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Biomedical subjects

A J Maxwell

Publications and source records attributed to A J Maxwell.

At least 19 recordsLinked to original sources
PubMed2002

Crude open biopsy rates for benign screen detected lesions no longer reflect breast screening quality--time to change the standard.

OBJECTIVES: To investigate the changing nature of the benign screen detected breast abnormalities removed at open biopsy over a seven year period and to compare this with the improving cancer detection rate and non-operative diagnosis rate. SETTING: The Bolton, Bury, and Rochdale Breast Screening Programme. METHODS: The histopathology reports of the benign lesions removed from patients undergoing open biopsy for screen detected abnormalities between 1 April 1994 and 31 March 2001 were reviewed and the lesions classified on the B1 to B5 scale. Cancer detection rates and non-operative cancer diagnosis rates were ascertained from the breast screening computer system. RESULTS: 148 benign surgical biopsies were performed in the seven year period. There was a moderate increase in the overall benign biopsy rate over the period (from 1.26 open biopsies per 1000 women screened for the three years 1994-97 to 1.63 open biopsies per 1000 women screened for the three years 1998-2001). The biopsy rate for B2 (benign) lesions decreased slightly over the study period but the biopsy rate for B3 lesions (that is, of uncertain malignant potential) more than doubled. The majority (84%) of the B3 lesions were radial scars. There was a steady improvement in the cancer detection rate and the non-operative cancer diagnosis rate over the period, similar to that seen nationally. CONCLUSIONS: Improvements in screening technique and detection ability result in an increase in the number of subtle radiologically indeterminate or suspicious lesions detected. Many of these are radial scars, which require excision. Crude benign open biopsy rates for screening programmes are no longer meaningful, and should now be refined with separate rates for B2 lesions and B3 lesions. High quality programmes can expect to have low B2 open biopsy rates and high B3 open biopsy rates. It is inappropriate to have an upper limit for the B3 open biopsy rate.

Biomarkers↗
PubMed2001

Uric acid is closely linked to vascular nitric oxide activity. Evidence for mechanism of association with cardiovascular disease.

OBJECTIVES: The study was undertaken to determine whether the mechanism of association of elevated serum uric acid level (SUA) with cardiovascular disease (CVD) is secondary to a common link with vascular nitric oxide (NO) activity. BACKGROUND: Epidemiologic studies demonstrate an association of elevated SUA with CVD. The mechanism of this association is unknown, but both may be linked via an impairment in vascular NO activity. To examine this, we determined the relationship of SUA to vascular NO activity and to CVD risk. We then determined the effect of enhancing vascular NO activity on SUA. METHODS: In part 1, individuals with various degrees of CVD (n = 458) were surveyed and underwent measurement of flow-mediated brachial artery vasodilation (FMV), a measure of vascular NO activity. In part 2, we performed an analysis of data pooled from six separate clinical trials of a medical food designed to enhance vascular NO activity in individuals with CVD (n = 217 subjects representing 253 treatment periods) to determine the effect on SUA. RESULTS: In part 1, of all risk factors tested, SUA was second only to age in correlation with FMV, accounting for 7% (p < 0.0001) of the variability in FMV. Both SUA and FMV were related to the degree of disease risk (p < 0.0001 and p = 0.00025 by analysis of variance, respectively). By multivariate analysis, SUA did not continue to contribute significantly to the determination of FMV. In part 2, enhancement of FMV (5.8 +/- 4 to 8.6 +/- 5, p < 0.0001) was associated with a decrease in SUA (5.5 +/- 1.5 to 5.0 +/- 1.5, p < 0.0001). There was no placebo effect on FMV or SUA. CONCLUSIONS: These results suggest that the association of elevated SUA with CVD may be a consequence of an impairment of vascular NO activity. This may be owing to an ability of NO to modulate uric acid production through its influence on xanthine oxidase activity.

Adult↗
PubMed2001

Primary and metastatic lobular carcinoma of the breast.

Invasive lobular carcinoma of the breast is the second most common type of primary breast cancer, accounting for 8-14% of cases, but is often difficult to diagnose early. It typically shows a diffuse pattern of infiltration within the breast, resulting in a variety of often subtle radiological appearances. A similar infiltrative pattern is seen in its metastatic form, with involvement of the gastrointestinal tract, peritoneum, retroperitoneum, bone marrow, meninges and uterus occurring more frequently than with the more common infiltrating ductal carcinoma of the breast. This pictorial essay illustrates the spectrum of radiological appearances which may be encountered with both primary and secondary lobular carcinoma.

Aged↗
PubMed2001

A study of breast cancers detected in the incident round of the UK NHS Breast Screening Programme: the importance of early detection and treatment of ductal carcinoma in situ.

One hundred and seventy eight cancers detected on incident round screening in the UK National Health Service Breast Screening Programme were reviewed. Critical review of the immediately preceding screening films (from 3 years previously) found abnormalities at the site of the subsequently detected cancer in 93 cases (52%). Forty-eight of these (27% of the total) had microcalcification as the sole abnormality. All of these 48 women had invasive ductal carcinoma and/or ductal carcinoma in situ (DCIS) (including four cases in which DCIS was associated with another type of primary invasive breast cancer). The finding of microcalcification on the previous mammograms at the site of a subsequently detected cancer was a strong predictor for the presence of DCIS (with or without associated invasive disease) (P<0.0001). Of the women with invasive ductal carcinoma, those with microcalcification on previous films were significantly more likely to have intermediate or high grade (grade 2 or 3) tumours than those women without microcalcification on previous films (P=0.0015). Previous films were also read blind by two independent experienced breast radiologists. Cancers were correctly identified by one or both readers in 39 cases. However, 35 of the remaining 139 cases showed microcalcification which was not detected or considered significant by the readers. If only these 139 'true negative' screens are analysed, similar associations are seen between microcalcification on previous films and subsequent finding of DCIS (P=0.03) and between microcalcification on previous films and high grade invasive ductal carcinomas (P=0.015). These findings provide support for the hypothesis that microcalcification seen on previous screening films at the site of a subsequently detected invasive ductal carcinoma represents ductal carcinoma in situ. In this series, 19 of 82 women (23%) with invasive ductal carcinoma in the 'true negative' screen group had microcalcification suggestive of DCIS on mammograms taken, on average, 3 years previously. Significant microcalcification is often overlooked using current detection criteria. Early detection and treatment of DCIS is essential in order to prevent the development of aggressive invasive disease. Revision of the NHSBSP targets for DCIS detection is recommended.

Journal Article↗
PubMed2001

L-arginine enhances aerobic exercise capacity in association with augmented nitric oxide production.

We tested whether supplementation with L-arginine can augment aerobic capacity, particularly in conditions where endothelium-derived nitric oxide (EDNO) activity is reduced. Eight-week-old wild-type (E(+)) and apolipoprotein E-deficient mice (E(-)) were divided into six groups; two groups (LE(+) and LE(-)) were given L-arginine (6% in drinking water), two were given D-arginine (DE(+) and DE(-)), and two control groups (NE(+) and NE(-)) received no arginine supplementation. At 12-16 wk of age, the mice were treadmill tested, and urine was collected after exercise for determination of EDNO production. NE(-) mice demonstrated a reduced aerobic capacity compared with NE(+) controls [maximal oxygen uptake (VO(2 max)) of NE(-) = 110 +/- 2 (SE) vs. NE(+) = 122 +/- 3 ml O(2). min(-1). kg(-1), P < 0.001]. This decline in aerobic capacity was associated with a diminished postexercise urinary nitrate excretion. Mice given L-arginine demonstrated an increase in postexercise urinary nitrate excretion and aerobic capacity in both groups (VO(2 max) of LE(-) = 120 +/- 1 ml O(2). min(-1). kg(-1), P < 0.05 vs. NE(-); VO(2 max) of LE(+) = 133 +/- 4 ml O(2). min(-1). kg(-1), P < 0.01 vs. NE(+)). Mice administered D-arginine demonstrated an intermediate increase in aerobic capacity in both groups. We conclude that administration of L-arginine restores exercise-induced EDNO synthesis and normalizes aerobic capacity in hypercholesterolemic mice. In normal mice, L-arginine enhances exercise-induced EDNO synthesis and aerobic capacity.

Aerobiosis↗
PubMed2000

Endothelial dysfunction in hypercholesterolemia is reversed by a nutritional product designed to enhance nitric oxide activity.

The objective of this study was to investigate the vascular and biochemical effects of a formulated product in the form of a bar enriched with a combination of nutrients known to enhance the synthesis or activity of endothelium-derived nitric oxide (EDNO). Individuals with hypercholesterolemia manifest impaired flow-mediated vasodilation, which is largely due to a reduction in EDNO activity. Oral supplementation with large amounts (6-21 g/day) of L-arginine, the precursor of EDNO, have been shown to improve endothelium-mediated vasodilation in hypercholesterolemia. Such large doses are effective but may be impractical to take in capsule form. Accordingly, we have developed a nutrient bar enriched with L-arginine as well as other ingredients that additively enhance EDNO activity. A pilot study in 41 hypercholesterolemic individuals indicated that the bar was well tolerated, had no adverse effects on serum chemistries or lipid profile, and normalized endothelial vasodilator function. To definitively determine if the nutrient bar normalizes endothelial function, a double-blind, placebo-controlled study was performed. Flow-mediated endothelium-dependent vasodilation was assessed by high-resolution ultrasonography before and after 1 week of bar use (2 bars/day) in an additional group of 43 volunteer subjects (57 +/- 10 years old; 22 men, 21 women) with hypercholesterolemia. Subjects manifested an impaired flow-mediated vasodilation before the intervention. Vasodilator function in the active bar group improved to within a normal range (6.5 +/- 3% before to 10 +/- 5% after, P = 0.02; normal, 12 +/- 3%) and was significantly better (P < 0.01) than in the placebo bar group (7.1 +/- 3% before to 6.7 +/- 4% after). These findings reveal that use of a nutrient bar designed to enhance EDNO activity improves flow-mediated endothelium-dependent vasodilation in hypercholesterolemic individuals.

Adult↗
PubMed2000

Relocation of a static breast screening unit: a study of factors affecting attendance.

OBJECTIVE: To assess the effect of relocation of an urban static breast screening unit on the attendance rates (uptake) in different parts of the catchment area. SETTING: The Bolton Breast Screening Programme. METHODS: The attendance rates for screening for patients in each of the seven Bolton postcode districts were obtained from the breast screening computer system for the 29 months prior to and 38 months following the relocation of the screening unit. RESULTS: The overall attendance rate for screening in Bolton fell by 1%. The fall was most marked in BL1 (2.0%), the location of the original screening unit. BL4, the district housing the new unit, showed an increase in attendance of 1.1%. The other districts showed a similar trend with smaller reductions in attendances from districts that were closer to the screening unit than before, and vice versa. The direct distance between the centre of the women's home postcode district and the screening unit had a significant effect on the attendance rate (p = 0.045). For each kilometre further from the screening unit, the attendance decreased by approximately 2%. However, there was a 6.4% difference between the highest and lowest district attendance rates, the highest rates being in the less deprived areas. CONCLUSIONS: There is a significant inverse relationship between the distance a woman must travel for screening and her likelihood of attending. However, this has a relatively minor effect on attendance rates compared to that of socioeconomic factors.

Breast Neoplasms↗
PubMed2000

Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar.

We investigated the clinical effects of a food bar enriched with L-arginine and a combination of other nutrients known to enhance the activity of endothelium-derived nitric oxide (EDNO) in individuals with claudication from atherosclerotic peripheral arterial disease. The study was a 2-week, double-blind, placebo-controlled trial of subjects randomized to three groups (two active bars, one active and one placebo bar, and two placebo bars per day) followed by an 8-week open-label period. Subjects (n=41) were outpatient volunteers with intermittent claudication. Pain-free and total walking distances were measured by variable-grade, treadmill exercise testing. Quality of life was assessed using the Medical Outcome Survey (SF-36). After 2 weeks of treatment, the pain-free walking distance increased 66% while the total walking distance increased 23% in the group taking two active bars/day. The general and emotional/social functioning components of the SF-36 also improved. These effects were not observed in the one active bar/day and placebo groups. The effects were maintained after 10 weeks and, in addition, an improvement in walking distance was observed in the group taking one active bar. These findings reveal that use of a nutrient bar designed to enhance EDNO activity improves pain-free and total walking distance as well as quality of life in individuals with intermittent claudication.

Aged↗
PubMed1999

Breast cancers missed in the prevalent screening round: effect upon the size distribution of incident round detected cancers.

OBJECTIVE: To determine the effect of false negative screens (missed cancers) in the prevalent screening round on the relative size distribution of cancers detected at the first incident screen. SETTING: The Bolton, Bury, and Rochdale breast screening programme. METHODS: One hundred and three breast cancers detected in the first incident round of screening were analysed. The previous (prevalent round) screening films taken between two and four years earlier were subjected to blinded review and classified as either true negatives (no significant abnormality visible) or false negatives (a suspicious abnormality visible at the site of the subsequently detected cancer). The pathological size, type, and grade (where appropriate) of the cancers were recorded. RESULTS: Fifty one of the 103 cancers (49%) detected in the first incident round screen measured < 15 mm in diameter. A total of 32 cases were classified as false negatives. Of these, 12 (38%) measured < 15 mm in diameter. If all the false negative cancers had been detected at the prevalent screen, 39 (55%) of the remaining 71 cancers detected in the first incident round screen would have measured < 15 mm. A relative excess of lobular carcinomas was found among the false negatives. CONCLUSIONS: The findings suggest that although false negative screens in the prevalent round increase the number of cancers available for detection at the first incident round screen, many of these cancers are still < 15 mm in diameter at detection. Cancer detection performance in the prevalent screening round has only a minor influence on the relative proportion of small and large cancers detected at the first incident round screen.

Breast Neoplasms↗
PubMed1999

Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by exercise training.

The present study assessed whether impaired aerobic capacity previously observed in hypercholesterolemic mice is reversible by exercise training. Seventy-two 8-wk-old female C57BL/6J wild-type (+, n = 42) and apolipoprotein E-deficient (-, n = 30) mice were assigned to the following eight interventions: normal chow, sedentary (E+, n = 17; E-, n = 8) or exercised (E+ex, n = 13; E-ex, n = 7) and high-fat chow, sedentary (E+chol, n = 6; E-chol, n = 8) or exercised (E+chol-ex, n = 6; E-chol-ex, n = 7). Mice were trained on a treadmill 2 x 1 h/day, 6 days/wk, for 4 wk. Cholesterol levels correlated inversely with maximum oxygen uptake (r = -0.35; P < 0. 02), which was blunted in all hypercholesterolemic sedentary groups (all P < 0.05). Maximum oxygen uptake improved in all training groups but failed to match E+ex (all P < 0.05). Vascular reactivity and nitric oxide (NO) synthesis correlated with anaerobic threshold (r = 0.36; P < 0.025) and maximal distance run (r = 0.59; P < 0.007). We conclude that genetically induced hypercholesterolemia impairs aerobic capacity. This adverse impact of hypercholesterolemia on aerobic capacity may be related to its impairment of vascular NO synthesis and/or vascular smooth muscle sensitivity to nitrovasodilators. Aerobic capacity is improved to the same degree by exercise training in normal and genetically hypercholesterolemic mice, although there remains a persistent difference between these groups after training.

Aerobiosis↗
PubMed1998

Limb blood flow during exercise is dependent on nitric oxide.

BACKGROUND: We have recently reported that hypercholesterolemia reduces aerobic exercise capacity in mice and that this is associated with a reduced endothelium-dependent vasodilator function, endothelium-derived nitric oxide (EDNO) production, and urinary nitrate excretion. These findings led us to test the hypothesis that EDNO production contributes significantly to limb blood flow during exercise and to determine whether loss of EDNO production is responsible for the decline in exercise capacity observed in hypercholesterolemia. METHODS AND RESULTS: Twelve-week-old wild-type (E+; n=9) and apoE-deficient (E-; n=9) C57BL/6J mice were treadmill-tested to measure indices defining exercise capacity on a metabolic chamber-enclosed treadmill capable of measuring oxygen uptake and carbon dioxide excretion. Urine was collected before and after treadmill exercise for determination of vascular NO production assessed by urinary nitrate excretion. The wild-type mice were then given nitro-L-arginine (E+LNA) in the drinking water (6 mg/dL) for 4 days before undergoing a second treadmill testing and urinary nitrate measurement. An additional set of 12-week-old wild-type mice was divided into 2 groups: 1 receiving regular water (E+; n=8) and 1 administered LNA for 4 days (E+LNA; n=8). These mice, along with an additional set of E mice (n=8), underwent treadmill testing to determine maximal oxygen uptake (VO2max). The mice were then cannulated such that the tip of the tubing was positioned in the ascending aorta. Fluorescent microspheres (20000) were infused into the carotid cannula while the mice were sedentary and again while approaching VO2max. When the mice were euthanized, the running muscles were collected and fluorescence intensity was measured to determine the peak-exercise redistribution of blood flow to the running muscles (expressed as percentage of total cardiac output, %COrm) during both states. Both E+LNA and E- mice demonstrated a markedly reduced postexercise urinary nitrate excretion, aerobic capacity, and %COrm at VO2max compared with E+. CONCLUSIONS: EDNO contributes significantly to limb blood flow during exercise. Conditions that reduce EDNO production disturb the hyperemic response to exercise, resulting in a reduced exercise capacity.

Animals↗
PubMed1998

Cardiovascular effects of L-arginine.

Most of the known cardiovascular effects of L-arginine are exerted via its conversion to nitric oxide by nitric oxide synthase. Accumulating evidence indicates that supplemental administration of L-arginine is sufficient to restore endothelium-derived nitric oxide production in many disorders in which endothelium-derived nitric oxide production is altered. L-arginine may enhance nitric oxide production by competing as a substrate with an endogenous antagonist for nitric oxide synthase. In other cases, L-arginine may act by competing with molecular oxygen as a substrate so as to reduce the production of superoxide anion. It is likely that other mechanisms exist by which the nitric oxide synthase pathway can be perturbed. Regardless of the mechanism, a wide array of cardiovascular disorders characterized by endothelial dysfunction are reversible by L-arginine.

Animals↗
PubMed1997

Assessing residents' readiness for working in a managed care environment.

PURPOSE: A the pilot study to assess the state of residents' training for practice in a managed care environment. METHOD: In May and June 1996, all 178 residents at the University of Kentucky College of Medicine in six programs were approached to participate in the study. An instrument was created to assess the residents' knowledge of, attitudes toward, and exposure to managed care, as well as their perceptions of their residency experience. Attitudinal items were measured using a five-point Likert scale (1 = strongly agree, 5 = strongly disagree), as were the assessments of experience (1 = excellent, 5 = poor). Bivariate statistics were computed between the number of correct responses to the knowledge questions and both the year of training and reported exposure to managed care. The relationship between exposure and knowledge was analyzed using a two-tailed t-test. A Pearson product-moment correlation was computed between residents' knowledge and year of training. RESULTS: In all, 140 (79%) residents participated, 76% of whom were men. Seventy-three percent of the residents rated their experiences as fair or poor; the mean rating across all the residents was 3.8 (SD, 0.8). Among those reporting some exposure, attitudes toward the effectiveness of their exposure generally ranged from neutral to negative. Across all the residents, the mean number of correct responses to the five knowledge questions was 3.2 (SD, 1.1). No statistically significant relationship was found between year of training and the number of correct responses. The residents who reported some exposure to managed care had a significantly higher mean number of correct responses than did those with no reported exposure (3.4, SD, 1.1, vs 2.8, SD, 1.3, p = .04). CONCLUSION: The residents reported limited exposure to managed care and that their training experience did not prepare them for working in managed care; this was confirmed (in a limited way) by the responses to the knowledge questions. As managed care expands in the United States, the systematic incorporation of managed care instruction into training is necessary to appropriately prepare residents for future practice.

Attitude of Health Personnel↗
PubMed1996

Normal versus pathological aging: knowledge of family practice residents.

Family physicians may lack discriminatory ability to differentiate normal aging from disease states. To assess such ability, 53 aging-related indicators or symptoms were presented to 65 physicians in three family practice residency programs. Respondents classified each symptom as normal aging or disease. On average, residents classified 73.4% of symptoms correctly. They were more likely to classify disease states correctly (80.0%) than to classify signs of normal aging correctly (66.8%). Misattribution of normal aging signs as disease may prompt physicians to overmedicate and overtreat patients, resulting in adverse clinical outcomes.

Activities of Daily Living↗