Biomedical subjects

T Tracy

Publications and source records attributed to T Tracy.

At least 37 records · Page 2Linked to original sources

PubMed1997

Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis.

In 31 patients with osteonecrosis (primarily of the hip), 74% had 1 or more primary coagulation disorders. In 18 patients, 15 (83%) who had coagulation disorders, the osteonecrosis was initially identified as idiopathic and was not associated with known underlying drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease, Gaucher's disease). In 13 patients, 8 (62 %) who had coagulation disorders, the osteonecrosis was initially identified as secondary, and was associated with glucocorticoids in 12 patients, and with alcoholism in 1. The coagulation disorders included thrombhophilia (increased tendency to intravascular thrombosis) and hypofibrinolysis (reduced ability to lyse thrombi). Of the 18 patients initially thought to have idiopathic osteonecrosis, thrombophilia alone was found in 12% (resistance to activated protein C in 6%, low protein C in 6%), hypofibrinolysis alone was found in 50% (high lipoprotein(a) in 44%, low stimulated tissue plasminogen activator activity was found in 6%), and mixed thrombophilia hypofibrinolysis was found in 22%. Resistance to activated protein C was more common in these 18 patients than in healthy controls (11% versus 0%), as was high lipoprotein(a) (67% versus 20%). Of the 13 patients with secondary osteonecrosis, thrombophilia alone was found in 8% (low protein C), hypofibrinolysis alone was found in 30% (high Lp(a) in 15%, low tissue plasminogen activator activity in 15%), and mixed thrombophilia hypofibrinolysis was found in 23%. Low tissue plasminogen activator activity was more common in the 13 patients with secondary osteonecrosis than in controls (27% versus 7%), as was low protein C (23% versus 0%). In aggregate, these findings lead us to the speculation that primary, heritable thrombophilia or hypofibrinolysis causes thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic death of bone (osteonecrosis).

Adult↗

PubMed1996

Risk factors for coronary heart disease among firefighters in Cincinnati.

Since 1984, coronary heart disease (CHD) risk factors have been prospectively assessed among Cincinnati firefighters free of CHD at study entry. In total, 806 firemen with a mean age of 37 years at entry have been followed for 6.4 years on average, contributing 5,173 person-years. CHD risk factors were measured every 1-4 years and included weight, blood pressure, cigarette use, fasting glucose, and lipid profile. When, in aggregate, these CHD risk factors were found to be in a high risk range, suggestions were made serially to reduce CHD risk. A composite high CHD risk factor score led to an exercise electrocardiogram (ECG) with thallium scan, which was repeated every 1-4 years. Myocardial infarction (MI) occurred in 7 men, with 1.35 MIs/1,000 man-years; 15 others developed CHD, with 4.25 MI + CHD/1,000 man-years. The firefighters' MI event rate (1.35 MIs/1,000 man-years) was lower (but not significantly, p > 0.1) than that for employed 30- to 39-year-old men free of CHD at entry (2.07/1,000 man years), who had an average follow-up of 5.4 years in the NHANES I study. At study entry, the 22 men who later developed CHD (vs. the 784 who did not develop CHD) were older (p = .0001), smoked more (p = .0001), and were more likely to have first degree relatives with CHD before age 60 (p = .017). After covariance adjusting for age, race, and Quetelet index, men with CHD (vs. those CHD free) had higher systolic and diastolic blood pressures (p = .0001, .0001), higher LDL cholesterol (p = .04), higher total cholesterol (p = .014), and higher triglycerides (p = .03). By Poisson regression, significant independent predictors of CHD events were age (p = .0007), cigarette smoking (p = .001), diastolic blood pressure (p = .056), and family history of CHD at age < or = 60 (p = .048). Men who later developed CHD and those without CHD did not differ by history of smoke inhalation (p > 0.3). The calculated ratio of savings to cost attributable to the program per year was 5.9/1 ($258,500/$43,600). In the current study, firefighting as an occupation was not associated with increased CHD event rates. CHD events that did develop were, for the most part, associated with modifiable CHD risk factors.

Adult↗

PubMed1996

The pathophysiology of alveolar osteonecrosis of the jaw: anticardiolipin antibodies, thrombophilia, and hypofibrinolysis.

We studied 55 patients (50 women, 5 men) with severe facial pain and biopsy-proven neuralgia-inducing cavitational osteonecrosis (NICO) of the alveolar bone of the jaws. Our aim was to assess the pathophysiologic contributions to NICO of anticardiolipin antibodies (aCLA), thrombophilia (increased tendency to intravascular thrombi), and hypofibrinolysis (reduced ability to lyse thrombi). Of the 55 patients, 43 (78%) had one or more tests positive for thrombophilia or hypofibrinolysis (or both), and only 12 (22%) were normal. Eighteen of 55 (33%) patients had high aCLA (> 2 SD above mean value for control subjects); immunoglobulin G (IgG) (p = 0.01) and immunoglobulin A (IgA)(p = 0.001) levels were higher in patients than in controls. The distribution of elevated aCLA immunoglobulin classes among patients was as follows: IgG alone, 5 (9%); IgA alone, 7 (13%); and IgM alone, 3 (5%). Three patients (5%) had high levels of both IgG and IgA aCLA. Other defects of the thrombotic or fibrinolytic systems in the 55 patients included high lipoprotein(a) in 36% (vs 20% in control subjects (p = 0.03)), low stimulated tissue plasminogen activator activity (tPA-Fx) in 22% (vs 7% in control subjects (p = 0.08)), high plasminogen activator inhibitor activity (PAI-Fx) in 18% (vs 8% in control subjects (p = 0.03)), resistance to activated protein C in 16% (vs 0% in control subjects (p = 0.007)), low antigenic protein C in 4+ (vs 0% in control subjects (p > 0.2)), and low antigenic protein S in 4% (vs 0% in control subjects (p > 0.2)). Anticardiolipin antibodies and other defects of the thrombotic and fibrinolytic systems appear to be common, potentially reversible pathogenetic risk factors associated with osteonecrosis of the jaw.

Adolescent↗

PubMed1996

Thrombophilia, hypofibrinolysis, and alveolar osteonecrosis of the jaws.

OBJECTIVES: Our specific aim in 49 patients (42 women, 7 men) with osteonecrosis of the jaw was to determine whether thrombophilia (increased tendency to intravascular thrombosis) or hypofibrinolysis (reduced ability to lyse thrombi) were associated with this regional avascular necrosis. STUDY DESIGN: Determinants of thrombosis and fibrinolysis were compared in healthy controls and in 42 women and 7 men who had biopsy-proven idiopathic osteonecrosis of the jaw with severe chronic jaw or facial pain syndromes and failure to respond to conventional medical and dental treatments. RESULTS: Of the 49 patients, 35 (71%) had thrombophilia or hypofibrinolysis and only 14 were normal. Thrombophilia as a sole coagulation defect was found in 10 patients, 7 with resistance to activated protein C and 3 with low protein C (deficiency of an antithrombotic protein). Hypofibrinolysis with low stimulated tissue plasminogen activator activity and high lipoprotein (a) (an atherogenic, hypofibrinolytic lipoprotein) were found as sole coagulation defects in seven and eight patients, respectively. Ten patients had mixed defects; 7 of these 10 had thrombophilia with resistance to activated protein C. Sinusoidal dilatation was a constant feature in maxillary and mandibular bone biopsies, suggesting venous occlusion with intramedullary hypertension. Marrow fibrosis and occasional fibrin plugs were additional microscopic features believed to impair venous drainage and to contribute to ischemic necrosis of the alveolar bone. CONCLUSIONS: Primary thrombophilia and hypofibrinolysis appear to be common, heritable, pathophysiologic risk factors for idiopathic osteonecrosis of the jaws. These coagulation defects may also contribute to alveolar neuralgia, atypical odontalgia and facial neuralgia, idiopathic trigeminal neuralgia, and to treatment failures so often encountered in patients with alveolar osteonecrosis and disabling chronic facial and jawbone pain syndromes.

Adult↗

PubMed1995

Whether, to what degree, and why lipoprotein(a) levels change over time.

Our specific aim in this study of 6 +/- 2 serial lipoprotein(a) (Lp(a)) measurements over 1.7 +/- 0.5 years in 145 patients (64 men, 81 women, 135 whites, 10 blacks, mean age 63 years) with high Lp(a) (> or = 25 mg/dl) was to assess whether, to what degree, and why Lp(a) levels change over time. A second specific aim was to study the biological coefficient of variation of Lp(a) (C.V.b). No Lp(a) lowering drugs were given. In the 145 patients, mean (S.D.) and median Lp(a) on entry (70 +/- 34 and 59 mg/dl) did not differ from levels on follow-up (72 +/- 34 and 64 mg/dl) (P > 0.4). Mean (S.D.) C.V.b was 18 +/- 9%, median 17%, minimum 1.7% and maximum 58%. Three or four samples for Lp(a) measurement should be very adequate to establish a 'true' Lp(a) value, since C.V.bs based on three to four samples did not differ (P > 0.1) from those based on five to six, seven, eight, or nine samples. For patients with mean +/- S.D. baseline Lp(a) levels of 39 +/- 3, 49 +/- 3 and 59 +/- 2, 95% of the follow-up values fell in the following ranges: 25-78, 24-93 and 34-104 mg/dl. Lp(a) on study entry was highly correlated with Lp(a) on follow-up (r = 0.84, P = 0.0001) and with Lp(a)'s C.V.b on follow-up (r = 0.24, P = 0.003). Entry Lp(a) was inversely correlated with absolute and percent change in Lp(a) on follow-up (r = -0.38, P = 0.0001 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients.

In 482 patients sequentially referred for diagnosis and therapy of hyperlipidemia, our specific aim was to determine the prevalence of homocysteinemia, to assess whether it was independently associated with atherosclerotic vascular disease, and to determine how effectively high homocysteine could be treated with folic acid and pyridoxine. Of the 482 patients, 18 (3.7%) had high homocysteine (> or = 16.2 mumol/L, median = 19), 31 had high cystathionine (> or = 342 nmol/L) with normal homocysteine (median = 12), and 433 had normal cystathionine and homocysteine (median = 9). Of the 18 patients with high homocysteine, 13 (72%) had atherosclerotic vascular disease, much higher than the 44% (192 of 433 patients) with normal homocysteine (chi-square = 5.4, p = 0.02). In the 18 kindreds with a homocysteinemic proband, 14 (78%) had > or = 1 first-degree relatives with atherosclerotic vascular disease before age 65, compared with 50% (215 of 433) of the families where the proband had normal homocysteine (chi-square = 5.5, p = 0.02). In the 482 patients already at high risk for atherosclerotic vascular disease by virtue of hyperlipidemia, when assessed by logistic regression, homocysteine was an independent positive predictor of atherosclerotic vascular disease (p = 0.007); relative risk for atherosclerotic events was 2.8 times higher (p = 0.0004) in patients with top (> or = 11.4 mumol/L) than with bottom (< 6.9 mumol/L) quintile homocysteine. After 15 weeks of folic acid (5 mg/day) and pyridoxine (100 mg/day) therapy in 10 patients with high homocysteine, median homocysteine normalized, decreasing from 18 to 11 mumol/L (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with Stanozolol.

In five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI-Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic-androgenic steroid, Stanozolol (6 mg/day), would normalize PAI-Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI-Fx could normally elevate tissue plasminogen activator (tPA-Fx) after 10 min venous occlusion at 100 mm Hg. After 12-18 weeks on Rx, PAI-Fx and stimulated tPA-Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA-Fx was low, 0.4 +/- 0.3 IU/ml (lower limit of normal 2.28 IU/ml). On Rx, stimulated tPA-Fx normalized, rising to 2.83 +/- 1.9 IU/ml, P = .004. Prior to Rx, mean (SD) basal PAI-Fx was high, 99 +/- 68 (upper limit of normal 26.9 U/ml), and fell on Rx to 22.5 +/- 22, P = .004. In two of the five patients normalization of hypofibrinolysis or high Lp(a) was accompanied by major symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip pain, one of the four patients with high PAI-Fx and low stimulated tPA-Fx could walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing through 54 weeks on Rx, he walked 2 miles per day without pain, despite radiographic progression of ON. In three of the four patients with high PAI and with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was no clinical improvement after 14-156 weeks of Rx despite normalization of stimulated tPA-Fx and PAI-Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI-Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone marrow edema ("transient osteoporosis").(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Hypofibrinolysis: a common, major cause of osteonecrosis.

In 30 patients with osteonecrosis of the hip (12 idiopathic, 18 secondary), we assessed the role of hypofibrinolysis mediated by high levels of plasminogen activator inhibitor (PAI). We evaluated hypofibrinolysis as a common, potentially reversible, pathophysiologic cause of idiopathic osteonecrosis. In all 18 patients with secondary osteonecrosis, PAI was normal, as was the ability to activate fibrinolysis. Nine of the 12 patients with idiopathic osteonecrosis had exceptionally high PAI levels and could not normally elevate tissue plasminogen activator (tPA-Fx), the major stimulator of fibrinolysis, after 10 min of venous occlusion at 100 mm Hg. The group of 12 patients with idiopathic osteonecrosis, compared to the 18 with secondary osteonecrosis, had low mean stimulated tPA-Fx (1.92 vs. 7.6 IU/ml, P < or = .001) and very high stimulated PAI-Fx (70 vs. 7.6 U/ml, P < or = .01). Three of the 12 patients with idiopathic osteonecrosis had both normal PAI and normal stimulated tPA-Fx. These three patients and 14 of the 18 with secondary osteonecrosis had high lipoprotein (a) [Lp(a)] (> 20 mg/dl). Mean Lp(a) was much higher (60 mg/dl) in the patients with secondary osteonecrosis than Lp(a) (16 mg/dl, P < or = .001) in the 12 patients with idiopathic osteonecrosis. These findings suggest that hypofibrinolysis mediated by high PAI is a common cause of idiopathic osteonecrosis, whereas high Lp(a) may play an etiologic role in secondary osteonecrosis. Prospective studies of patients with high PAI and/or high Lp(a) should be carried out to assess further their apparently causal roles in osteonecrosis.

Adult↗

PubMed1994

Beta blockers, Lp(a), hypertension, and reduced basal fibrinolytic activity.

To assess the hypothesis that beta blocker use and hypertension are associated with high lipoprotein(a) [Lp(a)] or with reduced basal fibrinolytic activity, the authors studied relationships of hypertension and beta blockers to Lp(a), lipids, lipoproteins, apolipoproteins, and basal fibrinolytic activity in 385 patients consecutively referred for diagnosis and therapy of hyperlipidemia. A second aim was to determine possible gender differences in fibrinolytic activity among patients with hypertension. Ninety-nine patients (58 women [88% post-menopausal] and 41 men) had drug-treated hypertension. In women, hypertension was a positive, independent predictor of the major inhibitors of fibrinolysis, plasminogen activator inhibitor antigen (p = 0.017), and plasminogen activator inhibitor activity (p = 0.004). In men and women, major risk factors for atherosclerosis were significant, independent predictors of reduced basal fibrinolysis. Median Lp(a) in the 99 patients with hypertension (16 mg/dL) did not differ from Lp(a) (18 mg/dL) in normotensive patients (p > 0.1). Of the 385 patients, the 39 beta blocker users had higher plasminogen activator inhibitor activity (p = 0.01), higher triglyceride (p = 0.02) levels, and higher Quetelet Indices (p = 0.01) than non-users (n = 346). After covariance adjusting for age, Quetelet Indices, sex, and triglycerides, plasminogen activator inhibitor activity was not higher in beta blocker users than in non-users (p > 0.1). Median Lp(a) did not differ in beta blocker users (16 mg/dL) and in non-users (17 mg/dL), p greater than 0.1. Hypertensive, predominantly post-menopausal women are likely to have high plasminogen activator inhibitor activity and plasminogen activator inhibitor antigen with concurrent reduced fibrinolytic activity, as well as high fibrinogen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1994

Hypocholesterolemia and affective disorders.

The authors' specific aim was to assess hypocholesterolemia in 203 patients hospitalized because of affective disorders (depression, bipolar disorder, and schizoaffective disorder) compared with 1,595 self-referred subjects in an urban supermarket screening and with 11,864 subjects in the National Health and Nutrition Examination Survey II, a national probability sample. Low plasma cholesterol concentrations (< 160 mg/dL) were much more common in patients with affective disorders (20%) than in urban supermarket screenees (4%, P < or = 0.001) or in the National Health and Nutrition Examination Survey II subjects (10%, P < or = 0.001). When paired with supermarket screenees by age and sex, patients with affective disorders had much lower plasma total cholesterol (P < or = 0.0002), low-density lipoprotein cholesterol (P < or = 0.001), and high-density lipoprotein cholesterol (P < or = 0.0001), and higher triglyceride concentrations (P < or = 0.03). Neither the severity of the affective disorders nor severity-age interactions were associated with plasma cholesterol concentrations (P > 0.1); age and plasma cholesterol were positively associated (P = 0.01). None of the psychoactive drugs had a significant independent association with the patients' low-density lipoprotein cholesterol. Plasma cholesterol in patients hospitalized with affective disorders is shifted markedly downward toward hypocholesterolemic concentrations (< 160 mg/dL). There is no evidence that low plasma cholesterol could cause or worsen affective disorders.

Bipolar Disorder↗

PubMed1994

Increased expression of intercellular adhesion molecules in biliary atresia.

The expression of the inflammatory adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1, was studied in six infants with biliary atresia using an immunoperoxidase technique on frozen sections. Controls consisted of five patients with various conditions including total parenteral nutrition-induced cholestasis, choledochal cyst, viral hepatitis, metastatic carcinoma, and thrombotic thrombocytopenic purpura. None of the patients were in liver failure. Bile ducts from the control subjects did not express any of the inflammatory adhesion molecules on ductal epithelium. In marked contrast, all of the biliary atresia specimens demonstrated strong intercellular adhesion molecule-1 expression and occasional vascular cell adhesion molecule-1 staining on epithelial cell membranes of both intra- and extrahepatic ductal structures. Hepatocytes and sinusoidal lining cells including Kupffer cells showed a pattern of intense intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in all specimens with active inflammation that could not differentiate the biliary atresia cases from the control group. Lymphocyte function-associated antigen-1 intensely stained the inflammatory cell infiltrate in the biliary atresia and inflamed control specimens. The strong expression of intercellular adhesion molecule-1 on biliary ductal epithelium in patients with biliary atresia suggests a potential role for this adhesion molecule in the pathogenesis of this devastating neonatal hepatic disorder.

Bile Ducts↗

PubMed1994

Protein C and S deficiency, thrombophilia, and hypofibrinolysis: pathophysiologic causes of Legg-Perthes disease.

In eight patients with Legg-Perthes disease, we assessed the etiologic roles of thrombophilia caused by protein C and protein S deficiency and hypofibrinolysis mediated by low levels of tissue plasminogen activator activity. We speculated that thrombosis or hypofibrinolysis were common causes of Legg-Perthes disease. Three of the eight patients had protein C deficiency; they came from kindreds with previously undiagnosed protein C deficiency. In one of these three kindreds there were six protein C-deficient family members (beyond the proband child), four of whom had thrombotic events as adults. One of the eight patients had protein S deficiency, as did his brother who had sustained mesenteric vein thrombosis at age 43. One of the eight patients who had normal proteins C, S, and antithrombin III had hypofibrinolysis, failing to elevate tissue plasminogen activator activity after 10 min of venous occlusion at 100 mm Hg. Plasminogen activator inhibitor, alpha 2-antiplasmin, and fibrinogen values were normal in all eight patients. Beyond their Legg-Perthes disease, none of the eight patients had evidence for venous thrombosis. Of the eight patients, four had thrombophilia and one had hypofibrinolysis, disorders that we believe contributed to thrombotic venous occlusion of the femur with subsequent venous hypertension and bone death that characterize Legg-Perthes disease.

Adolescent↗

PubMed1994

Familial idiopathic osteonecrosis mediated by familial hypofibrinolysis with high levels of plasminogen activator inhibitor.

Familial hypofibrinolysis with 3 generation, autosomal dominant, very high levels of plasminogen activator inhibitor activity (PAI-Fx) and antigen (PAI-Ag) was etiologically associated with bilateral idiopathic osteonecrosis in 2 brothers. They, their mother, 2 brothers, sister, and all 4 of her children (none of whom had yet developed osteonecrosis), all had very high PAI and could not elevate tissue plasminogen activator after 10 minutes of venous occlusion at 100 mmHg. Familial high PAI levels with concurrent hypofibrinolysis co-segregated with familial combined hyperlipidemia, both being independent risk factors for premature coronary heart disease. If thrombi block venous drainage in the femur, familial hypofibrinolysis mediated by familial high PAI with inability to lyse thrombi would contribute to venous hypertension of bone, bone anoxia, and bone death characteristic of osteonecrosis.

Adolescent↗

PubMed1994

Severe hypertriglyceridemia and pancreatitis when estrogen replacement therapy is given to hypertriglyceridemic women.

Our specific aim was to assess severe hypertriglyceridemia and pancreatitis that occurred when postmenopausal estrogen replacement therapy (ERT) or tamoxifen had been given by their physicians to women with preexisting, usually covert, primary familial hypertriglyceridemia. We retrospectively studied 31 women referred for diagnosis and therapy of hypertriglyceridemia over 2.75 years whose initial visit fasting plasma triglyceride levels were > 750 mg/dl. Of the 31 women with hypertriglyceridemia, 12 (39%) had been given exogenous estrogen by their physicians (11 ERT, one tamoxifen). Ten of the 12 women, while undergoing ERT, had triglyceride levels > 1200 mg/dl. In triglyceride referral categories 750 to 1000, 1000-1500, and > 1500 mg/dl, 17% (2 of 12), 33% (3 of 9), and 70% (7 of 10), respectively, of the 31 women with hypertriglyceridemia were receiving ERT. The higher the triglycerides were at referral, the greater was the likelihood that women were taking ERT (x2 = 6.6, p = 0.035). Four of the seven women with triglyceride levels > 1500 mg/dl while undergoing ERT were hospitalized with severe acute pancreatitis; another two had severe abdominal pain thought to be pancreatic in origin. To quickly lower dangerously high triglyceride levels, ERT was stopped in all 12 women. Lopid (1.2 to 1.5 gm/day) was given to the seven women not already taking it, and four were also given omega-3 fatty acids (4 to 15 gm/day). Median plasma triglyceride level at the initial visit in the 12 women undergoing ERT was 1665 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗

PubMed1993

Improvement in symptoms of depression and in an index of life stressors accompany treatment of severe hypertriglyceridemia.

In 14 men and nine women referred because of severe primary hypertriglyceridemia, our specific aim in a 54-week single-blind treatment (Rx) period was to determine whether triglyceride (TG) lowering with a Type V diet and Lopid would lead to improvement in symptoms of depression, improvement in an index of life stressors, change in locus of control index, and improved cognition, as serially tested by Beck (BDI), Hassles (HAS) and HAS intensity indices, Locus of Control index, and the Folstein Mini-Mental status exam. On Rx, median TG fell 47%, total cholesterol (TC) fell 15%, and HDLC rose 19% (all p < or = 0.001). BDI fell at all nine Rx visits (p < or = 0.001), a major reduction in a test of depressive symptoms. The HAS score also fell at all nine visits (p < or = 0.05 - < or = 0.001). Comparing pre-Rx baseline BDI vs BDI at 30 and 54 weeks on Rx, there was a major shift towards absence or amelioration of depressive symptoms (chi 2= 5.9, p = 0.016). On Rx, the greater the percent reduction in TG, the greater the percent fall in BDI (r = 0.47, p < or = 0.05); the greater the percent reduction in TC, the greater the percent fall in HAS (r = 0.41, p < or = 0.05). Improvement in the BDI and HAS accompanied treatment of severe hypertriglyceridemia, possibly by virtue of improved cerebral perfusion and oxygenation. There may be a reversible causal relationship between high TG and symptoms of depression.

Adult↗

PubMed1993

Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?

In a 29 year old white male with osteonecrosis of both hips and a shoulder, and in his family, we measured basal and stimulated (10 min cuff venous occlusion at 100 mgHg) fibrinolytic activity to determine whether low fibrinolytic activity might be heritable and etiologically associated with osteonecrosis. The proband's basal tPA-Fx was low, 0.08 IU/ml (normal 0.11-1.94), tPA-Ag was normal (11.6 ng/ml), plasminogen activator inhibitor activity (PAI-Fx) was very high, 119 U/ml (normal 3.5-27), as was his plasminogen activator inhibitor antigen (PAI-Ag), 202 ng/ml (normal 3.2-37.1). The proband's basal PAI-Fx (119) and PAI-Ag (202) were respectively 6 and 13 standard deviations greater than the mean PAI-Fx (17 +/- 15 U/ml) and the mean PAI-Ag (25 +/- 13 ng/ml) in 172 concomitantly studied hyperlipidemic men. Alpha-2 antiplasmin, fibrinogen, plasminogen and Lp(a) were normal. Despite lowering TG to 301 mg/dl, basal tPA-Fx remained low, 0.05; PAI-Fx and PAI-Ag remained very high (109 and 191). Following venous occlusion, stimulated tPA-Fx remained very low, 0.1 (normal 2.3-11.3), but tPA-Ag rose normally to 17 (normal 8.4-31.4); stimulated PAI-Fx and PAI-Ag were very high, 134 and 223, (normal PAI-Fx 3.6-24, PAI-Ag 12-96). Stimulated D-dimer was < the 10th percentile, 0.084 micrograms/ml. With such high PAI-Fx available to bind tPA, occlusion-stimulated tPA-Fx could not rise, and fibrinolysis could not be initiated. Neither diseases nor drugs could explain the high PAI-Fx and PAI-Ag, low tPA-Fx; or osteonecrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Nitrogen balance in patients treated with extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a commonly used technique in the management of newborn respiratory failure. However, few studies have addressed the optimal nutritional support of these critically ill neonates. Eleven newborns undergoing ECMO for respiratory failure were studied at various levels of intravenous caloric and nitrogen intake, using nitrogen balance techniques, to assess optimal nutritional support necessary to achieve positive nitrogen balance. Nonprotein nitrogen calories > 60 kcal/kg/d, and nitrogen > 240 mg/kg/d were necessary to achieve positive nitrogen balance, while maximum positive balance was seen with nitrogen intake > 400 mg/kg/d. These data suggest that newborns treated with ECMO can achieve positive nitrogen balance with modest amounts of caloric and nitrogen intake.

Energy Intake↗

PubMed1993

Relationships between lipoprotein(a), lipids, apolipoproteins, basal and stimulated fibrinolytic regulators, and D-dimer.

In 191 newly referred hyperlipidemic patients, our specific aim was to assess relationships between levels of lipoprotein(a) [Lp(a)], lipids, apolipoproteins, regulators of basal and stimulated fibrinolytic activity, and D-dimer, a measure of in vivo fibrinolysis. Lp(a) levels correlated with none of the measures of basal fibrinolytic regulators or D-dimer. In 25 patients, levels of stimulated regulators of fibrinolytic activity and D-dimer were measured after 10-minute cuff venous occlusion. Lp(a) levels again correlated with none of the stimulated regulators of fibrinolytic activity or D-dimer. However, both basal and stimulated levels of fibrinolytic regulators and D-dimer were closely related to other major risk factors for coronary heart disease (CHD) including triglyceride, apolipoprotein (apo) A1, apo B, Quetelet index (QI), and sex. By stepwise regression in 191 patients, the following standardized partial regression coefficients were significant (P < or = .05), and model R2 and P values were as follows: basal tissue plasminogen activator (tPA) with apo B-.18, with time .17, with QI -.28, R2 = 17%, P < or = .0001; basal plasminogen activator inhibitor (PAI) with apo B..25, with time -.15, with QI .17, R2 = 14%, P < or = .0001; basal alpha 2-antiplasmin with apo A1.14, with apo B.24, with QI.17, with sex .30, R2 = 25%, P < .0001; basal plasminogen with A1.15, with apo B.21, with QI.17, with sex.17, R2 = 15%, P < or = .0001; basal fibrinogen with Lp(a).17, with QI.21, with sex.26, R2 = 14%, P < or = .0001; D-dimer with sex.15, R2 = 21%, P < or = .048. Given the absence of any relationship between Lp(a) levels and inhibition or stimulation of fibrinolysis regulators or D-dimer either in the basal or stimulated state, we postulate that Lp(a)'s major atherogenic effects are mediated by mechanisms other than reduction of fibrinolysis stimulation or in vivo fibrinolysis.

Apolipoproteins↗