An unusual peripheral vascular response to dopamine in a neonate.

We report a case of a neonate who developed hypotension immediately after birth, and needed dopamine infusion to sustain his blood pressure and tissue perfusion. He developed cyanosis of his extremity immediately after dopamine was started via peripheral line and improved spontaneously after dopamine was stopped. This happened repeatedly at various sites and at lower concentrations of dopamine. Subsequently, dopamine was replaced by dobutamine and the patient did well. We conclude that some neonates can show heightened alpha-adrenergic response to dopamine and this can lead to ischemic vascular events. Dopamine infusion in neonates should be started at a low-dose via central line.

Evaluation of the "Sunny Days, Healthy Ways" sun safety CD-ROM program for children in grades 4 and 5.

Computer-based sun safety instruction has many advantages that may be attractive to health educators in schools. An educational multimedia computer program on sun safety was produced on CD-ROM for children in grades 4 and 5, which was based on the "Sunny Days, Healthy Ways" sun safety curriculum (SDHW). Its effects on children's sun safety knowledge, attitudes and behaviour were evaluated with 162 students in 8 fourth and fifth grade classes in a randomized pretest-posttest 2 x 2 factorial design. Children interacting with the CD-ROM program showed significant improvements in knowledge (p = 0.007). The effect on knowledge may have indirectly improved children's sun protection (r = 0.201, p = 0.013), even though the CD-ROM program did not directly increase sun protection (p > .05) or improve attitudes (p > .05). The CD-ROM program may be a cost-effective and administratively acceptable sun safety instructional strategy, however, like many short prevention strategies, it will be most successful at conveying information on sun safety to children.

Low-molecular-weight heparinoid orgaran is more effective than aspirin in the prevention of venous thromboembolism after surgery for hip fracture.

BACKGROUND: The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals. METHODS AND RESULTS: Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti-Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative 125I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran (P=.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran (P=.137; 95% confidence interval, -30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin (P=.10). There was one major bleed in the Orgaran group compared with four in the aspirin group. CONCLUSIONS: This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.

A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study.

OBJECTIVE: To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. DESIGN: Double-blind randomized trial. SETTING: Seven Canadian university-affiliated hospitals. PARTICIPANTS: Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis. INTERVENTION: Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner. MEASUREMENTS: Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically. RESULTS: Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups. CONCLUSION: Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.

Investigation of an outbreak of bloody diarrhea: association with endoscopic cleaning solution and demonstration of lesions in an animal model.

UNLABELLED: OUTBREAK INVESTIGATION: An outbreak of diarrhea, bloody diarrhea, and abdominal cramps occurred among persons undergoing flexible sigmoidoscopy at a branch clinic of a local health center. Illness was associated with use of sigmoidoscopes cleaned by one clinic assistant and appeared to be caused by 2% glutaraldehyde disinfectant solution left in the instruments after cleaning. ANIMAL STUDIES: In subsequent animal studies, colonic instillation of 2% glutaraldehyde solutions caused bloody diarrhea and a distinctive pattern of mucosal damage; similar changes were seen in a review of pathologic samples from other human cases of glutaraldehyde disinfectant-associated diarrhea. CONCLUSION: Our data indicate that improper endoscopic reprocessing can result in serious illness and underscore the importance of adequate training and quality control in this area.

Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin.

OBJECTIVE: To determine the relative efficacy and safety of low molecular weight (LMW) heparin (Enoxaparin) compared with standard calcium heparin for the prevention of postoperative deep vein thrombosis in patients undergoing elective hip surgery. DESIGN: A double-blind, randomized, controlled trial. PATIENTS: Six hundred sixty-five consecutive patients undergoing hip replacement at five participating hospitals. INTERVENTIONS: Patients received either fixed-dose LMW heparin, 30 mg subcutaneously twice daily, or fixed-dose standard calcium heparin, 7500 units subcutaneously twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge if sooner. MEASUREMENTS: All patients had postoperative I-125-fibrinogen leg scanning and impedance plethysmography. If results of one or both tests were positive, then venography was done. Otherwise, venography was done between day 10 and day 14, or sooner if the patient was ready for discharge. RESULTS: Evaluable venograms were obtained in 258 of the 333 patients randomly assigned to receive LMW heparin and in 263 of the 332 patients assigned to receive calcium heparin. For patients with evaluable venograms, thrombosis was detected in 50 patients (19.4%) who received LMW heparin compared with 61 patients (23.2%) who received standard heparin (difference, -3.8%; 95% CI, -11.1% to 3.6%) (P greater than 0.2). Proximal deep vein thrombosis was detected in 5.4% of the patients receiving LMW heparin and in 6.5% of the patients receiving standard heparin (difference, -1.1%; CI, - 5.2% to 3.3%) (P greater than 0.2). For the entire group of 665 patients, venous thrombosis occurred in 17.1% given LMW heparin and in 19.0% given standard heparin. Hemorrhagic complications occurred in 31 patients (9.3%) given standard heparin and in 17 patients (5.1%) given LMW heparin (difference, 4.2%; CI, 0.3% to 8.2%) (P = 0.035). The relative risk reduction was 45%. The rate of major bleeding in the standard heparin group was 5.7% compared with 3.3% in the LMW heparin group (difference, 2.4%; CI, -1.0% to 5.4%) (P = 0.13). The relative risk reduction was 42%. CONCLUSION: Low molecular weight heparin is significantly less hemorrhagic than standard unfractionated heparin; the difference in the rate of deep vein thrombosis, although not statistically significant (P greater than 0.2), favors the use of LMW heparin.

A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip.

A randomized trial was carried out with 194 patients to compare the effectiveness of sodium warfarin or aspirin with that of placebo in the prevention of venous thromboembolism after surgery for fractured hip. Prophylaxis was commenced postoperatively and continued for 21 days or until patient discharge, whichever was earlier. All patients underwent surveillance with iodine 125-fibrinogen leg scanning and impedance plethysmography, with subsequent venography. Venous thromboembolism occurred in 13 patients (20.0%) in the warfarin group, 27 patients (40.9%) in the aspirin group, and 29 patients (46.0%) in the placebo group. Proximal vein thrombosis or pulmonary embolism occurred in 6 patients (9.2%) in the warfarin group, 7 patients (10.6%) in the aspirin group, and 19 patients (30.2%) in the placebo group. The results of this study show that sodium warfarin therapy is safe and effective in preventing thromboembolic complications in patients undergoing surgery for fractured hip, and that aspirin therapy is an equally safe and effective method for preventing proximal vein thrombosis or pulmonary embolism.

Gold induced thrombocytopenia: 12 cases and a review of the literature.

Gold induced thrombocytopenia is immune mediated, with the production of platelet associated IgG leading to peripheral platelet destruction. An association with HLA-DR3 has been demonstrated. Corticosteroid therapy is effective in treatment, although other modes of therapy may be as efficacious.

Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke.

In a double-blind, randomised trial Org 10172 low-molecular-weight (LMW) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke. Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously; it was continued for 14 days or until hospital discharge, if earlier. 50 patients were randomised to receive Org 10172 and 25 to receive placebo. All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became positive. Venous thrombosis occurred in 2 of 50 patients (4.0%) given Org 10172 and 7 of 25 patients (28.0%) given placebo (p = 0.005); the corresponding rates of proximal-vein thrombosis were 0% and 16%, respectively (p = 0.01). There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group.

A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery.

There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the standard form but cause less bleeding. We therefore performed a double-blind, randomized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery. Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days. Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography. In the first 24 patients, venography was performed only if either surveillance test was positive. Because the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 76 patients, even if the screening tests were negative. In this latter group, venous thrombosis occurred in 4 patients (10.8 percent) given PK10169 heparin and 20 patients (51.3 percent) given placebo (P = 0.0002); the corresponding rates for proximal-vein thrombosis were 5.4 percent and 23.1 percent, respectively (P = 0.029). In the entire group of 100 patients, venous thrombosis occurred in 12 percent of those given PK10169 heparin and 42 percent of those given placebo (P = 0.0007), and the corresponding rates for proximalvein thrombi were 4 percent and 20 percent, respectively (P = 0.014). The observed hemorrhagic rate was 4 percent in each treatment group. We conclude that prophylaxis with fixed-dose PK10169 heparin is effective and safe for patients undergoing elective hip replacement.

Lidocaine and the reduction of post-venographic pain.

Venography remains the standard method for the diagnosis of deep venous thrombosis but it is invasive and frequently causes discomfort. A randomised double-blind study was performed to determine the efficacy of lidocaine in reducing pain and discomfort associated with venography. Sixty patients undergoing ascending venography received 40 mg of lidocaine (2 ml of 2% lidocaine mixed with 50 ml of contrast medium) in one leg and saline in the other. Assessment of pain was by a standard questionnaire administered by an investigator unaware of the sequence of administration of lidocaine or saline placebo. Twenty-four patients reported no difference in pain or discomfort between the two limbs. Of the 36 patients experiencing an overall difference in pain between the two legs, 12 reported more pain in the leg receiving lidocaine and 24 reported more pain in the leg receiving saline (p = 0.023). There were no significant side effects attributable to lidocaine. These results indicate that lidocaine is beneficial in reducing pain and discomfort associated with venography.

Gold induced thrombocytopenia: platelet associated IgG and HLA typing in three patients.

Three patients who developed thrombocytopenia while taking gold therapy are reviewed. Bone marrow examinations at the time of thrombocytopenia revealed adequate numbers of megakaryocytes. Elevated levels of platelet associated IgG (PAIgG) were demonstrated in relationship to the thrombocytopenia. A response to prednisone therapy was seen with a rise in platelet count and a fall in PAIgG. All 3 patients were found to have the following alloantigens of the major histocompatibility complex, HLA-B8, DR3. These findings suggest that gold induced thrombocytopenia is immunologically mediated and possibly related to the genes of the major histocompatibility complex.

Clinical usefulness of testing for a heparin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia.

It is important to confirm the diagnosis of heparin-associated thrombocytopenia, because discontinuation of heparin requires the institution of other antithrombotic therapy. Reports describing a heparin-dependent platelet-aggregating factor in the serum of patients with heparin-associated thrombocytopenia suggest the potential for a specific diagnostic test. No study has evaluated the diagnostic usefulness of testing for this factor, and we tested for a heparin-dependent platelet-aggregating factor in sera from (1) 14 patients with heparin-associated thrombocytopenia, (2) 14 nonthrombocytopenic controls given heparin, (3) 16 patients with consumptive thrombocytopenic disorders not associated with heparin, and (4) 13 healthy laboratory personnel. Coded serum samples plus varying concentrations of heparin (final concentration 0.01, 0.1, 1.0, and 5 U/ml) plus platelets from healthy individuals were incubated together, and aggregation was measured. Positive results (greater than 20% aggregation) occurred in (1) five of 14 patients with heparin-associated thrombocytopenia, (2) 0 of 16 consumptive thrombocytopenic controls not given heparin therapy, (3) one of 14 nonthrombocytopenic controls given heparin, and (4) one of 13 healthy controls, giving a sensitivity of 36% and specificities of 100%, 93%, and 92%, respectively. No unique clinical or laboratory feature distinguished those patients with heparin-associated thrombocytopenia with positive aggregation results from those patients with heparin-associated thrombocytopenia with negative results. Fourteen of the 16 patients (86%) with heparin-associated thrombocytopenia had elevated levels of platelet-associated IgG; however, the test was also positive in 67% of the 16 patients with other consumptive (and probably immune) thrombocytopenic disorders not associated with heparin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

The diagnosis of acute, recurrent, deep-vein thrombosis: a diagnostic challenge.

Recurrent venous thrombosis presents a diagnostic challenge. Venography, impedance plethysmography and fibrinogen leg scanning all have potential limitations, and their role in this context has not been evaluated. We performed a prospective cohort study evaluating impedance plethysmography and leg scanning, plus venography, using outcome on long-term follow-up as the end point in 270 patients with clinically suspected recurrent deep-vein thrombosis. Anticoagulant treatment was withheld in the 181 patients negative by noninvasive testing and was given in patients positive by impedance plethysmography if leg scanning was positive or if intraluminal filling defects were detected by venography. The validity of this approach was tested by long-term follow-up. Three of 181 patients (1.7%) negative by noninvasive testing had a recurrence, compared with 18 of 89 (20%) with positive findings (p less than 0.001). Our objective diagnostic approach has high clinical utility; an objective rationale for withholding or giving treatment was established in 95% of patients.

The prenatal prediction of thrombocytopenia in infants of mothers with clinically diagnosed immune thrombocytopenia.

The management of the pregnant patient with immune thrombocytopenia is complicated by the unavailability of the fetal platelet count. Since the transplacental passage of antiplatelet antibodies mediates infant thrombocytopenia, measurement of maternal platelet-associated IgG might predict infant outcome. We related the maternal platelet count and platelet-associated IgG level to the infant's platelet count in 41 pregnancies in 38 patients who were clinically diagnosed as having immune thrombocytopenia. Fifteen of 39 live-born infants were thrombocytopenic at delivery. Maternal platelet-associated IgG was predictive of infant platelet count but maternal platelet count was not; only one of the 20 infants delivered of the 18 thrombocytopenic mothers with normal platelet-associated IgG was affected, whereas 11 of 12 thrombocytopenic mothers with elevated platelet-associated IgG had thrombocytopenic infants. Five infants died in utero between 18 and 28 weeks' gestation, but otherwise there was no significant morbidity in the live births. Measurement of platelet associated IgG in mothers with immune thrombocytopenia during pregnancy can be used to predict infant thrombocytopenia, although it does not predict the severity of the thrombocytopenia.

A prospective study of the usefulness of the measurement of platelet-associated IgG for the diagnosis of idiopathic thrombocytopenic purpura.

The measurement of platelet-associated IgG (PAIgG) is a potentially useful diagnostic test for idiopathic thrombocytopenia purpura (ITP). However, the restricted application of PAIgG measurements to thrombocytopenic populations primarily comprised of ITP patients will artificially enhance its diagnosis specificity. For this reason, we performed a prospective study in which the results of a sensitive technique for quantitating PAIgG were related to the cause of the thrombocytopenia. Over a 1-yr period, clinicians were invited to submit patient blood samples encompassing as wide a spectrum of thrombocytopenic disorders as possible for PAIgG measurements. The physician was then contacted and requested to indicate the likeliest cause for the thrombocytopenia. The PAIgG was elevated in only 24 of 254 samples obtained from nonthrombocytopenic patients. In contrast, 134 (79%) of the 169 thrombocytopenic patients had elevated PAIgG results, and the increased levels were apparent in all diagnostic categories. The sensitivity of the PAIgG test for clinically diagnosed idiopathic thrombocytopenic purpura was 91% and the specificity was 27%. The positive predictive value for a raised PAIgG as a diagnostic test for ITP in a thrombocytopenic patient was only 46%, while the negative predictive value was 82%. This study indicates that the presence of increased PAIgG provides little additional information in the diagnosis of ITP. This study also suggests that immune mechanisms may mediate many more thrombocytopenic disorders than have been previously thought likely.

Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro.

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet-associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.

Thrombocytopenia found uncommonly during heparin therapy.

In a prospective study to determine the frequency of thrombocytopenia in patients treated with intravenous heparin sodium of porcine gut origin, only four of 120 patients with suspected venous thromboembolism showed a depression of the platelet count to below 150 x 10(9)/L. In two of these patients, heparin was not considered to be the cause of thrombocytopenia because the platelet count, which fell transiently, rose again while heparin therapy was continued. These results indicate that thrombocytopenia is an uncommon complication of anticoagulant therapy with heparin derived from porcine gut mucosa.