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J Fox

Publications and source records attributed to J Fox.

At least 163 records · Page 9Linked to original sources
PubMed1992

Angiotensin and angiotensin converting enzyme tissue levels in two-kidney, one clip hypertensive rats.

Renal tissue angiotensin I (Ang I) and II (Ang II) content and angiotensin converting enzyme activity were assessed in both kidneys during initial (7 days) and maintenance (25 days) phases of two-kidney, one clip hypertension in rats. At 7 and 25 days, systolic arterial pressure was 146 +/- 2 and 170 +/- 7 mm Hg, respectively. After 7 days, Ang I content of clipped kidneys was 64% and 70% higher (p < 0.001) than in nonclipped and sham-operated kidneys, respectively, when compared with levels in kidneys from sham-operated rats. In kidneys harvested 25 days after clipping one renal artery, Ang I and Ang II contents in clipped kidneys were increased 102% and 24% (p < 0.01), respectively. Ang II content was also 32% higher in nonclipped kidneys. Angiotensin converting enzyme activity in nonclipped kidneys was greater (p < 0.05) than that in either clipped (46% higher) or sham-operated kidneys (57% higher). Plasma Ang I and Ang II levels were elevated at 7 days but were not different at 25 days in clipped rats. These results demonstrate a dissociation between intrarenal and circulating levels of Ang I and Ang II and suggest that qualitatively different mechanisms may be responsible for the elevated intrarenal Ang II levels during the initial and maintenance phases of renal hypertension.

Angiotensin I↗
PubMed1991

Drake Chemical Workers' Health Registry Study: I. Notification and medical surveillance of a group of workers at high risk of developing bladder cancer.

A medical surveillance program and epidemiologic study of 408 former workers of the Drake Chemical Company (now a Superfund waste site) was established in 1986. The Drake Health Registry Study was initiated because these workers had probable past exposures to beta-naphthylamine (BNA), a potent bladder carcinogen. The registry is widely viewed as a model for notification of workers at high risk of disease due to past occupational exposures. By the 40th month, 90% of the 366 living workers had been notified of the existence of the registry; 262 had been enrolled in the annual or semi-annual screening for bladder cancer. Among these, 27 persons have had abnormal screening results indicating moderate to high risk of bladder cancer and have been made eligible for further diagnostic tests. While no invasive bladder tumors were found among 18 persons completing the extended diagnostic evaluation, two diagnoses of moderate to severe dysplasia have been made. The registry has also identified three living and three deceased cases of bladder cancer in the cohort; a mortality analysis showed a 20- to 30-fold excess of bladder cancer. An incidence projection, based on the six identified cases, reveals that between six and ten new bladder cancer cases are likely to occur among the Drake cohort over the next 20 year period.

2-Naphthylamine↗
PubMed1991

Mortality of employed men and women.

This paper presents mortality data for a 1% sample of men and women in England and Wales who were employed at the time of the 1971 Census of Population. It provides background information on the "healthy worker effect" by age, social class (as determined by occupation), cause of death, and length of follow-up. As expected, relative mortality of those employed at census rose with subsequent follow-up. This effect was strongly age-related, apparently as a consequence of the development (and increasing predominance) of chronic diseases with age. This suggests a unified explanation for some of the variation described in the literature. Statistical modelling of the relationship between mortality and length of follow-up confirmed that the healthy worker effect did not entirely disappear as follow-up progressed in this study. We examined social background as an explanation for this persistently low mortality, but found no evidence to suggest that it was an important factor.

Adult↗
PubMed1991

Normocalcemia without hyperparathyroidism in vitamin D-deficient rats.

Despite numerous attempts, no reliable dietary regimen exists to achieve vitamin D deficiency (-D) in rats without attendant changes in plasma parathyroid hormone (PTH), Ca, or phosphate. This represents an important obstacle to proper investigations of the physiologic role(s) of vitamin D metabolites in the function of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] target tissues. This paper describes the successful development of such a diet, which uses a combination of high Ca content, properly controlled Ca/P ratio, and lactose. Normal weanling rats were fed diets containing A, 0.8% Ca, 0.5% P, +D3, or -D diets containing B, 0.8% Ca and 0.5% P; C, 2.0% Ca and 1.25% P; or D, 2.0% Ca, 1.25% P, and 20% lactose. After 6 diet weeks group D rats remained normocalcemic and normophosphatemic, but diet groups B and C became hypocalcemic (6.9 +/- 0.8 and 7.2 +/- 0.4 mg/dl, respectively). Thus high dietary Ca and P was incapable of maintaining normal plasma Ca levels in the absence of dietary lactose. The normocalcemia in group D was not maintained by elevated PTH secretion because N-terminal PTH levels were also normal (14 +/- 3 versus 20 +/- 5 pg/ml). In contrast, PTH levels were markedly elevated in hypocalcemic groups B and C (47 +/- 7 and 48 +/- 10 pg/ml, respectively). Plasma 25-OHD3 and 1,25-(OH)2D3 levels were reduced to less than 120 and less than 12 pg/ml, respectively, in all -D groups. Thus the high-Ca diet and the use of normal weanlings did not impede the development of vitamin D deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Presence of blood significantly decreases transmission of 630 nm laser light.

Application of 630 nm light in the presence of blood is often necessary during photodynamic therapy, particularly for proposed intravascular applications. The effect of blood on transmission of 630 nm light was studied using a three dimensional irradiation model and an integrating sphere for measuring light transmitted in any direction through blood layers of different hematocrit (25 to 75) and thickness (.15 to .98 mm). There was an inverse relationship between transmission and hematocrit and transmission and blood thickness, p = .000 for both. At a physiologic hematocrit of 46, transmission through blood layers of .98, .41, .28, and .15 mm were 21%, 33%, 29%, and 58% respectively. These blood thicknesses or more are likely in the clinical environment, and can be expected to result in significant transmission losses. The marked absorption of 630 nm light by blood indicates that removal of the blood or correction for power loss should be employed when 630 nm light is applied in a blood containing environment.

Absorption↗
PubMed1991

In vivo canine coronary artery laser irradiation: photodynamic therapy using dihematoporphyrin ether and 632 nm laser. A safety and dose-response relationship study.

This study examined the safety and dose-response relationships of 632-nm laser irradiation of photosensitized normal coronary arteries in 27 dogs. Fifteen received 2.5 mg/kg dihematoporphyrin ether (DHE), seven received no sensitizer, and five had coronary instrumentation but no laser (sham laser procedures) at nine coronary sites--four sensitized, five non-sensitized. Laser energy of 82 to 1,640 J/cm2 was delivered via a 584 microns diffusing-tip optical fiber, providing estimated tissue fluences of 20 to 410 J/cm2. Serial electrocardiograms and selective coronary arteriograms were performed up to 1 month post laser irradiation. Histologic examination was performed of all treated sites. Tissue fluences less than 200 J/cm2 produced no permanent electrocardiographic or angiographic changes; reversible spasm occurred in 2/8 photosensitized-lased, 0/2 non-photosensitized-lased. Minor medial damage occurred in 1/8 sensitized-lased, 1/2 non-sensitized-lased, and 0/9 sham-lased sites. At tissue fluences greater than 200 J/cm2 4/7 sensitized-lased animals died prematurely--one due to immediate and irreversible coronary spasm and Q wave infarction, one due to fibrillation during 48-hour follow-up coronary angiography (normal angiograms), two with normal electrocardiograms and angiograms within one day of undetermined death; 0/5 non-sensitized-lased animals expired or had coronary spasm; and 3/7 sensitized-lased and 0/5 non-sensitized/lased had significant medial to adventitial histologic damage. Coronary irradiation at less than 200 J/cm2 appears to be safe for photodynamic treatment of atherosclerotic lesions. Pretreatment for coronary spasm is appropriate.

Angioplasty, Balloon, Coronary↗
PubMed1991

Deficiency of vitamin D metabolites directly stimulates renal 25-hydroxyvitamin D3-1-hydroxylase activity in rats.

Renal 25-hydroxyvitamin D3-1-hydroxylase (1-hydroxylase) enzyme activity in rats is known to be increased by parathyroid hormone (PTH), hypophosphatemia, and hypocalcemia. Thus, enzyme activity is markedly increased in vitamin D-deficient states, but whether this stimulation is a direct response to the vitamin D deficiency or only occurs following the associated changes in plasma calcium, phosphate, or PTH is unclear. We tested whether vitamin D deficiency per se influences 1-hydroxylase activity in renal cortical slices using a normocalcemic rat model of vitamin D deficiency. Weanling male rats were fed one of the following three diets: (A) 0.8% Ca, 0.5% P, 2.2 IU vitamin D3/g; or vitamin D-deficient diets containing, (B) 0.8% Ca, 0.5% P; and (C) 2.0% Ca, 1.25% P, 20% lactose. Vitamin D-deficient rats fed diet B were hypocalcemic with elevated PTH at both test periods, and 1-hydroxylase activity was increased more than 100-fold compared with rats fed diet A. Plasma calcium, phosphate, and PTH levels were the same in groups A and C, but 1-hydroxylase activity was also substantially elevated in group C versus group A rats (104- and 17-fold increases after 10 and 19 diet weeks, respectively). These data lead to the important conclusion that severe deficiency of vitamin D metabolites per se provides a strong and independent stimulus to renal 1-hydroxylase activity in rats, perhaps due to the absence of 1,25(OH)2D3-mediated enzyme inhibition.

Animals↗
PubMed1991

An evaluation of potential prognostic indicators in cardiac patients.

Cardiovascular disease results in more deaths and higher medical costs than any other medical problem. Cardiac patients may be transported to centers for specialized care. We evaluated historical, current event, and physiologic items (n = 32) for ability to predict use of specialized care and hospital costs. For 199 patients studied, seven items were prognostic. A model classifying patients by presence of predictors was developed. For the group without predictors and the group with multiple predictors, sensitivity and specificity were respectively very good. For 125 (63%) of the patients in middle categories, the model was not sufficiently sensitive to be prognostic. A scoring system for all cardiac patients could not be developed. Patients requiring only diagnostics were responsible for financial deficits, as were all Medicare patient groups. Patients staying longer than seven days, or having surgery, or both, were responsible for the largest deficits (if on Medicare) and the highest profits (if not on Medicare). Advance validation of the need to transport is difficult, with far-reaching medical and financial implications.

Adult↗
PubMed1991

Regulation of parathyroid hormone secretion by plasma calcium in aging rats.

Plasma immunoreactive parathyroid hormone (irPTH) levels increase with aging. This study determined 1) whether NH2-terminal irPTH secretory responses to induced hypocalcemia differ between adult (6-mo-old) and aged (24- to 26-mo-old) male rats and 2) whether a higher set point for irPTH release by Ca is responsible for the elevated irPTH levels with aging. Basal irPTH levels were 68% higher and 1,25-dihydroxyvitamin D3 levels were 44% lower in aged rats. An acutely induced, constant hypocalcemic stimulus [0.32 mM decrement in ionized Ca (Ca2+) for 2 h] was developed in catheterized conscious adult and aged rats by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) infusion using the Ca clamp technique. The initial irPTH secretory response to acute hypocalcemia (5-10 min) was reduced in aged rats (1.9- vs. 3.1-fold increase), suggesting reduced hormone stores. However, higher sustained irPTH levels (30 min to 2 h) were maintained in aged rats, indicating increased irPTH synthesis and release. The EGTA infusion rate necessary to maintain constant hypocalcemia was less in aged rats, suggesting skeletal resistance to PTH. Slow EGTA and Ca infusions were used to determine irPTH secretion at plasma Ca2+ levels from 0.7 to 1.5 mM. In aged rats, irPTH levels were higher at all Ca2+ concentrations, but the set point for irPTH release by Ca2+ was the same as in adult rats. Thus the elevated irPTH secretion in aged rats is not caused by a change in the set point for irPTH release but does result in decreased irPTH stores.

Aging↗
PubMed1991

Plasma Ca influences vitamin D metabolite levels as rats develop vitamin D deficiency.

The hypocalcemia that accompanies vitamin D deficiency is a major obstacle to proper interpretation of the role(s) of vitamin D metabolites in Ca-sensitive tissues. This paper describes the development and complete characterization of a dietary regimen with which normocalcemia was maintained in rats throughout the development of vitamin D deficiency. Normal weanling rats were fed diets containing 0.8% Ca, 0.5% P, and vitamin D3 (group A), or vitamin D-deficient diets containing 0.8% Ca and 0.5% P (group B); 2.0% Ca and 1.25% P (group C); or 2.0% Ca, 1.25% P, and 20% lactose (group D) for 19 wk. Group D rats were normocalcemic and normophosphatemic with normal parathyroid hormone (PTH) levels throughout the study. In contrast, from 4-19 diet wk, groups B and C were hypocalcemic with elevated PTH. Initially, plasma 25-hydroxyvitamin D3 [25(OH)D3] levels decreased most rapidly, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels decreased least rapidly in group B rats, such that plasma 25(OH)D3 levels were reduced to 200-300 pg/ml before a decrease in 1,25(OH)2D3 levels was observed. However, vitamin D metabolite levels were similar in groups B, C, and D from 4-19 wk. Duodenal active Ca transport mirrored changes in plasma 1,25(OH)2D3 levels and was abolished after 10 wk. The results also suggested that vitamin D may not be necessary for normal bone mineralization since tibia mineral content and plasma alkaline phosphatase levels were similar in normocalcemic groups A and D throughout the study.

Animals↗
PubMed1991

Heterogeneous response to PTH in aging rats: evidence for skeletal PTH resistance.

Plasma immunoreactive parathyroid hormone (irPTH) levels increase and renal responsiveness to pharmacological doses of PTH decreases with advancing age. This study tested whether 1) decreased irPTH clearance contributes to the elevated NH2-terminal irPTH levels seen in aged rats and 2) aged rats respond to physiological levels of rat PTH. Conscious adult (7-mo-old) and aged (25-mo-old) male Sprague-Dawley rats were infused for 2 h with rat PTH-(1-34) to achieve steady-state levels in plasma (110-120 pg/ml). Basal irPTH levels were 77% higher (P less than 0.01), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels were 46% lower (P less than 0.05) in the aged rats. Renal function was not significantly different in these two groups. The metabolic clearance rate of irPTH was rapid and not different in adult and aged rats (99 +/- 8 vs. 111 +/- 7 ml.min-1.kg-1, respectively). After the PTH infusion, plasma ionized and total calcium and 1,25(OH)2D3 levels increased significantly in adult rats, whereas no changes were observed in aged rats. In contrast, a similar significant hypophosphatemic response (23-25% decrease) was seen in both age groups, but the hypophosphatemia was maintained for longer in aged rats. Thus the elevated plasma irPTH levels in aged rats are caused solely by increased secretion. Finally, there is a heterogeneity in the responses to PTH infusion in aged rats, suggesting that the aged rat skeleton, like the kidney, is PTH resistant.

Aging↗
PubMed1991

Homologous amino-terminal radioimmunoassay for rat parathyroid hormone.

Existing radioimmunoassays for parathyroid hormone (PTH) in rat plasma are based on cross-reactivity of rat PTH (rPTH) with heterologous antisera. We used the synthetic NH2-terminal fragment of rPTH [rPTH-(1-34)] to develop a homologous radioimmunoassay for circulating PTH. An antiserum to rPTH-(1-34) was raised in a goat (G-813), and the same peptide was used as radioligand (125I) and standard. Purification of the label by high-performance liquid chromatography (HPLC) increased specific binding greater than twofold and sensitivity by 50-100%. With a final antiserum dilution of 1:70,000, maximum specific binding of 30-33%, nonspecific binding of 1-5%, and 50-microliters sample additions, the assay detection limit was 1.8-2.5 pmol/l. A midregional fragment of human PTH did not displace 125I-labeled rPTH-(1-34). HPLC of extracts of rat parathyroid glands and hyperparathyroid plasma showed only a single peak of immunoreactivity that eluted 2 min after rPTH-(1-34). Dose dilution curves for rat parathyroid gland extracts, rPTH-(1-34) added to rat plasma, and endogenous rat plasma PTH all paralleled the standard curve. Immunoreactive PTH (irPTH) was detectable in greater than 90% of fasting normal rat plasma and changed appropriately in response to hyper- and hypocalcemia induced by low-calcium and vitamin D-deficient diets, injections of calcium and EDTA, and after thyroparathyroidectomy. The normal range for rat plasma irPTH was less than 2.0-12 pmol/l, in general agreement with bioassay results of others. Thus rPTH-(1-34) is an excellent immunogen for raising antisera to rPTH, and assays incorporating it may be of great value in studying rat parathyroid physiology.

Animals↗
PubMed1991

An insight into early reproductive processes through the in vivo model of ovum donation.

To gain insight into early reproductive processes we have prospectively designed ovum donation protocols to elucidate several phenomena relating to embryo implantation and pregnancy sustenance. Artificial endometrial cycles with variable follicular phases were induced in 60 recipients by sequential estrogen and progesterone. A total of 964 oocytes were retrieved throughout 43 ovum donation attempts, for an average of 22.4 (range, 16-41) eggs/retrieval. The overall delivery rate per egg retrieval (donors and recipients combined) was 72.1% (31 of 43). The shortest estrogen stimulation (short follicular phase) resulting in ongoing pregnancies was 5 days in duration, while the longest (long follicular phase) was 35 days in duration before progesterone initiation. Utilization of variable length follicular phases, artificially extended the stage of endometrial receptivity to over 4 weeks. To assess the window of implantation, same age embryos were transferred onto endometrium of different maturational stages. Pregnancies were documented with embryo transfers between luteal day 1 (day 15) to luteal day 6 (day 20), extending the window of implantation in the human to at least 6 consecutive days. To evaluate the relative contribution of oocyte quality and endometrial receptivity to pregnancy outcome, common source ova were transferred onto endometrium with variable hormonal exposure. Despite the drastically different follicular phase estradiol levels and periods of exposure, similar delivery rates were attained in donor cycles (29.4%) and recipient cycles during short follicular phases (29.6%). Slightly higher delivery rates (39.4%) were observed with long follicular phases. The comparable pregnancy rates in donors and recipients are attributed to the common source oocytes regardless of endometrial stimulation.

Adult↗
PubMed1991

Humanizing patient care. A new medical paradigm.

Is the body of man merely a machine, with disease representing the breakdown of that machine, or should we adopt a more holistic view that reflects the integral relationship of mind, body and the environment?

Burnout, Professional↗
PubMed1990

Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks.

This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. The highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. In the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. The prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Children's Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection.

Adolescent↗
PubMed1990

International trends in cancer mortality in France, West Germany, Italy, Japan, England and Wales, and the USA.

Age-specific worldwide trends in cancer mortality were reviewed, with emphasis on cancer sites where increases have been reported in the USA. Cancer rates vary by factors as high as 30 between all countries, and 5-fold within and between industrialised countries. In Italy, Japan, Federal Republic of Germany, England and Wales, and the USA, patterns of cancer mortality have shifted uniformly over the past two decades. Stomach cancer continues to decline, while brain and other central-nervous-system cancer, breast cancer, multiple myeloma, kidney cancer, non-Hodgkin lymphoma, and melanoma have increased in persons aged 55 and older. Cancer of the lung is starting to decline for men under age 85 and women under age 60 in England and Wales and men under age 45 in the USA, but is still rising for men and women in other countries. All forms of cancer are increasing in persons over age 54 except lung and stomach (which together comprise between 20% and 43% of all cancer in males in these countries). Studies of the quality of ascertainment and enumeration indicate that these increases are not attributable solely to diagnostic artifacts or to increased access to health care, although both these factors may be involved. These recorded increases in cancer should be assessed in greater detail to provide better projections of health care needs and to identify causal factors that may be controlled. The changes in cancer other than lung are so great and rapid that their causes demand intensive investigation.

Adult↗