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Biomedical subjects

N Stern

Publications and source records attributed to N Stern.

At least 37 records · Page 2Linked to original sources

Thyroxine replacement therapy enhances clearance of chylomicron remnants in patients with hypothyroidism.

To further confirm the benefit of replacement therapy in terms of risk for coronary artery disease, we evaluated the effect of T4 on postprandial lipoproteins in patients with hypothyroidism. Nine normolipidemic patients (aged 62.75+/-7.6 yr) with TSH of 32.2+/-13.2 mU/L and free T4 of 0.66+/-0.17 ng/mL were treated with T4 (50-100 microg/day) for at least 4 months. The behavior of postprandial lipoproteins was assessed before and during treatment by determining retinyl palmitate levels in the total plasma, chylomicrons (Sf >1000) and chylomicron remnants (Sf <1000) fractions for 8 h after a mixed meal plus vitamin A. During T4 treatment, serum levels of TSH and FT4 were 4.4+/-4.9 mU/L and 1.2+/-0.34 ng/mL (P = 0.001 and P = 0.002), respectively. Fasting low density lipoprotein cholesterol decreased from 166+/-35 to 135+/-23 mg/dL (P = 0.035). Retinyl palmitate (RP) levels in the chylomicron remnant fraction was reduced significantly during therapy from 6948+/-2790 to 5174+/-2401 microg/L x h (area under the curve +/-SD; P = 0.014). Total plasma RP and chylomicron RP remained unchanged. We conclude that T4 enhances the clearance of chylomicron remnants in normolipidemic patients with hypothyroidism.

Cholesterol, HDL↗

Effect of TRH on beta-gonadotropin subunits in patients with pituitary microincidentalomas.

OBJECTIVE: To explore the hypothesis that most of the pituitary abnormalities compatible with the diagnosis of microadenoma, and detected in about 10% of the normal adult population, represent asymptomatic gonadotropinomas. DESIGN: Patients diagnosed with pituitary microincidentalomas at the Institute of Endocrinology of the Tel Aviv Medical Center were evaluated. Circulating beta-subunits of gonadotropin hormones were measured before and 30, 45, 60 and 90 min after the intravenous injection of 400 microgram TRH. PATIENTS: Twenty-two patients with pituitary incidentaloma and 16 normal volunteers were tested. RESULTS: In 16 of the 22 patients, an abnormal beta-subunit response was detected after the TRH challenge. Three patients had an abnormal increase in both beta-FSH and beta-LH after TRH administration. Isolated pathological beta-FSH or beta-LH responses were demonstrated in five and eight patients respectively. Six patients had normal basal and stimulated gonadotropin subunit values, raising the possibility that their lesions were not pituitary microadenomas. There was a significant overall difference between the response to TRH of the patient and control groups. In the gonadotropin positive group, comprising 16 patients, serum beta-FSH increased from 6.4+/-1.6 ng/ml to 9.2+/-1.3 ng/ml (P=0.042) 1 h after TRH stimulation, whereas no changes were detected in the control group after TRH injection (basal: 4.1+/-0.8 ng/ml, peak: 5.1+/-0.8 ng/ml; P=0.15). Serum beta-LH increased from 10.5+/-3.2 ng/ml to 23.4+/-4.9 ng/ml (P=0.0037) at this time, in contrast to a lack of response in controls (basal: 6.4+/-1.5 ng/ml, peak: 8.2+/-2.3 ng/ml; P=0.24). CONCLUSION: In about 73% of patients with pituitary incidentalomas smaller than 10 mm, TRH elicits an increase in gonadotropin beta-subunits. This observation raises the possibility that non-functioning pituitary micro- and macroadenomas, which share a similar response to TRH, originate in a common ancestor cell type, probably a pituitary gonadotrope.

Adenoma↗

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure.

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

Analysis of Variance↗

Fluorescence derivatisation of urinary corticosteroids for high-performance liquid chromatographic analysis.

Corticosteroids containing a C21 primary hydroxyl group were derivatised with 9-anthroyl cyanide. The reagent was prepared as a solution in acetonitrile, containing 0.1% triethylamine, at a concentration of 2 mg/ml. Approximately 1 microg of corticosteroid was reacted with 100 microl of this reagent, at 45 degrees C for 2 h. The fluorescent derivatives were separated by HPLC on a silica column, 250x4.6 mm I.D., by stepwise elution, with a mobile phase of 2-propanol-hexane (2:98) for 20 min, followed by 2-propanol-hexane (7:93) from 20 to 40 min. The fluorescence detector was set to 370-nm excitation and 470-nm emission. The relatively low temperature for derivatisation avoided reaction with secondary hydroxyl groups and also prevented thermal degradation of the corticosteroids.

Adrenal Cortex Hormones↗

Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels.

OBJECTIVE: Hyperprolactinaemia in humans may be associated with a high prevalence of obesity but the nature of this link is poorly defined. The aim of this study was to establish the relationship between hyperprolactinaemia and body weight in patients with prolactin-secreting pituitary tumours. DESIGN: We conducted a retrospective study of prolactinoma patients treated at the Endocrine Institute of the Tel Aviv Medical Center, Israel, during the period 1989-1996. Patients with clinically non-functioning pituitary macroadenomas (NFA) served as the control group. Data on demographic parameters, body weight before and during treatment, clinical presentation including history of weight fluctuations, tumour size as measured by computed tomography or magnetic resonance imaging, modalities and response to treatment, and pituitary function before and during treatment were recorded from medical files. PATIENTS: Forty-two patients with prolactinomas (PR) and 36 patients with clinically non-functioning macroadenomas (NFA) comprised the study population. RESULTS: Mean weight was 93 +/- 3.4 kg and 78 +/- 2.7 kg in male patients with PR and NFA respectively (P = 0.0007). Recent weight gain (8 to 22 kg) was a presenting symptom in 13 PR patients, whereas only one NFA patient had this clinical presentation (P = 0.001). Seventeen PR patients lost weight (mean change -8.3 +/- 1.5 kg, range -2-28 kg), during prolactin lowering therapy, 11 of whom had entirely normalized prolactin levels. Fourteen of the 18 patients who did not lose weight still had elevated prolactin levels (P = 0.01). Weight loss in patients with PR could not be attributed to altered pituitary function nor to compression of the third ventricle. In contrast to PR, no significant weight loss was observed in NFA patients. CONCLUSION: Weight gain and elevated body weight are frequently associated with prolactinomas regardless of a mass effect on the hypothalamus or pituitary function. In this series, weight loss was recorded in 70% of prolactinomas patients and in 90% of male patients who normalized their prolactin levels. We propose the inclusion of hyperprolactinaemia in the differential diagnosis of endocrine obesity and weight gain.

Adult↗

The use of beta-subunits of gonadotrophin hormones in the follow-up of clinically non-functioning pituitary tumours.

OBJECTIVE: Clinically nonfunctioning pituitary adenomas (NFA) are mostly of gonadotroph origin. However, increased levels of circulating hormones or subunits in patients with NFA usually do not cause clinical symptoms, nor are they used as biological tumour markers. In this study we assessed the value of measuring beta subunits of gonadotrophin hormones in the post-operative follow-up of patients bearing these tumours. DESIGN: Patients harbouring NFA were studied before and three months after transphenoidal pituitary surgery. beta-LH and beta-FSH levels were measured before and following TRH administration on the two occasions. Hormone levels were analyzed in relation to imaging studies performed before and after surgery. PATIENTS: Twenty four patients operated at the Tel Aviv-Sourasky Medical Centre for NFA. RESULTS: Pathological beta-FSH and beta-LH levels were detected in 79% and 60% of patients respectively. beta-LH levels decreased after surgery but there were no significant changes in beta-FSH levels. There was a tendency for tumours with high basal beta-LH levels to be larger and to have a poor surgical outcome. Normalization of beta-LH levels post-operatively was usually associated with a decrease in tumour mass or complete removal of the tumour. Persistent pathological responses of beta-LH to TRH after surgery were common in patients with residual tumours on imaging. Nevertheless there were exceptions to this pattern, rendering post-operative beta-LH levels insufficiently reliable as a marker for the presence of residual tumour. CONCLUSION: Although there appears to be a relationship between beta-LH levels, tumour size and surgical outcome, this association is presently insufficient to allow the routine use of either basal or TRH induced beta-LH responses in the post-surgical follow-up of clinically nonfunctioning pituitary adenomas.

Adenoma↗

Bond strength of photocured composite resin facings: clinical versus laboratory procedures.

The tensile strengths of laboratory versus clinical photocured composite resins have been investigated. Metal surfaces were bonded to photocured composite resin by either retentive beads, Sebond or Silicoating. The bond strengths were measured by an Instron machine and the fracture sites observed. Following repair with the adhesives Dentacolor Opaquer, Fusion and Cover up 2, the Instron measurements were repeated. The metal/facing bond strength was the highest in samples fabricated by the Silicoating technique, the bond strength exceeding the cohesive forces in the composite resin facing. The tensile strengths of metal/facing bonded by Sebond and retentive beads were similar. Fractures that include the facing and partially reveal the metal are the least resistant to tension after repair. Renewal of the Opaque layer and completion of the facing is superior to any of the repair methods used in this paper. The original fracture point is the weakest after repair. All the repair kits tested were inferior to the original restoration materials.

Adhesiveness↗

Effects of gonadal steroids and their antagonists on DNA synthesis in human vascular cells.

The cardiovascular effect of estrogen is currently under intense investigation, but the role of androgens in vascular biology has attracted little attention. Because endothelial repair and vascular smooth muscle cell (VSMC) proliferation affect atherogenesis, we analyzed the effects of 17beta-estradiol (E2), dihydrotestosterone (DHT), and sex hormone antagonists on DNA synthesis in human umbilical VSMCs and in E304 cells (a human umbilical endothelial cell line). In VSMCs, both E2 and DHT had a biphasic effect on [3H]thymidine incorporation into DNA: low concentrations (0.3 nmol/L for E2, 3 nmol/L for DHT) stimulated [3H]thymidine incorporation (+35% and +41%, respectively), whereas high concentrations (30 nmol/L for E2, 300 nmol/L for DHT) inhibited [3H]thymidine incorporation (-40%). In contrast, E2 (0.3 to 300 nmol/L) and DHT (3 to 3000 nmol/L) dose-dependently enhanced [3H]thymidine incorporation in E304 cells (peak, +85% for both). In VSMCs, high concentrations of E2 and DHT inhibited platelet-derived growth factor (PDGF)-or insulin-like growth factor (IGF-1)-induced DNA synthesis (-50% to 80%), whereas PDGF- or IGF-1-dependent DNA synthesis in E304 cells was further increased by E2. The antiestrogens tamoxifen and raloxifene mimicked the effects of E2 on DNA synthesis in both VSMCs and E304 cells. However, when coincubated with a stimulatory concentration of E2 (0.3 nmol/L), tamoxifen and raloxifene blocked E2-induced [3H]thymidine incorporation in E304 cells but not in VSMCs. Finally, the androgen antagonist flutamide inhibited the biphasic effects of DHT on VSMCs and blocked the increase in DNA elicited by DHT in E304 cells. The results suggest complex, dose-dependent, and cell-specific interactions of estrogens, androgens, and their respective antagonists in the control of cellular proliferation in the vascular wall. Gonadal steroid-dependent inhibition of VSMC proliferation and stimulation of endothelial replication may contribute to vascular protection and remodeling responses to vascular injury.

Analysis of Variance↗

[Follow-up and therapy of acute colchicine poisoning].

Colchicine poisoning is a rare event. Its outcome is, compared to other drug intoxications, often serious or even fatal. Intaxications with colchicine may occur by ingestion of tablets as well as by consumption of meadow saffron leaves (Colchicum autumnale) that are often mistakenly collected instead of the leaves of ramson herb (Allium ursinum). Colchicine poisoning typically shows three phases: initially gastrointestinal symptoms predominate, in the second phase multiorgan failure may occur possibly leading to death. In case the patient survives, the third phase of recovery follows during which the patients often present with hair loss. The fatal dose of acute colchicine poisoning is estimated at about 0.9 mg/kg. Since hemodialysis and hemoperfusion are not effective measures because of the high volume of distribution, an aggressive primary decontamination with gastric lavage and activated charcoal is required as early as possible. A promising new aspect in the treatment of heavy colchicine overdose is the immunotherapy with colchicine-specific fab-fragments. At present this treatment is still in an experimental stage and has been applied so far to one patient with beneficial effects. Unfortunately colchicine-specific antibodies are not yet commercially available.

Adult↗

Combined beta FSH and beta LH response to TRH in patients with clinically non-functioning pituitary adenomas.

OBJECTIVE: 'Paradoxical' responses of LH, FSH, alpha-subunits and beta LH to TRH have previously been reported in individuals with clinically non-functioning pituitary tumours (NFT). The present study was designed to assess the in vivo and in vitro responses of beta FSH to TRH in NFT. We further examined the possibility that a TRH challenge with combined measurement of beta FSH and beta LH will identify a common anomalous secretory pattern in patients with NFT. DESIGN, PATIENTS AND MEASUREMENTS: Forty patients with NFT underwent a standard TRH test (400 micrograms intravenously). Blood samples for the determination of beta FSH, beta LH, FSH and LH were collected prior to TRH as well as 15, 30, 45, 60 and 90 minutes following injection. Additionally, cultured adenomatous cells from eight to these patients were exposed to TRH in the absence and presence of octreotide and gonadotropin subunits were determined. RESULTS: TRH elicited a marked rise in circulating beta FSH in 29 of 40 individuals and in beta LH in 28 of 36 patients with NFT. In a subgroup of eight individuals whose tumours were harvested during surgery and cultured for 7-21 days, TRH increased beta FSH or beta LH and alpha-subunit release in cultured adenomatous cells in all cases, including tumours from subjects not responding to TRH in vivo. In this subgroup of patients octreotide inhibited basal beta FSH secretion but not basal beta LH secretion both in vivo and in primary cultures of NFT cells. Both the in vivo and in vitro beta FSH, beta LH and alpha-subunit responses to TRH were entirely inhibited by octreotide. In all, 38 of the 40 subjects could be identified by either elevated basal beta FSH or beta LH levels and/or an abnormal rise in either beta FSH or beta LH in response to TRH. CONCLUSION: The measurement of basal and TRH-stimulated beta-FSH and beta-LH levels identifies an abnormal hormonal secretory pattern in the vast majority (> 90%) of patients with clinically nonfunctioning pituitary tumours.

Adenoma↗

Role of the lipoxygenase pathway in angiotensin II-induced vasoconstriction in the human placenta.

We have previously shown that the vasopressor effect of angiotensin II (Ang II) is inhibited by lipoxygenase (LO) blockers. To elucidate the specific mechanism involved, we studied the relationship between the contractile effect of Ang II and LO products in a human placental preparation. In perfused placental cotyledons, Ang II (boluses of 1 to 10 microg) increased perfusion pressure and 12-hydroxyeicosatetraenoic acid (12-HETE) release. The LO blockers phenidone and n-propyl gallate reduced the maximal Ang II-induced increment in pressure from 26+/-3 to 16+/-3 and 18+/-4 mm Hg, respectively (P<.05 for both). Ang II alone (10 microg) increased 12-HETE release from 8.9+/-3.6 to 37.6+/-0.4 ng/min, and this rise was entirely blocked by both phenidone and n-propyl gallate. Pressure increase generated by an increase in flow rate had no effect on 12-HETE formation. In deendothelialized umbilical artery segments, Ang II (10(-7) mol/L) increased 12-HETE formation by 47+/-5% (n=20). In cultured umbilical artery smooth muscle cells, Ang II increased 12-HETE formation from 48.1+/-7.2 to 75.1+/-15.3 ng/mg protein, and this effect was also blocked by the specific LO inhibitor baicalein (10(-6) mol/L). These results provide evidence that the vasopressor effect of Ang II is functionally coupled to 12-LO activation, which apparently takes place in arterial smooth muscle cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Platelet lipoxygenase in spontaneously hypertensive rats.

We have previously reported that the nonselective lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat (SHR). In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention. Basal generation rate of 12-HETE by platelets collected from the SHR was approximately 3.7-fold higher than in the WKY (0.86 +/- 0.24 versus 0.23 +/- 0.05 nmol/mL per 10 minutes, respectively; P < .01). Systolic arterial pressure was positively related to platelet 12-HETE formation rate when the entire rat population was considered (r = .70, P < .001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycyanocinnamate induced lowering of both arterial blood pressure and platelet 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydroxycyanocinnamate elicited a marked hypotensive effect in SHR but not in WKY. This reduction in arterial pressure was accompanied by an approximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significant rise in the production of platelet 12-HETE toward control values (baseline, 0.97 +/- 0.33 nmol/mL per 10 minutes; nadir of blood pressure, 0.19 +/- 0.03; resumption of basal pressure, 0.42 +/- 0.14). In contrast, captopril (15 mg/kg) induced a quantitatively similar decrease in blood pressure but had no effect on platelet 12-HETE generation rate. Thus, hypertension in SHR is linked to increased production rate of platelet 12-HETE. Acute blood pressure reduction attained during lipoxygenase inhibition but not by angiotensin converting enzyme inhibition leads to a concomitant reduction in the production of platelet 12-HETE. We speculate that since rat arterial tissue produces 12-HETE, increased 12-lipoxygenase activity in SHR may contribute to the maintenance of elevated arterial pressure in this strain.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Erectile dysfunction in hypertensive subjects. Assessment of potential determinants.

Hypertension is often cited as a risk factor for erectile dysfunction. To clarify the relation between hypertension and erectile dysfunction, we evaluated 32 consecutive hypertensive and 78 normotensive impotent men with respect to multiple potential determinants and parameters of erectile function, including medical and sexual history, depression, hormonal profile, penile nocturnal tumescence, penile vascular supply, and pudendal nerve conduction. The hypertensive men were older, had higher body mass index, and used more medications than the normotensive men. The groups were not different with respect to the prevalence of smoking and peripheral vascular disease, but the hypertensive men had a marginally higher rate of ischemic heart disease (P = .06). The prevalence of depression, abnormal nocturnal penile tumescence, anomalous pudendal nerve conduction, and impairment in arterial supply as determined by penile brachial index were similar in the two groups. Testosterone and bioavailable testosterone levels were lower in the hypertensive men. After stratification by age and body mass index, hypertensive men younger than 50 years with body mass index less than 30 kg/m2 had significantly lower testosterone levels (12.0 +/- 1.7 versus 21.3 +/- 1.4 nmol/L, P < .02) but not bioavailable testosterone levels (3.9 +/- 0.7 versus 6.4 +/- 0.7 nmol/L, P < .17) than the corresponding normotensive group. Prolactin, follicle-stimulating hormone, and luteinizing hormone levels of the two groups were not significantly different. Contrary to common belief and with the exception of lower circulating testosterone levels, the overall analysis showed little difference between hypertensive and normotensive men with respect to a wide range of classic determinants of erectile function. Direct study of the local vascular erectile apparatus appears necessary for further elucidation of the mechanisms underlying erectile dysfunction in hypertensive men.

Adult↗

Tonic inhibition of renin secretion by the 12 lipoxygenase pathway: augmentation by high salt intake.

Recent evidence suggests that lipoxygenase (LO) metabolites inhibit renin production in vitro. However, the physiological significance of this effect has not been determined. This study examined the role of the LO pathway in the regulation of plasma renin concentration (PRC) in vivo. The acute administration of two structurally unrelated LO inhibitors, phenidone (30 and 60 mg/kg) and esculetin (60 mg/kg), resulted in suppression of platelet 12 hydroxyeicosatetraenoic acid (12HETE) production, reduction in systemic arterial pressure and a 2- to 3-fold increase in PRC. To determine whether the esculetin-induced increase in PRC was secondary to hypotension, esculetin was also administered to rats preinfused with a pressor dose of norepinephrine. In these acutely hypertensive rats, esculetin still induced a 2.5-fold increase in PRC, whereas blood pressure remained over 40 mm Hg above basal levels. Further, esculetin (10(-6)M) increased renin release in renal slices from 150 +/- 10 to 310 +/- 20 ng/ml.h (P < 0.05) and this rise was entirely blocked in the presence of 12HETE (10(-7)M; 130 +/- 40 ng/ml.h). In rats placed on high salt intake, 12HETE concentration in renal slices from the outer cortex was considerably higher than in renal slices from salt-restricted rats (116.5 +/- 15.7 vs. 65 +/- 12 pg/mg protein; P < 0.05). Chronic administration of the LO inhibitor phenidone also resulted in an increase of PRC, which was independent of changes in blood pressure. On either high salt (3.15%0 or low salt (0.05%) diet phenidone-treated rats had higher PRC levels than the respective control groups [high salt 9.7 +/- 3.5 vs. 1.9 +/- 1.4 ng/ml.h; P < 0.05; low salt 33.2 +/- 5.3 vs. 19.4 +/- 3.10 ng/ml.h; P < 0.05]. The finding that LO blockers are potent stimulators of PRC in vivo suggests the existence of a physiological tonic inhibition of renin secretion by LO products that is operative under a wide range of salt intake. High salt intake enhances this inhibitory tone by increasing renal cortical 12 LO activity and, in fact, normal suppression of PRC during high salt diet does not occur in LO-blocked animals. Thus, the LO pathway exerts a tonic inhibitory effect on renin release, which appears particularly important for renin suppression during high salt intake.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Prosthodontics--from craft to science.

Prosthodontics has evolved slowly from being an ancient craft into a modern science. The literature of the ancient world is replete with dental references which provide insights into the way dentistry was once practiced. The scientific breakthroughs of the past century have most prominently accelerated dentistry's modernization. The dentistry of the past has paved the way to modern day dental science and treatment.

Esthetics, Dental↗

A CAD/CAM system for the production of metal copings for porcelain-fused-to-metal restorations.

A computer-aided design and manufacture system for the production of metal copings for porcelain-fused-to-metal restorations is described and evaluated. The three stages of production: digitizing, mathematical processing, and milling are described, with emphasis on the system's ability to produce metal copings for both single-unit and multiple-unit restorations. Evaluation of the marginal fit of the produced copings demonstrates the potential for clinically acceptable results.

Analog-Digital Conversion↗