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Biomedical subjects

J Ginsberg

Publications and source records attributed to J Ginsberg.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hashimoto's thyroiditis: cytodiagnostic accuracy and pitfalls.

To determine the cytodiagnostic accuracy rate and pitfalls of Hashimoto's thyroiditis (HT), the files and smears prepared from the thyroid needle aspirates of 146 patients with suspected HT and/or clinically and serologically confirmed HT were reviewed. Of those patients, 105 presented with a diffuse and rubbery thyroid enlargement, and 41 with one or two prominent nodules. For the first group (105 patients), the needle aspiration biopsy (NAB) was performed on one or two thyroid lobes during their initial endocrinologic consultation, and for the second group (41 patients), the NAB was performed on and around the predominant nodules that were found either at initial physical examination or during the patients' routine follow-ups. In 134 cases, a cytodiagnosis of HT was made on the first NAB. Among the 41 patients with a prominent thyroid nodule, a thyroid neoplasm was suspected clinically in four because their thyroid nodules increased in size. In the other 12 patients, a cytodiagnosis of follicular neoplasm (FN) was made in five cases, and a Hürthle cell tumor (HCT) was diagnosed or suspected in seven patients. All 16 patients had thyroid surgery, and a HT was histologically confirmed in all cases. In the first four patients, no tumor was found. Among five patients with a cytodiagnosis of FN, one had a hyperplastic follicular cell nodule (HFCN), two had follicular adenomas, and two had papillary carcinomas of follicular variant. For the seven patients with a cytodiagnosis of HCT, HCT was confirmed in three, three were found to have hyperplastic Hürthle cell nodules (HHCN), and one showed a benign colloid nodule with Hürthle cell changes and remote hemorrhagic necrosis. It is concluded that NAB is highly sensitive in diagnosing HT, with a diagnostic accuracy rate of 92% by the first biopsy attempt. The cytologic differential diagnosis between an HFCN and a follicular neoplasm and between an HHCN and an HCT is impossible in some cases.

Adolescent↗
PubMed1997

Acute neurologic dysfunction associated with high-dose chemotherapy and autologous bone marrow rescue for primary malignant brain tumors.

UNLABELLED: Acute neurologic complications occurred 103 times in 50 (54%) of 92 patients (primarily children) treated with high-dose chemotherapy and autologous bone marrow rescue for primary central nervous tumors. Different types of neurologic compromise occurred during the chemotherapy infusion as compared to the first 100 days after the chemotherapy and the greater-than-100-day time period. The causes of the neurologic compromise were also time sensitive. BACKGROUND: Results of treatment for children with primary brain tumors using high-dose chemotherapy with autologous marrow rescue (ABMR) have been encouraging. However, the neurotoxicity associated with this technique remains a major concern. We reviewed the records of 92 patients who underwent ABMR for malignant brain tumors between 1986 and 1992 for the occurrence and timing of acute neurologic dysfunction (AND). METHODS: Individual investigators at the participating institutions retrospectively completed standardized forms on each patient. The manner in which the distribution of AND versus time of treatment emerged led to the establishment of distinct time periods for data analysis and discussion. The pre-ABMR period included those events that occurred during the chemotherapy infusion, the early posttreatment period included the first 100 days following bone marrow rescue, and the late posttreatment period was greater than 100 days following bone marrow rescue. RESULTS: Fifty patients (54%) had 103 episodes of AND. AND included encephalopathies with or without hallucinations or coma (32), seizures (23), headaches (9), ataxia-tremor-dysarthria syndrome (7), anorexia and nausea syndrome (7) and others (25). During the chemotherapy infusion, encephalopathies and seizures were most common. Hallucinations occurred primarily related to drug infusion, while encephalopathies without hallucinations were usually due to demonstrable dysmetabolic states. In the 100 days following ABMR, dysmetabolic states and iatrogenic factors caused 45% and progressive disease caused 33% of AND. Greater than 100 days from ABMR, progressive disease caused 55% of AND; 7 patients were noted to develop chronic anorexia and nausea of unclear etiology. The occurrence of neurologic compromise was not related to the chemotherapy regimens, tumor histology, tumor location, patient age, prior treatment, or the amount of tumor at time of treatment. Dexamethasone use was the only clinical factor associated with AND (p < 0.004). CONCLUSIONS: The cause of AND was definable for 95% of instances that occurred within 100 days of ABMR. Early AND was often iatrogenic and reversible. The greater the time from ABMR the more likely AND was due to progressive disease. Clinical factors could not predict the occurrence of AND as only the concurrent use of dexamethasone at the time of treatment proved significant. Although frequent, AND should not be considered a limiting toxicity of this approach or preclude the use of this technique.

Acute Disease↗
PubMed1997

Activation of phospholipase D in FRTL-5 thyroid cells by forskolin and dibutyryl-cyclic adenosine monophosphate.

We demonstrated previously that TSH activates phospholipase D (PLD) via stimulation of protein kinase C (PKC) in Fischer rat thyroid line (FRTL)-5 thyroid cells. To examine the role of the cAMP pathway in the regulation of PLD, we studied the effects of forskolin (0-100 microM; 30 min) and dibutyryl cAMP (dbcAMP; 0-1 mM; 30 min) on PLD activation. FRTL-5 thyroid cells were labeled mainly in phosphatidylcholine with [3H]myristate followed by incubation with 200 mM ethanol before the addition of agonist. PLD was assessed by the measurement of [3H]phosphatidylethanol. Forskolin (100 nM to 100 microM) and dbcAMP (100 pM to 100 microM) increased PLD activity significantly. Maximal responses to forskolin and dbcAMP exceed the PLD responses produced by 100 microU/ml of TSH. To determine whether the effects of forskolin and dbcAMP on PLD occurred as a consequence of PKC activation, FRTL-5 thyroid cells were preincubated for 10 min with the PKC inhibitors, chelerythrine (1 microM) or calphostin C (1 microM), or they were pretreated for 24 h with phorbol myristate acetate (100 nM) to down-regulate PKC. Unlike TSH-mediated PLD activation, these treatments had no effect on PLD activation by cAMP agonists. Forskolin (10 microM; 30 min) had no effect on the subcellular distribution of PKC alpha-, epsilon-, or zeta-isoforms, confirming the lack of involvement of PKC. The protein kinase A (PKA) inhibitors, H-89 (10 microM; 30 min) and dideoxyadenosine (5 nM; 10 min) significantly decreased the forskolin- and dbcAMP-mediated PLD activation without any effect on the phorbol ester-mediated PLD response. Following pretreatment with H-89 or dideoxyadenosine, the TSH-mediated PLD response was also significantly reduced. These studies indicate that forskolin and dbcAMP stimulate PLD in FRTL-5 thyroid cells directly via PKA without involvement of PKC. Studies of cells in the presence and absence of ethanol revealed approximately 60% of the phosphatidate plus diacylglycerol produced via TSH occurs via PLD activation. Although TSH-mediated inositol phosphate generation occurred with similar concentrations of TSH that led to PLD activation, 10-fold higher TSH concentrations were required to increase intracellular Ca2+. These results and the lack of a rapid Ca2+ transient following physiological TSH concentrations suggest that alternatives to conventional hydrolysis of phosphatidylinositol 4,5-bisphosphate may initiate PKC activation. Thus, the two major signal transduction systems in the FRTL-5 thyroid cell (PKA and PKC) appear to converge on PLD activation. Stimulation of both of these pathways by TSH may be required for optimal physiological activation of PLD.

Alkaloids↗
PubMed1997

The cost and benefit of prophylaxis against deep vein thrombosis in elective hip replacement. DVT/PE Prophylaxis Consensus Forum.

UNLABELLED: A consensus forum was convened to evaluate the economic considerations associated with prophylaxis against thrombo-embolic disease in patients undergoing hip replacement therapy in South Africa. This forum consists of orthopaedic surgeons, vascular surgeons and a statistician. METHODS: The forum was instructed to evaluate the economic costs of the commonly used forms of prophylaxis of thrombo-embolism in patients undergoing hip replacement surgery in South Africa, looking at short-term events only. The methods used for the prophylaxis of thrombo-embolism in South Africa were determined by a postal survey. A decision tree was constructed to determine the events that will occur after a clinical decision to use no prophylaxis. The probabilities of these events were then determined. Protocols for and costs of prophylaxis and treatment were established. With the decision tree and these costs, the cost of the various modalities of prophylaxis was then determined. RESULTS: The probability, determined by the forum, of developing a deep-vein thrombosis (DVT) when no prophylaxis is used was 0.5, with a mortality rate of 2.1%. The cost of this decision was R875. No prophylaxis given, but a venogram performed on day 7, reduced the mortality rate to 0.7%; however, this cost R3 017. The cost of low-molecular-weight heparin was R1 223 (probability 0.26, mortality rate 1.1%), while unfractionated heparin with a graduated compression stocking (GCS) cost R1 351 (probability 0.24, mortality rate 1%). Aspirin with a GCS cost R777 (probability 0.35, mortality rate 1.5%).

Anticoagulants↗
PubMed1996

A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.

BACKGROUND: Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous standard (unfractionated) heparin. However, the longer plasma half-life, better bioavailability after subcutaneous administration, and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use. We compared these two approaches. METHODS: Patients with acute proximal deep-vein thrombosis were randomly assigned to receive either intravenous standard heparin in the hospital (253 patients) or low-molecular-weight heparin (1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily) administered primarily at home (247 patients). The study design allowed outpatients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early. All the patients received warfarin starting on the second day. RESULTS: Thirteen of the 247 patients receiving low-molecular-weight heparin (5.3 percent) had recurrent thromboembolism, as compared with 17 of the 253 patients receiving standard heparin (6.7 percent; P=0.57; absolute difference, 1.4 percentage points; 95 percent confidence interval, -3.0 to 5.7). Five patients receiving low-molecular-weight heparin had major bleeding, as compared with three patients receiving standard heparin. After randomization, the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital, as compared with 6.5 days for the standard-heparin group; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all. CONCLUSIONS: Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home.

Aged↗
PubMed1996

Thrombocytopenia in pregnancy: diagnosis, pathogenesis and management.

Maternal thrombocytopenia is a common find during pregnancy. The rapid determination of its cause can often be difficult, with the diagnosis only being made in retrospect once the course of the platelet count is known. The majority of patients with thrombocytopenia in pregnancy will have incidental thrombocytopenia of pregnancy which is of no clinical significance.

Female↗
PubMed1996

Regulation of protein kinase C isoforms in FRTL-5 thyroid cells by TSH and phorbol ester.

Activation of protein kinase C (PKC) has been observed following TSH exposure in FRTL-5 thyroid cells. However, PKC exists as a family of isoforms displaying individual characteristics. Recently, Wang et al. identified alpha-, delta-, epsilon-, and zeta-PKC in FRTL-5 thyroid cells chronically exposed to TSH. To determine if these PKC isoforms are regulated by TSH, we examined PKC isoforms by Western blotting in FRTL-5 thyroid cells after depletion of TSH followed by short-term TSH exposure (100 microU/mL; 30 min). Phorbol 12-myristate 13-acetate (PMA; 100 nM, 10 min) served as a positive control. In untreated cells, alpha-, epsilon-, and zeta-PKC isoforms were identified in both cytosolic and membrane fractions. Using the specific antigenic peptide to the respective PKC isoforms identified, each band could be appropriately displaced. PMA caused the translocation of alpha-PKC from the cytosol to the membrane-bound fraction. Although membrane-bound epsilon-PKC and zeta-PKC were increased following PMA exposure, the cytosolic fraction was unaffected. TSH had no effect on the cytosolic fractions of any of the PKC isoforms identified but was able to increase the membrane-bound fractions of alpha-, epsilon-, and zeta-PKC. Although delta-PKC was observed in FRTL-5 thyroid cells cultured in TSH-supplemented medium, delta-PKC disappeared within 24 h of TSH depletion and reappeared 24 h after TSH reexposure with further increases up to 72 h. These studies indicate that the PKC isoforms present in FRTL-5 thyroid cells are regulated by both phorbol ester and TSH and that the duration of TSH exposure differentially regulates delta-PKC. These observations provide further evidence that PKC is a mediator of TSH action in FRTL-5 thyroid cells in vitro.

Blotting, Western↗
PubMed1996

Effects of the diacylglycerol kinase inhibitor, R59022, on TSH-stimulated iodide organification in porcine thyroid cells.

We and others have demonstrated that protein kinase C (PKC) activators such as the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibit differentiated thyroid function in vitro. However, phorbol-mediated PKC activation differs from that induced by analogues of the endogenous PKC activator, diacylglycerol (DAG). To explore the effects of endogenous PKC activation on differentiated thyroid function, we examined the effects of the DAG kinase inhibitor, R59022, on TSH-mediated iodide organification in porcine thyroid cells. Following incubation of the thyroid cells for 30 min, 20 and 50 mumol/l R59022 inhibited TSH-stimulated iodide organification by 20 and 41%, respectively. Prolonged exposure (36 h) to R59022 was also studied since similar treatment with TPA downregulates PKC activity. Inhibition of TSH-mediated iodide organification was observed with as little as 5 mumol/l R59022 (56% of control, p < 0.01) with maximal inhibition using 50 mumol/l R59022 to 13% of control values (p < 0.001). To demonstrate that these effects were mediated by PKC activation, PKC isoforms were measured by Western blotting following R59022 exposure (50 mumol/l, 30 min). Increased membrane-bound alpha- and zeta-PKC isozymes were observed. This is the first demonstration linking specific PKC isoforms to changes in differentiated thyroid function in vitro. The present data suggest that alpha- and/or zeta-PKC mediate the effects of R59022 on differentiated thyroid function in vitro. Further, a PKC inhibitor, chelerythrine (1 mumol/l) was able to partially reverse the effects of prolonged R59022 exposure on TSH-mediated iodide organification. These studies demonstrate that R59022 exposure inhibits TSH-mediated iodide organification in porcine thyroid cells and that these effects are mediated via endogenous PKC activation. These data are consistent with the concept that endogenous PKC acts as a negative modulator of differentiated thyroid function in the porcine thyroid cell.

Animals↗
PubMed1995

Fetal thyrotoxicosis: a case report and recommendations for prediction, diagnosis, and treatment.

A maternal history of Graves' disease places the fetus at risk for thyrotoxicosis in utero via the placental transfer of thyroid-stimulating immunoglobulins. Methods for prediction of fetal hyperthyroidism are available, but are not widely used. Clinical assessment of fetal thyroid status by monitoring of fetal heart rate and growth may be inaccurate. This raises some uncertainty in the initial diagnosis of fetal thyrotoxicosis and complicates the assessment of fetal response to maternal propylthiouracil therapy. A case illustrating these pitfalls in the diagnosis and management of fetal hyperthyroidism is presented. The condition was correctly diagnosed, but treatment based on fetal heart rate resulted in biochemical hypothyroidism in the infant at birth. Current recommendations for diagnosis and treatment of fetal hyperthyroidism are reviewed along with recent developments in the field. A modified approach is proposed.

Adult↗
PubMed1995

Thyroid-stimulating hormone activates phospholipase D in FRTL-5 thyroid cells via stimulation of protein kinase C.

We studied whether TSH or phorbol myristate acetate (PMA) stimulates the hydrolysis of phospholipids, predominantly phosphatidylcholine, via phospholipase D (PLD) in FRTL-5 thyroid cells and whether this occurs as a consequence of protein kinase C (PKC) activation. FRTL-5 thyroid cells were labeled with [3H]myristate followed by incubation with 200 mM ethanol before the addition of agonist. PLD activity was assessed by the measurement of [3H]phosphatidylethanol from [3H]phospholipid (predominantly [3H]phosphatidylcholine). Compared to control values, bovine TSH (100 microU/ml) increased PLD activity by 480% and 600%, respectively, after 30 and 60 min of exposure. Studies with purified human and bovine TSH revealed similar results, indicating that this effect was due to TSH itself. PMA (100 nM) increased PLD activity at 10 min (630% of the control value), and this effect persisted up to 60 min (600% of the control value). To determine whether the effects of TSH on PLD occurred as a consequence of PKC activation, FRTL-5 thyroid cells were preincubated with the PKC inhibitor, chelerythrine (1 microM for 10 min), or were pretreated for 24 h with PMA (100 nM) to down-regulate PKC. PLD stimulation by TSH and PMA was largely abolished by such treatments. These studies indicate that in FRTL-5 thyroid cells, TSH and PMA are capable of stimulating PLD, and that PKC activation is responsible for this stimulation. The role of PLD activation could be to amplify and prolong the PKC signal by further production of diacylglycerol.

Animals↗
PubMed1995

Inhibition of thrombin by antithrombin III and heparin cofactor II in vivo.

The critical role of thrombin in the pathogenesis of venous and arterial thrombosis, and the effectiveness of glycosaminoglycans as antithrombotic drugs are well known. Antithrombin III is a major inhibitor of thrombin and augmentation of its inhibitory actions by heparin is the basis for the clinical uses of heparin. Recent clinical and experimental studies have demonstrated that another glycosaminoglycan, dermatan sulfate, is an effective antithrombotic drug. Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital antithrombin III deficiency and pregnant women than controls. The role of heparin cofactor II as a physiologic thrombin inhibitor is unknown. Enzyme-linked immunosorbent assays were used to quantify thrombin-heparin cofactor II and thrombin-antithrombin III endogenous to the plasmas of adult antithrombin III-Hamilton deficient subjects, their siblings with normal antithrombin III levels, pregnant women at term and 3 to 5 days after delivery. Both thrombin-antithrombin III and thrombin-heparin cofactor II complexed with vitronectin were detected in all the plasmas. Significantly, the concentrations of thrombin-heparin cofactor II-vitronectin were higher in the plasmas of congenital antithrombin III deficient subjects and in pre- and post-delivery plasmas than those of normal subjects. In addition, the concentrations of thrombin-heparin cofactor II decreased 3 to 5 days after delivery, reflecting the disappearance of the catalytically active dermatan sulfate elaborated by the placenta. Thus, heparin cofactor II normally inactivates thrombin in vivo, with its role increasing in conditions associated with high levels of heparin cofactor II and/or dermatan sulfate.

Adult↗
PubMed1995

Increased membrane-bound protein kinase C in porcine thyroid cells following TSH exposure.

Activation of protein kinase C (PKC) follows its translocation from the cytosol to an active membrane-bound form. Previously, we demonstrated that only high concentrations of partially-purified bovine thyroid-stimulating hormone (TSH) could translocate PKC in vitro when measured by histone phosphorylation. Measuring PKC by Western blotting, we assessed whether physiological concentrations of human TSH could translocate PKC in porcine thyroid cells. The known PKC stimulator, phorbol ester 12-0-tetradecanoylphorbol 13-acetate (TPA), caused maximal translocation of PKC at 100 nM with a 84.5% decrease in cytosolic PKC and a corresponding 252.1% increase in membrane-bound PKC. Although TSH did not affect cytosolic PKC, human TSH at 1, 10 and 100 microU/ml produced increases compared to control values in membrane-bound PKC of 80.3 +/- 15.8, 66.8 +/- 9.7 and 74.0 +/- 19.8%, respectively (mean +/- SE, p < 0.01 at all TSH concentrations used). These studies provide evidence that physiological concentrations of TSH increase membrane-bound PKC in vitro, a process linked to its activation. In addition, we observed qualitative differences in phorbol ester and TSH-mediated PKC activation.

Animals↗
PubMed1995

Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis.

The optimal duration of oral anticoagulant therapy for patients with acute proximal deep vein thrombosis (DVT) is uncertain. Based on the hypothesis that a normal impedance plethysmogram (IPG) following DVT defines a group of patients at low risk of recurrent venous thromboembolism (VTE), a trial was conducted to evaluate the efficacy of only four weeks of warfarin. Patients with venographically confirmed acute proximal DVT who had received four weeks of warfarin after initial heparin and whose four week IPG was normal were allocated to either continue warfarin (targeted International Normalized Ratio 2.0 to 3.0) for a further eight weeks or receive placebo. Patients with an abnormal four week IPG received warfarin for a further eight weeks. Based on clinical characteristics at the time of the qualifying thrombosis, all patients were classified as having either continuing or transient risk factors for recurrent VTE. During the eight weeks following randomization, nine (8.6%) of the 105 placebo patients developed recurrent VTE compared to one (0.9%) of the 109 warfarin patients, P = 0.009. Over the entire 11 months of follow-up, 12 placebo patients developed recurrence compared to seven warfarin patients, P = 0.3. Nineteen of the 192 patients with an abnormal four week IPG experienced recurrence during the nine months after discontinuing warfarin. In the 301 patients who received three months of warfarin in the randomized trial or in the cohort study, all 26 recurrent events were in the 212 patients with continuing risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Plasma cell lesions of the thyroid: report of a case of solitary plasmacytoma and a review of the literature.

We report a case of a solitary plasmacytoma arising from a thyroid with longstanding Hashimoto's disease, and diagnosed by fine-needle aspiration cytology. Serum protein electrophoresis revealed an M-spike in the gamma-globulin region due to monoclonal IgG-lambda immunoglobulin. The thyroid tumor was treated with near-total thyroidectomy and irradiation, and the patient was well 6 years after surgery without evidence of multiple myeloma. The serum M-spike disappeared after the tumor resection and radiation therapy. Plasma cell lesions of the thyroid reported in the world literature are extensively reviewed. Solitary plasmacytomas occur most commonly in patients with Hashimoto's disease, and must be distinguished from plasma cell granulomas and involvement of the thyroid in multiple myeloma. Plasmacytomas should be considered in the differential diagnosis of a rapidly enlarging thyroid mass in a patient with known Hashimoto's disease.

Antibodies, Monoclonal↗
PubMed1994

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Oral anticoagulation therapy in pediatric patients: a prospective study.

There are no validated guidelines for administering or monitoring oral anticoagulant therapy in pediatric patients. A pediatric thromboembolism program at the Hospital for Sick Children, Toronto, prospectively monitored consecutive children requiring warfarin over an 18 month period. A uniform protocol was followed and dose adjustments based upon international normalized ratios (INRs). One hundred and fifteen consecutive children; 68 males and 47 females, received warfarin. The age distribution was: <1y (19); 1-5 ys (33); 6-10 ys (20); 11-18 ys (43). Warfarin was used for secondary prevention of venous thromboembolism (n = 56) and primary prevention of thromboembolism (n = 59). Underlying disorders included: congenital heart disease (CHD) without mechanical valves (MV) (49); CHD with MV (18); cancer (8); longterm total parenteral nutrition (7); renal disorders (10); other (23). Treatment length was considered as short term (3-6 mths) n = 37 (32%); longterm (> 6 mths) n = 38 (33%); and life-long n = 40 (35%) of children. While receiving warfarin, 95 children received concurrent longterm treatment with other drugs: 1 drug (28); 2 drugs (27); 3 drugs (21); 4 or more drugs (19). The amounts of warfarin/kg required to achieve INRs of 2 to 3 decreased with increasing age. Children <1 year of age required 0.32 +/- 0.05 mg/kg whereas children 11-18 yrs required 0.09 +/- 0.01 mg/kg; P < 0.001. Monitoring warfarin required an average of 4.0 measurements per month and 1.5 dose changes per month. Changes in warfarin doses were primarily precipitated by drugs, intermittent illness, and changes in diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

The effects of TSH receptor antibodies on protein kinase C in the thyroid.

OBJECTIVE: There is increasing evidence that TSH activates a non-cyclic-AMP-dependent pathway in the thyroid resulting in protein kinase C activation. We have previously demonstrated that TSH activates protein kinase C by causing translocation of protein kinase C from an inactive cytosolic site to its active membrane-bound form in porcine thyroid cells. In addition, TSH can modify the protein kinase C translocation induced by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. We tested six TSH receptor antibodies for their ability to activate protein kinase C in vitro. DESIGN: Porcine thyroid cells were incubated with either TSH receptor antibody or immunoglobulin from pooled normal sera. Subsequently, cytosol and membrane compartments were separated and protein kinase C assessed in each compartment. PATIENTS: The sera utilized in this study were obtained from patients with confirmed Graves' disease as defined by clinical evidence of thyrotoxicosis, increased free thyroxine index and suppressed TSH and increased radioactive iodine uptakes. MEASUREMENTS: Protein kinase C was measured in the cytosol and membrane compartments of the porcine thyroid cells using an enzyme assay. RESULTS: Compared to immunoglobulin from pooled normal sera, none of the six TSH receptor antibodies affected either cytosolic or membrane-bound protein kinase C in porcine thyroid cells. The tumour-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, caused protein kinase C translocation. However, the presence of TSH receptor antibody did not modify the phorbol-induced protein kinase C translocation. CONCLUSION: These results indicate that unlike TSH, TSH receptor antibodies neither cause translocation of protein kinase C nor modify phorbol-mediated protein kinase C translocation in porcine thyroid cells.

Animals↗