantly related to the residual 24-h (systolic, r = 0.30; diastolic, r = 0.31), daytime systolic (r = 0.20) and night-time (systolic, r = 0.31; diastolic, r = 0.29) ambulatory blood pressure monitoring levels. CONCLUSION: Ambulatory blood pressure monitoring adds to the diagnostic precision of clinic blood pressure measurement in assessing the severity of hypertension in this population. The ongoing side project on ambulatory blood pressure monitoring in the Syst-Eur study should establish whether these findings hold true for morbidity and mortality.

Aged↗

Bradykinin does not modulate the natriuretic response to atrial natriuretic factor in rats with aortocaval fistula.

Rats with aortocaval fistula, an experimental model of congestive heart failure (CHF), display two distinct patterns of sodium excretion: some rats develop marked sodium retention and worsening edema with urinary excretion of sodium (UNaV) < 200 microEq per 24 hours, i.e., uncompensated CHF, whereas in others sodium balance rapidly returns to normal (UNaV > 1,400 microEq per 24 hours), i.e., compensated CHF. Similar patterns of sodium excretion are found in patients with CHF. The mechanisms underlying these responses are not fully understood. The present study was designed to assess whether bradykinin plays a role in the compensatory response to CHF. Infusions of either 10 or 50 micrograms/kg per minute of synthetic atrial natriuretic factor (ANF)8-33 into sham-operated control animals produced significant increases in urine flow and fractional excretion of sodium (FENa). Infusions of ANF at the same doses into rats with compensated CHF increased FENa from 0.11 +/- 0.03% to a maximum of 6.10 +/- 1.30%, whereas the rise in FENa in animals with uncompensated CHF was significantly reduced (0.05 +/- 0.01% to 0.59 +/- 0.18%) compared with sham-operated controls (0.23 +/- 0.05% to 8.32 +/- 1.0%) or the group with compensated CHF. Treatment of the compensated rats with the bradykinin antagonist HOE-140 (D-Arg,[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) given at a rate of 100 nmol/kg per hour did not affect their renal response to the ANF. In addition, infusion of the bradykinin antagonist alone into compensated rats with aortocaval fistula had no significant effect on their basal urinary flow rate or sodium excretion during the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Tackling language delay: a groupwork approach.

Communication, Articulation and Terrific fun adds up to Speech. Jacqueline Cox and Sylvia Hill describe CATS, a speech and language group for language-delayed children run by health visitors.

Child, Preschool↗

Male infertility: artificial insemination by donor.

It is now known that in about 40 per cent of couples attending infertility clinics, it is the man who has the underlying problem. Jacquie Cox looks at artificial insemination by donor as an alternative to treatment for infertility.

Humans↗

The Canadian Cardiovascular Society grading scale for angina pectoris: is it time for refinements?

OBJECTIVE: To appraise the measurement properties of the Canadian Cardiovascular Society (CCS) classification of stable angina pectoris. DATA SOURCES: Relevant articles were identified through a MEDLINE search (1976 to November 1991). Bibliographies of retrieved articles were also reviewed. STUDY SELECTION: Studies chosen directly addressed the validity and reliability of the CCS scale. Recent studies and reviews of related topics (for example, silent ischemia) are selectively cited. DATA SYNTHESIS: No data address the scale's applicability, that is, how clinicians typically assign angina grades in practice. Comprehensiveness would be improved by coverage of the patient's perceptions of symptom burden; mixed exertional and rest symptoms; episodic or changing symptoms; and modifying factors. Reliability was assessed in one study with two clinicians; the interobserver, chance-corrected agreement on patient grading was 60%. Content validity (the ability of the scale to measure what it claims) is threatened by the unproven assumption of symptomatic or physiologic equivalence among diverse levels of different activities within any given grade of angina. Construct validity is uncertain, given weak relations between angina grade and noninvasive markers of ischemia, anatomical disease, or prognosis. The scale's responsiveness (the ability to detect the smallest clinically important changes) is limited by the reliance on four coarse gradations based on only ambulation or stair-climbing. CONCLUSIONS: The CCS scale for stable angina might be made more useful by developing measurements for patients' self-rated symptom burden and the changes they deem important; by adding items on clinical instability (that is, progressive symptoms or pain at rest); and by empirically testing the current scale to eliminate redundant or inconsistent elements.

Angina Pectoris↗

The increase in blood pressure with age and body mass index is overestimated by conventional sphygmomanometry.

This cross-sectional study investigated whether the technique of blood pressure measurement used (conventional sphygmomanometry vs. ambulatory monitoring) affects the relation between blood pressure and both age and body mass index. Two independent data sets were analyzed. The first comprised 328 subjects (48% men) drawn from the population of a small Belgian town, and the second comprised 776 Irish bank employees (51% men). Age ranged from 17 years to 81 years, and body mass index (weight (kg)/height (m)2) ranged from 16.6 to 40.2. Twenty-four-hour ambulatory blood pressure was lower than blood pressure measured by a nurse in both the Belgian population sample (118/71 mmHg vs. 122/73 mmHg) and the Irish employees (118/72 mmHg vs. 119/76 mmHg). When blood pressure was measured by an observer, the well-established relations between systolic and diastolic blood pressure and both age and body mass index were evident. When the analyses were repeated using 24-hour measurements, the increment (cross-sectionally assessed) in blood pressure with age was weaker, especially in young and middle-aged subjects (20-60 years), while the increase in blood pressure with body mass index was also reduced. The within-subject differences between the conventional and ambulatory blood pressure measurements increased with older age and greater body mass index. Several other relations with blood pressure as the response variable may require revision in light of the present findings.

Adult↗

The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures.

The high mobility group (HMG) domain is a DNA-binding motif that is associated with several eukaryotic regulatory proteins, including the lymphoid enhancer-binding factor LEF-1 and the testis-determining factor SRY. Here, we provide evidence that DNA binding by the HMG domain of LEF-1 involves primarily minor groove contacts and induces a bend of approximately 130 degrees in the DNA helix. Bending was also found to accompany sequence-specific DNA binding by the SRY-HMG domain. Examining possible regulatory roles of HMG domain-induced DNA bends, we found that LEF-1 can function in a manner similar to bacterial integration host factor and facilitate communication between widely separated protein-binding sites in a recombination assay. Together with the previous observation that LEF-1 by itself is unable to augment basal promoter activity, these data suggest that HMG domain proteins can serve as "architectural" elements in the assembly of higher-order nucleoprotein structures.

Base Sequence↗

Solitary rectal ulcer: an unusual cause of rectal bleeding in children.

The solitary rectal ulcer syndrome (SRUS) is a disease which is commonly diagnosed in adults but only rarely described in children. Rectal prolapse and intussusception are frequently associated with this entity. A relationship between SRUS and chronic constipation due to spastic pelvic floor syndrome (SPFS) is often observed. Thus biofeedback defaecation training is an efficient treatment of both conditions. We describe two paediatric patients suffering from SRUS associated with SPFS who showed complete recovery after biofeedback defaecation training.

Child↗

Twenty-four hour blood pressure monitoring in the Syst-Eur trial.

This article describes the objectives and protocol of a study on ambulatory blood pressure in elderly patients with isolated systolic hypertension. This study constitutes an optional side-project to the Syst-Eur trial. The multicentre Syst-Eur trial investigates whether antihypertensive treatment of elderly patients with isolated systolic hypertension will influence the incidence of stroke. Secondary endpoints include cardiovascular events, such as myocardial infarction. The main objective of the side-project is to investigate whether ambulatory blood pressure monitoring will improve the prediction of cardiovascular complications based on blood pressure measurement in the clinic. The side-project also provides the opportunity to evaluate the diurnal profile of blood pressure in elderly patients with isolated systolic hypertension randomized to placebo or active antihypertensive treatment.

Aged↗

The diurnal blood pressure profile. A population study.

This population study included 399 subjects, of whom 370 (93%) showed a significant diurnal blood pressure (BP) rhythm. The nocturnal BP fall was normally distributed and averaged 16 +/- 9 mm Hg systolic and 14 +/- 7 mm Hg diastolic (mean +/- SD). The amplitude of the diurnal BP curve followed a positively skewed distribution, with a mean of 16 +/- 5 mm Hg for systolic BP and 14 +/- 4 mm Hg for diastolic BP. The daily BP maximum occurred at 15:54 +/- 4:47 for systolic BP and at 15:11 +/- 4:20 for diastolic BP. Thirty-four subjects were reexamined after a median interval of 350 days. The test for the presence of a significant diurnal rhythm was discordant in only two subjects. Repeatability (twice the standard deviation of the differences between paired recordings expressed as a percentage of the mean) varied from 11 to 25% for the 24 h, daytime, and overnight BP, and from 76 to 138% for the parameters describing the diurnal BP rhythm. In nine subjects with an initial night/day ratio of mean BP less than 0.78, the nighttime BP was significantly increased at the repeat examination, whereas the opposite tendency was observed in nine subjects with an initial ratio greater than 0.87. In conclusion, the distribution of the nocturnal BP fall is unimodal. The reproducibility of the ambulatory BP is satisfactory for the level of BP and for the presence of a diurnal BP rhythm, but not for the parameters of the diurnal BP curve. Thus, one 24 h recording is insufficient to fully characterize an individual's diurnal BP profile.

Adult↗

Syst-Eur--a multicenter trial on the treatment of isolated systolic hypertension in the elderly: first interim report.

Syst-Eur is a multicenter placebo-controlled outcome trial designed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg with a diastolic blood pressure less than 95 mm Hg. The present paper is an interim report on the first 316 patients randomized into this trial. The placebo (n = 170) and active treatment (n = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/- 12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p less than 0.001) in patients on active treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10 mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained. New centers are being recruited in order to randomize a total of 3,000 patients.

Aged↗

[Comparative histological study of the reproductive system of the female llama (Lama guanicoe glama). I. Ovary].

In the present study a cytological, histological and morphometrical comparison between the ovaries of the llama, the cow and the sheep is presented, at two phases of the ovarian cycle. There were found differences in the amount of primordial and primary follicles, the size of secondary follicles and follicular cells, and type and distribution of the connective tissue inside the stroma of the ovary. It would be necessary to study the fine structure of the ovary and the so-called "embryological remnants", for its permanent appearance in most (50%) of the ovaries.

Animals↗

Vitamin-D-fortified liquid milk--a highly effective method of vitamin D administration for house-bound and institutionalised elderly.

The aim of the study was to assess the efficacy and acceptability of vitamin-D-fortified liquid milk in the management of hypovitaminosis D in an elderly institutionalised population. The design was a single-blind randomised controlled study. In phase I, patients were encouraged to drink an increased quantity of either fortified or unsupplemented milk for 3 months. In phase II, patients were continued on either fortified or on unsupplemented milk which was given as part of the everyday diet for a further 6 months with no extra encouragement of any patient to take additional amounts. Ninety-eight patients (mean age 84 years) from extended care wards at the Department of Medicine for the Elderly, St. James's Hospital, Dublin, Ireland, participated in the study. Seventy-eight patients completed phase I, and 62 completed phase II. A general biochemical screen and 25-hydroxy vitamin D measurements were performed at entry and repeated 3 and 9 months later. The average milk intake per patient in phase I was 454 ml/day in the unsupplemented group and 359 ml/day in the fortified milk group. In phase II, the average daily milk intake per patient was 235 ml in the unsupplemented milk group and 140 ml in the fortified milk group. Seventy-four patients (94%) of the total who completed phase I had serum vitamin D baseline levels below the normal range. In the fortified milk group, mean vitamin D levels rose from 2.4 to 14.80 ng/ml (p < 0.001) at the end of phase I and remained significantly elevated at 10.2 ng/ml (p < 0.001) at the end of phase II.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Cumulative sums in quantifying circadian blood pressure patterns.

The plotting of cumulative sums (cusums), a technique of proven value in the detection of trends in data collected at intervals of time, may be modified to analyze circadian blood pressure patterns quantitatively. Mean 24-hour ambulatory blood pressure is taken as the reference value and is subtracted from each pressure value. The products of the remainders and the corresponding time intervals are summed in sequence and are plotted against time to form a modified cusum plot. The slope of the plot over any given time period equals the difference between mean blood pressure during that period and mean 24-hour blood pressure. Crest and trough blood pressures (the mean blood pressures of the 6-hour periods of highest and lowest pressures) may be identified as the 6-hour periods where plot slopes are most steeply ascending and descending, respectively. The magnitude of the circadian blood pressure change, defined as the difference between crest and trough blood pressure, is calculated from the difference between crest and trough plot slopes. The height of the cusum plot, which reflects pressure alteration extent and duration, may also be used as a measure of circadian pattern. The modified cusums technique and cusum-derived statistics are illustrated using ambulatory blood pressure profiles of hypothetical and actual hypertensive subjects. Independence from fixed time periods improves precision and reproducibility. Cusum-derived statistics are simply calculated from raw ambulatory data and should prove useful in the quantitative analysis of circadian blood pressure profiles.

Adult↗

Aluminium administered in drinking water but not in the diet influences biopterin metabolism in the rodent.

To investigate the neurotoxic effects of aluminium (Al) Al was administered: 1) in the diet of the rat (30 mg Al/kg body weight for 6 weeks); 2) as a suspension of aluminium acetate in drinking water of the rat for 3 months and 3) in a long-term study in the mouse in which aluminosilicates were incorporated into a pelleted diet (1035 mg/kg of food over 23 months). In the latter treatment, increased Al was combined with a reduction in calcium and magnesium; a treatment designed to increase absorption of Al into the body. Administration of Al in the drinking water significantly reduced total brain biopterins and BH4 synthesis. However, no significant affect of Al in the diet on total biopterins or BH4 synthesis was found either in the rat or in the long-term study in the mouse. In addition, in the mouse no significant effects of the Al diet on levels of noradrenaline, serotonin, dopamine, 5-HIAA or CAT could be demonstrated. Hence, the occurrence of brain alterations may depend on the Al species present and the method of administration. Al salts in drinking water may increase brain tissue levels compared with the administration of a more insoluble species. Since alterations in biopterin metabolism are also a feature of Alzheimer's disease (AD) these results support the hypothesis that Al in the water supply may be a factor in AD.

Aluminum↗