Biomedical subjects

D Roy

Publications and source records attributed to D Roy.

At least 145 records · Page 8Linked to original sources

PubMed1997

Electrical stimulation induces fiber type-specific translocation of GLUT-4 to T tubules in skeletal muscle.

Insulin and contraction independently stimulate glucose transport in skeletal muscle. Whereas insulin activates glucose transport more in muscles composed of type I and IIa fibers, electrical stimulation increases glucose transport at least as much in type IIb fiber-enriched muscles despite the fact that the latter fiber type contains less GLUT-4 glucose transporters. The aim of the present study was to test the hypothesis that a greater GLUT-4 translocation to the cell surface may underlie the higher contraction-stimulated glucose transport in type IIb myofibers. Leg muscles from rats were stimulated in situ at 100 Hz (200 ms) each 2 s via the sciatic nerve over a period of 20 min while the contralateral leg was kept at rest. Muscle 2-[3H]deoxy-D-glucose uptake (2-DG) was measured in separated red gastrocnemius (RG, type I and IIa fibers) and white gastrocnemius (WG, type IIb fibers) muscles. Resting 2-DG uptake was greater in RG than WG. Electrical stimulation increased 2-DG uptake over resting values similarly in WG and RG. Fractions enriched with either plasma membranes, transverse (T) tubules, triads, or GLUT-4-enriched intracellular membranes were isolated from RG and WG using a recently developed subcellular fractionation procedure. Electrical stimulation similarly increased GLUT-4 protein content in plasma membranes of RG and WG, whereas it stimulated GLUT-4 translocation more (approximately 50%) in T tubules of WG than in RG. GLUT-4 content was not changed in triads of both muscle types. The increments in cell surface GLUT-4 protein levels were paralleled by significant reductions in the amount of the transporter in the intracellular membrane fractions of both muscle types (by 60% in RG and 56% in WG). It is concluded that electrically induced contraction stimulates GLUT-4 translocation more in T tubules of WG than RG. The physiological implications of this finding for glucose uptake by contracting RG and WG muscles is discussed.

Animals↗

PubMed1997

Endovascular treatment of acutely ruptured and unruptured aneurysms of the basilar bifurcation.

The surgical treatment of basilar bifurcation aneurysms is difficult and the need for an alternative approach is frequently stated. To assess the efficacy and safety of endovascular treatment of aneurysms located at the basilar bifurcation, the authors prospectively studied angiographic results, clinical results, and complications in 31 patients treated with Guglielmi detachable coils (GDCs). Patients treated acutely after subarachnoid hemorrhage (SAH) were graded according to the Hunt and Hess classification and clinical outcome was determined at 1- and 6-month intervals according to the Glasgow Outcome Scale (GOS). There were 18 women and 13 men, ranging in age from 34 to 67 years (mean age 48 years). Twenty-three were treated acutely after SAH. Clinical Hunt and Hess grades at presentation were as follows: Grade I, six patients; Grade II, three; Grade III, 11; Grade IV, two; and Grade V, one. The GOS score for the group of patients treated acutely was: GOS I, 18 patients; GOS II, III, and IV, one patient each; and GOS V, two patients. There were seven technical complications in this group, most often asymptomatic, but one patient died after aneurysm rupture during treatment and one had residual diplopia at 4 months. Eight patients were treated for incidental basilar bifurcation aneurysms. One technical complication with no neurological deficit occurred in this group of patients with incidental aneurysms. Immediate angiographic results were considered to be satisfactory in 94% of patients, with complete obliteration in 42% and residual neck and dog ears in 52%. There was no bleeding episode after treatment during clinical follow-up periods ranging from 3 to 42 months (mean 15.5 months in 29 surviving patients). Angiographic results were available for 27 patients at 6 months and were as follows: 30% of the lesions were completely obliterated, 59% presented some residual neck, and 11% showed some opacification of the aneurysm sac. During the follow-up period of up to 42 months, a total of seven recurrences were noted, necessitating retreatment with GDCs in five patients. Endovascular treatment of basilar bifurcation aneurysms prevented rebleeding and could be performed without clinically significant complications in 94% of patients. Clinical results after SAH compared favorably with surgical series. Morphological results appear less satisfactory, and long-term angiographic follow-up review is mandatory to detect recurrences.

Adult↗

PubMed1997

Arterial injuries in transsphenoidal surgery for pituitary adenoma; the role of angiography and endovascular treatment.

PURPOSE: To define the role of angiography and embolization in the treatment of patients who have arterial injuries during transsphenoidal surgery. METHODS: We retrospectively studied the arterial hemorrhagic complications, their management, and the clinical outcomes that occurred in 21 of the more than 1800 patients who had transsphenoidal surgery for pituitary adenomas. RESULTS: Of the 21 patients who had complications, 17 had internal carotid injuries and four had injuries of the sphenopalatine artery. Angiography was performed in 18 patients. Bleeding occurred and was controlled during surgery in 16 cases. Delayed epistaxis occurred in 10 patients, including five whose surgery was uneventful. After internal carotid injury, the most frequent angiographic findings were carotid occlusion (eight patients), stenosis (five patients), and false aneurysms (three patients). Internal carotid balloon occlusion was performed in five patients. No rebleeding occurred in patients who had complete carotid occlusion either from surgical packing or balloon embolization. Two of the patients who had carotid stenosis after surgical packing had delayed epistaxis necessitating balloon occlusion. Injuries to the sphenopalatine artery were successfully treated by surgery (one patient) or by endovascular treatment (three patients) without complication. Three deaths and five permanent deficits were directly related to the arterial injury or its treatment. CONCLUSION: Profuse bleeding during and after transsphenoidal surgery should be investigated by angiography. Lesions of the sphenopalatine arteries are effectively treated by embolization. Internal carotid injuries are best treated by carotid infusion to prevent life-threatening epistaxis.

Adenoma↗

PubMed1997

Radiofrequency ablation of bundle branch reentrant tachycardia in a patient with atrial septal defect.

A 22-year-old woman with an atrial septal defect surgically corrected during childhood presented with a wide QRS complex tachycardia with left bundle branch block morphology. Electrophysiological study was performed and bundle branch reentrant tachycardia was induced with morphology identical to clinical tachycardia. Radiofrequency catheter ablation of the right bundle branch was successful, resulting in complete right bundle branch block and cure of her ventricular arrhythmia.

Adult↗

PubMed1997

Endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable coils.

PURPOSE: To evaluate the safety and efficacy of endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable coils (GDCs), as well as the primary indications for such treatment. METHODS: We conducted a prospective study of 26 patients with 28 aneurysms of the ophthalmic segment in whom treatment with GDCs was attempted. Anatomic results were measured by statistical analysis of variance for such factors as age, sex, presence of subarachnoid hemorrhage, anatomic type (ophthalmic or superior hypophyseal), size of aneurysmal sac, and width of aneurysmal neck. Clinical evaluation and control angiography were performed at 6 and 18 months. RESULTS: Overall, complete occlusion was obtained in 14 aneurysms (50%) and small residual necks were left in 11 aneurysms (39%). Three treatment attempts failed (11%). Complete occlusion was obtained in 76% of small-necked aneurysms as opposed to 9% of aneurysms with a large neck. The best predictor of anatomic result was the size of the aneurysmal neck. Complete occlusion was obtained in 85% of superior hypophyseal aneurysms of the paraclinoid variant. One permanent complication was related to treatment. CONCLUSION: Endovascular treatment with GDCs appears to be a safe and efficient alternative approach for ophthalmic segment aneurysms, especially for paraclinoid variants of superior hypophyseal aneurysms, which tend to have a small neck.

Adult↗

PubMed1996

Control of heart rate during transition from intravenous to oral diltiazem in atrial fibrillation or flutter.

We tested whether patients presenting with atrial fibrillation (AF) or flutter (AFl) with a rapid ventricular response could maintain control of heart rate while transferring from a bolus and continuous infusion of intravenous diltiazem to oral diltiazem. Forty patients with AF or AFI and sustained ventricular rate > or = 120 beats/min received intravenous diltiazem "bolus" (20 to 25 mg for 2 minutes) and "infusion" (5 to 15 mg/hour for 6 to 20 hours). Oral long-acting diltiazem (diltiazem CD 180, 300, or 360 mg/24 hours) was administered in patients in whom stable heart rate control was attained during constant infusion. Intravenous diltiazem infusion was discontinued 4 hours after the first oral dose, and patients were monitored during 48 subsequent hours of "transition" to oral therapy. Response to diltiazem was defined as heart rate <100 beats/min, > or = 20% decrease in heart rate from baseline, or conversion to sinus rhythm. Other rate control or antiarrhythmic medications were not allowed during the study period. Thirty-seven of 40 patients maintained heart rate control during the bolus, and 35 of the remaining 37 maintained control during the infusion of intravenous diltiazem. Of the 35 patients achieving heart rate control with intravenous diltiazem who entered the transition to oral therapy, 27 maintained heart rate control (response rate of 77%/, 95% confidence interval 63% to 91%). The median infusion rate of intravenous diltiazem was 10 mg/hour, and the median dose of oral diltiazem CD was 300 mg/day. Oral long-acting diltiazem was 77% effective in controlling ventricular response over 48 hours in patients with AF or AFl in whom ventricular response was initially controlled with intravenous diltiazem.

Administration, Oral↗

PubMed1996

Apoptosis of cardiac myocytes during cardiac allograft rejection. Relation to induction of nitric oxide synthase.

BACKGROUND: Apoptosis is a distinct form of programmed cell death characterized by activation of endonucleases that cleave nuclear DNA, condensation and fragmentation of nuclear chromatin, blebbing of intact membranes, and cell shrinkage and fragmentation. The mechanisms responsible are unclear, but nitric oxide (NO) generated by inducible NO synthase (iNOS) has been demonstrated to induce apoptosis in macrophages in vitro. This study investigated whether apoptosis occurs during cardiac allograft rejection and examined the relationship of apoptosis to iNOS expression. METHODS AND RESULTS: Heterotopic abdominal transplantation from Lewis to Wistar-Furth rats was used as a model of cardiac allograft rejection; Lewis-to-Lewis grafts served as controls. Apoptosis was identified by DNA ladders after electrophoresis on agarose gels and by in situ labeling of DNA fragments; cell types were determined by immunohistochemistry. The number of apoptotic cardiac myocytes increased sharply from day 3 (0.31/mm2 ventricular tissue) to day 5 (1.27/mm2) after transplantation. At day 5, allografts showed a significant increase (P < .01) in apoptotic cardiac myocytes, macrophages, and endothelial cells compared with syngeneic grafts. The expression of iNOS mRNA, protein, and enzyme activity paralleled in time and extent the apoptosis of cardiac myocytes. iNOS immunostaining of infiltrating macrophages and cardiac muscle fibers increased significantly in the allografts at days 3 to 5 and was accompanied by immunostaining of both cell types for nitrotyrosine, which is indicative of peroxynitrite formation. CONCLUSIONS: Apoptosis of myocardial cells occurs during cardiac allograft rejection. Apoptosis during rejection parallels the expression of iNOS, which suggests that apoptosis may be triggered by NO and peroxynitrite.

Animals↗

PubMed1996

Inhibition of stilbene estrogen-induced cell proliferation of renal epithelial cells through the modulation of insulin-like growth factor-I receptor expression.

In the present study, we have investigated the effects of stilbene estrogen, diethylstilbestrol (DES), on the proliferative activity and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. DES exposure to renal epithelial cells caused both dose- and time-dependent increases in proliferative activity. We also tested the effects of antiestrogen ICI 182780 and insulin-like growth factor-I receptor (IGF-IR) antibody on cell proliferation. Cotreatment of cells with ICI 182780 (250 nM) and DES resulted in a 50% decrease in cell growth compared to DES alone. Treatment of cells with an anti-IGF-IR antibody (alpha IR3, 1 microgram/ml) also significantly reversed the growth-stimulatory effects of DES. A nuclear binding assay revealed that an enhanced level (approximately 2-fold) of [125I]IGF-I binding to nuclear protein occurred in DES treated renal epithelial cell nuclei compared to controls. IGF-I receptor gene expression analyzed by Northern blotting revealed that DES treatment increased the level of IGF-IR mRNA by 2-fold compared to controls. We also tested the effect of ICI compound on the induction of IGF-I receptor gene. The cotreatment of ICI 182780 strongly inhibited DES-induced IGF-I receptor gene expression (50-60% inhibition). Stimulation of the proliferative activity of renal epithelial cells by stilbene estrogen, its prevention by IGF-I receptor antibody, and inhibition of DES-induced proliferative activity and the expression of IGF-I receptors by ICI 182780 suggest the possibility that the stimulatory effect of DES on the proliferative activity of renal epithelial cells may be mediated through the up-regulation of IGF-I receptors.

Animals↗

PubMed1996

Exercise induces the translocation of GLUT4 to transverse tubules from an intracellular pool in rat skeletal muscle.

Exercise stimulates glucose transport in skeletal muscle by increasing the number of GLUT4 glucose transporters at the cell surface. The effect of exercise on GLUT4 content in transverse tubules, which are deep extensions of the plasma membrane involved in myofiber contraction, has never been studied. In the present study, we have investigated whether acute exercise induces translocation of GLUT4 to the transverse tubules. Plasma membranes and transverse tubules were isolated from control and exercised rats by a newly developed membrane fractionation procedure. As expected, acute exercise increased GLUT4 content in plasma membranes (95%; p < 0.01). Importantly, exercise also significantly increased GLUT4 content in a transverse tubule-enriched fraction (60%; p < 0.05). Furthermore, acute exercise was found to decrease GLUT4 content in an intracellular membrane fraction (-40%; p < 0.001). In conclusion, this study demonstrates that GLUT4 is translocated not only to the plasma membranes but also to the transverse tubules in acutely exercised muscles. The results also indicate that GLUT4 is recruited from a novel intracellular membrane fraction.

5'-Nucleotidase↗

PubMed1996

Factors determining compliance with screening mammography.

OBJECTIVE: To determine factors affecting compliance with screening mammography prescribed by family physicians. DESIGN: Secondary analysis of a nonrandomized trial. SETTING: University-affiliated family medicine clinic in Montreal. PATIENTS: Women aged 50 to 69 years who were given a written prescription for a screening mammography during their visit at the clinic between Oct. 12, 1991, and May 31, 1992, and who had not undergone mammography in the preceding 2 years and had never been treated for breast cancer. Information on the potential factors was obtained through a telephone questionnaire 2 months after the visit. OUTCOME MEASURES: Indicator of compliance presence of result of screening mammography in patient chart, potential factors influencing compliance: age, level of education, marital status, socioeconomic level, smoking status, perceived health status, perceived psychological well-being, risk factors for breast cancer, use of health services including frequency of Papanicolaou test, Health Belief Model variables. RESULTS: Of the 171 eligible women, 113 (66.1%) underwent the prescribed mammography within 2 months after the visit to the clinic, and 149 (87.1%) responded to the questionnaire. The patients' socioeconomic characteristics, perceived health status, health utilization indices and risk factors for breast cancer were not found to be predictors of compliance. The strongest predictor of compliance was the number of previous mammograms. Women who had undergone mammography previously were less likely to be noncompliant than those who had not (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.02 to 0.51; p = 0.005). Women who did not comply were less likely than those who did to believe that a prescription from their physician would convince them to undergo mammography (OR 0.21, 95% CI 0.007 to 0.60; p = 0.004). Other factors associated with noncompliance were the expression of fear of mammography (OR 2.09, 95% CI 1.08 to 4.02; p = 0.03) and the lack of time to take the test (OR 3.07, 95% CI 1.21 to 7.80 p = 0.02). Being a smoker was negatively associated with compliance (OR 0.43; 95% CI 0.22 to 0.86; p = 0.02). The stepwise logistic regression model accounted for 87.5% of the outcome (chi2 for goodness of fit = 164.4; p = 0.0001). CONCLUSION: Family physicians who prescribe screening mammography, even to women who consult for other reasons, are likely to overcome some of the barriers observed in association with population screening rates. However, physician-oriented approaches are not likely to reach the 30% to 40% of reluctant women who appear to hold negative views toward physicians' recommendations. Further study is necessary to determine how better to reach these women.

Aged↗

PubMed1996

Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol.

In the present study we report the novel findings that IGF-I receptors are present in the nucleus based on the evidence from binding assay, detection of receptors by affinity labeling and Western blotting, and localization by immunofluorescence. The level of nuclear IGF-I receptors (nIGF-IRs) almost doubled in stilbene estrogen (diethylstilbestrol, DES) treated hamster kidneys compared to the controls. The binding constants Kd and Bmax of nIGF-IR of controls, 22.1 nM and 6.6 nmol/mg protein, respectively, were changed in response to DES treatment to 5.3 nM and 16.3 nmol/mg protein (P < 0.001), respectively. The enhanced level of IGF-IR in DES-treated nuclei was confirmed by both affinity labeling and Western blotting. These data suggest that IGFs may exert their biological effect through the IGF-I receptor present in the nucleus. Whether the up-regulation of nIGF-IR by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters, is not clear.

Animals↗

PubMed1996

Biochemical characterization of a mitomycin C-resistant human bladder cancer cell line.

This study describes characteristics of a mitomycin C (MMC)-resistant human bladder cancer cell line, J82/MMC-2, which was established by repeated in vitro exposures of a 6-fold MMC-resistant variant (J82/MMC) to 18 nM MMC. A 9.6-fold higher concentration of MMC was required to kill 50% of the J82/MMC-2 sub-line compared with parental cells (J82/WT). NADPH cytochrome P450 reductase and DT-diaphorase activities were significantly lower in J82/MMC-2 cells compared with J82/WT, suggesting that reduced sensitivity of J82/MMC-2 cells to MMC resulted from impaired drug activation. Consistent with this hypothesis, the formation of MMC-alkylating metabolites was significantly lower in J82/MMC-2 cells compared with J82/WT. Furthermore, DT-diaphorase activity in J82/MMC-2 cells was significantly lower compared with the 6-fold MMC-resistant variant. Glutathione (GSH) levels were comparable in all 3 cell lines. Although GSH transferase (GST) activity was significantly higher in the J82/MMC-2 cells compared with J82/WT, this enzyme activity did not differ between 6- and 9.6-fold MMC-resistant variants. Whereas DNA polymerase alpha mRNA expression was comparable in these cell lines, levels of DNA ligase I mRNA were slightly lower in both MMC-resistant variants relative to J82/WT. However, the DNA polymerase beta mRNA level was markedly higher in the J82/MMC-2 cell line compared with either J82/WT or J82/MMC. Thus, emergence of a higher level of resistance to MMC in J82/MMC-2 cells compared with J82/MMC may be attributed to (i) impaired drug activation through further reduction in DT-diaphorase activity and (ii) enhanced DNA repair through over-expression of DNA polymerase beta.

Antibiotics, Antineoplastic↗

PubMed1996

Zinc and iron as bioindicators of precancerous nature of oral submucous fibrosis.

Oral Submucous Fibrosis (OSF) is a precancerous condition of oral cavity and oropharynx. Its etiopathogenesis is still obscure. Epithelial dysplasia is considered an important indicator of it. In the present study, the authors try to ascertain bioinorganic parameters as alternate indicators of malignant potential of OSF along with other clinicopathological attributes. They also try to identify causative factors. Thirty-six OSF patients, showing different degrees of epithelial dysplasia, and 12 normal individuals are studied with special reference to trace metal contents (Zn and Fe) in oral tissues. Statistical analyses of data indicate that trace metal contents can be regarded as an alternate indicator of the precancerous nature of OSF. Some clinicopathological attributes that are easier and cheaper to measure may also indicate OSF.

Adult↗

PubMed1996

Differentiation of bifidobacteria by use of pulsed-field gel electrophoresis and polymerase chain reaction.

Several different genomic fingerprints can be obtained from various commercially-important species of Bifidobacterium using pulsed-field gel electrophoresis (PFGE) following digestion of DNA with XbaI and SpeI. Four different genomic finger printings were discernible for reference strains of Bifidobacterium animalis, five for B. bifidum, three for B. breve, five for B. infantis and three for B. longum. Standard commercially-available industrial strains of B. animalis are identical to the reference strain ATCC 27536, previously isolated from chicken feces. There was more genomic heterogeneity among industrial strains of B. longum, in that only one gave profiles similar to the type strain of this species (ATCC 15707). The other 14 commercially-available strains of B. longum (mainly isolated from Japanese commercial preparations) were divided into four new molecular types based on their PFGE patterns. The PFGE method indicated that only five distinct strains of B. longum and one strain of B. animalis are used in commercial preparations. Additionally, the use of polymerase chain reaction amplification of portions of 16S rDNA provides a highly specific technique to discriminate between the species B. breve, B. infantis and B. longum.

Adult↗

PubMed1996

Insulin-induced translocation of Na+-K+-ATPase subunits to the plasma membrane is muscle fiber type specific.

We have previously shown that an acute insulin treatment induces redistribution of the alpha 2- and beta 1- isoforms of the Na+-K+-ATPase from intracellular membranes to plasma membranes detected on subcellular fractionation of mixed muscles and immunoblotting with isoform-specific antibodies (H. S. Hundal et al. J. Biol. Chem. 267: 5040-5043, 1992). In the present study we give both biochemical and morphological evidence that this insulin effect is operative in muscles composed mostly of oxidative (red) fibers but not in muscles composed mostly of glycolytic (white) fibers. The redistribution of the Na+-K+-ATPase alpha 2- and beta 1-isoforms after insulin injection was detected in membranes isolated from and muscles (soleus, red gastrocnemius, red rectus femoris, and red vastus lateralis) but not in membranes from white muscles (white gastrocnemius, tensor fasciae latae, white rectus femoris, and white vastus lateralis). After insulin injection, the potassium-dependent 3-O-methylfluorescein phosphatase activity of the enzyme was higher by 22% in the plasma membrane-enriched fraction and lower by 15% in the internal membrane fraction isolated from red but not from white muscles. Quantitative immunoelectron microscopy of ultrathin muscle cryosections showed that in vivo insulin stimulation augmented the density of Na+-K+-ATPase alpha 2- and beta 1- isoforms at the plasma membrane of soleus muscle by 80 and 124%, respectively, with no change in white gastrocnemius muscle. The effect of insulin to increase the content of Na+-K+-ATPase alpha 2- and beta 1-subunits in isolated plasma membranes was still observed when glycemia was prevented from dropping by using hyperinsulinemic-euglycemic clamps. We conclude that the insulin-induced redistribution of the alpha 2- and beta 1-isoforms of the Na+-K+-ATPase from an intracellular pool to the plasma membrane in restricted to oxidative fiber-type skeletal muscles. This may be related to the selective expression of beta 1-subunits in these fibers and implies that the beta 2-subunit, typical of glycolytic muscles, does not sustain translocation of alpha 2 beta 2-complexes.

Animals↗

PubMed1996

A new procedure for the isolation of plasma membranes, T tubules, and internal membranes from skeletal muscle.

A new subcellular fractionation procedure for the simultaneous isolation of plasma membranes and transverse (T) tubule membranes from a rat skeletal muscle was developed. This new technique allows the isolation and separation of plasma membranes and T tubules in distinct subcellular fractions, as revealed by the membrane distribution of enzymatic and immunologic markers of both cell surface compartments. The procedure also yields a novel membrane fraction that is devoid of markers of both surface domains but is markedly enriched with GLUT-4 glucose transporters, thus strongly suggesting that it represents an intracellular pool of GLUT-4. Using this new procedure, we found that acute in vivo insulin administration (30 min) increased GLUT-4 protein content in the plasma membrane and a T tubule fraction (by approximately 80%), whereas a smaller elevation (35%) was observed in another fraction enriched with T tubules. Insulin induced a concomitant reduction (approximately 40%) in GLUT-4 abundance in the intracellular fraction. These results further support the hypothesis that T tubules are involved in the regulation of glucose transport in skeletal muscle. This novel fractionation method will be useful in investigating the regulation of muscle GLUT-4 transporters in other physiological and disease states such as diabetes, where defective translocation of the transporter protein to either one or both cell surface domains is suspected to occur.

Animals↗

PubMed1996

Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease.

Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.

Adolescent↗

PubMed1996

Direct intraoperative sclerotherapy of an aneurysmal bone cyst of the sphenoid.

A young boy presented with a symptomatic aneurysmal bone cyst of the left great wing of the sphenoid bone. Arterial embolization had failed to produce thrombosis, and the lesion could not be resected surgically. Direct intraoperative sclerotherapy resulted in immediate thrombosis of 80% of the volume of the vascular malformation with no progression of symptoms. Two years later, the symptoms had completely resolved, and CT scans showed total ossification of the lesion.

Arteriovenous Malformations↗