Does central sleep apnea occur in children with syndromic craniosynostosis?

AIM: To evaluate the prevalence and cause of central sleep apnea (CSA) and central sleep apnea syndrome (CAS) in patients with syndromic craniosynostosis. MATERIALS AND METHODS: This prospective study included ambulant sleep study data to assess, central apneas and obstructive apneas. Data on hindbrain herniation were obtained using cerebral magnetic resonance imaging. RESULTS: One-hundred and thirty-eight syndromic craniosynostosis patients with a median (range) age of 7.8 (1.0-18.0) were included. Central apneas decreased significantly with increasing age (R=-0.25, p=0.003). An increased central apnea index according to the AASM was present in 5 of 138 patients (3.6%; median central apnea index 2.38 (1.12-3.04)). The prevalence of OSAS was 34%, but the median central apnea index in OSAS patients was not pathologically increased. Patients with hindbrain herniation did not have more central apneas compared to patients without hindbrain herniation (F=1.38, p=0.24). CONCLUSION: There is no CSA syndrome in children with syndromic craniosynostosis despite white matter abnormalities, OSAS and hindbrain herniation.

Vaccination responses and lymphocyte subsets after autologous stem cell transplantation.

Twenty autologous stem cell transplant recipients were vaccinated with three doses of Diphtheria-Tetanus-Poliomyelitis vaccine and conjugated Haemophilus influenzae type b (Hib) vaccine. Pneumococcal vaccination consisted of two doses of conjugated vaccine followed by a single dose of polysaccharide vaccine, at 6, 8 and 14 months after transplantation, respectively. Mean anti-tetanus, anti-Hib and anti-pneumococcal IgG antibodies significantly increased after each vaccination. Response rates after the full vaccination schedule were 94%, 78% and 61% for Hib, conjugated 7-valent pneumococcal vaccine and non-conjugated 23-valent pneumococcal vaccine, respectively. Three months after transplantation, CD16(+)CD56(+) NK cells were in the normal range and remained so. The total number of T lymphocytes at 3 months was and remained in the normal range. The mean CD4/CD8 ratio was 0.43 at 3 months post aSCT and, while gradually increasing, remained subnormal. The mean number of CD19(+) B lymphocytes significantly increased during the study period. Patients with CD19 counts <0.10 x 10(9)L(-1) required at least two Hib vaccinations to show a response, while the majority of patients with CD19 counts > or = 0.20 x 10(9)L(-1) showed a response to Hib after one vaccination only. Thus, a minimum threshold level of CD19(+) cells appears to be required for adequate responses to vaccination.

[Pregnancy and chemotherapy; an apparent contradiction]. / Zwangerschap en chemotherapie; een schijnbare tegenstelling.

Two women aged 34 and 32, were diagnosed with cancer during pregnancy. The 34-year-old woman with breast cancer diagnosed during the first trimester of pregnancy, had just undergone breast-conserving surgery. She chose to have an abortion before adjuvant chemotherapy was started. A year after chemotherapy ended she became pregnant again and gave birth to a healthy child. After 3 years there were no signs of metastases. In the 32-year-old woman with a malignant lymphoma diagnosed during the third trimester of pregnancy, chemotherapy had to be started because she developed V. cava superior syndrome. The dyspnoea disappeared and a week after the first treatment she gave birth to a healthy child. A year after completion of treatment she was in complete remission and her child was developing well. Pregnancy is not always a contraindication for starting chemotherapy. However, in order to reduce the risk to mother and child as much as possible, the duration of the pregnancy as well as different groups of cytostatic drugs have to be taken into consideration. A multidisciplinary approach to mother and child is essential.

Can causes of false-normal D-dimer test [SimpliRED] results be identified?

BACKGROUND: To simplify the diagnostic strategy of patients suspected for venous thromboembolism, the use of D-dimer tests has been advocated. Very important for the safety of such diagnostic strategies would be the capacity to recognise false-normal D-dimer results, in order to prevent inadequately withholding anticoagulant treatment in patients who actually have the disease. Insight in the causes of false-normal D-dimer results would therefore be necessary. We hypothesised that certain patient characteristics are associated with relatively low plasma D-dimer levels and, therefore, could increase the risk of false-normal results. METHODS: Consecutive patients with an objectively confirmed venous thromboembolic event and an independently obtained false-normal SimpliRED D-dimer test result were included in the study. For each patient, two controls with objectively confirmed venous thromboembolism and an adequate abnormal D-dimer result were selected. Baseline patient characteristics, obtained by standardised questionnaires, were compared between the two groups of patients. RESULTS: In total, 686 patients had a venous thromboembolic event and 47 of these patients had a false-normal SimpliRED result. Therefore, the overall sensitivity of the SimpliRED test for venous thromboembolism was 94% (95% CI: 92-95%). Although the prevalence of certain clinical characteristics was significantly higher in patients with a false-normal D-dimer result than in the controls [odds ratios for (LMW)heparin treatment and symptoms lasting more than 10 days: 5.1 (95% CI: 1.5-18.7) and 3.2 (95% CI:1.4-7.4), respectively], the prevalence of these characteristics was also high in the control group with an adequate abnormal D-dimer. Combining two or more of these characteristics had a low prevalence and did not further improve the ability to identify those patients with a false-normal D-dimer test at presentation. CONCLUSIONS: Although these findings clearly indicate an association between certain baseline clinical characteristics and the occurrence of a false-normal SimpliRED test, the clinical utility for these characteristics is limited.

HIV infection in critically ill obstetrical patients.

OBJECTIVES: The effect of HIV-infection on the clinical course of critically ill obstetrical patients by means of a case-control study was evaluated. METHODS: Over one calendar year 440 patients were admitted to a high risk obstetrical unit. All patients were tested for HIV-infection. HIV-positive patients were included in the study group and two HIV-negative patients for every HIV-positive patient were included in the control group. RESULTS: No differences were found between the two groups regarding demographic data, diagnosis, antibiotic use, mode of delivery, duration of hospital stay and mortality. More complications occurred in the HIV-negative group. Eclampsia recorded for the HIV-negative group was 17.1% and 4.7% for the HIV-positive group (P=0.04; 95% CI: -17.1%; -0.9%) and lung edema was 18.2% and 6.2%, respectively (P=0.01; 95% CI: -19.3%; -3.5%). The median CD4/CD8 ratio was significantly lower in the HIV-positive group (0.43) than the HIV-negative group (1.37) (P<0.01; 95% CI: -1.04; -0.79). CONCLUSIONS: HIV-infection did not significantly alter the clinical course of critically ill patients in an obstetrical high care unit.

Abrupt versus gradual withdrawal of vitamin K antagonist treatment in patients with venous thromboembolic disease: assessment of hypercoagulability and clinical outcome.

BACKGROUND: It is yet unclear whether vitamin K antagonist treatment should be stopped abruptly or gradually after an episode of venous thromboembolism. The mode of withdrawal might influence a potential development of a hypercoagulable state, which could influence the risk for recurrent disease. METHODS: We prospectively studied 37 consecutive patients in whom acenocoumarol was discontinued either abrupt (18) or gradually (19) (2/3 and 1/3 of the initial dose for one week). Blood sampling was performed at various time points up to 18 days after complete withdrawal and was analysed for INR, prothrombin fragment F1 + 2 and D-dimer. All patients were clinically followed-up for the assessment of the association between hypercoagulability and occurrence of disease such as recurrent venous thromboembolism or malignancy. RESULTS: An approximately fourfold increase was observed (median increase from 0.3 to 1.3 nmol/l) in the F1 + 2 levels after both abrupt and gradual withdrawal and in the D-dimer concentrations in the abrupt withdrawal group (0.10 to 0.44 mg/l), while those in whom acenocoumarol was discontinued gradually showed a less pronounced increase of the D-dimer levels (0.11 to 0.29 mg/L) (not significant). During follow-up one recurrent venous thromboembolic event occurred in each group, and a diagnosis of cancer was made four times. All these patients had the highest D-dimer concentrations measured in the entire study group. CONCLUSIONS: This study indicates the potential for a hypercoagulable state after acenocoumarol discontinuation, which was not prevented by tapering the acenocoumarol dose. D-dimer, measured 2 to 3 weeks after acenocoumarol withdrawal, might be an important tool to identify patients at risk for recurrent venous thromboembolism and/or for the presence of an underlying malignancy.

Changes in perfusion scintigraphy in the first days of heparin therapy in patients with acute pulmonary embolism.

Patients with suspected pulmonary embolism often receive heparin therapy for hours to days before ventilation/perfusion scintigraphy is completed. We assessed to what extent the lung scan classification and pulmonary vascular perfusion changed over a period of 2-4 days of full anticoagulant therapy. In 312 consecutive patients with at least one segmental perfusion defect on the initial perfusion scan, classification of both the initial and the final lung scan allowed us to study alteration in scan classification. Changes in pulmonary perfusion were assessed scintigraphically in a subgroup of 64 patients with proven pulmonary embolism. Among 79 patients with an initial high-probability lung scan, the final scan remained high probability in 77 whereas it became non-diagnostic and normal in one patient each. The lung scan classification did not change in any of the 233 patients who initially had a non-diagnostic scan. Thus, a different lung scan category was observed in only 2 out of 312 patients (0.6%; 95% CI 0.1%-2.3%). The mean pulmonary perfusion at baseline in the subgroup of 64 patients with pulmonary embolism was 62% (SD +/-17%; range 26%-89%). A mean absolute improvement in pulmonary perfusion of only 4%+/-11% (NS) was observed in the 2-4 days of observation. It is concluded that intravenous heparin therapy for a period of 2-4 days has only a minimal influence on the diagnostic lung scan classification and induces only minor changes in pulmonary vascular obstruction in the majority of patients.

Toxin-mediated haemolytic uraemic syndrome without diarrhoea.

A 52-year-old previously healthy man was admitted to the hospital with haematuria, painful micturition and fever. Laboratory investigation showed the presence of a haemolytic uraemic syndrome (HUS), characterized by haemolysis, renal insufficiency and mental disturbances. A urinary tract infection caused by a verotoxin-producing E. coli other than O157:H7 was diagnosed. Treatment of this infection resulted in his complete recovery from the illness. Both the search for a focus outside the gastrointestinal tract and the search for verotoxin genes by specific polymerase chain reaction can be crucial in a patient with HUS without preceding diarrhoea.

[Identification of a new mutation (CysII6Gly) in a family with neurogenic diabetes insipidus]. / Identificatie van een nieuwe mutatie (CysII6Gly) bij een familie met neurogene diabetes insipidus.

OBJECTIVE: Elucidation and identification of the molecular biological alteration in the arginine-vasopressin neurophysin II AVP-NPII gene in a family with familial neurohypophysial diabetes insipidus (FNDI). DESIGN: Descriptive. METHODS: Following the finding of diabetes insipidus in a 2-year-old boy and his father a molecular genetic investigation was performed in the Isala Klinieken, Sophia location, in Zwolle, the Netherlands, to determine the nature of a possible gene mutation. Thereafter the AVP-NPII gene was screened in the family with polymerase chain reaction (PCR) and restriction enzyme analysis on DNA isolated from peripheral blood. An extensive pedigree was made. RESULTS: A new mutation in the AVP-NPII gene was identified in the part encoding the transport peptide neurophysin II. in exon 3, on codon 116, in which thymine was replaced by guanine, leading to the amino acid glycine instead of cysteine in the gene product. CONCLUSION: In a Dutch family with familial neurohypophysial diabetes insipidus a new gene mutation was found (CysII6Gly). Clarification of the molecular background of FNDI in this family made it possible to test family members in a relatively simple and friendly way (without the thirsting test) by PCR and restriction enzyme analysis for the presence of the mutation and the predisposition for diabetes insipidus.

Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.

BACKGROUND: The main purpose of ventilation scanning, as adjunct to perfusion lung scintigraphy, in acute pulmonary embolism is to allow for the classification of segmental perfusion defects as mismatched, which is generally accepted as proof for the presence of pulmonary embolism. We examined whether this function of the ventilation scan could be replaced by the chest X-ray. METHODS: In 389 consecutive patients with suspected pulmonary embolism and at least one segmental perfusion defect we classified the ventilation/perfusion (V/Q) scan and chest X-ray/perfusion (X/Q) scan as either mismatched or matched. Furthermore we analyzed whether this comparison was different in subgroups of patients with concomitant congestive heart failure or chronic obstructive pulmonary disease. RESULTS: Overall agreement between the X/Q and V/Q scan diagnostic category was found in 341 of 389 patients (88%; 95% CI 84-92%). The positive predictive value for obtaining a mismatched V/Q scan result in case of a mismatched X/Q scan result was 86% (95% CI 81-90%). If the X/Q scan yielded only matched defects the V/Q scan resulted in the same classification in 90% (95% CI 85-95%). Analysis of the small subgroup of patients with chronic obstructive pulmonary disease showed that a mismatched X/Q scan was confirmed by V/Q scanning in 21 of 34 cases (62%; 95% CI 45-78%). CONCLUSION: This study shows that in the great majority of patients with clinically suspected acute pulmonary embolism combination of chest X-ray with perfusion scintigraphy reliably replaced ventilation/perfusion scintigraphy in defining (mis)-matching of segmental perfusion defects. These results need confirmation before the chest X-ray can fully obviate the use of ventilation scintigraphy.

The use of a rapid D-dimer blood test in the diagnostic work-up for pulmonary embolism: a management study.

BACKGROUND: D-dimer assays have a potential to rule out pulmonary embolism in case of a normal test result. We studied the clinical utility of incorporating the SimpliRED D-dimer test result and clinical probability in the routine diagnostic work-up of patients with suspected acute pulmonary embolism. METHODS: In a prospective management study 245 consecutive patients, hospitalised as well as outpatients, were included. A SimpliRED D-dimer test and perfusion/(ventilation) scintigraphy were obtained in all patients, whereas clinical probability was determined in the subgroup of patients with a non-diagnostic scan and normal D-dimer result. A diagnostic algorithm determined the necessity for further testing and decisions about treatment. All patients were followed up for 3 months. RESULTS: In 54 patients (22%) with a normal lung scan and 50 patients (21%) with a high probability lung scan, antithrombotic therapy was withheld or started respectively, irrespective of the D-dimer result. A non-diagnostic lung scan was found in 137 (56%) patients, of whom 70 patients had an abnormal D-dimer test, in whom further testing was ordered. Of the remaining 67 patients with a non-diagnostic lung scan and normal D-dimer test 8 patients had a high clinical probability, and the subsequent ultrasonography and pulmonary angiography yielded pulmonary emboli in 1 patient. In the remaining 66 patients, pulmonary embolism was considered to be absent and antithrombotic treatment was stopped/withheld. During follow-up of these patients only one patient experienced a possible venous thromboembolic event (failure rate 1,5%; 95% CI 0-8%). The SimpliRED D-dimer was normal in 6 of 61 patients with proven pulmonary embolism (sensitivity 90%; 95% CI 80-96%). CONCLUSION: Our findings suggest that it is safe to withhold anticoagulant therapy in those patients with a non-diagnostic lung scan, a normal SimpliRED D-dimer test result, and without a high clinical probability. This results in a substantial decreased need for ultrasonography and pulmonary angiography. The SimpliRED should not be used in isolation to exclude pulmonary embolism.

Use of a heparin nomogram for treatment of patients with venous thromboembolism in a community hospital.

BACKGROUND: The application of a heparin dosing nomogram in the treatment of patients with venous thromboembolism resulted in improvement of heparin therapy in clinical research settings. In 1992 a heparin nomogram was introduced in our hospital, which is a community hospital where anticoagulant therapy is supervised by the attending physicians. We studied whether comparable improvements were achieved in such a non-surveyed clinical setting. METHODS: Patients were identified from computerized discharge records, and classified into a pre-nomogram (discharged in 1990 or 1991) and a nomogram patient group (discharged in 1993 or 1994). The use of the nomogram was encouraged but the application remained on a voluntary basis. Since the definition of the target APTT range was different in the pre-nomogram period as compared to the nomogram period, a formal analysis of pre- and post-nomogram results was not considered justified. RESULTS: The APTT ratio, six hours after the start of heparin treatment, was below the predefined lower limit in 72% of 127 patients in the pre-nomogram group and in 13% of 127 patients in the nomogram group. During 1043 days heparin therapy in the nomogram group the morning APTT ratio was subtherapeutic in 8%. In 58% of all APTT results the physician responded according to the nomogram. The subsequent APTT was in the target range in 64% of the cases compared to 31% if the adjustement was not performed according to the nomogram (P<.0001). Major bleeding episodes occurred in 3.1% in the pre-nomogram period and in 0.7% in the nomogram period. CONCLUSION: The present study shows that the introduction of a heparin dosing nomogram in a non-research clinical setting results in more adequate heparin anticoagulation with low risks of bleeding.