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Biomedical subjects

J Carpenter

Publications and source records attributed to J Carpenter.

At least 55 records · Page 3Linked to original sources

Interleukin 4 expressed in situ selectively alters thymocyte development.

Using a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL-4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization of calcium mediated by these receptors. In contrast, transgenic single-positive (CD4+CD8- and CD4-CD8+) thymocytes and peripheral T cells exhibit decreased TCR-mediated calcium mobilization. The development of CD4-CD8+ thymocytes is significantly perturbed by IL-4 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4-CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers of B cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that IL-4 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.

Animals↗

Cardiovascular pharmacology of dopexamine in low output congestive heart failure.

Dose-response infusions (0.25 to 4.0 micrograms/kg/min) and extended infusions of dopexamine, a new synthetic catechol with beta 2 adrenergic and dopaminergic agonist effects, were performed in 12 patients with low output congestive heart failure (CHF). The central and regional hemodynamic effects and responses in renal function were determined and compared with those of saline-placebo control patients in a randomized, double-blind, crossover design. Dopexamine significantly increased cardiac output at a dose greater than or equal to 0.25 micrograms/kg/min secondary to an increase in stroke volume at greater than or equal to 0.25 micrograms/kg/min and heart rate at greater than or equal to 0.50 micrograms/kg/min. Dopexamine evoked a significant decrease in systemic and pulmonary vascular resistances, with mild reductions noted for systemic and pulmonary diastolic pressures. Right and left ventricular filling pressures decreased over the entire dose range of dopexamine concomitant with a demonstrable improvement in the indexes of ventricular performance. Dopexamine preferentially increased visceral (renal, hepatic-splanchnic) blood flow over that of limb. Urine volume and sodium excretion increased slightly with dopexamine. Dopexamine elicits rather prominent vasodilating effects (particularly of visceral vascular beds), some positive inotropy and chronotropy and favorable responses in renal function.

Adrenergic Agonists↗

Megestrol acetate v tamoxifen in advanced breast cancer: correlation of hormone receptors and response.

This report describes the preliminary results from a randomized study comparing megestrol acetate with tamoxifen in the treatment of postmenopausal women with advanced breast cancer, correlating estrogen receptors (ER) and progesterone receptor (PgR) status with response. Patients received megestrol acetate (40 mg) orally four times daily or tamoxifen (10 mg) orally twice daily. If the initial therapy failed, patients were crossed over to the alternate treatment. Of 197 patients entered in the study, 190 were considered evaluable. The overall response rates were 35% with megestrol acetate and 42% with tamoxifen. Twenty-three percent (7/30) of patients responded to megestrol acetate after being crossed over from tamoxifen, while 22% (6/27) responded to tamoxifen after being crossed over from megestrol acetate. Response did not correlate significantly with combined receptor (ie, ER plus PgR) levels. A significant trend was seen between ER level and response only in the tamoxifen group. There was no association between PgR levels and response for either tamoxifen or megestrol acetate.

Antineoplastic Agents↗

High count rate first-pass radionuclide angiography using a digital gamma camera.

In this study, first-pass radionuclide angiography (FPRNA) was performed using a digital single-crystal gamma camera. Twenty-nine men and six women (ages 43-80, mean 61 yr) underwent FPRNA in the supine position immediately prior to cardiac catheterization. Total counts/sec in the whole field-of-view in the right ventricular phase were 150,352 +/- 26,006. Background uncorrected counts in the representative cycle were 7,651 +/- 2,527 at end-diastolie and 4,904 +/- 2,314 at end-systolie. A linear correlation between FPRNA left ventricular (LV) ejection fraction and contrast LV ejection fraction gave an r = 0.95 with an s.e.e. of 0.05. Analyses of intra- and interobserver variability gave r = 0.99 and 0.98 and an s.e.e. of 0.02 and 0.03, respectively. Spearman-Rank correlation coefficients between FPRNA and contrast angiographic wall-motion scores were greater than 0.8 for all walls, while sensitivity/specificity were 0.86/0.90, 0.76/1.00, 0.76/1.00 for anterior, apical, and inferior wall-motion abnormalities, respectively. We conclude that satisfactory counting statistics for FPRNA can be obtained with a digital gamma camera, and that accurate and reproducible measurements of global and regional left ventricular function can be obtained with this technique.

Adult↗

Metastatic breast cancer: preliminary results with oral hormonal therapy.

Hormonal therapy is very effective in the treatment of patients with metastatic breast cancer. Response to various therapies leads to improved quality of life and prolonged survival. This clinical trial compared two commonly utilized additive hormonal agents, tamoxifen citrate and megestrol acetate (Megace). Preliminary data indicate equal efficacy and equal toxicity of these two hormones and suggests that both are suitable for first-line hormonal treatment of stage IV breast cancer.

Administration, Oral↗

Potential for percutaneous transluminal coronary angioplasty before initial and repeat coronary artery bypass grafting in the Coronary Artery Surgery Study (CASS) Registry population.

Retrospective analysis of preoperative angiograms was conducted to determine potential candidacy for PTCA among the NHLBI Coronary Artery Surgery Study (CASS) Registry population undergoing initial and repeat CABG. Conservative criteria believed to be universally acceptable for PTCA were used. Patients were considered potential PTCA candidates if: (1) CABG had been performed to only 1 coronary artery system; (2) the critical disease was localized to the most proximal segment of that coronary artery system; (3) all distal segments of that coronary artery system were free of critical disease; and (4) the morphologic characteristics of the obstructing lesion were discrete and isolated. Left main CAD was excluded. Among persons who underwent initial CABG, 2.8% (261 of 9,369) were PTCA candidates, and 7.1% (20 of 283) of those who underwent repeat CABG were considered suitable for PTCA. The operative mortality risk of the PTCA candidates who underwent initial CABG was 0.4% (1 of 261). No PTCA candidates died during repeat CABG. Perioperative MI occurred in 2.3% (6 of 261) of the PTCA candidates who had initial CABG; none occurred among those who underwent repeat surgery. Total surgical complications occurred in 15.7% (41 of 261) of the PTCA candidates at initial CABG and in 5% (1 of 20) who had repeat CABG. These operative mortality and morbidity risks are lower than those reported for similar patients who undergo PTCA.

Adult↗

Peak exercise and immediate postexercise imaging for the detection of left ventricular functional abnormalities in coronary artery disease.

Eleven patients without significant coronary artery disease (CAD) (group A), 22 patients with significant CAD and no prior myocardial infarction (MI) (group B), and 10 patients with CAD and a previous MI (group C) were imaged at rest, at peak exercise and immediately after exercise by first-pass radionuclide angiography. At peak exercise, mean left ventricular (LV) ejection fraction (EF) did not change significantly in group A or C and decreased significantly in group B. However, in all groups mean LVEF increased significantly immediately after exercise. Examination of potential criteria for an abnormal LVEF response showed that changes from rest to peak exercise were sensitive for detection of CAD but were not specific. Postexercise criteria were more specific but relatively insensitive: 15 of 32 patients (47%) with CAD showed a normal (greater than 5% increase over rest) response after exercise. Similarly, a regional abnormality at peak exercise was 100% sensitive, compared with a sensitivity of 78% after exercise for the whole group, and only 68% in patients without prior MI. Seven patients would have been misclassified as normal if postexercise imaging alone had been performed. The likelihood of an abnormal postexercise EF response was related to the extent of CAD: No patient with 1-vessel, 8 of 17 with 2-vessel and 9 of 12 with 3-vessel CAD showed such a response. Peak exercise imaging is necessary to achieve maximal sensitivity for the detection of CAD, and a high false-negative rate will be obtained if postexercise imaging only is used. The combination of peak exercise and postexercise imaging may be of value in assessing the severity of CAD.

Adult↗

Intestinal sclerosis with pseudo-obstruction in three dogs.

Intestinal sclerosis causing chronic intestinal pseudo-obstruction was diagnosed in 3 dogs. The pseudo-obstruction was characterized by vomiting and weight loss of 2 weeks' to 3 months' duration. A patent intestinal lumen was determined by contrast radiography and verified at surgery. Intestinal biopsy revealed diffuse atrophy, fibrosis, and mononuclear cell infiltration of the tunica muscularis. Each dog was euthanatized because of a progressive, deteriorating clinical course.

Animals↗

Intramural intestinal hematoma causing obstruction in three dogs.

Intramural hematoma of the intestine caused intestinal obstruction in three dogs. Two dogs were examined because of vomiting and anorexia of several weeks' duration. In one of these, an intramural hematoma of the duodenum was associated with chronic pancreatitis. A cause was not found in the second dog. The third dog, which had clinical and radiographic evidence of gastric dilatation, was found at surgery to have hemoperitoneum associated with a ruptured intramural intestinal hematoma. In 1 dog, the hematoma was evacuated through a serosal incision. In the other 2 dogs, the problem was resolved by resection of the involved segment of intestine, followed by anastomosis. All 3 dogs recovered without complications.

Animals↗

Clinical correlations between serum glucose variance and reported symptoms in human subjects.

The evidence presented in this report suggests that, in both a healthy people and patient populations, there are clinical and biochemical (fasting serum glucose) gradations of health and sickness. What is particularly fascinating is the fact that, as one progressively develops a symptomless and signfree subset, the blood glucose levels become more homogeneous, meaning that glucose scores cluster to the mean. This enhances the diagnostic, therapeutic and predictive utility of blood glucose scores. While such clinico-biochemical parallelisms are clear, it is essential to mention the point that they do not necessarily prove cause-and-effect. But our interest has been sufficiently stimulated to study several other possible correlates between biochemical variances and the degree of reported symptomatology.

Adolescent↗

First-pass radionuclide angiography via pulmonary arterial catheters. A critical analysis of background components.

Residual background activity following first-pass radionuclide angiography was assessed in 44 patients after eliminating activity in the right heart, left lung, and most of the right lung. The ejection fraction (EF) was calculated in two ways: (a) assuming background activity was present only in the right heart and lungs, and (b) correcting for scattered radiation by placing a circular region of interest around the left ventricle. With the first method, contrast EF was significantly underestimated in both AP and RAO views. With the second method, correlation was close in both views and absolute values agreed well with contrast EF. These results indicate that there is a substantial and measurable background component, due mainly to Compton scatter, even when activity from the right heart and lungs is eliminated.

Adult↗

Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a "cycle active" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.

Agranulocytosis↗

A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer.

The Southeastern Cancer Study Group, in a prospectively randomized study involving patients with advanced breast cancer, has compared a low dose intermittently administered five-drug regimen including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) with an aggressively administered three-drug regimen including cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF). CAF induced more responses and more complete responses and a longer duration of disease control. However, only a marginal difference was demonstrated in overall survival between the two regimens (p = less than 0.10). Patients with a good risk pattern of metastases, i.e. those with nodular local chest wall recurrence, nodular pulmonary metastases, or bone-only metastases were more likely to achieve a response and survive longer than those with a poor risk pattern, i.e. lymphangitic pulmonary metastases, pleural effusion with chest wall ulceration, or widespread metastases, including hepatic. All of the differences between the two regimens were noted in the good risk pattern groups. CAF provided no additional benefit to patients presenting with poor risk patterns of metastases. Adriamycin-containing combinations may achieve a greater degree of tumor cell kill in certain subsets of patients with advanced breast cancer, but this provides only a marginal increase in survival.

Antineoplastic Agents↗