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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current concepts concerning the deposition, distribution and radiological demonstration of lead in the skeleton were investigated in five series of rats; some of these were young and others more than a year old. 10 mg of lead acetate/kg body weight were administered over a period of five to 41 days, giving a minimum of 8.4 mg and maximum of 40.4 mg of lead. A comparable control group was given similar amounts of sodium acetate. The distribution and concentration of lead in the femur was determined by the use of 210Pb. Contact autoradiographs showed band-shaped lead accumulation in the endosteal and periosteal growth regions. The degree of darkening depended on the amount of lead administered and permitted a rather coarse quantitative relationship to be drawn. Measurements of radioactivity produced similar distribution patterns. The relationship of lead concentration of epi- and metaphysis to the diaphysis averaged 2:1. The factor mainly responsible for lead deposition depended on the metabolic potential of the tissue, which itself depends largely on the growth regions. Radiologically, there was definite evidence of demineralization in the areas of lead deposition; this could be confirmed histologically by lack of trabeculae, thinning of the cortex and destruction of bone matrix. Despite its much greater absorption co-efficient, the tiny quantities of lead, compared with the bone mass (even in the highest concentrations in our experiments) cannot be detected radiologically. Biophysical calculations have been made which indicate that similar conditions occur in man. Radiological examination of the skeleton, which is used as a screening method for chronic lead poisoning, is not suitable for this purpose.
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PMID:[Lead deposits in bone--the roentgen picture as a demonstration method?]. 640 66

Local calcergy is an ectopic calcification reaction (due to hydroxyapatite formation) induced in connective tissue sites by the application of dilute solutions of certain metallic salts (calcergens). The phenomenon is usually produced in the subcutaneous tissues of the experimental animal. The single intra-articular injection of lead acetate (PbAc) solution (a known calcergen) into the knee joint of the rat is followed by opacity of the synovial membrane and para-articular tissues with the aggregation of macrophages and multinucleated giant cells and the formation of some granulation tissue. This lesion ultimately resolves and there is no cartilaginous degeneration. Repeated intra-articular injections of PbAc produce pronounced changes in the synovium and para-articular tissues. There is extensive calcific deposition with exuberant macrophage and giant cell accumulation and fibroblastic proliferation. The proliferated synovial membrance becomes adherent to articular cartilage. There is thinning and fragmentation of the latter with focal loss and replacement by fibrous tissue. Therefore, in contrast to the effects of a single injection, repeated calcergenic stimulation of the knee joint is associated with a destructive arthropathy.
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PMID:Intra-articular calcergy and its arthropathic sequelae. 669 51

A double-blind, half-side comparative dermal atrophy study of fluocortin butylester 0.75% clobetasone butyrate 0.05%, hydrocortisone acetate 1% and placebo creams was carried out in 29 healthy human male volunteers. Skin thickness was measured by a modified radiographic technique before and after an 8-week application period of the test preparations. Significant skin thinning occurred in 3 of the 10 subjects treated with clobetasone butyrate and atrophy of marginal significance in 1 of the 29 subjects treated with fluocortin butylester. The results suggest that, compared with other fluorinated topical steroids, fluocortin butylester 0.75% is unlikely to produce significant dermal atrophy when used in the short and medium term.
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PMID:A study of potential skin atrophy following topical application of weak corticosteroids. 726 64

A collagen network, composed largely of type I and III fibrillar collagens, is found in the extracellular space of the myocardium. This network has multiple functions which includes a preservation of tissue architecture and chamber geometry. Given its tensile strength, collagen is a major determinant of tissue stiffness. Its disproportionate accumulation, in the form of either a reactive or a reparative fibrosis, further increases stiffness. A degradation of collagen tethers, on the other hand, is an anatomic requisite for a distortion in tissue architecture and a reduction in stiffness that can lead to chamber dilatation, wall thinning, and even rupture of the myocardium. Collagen turnover in the myocardium is dynamic. When synthesis exceeds degradation, an adverse accumulation of collagen appears to distort tissue structure. This is true for either the hypertrophied and/or nonhypertrophied ventricle. Factors that contribute to the appearance of myocardial fibrosis are largely different from those that promote cardiac myocyte growth. Included amongst these fibrogenic factors are effector hormones of the reinin-angiotensin-aldosterone system (RAAS). Studies conducted both in intact animals (relative to dietary sodium intake) and in cultured adult cardiac fibroblasts have pointed toward the association between collagen accumulation and chronic elevations in circulating angiotensin II and aldosterone. A tissue hormonal system involving angiotensin II, endothelins and bradykinin, may likewise regulate fibrogenesis. In this regard, angiotensin converting enzyme is found in connective tissue of the normal heart, including the matrix of heart valves and the adventitia of the intramural coronary arteries, and fibrous tissue that forms following infarction or with chronic RAAS activation. The importance of ACE in the regulation of local angiotensin II and bradykinin levels and their contribution to collagen turnover is a fruitful area of research with important clinical implications. The myocardium also contains a proteolytic system, including collagenase. The characteristics and regulation of matrix metalloproteinases and their tissue inhibitors in various cardiovascular disease states requires further investigation.
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PMID:Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. 802 11

Keratoconus is a noninflammatory corneal disorder characterized by gradual stromal thinning and astigmatism. Altered degradation of corneal extracellular matrix is a suggested etiology for this disorder. In the present study we established keratocyte cultures from normal and keratoconus corneas and investigated the roles that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP, TIMP-2) may play. After chemical modification (reduction and alkylation) to remove the inhibitor and activation of enzyme with p-aminophenylmercuric acetate (APMA), keratoconus-conditioned media displayed a significant increase (p < 0.05) in the total potential gelatinolytic activity when compared with normal culture media treated in a similar manner. Basal levels of gelatinolytic activity in keratoconus culture media (no reduction, alkylation, or APMA treatment), determined by two different assay methods, tended to be about twice that of normal cell cultures. By zymography, both keratoconus and normal cultures showed identical enzyme patterns, which represented MMP-2 (72 kDa) in its proform and, depending on the treatment of the media, varying amounts of activated MMP-2 (65 kDa). This suggests that the increased gelatinolytic activity in keratoconus was not correlated with an increased appearance of either the 65-kDa-activated form of MMP-2 or a new MMP species. In addition, no differences in the amount of MMP-2 were detected that could account for the increased activities in keratoconus cultures. However, a relative decline in the detectable TIMP levels in keratoconus cultures resulted in an apparent three-fold increase in the ratio of MMP-2/TIMP. Northern blots showed no significant changes in mRNA levels for MMP-1, MMP-2, MMP-3, TIMP, or TIMP-2. These data suggest that a possible alteration in the interaction between MMP-2 and TIMP may play a role in the increased gelatinolytic activity seen in keratoconus tissues.
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PMID:Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio. 815 82

It has been suggested repeatedly that the non-heritable factors in the pathogenesis of schizophrenia involve abnormalities of prenatal neurodevelopment. Furthermore, post-mortem studies show neuropathology of apparently developmental origin in the entorhinal cortex and other brain regions of schizophrenic subjects. In an attempt to model a developmental defect of the entorhinal region in the rat, cerebrocortical proliferation was briefly interrupted during its earliest stages, when the entorhinal area is thought to undergo major cell division. Specifically, the experimental set-up involved the administration of methylazoxymethanol acetate (MAM) on 1 of 4 consecutive days of embryonal development, from E9 to E12. Analysis of the forebrain in adult animals shows reduction of the entorhinal cortex in rats treated on each of these days. This effect shifts from lateral to medial divisions of the entorhinal cortex with later administration of MAM, following a known developmental gradient. Morphological consequences of MAM administration appear to be largely confined to the entorhinal cortex in the groups treated on E9 to E11, although slight reductions of the frontal and occipital neocortex were also observed in these animals. MAM treatment on E12 produces relatively more widespread damage, as reflected among other in a small reduction of brain weight. The described brain abnormalities are not accompanied by obvious phenotypical changes in any, but the E12-treated group. They, moreover, involve cortical thinning, disorganised cortical layering, and abnormal temporal asymmetries. These finding bare some similarity to observations in brains of schizophrenic subjects. The possible relevance of this approach in modeling neurodevelopmental aspects of schizophrenia is discussed.
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PMID:Methylazoxymethanol acetate-induced abnormalities in the entorhinal cortex of the rat; parallels with morphological findings in schizophrenia. 957 86

The objective of this study was to determine whether progestin-only contraceptives induce thinning of the vaginal epithelium in nonhuman primates. Eight intact rhesus monkeys (four per group) were treated with either a single intramuscular injection of 30 mg of Depo-Provera or a subcutaneous insertion of Norplant-II (2 x 75 mg rods; day 0). Norplant-II rods were removed 90 days after insertion. Vaginal biopsies were obtained during a pretreatment menstrual cycle and following treatment on days 10, 30, 60, 118, and 146. Formalin-fixed vaginal biopsies were evaluated for epithelial thickness and the degree of keratinization. The circulating levels of estradiol, progesterone, medroxyprogesterone acetate (MPA), or levonorgestrel (LNG) were monitored throughout the study by specific radioimmunoassays. Circulating levels of estradiol and progesterone confirmed the stage of the menstrual cycle in which pretreatment biopsies were obtained. Following treatment with Depo-Provera, serum levels of MPA increased to 2.3 +/- 0.6 ng/ml (x +/- SE, n = 4) within 24 hr. Serum levels of MPA were maximal on day 14 (5.5 +/- 0.9 ng/ml), dropped below 1 ng/ml by day 50, and were nondetectable by day 70. Circulating levels of LNG were elevated 24 hr after insertion of Norplant-II (5.8 +/- 3.0 ng/ml), peaked on day 2 (7.6 +/- 4.2 ng/ml), remained between 1.4 and 6.2 ng/ml from days 14 to 90, and were nondetectable by day 118, the first serum sample after removal of Norplant-II. There were no significant differences (p > 0.05) in the epithelial thickness (microm), number of epithelial cell layers, or type of epithelium present in vaginal biopsies obtained during the follicular or luteal phases of the pretreatment menstrual cycle. Conversely, a pronounced effect of progestin treatment was observed on the vaginal epithelium. There were no significant differences (p > 0.05) between the two progestin treatment groups, but a significant effect (p < 0.05) over time was observed (two-way ANOVA). Compared with pretreatment menstrual cycle controls, the vaginal epithelial thickness was decreased (p < 0.05) by day 30 or 60 following Norplant-II insertion or Depo-Provera injection, respectively. The number of epithelial cell layers was also decreased (p < 0.05) on days 30 and/or 60 in progestin-treated monkeys compared with pretreatment control cycles. Following removal of Norplant-II or metabolic excretion of MPA, the vaginal epithellium regenerated and the thickness was no longer different (p > 0.05) from the pretreatment control cycle. These data demonstrate that progestin-only contraceptives induced thinning of the vaginal epithelium in rhesus monkeys, and this effect was rapidly reversible following physical or metabolic removal of the progestin.
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PMID:Effects of two progestin-only contraceptives, Depo-Provera and Norplant-II, on the vaginal epithelium of rhesus monkeys. 958 96

The objective of the study was to evaluate the effect of long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) on human vaginal histology. Twenty premenopausal women currently using DMPA as a contraceptive method for two and three years were compared with 20 regularly menstruating women, who never used Depo-Provera and/or other kind of hormonal contraceptive in the last 6 months prior to the study. Subjects and controls were matched by age (+/-1 year), body mass index (kg/m2) (+/-1.0), number of pregnancies (+/-1), age at first intercourse (+/-1 year), years of sexual activity (+/-1 year), and number of partners during their life (+/-1). Vaginal biopsies were performed in users at 90+/-7 days after the last injection and in nonusers at day 20-25 of the menstrual cycle. In addition, at the day of the biopsy a blood sample was collected to measure estradiol (in all women) and DMPA in users. The level of serum estradiol was significant lower in Depo-Provera users than in controls (p < 0.001). The thickness of the vaginal epithelium was not smaller among DMPA users than among controls, the mean count of Langerhans cells per mm of epithelium were almost identical in both groups, and no significant differences were found on the vaginal maturation indices. In conclusion, the use of Depo-Provera between two and three years did not affect vaginal thinning of the epithelium, Langerhans cell count or maturation index.
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PMID:The effect upon the human vaginal histology of the long-term use of the injectable contraceptive Depo-Provera. 1102 25

The Philippine Family Planning Program formally re-introduced depomedroxyprogesterone acetate (DMPA) or DepoProvera as a program method last March 22, 1994. DMPA will be added to the choices available to couples who desire to practice responsible parenthood. DMPA is an injectable contraceptive containing synthetic progestin which resembles progesterone. It is a scientifically effective, medically safe and legal contraceptive which is injected every three months. Its effectivity reaches up to 99.7% in the first year of use. A WHO [World Health Organization] study had shown that its effectiveness is comparable to bilateral tubal ligation. DMPA's mechanism of action is the inhibition of ovulation and the thinning of the endometrium. It is a safe contraceptive which the US Drug and Food Authority (USDFA) and our own Bureau of Food and Drug Authority had approved for contraceptive use. WHO studies had shown that DMPA does not lead to increased cancer risk, congenital malformation and infertility. DMPA was initially developed in the 1960s as a treatment for endometrial and renal cancer. Its contraceptive effects then led to its use as a family planning method. Over 9 million women had used DMPA. It is a very safe, reversible and effective family planning method with manageable side effects. These include: menstrual irregularities, amenorrhea, weight gain, nausea and vomiting. These effects can be adequately managed by a trained service provider. DMPA will be initially introduced by the Department of Health in 10 pilot areas. IMCH will soon introduce the method in our clinics once the supplies are available and the clinic staff are prepared in the service provision of DMPA.
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PMID:PFPP re-introduces DMPA. 1231 88

Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate. Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring. In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.
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PMID:Letrozole: a review of its use in postmenopausal women with breast cancer. 1516 28


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