Mourner among the children. The psychological crisis of Emily Dickinson. I.
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On a macroscopic scale, the structural characteristics of whole bone are likely dependent on the distribution of typically applied loads to the bone surface, the full bone shape, the thickness of the cortex at the various surface positions, and the distribution of cancellous bone material. X-ray computed tomography is presently the best available method for assessing the macroarchitecture of bone in-vivo. Fine detail, three-dimensional CT methods are available to measure regional bone mineral density (rBMD) in contiguously spaced small volumes and have been applied to the assessment of macroarchitecture in vertebrae. The more detailed rBMD methods produce radiation exposures to the subject similar to lumbar radiography and substantially higher than traditional QCT. The cancellous bone within lumbar vertebral bodies has been found in cross-sectional studies to have increased density in the inferior, posterior and lateral regions. Notably, regions with higher density at age 40 have a larger decline with age. The vertebral body cortex declines with age at a slower rate than observed for cancellous bone; however, the decline with age of cortical bone appears to vary substantially amongst subjects. The amount of cortical bone in the anterior portion of the body is less than in the lateral portion, which may explain previous discrepancies in assessing the fraction of vertebral body bone in the cortex.
The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.
We noted the earliest morphological changes in the motor endplates 8 weeks after the induction of streptozotocin diabetes in rats. Morphometric measurements showed reduced axonal areas of the lateral plantar and the sciatic nerves in the diabetic rats 28 but not 2 and 8 weeks after the experiment. These findings suggested distal axonopathy.
BACKGROUND: Although epidemiological studies have failed to demonstrate an increased incidence of breast cancer in women who had undergone prior prosthetic augmentation mammoplasty (PAM), it has been reported that when breast cancer arises in this group it presents mostly in a palpable form and at a more advanced stage. This is thought to be secondary to suboptimal mammographic evaluation caused by the masking effect of the implant. This study was undertaken to determine, in our experience, whether breast cancer arising in women who had undergone PAM could be detected in a prepalpable form by mammography and whether it presented at a more advanced stage as compared with nonaugmented women with breast cancer. METHODS: The charts of 22 patients, treated by at least one of the authors, in whom 23 breast cancers developed after PAM (group A) were retrospectively reviewed. The comparison groups consisted of 611 nonaugmented patients who underwent 636 procedures for the treatment of primary breast cancer at our institution (group B) and the surveillance, epidemiology, and end results (SEER) data (group C). Parameters studied were mode of detection, tumor size, axillary lymph node involvement, and histopathology. RESULTS: No significant differences between the groups were found in mean tumor size (group A vs. group B), the incidence of preinvasive cancer (group A vs. group B) or axillary lymph node involvement (group A vs. group B and group A vs. group C). Breast-preserving surgery was performed significantly less in augmented patients (group A vs. group B). CONCLUSION: We conclude that prepalpable and preinvasive breast cancer can be detected in the PAM patient by mammography and that the stage of presentation in this group is not significantly different than in nonaugmented patients. Total mastectomy is preferred over breast-preserving procedures for the treatment of breast cancer in the PAM patient.
BACKGROUND: The internal mammary lymph nodes (IMN) have received little attention in recent years, yet are a well-documented site of metastasis and a major prognostic factor in early-stage breast cancer. METHODS/RESULTS: Ten-year follow-up of the final 195 patients treated by extended radical mastectomy (ERM) in this practice (selected largely on the basis of medial tumor location, and comprising 15% of all patients treated from 1965 to 1978) found IMN+ in 24% of all cases: 36% of AX+ versus 18% of AX- patients (p = 0.0023). In a multivariate analysis, the disease-free survival impact of IMN+ (p = 0.004) was second only to axillary node involvement (p < 0.0005), and surpassed tumor size (p = 0.077). IMN+ was equally frequent for tumors less than, or greater than, 2 cm (24%), and was not significantly related to patient age. Among AX- patients, there was a twofold greater risk of recurrence or death at 10 years for IMN+ than for IMN-. Among T1N0 patients, 19.6% were IMN+. CONCLUSIONS: Failure to consider IMN status in the steadily enlarging cohort of T1N0 breast cancers may result in the undertreatment of a significant proportion of stage I patients. Systemic adjuvant therapy should be considered for T1N0 patients with central or medial tumors.
From 1949 to 1977, 39 patients with localized malignant retrorectal tumors were treated at Memorial Sloan-Kettering Cancer Center. Chordomas were the most frequent histologic type (38 per cent of patients) followed by neurogenic tumors (15 per cent) chondrosarcomas, hemangiopericytomas, and embryonal adenocarcinomas (8 per cent each). Treatment consisted of surgical excision in 28 patients (18 of whom received adjuvant radiotherapy and/or chemotherapy). Ten patients were treated nonsurgically, receiving radiation and/or chemotherapy alone. Large tumors were most successfully managed by a combined surgical approach consisting of exploratory celiotomy, rectal mobilization, and bilateral hypogastric artery (with middle sacral artery and vein) ligation, followed by transsacral tumor excision with incontinuity sacrectomy. For all treated patients, survival at 5, 10, 15 and 20 years was 69 per cent, 50 per cent, 37 per cent and 20 per cent, respectively. Long-term disease-free survival (17 to 25 years post treatment) was noted in six patients. [Key words: Tumor(s), retrorectal, malignant; Tumor(s), treatment].
Epithelial cells were isolated from fetal bovine trachea by exposing and stripping the mucosal epithelium from the adjacent connective tissue. The tissue was minced and enzymically dissociated in Ca-Mg-free medium containing dispase and dithiothreitol. The stripping procedure and selective trypsinization produced epithelial cell cultures free of fibroblasts. Seeded on plastic, the plating efficiency was 21.5% with a doubling time of 24 h. Dome formation, evidence of occluding junctions and active ion transport characteristic of epithelial cells, was common. Growth of the cells on glass, collagen, and Engelbreth-Holm-Swarm (EHS) substrate demonstrated a striking difference in morphology. Cells grown on EHS presented a more distinctly three-dimensional growth pattern and many more microvilli when compared to cells grown on glass or collagen. The cells retained their epithelioid characteristics through more than 30 passages as shown by the presence of distinct apical and basolateral membranes, tight junctions, and positive keratin staining.
The failure of many cell culture isolates of Mycoplasma hyorhinis to grow on microbiological media has stressed the need for alternate assays to detect these organisms. The use of freshly prepared yeast extract in mycoplasmal media together with incubation in 5% CO2/air successfully detected M. hyorhinis in 12 of 12 infected cultures. These were not detected by the use of conventional mycoplasmal media using aerobic or anaerobic incubation. This assay may also be helpful in detection of other mycoplasmal species commonly isolated from cell cultures.
We have investigated the molecular phenotypic differences between Syrian hamster embryo (SHE) cells cultured at pH 6.7 or 7.3. Multiple pH-sensitive phenotypic differences were noted including changes in cellular morphology, a unique charge differential in a major cellular protein, nine uniquely expressed proteins, two unique phosphoserine/threonine phosphoproteins, one unique phosphotyrosine phosphoprotein, and the pH dependent mRNA level of a gap junctional gene (connexin 43). These differences, combined with previously described pH-specific differences (differential transformation rates and gap junctional communication), illustrate that culturing SHE cells in media that differ by 0.6 pH units (0.3 units on either side of pH 7.0) can have a profound influence on the cellular phenotype.
We developed methodology to isolate and culture rat alveolar Type II cells under conditions that preserved their proliferative capacity, and applied lipofection to introduce an immortalizing gene into the cells. Briefly, the alveolar Type II cells were isolated from male F344 rats using airway perfusion with a pronase solution followed by incubation for 30 min at 37 degrees C. Cells obtained by pronase digestion were predominantly epithelial in morphology and were positive for Papanicolaou and alkaline phosphatase staining. These cells could be maintained on an extracellular matrix of fibronectin and Type IV collagen in a low serum, insulin-supplemented Ham's F12 growth medium for four to five passages. Rat alveolar epithelial cells obtained by this method were transformed with the SV40-T antigen gene and two immortalized cell lines (RLE-6T and RLE-6TN) were obtained. The RLE-6T line exhibits positive nuclear immunostaining for the SV40-T antigen and the RLE-6TN line does not. PCR analysis of genomic DNA from the RLE-6T and RLE-6TN cells demonstrated the T-antigen gene was present only in the RLE-6T line indicating the RLE-6TN line is likely derived from a spontaneous transformant. After more than 50 population doublings, the RLE-6T cells stained positive for cytokeratin, possessed alkaline phosphatase activity, and contained lipid-containing inclusion bodies (phosphine 3R staining); all characteristics of alveolar Type II cells. The RLE-6TN cells exhibited similar characteristics except they did not express alkaline phosphatase activity. Early passage RLE-6T and 6TN cells showed a near diploid chromosome number.(ABSTRACT TRUNCATED AT 250 WORDS)
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Twelve patients with severe chronic congestive heart failure (CHF) underwent simultaneous evaluation of the pharmacokinetic, pharmacodynamic, and neurohumoral actions of a single 25 mg oral dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (CPT). Following drug administration, which raised plasma renin activity (PRA) and thereby indicated significant ACE inhibition, both free (unchanged) and total CPT (including active metabolites) were detectable in the blood with 40 minutes and peak blood levels of the agent were recorded 1 hour after CPT. Total CPT concentration was higher and persisted longer than free CPT, which became virtually nondetectable 8 hours after ingestion. Concomitantly, left ventricular function was markedly augmented by the oral ACE inhibition in all patients, with the magnitude of this improvement being closely related to the baseline PRA. Thus, the overall hemodynamic response to CPT, which rapidly appears in the bloodstream following drug intake in patients with advanced CHF, is a function of the extent of baseline renin-angiotensin-aldosterone activity.
Although the renin-angiotensin-aldosterone system has been implicated in the pathophysiology of chronic heart failure, the factors influencing the extent of renin activity have not been clarified. In the present study, we evaluated 34 patients with severe chronic congestive heart failure in terms of baseline plasma renin activity (PRA). No uniform relationships between PRA and urinary sodium excretion have been established. Although baseline PRA did not correlate with the baseline hemodynamic values, the extent of hemodynamic improvement following acute oral captopril (CPT) therapy (25 mg) was highly correlated with baseline PRA. The onset of action was rapid, so that the initial acute response could be readily assessed and at the same time could be used as a means to estimate baseline renin-angiotension-aldosterone activity. For long-term therapy, however, the response to CPT must be assessed in the context of several potentially simultaneous factors that might either enhance or compromise its effectiveness.
Both postural abnormalities and autonomic dysfunction have been identified in patients with chronic congestive heart failure (CHF). However, the effect of long-term vasodilator therapy on these phenomena has not been assessed. In this study the hemodynamic and plasma norepinephrine (PNE) responses to upright posture, as well as the cold pressor test and Valsalva's maneuver in 12 patients with severe chronic CHF during both acute and long-term captopril (CPT) therapy, were evaluated. This revealed an absence of the normal hemodynamic adjustments to upright posture and a blunted response of PNE. The heart rate and blood pressure responses to the cold pressor test and Valsalva's maneuver were similarly blunted. The reflex adjustments of systemic resistance during tilt improved with CPT therapy, but the absence of reflex tachycardia in the upright posture persisted. Additionally, there was improvement of the PNE response, and the responses of heart rate and blood pressure to the cold pressor test were virtually normalized during long-term CPT therapy. The abnormal response to the Valsalva maneuver persisted. In conclusion, hemodynamic and reflex-mediated responses to upright posture and the standard assessment of autonomic control mechanisms revealed abnormal patterns in heart failure. While the hemodynamic adjustment to postural changes and sympathetic responsiveness were improved with CPT, complete correction of these abnormalities did not occur. Whether the improvement was a nonspecific vasodilator effect or the result of specific CPT therapy remains to be determined.
The hemodynamic mechanism by which patients with chronic congestive heart failure (CHF) maintain their blood pressure (BP) in the upright posture is distinct from that of normal and hypertensive individuals. There are little data regarding the effects of chronic vasodilator therapy on the mechanisms controlling this response, especially in the presence of diuretic therapy. Therefore, 10 consecutive patients with severe chronic CHF underwent hemodynamic tilt study following acute and chronic captopril therapy. One patient developed orthostatic hypotension following first-dose captopril, but 6 of 10 had a mean BP decrease of 70 +/- 6 to 56 +/- 3 mm Hg on tilt following chronic captopril. This associated with significant reduction of plasma aldosterone, and was abolished on re-tilt following acute saline infusion. Therefore, during chronic captopril therapy of CHF, a reduction of diuretic dosage may be necessary to prevent orthostatic hypotension.