Faster Atlantic currents drive poleward expansion of temperate phytoplankton in the Arctic Ocean.

The Arctic marine biome, shrinking with increasing temperature and receding sea-ice cover, is tightly connected to lower latitudes through the North Atlantic. By flowing northward through the European Arctic Corridor (the main Arctic gateway where 80% of in- and outflow takes place), the North Atlantic Waters transport most of the ocean heat, but also nutrients and planktonic organisms toward the Arctic Ocean. Using satellite-derived altimetry observations, we reveal an increase, up to two-fold, in North Atlantic current surface velocities over the last 24 years. More importantly, we show evidence that the North Atlantic current and its variability shape the spatial distribution of the coccolithophore Emiliania huxleyi (Ehux), a tracer for temperate ecosystems. We further demonstrate that bio-advection, rather than water temperature as previously assumed, is a major mechanism responsible for the recent poleward intrusions of southern species like Ehux. Our findings confirm the biological and physical "Atlantification" of the Arctic Ocean with potential alterations of the Arctic marine food web and biogeochemical cycles.

The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.

OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.

Thromboembolic diseases of childhood.

Over the last decade, pediatric thrombophilia programs have emerged around the world as a new discipline in pediatric hematology. These programs specialize in the diagnosis, prevention and treatment of children with thromboembolic events (TEs) in both the venous and arterial systems. The need for separate pediatric programs has been discussed previously. (J Pediatr Hematol Oncol 1997; 19: 7-22.) The following article will update previous reviews (Hematol Oncol Clin North Am 1998; 12: 1283-1312; Thromb Haemost 1997; 78: 715-725) and will concentrate on three aspects: (1) The risk factors for acquiring TEs; (2) The confirmatory diagnostic tests used in children with TEs; and (3) The different antithrombotic agents used for prevention and treatment. The current knowledge in respect to the above points is only the "tip of the iceberg". Well-designed prospective trials are required to establish the contribution of congenital prothrombotic disorders, appropriate diagnostic strategies, and optimal therapy for children with TEs.

Anticoagulation therapy in pediatric patients with sinovenous thrombosis: a cohort study.

OBJECTIVE: To assess the use of anticoagulant therapy in a consecutive cohort study of children with sinovenous thrombosis (SVT). METHODS: A single institutional pilot study of anticoagulant therapy was conducted from January 1992 to December 1996 at the Hospital for Sick Children, Toronto, Ontario. Consecutive children with the diagnosis of SVT, made by computed tomography, magnetic resonance imaging (MRI), MRI with venography, ultrasonography, nuclear brain scanning, or conventional angiography were eligible for anticoagulant therapy. RADIOGRAPHIC EVALUATION: Most children underwent multiple radiographic tests for evaluation of the central nervous system. Of the 32 episodes of SVT, CT was performed in 30, MRI with or without venography in 26, ultrasonography in 11, and nuclear brain scanning in 5. The majority of the SVTs were located at the superior sagittal sinus (50%) and right lateral sinus complex (44%). RESULTS: There were 30 consecutive children with 32 episodes of SVT during the 5-year study (2 girls had recurrent SVT). The median age was 6.2 years (age range, 3 days to 18 years), and the sex of the patients was evenly distributed (15 girls and 15 boys). The primary associated clinical conditions consisted of systemic lupus erythematosus (n = 5), renal disease (n = 3), perinatal distress (n = 2), congenital heart disease (n = 1), cerebral arteriovenous malformation (n = 1), and neurosurgery for refractory seizures (n= 1). The remainder were previously healthy children older than 1 month (n = 10) and newborns (n = 7). Eight children were ineligible for anticoagulant therapy because of an associated intracranial hemorrhage (n = 6), a postoperative bleeding risk after neurosurgery (n = 1), or a prolonged delay from the diagnosis to the time of referral (n = 1). Ten children received standard heparin, and 12 children received low-molecular-weight heparin (LMWH) (enoxaparin sodium). Eighteen children were treated with oral anticoagulants for 3 months after initial heparin therapy, and 4 patients received LMWH for the entire course of treatment. There was no intracranial hemorrhage in the 12 patients treated with LMWH, but there was 1 case of clinically silent bleeding in the standard heparin group. CONCLUSIONS: The results of this pilot study suggest that anticoagulant therapy, in particular LMWH, is safe and may have a role in the treatment of children with SVT. A randomized controlled trial is warranted.

Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease.

Venous thromboembolic events (VTEs) in children are usually associated with underlying clinical conditions. The added contribution of prothrombotic conditions to the occurrence of VTEs in children is not clear. This study reports the prevalence of prothrombotic conditions in 171 consecutive children with VTE followed in the Hospital for Sick Children Thrombosis Outpatient Clinic. The median age of the children at the time of VTE was 2.3 months (range 1 day to 16.5 years). An underlying medical condition and a central venous line (CVL) were present in 156 (91%) and 132 (77%) of 171 children, respectively. A positive family history was present in 8% of children. The prevalence of factor V Leiden was 4.7%, prothrombin G20210A polymorphism was 2.3%, protein S deficiency was 1.2%, protein C deficiency was 0.6% and increased plasma lipoprotein (a) concentration (>30 mg dL-1) was 7.5% (tested in 107 children). The overall frequency of inherited prothrombotic coagulation proteins was 13% (95% confidence interval 7 to 19%) and the frequency was not significantly different between neonates and older children with VTE. Inherited prothrombotic coagulation proteins were not associated with gender, CVL-related VTE, a positive family history of thrombosis or spontaneous VTE in neonates. Increased frequency of inherited prothrombotic coagulation proteins was, however, found in older children with spontaneous VTE (60%) compared with older children with VTEs secondary to an underlying medical condition (10%) (P = 0.02). In conclusion, this study indicates that inherited prothrombotic coagulation proteins do not contribute significantly to the pathogenesis of VTEs in neonates and children, in whom the most significant etiological factors are the presence of a CVL and/or other medical conditions.

Natural history of arterial and venous thrombosis in children treated with low molecular weight heparin: a longitudinal study by ultrasound.

Low molecular weight heparin (LMWH) is efficacious in preventing recurrent thromboembolic events (TEs) in children. The efficacy of LMWH in resolving thrombus in children is, however, unknown and may differ from what has been observed in adults due to known differences in the hemostatic system. We reviewed the ultrasound (US) scanning reports of children treated with LMWH in order to determine the rate and predictors of thrombus resolution. Of 245 children consecutively treated for a non-cerebral TE with enoxaparin (Lovenox, Aventis Pharma Inc., QC, Canada) for at least 5 consecutive days, 190 (78%) had serial ultrasound available for analysis. The mean follow-up time was 7 months (median 3 months, range 3 days to 6.6 years). The rate of complete thrombus resolution was 101/190 (53%, 95% confidence interval 46.2-60.2%). On univariate analysis, arterial and non-occlusive thrombus had an increased rate of resolution when compared with venous and occlusive thrombus. Age at time of TE (neonates vs. non-neonates), location of TE, initial treatment (unfractionated heparin vs. LMWH) and dose of enoxaparin were not related to outcome. On multivariate analysis, type of vessel (vein vs. artery) and occlusion (occlusive vs. non-occlusive thrombus) independently predicted outcome. In children, the rate of complete thrombus resolution is similar to the rate in adults. The clinical significance of residual abnormal vessels, specifically to the occurrence of post-thrombotic syndrome and for the diagnosis of recurrence, needs to be explored in prospective studies.

Venous thrombosis in children.

Venous thromboembolic (VTE) events are being increasingly diagnosed in systemic and cerebral vessels in children. Systemic VTE are increasing in children as a result of therapeutic advances and improved clinical acumen in primary illnesses that previously caused mortality. The epidemiology of systemic VTE has been studied in international registries. In children older than 3 months, teenagers are the largest group developing VTE. The most common etiologic factor is the presence of central venous lines. Clinical studies have determined the most sensitive diagnostic method for diagnosing upper system VTE are ultrasound for jugular venous thrombosis and venography for intrathoracic vessels. However, the most sensitive diagnostic methods for lower system VTE and pulmonary embolism (PE) have not been established. Treatment studies for VTE consist of inadequately powered randomized controlled trials or prospective cohort studies. The long-term outcome of systemic VTE, post-thrombotic syndrome, has been reported in children. Cerebral sinovenous thrombosis (CSVT) is becoming increasingly diagnosed in children due to the recognition of the associated subtle clinical symptoms and improved cerebrovascular imaging. The etiology of CSVT includes thrombophilia, head and neck infections, and systemic illness. Estimates of the incidence and outcome of childhood CSVT have recently become available through the Canadian Pediatric Ischaemic Stroke Registry. Clinical studies have not yet been carried out in children to determine the best method of diagnosis or treatment. There have only been case-series studies carried out in the treatment of CSVT. Properly designed clinical trials are urgently required in children with systemic VTE/PE and CSVT to define the best methods of diagnosis, treatment and long-term management.

Enhanced thrombin regulation during warfarin therapy in children compared to adults.

The intensity of warfarin therapy for prevention of primary and secondary thromboembolic complications in paediatric patients, is extrapolated from guidelines for adults, which may not be optimal. Therefore, we assessed thrombin regulation ex vivo and in vitro in plasmas from 40 children (1 to 18 years old with a median age of 13 years) and 27 adults receiving warfarin with an international normalized ratio of 2 to 3 (child: 2.5 +/- 0.15; adult: 2.4 +/- 0.14). Ex vivo concentrations of prothrombin fragment 1.2 were significantly lower in children (0.30 +/- 0.03 nM) compared to adults (0.45 +/- 0.04 nM; p <0.01). Thrombin generation in defibrinated plasmas (Arvin) was decreased and delayed for children compared to adults when activated by either activated partial thromboplastin time (child = 32 +/- 1.7, adult = 45 +/- 1.9 microM x s) or prothrombin time (child = 35 +/- 0.7, adult = 46 +/- 1.0 microM x s) reagents (p <0.01 for both). Although plasma concentrations of factors (F) II, FVII, FIX, F X, protein C and protein S were similar, more of the thrombin generated was complexed to alpha2 macroglobulin (alpha2M) at times close to peak thrombin activity (60 s) in plasma from children (general linear analysis of variance; p <0.03). Thus, increased alpha2M levels may enhance thrombin regulation in paediatric compared to adult patients receiving warfarin, suggesting that clinical trials in children, using less intense warfarin treatment, may be required to determine optimum therapy.

The influence of developmental haemostasis on the laboratory diagnosis and management of haemostatic disorders during infancy and childhood.

The physiology of the hemostatic system in children is different from that in adults. Reference ranges for components of the hemostatic system are age dependent. During early childhood, physiologic values may overlap with values observed in congenital deficiencies of acquired pathological conditions. Physiologically decreased plasma concentrations of hemostatic components also influence the response to antithrombotic therapy. The relevance of developmental hemostasis for the laboratory diagnosis and management of hemorrhagic and thrombotic disorders during childhood is discussed.

Prevalence of post-thrombotic syndrome following asymptomatic thrombosis in survivors of acute lymphoblastic leukemia.

BACKGROUND: Deep vein thrombosis (DVT) is a complication of treatment of acute lymphoblastic leukemia (ALL) in children but little is known about the long-term outcomes of these DVT. OBJECTIVE: To determine the incidence of post-thrombotic syndrome (PTS) in (i) children with ALL diagnosed with asymptomatic DVT using radiographic testing and (ii) an unselected group of ALL survivors. METHODS: Cross-sectional study in two populations. Group I comprised children in the Prophylactic Antithrombin Replacement in Kids with ALL treated with L-Asparaginase (PARKAA) study diagnosed with DVT by radiographic tests. Group II consisted of non-selected childhood ALL survivors <21 years. PTS was assessed using a standardized scoring sheet. RESULTS: Group I: 13 PARKAA patients (median age 12 years) were assessed, and 7 had PTS (54%; 95% CI, 25-81). All patients had collaterals, three also had increased arm circumference. Group II: 41 patients (median age 13 years) with a history of ALL were enrolled, and 10 had PTS (24%; 95% CI, 11-38). All patients had collaterals; five also had increased arm circumference. CONCLUSION: There is a high incidence of PTS in survivors of childhood ALL with radiographically diagnosed asymptomatic DVT. A significant proportion of ALL survivors develop PTS, indicating previously undiagnosed DVT.

A comparative study of coagulation systems in newborn animals.

Appropriate animal experimentation can enhance our understanding of thrombotic and hemorrhagic problems in the human neonate. Which newborn animal species' coagulation system most closely resembles the human neonate is unknown. The objective of the study was to assess the newborn coagulation system in four animal species and compare them with the human neonate. Blood samples were drawn on days 1 and 7 of life from lambs (n = 10), piglets, (n = 12), rabbit pups (n = 12), and beagle pups (n = 7). Coagulation screening tests, specific factor assays, and specific inhibitors of the coagulation system were measured. All factor assays were expressed as a percent of the respective species pooled adult plasma. The results from the animals were compared to normal values from our laboratory for healthy full-term infants. The coagulation systems of all species tested, except the rabbit pup, were immature at birth with most factor levels being lower than the adult of their species. The coagulation systems were influenced by the postnatal age of the animal and the factor levels reached adult values in fewer days relative to the human. The coagulation system for the piglet most closely approximated the human neonate. The shared characteristics were prolonged screening tests, increased factor VIII:C, generally low levels for the contact and vitamin K-dependent factors, and low antithrombin III levels relative to the adult. The beagle pup also showed many similar characteristics but in contrast to the human neonate factor VIII:C and V were low on day 1 of life and prekallikrein was not measurable in the adult or newborn beagle.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin therapy in pediatric patients.

Advances in tertiary care pediatrics have resulted in heparin being one of the most frequently prescribed drugs in children's hospitals. Heparin is essential for cardiopulmonary bypass, extracorporeal membrane oxygenation, renal dialyses, maintenance of patency of venous and arterial catheters, and treatment of thromboembolic events. Currently, protocols validated in adults are used for children. However, optimal use of heparin in pediatric patients will likely differ from adults because of age-dependent physiologic and pathologic differences in hemostasis that influence the activities of heparin. The following review summarizes the influence of age on heparin anticoagulant activities, and pharmacokinetics. The indications, monitoring, therapeutic range, factors influencing dose-response relationships, and side effects of heparin therapy in pediatric patients are discussed. Finally the current and future indications for low-molecular-weight heparins in pediatric patients are summarized. Multi-centered, international clinical trials are urgently needed to assess and optimize the use of heparin in pediatric patients in a variety of clinical settings. Until these studies are completed, recommendations for adults provide guidelines for children.

Intracranial hemorrhage in neonates with unrecognized hemophilia A: a persisting problem.

Hemophilia is a rare disorder, and an uncommon cause of intracranial hemorrhage in neonates. We present 2 patients with hemophilia A, who presented with massive subdural hemorrhages on day 5 and day 4 postpartum. Both were taken urgently to surgery without a diagnosis of hemophilia being established. Neither patient had a family history of hemophilia, and both were born following difficult deliveries. The activated partial thromboplastin time (APTT) was normal in patient No. 1 (subsequent factor VIII level 10%). In patient No. 2, the APTT was slightly prolonged, but initially interpreted as being within the normal range for age (subsequent factor VII level of < 1%). Patient 1 rebled, required a second operation, and had a poor outcome. Patient 2 was given prophylactic fresh frozen plasma, and made a good recovery. Factor VIII assay should be performed in all term male babies presenting with intracranial hemorrhage. In urgent circumstances, prophylactic clotting therapy should be administered during surgery to prevent postoperative bleeding in an undiagnosed hemophiliac.

[Teaching of geriatric dentistry; training of "mobile dental service" dentists]. / L'enseignement de la dentisterie gériatrique; formation offerte aux chirurgiens dentistes du "service dentaire mobile".

Quebec presently has 650,000 people over 65 years of age and as many as 900,000 will be alive at the beginning of the 21st century. Quebec epidemiological studies have shown that this group's dental condition is very poor. They feel no need to see a dentist, but 96% of them need treatment and the time elapsed since their last dental visit averages 13 years. It is forecasted that the dental needs of this group will rise, not only because of their increase in number but also because they will retain more teeth. Training in geriatric dentistry is presently deficient in the United States, Canada and particularly Quebec. Researchers have concluded, after studying the U.S. dental schools' current status of geriatric dentistry educational activities, that unless dental students receive training in geriatrics while at dental school, it is likely that they will not treat a lot of seniors in their practice. The teaching of geriatric dentistry is in full swing in the U.S. but knows a difficult birth in Quebec. There is no formal, extensive training program in geriatric dentistry given by the three dental schools in the province. Practicing geriatric dentistry requires special knowledge and skills. If treatment is to be successful, the practitioner must adopt a humanitarian approach and develop close relations and a better understanding of the feelings and attitudes of the elderly. The dentist must know and understand the special dental problems that makes them different from other groups.

The teaching of geriatric dentistry in Canada.

Very little is known about the current status of geriatric training programs at Canadian universities because of the scarcity of information published on the subject. A study of the geriatric dentistry training programs offered by Canada's 10 dental schools has been completed. Its intent was to determine what type of educational activities in geriatric dentistry have either been offered in the past, are being offered now, will be offered in the next academic year, or are planned for the next five years. The results indicate that the 10 schools are doing very little in this regard. To keep pace with the level of geriatric dentistry training currently being offered in the United States, the dental profession must convince Canadian faculty members that the teaching of geriatric dentistry is crucial to both the undergraduate student and the graduate dentist. Continuing education in geriatric dentistry could be used to meet the oral health needs of our frail and dependent senior citizens. Geriatric dentistry must be taught at all levels of the profession so that this special clientele can receive the necessary treatment either within or outside of the dental office.

Home monitoring of warfarin therapy in children with a whole blood prothrombin time monitor.

We prospectively evaluated a capillary whole blood prothrombin time (PT) monitor (Biotrack, Ciba Corning) in an outpatient pediatric anticoagulation clinic (40 clinic patients) and in age-matched healthy subjects (30 control subjects). Subsequently, 23 children requiring warfarin therapy were placed on a home program (home patients) using the PT monitor; their parents were trained and the results followed by clinic staff. The PT results were reported as internationalized normalized ratios (INRs). The laboratory and PT-monitor INR values were similar for the clinic patients and the control subjects (y = 0.76x + 0.38; r = 0.93; p < 0.001). The accuracy of the PT monitor (the difference between INR values and the laboratory INR) was best at an INR of 2.5 to 3.5; 90% of paired INR values were within 0.8 INR units. The average duration of monitoring for home patients was 13 months (range, 2 to 60 months). They had an average of 3 dose measurements (range, 1 to 11 measurements) and 1.8 dose changes (range, 0.6 to 4.5 changes) per month. Of the 599 measurements, 63% were within the therapeutic range, similar to those for clinic patients; the dose requirements were also similar. There was 1 significant bleeding event, a subdural hematoma in a patient with an INR of 4.1, and 1 catheter-related thrombotic event with an INR of 1.2; both children recovered. Of the 23 families, one discontinued home monitoring because of parental discomfort, 2 children died of their primary disease, 6 completed warfarin therapy, and 14 remain on the home program. We conclude that the whole blood PT/INR monitor is safe and offers practical advantages to children requiring anticoagulation.

The state of oral and dental health of the homeless and vagrant population of Montreal.

Not much is known about the state of oral and dental health of homeless and vagrant people in Montreal. However, a study conducted during April 1993, in conjunction with dental health month, has made it possible to undertake a better evaluation of their oral health status and to identify ways of making dental treatment available to them. Once the oral health status of this population is known, the official body responsible for homeless and vagrant individuals, the "Régie régionale Montréal-Centre," can be given possible solutions for their treatment and care. Most of the homeless are welfare recipients and have access to some basic benefits from this source. One of these benefits is free access to all assured basic dental services. These services are available after a six-month waiting period, and are provided by a dentist of the homeless person's choice. At the beginning of this study, the authors hypothesized that homeless people would prefer to be treated in the hostels and shelters where they sleep, which is currently the situation in Boston. But in 65 per cent of cases, their responses to a questionnaire administered as part of this study were quite different, and indicated that they would prefer to visit a private dentist of their choice. However, there is another important group (35 per cent) who wish to receive dental treatment in the hostels they presently frequent. Any proposed solution should take into consideration both groups of homeless and vagrant persons.

Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study.

OBJECTIVE: To compare low-molecular-weight preparations of heparin (LMWH) with standard heparin in children requiring anticoagulant treatment for thromboembolic disease. METHODS: We treated 25 children who required heparin, but were at significant risk of bleeding, with LMWH (enoxaparin, Rhone-Poulenc Rorer). The median age was 4 years (range, newborn to 17 years), with nine infants less than 2 months of age. Fourteen children had a deep vein thrombosis or pulmonary embolism, nine had thrombotic complications in the central nervous system, and two had complex congenital heart disease, for which they received prophylaxis at a lower dosage (0.5 mg/kg given subcutaneously twice a day). The remaining 23 children received an initial dose of 1 mg/kg, every 12 hours subcutaneously, with subsequent doses adjusted to achieve a 4-hour anti-factor Xa level between 0.5 and 1.0 unit/ml. RESULTS: Newborn infants had increased dose requirements; an average of 1.60 units/kg was required to achieve therapeutic heparin levels. For the remaining children, the initial dose of 1.0 mg/kg was sufficient. After the initial dose adjustment, LMWH was administered with twice-weekly monitoring. The median duration of therapy with LMWH was 14 days. Two children with previously documented gastrointestinal ulcers bled and required transfusion therapy. Therapy with LMWH was continued without further events. There were no new thrombotic events during the treatment with LMWH. The cost of administering LMWH compared with heparin was reduced by 30% because of decreased laboratory monitoring, blood sampling times, intravenous starts, and nursing time. Needle punctures were reduced with LMWH therapy by the placement of a subcutaneous catheter. CONCLUSION: These results provide the basis for a randomized, controlled trial comparing LMWH with standard heparin in pediatric patients.

Capillary whole blood monitoring of oral anticoagulants in children in outpatient clinics and the home setting.

A whole blood prothrombin time/international normalized ratio (PT/INR) monitor (CoaguChek, Roche Diagnostics Corp., Indianapolis, IN) was assessed in children for its accuracy, reliability, safety, and acceptance by health care personnel and patient's families. The PT/INR values measured by the CoaguChek monitor showed an excellent correlation with PT/INR values measured by the Hospital for Sick Children (HSC) laboratory (r = 0.96) and Hamilton Civic Hospitals Research Centre (HCHRC) laboratory (r = 0.92) in clinic patients and a close correlation with PT/INR values measured by the HSC laboratory (r = 0.76) and HCHRC laboratory (r = 0.74) in patients at home. Reduced correlation in the home setting did not adversely affect clinical management. The whole blood PT/INR monitor is safe and accurate for children requiring oral anticoagulation therapy in either the outpatient clinic or home setting.