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Biomedical subjects

Y Liel

Publications and source records attributed to Y Liel.

At least 19 recordsLinked to original sources

Awareness of osteoporosis and compliance with management guidelines in patients with newly diagnosed low-impact fractures.

A pre-existing fracture is a strong predictor of additional osteoporotic fractures. Consequently, current guidelines emphasize the need for treating patients with existing osteoporotic fractures. The present study aimed to assess the implementation of osteoporosis guidelines in routine practice. To this end, we reviewed the hospital charts of women and men aged 50 years and older with new fractures due to low or moderate impact treated in the emergency room, orthopedic surgery and rehabilitation departments. Notation of osteoporosis as a contributing cause for the fracture, performance of screening laboratory tests for possible secondary causes and treatment recommendations were abstracted from the record. In addition, we utilized the centralized pharmacy and laboratory computerized databases of the largest health maintenance organization in the area to follow dispensation of osteoporosis drugs and performance of screening laboratory tests in the community following fracture incidents. During the corresponding periods of January and February 1998 and 1999, 183 patients aged 50 years and older with low-impact fractures were treated in the emergency room only and 113 were hospitalized. Osteoporosis was rarely mentioned in the medical documentation. During the 6 month period after the fracture incident at least 70% of the emergency room patients and 62% of the hospitalized patients received no osteoporosis drugs. However, an encouraging significant trend toward increasing use of osteoporosis drugs, both prior to and after a fracture incident, was noted between the two survey periods among the emergency room fracture patients, but not among the hospitalized patients. Calcium supplements were the most commonly used osteoporosis drug. Bisphosphonates, hormone replacement therapy, raloxifene and calcitonin were rarely prescribed. Men were less likely than women to receive treatment for osteoporosis. Systematic laboratory evaluations for secondary causes of osteoporosis were not performed. We conclude that despite extensive attempts at increasing awareness among health professionals and the public at large, osteoporosis is still rarely singled out as a problem in patients with newly diagnosed low-impact fractures, and the majority of them are not managed according to guidelines. Further studies should address specific problems in physicians' and patients' attitude that may account for the present situation.

Aged↗

Long-term follow-up of patients with initially benign thyroid fine-needle aspirations.

Fine-needle aspiration (FNA) is currently the most reliable diagnostic means in the clinical work-up of thyroid nodules. However, most of the available data on the diagnostic reliability of thyroid FNA derives from biopsies done just before surgery or from short-term observations, whereas data on the long-term reliability of benign FNA results, is extremely limited. Over the 17-year period between 1979 and 1996, thyroid FNA performed on 849 patients in our endocrine clinic. An initially benign result was reported in 578 patients for a total of 631 nodules. Mean follow-up period was 8.1 +/- 4.4 years (+/-standard deviation [SD]; median, 6.9 years). In order to ensure the completeness of our follow-up data, we supplemented our own patients' data with data from the Israel Cancer Registry for documentation of thyroid malignancy. Sixty-six of the patients with an initially benign FNA diagnosis were rebiopsied during follow-up. Five patients (0.85%) of all those with an initial benign FNA diagnosis, were subsequently found to have thyroid malignancy diagnosed 6 months or more after the initial evaluation. Three of the newly diagnosed malignancies were follicular and two were papillary carcinomas. Three of the patients had elements of being at high-risk: previous head irradiation, previous thyroid surgery with an occult cancer, and a growing goiter, respectively. Only 1 of 35 patients who had more than one benign FNA results was subsequently diagnosed with thyroid malignancy (follicular carcinoma). These results indicate that the rate of subsequent thyroid malignancies in patients with an initial benign FNA diagnosis is low, and thus benign thyroid FNA results provide a high level of long-term assurance. Still, repeating FNA is warranted in patients with longstanding thyroid nodules, particularly if at increased risk for cancer, or if a goiter is found to have changed its morphological characteristics over time.

Adult↗

Primary bilateral adrenal lymphoma relapsing as a solid cerebral mass after complete clinical remission: a case report.

Primary adrenal lymphoma is extremely rare. Only 75 cases have been reported in the medical literature. A case of non-Hodgkin's lymphoma originating in both adrenal glands is presented. Combination chemotherapy apparently produced complete disappearance of the primary lymphomatous lesions, but subsequently a cerebral relapse was discovered 6 months later, in the form of a solid brain mass. Cranial extension of primary adrenal lymphoma is extremely unusual, and the presentation as a solid mass seems to be unique.

Adrenal Gland Neoplasms↗

Estrogen controls expression and bioresponse of 1,25-dihydroxyvitamin D receptors in the rat colon.

Estrogen receptors are extensively expressed in the gastrointestinal tract, however their physiological role is not clear yet. Estrogen and 1,25-dihydroxyvitamin D [1,25(OH)2D3] apparently share common activities in the intestine such as growth-suppressing effects on the colonic mucosa and positively influence intestinal calcium absorption. In view of our previous studies showing up-regulation of vitamin D receptors (VDR) in the duodenal mucosa and in osteoblasts, the present study was designed to address a possible interaction between estrogen and the vitamin D endocrine system in the colonic mucosa. Three groups of female rats were studied: sham operated ('Sham'), ovariectomized ('OVX'), and ovariectomized estrogen-treated ('OVX+E'). VDR gene expression was assessed by Northern blot analysis, VDR protein expression was assessed by ligand-binding assays, and Western-blotting. Endogenous 1,25(OH)2D3 bioactivity in colonic mucosal extracts was assessed by alkaline phosphatase activity and calbindin-9kD mRNA expression. Northern blots revealed marked increase in band intensity corresponding with the VDR mRNA product in 'Sham' or 'OVX+E' vs. 'OVX'. In ligand-binding experiments, 1,25(OH)2D3 was shown to bind specifically to a single class of receptors in extracts obtained from each of the groups (Kd--0.03 nM). The maximal VDR binding capacity of colonic mucosal extracts was 203 +/- 23 fmol/mg protein in 'Sham', 362 +/- 41 in 'OVX+E' and 102 +/- 15 in 'OVX' ('Sham' or 'OVX+E' vs. 'OVX', p < 0.001). Western-blot analysis also revealed higher VDR protein expression in the estrogen-exposed animals. Alkaline phosphatase activity and calbindin-9kD mRNA expression were significantly higher in colonic mucosal extracts from estrogen-exposed rats. Estrogen increases VDR gene transcript level, protein expression and endogenous 1,25(OH)2D3 bioactivity in colonic mucosa, which may suggest that some of the estrogen activities in the colonic mucosa, such as its growth-suppressing effect, could be mediated, at least in part, by an increase in colonic mucosa responsiveness to endogenous 1,25(OH)2D3.

Animals↗

Differential effect of TPA on PGE2 and cicaprost-induced cAMP synthesis in UMR-106 cells.

PGE2 and prostacyclin each enhance cAMP synthesis in the osteoblast-like cell line UMR-106. The amount of cAMP induced by PGE2 was 5-7-fold greater than the amount induced by cicaprost or iloprost, stable prostacyclin analogues. Both PGE2 and the two prostacyclin analogues enhanced cAMP synthesis with similar time dependence. The EC50 values of PGE2 and cicaprost were 3 X 10(-6) and 5 x 10(-8) M, respectively. Short-term incubation of the cells with 12-o-tetradecanoylphorbol 13-acetate (TPA) markedly reduced the PGE2-induced cAMP synthesis. In contrast, cells that were incubated with the same concentrations of TPA in the presence of cicaprost or iloprost showed a 1.6-fold increase in cAMP formation. The marked disparity between the cAMP response to cicaprost and PGE2 in the presence of TPA suggests that the two prostanoids induce cAMP synthesis in the UMR-106 cells by interaction with different receptors. These observations support the idea that the osteoblastic UMR-106 cells may express specific prostacyclin receptors and suggest that prostacyclin may have a unique role in osteoblasts.

Animals↗

The yield of adequate and conclusive fine-needle aspiration results in thyroid nodules is uniform across functional and goiter types.

Relatively little is known about the cytological characteristics of hyperfunctioning (hot) thyroid nodules. Concern has been expressed that fine-needle aspiration (FNA) identifies hot nodules as follicular tumors or indeterminate, and as a consequence patients could be unnecessarily referred for surgery. Between 1979 and 1996, thyroid FNA was performed on 829 patients. Result of thyroid scan was available in 326; 69 (21%) patients had hot, and 257 (79%) had warm or cold thyroid nodules. Nodules in each of these major groups were divided into 2 subgroups: clinically solitary nodules and dominant nodules in multinodular goiters (MNG). The frequencies of adequate versus inadequate FNA samples, and of conclusive versus indeterminate FNA results were determined separately for each of the groups and subgroups. In addition, patients with hot nodules and overt hyperthyroidism were identified and evaluated separately. Bivariate analyses were performed for the frequency of adequate versus inadequate smears and conclusive versus indeterminate results between hot, toxic, and cold-warm nodules, and between solitary nodules and MNG. The frequency of adequate aspirations and conclusive results in the various groups and subgroups was found to be statistically indistinguishable. In conclusion, the yield of adequate samples and the rate of conclusive results of FNA in thyroid nodules is similar, irrespective of the functional state or of goiter presentation. Hot thyroid nodules do not seem to produce an increase in the rate of inadequate or indeterminate FNA results, and therefore, do not affect the overall performance of thyroid FNA.

Adolescent↗

Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa.

Menopause and estrogen deficiency are associated with apparent intestinal resistance to vitamin D, which can be reversed by estrogen replacement. The in vivo influence of estrogens on duodenal vitamin D receptor (VDR) was studied in three groups of rats: ovariectomized (OVX), sham-operated, and ovariectomized rats treated daily with estrogen (40 microg/kg BW) for 2 weeks (OVX + E). Estrogen administration to OVX rats resulted in a 2-fold increase in VDR messenger RNA transcripts. 1,25(OH)2D3 was shown to bind specifically to one class of receptors in duodenal mucosal extracts, with a dissociation constant of 0.03 nM. Binding was significantly increased in duodenal extracts from OVX + E rats, compared with OVX rats (735 +/- 81 vs. 295 +/- 26 fmol/mg protein; P < 0.001); a comparable, 1.5- to 2-fold increase in VDR protein expression was observed in Western blot analyzes of the duodenal mucosa. Markers of VDR activity were increased in estrogen-exposed rats: calbindin-9k messenger RNA transcript content was 1.4- to 1.6-fold higher, and alkaline phosphatase activity was 1.4- to 3-fold higher in sham-operated and OVX + E, respectively, compared with OVX. 25(OH)D, 1,25(OH)2D, or PTH levels were not altered by estrogen treatment. Cumulatively, these findings suggest that estrogen up-regulates VDR expression in the duodenal mucosa and concurrently increases the responsiveness to endogenous 1,25(OH)2D. Modulation of intestinal VDR activity by estrogen, and subsequent influence on intestinal calcium absorption, could be one of the major protective mechanisms of estrogen against osteoporosis.

Alkaline Phosphatase↗

The protective effect of estrogen against chemically induced murine colon carcinogenesis is associated with decreased CpG island methylation and increased mRNA and protein expression of the colonic vitamin D receptor.

Epidemiological studies suggest that estrogen prevents neoplastic transformation in the intestinal mucosa. Estrogen was shown to increase the expression of vitamin D receptors (VDR) in a variety of tissues. 1,25-Dihydroxyvitamin D [1,25-(OH)2D] and several of its analogues are known as potent antineoplastic and prodifferentiative in many cell types, including colon-derived cells. The present study was designed to examine the effect of estradiol (E2) on dimethylhydrazine (DMH)-induced colon cancer in rats, and the possibility that E2 may exert its protective effect on the colon through modulation of the vitamin D-endocrine system. The in vivo effect of E2 on DMH-induced colorectal cancer was studied in four groups of ovariectomized female rats: (I) untreated control, (II) E2 treated, (III) DMH treated, and (IV) combined E2 and DMH treated. Significantly higher uterine weights and higher colonic estrogen receptor content confirmed the effectiveness of ovariectomy and E2 replacement. The number of malignant tumors in group IV was 2.3+/-1.1 (mean +/- SE) per rat, compared with 8.1+/-1.9 in group III (P < 0.001). Exposure to estrogen was associated with a marked increase in VDR mRNA content and VDR protein expression in the normal colonic mucosa. In tumor extracts VDR protein expression was considerably lower compared with normal mucosa. Estrogen treatment did not affect serum levels of 25(OH)D, 1,25(OH)2D, and PTH. Significant CpG island methylation in the VDR gene was observed in colonic tissue DNA harvested from rats treated with DMH, but not in colonic mucosae from rats treated with DMH + E2. The highest frequency of CpG methylation in the VDR gene was detected in DNA extracted from cancer tissue rims. In summary, the protective effect of estrogen against chemically induced colonic carcinogenesis is associated with reduced methylation of the VDR gene and with upregulation of both VDR gene transcription and protein expression. We suggest that estrogen may interfere with the process of CpG DNA methylation in the colonic mucosa to prevent silencing of the VDR gene. Increased VDR activity could be one of the mechanisms by which estrogen protects against neoplastic transformation in the colon.

Animals↗

Severe, diffuse osteosclerosis: A new manifestation of transitional cell carcinoma of the urinary bladder.

A 56 year-old man with a 2-year history of transitional-cell carcinoma of the urinary bladder presented with back pain and diffuse radiological osteosclerosis. Laboratory studies revealed borderline-low ionized serum calcium, and markedly elevated serum alkaline phosphatase (ALP) activity and serum osteocalcin. Serum acid phosphatase and prostatic-specific antigen (PSA) were normal. Serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were just below the normal limit and parathyroid hormone was moderately elevated. A transiliac bone biopsy specimen revealed expanded bone trabeculae, abundance of osteoid-covered surfaces, and heavy metastatic spread. To the best of our knowledge, this is the first description of the association of osteosclerosis and metastatic transitional-cell carcinoma of the bladder.

Bone and Bones↗

Pregnancy-associated osteoporosis: preliminary densitometric evidence of extremely rapid recovery of bone mineral density.

Pregnancy-associated osteoporosis (PAO) is considered a rare complication of pregnancy and lactation, but the actual incidence is unknown. Pregnancy-associated osteoporosis is self-limited and usually does not recur during subsequent pregnancies, but little is known about its pathogenesis or the dynamics of bone density during the evolution and recovery phases of an acute episode. We report a case of idiopathic PAO. Follow-up included repeat measurements of bone density, which revealed a striking rate of improvement during the first 6 months after delivery (50% increase) and continuous improvement, at a diminished though still relatively high rate, during the successive year. This observation provides insight into the early stages of recovery from PAO.

Absorptiometry, Photon↗

'Travelers' thyrotoxicosis'. Transitory thyrotoxicosis induced by iodinated preparations for water purification.

Two young adults presented with thyrotoxicosis after increased iodide ingestion in the course of backpacking trips to Central and South America, during which each of them used an iodinated preparation for water purification. In both cases, serologic tests were positive for antithyroid peroxidase antibodies, and one had a family history of immune thyroid disease. We suggest that in these two cases the condition was a variant of iodide-induced thyrotoxicosis, reflecting an inadequate response to iodide excess in association with a presumed preexisting asymptomatic immune thyroid disease. This observation adds a new consideration for travelers' consultation.

Adult↗

Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients.

To evaluate the effect of dietary fiber supplements on levothyroxine (T4) bioavailability in hypothyroid patients, dietary fiber-containing supplementation was withheld from patients requiring disproportionately high doses of T4, in whom a dietary history revealed ingestion of a dietary fiber supplement. The dose of T4 was maintained at a constant level. Serum thyrotropin (TSH) was assessed before and after removal of the dietary fiber supplements. T4 requirements, reflected by either decreased serum TSH or by decreased T4 dose, was observed in conjunction with decreased dietary fiber intake compared with T4 requirement during increased dietary fiber intake. In vitro experiments carried out to determine the mechanism of interaction between dietary fiber and T4 revealed dose dependent, nonspecific adsorption of levothyroxine by wheat bran. These results indicate a decrease in T4 bioavailability by dietary fiber through a mechanism involving nonspecific adsorption of T4 to dietary fibers. Increased intake of dietary fiber may account for the need for larger than expected doses of T4 in some hypothyroid patients.

Adsorption↗