Management of asymptomatic anthracycline-induced cardiac damage after treatment for childhood cancer: a postal survey among Dutch adult and pediatric cardiologists

Asymptomatic anthracycline-induced cardiac damage (A-CD) is a serious problem among young childhood cancer survivors. The aim of this survey was to assess the current treatment policy in these patients in the Netherlands. A questionnaire was sent to all 136 departments of adult or pediatric cardiology in the Netherlands. It was returned by 61% of the departments. Sixty-six percent of the respondents started medical treatment (ie, an ACE inhibitor and/or a beta-blocker) in childhood cancer survivors with asymptomatic A-CD. Fifty-eight percent of the respondents indicated that their treatment decision was based on published findings in the literature, but none of them referred to studies evaluating the treatment of asymptomatic A-CD. A majority of adult and pediatric cardiologists started medical treatment in childhood cancer survivors with asymptomatic A-CD without knowledge of the benefits and risks of treatment in this patient group. Before ACE inhibitors and/or beta-blockers can be recommended as routine practice in childhood cancer survivors with asymptomatic A-CD, randomized controlled trials should be performed. Until then, the authors recommend centralizing the treatment of childhood cancer survivors with asymptomatic A-CD in a specialized center to cluster the available knowledge and experience.     

Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations

RPGR-interacting protein 1 (RPGRIP1) is a key component of cone and rod photoreceptor cells, where it interacts with RPGR (retinitis pigmentosa GTPase regulator). Mutations in RPGRIP1 lead to autosomal recessive congenital blindness [Leber congenital amaurosis (LCA)]. Most LCA-associated missense mutations in RPGRIP1 are located in a segment that encodes two C2 domains. Based on the C2 domain of novel protein kinase C epsilon (PKC epsilon), we built a 3D-homology model for the C-terminal C2 domain of RPGRIP1. This model revealed a potential Ca2+-binding site that was predicted to be disrupted by a missense mutation in RPGRIP1, which was previously identified in an LCA patient. Through yeast two-hybrid screening of a retinal cDNA library, we found this C2 domain to specifically bind to nephrocystin-4, encoded by NPHP4. Mutations in NPHP4 are associated with nephronophthisis and a combination of nephronophthisis and retinitis pigmentosa called Senior-L?ken syndrome (SLSN). We show that RPGRIP1 and nephrocystin-4 interact strongly in vitro and in vivo, and that they colocalize in the retina, matching the panretinal localization pattern of specific RPGRIP1 isoforms. Their interaction is disrupted by either mutations in RPGRIP1, found in patients with LCA, or by mutations in NPHP4, found in patients with nephronophthisis or SLSN. Thus, we provide evidence for the involvement of this disrupted interaction in the retinal dystrophy of both SLSN and LCA patients.     

Adnexal torsion in very young girls: diagnostic pitfalls

OBJECTIVE: Evaluation of cases of young girls diagnosed with adnexal torsion. STUDY DESIGN: Retrospective cohort study of 39 girls born between January 1980 and January 2000 who presented with acute abdominal pain and/or the diagnosis adnexal torsion in the Groene Hart Hospital. Seven patients, aged 6-13 years, with adnexal torsion were further evaluated. RESULTS: In three patients, it was possible to save the adnexa. Only the time relapse between the onset of complaints and the surgical intervention correlated with the presence of microscopic necrosis in the ovary. Bluish-black appearance of an ovary did not correlate with the presence of microscopic necrosis. CONCLUSIONS: Early recognition and treatment are essential to minimise the risk of decreased fertility after adnexal torsion in young girls. We therefore advocate prompt diagnostic laparoscopy and detorsion of the adnexa. In case a cyst is present, it should not be resected, but checked on a regular basis using ultrasound.     

The value of the Rehabilitation Activities Profile (RAP) as a quality sub-system in rehabilitation medicine

Purpose: To determine whether interdisciplinary team care, using the Rehabilitation Activities Profile (RAP) as a team tool, results in a better rehabilitation outcome.

Method: A multilevel prospective cohort study, with a controlled before and after design. Eighteen rehabilitation teams in eight rehabilitation centres in the Netherlands and Belgium participated. Based on the level of implementation of the RAP, we compared three study groups. Consecutive adult patients (n = 933) with stroke, amputation of the lower limb, spinal cord injury, multiple sclerosis, or other neuromuscular disorders, were followed during inpatient or outpatient rehabilitation. Main outcome measures were Barthel Index, RAP-CPM (sum score of the domains communication, personal care and mobility), Nottingham Health Profile (NHP), length of rehabilitation (LOR) and discharge destination (home vs elsewhere).

Results: Overall results show that scores on the Barthel Index, the RAP-CPM and the NHP improved, on average, by 18.4%, 12.7%, and 6.7%, respectively. However, treatment from a rehabilitation team that uses the RAP was associated with a significantly lower Barthel score, and small, non-significant effects on the RAP-CPM and the NHP. Partial use of the RAP resulted in non-significant, lower scores on these measures. With respect to discharge destination and LOR, there were also no significant differences between the three study groups, with the exception of a shorter outpatient rehabilitation period for the group in which partial use was made of the RAP.

Conclusion: The RAP, at the current level of implementation, does not improve rehabilitation outcome.     

Trisomy 13 or 18 (mosaicism) in first trimester cytotrophoblast cells: false-positive results in 11 out of 51 cases

OBJECTIVE: The finding of full or mosaic trisomy 13 or 18 in first trimester chorionic villus sampling (CVS) may be a false-positive result. This report provides incidence and outcome information that may be helpful in counselling individual patients and in choosing adequate follow-up. STUDY DESIGN: From a series of 6820 CVS cases, we retrospectively collected data on all patients (n=51) with full (n=30) or mosaic (n=5) trisomy 18, and full (n=13) or mosaic (n=3) trisomy 13 in cytotrophoblast cells. RESULTS: Five false-positives were seen in patients with full trisomy 18 and three in the mosaic cases. One false-positive result was observed in full trisomy 13 and two false-positives in cases of mosaicism. No false-negative results were reported. CONCLUSION: The diagnosis of trisomy 13 or 18 in cytotrophoblasts should be confirmed in other tissues, unless fetal abnormalities are seen at ultrasound. In case of mosaicism, follow-up amniocentesis is advised.     

Intensive care information system reduces documentation time of the nurses after cardiothoracic surgery

OBJECTIVE: Nowadays, registration of patient data on paper is gradually being replaced by registration using an intensive care information system (ICIS). The aim of this study was to evaluate the effect of the use of an ICIS on nursing activity. DESIGN: Randomized controlled trial with a crossover design. SETTING: An 18-bed medical-surgical ICU in a teaching hospital. PATIENTS, NURSES AND INTERVENTIONS: During a 6week period 145 consecutive adult patients admitted to the ICU after uncomplicated cardiothoracic surgery were randomized into two groups: for one group the documentation was carried out using a paper-based registration (Paper), in the second group an ICIS was used for documentation. MEASUREMENTS AND RESULTS: The nursing activities for these patients were studied during two separate periods: the admission period and the registration phase (the period directly following the admission procedure). The duration of the admission procedure was measured by time-motion analysis and the nursing activities in the registration phase were studied by work sampling methodology. All nursing activities during the registration phase were grouped in four main categories: patient care, documentation, unit-related and personal time. The duration of the admission procedure was longer in the ICIS group (18.1+/-4.1 versus 16.8+/-3.1 min, p<0.05). In the registration phase, a 30% reduction in documentation time (Paper 20.5% of total nursing time versus ICIS 14.4%, p<0.001), corresponding to 29 min (per 8h nursing shift) was achieved. This time was completely re-allocated to patient care. CONCLUSIONS: The use of the present ICIS in patients after cardiothoracic surgery alters nursing activity; it reduces the time for documentation and increases the time devoted to patient care. Electronic supplementary material: is available if you access this article at http://dx.org/10.1007/s00134-002-1542-9. On that page (frame on the left side), a link takes you directly to the supplementary material.     

Human immunodeficiency virus infection in children hospitalised with tuberculosis

The impact of HIV infection on clinical presentation and outcome of tuberculosis (TB) was studied in children hospitalised at the Brooklyn Hospital for Chest Diseases (BCH), Cape Town over the 2-year period January 1998 to December 1999. Clinical data were extracted from a prospectively compiled patient register. Of 261 children with TB, 114 (median age 24 mths) were not HIV-infected and 36 (median age 23 mths) were HIV-infected. The HIV status of 111 children (median age 37 mths) was not determined. Pulmonary TB with or without extrapulmonary TB occurred in 97 (85%) children who were not HIV-infected, 35 (97%) HIV-infected children and 87 (78%) of those not tested (p = 0.025). A tuberculin reaction > or = 15 mm was elicited in ten (31%) of 32 HIV-infected children, 76 (72%) of 106 non-HIV-infected and 62 (71%) of those not tested (p < 0.001). Mycobacterium tuberculosis was cultured from 116 (49%) of 238 children and drug sensitivity was evaluated in 79. Nine isolates (11%) were resistant to isoniazid (INH) and 11 (14%) to INH and rifampicin (RMP). Two HIV-infected children treated previously in BCH for drug-sensitive TB were re-admitted with INH and RMP resistance. Two (2%) non-HIV-infected children, six (17%) HIV-infected children and one (1%) child with undetermined HIV status died (p < 0.001).     

Synergistic activity of the N-terminal peptide of human lactoferrin and fluconazole against Candida species

In light of the need for new antifungal regimens, we report that at noncandidacidal concentrations, the lactoferrin-derived peptide hLF(1-11), which is highly active against fluconazole-resistant Candida albicans, acts synergistically with fluconazole against this yeast and a fluconazole-sensitive C. albicans strain as well as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis. When these yeasts were exposed to hLF(1-11) for 5 min and then incubated with fluconazole, they were killed effectively, while no candidacidal activity was observed when they were incubated first with fluconazole and then exposed to the peptide, indicating that the candidacidal activity is initiated by the peptide while fluconazole is only required during the effector phase. Investigations of the effect of azide, which inhibits mitochondrial respiration, on the activity of combinations of hLF(1-11) and fluconazole against fluconazole-resistant C. albicans revealed that it inhibits this activity, even when added during the effector phase only. As expected, azide inhibited the accumulation of rhodamine 123 in mitochondria and the production and release of ATP by C. albicans that occurred upon exposure to the combination of hLF(1-11) and fluconazole. Accordingly, oxidized ATP (oATP), an antagonist of ATP receptors, completely blocked the candidacidal activity of the hLF(1-11)-fluconazole combination, whereas oATP did not block the activity when its presence was restricted to the effector phase. The candidacidal activity of combinations of hLF(1-11) and fluconazole, which is initiated by the peptide through the involvement of energized mitochondria, renders fluconazole-resistant C. albicans sensitive to this azole.